Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats
Identifieur interne : 000413 ( Pmc/Corpus ); précédent : 000412; suivant : 000414Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats
Auteurs : Vez Repunte-Canonigo ; Celine Lefebvre ; Olivier George ; Tomoya Kawamura ; Marisela Morales ; George F. Koob ; Andrea Califano ; Eliezer Masliah ; Pietro Paolo SannaSource :
- Molecular Neurodegeneration [ 1750-1326 ] ; 2014.
Abstract
A thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS.
We report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 proteins are expressed under the control of the viral LTR promoter in disease-relevant cells including microglia and astrocytes. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis. Gene expression changes observed are consistent with astrogliosis and microgliosis and include evidence of inflammation and cell proliferation. Among the genes with increased expression in HIV-1 Tg rats was the interferon stimulated gene 15 (ISG-15), which was previously shown to be increased in the cerebrospinal fluid (CSF) of HIV patients and to correlate with neuropsychological impairment and neuropathology, and prostaglandin D2 (PGD2) synthase (Ptgds), which has been associated with immune activation and the induction of astrogliosis and microgliosis. GSEA-based pathway analysis highlighted a broad dysregulation of genes involved in neuronal trophism and neurodegenerative disorders. Among the latter are genesets associated with Huntington’s disease, Parkinson’s disease, mitochondrial, peroxisome function, and synaptic trophism and plasticity, such as IGF, ErbB and netrin signaling and the PI3K signal transduction pathway, a mediator of neural plasticity and of a vast array of trophic signals. Additionally, gene expression analyses also show altered lipid metabolism and peroxisomes dysfunction. Supporting the functional significance of these gene expression alterations, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function.
Altogether, differentially regulated genes and pathway analysis identify specific pathways that can be targeted therapeutically to increase trophic support, e.g. IGF, ErbB and netrin signaling, and reduce neuroinflammation, e.g. PGD2 synthesis, which may be beneficial in the treatment of chronic forms of HIV-associated neurocognitive disorders in the setting of viral suppression.
Url:
DOI: 10.1186/1750-1326-9-26
PubMed: 24980976
PubMed Central: 4107468
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PMC:4107468Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats</title><author><name sortKey="Repunte Canonigo, Vez" sort="Repunte Canonigo, Vez" uniqKey="Repunte Canonigo V" first="Vez" last="Repunte-Canonigo">Vez Repunte-Canonigo</name><affiliation><nlm:aff id="I1">Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</nlm:aff></affiliation></author><author><name sortKey="Lefebvre, Celine" sort="Lefebvre, Celine" uniqKey="Lefebvre C" first="Celine" last="Lefebvre">Celine Lefebvre</name><affiliation><nlm:aff id="I3">INSERM Unit U981, Gustave Roussy Institute, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="George, Olivier" sort="George, Olivier" uniqKey="George O" first="Olivier" last="George">Olivier George</name><affiliation><nlm:aff id="I2">Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff></affiliation></author><author><name sortKey="Kawamura, Tomoya" sort="Kawamura, Tomoya" uniqKey="Kawamura T" first="Tomoya" last="Kawamura">Tomoya Kawamura</name><affiliation><nlm:aff id="I1">Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</nlm:aff></affiliation></author><author><name sortKey="Morales, Marisela" sort="Morales, Marisela" uniqKey="Morales M" first="Marisela" last="Morales">Marisela Morales</name><affiliation><nlm:aff id="I4">National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Koob, George F" sort="Koob, George F" uniqKey="Koob G" first="George F" last="Koob">George F. Koob</name><affiliation><nlm:aff id="I2">Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I5">National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Ln, Rockville, MD 20852, USA</nlm:aff></affiliation></author><author><name sortKey="Califano, Andrea" sort="Califano, Andrea" uniqKey="Califano A" first="Andrea" last="Califano">Andrea Califano</name><affiliation><nlm:aff id="I6">Department of Systems Biology, Columbia University, New York, New York 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Masliah, Eliezer" sort="Masliah, Eliezer" uniqKey="Masliah E" first="Eliezer" last="Masliah">Eliezer Masliah</name><affiliation><nlm:aff id="I7">Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093, USA</nlm:aff></affiliation></author><author><name sortKey="Sanna, Pietro Paolo" sort="Sanna, Pietro Paolo" uniqKey="Sanna P" first="Pietro Paolo" last="Sanna">Pietro Paolo Sanna</name><affiliation><nlm:aff id="I1">Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24980976</idno><idno type="pmc">4107468</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107468</idno><idno type="RBID">PMC:4107468</idno><idno type="doi">10.1186/1750-1326-9-26</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000413</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000413</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats</title><author><name sortKey="Repunte Canonigo, Vez" sort="Repunte Canonigo, Vez" uniqKey="Repunte Canonigo V" first="Vez" last="Repunte-Canonigo">Vez Repunte-Canonigo</name><affiliation><nlm:aff id="I1">Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</nlm:aff></affiliation></author><author><name sortKey="Lefebvre, Celine" sort="Lefebvre, Celine" uniqKey="Lefebvre C" first="Celine" last="Lefebvre">Celine Lefebvre</name><affiliation><nlm:aff id="I3">INSERM Unit U981, Gustave Roussy Institute, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="George, Olivier" sort="George, Olivier" uniqKey="George O" first="Olivier" last="George">Olivier George</name><affiliation><nlm:aff id="I2">Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff></affiliation></author><author><name sortKey="Kawamura, Tomoya" sort="Kawamura, Tomoya" uniqKey="Kawamura T" first="Tomoya" last="Kawamura">Tomoya Kawamura</name><affiliation><nlm:aff id="I1">Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</nlm:aff></affiliation></author><author><name sortKey="Morales, Marisela" sort="Morales, Marisela" uniqKey="Morales M" first="Marisela" last="Morales">Marisela Morales</name><affiliation><nlm:aff id="I4">National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Koob, George F" sort="Koob, George F" uniqKey="Koob G" first="George F" last="Koob">George F. Koob</name><affiliation><nlm:aff id="I2">Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I5">National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Ln, Rockville, MD 20852, USA</nlm:aff></affiliation></author><author><name sortKey="Califano, Andrea" sort="Califano, Andrea" uniqKey="Califano A" first="Andrea" last="Califano">Andrea Califano</name><affiliation><nlm:aff id="I6">Department of Systems Biology, Columbia University, New York, New York 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Masliah, Eliezer" sort="Masliah, Eliezer" uniqKey="Masliah E" first="Eliezer" last="Masliah">Eliezer Masliah</name><affiliation><nlm:aff id="I7">Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093, USA</nlm:aff></affiliation></author><author><name sortKey="Sanna, Pietro Paolo" sort="Sanna, Pietro Paolo" uniqKey="Sanna P" first="Pietro Paolo" last="Sanna">Pietro Paolo Sanna</name><affiliation><nlm:aff id="I1">Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Molecular Neurodegeneration</title><idno type="eISSN">1750-1326</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>A thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS.</p></sec><sec><title>Results</title><p>We report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 proteins are expressed under the control of the viral LTR promoter in disease-relevant cells including microglia and astrocytes. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis. Gene expression changes observed are consistent with astrogliosis and microgliosis and include evidence of inflammation and cell proliferation. Among the genes with increased expression in HIV-1 Tg rats was the interferon stimulated gene 15 (ISG-15), which was previously shown to be increased in the cerebrospinal fluid (CSF) of HIV patients and to correlate with neuropsychological impairment and neuropathology, and prostaglandin D2 (PGD2) synthase (Ptgds), which has been associated with immune activation and the induction of astrogliosis and microgliosis. GSEA-based pathway analysis highlighted a broad dysregulation of genes involved in neuronal trophism and neurodegenerative disorders. Among the latter are genesets associated with Huntington’s disease, Parkinson’s disease, mitochondrial, peroxisome function, and synaptic trophism and plasticity, such as IGF, ErbB and netrin signaling and the PI3K signal transduction pathway, a mediator of neural plasticity and of a vast array of trophic signals. Additionally, gene expression analyses also show altered lipid metabolism and peroxisomes dysfunction. Supporting the functional significance of these gene expression alterations, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function.</p></sec><sec><title>Conclusions</title><p>Altogether, differentially regulated genes and pathway analysis identify specific pathways that can be targeted therapeutically to increase trophic support, e.g. IGF, ErbB and netrin signaling, and reduce neuroinflammation, e.g. PGD2 synthesis, which may be beneficial in the treatment of chronic forms of HIV-associated neurocognitive disorders in the setting of viral suppression.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Maschke, M" uniqKey="Maschke M">M Maschke</name></author><author><name sortKey="Kastrup, O" uniqKey="Kastrup O">O Kastrup</name></author><author><name sortKey="Esser, S" uniqKey="Esser S">S Esser</name></author><author><name sortKey="Ross, B" uniqKey="Ross B">B Ross</name></author><author><name sortKey="Hengge, U" uniqKey="Hengge U">U Hengge</name></author><author><name sortKey="Hufnagel, A" uniqKey="Hufnagel A">A Hufnagel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Arminio Monforte, A" uniqKey="D Arminio Monforte A">A D'Arminio Monforte</name></author><author><name sortKey="Cinque, P" uniqKey="Cinque P">P Cinque</name></author><author><name sortKey="Mocroft, A" uniqKey="Mocroft A">A Mocroft</name></author><author><name sortKey="Goebel, Fd" uniqKey="Goebel F">FD Goebel</name></author><author><name sortKey="Antunes, F" uniqKey="Antunes F">F Antunes</name></author><author><name sortKey="Katlama, C" uniqKey="Katlama C">C Katlama</name></author><author><name sortKey="Justesen, Us" uniqKey="Justesen U">US Justesen</name></author><author><name sortKey="Vella, S" uniqKey="Vella S">S Vella</name></author><author><name sortKey="Kirk, O" uniqKey="Kirk O">O Kirk</name></author><author><name sortKey="Lundgren, J" uniqKey="Lundgren J">J Lundgren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Everall, Ip" uniqKey="Everall I">IP Everall</name></author><author><name sortKey="Hansen, La" uniqKey="Hansen L">LA Hansen</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Everall, I" uniqKey="Everall I">I Everall</name></author><author><name sortKey="Vaida, F" uniqKey="Vaida F">F Vaida</name></author><author><name sortKey="Khanlou, N" uniqKey="Khanlou N">N Khanlou</name></author><author><name sortKey="Lazzaretto, D" uniqKey="Lazzaretto D">D Lazzaretto</name></author><author><name sortKey="Achim, C" uniqKey="Achim C">C Achim</name></author><author><name sortKey="Letendre, S" uniqKey="Letendre S">S Letendre</name></author><author><name sortKey="Moore, D" uniqKey="Moore D">D Moore</name></author><author><name sortKey="Ellis, R" uniqKey="Ellis R">R Ellis</name></author><author><name sortKey="Cherne, M" uniqKey="Cherne M">M Cherne</name></author><author><name sortKey="Gelman, B" uniqKey="Gelman B">B Gelman</name></author><author><name sortKey="Morgello, S" uniqKey="Morgello S">S Morgello</name></author><author><name sortKey="Singer, E" uniqKey="Singer E">E Singer</name></author><author><name sortKey="Grant, I" uniqKey="Grant I">I Grant</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heaton, Rk" uniqKey="Heaton R">RK Heaton</name></author><author><name sortKey="Franklin, Dr" uniqKey="Franklin D">DR Franklin</name></author><author><name sortKey="Ellis, Rj" uniqKey="Ellis R">RJ Ellis</name></author><author><name sortKey="Mccutchan, Ja" uniqKey="Mccutchan J">JA McCutchan</name></author><author><name sortKey="Letendre, Sl" uniqKey="Letendre S">SL Letendre</name></author><author><name sortKey="Leblanc, S" uniqKey="Leblanc S">S Leblanc</name></author><author><name sortKey="Corkran, Sh" uniqKey="Corkran S">SH Corkran</name></author><author><name sortKey="Duarte, Na" uniqKey="Duarte N">NA Duarte</name></author><author><name sortKey="Clifford, Db" uniqKey="Clifford D">DB Clifford</name></author><author><name sortKey="Woods, Sp" uniqKey="Woods S">SP Woods</name></author><author><name sortKey="Collier, Ac" uniqKey="Collier A">AC Collier</name></author><author><name sortKey="Marra, Cm" uniqKey="Marra C">CM Marra</name></author><author><name sortKey="Morgello, S" uniqKey="Morgello S">S Morgello</name></author><author><name sortKey="Mindt, Mr" uniqKey="Mindt M">MR Mindt</name></author><author><name sortKey="Taylor, Mj" uniqKey="Taylor M">MJ Taylor</name></author><author><name sortKey="Marcotte, Td" uniqKey="Marcotte T">TD Marcotte</name></author><author><name sortKey="Atkinson, Jh" uniqKey="Atkinson J">JH Atkinson</name></author><author><name sortKey="Wolfson, T" uniqKey="Wolfson T">T Wolfson</name></author><author><name sortKey="Gelman, Bb" uniqKey="Gelman B">BB Gelman</name></author><author><name sortKey="Mcarthur, Jc" uniqKey="Mcarthur J">JC McArthur</name></author><author><name sortKey="Simpson, Dm" uniqKey="Simpson D">DM Simpson</name></author><author><name sortKey="Abramson, I" uniqKey="Abramson I">I Abramson</name></author><author><name sortKey="Gamst, A" uniqKey="Gamst A">A Gamst</name></author><author><name sortKey="Fennema Notestine, C" uniqKey="Fennema Notestine C">C Fennema-Notestine</name></author><author><name sortKey="Jernigan, Tl" uniqKey="Jernigan T">TL Jernigan</name></author><author><name sortKey="Wong, J" uniqKey="Wong J">J Wong</name></author><author><name sortKey="Grant, I" uniqKey="Grant I">I Grant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cysique, La" uniqKey="Cysique L">LA Cysique</name></author><author><name sortKey="Maruff, P" uniqKey="Maruff P">P Maruff</name></author><author><name sortKey="Brew, Bj" uniqKey="Brew B">BJ Brew</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tozzi, V" uniqKey="Tozzi V">V Tozzi</name></author><author><name sortKey="Balestra, P" uniqKey="Balestra P">P Balestra</name></author><author><name sortKey="Serraino, D" uniqKey="Serraino D">D Serraino</name></author><author><name sortKey="Bellagamba, R" uniqKey="Bellagamba R">R Bellagamba</name></author><author><name sortKey="Corpolongo, A" uniqKey="Corpolongo A">A Corpolongo</name></author><author><name sortKey="Piselli, P" uniqKey="Piselli P">P Piselli</name></author><author><name sortKey="Lorenzini, P" uniqKey="Lorenzini P">P Lorenzini</name></author><author><name sortKey="Visco Comandini, U" uniqKey="Visco Comandini U">U Visco-Comandini</name></author><author><name sortKey="Vlassi, C" uniqKey="Vlassi C">C Vlassi</name></author><author><name sortKey="Quartuccio, Me" uniqKey="Quartuccio M">ME Quartuccio</name></author><author><name sortKey="Giulianelli, M" uniqKey="Giulianelli M">M Giulianelli</name></author><author><name sortKey="Noto, P" uniqKey="Noto P">P Noto</name></author><author><name sortKey="Galgani, S" uniqKey="Galgani S">S Galgani</name></author><author><name sortKey="Ippolito, G" uniqKey="Ippolito G">G Ippolito</name></author><author><name sortKey="Antinori, A" uniqKey="Antinori A">A Antinori</name></author><author><name sortKey="Narciso, P" uniqKey="Narciso P">P Narciso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neuenburg, Jk" uniqKey="Neuenburg J">JK Neuenburg</name></author><author><name sortKey="Brodt, Hr" uniqKey="Brodt H">HR Brodt</name></author><author><name sortKey="Herndier, Bg" uniqKey="Herndier B">BG Herndier</name></author><author><name sortKey="Bickel, M" uniqKey="Bickel M">M Bickel</name></author><author><name sortKey="Bacchetti, P" uniqKey="Bacchetti P">P Bacchetti</name></author><author><name sortKey="Price, Rw" uniqKey="Price R">RW Price</name></author><author><name sortKey="Grant, Rm" uniqKey="Grant R">RM Grant</name></author><author><name sortKey="Schlote, W" uniqKey="Schlote W">W Schlote</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcarthur, Jc" uniqKey="Mcarthur J">JC McArthur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brew, Bj" uniqKey="Brew B">BJ Brew</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gendelman, He" uniqKey="Gendelman H">HE Gendelman</name></author><author><name sortKey="Lipton, Sa" uniqKey="Lipton S">SA Lipton</name></author><author><name sortKey="Tardieu, M" uniqKey="Tardieu M">M Tardieu</name></author><author><name sortKey="Bukrinsky, Mi" uniqKey="Bukrinsky M">MI Bukrinsky</name></author><author><name sortKey="Nottet, Hs" uniqKey="Nottet H">HS Nottet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gendelman, He" uniqKey="Gendelman H">HE Gendelman</name></author><author><name sortKey="Persidsky, Y" uniqKey="Persidsky Y">Y Persidsky</name></author><author><name sortKey="Ghorpade, A" uniqKey="Ghorpade A">A Ghorpade</name></author><author><name sortKey="Limoges, J" uniqKey="Limoges J">J Limoges</name></author><author><name sortKey="Stins, M" uniqKey="Stins M">M Stins</name></author><author><name sortKey="Fiala, M" uniqKey="Fiala M">M Fiala</name></author><author><name sortKey="Morrisett, R" uniqKey="Morrisett R">R Morrisett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patel, Ca" uniqKey="Patel C">CA Patel</name></author><author><name sortKey="Mukhtar, M" uniqKey="Mukhtar M">M Mukhtar</name></author><author><name sortKey="Harley, S" uniqKey="Harley S">S Harley</name></author><author><name sortKey="Kulkosky, J" uniqKey="Kulkosky J">J Kulkosky</name></author><author><name sortKey="Pomerantz, Rj" uniqKey="Pomerantz R">RJ Pomerantz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, Gj" uniqKey="Jones G">GJ Jones</name></author><author><name sortKey="Barsby, Nl" uniqKey="Barsby N">NL Barsby</name></author><author><name sortKey="Cohen, Ea" uniqKey="Cohen E">EA Cohen</name></author><author><name sortKey="Holden, J" uniqKey="Holden J">J Holden</name></author><author><name sortKey="Harris, K" uniqKey="Harris K">K Harris</name></author><author><name sortKey="Dickie, P" uniqKey="Dickie P">P Dickie</name></author><author><name sortKey="Jhamandas, J" uniqKey="Jhamandas J">J Jhamandas</name></author><author><name sortKey="Power, C" uniqKey="Power C">C Power</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van De Bovenkamp, M" uniqKey="Van De Bovenkamp M">M van de Bovenkamp</name></author><author><name sortKey="Nottet, Hs" uniqKey="Nottet H">HS Nottet</name></author><author><name sortKey="Pereira, Cf" uniqKey="Pereira C">CF Pereira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adamson, Dc" uniqKey="Adamson D">DC Adamson</name></author><author><name sortKey="Kopnisky, Kl" uniqKey="Kopnisky K">KL Kopnisky</name></author><author><name sortKey="Dawson, Tm" uniqKey="Dawson T">TM Dawson</name></author><author><name sortKey="Dawson, Vl" uniqKey="Dawson V">VL Dawson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ellis, R" uniqKey="Ellis R">R Ellis</name></author><author><name sortKey="Langford, D" uniqKey="Langford D">D Langford</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author><author><name sortKey="Heaton, Rk" uniqKey="Heaton R">RK Heaton</name></author><author><name sortKey="Marcotte, Td" uniqKey="Marcotte T">TD Marcotte</name></author><author><name sortKey="Ellis, Rj" uniqKey="Ellis R">RJ Ellis</name></author><author><name sortKey="Wiley, Ca" uniqKey="Wiley C">CA Wiley</name></author><author><name sortKey="Mallory, M" uniqKey="Mallory M">M Mallory</name></author><author><name sortKey="Achim, Cl" uniqKey="Achim C">CL Achim</name></author><author><name sortKey="Mccutchan, Ja" uniqKey="Mccutchan J">JA McCutchan</name></author><author><name sortKey="Nelson, Ja" uniqKey="Nelson J">JA Nelson</name></author><author><name sortKey="Atkinson, Jh" uniqKey="Atkinson J">JH Atkinson</name></author><author><name sortKey="Grant, I" uniqKey="Grant I">I Grant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iskander, S" uniqKey="Iskander S">S Iskander</name></author><author><name sortKey="Walsh, Ka" uniqKey="Walsh K">KA Walsh</name></author><author><name sortKey="Hammond, Rr" uniqKey="Hammond R">RR Hammond</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toggas, Sm" uniqKey="Toggas S">SM Toggas</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author><author><name sortKey="Rockenstein, Em" uniqKey="Rockenstein E">EM Rockenstein</name></author><author><name sortKey="Rall, Gf" uniqKey="Rall G">GF Rall</name></author><author><name sortKey="Abraham, Cr" uniqKey="Abraham C">CR Abraham</name></author><author><name sortKey="Mucke, L" uniqKey="Mucke L">L Mucke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Bo" uniqKey="Kim B">BO Kim</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Ruan, Y" uniqKey="Ruan Y">Y Ruan</name></author><author><name sortKey="Xu, Zc" uniqKey="Xu Z">ZC Xu</name></author><author><name sortKey="Schantz, L" uniqKey="Schantz L">L Schantz</name></author><author><name sortKey="He, Jj" uniqKey="He J">JJ He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reid, W" uniqKey="Reid W">W Reid</name></author><author><name sortKey="Sadowska, M" uniqKey="Sadowska M">M Sadowska</name></author><author><name sortKey="Denaro, F" uniqKey="Denaro F">F Denaro</name></author><author><name sortKey="Rao, S" uniqKey="Rao S">S Rao</name></author><author><name sortKey="Foulke, J" uniqKey="Foulke J">J Foulke</name></author><author><name sortKey="Hayes, N" uniqKey="Hayes N">N Hayes</name></author><author><name sortKey="Jones, O" uniqKey="Jones O">O Jones</name></author><author><name sortKey="Doodnauth, D" uniqKey="Doodnauth D">D Doodnauth</name></author><author><name sortKey="Davis, H" uniqKey="Davis H">H Davis</name></author><author><name sortKey="Sill, A" uniqKey="Sill A">A Sill</name></author><author><name sortKey="O Driscoll, P" uniqKey="O Driscoll P">P O'Driscoll</name></author><author><name sortKey="Huso, D" uniqKey="Huso D">D Huso</name></author><author><name sortKey="Fouts, T" uniqKey="Fouts T">T Fouts</name></author><author><name sortKey="Lewis, G" uniqKey="Lewis G">G Lewis</name></author><author><name sortKey="Hill, M" uniqKey="Hill M">M Hill</name></author><author><name sortKey="Kamin Lewis, R" uniqKey="Kamin Lewis R">R Kamin-Lewis</name></author><author><name sortKey="Wei, C" uniqKey="Wei C">C Wei</name></author><author><name sortKey="Ray, P" uniqKey="Ray P">P Ray</name></author><author><name sortKey="Gallo, Rc" uniqKey="Gallo R">RC Gallo</name></author><author><name sortKey="Reitz, M" uniqKey="Reitz M">M Reitz</name></author><author><name sortKey="Bryant, J" uniqKey="Bryant J">J Bryant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Royal, W" uniqKey="Royal W">W Royal</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Guo, M" uniqKey="Guo M">M Guo</name></author><author><name sortKey="Jones, O" uniqKey="Jones O">O Jones</name></author><author><name sortKey="Davis, H" uniqKey="Davis H">H Davis</name></author><author><name sortKey="Bryant, Jl" uniqKey="Bryant J">JL Bryant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoang, V" uniqKey="Hoang V">V Hoang</name></author><author><name sortKey="Withers Ward, E" uniqKey="Withers Ward E">E Withers-Ward</name></author><author><name sortKey="Camerini, D" uniqKey="Camerini D">D Camerini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dickie, P" uniqKey="Dickie P">P Dickie</name></author><author><name sortKey="Felser, J" uniqKey="Felser J">J Felser</name></author><author><name sortKey="Eckhaus, M" uniqKey="Eckhaus M">M Eckhaus</name></author><author><name sortKey="Bryant, J" uniqKey="Bryant J">J Bryant</name></author><author><name sortKey="Silver, J" uniqKey="Silver J">J Silver</name></author><author><name sortKey="Marinos, N" uniqKey="Marinos N">N Marinos</name></author><author><name sortKey="Notkins, Al" uniqKey="Notkins A">AL Notkins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wei, P" uniqKey="Wei P">P Wei</name></author><author><name sortKey="Garber, Me" uniqKey="Garber M">ME Garber</name></author><author><name sortKey="Fang, Sm" uniqKey="Fang S">SM Fang</name></author><author><name sortKey="Fischer, Wh" uniqKey="Fischer W">WH Fischer</name></author><author><name sortKey="Jones, Ka" uniqKey="Jones K">KA Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reid, W" uniqKey="Reid W">W Reid</name></author><author><name sortKey="Abdelwahab, S" uniqKey="Abdelwahab S">S Abdelwahab</name></author><author><name sortKey="Sadowska, M" uniqKey="Sadowska M">M Sadowska</name></author><author><name sortKey="Huso, D" uniqKey="Huso D">D Huso</name></author><author><name sortKey="Neal, A" uniqKey="Neal A">A Neal</name></author><author><name sortKey="Ahearn, A" uniqKey="Ahearn A">A Ahearn</name></author><author><name sortKey="Bryant, J" uniqKey="Bryant J">J Bryant</name></author><author><name sortKey="Gallo, Rc" uniqKey="Gallo R">RC Gallo</name></author><author><name sortKey="Lewis, Gk" uniqKey="Lewis G">GK Lewis</name></author><author><name sortKey="Reitz, M" uniqKey="Reitz M">M Reitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Subramanian, A" uniqKey="Subramanian A">A Subramanian</name></author><author><name sortKey="Tamayo, P" uniqKey="Tamayo P">P Tamayo</name></author><author><name sortKey="Mootha, Vk" uniqKey="Mootha V">VK Mootha</name></author><author><name sortKey="Mukherjee, S" uniqKey="Mukherjee S">S Mukherjee</name></author><author><name sortKey="Ebert, Bl" uniqKey="Ebert B">BL Ebert</name></author><author><name sortKey="Gillette, Ma" uniqKey="Gillette M">MA Gillette</name></author><author><name sortKey="Paulovich, A" uniqKey="Paulovich A">A Paulovich</name></author><author><name sortKey="Pomeroy, Sl" uniqKey="Pomeroy S">SL Pomeroy</name></author><author><name sortKey="Golub, Tr" uniqKey="Golub T">TR Golub</name></author><author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name></author><author><name sortKey="Mesirov, Jp" uniqKey="Mesirov J">JP Mesirov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerlai, R" uniqKey="Gerlai R">R Gerlai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerlai, R" uniqKey="Gerlai R">R Gerlai</name></author><author><name sortKey="Shinsky, N" uniqKey="Shinsky N">N Shinsky</name></author><author><name sortKey="Shih, A" uniqKey="Shih A">A Shih</name></author><author><name sortKey="Williams, P" uniqKey="Williams P">P Williams</name></author><author><name sortKey="Winer, J" uniqKey="Winer J">J Winer</name></author><author><name sortKey="Armanini, M" uniqKey="Armanini M">M Armanini</name></author><author><name sortKey="Cairns, B" uniqKey="Cairns B">B Cairns</name></author><author><name sortKey="Winslow, J" uniqKey="Winslow J">J Winslow</name></author><author><name sortKey="Gao, W" uniqKey="Gao W">W Gao</name></author><author><name sortKey="Phillips, Hs" uniqKey="Phillips H">HS Phillips</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clark, Re" uniqKey="Clark R">RE Clark</name></author><author><name sortKey="Zola, Sm" uniqKey="Zola S">SM Zola</name></author><author><name sortKey="Squire, Lr" uniqKey="Squire L">LR Squire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Ct" uniqKey="Johnson C">CT Johnson</name></author><author><name sortKey="Olton, Ds" uniqKey="Olton D">DS Olton</name></author><author><name sortKey="Gage, Fh" uniqKey="Gage F">FH Gage</name></author><author><name sortKey="Jenko, Pg" uniqKey="Jenko P">PG Jenko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Futter, Je" uniqKey="Futter J">JE Futter</name></author><author><name sortKey="Aggleton, Jp" uniqKey="Aggleton J">JP Aggleton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stone, Ws" uniqKey="Stone W">WS Stone</name></author><author><name sortKey="Rudd, Rj" uniqKey="Rudd R">RJ Rudd</name></author><author><name sortKey="Parsons, Mw" uniqKey="Parsons M">MW Parsons</name></author><author><name sortKey="Gold, Pe" uniqKey="Gold P">PE Gold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buhot, Mc" uniqKey="Buhot M">MC Buhot</name></author><author><name sortKey="Dubayle, D" uniqKey="Dubayle D">D Dubayle</name></author><author><name sortKey="Malleret, G" uniqKey="Malleret G">G Malleret</name></author><author><name sortKey="Javerzat, S" uniqKey="Javerzat S">S Javerzat</name></author><author><name sortKey="Segu, L" uniqKey="Segu L">L Segu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lashomb, Al" uniqKey="Lashomb A">AL Lashomb</name></author><author><name sortKey="Vigorito, M" uniqKey="Vigorito M">M Vigorito</name></author><author><name sortKey="Chang, Sl" uniqKey="Chang S">SL Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vigorito, M" uniqKey="Vigorito M">M Vigorito</name></author><author><name sortKey="Lashomb, Al" uniqKey="Lashomb A">AL LaShomb</name></author><author><name sortKey="Chang, Sl" uniqKey="Chang S">SL Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fields, J" uniqKey="Fields J">J Fields</name></author><author><name sortKey="Dumaop, W" uniqKey="Dumaop W">W Dumaop</name></author><author><name sortKey="Adame, A" uniqKey="Adame A">A Adame</name></author><author><name sortKey="Ellis, Rj" uniqKey="Ellis R">RJ Ellis</name></author><author><name sortKey="Letendre, S" uniqKey="Letendre S">S Letendre</name></author><author><name sortKey="Grant, I" uniqKey="Grant I">I Grant</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Rg" uniqKey="Wang R">RG Wang</name></author><author><name sortKey="Kaul, M" uniqKey="Kaul M">M Kaul</name></author><author><name sortKey="Zhang, Dx" uniqKey="Zhang D">DX Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katsounas, A" uniqKey="Katsounas A">A Katsounas</name></author><author><name sortKey="Hubbard, Jj" uniqKey="Hubbard J">JJ Hubbard</name></author><author><name sortKey="Wang, Ch" uniqKey="Wang C">CH Wang</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Dou, D" uniqKey="Dou D">D Dou</name></author><author><name sortKey="Shivakumar, B" uniqKey="Shivakumar B">B Shivakumar</name></author><author><name sortKey="Winter, S" uniqKey="Winter S">S Winter</name></author><author><name sortKey="Schlaak, Jf" uniqKey="Schlaak J">JF Schlaak</name></author><author><name sortKey="Lempicki, Ra" uniqKey="Lempicki R">RA Lempicki</name></author><author><name sortKey="Masur, H" uniqKey="Masur H">H Masur</name></author><author><name sortKey="Polis, M" uniqKey="Polis M">M Polis</name></author><author><name sortKey="Kottilil, S" uniqKey="Kottilil S">S Kottilil</name></author><author><name sortKey="Osinusi, A" uniqKey="Osinusi A">A Osinusi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meeker, Rb" uniqKey="Meeker R">RB Meeker</name></author><author><name sortKey="Poulton, W" uniqKey="Poulton W">W Poulton</name></author><author><name sortKey="Markovic Plese, S" uniqKey="Markovic Plese S">S Markovic-Plese</name></author><author><name sortKey="Hall, C" uniqKey="Hall C">C Hall</name></author><author><name sortKey="Robertson, K" uniqKey="Robertson K">K Robertson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Froldi, M" uniqKey="Froldi M">M Froldi</name></author><author><name sortKey="Castagna, A" uniqKey="Castagna A">A Castagna</name></author><author><name sortKey="Parma, M" uniqKey="Parma M">M Parma</name></author><author><name sortKey="Piona, A" uniqKey="Piona A">A Piona</name></author><author><name sortKey="Tedeschi, A" uniqKey="Tedeschi A">A Tedeschi</name></author><author><name sortKey="Miadonna, A" uniqKey="Miadonna A">A Miadonna</name></author><author><name sortKey="Lorini, M" uniqKey="Lorini M">M Lorini</name></author><author><name sortKey="Orazio, En" uniqKey="Orazio E">EN Orazio</name></author><author><name sortKey="Lazzarin, A" uniqKey="Lazzarin A">A Lazzarin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author><author><name sortKey="Roberts, Es" uniqKey="Roberts E">ES Roberts</name></author><author><name sortKey="Langford, D" uniqKey="Langford D">D Langford</name></author><author><name sortKey="Everall, I" uniqKey="Everall I">I Everall</name></author><author><name sortKey="Crews, L" uniqKey="Crews L">L Crews</name></author><author><name sortKey="Adame, A" uniqKey="Adame A">A Adame</name></author><author><name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E Rockenstein</name></author><author><name sortKey="Fox, Hs" uniqKey="Fox H">HS Fox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaw, Kn" uniqKey="Shaw K">KN Shaw</name></author><author><name sortKey="Commins, S" uniqKey="Commins S">S Commins</name></author><author><name sortKey="O Mara, Sm" uniqKey="O Mara S">SM O'Mara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Basselin, M" uniqKey="Basselin M">M Basselin</name></author><author><name sortKey="Ramadan, E" uniqKey="Ramadan E">E Ramadan</name></author><author><name sortKey="Igarashi, M" uniqKey="Igarashi M">M Igarashi</name></author><author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Kraft, Ad" uniqKey="Kraft A">AD Kraft</name></author><author><name sortKey="Harry, Gj" uniqKey="Harry G">GJ Harry</name></author><author><name sortKey="Rapoport, Si" uniqKey="Rapoport S">SI Rapoport</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mohri, I" uniqKey="Mohri I">I Mohri</name></author><author><name sortKey="Taniike, M" uniqKey="Taniike M">M Taniike</name></author><author><name sortKey="Taniguchi, H" uniqKey="Taniguchi H">H Taniguchi</name></author><author><name sortKey="Kanekiyo, T" uniqKey="Kanekiyo T">T Kanekiyo</name></author><author><name sortKey="Aritake, K" uniqKey="Aritake K">K Aritake</name></author><author><name sortKey="Inui, T" uniqKey="Inui T">T Inui</name></author><author><name sortKey="Fukumoto, N" uniqKey="Fukumoto N">N Fukumoto</name></author><author><name sortKey="Eguchi, N" uniqKey="Eguchi N">N Eguchi</name></author><author><name sortKey="Kushi, A" uniqKey="Kushi A">A Kushi</name></author><author><name sortKey="Sasai, H" uniqKey="Sasai H">H Sasai</name></author><author><name sortKey="Kanaoka, Y" uniqKey="Kanaoka Y">Y Kanaoka</name></author><author><name sortKey="Ozono, K" uniqKey="Ozono K">K Ozono</name></author><author><name sortKey="Narumiya, S" uniqKey="Narumiya S">S Narumiya</name></author><author><name sortKey="Suzuki, K" uniqKey="Suzuki K">K Suzuki</name></author><author><name sortKey="Urade, Y" uniqKey="Urade Y">Y Urade</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kalaria, Rn" uniqKey="Kalaria R">RN Kalaria</name></author><author><name sortKey="Pax, Ab" uniqKey="Pax A">AB Pax</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Horssen, J" uniqKey="Van Horssen J">J van Horssen</name></author><author><name sortKey="Bo, L" uniqKey="Bo L">L Bo</name></author><author><name sortKey="Dijkstra, Cd" uniqKey="Dijkstra C">CD Dijkstra</name></author><author><name sortKey="De Vries, He" uniqKey="De Vries H">HE de Vries</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Veznedaroglu, E" uniqKey="Veznedaroglu E">E Veznedaroglu</name></author><author><name sortKey="Van Bockstaele, Ej" uniqKey="Van Bockstaele E">EJ Van Bockstaele</name></author><author><name sortKey="O Connor, Mj" uniqKey="O Connor M">MJ O'Connor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gelman, Bb" uniqKey="Gelman B">BB Gelman</name></author><author><name sortKey="Chen, T" uniqKey="Chen T">T Chen</name></author><author><name sortKey="Lisinicchia, Jg" uniqKey="Lisinicchia J">JG Lisinicchia</name></author><author><name sortKey="Soukup, Vm" uniqKey="Soukup V">VM Soukup</name></author><author><name sortKey="Carmical, Jr" uniqKey="Carmical J">JR Carmical</name></author><author><name sortKey="Starkey, Jm" uniqKey="Starkey J">JM Starkey</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author><author><name sortKey="Commins, Dl" uniqKey="Commins D">DL Commins</name></author><author><name sortKey="Brandt, D" uniqKey="Brandt D">D Brandt</name></author><author><name sortKey="Grant, I" uniqKey="Grant I">I Grant</name></author><author><name sortKey="Singer, Ej" uniqKey="Singer E">EJ Singer</name></author><author><name sortKey="Levine, Aj" uniqKey="Levine A">AJ Levine</name></author><author><name sortKey="Miller, J" uniqKey="Miller J">J Miller</name></author><author><name sortKey="Winkler, Jm" uniqKey="Winkler J">JM Winkler</name></author><author><name sortKey="Fox, Hs" uniqKey="Fox H">HS Fox</name></author><author><name sortKey="Luxon, Ba" uniqKey="Luxon B">BA Luxon</name></author><author><name sortKey="Morgello, S" uniqKey="Morgello S">S Morgello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pocernich, Cb" uniqKey="Pocernich C">CB Pocernich</name></author><author><name sortKey="Poon, Hf" uniqKey="Poon H">HF Poon</name></author><author><name sortKey="Boyd Kimball, D" uniqKey="Boyd Kimball D">D Boyd-Kimball</name></author><author><name sortKey="Lynn, Bc" uniqKey="Lynn B">BC Lynn</name></author><author><name sortKey="Nath, A" uniqKey="Nath A">A Nath</name></author><author><name sortKey="Klein, Jb" uniqKey="Klein J">JB Klein</name></author><author><name sortKey="Butterfield, Da" uniqKey="Butterfield D">DA Butterfield</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Landi, S" uniqKey="Landi S">S Landi</name></author><author><name sortKey="Putignano, E" uniqKey="Putignano E">E Putignano</name></author><author><name sortKey="Boggio, Em" uniqKey="Boggio E">EM Boggio</name></author><author><name sortKey="Giustetto, M" uniqKey="Giustetto M">M Giustetto</name></author><author><name sortKey="Pizzorusso, T" uniqKey="Pizzorusso T">T Pizzorusso</name></author><author><name sortKey="Ratto, Gm" uniqKey="Ratto G">GM Ratto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barros, Cs" uniqKey="Barros C">CS Barros</name></author><author><name sortKey="Calabrese, B" uniqKey="Calabrese B">B Calabrese</name></author><author><name sortKey="Chamero, P" uniqKey="Chamero P">P Chamero</name></author><author><name sortKey="Roberts, Aj" uniqKey="Roberts A">AJ Roberts</name></author><author><name sortKey="Korzus, E" uniqKey="Korzus E">E Korzus</name></author><author><name sortKey="Lloyd, K" uniqKey="Lloyd K">K Lloyd</name></author><author><name sortKey="Stowers, L" uniqKey="Stowers L">L Stowers</name></author><author><name sortKey="Mayford, M" uniqKey="Mayford M">M Mayford</name></author><author><name sortKey="Halpain, S" uniqKey="Halpain S">S Halpain</name></author><author><name sortKey="Muller, U" uniqKey="Muller U">U Muller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grant, A" uniqKey="Grant A">A Grant</name></author><author><name sortKey="Hoops, D" uniqKey="Hoops D">D Hoops</name></author><author><name sortKey="Labelle Dumais, C" uniqKey="Labelle Dumais C">C Labelle-Dumais</name></author><author><name sortKey="Prevost, M" uniqKey="Prevost M">M Prevost</name></author><author><name sortKey="Rajabi, H" uniqKey="Rajabi H">H Rajabi</name></author><author><name sortKey="Kolb, B" uniqKey="Kolb B">B Kolb</name></author><author><name sortKey="Stewart, J" uniqKey="Stewart J">J Stewart</name></author><author><name sortKey="Arvanitogiannis, A" uniqKey="Arvanitogiannis A">A Arvanitogiannis</name></author><author><name sortKey="Flores, C" uniqKey="Flores C">C Flores</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benarroch, Ee" uniqKey="Benarroch E">EE Benarroch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szczesny, E" uniqKey="Szczesny E">E Szczesny</name></author><author><name sortKey="Slusarczyk, J" uniqKey="Slusarczyk J">J Slusarczyk</name></author><author><name sortKey="Glombik, K" uniqKey="Glombik K">K Glombik</name></author><author><name sortKey="Budziszewska, B" uniqKey="Budziszewska B">B Budziszewska</name></author><author><name sortKey="Kubera, M" uniqKey="Kubera M">M Kubera</name></author><author><name sortKey="Lason, W" uniqKey="Lason W">W Lason</name></author><author><name sortKey="Basta Kaim, A" uniqKey="Basta Kaim A">A Basta-Kaim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Von Bohlen Und Halbach, O" uniqKey="Von Bohlen Und Halbach O">O Von Bohlen Und Halbach</name></author><author><name sortKey="Unsicker, K" uniqKey="Unsicker K">K Unsicker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clemmons, Dr" uniqKey="Clemmons D">DR Clemmons</name></author><author><name sortKey="Busby, Wh" uniqKey="Busby W">WH Busby</name></author><author><name sortKey="Arai, T" uniqKey="Arai T">T Arai</name></author><author><name sortKey="Nam, Tj" uniqKey="Nam T">TJ Nam</name></author><author><name sortKey="Clarke, Jb" uniqKey="Clarke J">JB Clarke</name></author><author><name sortKey="Jones, Ji" uniqKey="Jones J">JI Jones</name></author><author><name sortKey="Ankrapp, Dk" uniqKey="Ankrapp D">DK Ankrapp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clemmons, Dr" uniqKey="Clemmons D">DR Clemmons</name></author><author><name sortKey="Jones, Ji" uniqKey="Jones J">JI Jones</name></author><author><name sortKey="Busby, Wh" uniqKey="Busby W">WH Busby</name></author><author><name sortKey="Wright, G" uniqKey="Wright G">G Wright</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Besset, V" uniqKey="Besset V">V Besset</name></author><author><name sortKey="Le Magueresse Battistoni, B" uniqKey="Le Magueresse Battistoni B">B Le Magueresse-Battistoni</name></author><author><name sortKey="Collette, J" uniqKey="Collette J">J Collette</name></author><author><name sortKey="Benahmed, M" uniqKey="Benahmed M">M Benahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scharla, Sh" uniqKey="Scharla S">SH Scharla</name></author><author><name sortKey="Strong, Dd" uniqKey="Strong D">DD Strong</name></author><author><name sortKey="Mohan, S" uniqKey="Mohan S">S Mohan</name></author><author><name sortKey="Chevalley, T" uniqKey="Chevalley T">T Chevalley</name></author><author><name sortKey="Linkhart, Ta" uniqKey="Linkhart T">TA Linkhart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Street, Me" uniqKey="Street M">ME Street</name></author><author><name sortKey="Ziveri, Ma" uniqKey="Ziveri M">MA Ziveri</name></author><author><name sortKey="Spaggiari, C" uniqKey="Spaggiari C">C Spaggiari</name></author><author><name sortKey="Viani, I" uniqKey="Viani I">I Viani</name></author><author><name sortKey="Volta, C" uniqKey="Volta C">C Volta</name></author><author><name sortKey="Grzincich, Gl" uniqKey="Grzincich G">GL Grzincich</name></author><author><name sortKey="Virdis, R" uniqKey="Virdis R">R Virdis</name></author><author><name sortKey="Bernasconi, S" uniqKey="Bernasconi S">S Bernasconi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tazearslan, C" uniqKey="Tazearslan C">C Tazearslan</name></author><author><name sortKey="Huang, J" uniqKey="Huang J">J Huang</name></author><author><name sortKey="Barzilai, N" uniqKey="Barzilai N">N Barzilai</name></author><author><name sortKey="Suh, Y" uniqKey="Suh Y">Y Suh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xi, Zq" uniqKey="Xi Z">ZQ Xi</name></author><author><name sortKey="Wang, Ly" uniqKey="Wang L">LY Wang</name></author><author><name sortKey="Sun, Jj" uniqKey="Sun J">JJ Sun</name></author><author><name sortKey="Liu, Xz" uniqKey="Liu X">XZ Liu</name></author><author><name sortKey="Zhu, X" uniqKey="Zhu X">X Zhu</name></author><author><name sortKey="Xiao, F" uniqKey="Xiao F">F Xiao</name></author><author><name sortKey="Guan, Lf" uniqKey="Guan L">LF Guan</name></author><author><name sortKey="Li, Jm" uniqKey="Li J">JM Li</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Wang, Xf" uniqKey="Wang X">XF Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Basseri, S" uniqKey="Basseri S">S Basseri</name></author><author><name sortKey="Lhotak, S" uniqKey="Lhotak S">S Lhotak</name></author><author><name sortKey="Fullerton, Md" uniqKey="Fullerton M">MD Fullerton</name></author><author><name sortKey="Palanivel, R" uniqKey="Palanivel R">R Palanivel</name></author><author><name sortKey="Jiang, H" uniqKey="Jiang H">H Jiang</name></author><author><name sortKey="Lynn, Eg" uniqKey="Lynn E">EG Lynn</name></author><author><name sortKey="Ford, Rj" uniqKey="Ford R">RJ Ford</name></author><author><name sortKey="Maclean, Kn" uniqKey="Maclean K">KN Maclean</name></author><author><name sortKey="Steinberg, Gr" uniqKey="Steinberg G">GR Steinberg</name></author><author><name sortKey="Austin, Rc" uniqKey="Austin R">RC Austin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murata, T" uniqKey="Murata T">T Murata</name></author><author><name sortKey="Sato, T" uniqKey="Sato T">T Sato</name></author><author><name sortKey="Kamoda, T" uniqKey="Kamoda T">T Kamoda</name></author><author><name sortKey="Moriyama, H" uniqKey="Moriyama H">H Moriyama</name></author><author><name sortKey="Kumazawa, Y" uniqKey="Kumazawa Y">Y Kumazawa</name></author><author><name sortKey="Hanada, N" uniqKey="Hanada N">N Hanada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Es" uniqKey="Park E">ES Park</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author><author><name sortKey="Ha, Tu" uniqKey="Ha T">TU Ha</name></author><author><name sortKey="Choi, Js" uniqKey="Choi J">JS Choi</name></author><author><name sortKey="Soo Hong, K" uniqKey="Soo Hong K">K Soo Hong</name></author><author><name sortKey="Rho, J" uniqKey="Rho J">J Rho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Cg" uniqKey="Park C">CG Park</name></author><author><name sortKey="Lee, Sy" uniqKey="Lee S">SY Lee</name></author><author><name sortKey="Kandala, G" uniqKey="Kandala G">G Kandala</name></author><author><name sortKey="Lee, Sy" uniqKey="Lee S">SY Lee</name></author><author><name sortKey="Choi, Y" uniqKey="Choi Y">Y Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mei, L" uniqKey="Mei L">L Mei</name></author><author><name sortKey="Xiong, Wc" uniqKey="Xiong W">WC Xiong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai Wing Sun, K" uniqKey="Lai Wing Sun K">K Lai Wing Sun</name></author><author><name sortKey="Correia, Jp" uniqKey="Correia J">JP Correia</name></author><author><name sortKey="Kennedy, Te" uniqKey="Kennedy T">TE Kennedy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Horn, Ke" uniqKey="Horn K">KE Horn</name></author><author><name sortKey="Glasgow, Sd" uniqKey="Glasgow S">SD Glasgow</name></author><author><name sortKey="Gobert, D" uniqKey="Gobert D">D Gobert</name></author><author><name sortKey="Bull, Sj" uniqKey="Bull S">SJ Bull</name></author><author><name sortKey="Luk, T" uniqKey="Luk T">T Luk</name></author><author><name sortKey="Girgis, J" uniqKey="Girgis J">J Girgis</name></author><author><name sortKey="Tremblay, Me" uniqKey="Tremblay M">ME Tremblay</name></author><author><name sortKey="Mceachern, D" uniqKey="Mceachern D">D McEachern</name></author><author><name sortKey="Bouchard, Jf" uniqKey="Bouchard J">JF Bouchard</name></author><author><name sortKey="Haber, M" uniqKey="Haber M">M Haber</name></author><author><name sortKey="Hamel, E" uniqKey="Hamel E">E Hamel</name></author><author><name sortKey="Krimpenfort, P" uniqKey="Krimpenfort P">P Krimpenfort</name></author><author><name sortKey="Murai, Kk" uniqKey="Murai K">KK Murai</name></author><author><name sortKey="Berns, A" uniqKey="Berns A">A Berns</name></author><author><name sortKey="Doucet, G" uniqKey="Doucet G">G Doucet</name></author><author><name sortKey="Chapman, Ca" uniqKey="Chapman C">CA Chapman</name></author><author><name sortKey="Ruthazer, Es" uniqKey="Ruthazer E">ES Ruthazer</name></author><author><name sortKey="Kennedy, Te" uniqKey="Kennedy T">TE Kennedy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Llambi, F" uniqKey="Llambi F">F Llambi</name></author><author><name sortKey="Lourenco, Fc" uniqKey="Lourenco F">FC Lourenco</name></author><author><name sortKey="Gozuacik, D" uniqKey="Gozuacik D">D Gozuacik</name></author><author><name sortKey="Guix, C" uniqKey="Guix C">C Guix</name></author><author><name sortKey="Pays, L" uniqKey="Pays L">L Pays</name></author><author><name sortKey="Del Rio, G" uniqKey="Del Rio G">G Del Rio</name></author><author><name sortKey="Kimchi, A" uniqKey="Kimchi A">A Kimchi</name></author><author><name sortKey="Mehlen, P" uniqKey="Mehlen P">P Mehlen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barallobre, Mj" uniqKey="Barallobre M">MJ Barallobre</name></author><author><name sortKey="Pascual, M" uniqKey="Pascual M">M Pascual</name></author><author><name sortKey="Del Rio, Ja" uniqKey="Del Rio J">JA Del Rio</name></author><author><name sortKey="Soriano, E" uniqKey="Soriano E">E Soriano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bradford, D" uniqKey="Bradford D">D Bradford</name></author><author><name sortKey="Faull, Rl" uniqKey="Faull R">RL Faull</name></author><author><name sortKey="Curtis, Ma" uniqKey="Curtis M">MA Curtis</name></author><author><name sortKey="Cooper, Hm" uniqKey="Cooper H">HM Cooper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Staquicini, Fi" uniqKey="Staquicini F">FI Staquicini</name></author><author><name sortKey="Dias Neto, E" uniqKey="Dias Neto E">E Dias-Neto</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author><author><name sortKey="Snyder, Ey" uniqKey="Snyder E">EY Snyder</name></author><author><name sortKey="Sidman, Rl" uniqKey="Sidman R">RL Sidman</name></author><author><name sortKey="Pasqualini, R" uniqKey="Pasqualini R">R Pasqualini</name></author><author><name sortKey="Arap, W" uniqKey="Arap W">W Arap</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cayre, M" uniqKey="Cayre M">M Cayre</name></author><author><name sortKey="Courtes, S" uniqKey="Courtes S">S Courtes</name></author><author><name sortKey="Martineau, F" uniqKey="Martineau F">F Martineau</name></author><author><name sortKey="Giordano, M" uniqKey="Giordano M">M Giordano</name></author><author><name sortKey="Arnaud, K" uniqKey="Arnaud K">K Arnaud</name></author><author><name sortKey="Zamaron, A" uniqKey="Zamaron A">A Zamaron</name></author><author><name sortKey="Durbec, P" uniqKey="Durbec P">P Durbec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peng, H" uniqKey="Peng H">H Peng</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L Sun</name></author><author><name sortKey="Jia, B" uniqKey="Jia B">B Jia</name></author><author><name sortKey="Lan, X" uniqKey="Lan X">X Lan</name></author><author><name sortKey="Zhu, B" uniqKey="Zhu B">B Zhu</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name></author><author><name sortKey="Zheng, J" uniqKey="Zheng J">J Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Swiech, L" uniqKey="Swiech L">L Swiech</name></author><author><name sortKey="Perycz, M" uniqKey="Perycz M">M Perycz</name></author><author><name sortKey="Malik, A" uniqKey="Malik A">A Malik</name></author><author><name sortKey="Jaworski, J" uniqKey="Jaworski J">J Jaworski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Germain, M" uniqKey="Germain M">M Germain</name></author><author><name sortKey="Nguyen, Ap" uniqKey="Nguyen A">AP Nguyen</name></author><author><name sortKey="Khacho, M" uniqKey="Khacho M">M Khacho</name></author><author><name sortKey="Patten, Da" uniqKey="Patten D">DA Patten</name></author><author><name sortKey="Screaton, Ra" uniqKey="Screaton R">RA Screaton</name></author><author><name sortKey="Park, Ds" uniqKey="Park D">DS Park</name></author><author><name sortKey="Slack, Rs" uniqKey="Slack R">RS Slack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cross, Da" uniqKey="Cross D">DA Cross</name></author><author><name sortKey="Alessi, Dr" uniqKey="Alessi D">DR Alessi</name></author><author><name sortKey="Cohen, P" uniqKey="Cohen P">P Cohen</name></author><author><name sortKey="Andjelkovich, M" uniqKey="Andjelkovich M">M Andjelkovich</name></author><author><name sortKey="Hemmings, Ba" uniqKey="Hemmings B">BA Hemmings</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mocchetti, I" uniqKey="Mocchetti I">I Mocchetti</name></author><author><name sortKey="Bachis, A" uniqKey="Bachis A">A Bachis</name></author><author><name sortKey="Campbell, La" uniqKey="Campbell L">LA Campbell</name></author><author><name sortKey="Avdoshina, V" uniqKey="Avdoshina V">V Avdoshina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woodbury, Me" uniqKey="Woodbury M">ME Woodbury</name></author><author><name sortKey="Ikezu, T" uniqKey="Ikezu T">T Ikezu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fields, J" uniqKey="Fields J">J Fields</name></author><author><name sortKey="Dumaop, W" uniqKey="Dumaop W">W Dumaop</name></author><author><name sortKey="Langford, Td" uniqKey="Langford T">TD Langford</name></author><author><name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E Rockenstein</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author><author><name sortKey="Cammalleri, M" uniqKey="Cammalleri M">M Cammalleri</name></author><author><name sortKey="Berton, F" uniqKey="Berton F">F Berton</name></author><author><name sortKey="Simpson, C" uniqKey="Simpson C">C Simpson</name></author><author><name sortKey="Lutjens, R" uniqKey="Lutjens R">R Lutjens</name></author><author><name sortKey="Bloom, Fe" uniqKey="Bloom F">FE Bloom</name></author><author><name sortKey="Francesconi, W" uniqKey="Francesconi W">W Francesconi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cammalleri, M" uniqKey="Cammalleri M">M Cammalleri</name></author><author><name sortKey="Lutjens, R" uniqKey="Lutjens R">R Lutjens</name></author><author><name sortKey="Berton, F" uniqKey="Berton F">F Berton</name></author><author><name sortKey="King, Ar" uniqKey="King A">AR King</name></author><author><name sortKey="Simpson, C" uniqKey="Simpson C">C Simpson</name></author><author><name sortKey="Francesconi, W" uniqKey="Francesconi W">W Francesconi</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Sj" uniqKey="Tang S">SJ Tang</name></author><author><name sortKey="Reis, G" uniqKey="Reis G">G Reis</name></author><author><name sortKey="Kang, H" uniqKey="Kang H">H Kang</name></author><author><name sortKey="Gingras, Ac" uniqKey="Gingras A">AC Gingras</name></author><author><name sortKey="Sonenberg, N" uniqKey="Sonenberg N">N Sonenberg</name></author><author><name sortKey="Schuman, Em" uniqKey="Schuman E">EM Schuman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diaz Ruiz, O" uniqKey="Diaz Ruiz O">O Diaz-Ruiz</name></author><author><name sortKey="Navarro, L" uniqKey="Navarro L">L Navarro</name></author><author><name sortKey="Mendez Diaz, M" uniqKey="Mendez Diaz M">M Mendez-Diaz</name></author><author><name sortKey="Galicia, O" uniqKey="Galicia O">O Galicia</name></author><author><name sortKey="Elder, Jh" uniqKey="Elder J">JH Elder</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author><author><name sortKey="Drucker Colin, R" uniqKey="Drucker Colin R">R Drucker-Colin</name></author><author><name sortKey="Prospero Garcia, O" uniqKey="Prospero Garcia O">O Prospero-Garcia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Veldhoven, Pp" uniqKey="Van Veldhoven P">PP Van Veldhoven</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ivashchenko, O" uniqKey="Ivashchenko O">O Ivashchenko</name></author><author><name sortKey="Van Veldhoven, Pp" uniqKey="Van Veldhoven P">PP Van Veldhoven</name></author><author><name sortKey="Brees, C" uniqKey="Brees C">C Brees</name></author><author><name sortKey="Ho, Ys" uniqKey="Ho Y">YS Ho</name></author><author><name sortKey="Terlecky, Sr" uniqKey="Terlecky S">SR Terlecky</name></author><author><name sortKey="Fransen, M" uniqKey="Fransen M">M Fransen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Louboutin, Jp" uniqKey="Louboutin J">JP Louboutin</name></author><author><name sortKey="Agrawal, L" uniqKey="Agrawal L">L Agrawal</name></author><author><name sortKey="Reyes, Ba" uniqKey="Reyes B">BA Reyes</name></author><author><name sortKey="Van Bockstaele, Ej" uniqKey="Van Bockstaele E">EJ Van Bockstaele</name></author><author><name sortKey="Strayer, Ds" uniqKey="Strayer D">DS Strayer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author><author><name sortKey="Ge, N" uniqKey="Ge N">N Ge</name></author><author><name sortKey="Mucke, L" uniqKey="Mucke L">L Mucke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cutler, Rg" uniqKey="Cutler R">RG Cutler</name></author><author><name sortKey="Haughey, Nj" uniqKey="Haughey N">NJ Haughey</name></author><author><name sortKey="Tammara, A" uniqKey="Tammara A">A Tammara</name></author><author><name sortKey="Mcarthur, Jc" uniqKey="Mcarthur J">JC McArthur</name></author><author><name sortKey="Nath, A" uniqKey="Nath A">A Nath</name></author><author><name sortKey="Reid, R" uniqKey="Reid R">R Reid</name></author><author><name sortKey="Vargas, Dl" uniqKey="Vargas D">DL Vargas</name></author><author><name sortKey="Pardo, Ca" uniqKey="Pardo C">CA Pardo</name></author><author><name sortKey="Mattson, Mp" uniqKey="Mattson M">MP Mattson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deicken, Rf" uniqKey="Deicken R">RF Deicken</name></author><author><name sortKey="Hubesch, B" uniqKey="Hubesch B">B Hubesch</name></author><author><name sortKey="Jensen, Pc" uniqKey="Jensen P">PC Jensen</name></author><author><name sortKey="Sappey Marinier, D" uniqKey="Sappey Marinier D">D Sappey-Marinier</name></author><author><name sortKey="Krell, P" uniqKey="Krell P">P Krell</name></author><author><name sortKey="Wisniewski, A" uniqKey="Wisniewski A">A Wisniewski</name></author><author><name sortKey="Vanderburg, D" uniqKey="Vanderburg D">D Vanderburg</name></author><author><name sortKey="Parks, R" uniqKey="Parks R">R Parks</name></author><author><name sortKey="Fein, G" uniqKey="Fein G">G Fein</name></author><author><name sortKey="Weiner, Mw" uniqKey="Weiner M">MW Weiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uzasci, L" uniqKey="Uzasci L">L Uzasci</name></author><author><name sortKey="Nath, A" uniqKey="Nath A">A Nath</name></author><author><name sortKey="Cotter, R" uniqKey="Cotter R">R Cotter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Margottin, F" uniqKey="Margottin F">F Margottin</name></author><author><name sortKey="Bour, Sp" uniqKey="Bour S">SP Bour</name></author><author><name sortKey="Durand, H" uniqKey="Durand H">H Durand</name></author><author><name sortKey="Selig, L" uniqKey="Selig L">L Selig</name></author><author><name sortKey="Benichou, S" uniqKey="Benichou S">S Benichou</name></author><author><name sortKey="Richard, V" uniqKey="Richard V">V Richard</name></author><author><name sortKey="Thomas, D" uniqKey="Thomas D">D Thomas</name></author><author><name sortKey="Strebel, K" uniqKey="Strebel K">K Strebel</name></author><author><name sortKey="Benarous, R" uniqKey="Benarous R">R Benarous</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Yp" uniqKey="Li Y">YP Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bisikirska, Bc" uniqKey="Bisikirska B">BC Bisikirska</name></author><author><name sortKey="Adam, Sj" uniqKey="Adam S">SJ Adam</name></author><author><name sortKey="Alvarez, Mj" uniqKey="Alvarez M">MJ Alvarez</name></author><author><name sortKey="Rajbhandari, P" uniqKey="Rajbhandari P">P Rajbhandari</name></author><author><name sortKey="Cox, R" uniqKey="Cox R">R Cox</name></author><author><name sortKey="Lefebvre, C" uniqKey="Lefebvre C">C Lefebvre</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K Wang</name></author><author><name sortKey="Rieckhof, Ge" uniqKey="Rieckhof G">GE Rieckhof</name></author><author><name sortKey="Felsher, Dw" uniqKey="Felsher D">DW Felsher</name></author><author><name sortKey="Califano, A" uniqKey="Califano A">A Califano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Conti, B" uniqKey="Conti B">B Conti</name></author><author><name sortKey="Maier, R" uniqKey="Maier R">R Maier</name></author><author><name sortKey="Barr, Am" uniqKey="Barr A">AM Barr</name></author><author><name sortKey="Morale, Mc" uniqKey="Morale M">MC Morale</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author><author><name sortKey="Bilbe, G" uniqKey="Bilbe G">G Bilbe</name></author><author><name sortKey="Hoyer, D" uniqKey="Hoyer D">D Hoyer</name></author><author><name sortKey="Bartfai, T" uniqKey="Bartfai T">T Bartfai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Yc" uniqKey="Huang Y">YC Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Letendre, S" uniqKey="Letendre S">S Letendre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nabha, L" uniqKey="Nabha L">L Nabha</name></author><author><name sortKey="Duong, L" uniqKey="Duong L">L Duong</name></author><author><name sortKey="Timpone, J" uniqKey="Timpone J">J Timpone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schifitto, G" uniqKey="Schifitto G">G Schifitto</name></author><author><name sortKey="Navia, Ba" uniqKey="Navia B">BA Navia</name></author><author><name sortKey="Yiannoutsos, Ct" uniqKey="Yiannoutsos C">CT Yiannoutsos</name></author><author><name sortKey="Marra, Cm" uniqKey="Marra C">CM Marra</name></author><author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name></author><author><name sortKey="Ernst, T" uniqKey="Ernst T">T Ernst</name></author><author><name sortKey="Jarvik, Jg" uniqKey="Jarvik J">JG Jarvik</name></author><author><name sortKey="Miller, En" uniqKey="Miller E">EN Miller</name></author><author><name sortKey="Singer, Ej" uniqKey="Singer E">EJ Singer</name></author><author><name sortKey="Ellis, Rj" uniqKey="Ellis R">RJ Ellis</name></author><author><name sortKey="Kolson, Dl" uniqKey="Kolson D">DL Kolson</name></author><author><name sortKey="Simpson, D" uniqKey="Simpson D">D Simpson</name></author><author><name sortKey="Nath, A" uniqKey="Nath A">A Nath</name></author><author><name sortKey="Berger, J" uniqKey="Berger J">J Berger</name></author><author><name sortKey="Shriver, Sl" uniqKey="Shriver S">SL Shriver</name></author><author><name sortKey="Millar, Ll" uniqKey="Millar L">LL Millar</name></author><author><name sortKey="Colquhoun, D" uniqKey="Colquhoun D">D Colquhoun</name></author><author><name sortKey="Lenkinski, R" uniqKey="Lenkinski R">R Lenkinski</name></author><author><name sortKey="Gonzalez, Rg" uniqKey="Gonzalez R">RG Gonzalez</name></author><author><name sortKey="Lipton, Sa" uniqKey="Lipton S">SA Lipton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y Zhao</name></author><author><name sortKey="Navia, Ba" uniqKey="Navia B">BA Navia</name></author><author><name sortKey="Marra, Cm" uniqKey="Marra C">CM Marra</name></author><author><name sortKey="Singer, Ej" uniqKey="Singer E">EJ Singer</name></author><author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name></author><author><name sortKey="Berger, J" uniqKey="Berger J">J Berger</name></author><author><name sortKey="Ellis, Rj" uniqKey="Ellis R">RJ Ellis</name></author><author><name sortKey="Kolson, Dl" uniqKey="Kolson D">DL Kolson</name></author><author><name sortKey="Simpson, D" uniqKey="Simpson D">D Simpson</name></author><author><name sortKey="Miller, En" uniqKey="Miller E">EN Miller</name></author><author><name sortKey="Lipton, Sa" uniqKey="Lipton S">SA Lipton</name></author><author><name sortKey="Evans, Sr" uniqKey="Evans S">SR Evans</name></author><author><name sortKey="Schifitto, G" uniqKey="Schifitto G">G Schifitto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fabbrini, G" uniqKey="Fabbrini G">G Fabbrini</name></author><author><name sortKey="Abbruzzese, G" uniqKey="Abbruzzese G">G Abbruzzese</name></author><author><name sortKey="Marconi, S" uniqKey="Marconi S">S Marconi</name></author><author><name sortKey="Zappia, M" uniqKey="Zappia M">M Zappia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shulman, Ki" uniqKey="Shulman K">KI Shulman</name></author><author><name sortKey="Herrmann, N" uniqKey="Herrmann N">N Herrmann</name></author><author><name sortKey="Walker, Se" uniqKey="Walker S">SE Walker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Breitbart, W" uniqKey="Breitbart W">W Breitbart</name></author><author><name sortKey="Rosenfeld, B" uniqKey="Rosenfeld B">B Rosenfeld</name></author><author><name sortKey="Kaim, M" uniqKey="Kaim M">M Kaim</name></author><author><name sortKey="Funesti Esch, J" uniqKey="Funesti Esch J">J Funesti-Esch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fiala, M" uniqKey="Fiala M">M Fiala</name></author><author><name sortKey="Liu, Qn" uniqKey="Liu Q">QN Liu</name></author><author><name sortKey="Sayre, J" uniqKey="Sayre J">J Sayre</name></author><author><name sortKey="Pop, V" uniqKey="Pop V">V Pop</name></author><author><name sortKey="Brahmandam, V" uniqKey="Brahmandam V">V Brahmandam</name></author><author><name sortKey="Graves, Mc" uniqKey="Graves M">MC Graves</name></author><author><name sortKey="Vinters, Hv" uniqKey="Vinters H">HV Vinters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graves, Mc" uniqKey="Graves M">MC Graves</name></author><author><name sortKey="Fiala, M" uniqKey="Fiala M">M Fiala</name></author><author><name sortKey="Dinglasan, La" uniqKey="Dinglasan L">LA Dinglasan</name></author><author><name sortKey="Liu, Nq" uniqKey="Liu N">NQ Liu</name></author><author><name sortKey="Sayre, J" uniqKey="Sayre J">J Sayre</name></author><author><name sortKey="Chiappelli, F" uniqKey="Chiappelli F">F Chiappelli</name></author><author><name sortKey="Van Kooten, C" uniqKey="Van Kooten C">C van Kooten</name></author><author><name sortKey="Vinters, Hv" uniqKey="Vinters H">HV Vinters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pettersen, Fo" uniqKey="Pettersen F">FO Pettersen</name></author><author><name sortKey="Torheim, Ea" uniqKey="Torheim E">EA Torheim</name></author><author><name sortKey="Dahm, Ae" uniqKey="Dahm A">AE Dahm</name></author><author><name sortKey="Aaberge, Is" uniqKey="Aaberge I">IS Aaberge</name></author><author><name sortKey="Lind, A" uniqKey="Lind A">A Lind</name></author><author><name sortKey="Holm, M" uniqKey="Holm M">M Holm</name></author><author><name sortKey="Aandahl, Em" uniqKey="Aandahl E">EM Aandahl</name></author><author><name sortKey="Sandset, Pm" uniqKey="Sandset P">PM Sandset</name></author><author><name sortKey="Tasken, K" uniqKey="Tasken K">K Tasken</name></author><author><name sortKey="Kvale, D" uniqKey="Kvale D">D Kvale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ebert, Ad" uniqKey="Ebert A">AD Ebert</name></author><author><name sortKey="Beres, Aj" uniqKey="Beres A">AJ Beres</name></author><author><name sortKey="Barber, Ae" uniqKey="Barber A">AE Barber</name></author><author><name sortKey="Svendsen, Cn" uniqKey="Svendsen C">CN Svendsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quesada, A" uniqKey="Quesada A">A Quesada</name></author><author><name sortKey="Lee, By" uniqKey="Lee B">BY Lee</name></author><author><name sortKey="Micevych, Pe" uniqKey="Micevych P">PE Micevych</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carro, E" uniqKey="Carro E">E Carro</name></author><author><name sortKey="Trejo, Jl" uniqKey="Trejo J">JL Trejo</name></author><author><name sortKey="Gerber, A" uniqKey="Gerber A">A Gerber</name></author><author><name sortKey="Loetscher, H" uniqKey="Loetscher H">H Loetscher</name></author><author><name sortKey="Torrado, J" uniqKey="Torrado J">J Torrado</name></author><author><name sortKey="Metzger, F" uniqKey="Metzger F">F Metzger</name></author><author><name sortKey="Torres Aleman, I" uniqKey="Torres Aleman I">I Torres-Aleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carro, E" uniqKey="Carro E">E Carro</name></author><author><name sortKey="Trejo, Jl" uniqKey="Trejo J">JL Trejo</name></author><author><name sortKey="Gomez Isla, T" uniqKey="Gomez Isla T">T Gomez-Isla</name></author><author><name sortKey="Leroith, D" uniqKey="Leroith D">D LeRoith</name></author><author><name sortKey="Torres Aleman, I" uniqKey="Torres Aleman I">I Torres-Aleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassil, F" uniqKey="Bassil F">F Bassil</name></author><author><name sortKey="Fernagut, Po" uniqKey="Fernagut P">PO Fernagut</name></author><author><name sortKey="Bezard, E" uniqKey="Bezard E">E Bezard</name></author><author><name sortKey="Meissner, Wg" uniqKey="Meissner W">WG Meissner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, Yj" uniqKey="Kang Y">YJ Kang</name></author><author><name sortKey="Digicaylioglu, M" uniqKey="Digicaylioglu M">M Digicaylioglu</name></author><author><name sortKey="Russo, R" uniqKey="Russo R">R Russo</name></author><author><name sortKey="Kaul, M" uniqKey="Kaul M">M Kaul</name></author><author><name sortKey="Achim, Cl" uniqKey="Achim C">CL Achim</name></author><author><name sortKey="Fletcher, L" uniqKey="Fletcher L">L Fletcher</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author><author><name sortKey="Lipton, Sa" uniqKey="Lipton S">SA Lipton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cabou, C" uniqKey="Cabou C">C Cabou</name></author><author><name sortKey="Campistron, G" uniqKey="Campistron G">G Campistron</name></author><author><name sortKey="Marsollier, N" uniqKey="Marsollier N">N Marsollier</name></author><author><name sortKey="Leloup, C" uniqKey="Leloup C">C Leloup</name></author><author><name sortKey="Cruciani Guglielmacci, C" uniqKey="Cruciani Guglielmacci C">C Cruciani-Guglielmacci</name></author><author><name sortKey="Penicaud, L" uniqKey="Penicaud L">L Penicaud</name></author><author><name sortKey="Drucker, Dj" uniqKey="Drucker D">DJ Drucker</name></author><author><name sortKey="Magnan, C" uniqKey="Magnan C">C Magnan</name></author><author><name sortKey="Burcelin, R" uniqKey="Burcelin R">R Burcelin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Duffy, Kb" uniqKey="Duffy K">KB Duffy</name></author><author><name sortKey="Ottinger, Ma" uniqKey="Ottinger M">MA Ottinger</name></author><author><name sortKey="Ray, B" uniqKey="Ray B">B Ray</name></author><author><name sortKey="Bailey, Ja" uniqKey="Bailey J">JA Bailey</name></author><author><name sortKey="Holloway, Hw" uniqKey="Holloway H">HW Holloway</name></author><author><name sortKey="Tweedie, D" uniqKey="Tweedie D">D Tweedie</name></author><author><name sortKey="Perry, T" uniqKey="Perry T">T Perry</name></author><author><name sortKey="Mattson, Mp" uniqKey="Mattson M">MP Mattson</name></author><author><name sortKey="Kapogiannis, D" uniqKey="Kapogiannis D">D Kapogiannis</name></author><author><name sortKey="Sambamurti, K" uniqKey="Sambamurti K">K Sambamurti</name></author><author><name sortKey="Lahiri, Dk" uniqKey="Lahiri D">DK Lahiri</name></author><author><name sortKey="Greig, Nh" uniqKey="Greig N">NH Greig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertilsson, G" uniqKey="Bertilsson G">G Bertilsson</name></author><author><name sortKey="Patrone, C" uniqKey="Patrone C">C Patrone</name></author><author><name sortKey="Zachrisson, O" uniqKey="Zachrisson O">O Zachrisson</name></author><author><name sortKey="Andersson, A" uniqKey="Andersson A">A Andersson</name></author><author><name sortKey="Dannaeus, K" uniqKey="Dannaeus K">K Dannaeus</name></author><author><name sortKey="Heidrich, J" uniqKey="Heidrich J">J Heidrich</name></author><author><name sortKey="Kortesmaa, J" uniqKey="Kortesmaa J">J Kortesmaa</name></author><author><name sortKey="Mercer, A" uniqKey="Mercer A">A Mercer</name></author><author><name sortKey="Nielsen, E" uniqKey="Nielsen E">E Nielsen</name></author><author><name sortKey="Ronnholm, H" uniqKey="Ronnholm H">H Ronnholm</name></author><author><name sortKey="Wikstrom, L" uniqKey="Wikstrom L">L Wikstrom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harkavyi, A" uniqKey="Harkavyi A">A Harkavyi</name></author><author><name sortKey="Abuirmeileh, A" uniqKey="Abuirmeileh A">A Abuirmeileh</name></author><author><name sortKey="Lever, R" uniqKey="Lever R">R Lever</name></author><author><name sortKey="Kingsbury, Ae" uniqKey="Kingsbury A">AE Kingsbury</name></author><author><name sortKey="Biggs, Cs" uniqKey="Biggs C">CS Biggs</name></author><author><name sortKey="Whitton, Ps" uniqKey="Whitton P">PS Whitton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gespach, C" uniqKey="Gespach C">C Gespach</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, C" uniqKey="Deng C">C Deng</name></author><author><name sortKey="Pan, B" uniqKey="Pan B">B Pan</name></author><author><name sortKey="Engel, M" uniqKey="Engel M">M Engel</name></author><author><name sortKey="Huang, Xf" uniqKey="Huang X">XF Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Contreras, X" uniqKey="Contreras X">X Contreras</name></author><author><name sortKey="Barboric, M" uniqKey="Barboric M">M Barboric</name></author><author><name sortKey="Lenasi, T" uniqKey="Lenasi T">T Lenasi</name></author><author><name sortKey="Peterlin, Bm" uniqKey="Peterlin B">BM Peterlin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doyon, G" uniqKey="Doyon G">G Doyon</name></author><author><name sortKey="Sobolewski, Md" uniqKey="Sobolewski M">MD Sobolewski</name></author><author><name sortKey="Huber, K" uniqKey="Huber K">K Huber</name></author><author><name sortKey="Mcmahon, D" uniqKey="Mcmahon D">D McMahon</name></author><author><name sortKey="Mellors, Jw" uniqKey="Mellors J">JW Mellors</name></author><author><name sortKey="Sluis Cremer, N" uniqKey="Sluis Cremer N">N Sluis-Cremer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patrick, C" uniqKey="Patrick C">C Patrick</name></author><author><name sortKey="Crews, L" uniqKey="Crews L">L Crews</name></author><author><name sortKey="Desplats, P" uniqKey="Desplats P">P Desplats</name></author><author><name sortKey="Dumaop, W" uniqKey="Dumaop W">W Dumaop</name></author><author><name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E Rockenstein</name></author><author><name sortKey="Achim, Cl" uniqKey="Achim C">CL Achim</name></author><author><name sortKey="Everall, Ip" uniqKey="Everall I">IP Everall</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahmed, Sh" uniqKey="Ahmed S">SH Ahmed</name></author><author><name sortKey="Lutjens, R" uniqKey="Lutjens R">R Lutjens</name></author><author><name sortKey="Van Der Stap, Ld" uniqKey="Van Der Stap L">LD van der Stap</name></author><author><name sortKey="Lekic, D" uniqKey="Lekic D">D Lekic</name></author><author><name sortKey="Romano Spica, V" uniqKey="Romano Spica V">V Romano-Spica</name></author><author><name sortKey="Morales, M" uniqKey="Morales M">M Morales</name></author><author><name sortKey="Koob, Gf" uniqKey="Koob G">GF Koob</name></author><author><name sortKey="Repunte Canonigo, V" uniqKey="Repunte Canonigo V">V Repunte-Canonigo</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Repunte Canonigo, V" uniqKey="Repunte Canonigo V">V Repunte-Canonigo</name></author><author><name sortKey="Van Der Stap, Ld" uniqKey="Van Der Stap L">LD van der Stap</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Sabino, V" uniqKey="Sabino V">V Sabino</name></author><author><name sortKey="Wagner, U" uniqKey="Wagner U">U Wagner</name></author><author><name sortKey="Zorrilla, Ep" uniqKey="Zorrilla E">EP Zorrilla</name></author><author><name sortKey="Schumann, G" uniqKey="Schumann G">G Schumann</name></author><author><name sortKey="Roberts, Aj" uniqKey="Roberts A">AJ Roberts</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Repunte Canonigo, V" uniqKey="Repunte Canonigo V">V Repunte-Canonigo</name></author><author><name sortKey="Lutjens, R" uniqKey="Lutjens R">R Lutjens</name></author><author><name sortKey="Van Der Stap, Ld" uniqKey="Van Der Stap L">LD van der Stap</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Repunte Canonigo, V" uniqKey="Repunte Canonigo V">V Repunte-Canonigo</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Lefebvre, C" uniqKey="Lefebvre C">C Lefebvre</name></author><author><name sortKey="Kawamura, T" uniqKey="Kawamura T">T Kawamura</name></author><author><name sortKey="Kreifeldt, M" uniqKey="Kreifeldt M">M Kreifeldt</name></author><author><name sortKey="Basson, O" uniqKey="Basson O">O Basson</name></author><author><name sortKey="Roberts, Aj" uniqKey="Roberts A">AJ Roberts</name></author><author><name sortKey="Sanna, Pp" uniqKey="Sanna P">PP Sanna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Livak, Kj" uniqKey="Livak K">KJ Livak</name></author><author><name sortKey="Schmittgen, Td" uniqKey="Schmittgen T">TD Schmittgen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Douglas, Rj" uniqKey="Douglas R">RJ Douglas</name></author><author><name sortKey="Raphelson, Ac" uniqKey="Raphelson A">AC Raphelson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article" xml:lang="en"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Neurodegener</journal-id><journal-id journal-id-type="iso-abbrev">Mol Neurodegener</journal-id><journal-title-group><journal-title>Molecular Neurodegeneration</journal-title></journal-title-group><issn pub-type="epub">1750-1326</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24980976</article-id><article-id pub-id-type="pmc">4107468</article-id><article-id pub-id-type="publisher-id">1750-1326-9-26</article-id><article-id pub-id-type="doi">10.1186/1750-1326-9-26</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats</article-title></title-group><contrib-group><contrib contrib-type="author" id="A1"><name><surname>Repunte-Canonigo</surname><given-names>Vez</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>Canonigo@scripps.edu</email></contrib><contrib contrib-type="author" id="A2"><name><surname>Lefebvre</surname><given-names>Celine</given-names></name><xref ref-type="aff" rid="I3">3</xref><email>celine.lefebvre@gustaveroussy.fr</email></contrib><contrib contrib-type="author" id="A3"><name><surname>George</surname><given-names>Olivier</given-names></name><xref ref-type="aff" rid="I2">2</xref><email>ogeorge@scripps.edu</email></contrib><contrib contrib-type="author" id="A4"><name><surname>Kawamura</surname><given-names>Tomoya</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>tomoya@scripps.edu</email></contrib><contrib contrib-type="author" id="A5"><name><surname>Morales</surname><given-names>Marisela</given-names></name><xref ref-type="aff" rid="I4">4</xref><email>marisela.morales@nih.gov</email></contrib><contrib contrib-type="author" id="A6"><name><surname>Koob</surname><given-names>George F</given-names></name><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I5">5</xref><email>george.koob@nih.gov</email></contrib><contrib contrib-type="author" id="A7"><name><surname>Califano</surname><given-names>Andrea</given-names></name><xref ref-type="aff" rid="I6">6</xref><email>ac2248@columbia.edu</email></contrib><contrib contrib-type="author" id="A8"><name><surname>Masliah</surname><given-names>Eliezer</given-names></name><xref ref-type="aff" rid="I7">7</xref><email>emasliah@ucsd.edu</email></contrib><contrib contrib-type="author" corresp="yes" id="A9"><name><surname>Sanna</surname><given-names>Pietro Paolo</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>psanna@scripps.edu</email></contrib></contrib-group><aff id="I1"><label>1</label>Molecular and Cellular Neuroscience Department, La Jolla, CA 92037, USA</aff><aff id="I2"><label>2</label>Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA</aff><aff id="I3"><label>3</label>INSERM Unit U981, Gustave Roussy Institute, Villejuif, France</aff><aff id="I4"><label>4</label>National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, Baltimore, MD 21224, USA</aff><aff id="I5"><label>5</label>National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Ln, Rockville, MD 20852, USA</aff><aff id="I6"><label>6</label>Department of Systems Biology, Columbia University, New York, New York 10032, USA</aff><aff id="I7"><label>7</label>Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093, USA</aff><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>1</day><month>7</month><year>2014</year></pub-date><volume>9</volume><fpage>26</fpage><lpage>26</lpage><history><date date-type="received"><day>4</day><month>3</month><year>2014</year></date><date date-type="accepted"><day>19</day><month>6</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 Repunte-Canonigo et al.; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Repunte-Canonigo et al.; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><self-uri xlink:href="http://www.molecularneurodegeneration.com/content/9/1/26"></self-uri><abstract><sec><title>Background</title><p>A thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS.</p></sec><sec><title>Results</title><p>We report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 proteins are expressed under the control of the viral LTR promoter in disease-relevant cells including microglia and astrocytes. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis. Gene expression changes observed are consistent with astrogliosis and microgliosis and include evidence of inflammation and cell proliferation. Among the genes with increased expression in HIV-1 Tg rats was the interferon stimulated gene 15 (ISG-15), which was previously shown to be increased in the cerebrospinal fluid (CSF) of HIV patients and to correlate with neuropsychological impairment and neuropathology, and prostaglandin D2 (PGD2) synthase (Ptgds), which has been associated with immune activation and the induction of astrogliosis and microgliosis. GSEA-based pathway analysis highlighted a broad dysregulation of genes involved in neuronal trophism and neurodegenerative disorders. Among the latter are genesets associated with Huntington’s disease, Parkinson’s disease, mitochondrial, peroxisome function, and synaptic trophism and plasticity, such as IGF, ErbB and netrin signaling and the PI3K signal transduction pathway, a mediator of neural plasticity and of a vast array of trophic signals. Additionally, gene expression analyses also show altered lipid metabolism and peroxisomes dysfunction. Supporting the functional significance of these gene expression alterations, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function.</p></sec><sec><title>Conclusions</title><p>Altogether, differentially regulated genes and pathway analysis identify specific pathways that can be targeted therapeutically to increase trophic support, e.g. IGF, ErbB and netrin signaling, and reduce neuroinflammation, e.g. PGD2 synthesis, which may be beneficial in the treatment of chronic forms of HIV-associated neurocognitive disorders in the setting of viral suppression.</p></sec></abstract></article-meta></front><body><sec><title>Background</title><p>HIV-associated dementia, opportunistic infections and neoplasms are significantly reduced since the introduction of combination antiretroviral therapy (cART)
[<xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B4">4</xref>]. However, decreased HIV-associated dementia has been associated with an increased prevalence of milder and chronic forms of HIV-associated neurocognitive disorders (HAND) and HIV-associated major depressive disorder along with increased life expectancy
[<xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B10">10</xref>].</p><p>Release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS parenchyma plays a central role in HIV-associated neurological disorders
[<xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref>]. Several HIV-1 proteins also possess neurotoxic potential including gp41, Vpr, Nef, Rev and Vpu
[<xref ref-type="bibr" rid="B13">13</xref>-<xref ref-type="bibr" rid="B16">16</xref>]. Evidence suggests that the toxic actions of low levels of HIV-1 products are key in the neuropathogenesis of persistent central nervous system HIV disease in the setting of cART. In fact, after the introduction of cART, HAND do not correlate with indicators of florid HIV replication such as plasma viral load and low CD4<sup>+</sup> counts
[<xref ref-type="bibr" rid="B4">4</xref>], but are correlated with synaptodendritic injury
[<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>], which in experimental settings can be induced by HIV-1 products even in the absence of virus replication
[<xref ref-type="bibr" rid="B19">19</xref>-<xref ref-type="bibr" rid="B21">21</xref>]. Therefore, there is a need to investigate the pathologic consequences of the expression of low levels of multiple HIV-1 proteins in disease relevant cell types.</p><p>The HIV-1 transgenic (Tg) rats used in the present study harbor a gag/pol-deleted HIV-1 provirus under the LTR promoter
[<xref ref-type="bibr" rid="B22">22</xref>], resulting in the co-expression of multiple HIV-1 proteins in disease-relevant central nervous system (CNS) cells such as microglia and astrocytes, but not in neurons
[<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B23">23</xref>]. Thus, the HIV-1 Tg rats differ from most other non-replicating small animal models expressing a single HIV-1 protein and from replicating models
[<xref ref-type="bibr" rid="B24">24</xref>]. The construct used in HIV-1 Tg rats was previously used in mice where it was characterized by ectopic expression
[<xref ref-type="bibr" rid="B25">25</xref>], possibly because of deficient interaction of Tat with the murine cyclin T
[<xref ref-type="bibr" rid="B26">26</xref>]. Despite lack of virus replication and production, HIV-1 Tg rats have a progressive clinical presentation leading to a picture reminiscent of some of AIDS features later in life that includes immunological abnormalities and neurological manifestations
[<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B27">27</xref>].</p><p>Here we studied global gene expression in the hippocampus of HIV-1 Tg rats before the appearance of overt symptomology to model the effects of concomitant expression of low levels of multiple HIV-1 products in the CNS in the absence of viral replication, as seen in the context of viral suppression in the setting of combination antiretroviral therapy (cART). Results show that HIV-1 Tg rats have gene expression changes reminiscent of neuroAIDS, significant astrogliosis and microgliosis, and working memory impairments. We used the Gene Set Enrichment Analysis (GSEA) algorithm
[<xref ref-type="bibr" rid="B28">28</xref>] to identify molecular pathways that are differentially activated in HIV-1 Tg rats. We observed dysregulation of pathways associated with gliosis, consistent with the morphological results in HIV-1 Tg rats, reduced trophic support and synaptic plasticity, mitochondrial function, as well as neurodegenerative diseases such as Huntington’s disease and Parkinson’s disease. HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function, supporting the functional significance of the gene expression changes observed.</p></sec><sec sec-type="results"><title>Results</title><sec><title>Astrogliosis and microgliosis in HIV-1 Tg rats</title><p>Characterization of the neuropathological alterations in the HIV-1 Tg rat was performed with antibodies against the astroglial marker GFAP and the microglial cell marker Iba1. Expression of HIV-1 proteins in the hippocampi of HIV-1 Tg rats was observed in both microglia and astrocytes (Figure
<xref ref-type="fig" rid="F1">1</xref>). As expected in the control animals, scattered astroglial cells were detected in the neocortex and more active astroglia was observed in the adjacent white matter and hippocampus (Figures
<xref ref-type="fig" rid="F1">1</xref> and
<xref ref-type="fig" rid="F2">2</xref>). In contrast, in HIV-1 Tg rats, levels of astrogliosis in the neocortex and hippocampus were significantly increased with the presence of enlarged astroglia with distended cytoplasm (Figure
<xref ref-type="fig" rid="F2">2</xref>A). Likewise, in control rats, moderate numbers of microglial cells were detected in the neocortex and hippocampus, in contrast in the HIV-1 Tg animals there was an increase in Iba1 positive microglial cells that was more prominent in the hippocampus than in the neocortex (Figure
<xref ref-type="fig" rid="F2">2</xref>C). These cells displayed abundant branches and processes and the cytoplasm was distended, suggesting the possibility of an activated state. Significant astrogliosis and microgliosis were observed by immunostaining in the hippocampi of HIV-1 Tg rats (Figure
<xref ref-type="fig" rid="F2">2</xref>B, D). Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) confirmed that the expression of astrogliosis and microgliosis markers was increased in the hippocampus of HIV-1 Tg rats (Figure
<xref ref-type="fig" rid="F3">3</xref>).</p><fig id="F1" position="float"><label>Figure 1</label><caption><p><bold>Expression of HIV-1 products in HIV-1 Tg rats. A)</bold> HIV protein Tat was detected by immunohistochemistry with peroxydase detection in the hippocampus in cells with microglia morphology (arrow) and <bold>B)</bold> by immunofluorescence with double labeling of HIV-1 Tat and the microglia marker Ionized calcium binding adaptor molecule 1 (Iba-1) (arrow). <bold>C-F)</bold> Double immunofluorescence for HIV-1 gp120 <bold>(C-D)</bold> and for the astrocytic marker glial fibrillary acidic protein (GFAP) <bold>(E-F)</bold> in the hippocampus of HIV-1 Tg rats revealed gp120-immunoreactive astrocytes (arrow). The location of the field shown in <bold>C-F</bold> is indicated by the inset in <bold>C</bold>.</p></caption><graphic xlink:href="1750-1326-9-26-1"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><p><bold>Astrogliosis and microgliosis in the brain of HIV-1 Tg rats. A)</bold> Immunostaining for the astrocytic marker GFAP in HIV-1 Tg and control rats. The panel to the left is a low power view (4X) of the neocortex and hippocampus, while the panels in the middle and right are at higher magnification (400X) <bold>(B)</bold> Computer aided image analysis of the numbers of GFAP positive cells in the neocortex and hippocampus demonstrate a significant increase in astroglial cells in the HIV-1 tg rats (Student’s <italic>t-</italic>test). <bold>C)</bold> Immunostaining for the microglial marker Iba-1 in HIV-1 Tg and control rats. The panel to the left is a low power view (4X) of the neocortex and hippocampus, while the panels in the middle and right are at higher magnification (400X); <bold>D)</bold> Computer aided image analysis of the numbers of Iba-1 positive cells in the neocortex and hippocampus demonstrate a significant increase in astroglial cells in the HIV-1 Tg rats (* = p < 0.01; n = 6, by <italic>t</italic>-test). Bar = 250 and 25 μm at 4X and 400x, respectively.</p></caption><graphic xlink:href="1750-1326-9-26-2"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><p><bold>RT-PCR validation of increased expression of astrogliosis and microgliosis markers in the hippocampus of HIV-1 Tg rats.</bold> The mRNA for the astrocytic marker GFAP, and the microglia markers Iba-1 and CD11b (Mac1) were significantly increased in HIV-1 Tg rats over controls, consistent with the immunohistochemistry results in Figure <xref ref-type="fig" rid="F2">2</xref> (<italic>n</italic> = 6, **<italic>p</italic> < 0.01, ****<italic>p</italic> < 0.0001, by <italic>t</italic>-test).</p></caption><graphic xlink:href="1750-1326-9-26-3"></graphic></fig></sec><sec><title>Gene expression changes in HIV-1 Tg rats</title><p>Gene expression was profiled in the hippocampi of HIV-1 Tg and wild-type rats with high-density Affymetrix arrays (Figures
<xref ref-type="fig" rid="F4">4</xref> and
<xref ref-type="fig" rid="F5">5</xref>, Additional files
<xref ref-type="supplementary-material" rid="S1">1</xref> and
<xref ref-type="supplementary-material" rid="S2">2</xref>: Tables S1 and S2). Pathway analysis with the GSEA algorithm
[<xref ref-type="bibr" rid="B28">28</xref>] revealed 23 pathways significantly differentially regulated with statistical significance of p ≤ 0.01 (Figures
<xref ref-type="fig" rid="F6">6</xref> and
<xref ref-type="fig" rid="F7">7</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3). Eight differentially regulated pathways showed increased activation, while the rest was decreased.</p><fig id="F4" position="float"><label>Figure 4</label><caption><p><bold>Hierarchical clustering of top differentially expressed genes in the hippocampus of HIV-1 Tg rats (HIV) versus wild-type littermate controls (Control).</bold> Gene expression was profiled in the hippocampi of HIV-1 and wild-type rats with high-density Affymetrix microarrays. The dendrogram shows 73 of the top 100 differentially expressed probesets that were found to be associated with gene names (Additional file <xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3). Genes are colored according to their expression values. Red indicates upregulated genes in HIV-1 Tg rats, while blue indicates downregulated genes. Brightness is proportional to the extent of change in gene expression.</p></caption><graphic xlink:href="1750-1326-9-26-4"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><p><bold>RT-PCR validation of differentially expressed genes in the hippocampus of HIV-1 Tg rats.</bold> Examples of genes that were found to be differentially regulated in the hippocamous of HIV-1 Tg rats include PGD2 synthase (Ptgds), interferon stimulated gene ISG-15 (ISG-15), IGF binding protein 6 (Igfbp6) and the IGF-activated gene T cell death-associated gene 51 (TDAG51), Col1A2 (procollagen type1-a2), and the mitochondrial protein ubiquitin domain containing 2 (Ubtd2). Lastly, among differentially expressed genes are Fbxw11 and Npm1, which interact with HIV-1 proteins Vpu and Tat, respectively. Please see text (<italic>n</italic> = 6, *<italic>p</italic> < 0.05, **<italic>p</italic> < 0.01, ***<italic>p</italic> < 0.001, ****<italic>p</italic> < 0.0001, by <italic>t</italic>-test).</p></caption><graphic xlink:href="1750-1326-9-26-5"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><p><bold>Top 23 differentially regulated pathways in the hippocampus of HIV-1 Tg rats and controls by GSEA.</bold> The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis using the MSigDB C2 canonical pathway collection [<xref ref-type="bibr" rid="B28">28</xref>]. Of the significantly differentially regulated pathways with statistical significance of p ≤ 0.01, 8 showed increased activation, while the rest was decreased. Among the increased ones are pathways consistent with astrocyte and microglia activation, inflammatory processes, and interferon activation. Decreased pathways indicate substantial downregulation of signaling systems involved in neuronal trophism and synaptic synaptic function. Pathways are colored according to their expression values: red indicates upregulated genes in HIV-1 Tg rats, while blue indicates downregulated pathways. Brightness is proportional to the extent of change in pathway expression.</p></caption><graphic xlink:href="1750-1326-9-26-6"></graphic></fig><fig id="F7" position="float"><label>Figure 7</label><caption><p><bold>GSEA plots of selected differentially regulated pathways.</bold> Representative differentially regulated pathways are shown including pathways with increased and reduced activation in the hippocampus of HIV-1 Tg rats. Pathways with increased activation included pathways indicative of <bold>(A)</bold> interferon activation; <bold>(B, C)</bold> cell division, consistent with astrogliosis and microgliosis; <bold>(D)</bold> peroxisome dysregulation. Pathways with reduced activation <bold>(E-H)</bold> are indicative of reduced neuronal trophism and neurodegeneration.</p></caption><graphic xlink:href="1750-1326-9-26-7"></graphic></fig><p>Results show that among the pathways and genes differentially expressed, several are consistent with astrocyte and microglia activation and inflammatory processes (Figures
<xref ref-type="fig" rid="F2">2</xref> and
<xref ref-type="fig" rid="F3">3</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3). In particular, pathways showing significant activation included 4 pathways indicative of DNA synthesis and cell proliferation, suggestive of astrocyte and microglia activation (“REACTOME_SYNTHESIS_OF_DNA” and “REACTOME_MITOTIC_G1_G1_S_PHASES”, “REACTOME_CDT1_ASSOCIATION_WITH_THE_CDC6_ORC_ORIGIN_COMPLEX” and “REACTOME_RNA_POL_I_TRANSCRIPTION_TERMINATION”, MSigDB geneset denomination; Figures
<xref ref-type="fig" rid="F4">4</xref> and
<xref ref-type="fig" rid="F7">7</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3). Two pathways indicative of interferon activation were also increased (“REACTOME_INTERFERON_SIGNALING” and “REACTOME_INTERFERON_ALPHA_BETA_SIGNALING”) (Figures
<xref ref-type="fig" rid="F5">5</xref> and
<xref ref-type="fig" rid="F6">6</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3). Among the interferon-related genes that were found to be increased in HIV-1 Tg rats is the interferon stimulated gene 15 (ISG-15) (Figure
<xref ref-type="fig" rid="F5">5</xref>, Additional file
<xref ref-type="supplementary-material" rid="S1">1</xref>: Table S1). Other inflammation- and astrogliosis-related genes increased in the hippocampi of HIV-1 Tg rats include prostaglandin D2 (PGD2) synthase (Ptgds) and procollagen type1-a2 (Col1A2) (Figure
<xref ref-type="fig" rid="F5">5</xref>, Additional file
<xref ref-type="supplementary-material" rid="S1">1</xref>: Tables 1).</p><p>The GSEA analysis highlights a substantial downregulation of intracellular signaling pathways relevant to trophic support. In particular, the PI3K-mTOR signaling pathway (“PID_MTOR_4PATHWAY”), the LKB1 pathway (“PID_LKB1_PATHWAY”), and the integrin-linked kinase (ILK) pathway (“PID_ILK_PATHWAY”), were downregulated (Figures
<xref ref-type="fig" rid="F6">6</xref> and
<xref ref-type="fig" rid="F7">7</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3). Various downregulated genesets also contain numerous MAP kinases (PID_MTOR_4PATHWAY; REACTOME_AXON_GUIDANCE; PID_PRLSIGNALINGEVENTSPATHWAY; REACTOME_L1CAM_INTERACTIONS; REACTOME_SIGNALING_BY_ERBB2; REACTOME_DOWNREGULATION_OF_ERBB2_ERBB3_SIGNALING”, “PID_ILK_PATHWAY”), such as ERK1 (MAPK3).</p><p>GSEA also showed downregulation of genesets related to neuronal function and synaptic plasticity such as “REACTOME_NEURONAL_SYSTEM” and “REACTOME_AXON_GUIDANCE” (Figures
<xref ref-type="fig" rid="F6">6</xref> and
<xref ref-type="fig" rid="F7">7</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3), which appears consistent with the reduced trophic tone suggested by the data.</p><p>GSEA pathway analysis also indicates that key roles in the downregulation of transduction pathways mediating trophic signals may be played by the insulin-like growth factor (IGF), Erb-neuregulin-1 (NRG1) and netrin systems. In particular, IGF binding proteins 2 and 6 (Igfbp2 and Igfbp6) and the IGF-activated gene T cell death-associated gene 51 (TDAG51), also known as pleckstrin homology-like domain family A member 1 (PHLDA), were differentially regulated in HIV-1 Tg rats (Figure
<xref ref-type="fig" rid="F5">5</xref>, Additional file
<xref ref-type="supplementary-material" rid="S1">1</xref>: Table S1) as was the IGF signaling pathways by GSEA (REACTOME_REGULATION_OF_INSULIN_LIKE_GROWTH_FACTOR_IGF_ACTIVITY_BY_INSULIN_LIKE_GROWTH_FACTOR_BINDING_PROTEINS_IGFBPS). GSEA also showed differential regulation of Erb-neuregulin-NRG1 and netrin signaling pathways (“REACTOME_SIGNALING_BY_ERBB2”, “REACTOME_DOWNREGULATION_OF_ERBB2_ERBB3_SIGNALING”, and “REACTOME_NETRIN1_SIGNALING”; Figures
<xref ref-type="fig" rid="F6">6</xref> and
<xref ref-type="fig" rid="F7">7</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3).</p><p>Pathways related to neurodegeneration associated with protein misfolding and mitochondrial dysfunction were differentially regulated including “KEGG_PARKINSONS_DISEASE” and “KEGG_HUNTINGTONS_DISEASE”. Another significantly dysregulated pathway is the “REACTOME_CALNEXIN_CALRETICULIN_CYCLE”, which involves unfolded protein response genes.</p><p>Multiple genesets are indicative of dysregulation of phospholipid metabolism (“EGG_GLYCEROPHOSPHOLIPID_METABOLISM”, “KEGG_GLYCEROLIPID_METABOLISM” and “KEGG_PEROXISOME”; Figures
<xref ref-type="fig" rid="F6">6</xref> and
<xref ref-type="fig" rid="F7">7</xref>, Additional file
<xref ref-type="supplementary-material" rid="S3">3</xref>: Table S3).</p><p>Lastly, two cellular targets of HIV-1 were differentially regulated in the hippocampus of HIV-1 Tg rats, Fbxw11 and the nuclear chaperone nucleophosmin/B23 encoded by the Npm1 gene (Figure
<xref ref-type="fig" rid="F5">5</xref> and Additional file
<xref ref-type="supplementary-material" rid="S1">1</xref>: Table S1).</p></sec><sec><title>Working memory impairments in HIV-1 Tg rats</title><p>To determine the functional correlates of the present gene expression and pathologic findings, we then investigated working memory in HIV-1 Tg rats using a hippocampus and prefrontal cortex-dependent task
[<xref ref-type="bibr" rid="B29">29</xref>-<xref ref-type="bibr" rid="B32">32</xref>]. Rats were tested in the dark in spontaneous alternations in the T-Maze, which is a paradigm sensitive to prefrontal cortex and hippocampal impairments
[<xref ref-type="bibr" rid="B29">29</xref>-<xref ref-type="bibr" rid="B32">32</xref>]. Visual cues were not provided in the T-Maze paradigm, as done by others
[<xref ref-type="bibr" rid="B33">33</xref>], to minimize the influence of cataracts in HIV-1 Tg rats. HIV-1 Tg rats exhibited a marked decrease of alternation behavior (SAB) compared to control rats (t<sub>10</sub> = 4.2, p < 0.01) (Figure
<xref ref-type="fig" rid="F8">8</xref>A). Only the control rats alternated significantly above chance (t<sub>6</sub> = 7.1, p < 0.001) whereas HIV-1 Tg rats were not significantly different from chance level (t<sub>4</sub> = 1.2, p = ns). There was no difference between the two groups in the latency to leave the start box or the latency to make a choice (Figure
<xref ref-type="fig" rid="F8">8</xref>B). Finally there was no difference between the two groups in the number of failed trials or in the response bias (Control: 0.55 ± 0.02; HIV-1 Tg: 0.58 ± 0.04, p = ns). These results indicate an impairment of hippocampal working memory in HIV-1 Tg rats that was not a consequence of an increase of anxiety-related behavior since we did not see increases in the latency to leave the start box or in the number of failed trials in HIV-1 Tg rats. Moreover this alteration of working memory is unlikely to come from an increase in the delay between the encoding and the recall of information or an alteration of locomotor activity since the latency to start and the latency to enter the arm were similar in both groups. Thus, the gene expression changes observed above are associated with neurocognitive impairments in HIV-1 Tg rats.</p><fig id="F8" position="float"><label>Figure 8</label><caption><p><bold>Working memory impairment in HIV-1 Tg rats.</bold> Working memory was significantly impaired in adult (4–5 months old) HIV-1 Tg rats compared to wild-type controls (CONT) using the <italic>spontaneous alternation behavior in the T-Maze</italic>, a paradigm sensitive to prefrontal cortex and hippocampal impairments. <bold>A)</bold> HIV-1 Tg rats exhibited a marked decrease of spontaneous alternation behavior (SAB), a measure of working memory, compared to control rats (n = 7 for both groups; t10 = 4.2, p < 0.01). Only the control rats alternated significantly above chance (t6 = 7.1, p < 0.001) whereas HIV-1 Tg rats were not significantly different from chance level (t4 = 1.2, p = ns). There was no difference between the two groups in the latency to leave the start box or the latency to make a choice <bold>(B)</bold>. ***p < 0.001 <italic>vs.</italic> chance; p < 0.01 <italic>vs.</italic> HIV-1 Tg rats.</p></caption><graphic xlink:href="1750-1326-9-26-8"></graphic></fig></sec></sec><sec sec-type="discussion"><title>Discussion</title><sec><title>HIV-1 Tg rats as a model of neuroAIDS</title><p>A thorough neurobiological investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the context of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS. The HIV-1 Tg rats are constitutive, making them a model of persistent exposure to viral proteins, although lack of induciblity of the HIV-1 provirus can be seen as a limitation. Here we show that HIV-1 Tg rats express viral proteins in microglia and astrocytes, display astrogliosis and microgliosis, and have gene expression changes consistent with human neuroAIDS. Collectively, these results support that HIV-1 Tg rats are a valid animal model of neuroAIDS.</p><p>Supporting the functional significance of the gene expression alterations reported here, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior (SAB) in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function. Rats were tested in the dark in the T-Maze with no visual cues provided to minimize the influence of cataracts in HIV-1 Tg rats, as done by others
[<xref ref-type="bibr" rid="B33">33</xref>]. In this regard it should be noted that spontaneous alternation behavior (SAB) has been used in aged rats with visual impairments
[<xref ref-type="bibr" rid="B34">34</xref>] and to compare anophthalmic mutant mice to wild-type controls
[<xref ref-type="bibr" rid="B35">35</xref>]. It has been previously shown that HIV transgenic rats exhibit impairment in a spatial reversal learning task
[<xref ref-type="bibr" rid="B36">36</xref>] without any deficit in spatial memory or motor activity
[<xref ref-type="bibr" rid="B37">37</xref>]. Our results extend these studies by showing that HIV rats also exhibit impairment in a working memory task. The deficits in the reversal learning task and the working memory task may both be explained by an impairment in the ability of HIV rats to shift attention to a new target, a decreased working memory capacity and/or an increase in perseveration.</p></sec><sec><title>Gene expression changes in HIV-1 Tg rats</title><p>Gene expression and pathway analysis with the GSEA algorithm show evidence of neuroinflammatory processes and gliosis and synaptodendritic injury that together with the impairment in working memory are reminiscent of HAND in humans. In particular, the GSEA-based pathway analysis that we employed suggests key dysregulation in IFN regulated pathways, including ISG-15, which exerts antiviral activities through members of the Endosomal sorting complex required for transport (ESCRT) proteins
[<xref ref-type="bibr" rid="B38">38</xref>]. ISG-15 was proposed to be a predictive biomarker for HAND
[<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B40">40</xref>]. In particular, ISG-15 was shown to correlate with neuropathology and viral load and ISG-15 CSF levels may be predictive of future neurocognitive impairments
[<xref ref-type="bibr" rid="B38">38</xref>]. Several other inflammation-related genes induced in the hippocampus of HIV-1 Tg rats were previously associated with neuroAIDS in humans including IGF binding proteins
[<xref ref-type="bibr" rid="B41">41</xref>], prostaglandin D2 (PGD2) synthase
[<xref ref-type="bibr" rid="B42">42</xref>], and the pro-alpha2 chain of type I collagen, Col1A2
[<xref ref-type="bibr" rid="B43">43</xref>]. Prostaglandins have been implicated in inflammation-induced working memory deficits
[<xref ref-type="bibr" rid="B44">44</xref>] and imaging evidence supports that brain arachidonic acid metabolism in HIV-1 transgenic rats is upregulated
[<xref ref-type="bibr" rid="B45">45</xref>]. PGD2 has been implicated in the induction of astrogliosis and demyelination
[<xref ref-type="bibr" rid="B42">42</xref>,<xref ref-type="bibr" rid="B46">46</xref>] and has been associated with immune activation, astrogliosis, microgliosis, and neuroAIDS in humans
[<xref ref-type="bibr" rid="B42">42</xref>]. Col1A2 has been associated with neuroAIDS in humans
[<xref ref-type="bibr" rid="B43">43</xref>]. Collagen induction in the CNS has been also observed in brain injury, Alzheimer’s disease, temporal lobe epilepsy, and multiple sclerosis plaques
[<xref ref-type="bibr" rid="B47">47</xref>-<xref ref-type="bibr" rid="B49">49</xref>].</p><p>GSEA analysis showed downregulation of genesets related to neuronal function, neuronal trophism, synaptic plasticity, as well as genes and pathways associated with degenerative diseases such as Huntington’s disease and Parkinson’s disease, which include genes involved in protein misfolding and mitochondrial function. Decreased expression of synaptic plasticity and axon guidance genes was also observed in patients with HIVE in the The National NeuroAIDS Tissue Consortium Brain Gene Array
[<xref ref-type="bibr" rid="B50">50</xref>] and in another study
[<xref ref-type="bibr" rid="B43">43</xref>], consistent with the notion that HAND in the cART setting correlates with synaptodendritic injury
[<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>]. Dysregulations of genes related to Parkinson’s disease and Huntington’s disease and mitochondrial function, is consistent with previous studies suggesting mitochondrial dysfunction and oxidative stress as potential contributors to HAND
[<xref ref-type="bibr" rid="B51">51</xref>].</p><p>Signaling systems involved in neuronal trophism and synaptic maturation and plasticity that were found to be differentially regulated in HIV-1 Tg rats involve IGF, ErbB and netrin, all of which have been shown to exert trophic actions on dendritic spines
[<xref ref-type="bibr" rid="B52">52</xref>-<xref ref-type="bibr" rid="B55">55</xref>], suggesting that dysregulation of these pathways can contribute to the synaptodendritic injury seen in neuroAIDS
[<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>].</p><p>IGF signaling has been implicated in synaptic trophism, depression and Parkinson’s disease
[<xref ref-type="bibr" rid="B55">55</xref>-<xref ref-type="bibr" rid="B57">57</xref>]. GSEA highlighted differential expression of IGF signaling genes including increased Igfbp2 and Igfbp6 expression, which were also found to be increased in the CSF of HIV-1 patients
[<xref ref-type="bibr" rid="B41">41</xref>]. The IGFBPs have high affinities for the IGFs
[<xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B59">59</xref>] and their increased expression may result in reduced trophic support as well as inflammatory processes
[<xref ref-type="bibr" rid="B60">60</xref>-<xref ref-type="bibr" rid="B62">62</xref>]. The IGF activated gene TDAG51/PHLDA1
[<xref ref-type="bibr" rid="B63">63</xref>], which is expressed in both neurons and glial cells
[<xref ref-type="bibr" rid="B64">64</xref>], is implicated in insulin signaling
[<xref ref-type="bibr" rid="B65">65</xref>] and has been shown to have differential effects on susceptibility to apoptosis
[<xref ref-type="bibr" rid="B66">66</xref>-<xref ref-type="bibr" rid="B68">68</xref>].</p><p>ErbB2/B4 receptors and their ligand neuregulin-1 (NRG1) are encoded by candidate susceptibility genes for schizophrenia
[<xref ref-type="bibr" rid="B69">69</xref>]. Functional NRG1 receptors consist of ErbB4 homodimers or heterodimers between ErbB2, ErbB3 and ErbB4 since NRG1 binds ErbB3 and ErbB4, and ErbB2 and ErbB4 have intrinsic tyrosine kinase activity
[<xref ref-type="bibr" rid="B69">69</xref>]. Mice that lack the ErbBs with intrinsic tyrosine kinase activity (ErbB2 and ErbB4) in the CNS have reduced dendritic spine density and behavioral abnormalities
[<xref ref-type="bibr" rid="B53">53</xref>], possibly implicating this ErbB signaling in synaptodendritic injury. Netrins are secreted mediators that exert multiple trophic actions including axon guidance
[<xref ref-type="bibr" rid="B70">70</xref>], synaptic plasticity
[<xref ref-type="bibr" rid="B71">71</xref>], prevention of apoptosis
[<xref ref-type="bibr" rid="B72">72</xref>,<xref ref-type="bibr" rid="B73">73</xref>], adult neurogenesis including in the course of CNS regeneration
[<xref ref-type="bibr" rid="B74">74</xref>-<xref ref-type="bibr" rid="B76">76</xref>], which is believed to be impaired in neuroAIDS
[<xref ref-type="bibr" rid="B77">77</xref>], and synaptic trophism
[<xref ref-type="bibr" rid="B54">54</xref>].</p><p>The GSEA analysis highlights a substantial downregulation of intracellular signaling pathways relevant to trophic support such as the PI3K-mTOR signaling pathway, which mediates a vast array of trophic signals
[<xref ref-type="bibr" rid="B78">78</xref>]; the LKB1 pathway, which is key to neuronal survival following mitochondrial insults
[<xref ref-type="bibr" rid="B79">79</xref>] and cross-talks with the PI3K-mTOR pathway; and the ILK pathway, which is involved in mediating trophic signals of the extracellular matrix and trophic factors as well as in the anti-apoptotic effect of the PI3K pathway
[<xref ref-type="bibr" rid="B80">80</xref>]. Recent studies have indicated impaired processing and transport of neurotrophic factors in HIV-1 neuropathogenesis
[<xref ref-type="bibr" rid="B81">81</xref>-<xref ref-type="bibr" rid="B83">83</xref>]. The PI3K-mTOR signaling pathway is involved in synaptic plasticity
[<xref ref-type="bibr" rid="B84">84</xref>-<xref ref-type="bibr" rid="B86">86</xref>] and was shown to be dysregulated in the frontal cortex of patients with neuroAIDS
[<xref ref-type="bibr" rid="B43">43</xref>]. Downregulated genesets also contain numerous MAP kinases including ERK1 (MAPK3), which was previously implicated in the neurological actions of HIV-1 products
[<xref ref-type="bibr" rid="B87">87</xref>].</p><p>The GSEA analysis also points to coordinated mitochondria and peroxisome dysregulations as well as dysregulation of phospholipid metabolism. Peroxisomes and mitochondria exhibit a functional interplay in fatty acid processing and intermediate metabolism
[<xref ref-type="bibr" rid="B88">88</xref>,<xref ref-type="bibr" rid="B89">89</xref>]. It could be envisioned that if peroxisomal metabolism is slowed, critical metabolic intermediates (e.g., acetyl-CoA) may not be adequately supplied to mitochondria and, conversely, disruption of mitochondrial metabolism can similarly affect peroxisomal function. Peroxisome dysfunction may also contribute to increased lipid peroxidation and cellular aging in HIV-1
[<xref ref-type="bibr" rid="B90">90</xref>,<xref ref-type="bibr" rid="B91">91</xref>]. In apparent agreement with the dysregulation of these pathways, evidence suggestive of altered phospholipid metabolism has been reported in HIV-1 patients
[<xref ref-type="bibr" rid="B92">92</xref>,<xref ref-type="bibr" rid="B93">93</xref>] and peroxisome dysregulation can be indicative of altered brain oxidative balance associated with HIV-1
[<xref ref-type="bibr" rid="B94">94</xref>].</p><p>Two cellular targets of HIV-1, Fbxw11 and nucleophosmin/B23, were also differentially regulated in the hippocampus of HIV-1 Tg rats. Fbxw11 is the gene coding for βTrCP, a cellular ubiquitin ligase that was found to be bound by the HIV-1 Vpu viral protein
[<xref ref-type="bibr" rid="B95">95</xref>]. Nucleophosmin/B23, encoded by the Npm1 gene, is a nuclear chaperone implicated in the nuclear transport of Tat
[<xref ref-type="bibr" rid="B96">96</xref>].</p></sec><sec><title>Potential therapeutic targets for neuroAIDS suggested by gene expression analysis of HIV-1 Tg rats</title><p>Gene expression analysis can be a useful tool both to gain insights in the pathogenesis and for the identification of potential new therapeutic targets by identifying the signaling pathways that have the potential to modify the disease pathophysiology
[<xref ref-type="bibr" rid="B97">97</xref>-<xref ref-type="bibr" rid="B99">99</xref>]. This is especially needed in neuroAIDS as no targeted therapy other than cART is currently recommended for the management of HAND
[<xref ref-type="bibr" rid="B100">100</xref>,<xref ref-type="bibr" rid="B101">101</xref>]. Adjunctive therapies for HAND explored to date include the low-affinity antagonist of the NMDA type glutamate receptor memantine, the calcium channel blocker nimodipine, and the monoamine oxidase B inhibitor selegiline, in addition to antioxidants and anti-inflammatory drugs such as minocycline. Memantine and nimodipine are intended to protect from excitotoxic neuronal damage associated with excessive glutamate release
[<xref ref-type="bibr" rid="B102">102</xref>,<xref ref-type="bibr" rid="B103">103</xref>]. Selegiline is a drug used for the treatment of early-stage Parkinson’s disease, depression and dementia
[<xref ref-type="bibr" rid="B104">104</xref>,<xref ref-type="bibr" rid="B105">105</xref>].</p><p>Our gene expression results showing decreased expression of Parkinson's disease-related genesets lend support for the use of selegiline in HAND and potentially for other therapeutics used in Parkinson's disease such as methylphenidate, a stimulant that reduces reuptake of dopamine and norepinephrine that has proven beneficial in lowering fatigue scores in HIV patients
[<xref ref-type="bibr" rid="B106">106</xref>]. The present results of increased PGD2 synthase (Ptgds), is in keeping with previous studies that showed elevated PGD2 levels in HIV-1-positive patients
[<xref ref-type="bibr" rid="B42">42</xref>]. A potential role of prostaglandins in HIV-1 neuropathogenesis is also indicated by increased expression of the prostaglandin synthetic enzyme COX-2, which is also a characteristic of other degenerative conditions such as Alzheimer's disease and amyotrophic lateral sclerosis
[<xref ref-type="bibr" rid="B107">107</xref>,<xref ref-type="bibr" rid="B108">108</xref>]. Dysregulation of prostaglandin synthesis in HAND lends support to the use of inhibitors of cyclooxygenase-2 (COX-2) as well as newer compounds targeting the PGD2 receptor. In this regard, a COX-2 inhibitor has shown promise in downregulating immune activation and improving T cell function in HIV-1 patients
[<xref ref-type="bibr" rid="B109">109</xref>].</p><p>The present gene expression results as well as the previous literature also point to a role in HAND of several signaling systems with the potential to provide trophic support to synapses and reverse the synaptodendritic injury associated with HAND
[<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>]. Among them are IGF, ErbB and netrin signaling and the PI3K-mTOR signal transduction pathway, which mediates trophic and plastic actions of various signaling systems.</p><p>IGF-1 therapy has shown potential in models of both Parkinson’s disease
[<xref ref-type="bibr" rid="B110">110</xref>,<xref ref-type="bibr" rid="B111">111</xref>] and Alzheimer's disease
[<xref ref-type="bibr" rid="B112">112</xref>,<xref ref-type="bibr" rid="B113">113</xref>]. These effects are at least in part mediated by recruitment of PI3K
[<xref ref-type="bibr" rid="B111">111</xref>,<xref ref-type="bibr" rid="B114">114</xref>]. Additionally, chronic treatment with IGF-1 was protective <italic>in vitro</italic> against gp120-mediated neuronal damage and was synergistic with erythropoietin (EPO), at least in part, through cooperative activation of PI3K
[<xref ref-type="bibr" rid="B115">115</xref>]. GLP-1 and GLP-1 analogs, which activate partially overlapping signal transduction pathways as insulin and IGF-1
[<xref ref-type="bibr" rid="B114">114</xref>], have also shown beneficial effects in preclinical models of neurodegenerative disorders
[<xref ref-type="bibr" rid="B116">116</xref>-<xref ref-type="bibr" rid="B119">119</xref>]. There is currently great interest in developing drugs to modulate NRG1<bold>–</bold>ErbB4 and netrin signalling
[<xref ref-type="bibr" rid="B120">120</xref>,<xref ref-type="bibr" rid="B121">121</xref>]. Netrin agonists may be potentially beneficial in neuroAIDS both by exerting neurotrophic actions and by reducing inflammation
[<xref ref-type="bibr" rid="B120">120</xref>]. The PI3K pathway is itself a potential target for reversal of the synaptodendritic injury associated with HAND. However, as PI3K appears to play a role in the regulation of the HIV-1 LTR promoter and virus latency
[<xref ref-type="bibr" rid="B122">122</xref>,<xref ref-type="bibr" rid="B123">123</xref>], activation of PI3K in the cells that harbor the provirus may increase levels of expression of HIV-1 products, potentially leading to detrimental effects on cognition.</p></sec></sec><sec sec-type="conclusions"><title>Conclusions</title><p>The investigation of HIV-induced CNS dysfunction in the context of viral suppression has been limited by the lack of validated small animal models with low level expression of multiple HIV-1 proteins in disease-relevant cells. Here we show that HIV-1 Tg rats express viral proteins in microglia and astrocytes and display astrogliosis and microgliosis and show gene expression changes that are reminiscent of HIV-1 infection in humans. Differentially regulated genes and pathway analysis also identify specific pathways that can be targeted therapeutically to increase trophic support and reduce neuroinflammation that may be beneficial in the treatment of chronic forms of HAND in the setting of cART.</p></sec><sec sec-type="methods"><title>Methods</title><sec><title>Animals</title><p>HIV-1 Tg and wild-type rats 4–5 months of age (Harlan Sprague–Dawley) were used for the study. For immunohistochemistry animals were perfused under deep isofluorane anesthesia with 4% paraformaldehyde in phosphate buffer; for microarray analyses, animals were sacrificed under deep isofluorane anesthesia and hippocampi were quickly removed and processed for RNA extraction.</p></sec><sec><title>Immunocytochemical analysis and image analysis</title><p>Brains were post-fixed in phosphate-buffered 4% paraformaldehyde at 4°C for 48 hrs and sectioned in the saggital plane at 40 μm with a Vibratome 2000 (Leica). Briefly as previously described
[<xref ref-type="bibr" rid="B124">124</xref>] saggital brain vibratome sections from the non-Tg and HIV-1 Tg rats were incubated overnight at 4°C with the rabbit polyclonal antibodies against Tat (NIH AIDS reagent program; cat# 1974) or mouse monoclonal antibodies against the astroglial marker - glial fibrillary acidic protein (GFAP, Millipore), or a monoclonal antibody against the microglial marker Iba-1 (1:1000, Sigma-Aldrich, Saint Louis, MO). Primary antibody incubation was followed by incubation with secondary biotinylated IgG, then avidin-HRP and diaminobenzidine (DAB) detection. All sections were processed under the same standardized conditions. Immunostained sections were imaged with a digital Olympus microscope and assessment of levels of Tat, GFAP and Iba-1 immunoreactivity was performed utilizing the Image-Pro Plus program (Media Cybernetics, Silver Spring, MD). For each case a total of three sections (10 digital images per section at 400x) were analyzed in order to estimate the average number of immunolabeled cells per unit area (mm2) and the average intensity of the immunostaining (corrected optical density). All slides were processed simultaneously under the same conditions and experiments were performed in triplicate to assess the reproducibility of results. To determine the co-localization between HIV-1 proteins and astroglial and microglial cells, double-labeling experiments were performed, as previously described. For this purpose, vibratome sections were immunolabeled with the rabbit polyclonal antibody against human Tat or gp120 (NIH AIDS reagent program) and the mouse monoclonal antibodies against GFAP (Millipore) and Iba-1 (Wako). Double-immunocytochemical analysis was performed utilizing the Tyramide Signal Amplification™-Direct (Red) system (NEN Life Sciences, Boston, MA) to detect Iba-1 or GFAP and fluorescein isothiocyanate (FITC)-conjugated secondary antibodies (1:75, Vector) to detect Tat or gp120. Sections were imaged with a laser scanning confocal microscope BioRad Radiance 2000 (Hercules, CA) equipped with a Nikon E600FN Ellipse microscope (Japan) and using a Nikon Plan Apo 60x oil objective (NA 1.4; oil immersion). Statistical significance of differences in the expression of GFAP and Iba-1 between HIV-1 Tg rats and controls was determined by unpaired Student’s <italic>t</italic>-test.</p></sec><sec><title>Gene expression profiling</title><p>Processing of Affymetrix microarrays was carried out as previously described, according to manufacturer’s procedures
[<xref ref-type="bibr" rid="B125">125</xref>,<xref ref-type="bibr" rid="B126">126</xref>]. All analyses were performed with R statistical software. We analyzed 11 samples (5 HIV-1 Tg rats; 6 controls) hybridized on Affymetrix Rat 230.2. One additional HIV sample was removed as it showed lower quality than the other samples. Differential expression was computed with functions from the package limma and takes into account sample phenotype and batch. False Discovery Rates were computed by Benjamini & Hochberg method. Differential expression between HIV-1 and control rats identifies 614 and 4 probes differentially expressed at p-value < 0.01 and FDR < 0.05, respectively.</p><p>Pathways for GSEA analysis were from the MSigDb collection C2 that contains major pathway databases including KEGG, REACTOME and PID (<ext-link ext-link-type="uri" xlink:href="http://www.broadinstitute.org/gsea/msigdb/index.jsp">http://www.broadinstitute.org/gsea/msigdb/index.jsp</ext-link>). We “humanized” the rat gene expression profiles by first selecting one probe per gene (the one with the highest coefficient of variation) and then kept the genes that had a unique human homologous gene (according to the database Homologene <ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/homologene">http://www.ncbi.nlm.nih.gov/homologene</ext-link>) for pathway analysis. Pathway differential activity was performed with GSEA using t-statistics obtained from the limma test as the reference list and pathway members as genesets; 24 pathways showed a p-value < 0.01. We report the pathways with the MSigDB terminology in the text and figures.</p></sec><sec><title>RT-PCR</title><p>RT-PCR was carried out as previously described
[<xref ref-type="bibr" rid="B125">125</xref>,<xref ref-type="bibr" rid="B127">127</xref>,<xref ref-type="bibr" rid="B128">128</xref>] with SYBR Green (BioRad) detection using an iQ5 Real-Time PCR Detection System (BioRad, Hercules, CA). The relative amounts of target mRNA were determined by the ΔCt method using β-actin for normalization
[<xref ref-type="bibr" rid="B129">129</xref>]. Statistical significance of differences between HIV-1 Tg rats and controls was determined by unpaired Student’s <italic>t</italic>-test.</p></sec><sec><title>Working memory</title><p>Rats were tested in the dark (<20 lux) during the nocturnal period using two identical T-Mazes constructed of black Plexiglas with no visual cues provided to minimize the influence of cataracts in HIV-1 Tg rats, as done by others
[<xref ref-type="bibr" rid="B33">33</xref>]. Rats were first habituated to the experimenters over 4 days (5 min/day) as described in
[<xref ref-type="bibr" rid="B29">29</xref>] and
[<xref ref-type="bibr" rid="B30">30</xref>]. On test day, rats were allowed to alternate between the left and right goal arms of the T-maze in 15 trial sessions. Each session consisted of 1 forced trial followed by 14 free choice trials. Once the rat entered a particular goal arm (4 paws inside), a guillotine door was lowered to block entry to the opposite arm. The door was removed only after the rat returned to the start arm, thus allowing a new alternation trial to be started. If the rat did not enter one of the two arms after 120 seconds, the rat was placed in the previously chosen arm and the trial was considered as failed. If after 30 seconds the rat did not spontaneously return to the start box, the experimenter manually positioned the rat in the start box for the next trial. The spontaneous alternation behavior (SAB) and the response bias were calculated with the formula below where <italic>n</italic> = number of choices, <italic>na’</italic> = number of non-alternation responses, ρ<sub>R</sub><sup>2</sup> = probability of a right turn, ρ<sub>L</sub><sup>2</sup> = probability of a left turn
[<xref ref-type="bibr" rid="B130">130</xref>]. The response bias corresponds to the tendency of an animal to favor one side over the other. The values of the response bias vary from 0.5 (no bias or same number of left and right choices) to 1.0 (full bias or exclusive left or right choices). Because animals with high response bias automatically exhibit low SAB that may be independent of any cognitive deficits, calculation of SAB without integrating the response bias may lead to wrong interpretations of the results by artificially producing low values below chance level. The formula was established so that a response bias of 0.5 (no bias) does not affect the calculation of SAB while a response of 1.0 (full bias) will neutralize the value of SAB to chance level (50%). This correction ensures that low levels of SAB are not due to a non-specific effect of response bias toward one side of the maze. The latency to leave the box and the latency to make a choice were also recorded.</p><p><disp-formula><mml:math id="M1" name="1750-1326-9-26-i1" overflow="scroll"><mml:mtable columnalign="left"><mml:mtr><mml:mtd><mml:mi mathvariant="italic">SAB</mml:mi><mml:mo>=</mml:mo><mml:mn>50</mml:mn><mml:mfenced open="{" close="}"><mml:mrow><mml:mn>1</mml:mn><mml:mo>+</mml:mo><mml:mfenced open="(" close=")"><mml:mfrac><mml:mrow><mml:mi mathvariant="italic">n</mml:mi><mml:mo>−</mml:mo><mml:mfenced open="(" close=")"><mml:mfrac><mml:mrow><mml:mi mathvariant="italic">na</mml:mi><mml:mo>'</mml:mo></mml:mrow><mml:mrow><mml:msup><mml:msub><mml:mi mathvariant="italic">ρ</mml:mi><mml:mi mathvariant="italic">L</mml:mi></mml:msub><mml:mn>2</mml:mn></mml:msup><mml:mo>+</mml:mo><mml:msup><mml:msub><mml:mi mathvariant="italic">ρ</mml:mi><mml:mi mathvariant="italic">R</mml:mi></mml:msub><mml:mn>2</mml:mn></mml:msup></mml:mrow></mml:mfrac></mml:mfenced></mml:mrow><mml:mi mathvariant="italic">n</mml:mi></mml:mfrac></mml:mfenced></mml:mrow></mml:mfenced><mml:mo>;</mml:mo></mml:mtd></mml:mtr><mml:mtr><mml:mtd><mml:mspace width="1em"></mml:mspace><mml:mi mathvariant="normal">Response</mml:mi><mml:mspace width="0.5em"></mml:mspace><mml:mi mathvariant="normal">Bia</mml:mi><mml:mo>=</mml:mo><mml:msup><mml:msub><mml:mi mathvariant="italic">ρ</mml:mi><mml:mi mathvariant="normal">L</mml:mi></mml:msub><mml:mn>2</mml:mn></mml:msup><mml:mo>+</mml:mo><mml:msup><mml:msub><mml:mi mathvariant="italic">ρ</mml:mi><mml:mi mathvariant="italic">R</mml:mi></mml:msub><mml:mn>2</mml:mn></mml:msup></mml:mtd></mml:mtr></mml:mtable></mml:math></disp-formula></p></sec></sec><sec><title>Abbreviations</title><p>cART: Combination antiretroviral therapy; CNS: Central nervous system; Col1A2: Procollagen type1-a2; COX-2: Cyclooxygenase-2; CSF: Cerebrospinal fluid; DAB: Diaminobenzidine; ERK1: Extracellular signal-regulated kinase 1; GFAP: Glial fibrillary acidic protein; GSEA: Gene Set Enrichment Analysis; HAD: HIV-associated dementia; HAND: HIV-associated neurocognitive disorders; HIVE: HIV encephalitis; IGF: Insulin-like growth factor; Igfbp: IGF binding protein; ILK: Integrin-linked kinase; ISG-15: Interferon stimulated gene 15; MAPK3: Mitogen-activated protein kinase 3; NRG1: Neuregulin-1; PGD2: Prostaglandin D2; PHLDA: Pleckstrin homology-like domain family A member 1; Ptgds: PGD2 synthase; SAB: Spontaneous alternation behavior; TDAG51: T cell death-associated gene 51; Tg: Transgenic.</p></sec><sec><title>Competing interests</title><p>The authors declare that they have no competing interests.</p></sec><sec><title>Authors’ contributions</title><p>PPS designed the study; VRC, CL, OG, MM, EM, carried out the studies; VRC, CL, OG, MM, GK, AC, EM, PPS wrote the paper. All authors read and approved the final manuscript.</p></sec><sec sec-type="supplementary-material"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="S1"><caption><title>Additional file 1: Table S1</title><p>Top 614 differentially expressed probesets.</p></caption><media xlink:href="1750-1326-9-26-S1.xlsx"><caption><p>Click here for file</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="S2"><caption><title>Additional file 2: Table S2</title><p>Top 100 differentially expressed probesets.</p></caption><media xlink:href="1750-1326-9-26-S2.xlsx"><caption><p>Click here for file</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="S3"><caption><title>Additional file 3: Table S3</title><p>Top 23 differentially expressed pathways by GSEA.</p></caption><media xlink:href="1750-1326-9-26-S3.docx"><caption><p>Click here for file</p></caption></media></supplementary-material></sec></body><back><sec><title>Acknowledgements</title><p>Supported by NIH grants AA006420, AA020608, DA004398 (OG); MH062962, MH062512 (EM); CA121852, AA021667, HL111566 (AC); and MH090956, MH064376 (PPS).</p></sec><ref-list><ref id="B1"><mixed-citation publication-type="journal"><name><surname>Maschke</surname><given-names>M</given-names></name><name><surname>Kastrup</surname><given-names>O</given-names></name><name><surname>Esser</surname><given-names>S</given-names></name><name><surname>Ross</surname><given-names>B</given-names></name><name><surname>Hengge</surname><given-names>U</given-names></name><name><surname>Hufnagel</surname><given-names>A</given-names></name><article-title>Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART)</article-title><source>J Neurol Neurosurg Psychiatry</source><year>2000</year><volume>69</volume><fpage>376</fpage><lpage>380</lpage><pub-id pub-id-type="pmid">10945813</pub-id></mixed-citation></ref><ref id="B2"><mixed-citation publication-type="journal"><name><surname>D'Arminio Monforte</surname><given-names>A</given-names></name><name><surname>Cinque</surname><given-names>P</given-names></name><name><surname>Mocroft</surname><given-names>A</given-names></name><name><surname>Goebel</surname><given-names>FD</given-names></name><name><surname>Antunes</surname><given-names>F</given-names></name><name><surname>Katlama</surname><given-names>C</given-names></name><name><surname>Justesen</surname><given-names>US</given-names></name><name><surname>Vella</surname><given-names>S</given-names></name><name><surname>Kirk</surname><given-names>O</given-names></name><name><surname>Lundgren</surname><given-names>J</given-names></name><article-title>Changing incidence of central nervous system diseases in the EuroSIDA cohort</article-title><source>Ann Neurol</source><year>2004</year><volume>55</volume><fpage>320</fpage><lpage>328</lpage><pub-id pub-id-type="pmid">14991809</pub-id></mixed-citation></ref><ref id="B3"><mixed-citation publication-type="journal"><name><surname>Everall</surname><given-names>IP</given-names></name><name><surname>Hansen</surname><given-names>LA</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><article-title>The shifting patterns of HIV encephalitis neuropathology</article-title><source>Neurotox Res</source><year>2005</year><volume>8</volume><fpage>51</fpage><lpage>61</lpage><pub-id pub-id-type="pmid">16260385</pub-id></mixed-citation></ref><ref id="B4"><mixed-citation publication-type="journal"><name><surname>Everall</surname><given-names>I</given-names></name><name><surname>Vaida</surname><given-names>F</given-names></name><name><surname>Khanlou</surname><given-names>N</given-names></name><name><surname>Lazzaretto</surname><given-names>D</given-names></name><name><surname>Achim</surname><given-names>C</given-names></name><name><surname>Letendre</surname><given-names>S</given-names></name><name><surname>Moore</surname><given-names>D</given-names></name><name><surname>Ellis</surname><given-names>R</given-names></name><name><surname>Cherne</surname><given-names>M</given-names></name><name><surname>Gelman</surname><given-names>B</given-names></name><name><surname>Morgello</surname><given-names>S</given-names></name><name><surname>Singer</surname><given-names>E</given-names></name><name><surname>Grant</surname><given-names>I</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><collab>National NeuroAIDS Tissue Consortium (NNTC)</collab><article-title>Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy</article-title><source>J Neurovirol</source><year>2009</year><volume>1</volume><fpage>11</fpage></mixed-citation></ref><ref id="B5"><mixed-citation publication-type="journal"><name><surname>Heaton</surname><given-names>RK</given-names></name><name><surname>Franklin</surname><given-names>DR</given-names></name><name><surname>Ellis</surname><given-names>RJ</given-names></name><name><surname>McCutchan</surname><given-names>JA</given-names></name><name><surname>Letendre</surname><given-names>SL</given-names></name><name><surname>Leblanc</surname><given-names>S</given-names></name><name><surname>Corkran</surname><given-names>SH</given-names></name><name><surname>Duarte</surname><given-names>NA</given-names></name><name><surname>Clifford</surname><given-names>DB</given-names></name><name><surname>Woods</surname><given-names>SP</given-names></name><name><surname>Collier</surname><given-names>AC</given-names></name><name><surname>Marra</surname><given-names>CM</given-names></name><name><surname>Morgello</surname><given-names>S</given-names></name><name><surname>Mindt</surname><given-names>MR</given-names></name><name><surname>Taylor</surname><given-names>MJ</given-names></name><name><surname>Marcotte</surname><given-names>TD</given-names></name><name><surname>Atkinson</surname><given-names>JH</given-names></name><name><surname>Wolfson</surname><given-names>T</given-names></name><name><surname>Gelman</surname><given-names>BB</given-names></name><name><surname>McArthur</surname><given-names>JC</given-names></name><name><surname>Simpson</surname><given-names>DM</given-names></name><name><surname>Abramson</surname><given-names>I</given-names></name><name><surname>Gamst</surname><given-names>A</given-names></name><name><surname>Fennema-Notestine</surname><given-names>C</given-names></name><name><surname>Jernigan</surname><given-names>TL</given-names></name><name><surname>Wong</surname><given-names>J</given-names></name><name><surname>Grant</surname><given-names>I</given-names></name><collab>CHARTER Group; HNRC Group</collab><article-title>HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors</article-title><source>J Neurovirol</source><year>2011</year><volume>17</volume><fpage>3</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">21174240</pub-id></mixed-citation></ref><ref id="B6"><mixed-citation publication-type="journal"><name><surname>Cysique</surname><given-names>LA</given-names></name><name><surname>Maruff</surname><given-names>P</given-names></name><name><surname>Brew</surname><given-names>BJ</given-names></name><article-title>Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts</article-title><source>J Neurovirol</source><year>2004</year><volume>10</volume><fpage>350</fpage><lpage>357</lpage><pub-id pub-id-type="pmid">15765806</pub-id></mixed-citation></ref><ref id="B7"><mixed-citation publication-type="journal"><name><surname>Tozzi</surname><given-names>V</given-names></name><name><surname>Balestra</surname><given-names>P</given-names></name><name><surname>Serraino</surname><given-names>D</given-names></name><name><surname>Bellagamba</surname><given-names>R</given-names></name><name><surname>Corpolongo</surname><given-names>A</given-names></name><name><surname>Piselli</surname><given-names>P</given-names></name><name><surname>Lorenzini</surname><given-names>P</given-names></name><name><surname>Visco-Comandini</surname><given-names>U</given-names></name><name><surname>Vlassi</surname><given-names>C</given-names></name><name><surname>Quartuccio</surname><given-names>ME</given-names></name><name><surname>Giulianelli</surname><given-names>M</given-names></name><name><surname>Noto</surname><given-names>P</given-names></name><name><surname>Galgani</surname><given-names>S</given-names></name><name><surname>Ippolito</surname><given-names>G</given-names></name><name><surname>Antinori</surname><given-names>A</given-names></name><name><surname>Narciso</surname><given-names>P</given-names></name><article-title>Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART</article-title><source>AIDS Res Hum Retroviruses</source><year>2005</year><volume>21</volume><fpage>706</fpage><lpage>713</lpage><pub-id pub-id-type="pmid">16131310</pub-id></mixed-citation></ref><ref id="B8"><mixed-citation publication-type="journal"><name><surname>Neuenburg</surname><given-names>JK</given-names></name><name><surname>Brodt</surname><given-names>HR</given-names></name><name><surname>Herndier</surname><given-names>BG</given-names></name><name><surname>Bickel</surname><given-names>M</given-names></name><name><surname>Bacchetti</surname><given-names>P</given-names></name><name><surname>Price</surname><given-names>RW</given-names></name><name><surname>Grant</surname><given-names>RM</given-names></name><name><surname>Schlote</surname><given-names>W</given-names></name><article-title>HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy</article-title><source>J Acquir Immune Defic Syndr</source><year>2002</year><volume>31</volume><fpage>171</fpage><lpage>177</lpage><pub-id pub-id-type="pmid">12394795</pub-id></mixed-citation></ref><ref id="B9"><mixed-citation publication-type="journal"><name><surname>McArthur</surname><given-names>JC</given-names></name><article-title>HIV dementia: an evolving disease</article-title><source>J Neuroimmunol</source><year>2004</year><volume>157</volume><fpage>3</fpage><lpage>10</lpage><pub-id pub-id-type="pmid">15579274</pub-id></mixed-citation></ref><ref id="B10"><mixed-citation publication-type="journal"><name><surname>Brew</surname><given-names>BJ</given-names></name><article-title>Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex</article-title><source>Aids</source><year>2004</year><volume>18</volume><issue>Suppl 1</issue><fpage>S75</fpage><lpage>S78</lpage><pub-id pub-id-type="pmid">15075501</pub-id></mixed-citation></ref><ref id="B11"><mixed-citation publication-type="journal"><name><surname>Gendelman</surname><given-names>HE</given-names></name><name><surname>Lipton</surname><given-names>SA</given-names></name><name><surname>Tardieu</surname><given-names>M</given-names></name><name><surname>Bukrinsky</surname><given-names>MI</given-names></name><name><surname>Nottet</surname><given-names>HS</given-names></name><article-title>The neuropathogenesis of HIV-1 infection</article-title><source>J Leukoc Biol</source><year>1994</year><volume>56</volume><fpage>389</fpage><lpage>398</lpage><pub-id pub-id-type="pmid">8083614</pub-id></mixed-citation></ref><ref id="B12"><mixed-citation publication-type="journal"><name><surname>Gendelman</surname><given-names>HE</given-names></name><name><surname>Persidsky</surname><given-names>Y</given-names></name><name><surname>Ghorpade</surname><given-names>A</given-names></name><name><surname>Limoges</surname><given-names>J</given-names></name><name><surname>Stins</surname><given-names>M</given-names></name><name><surname>Fiala</surname><given-names>M</given-names></name><name><surname>Morrisett</surname><given-names>R</given-names></name><article-title>The neuropathogenesis of the AIDS dementia complex</article-title><source>AIDS</source><year>1997</year><volume>11</volume><issue>Suppl A</issue><fpage>S35</fpage><lpage>S45</lpage><pub-id pub-id-type="pmid">9451964</pub-id></mixed-citation></ref><ref id="B13"><mixed-citation publication-type="journal"><name><surname>Patel</surname><given-names>CA</given-names></name><name><surname>Mukhtar</surname><given-names>M</given-names></name><name><surname>Harley</surname><given-names>S</given-names></name><name><surname>Kulkosky</surname><given-names>J</given-names></name><name><surname>Pomerantz</surname><given-names>RJ</given-names></name><article-title>Lentiviral expression of HIV-1 Vpr induces apoptosis in human neurons</article-title><source>J Neurovirol</source><year>2002</year><volume>8</volume><fpage>86</fpage><lpage>99</lpage><pub-id pub-id-type="pmid">11935461</pub-id></mixed-citation></ref><ref id="B14"><mixed-citation publication-type="journal"><name><surname>Jones</surname><given-names>GJ</given-names></name><name><surname>Barsby</surname><given-names>NL</given-names></name><name><surname>Cohen</surname><given-names>EA</given-names></name><name><surname>Holden</surname><given-names>J</given-names></name><name><surname>Harris</surname><given-names>K</given-names></name><name><surname>Dickie</surname><given-names>P</given-names></name><name><surname>Jhamandas</surname><given-names>J</given-names></name><name><surname>Power</surname><given-names>C</given-names></name><article-title>HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration</article-title><source>J Neurosci off J Soc Neurosci</source><year>2007</year><volume>27</volume><fpage>3703</fpage><lpage>3711</lpage></mixed-citation></ref><ref id="B15"><mixed-citation publication-type="journal"><name><surname>van de Bovenkamp</surname><given-names>M</given-names></name><name><surname>Nottet</surname><given-names>HS</given-names></name><name><surname>Pereira</surname><given-names>CF</given-names></name><article-title>Interactions of human immunodeficiency virus-1 proteins with neurons: possible role in the development of human immunodeficiency virus-1-associated dementia</article-title><source>Eur J Clin Invest</source><year>2002</year><volume>32</volume><fpage>619</fpage><lpage>627</lpage><pub-id pub-id-type="pmid">12190962</pub-id></mixed-citation></ref><ref id="B16"><mixed-citation publication-type="journal"><name><surname>Adamson</surname><given-names>DC</given-names></name><name><surname>Kopnisky</surname><given-names>KL</given-names></name><name><surname>Dawson</surname><given-names>TM</given-names></name><name><surname>Dawson</surname><given-names>VL</given-names></name><article-title>Mechanisms and structural determinants of HIV-1 coat protein, gp41-induced neurotoxicity</article-title><source>J Neurosci off J Soc Neurosci</source><year>1999</year><volume>19</volume><fpage>64</fpage><lpage>71</lpage></mixed-citation></ref><ref id="B17"><mixed-citation publication-type="journal"><name><surname>Ellis</surname><given-names>R</given-names></name><name><surname>Langford</surname><given-names>D</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><article-title>HIV and antiretroviral therapy in the brain: neuronal injury and repair</article-title><source>Nat Rev Neurosci</source><year>2007</year><volume>8</volume><fpage>33</fpage><lpage>44</lpage><pub-id pub-id-type="pmid">17180161</pub-id></mixed-citation></ref><ref id="B18"><mixed-citation publication-type="journal"><name><surname>Masliah</surname><given-names>E</given-names></name><name><surname>Heaton</surname><given-names>RK</given-names></name><name><surname>Marcotte</surname><given-names>TD</given-names></name><name><surname>Ellis</surname><given-names>RJ</given-names></name><name><surname>Wiley</surname><given-names>CA</given-names></name><name><surname>Mallory</surname><given-names>M</given-names></name><name><surname>Achim</surname><given-names>CL</given-names></name><name><surname>McCutchan</surname><given-names>JA</given-names></name><name><surname>Nelson</surname><given-names>JA</given-names></name><name><surname>Atkinson</surname><given-names>JH</given-names></name><name><surname>Grant</surname><given-names>I</given-names></name><article-title>Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center</article-title><source>Ann Neurol</source><year>1997</year><volume>42</volume><fpage>963</fpage><lpage>972</lpage><pub-id pub-id-type="pmid">9403489</pub-id></mixed-citation></ref><ref id="B19"><mixed-citation publication-type="journal"><name><surname>Iskander</surname><given-names>S</given-names></name><name><surname>Walsh</surname><given-names>KA</given-names></name><name><surname>Hammond</surname><given-names>RR</given-names></name><article-title>Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia</article-title><source>J Neuroinflammation</source><year>2004</year><volume>1</volume><fpage>7</fpage><pub-id pub-id-type="pmid">15285795</pub-id></mixed-citation></ref><ref id="B20"><mixed-citation publication-type="journal"><name><surname>Toggas</surname><given-names>SM</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><name><surname>Rockenstein</surname><given-names>EM</given-names></name><name><surname>Rall</surname><given-names>GF</given-names></name><name><surname>Abraham</surname><given-names>CR</given-names></name><name><surname>Mucke</surname><given-names>L</given-names></name><article-title>Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice</article-title><source>Nature</source><year>1994</year><volume>367</volume><fpage>188</fpage><lpage>193</lpage><pub-id pub-id-type="pmid">8114918</pub-id></mixed-citation></ref><ref id="B21"><mixed-citation publication-type="journal"><name><surname>Kim</surname><given-names>BO</given-names></name><name><surname>Liu</surname><given-names>Y</given-names></name><name><surname>Ruan</surname><given-names>Y</given-names></name><name><surname>Xu</surname><given-names>ZC</given-names></name><name><surname>Schantz</surname><given-names>L</given-names></name><name><surname>He</surname><given-names>JJ</given-names></name><article-title>Neuropathologies in transgenic mice expressing human immunodeficiency virus type 1 Tat protein under the regulation of the astrocyte-specific glial fibrillary acidic protein promoter and doxycycline</article-title><source>Am J Pathol</source><year>2003</year><volume>162</volume><fpage>1693</fpage><lpage>1707</lpage><pub-id pub-id-type="pmid">12707054</pub-id></mixed-citation></ref><ref id="B22"><mixed-citation publication-type="journal"><name><surname>Reid</surname><given-names>W</given-names></name><name><surname>Sadowska</surname><given-names>M</given-names></name><name><surname>Denaro</surname><given-names>F</given-names></name><name><surname>Rao</surname><given-names>S</given-names></name><name><surname>Foulke</surname><given-names>J</given-names><suffix>Jr</suffix></name><name><surname>Hayes</surname><given-names>N</given-names></name><name><surname>Jones</surname><given-names>O</given-names></name><name><surname>Doodnauth</surname><given-names>D</given-names></name><name><surname>Davis</surname><given-names>H</given-names></name><name><surname>Sill</surname><given-names>A</given-names></name><name><surname>O'Driscoll</surname><given-names>P</given-names></name><name><surname>Huso</surname><given-names>D</given-names></name><name><surname>Fouts</surname><given-names>T</given-names></name><name><surname>Lewis</surname><given-names>G</given-names></name><name><surname>Hill</surname><given-names>M</given-names></name><name><surname>Kamin-Lewis</surname><given-names>R</given-names></name><name><surname>Wei</surname><given-names>C</given-names></name><name><surname>Ray</surname><given-names>P</given-names></name><name><surname>Gallo</surname><given-names>RC</given-names></name><name><surname>Reitz</surname><given-names>M</given-names></name><name><surname>Bryant</surname><given-names>J</given-names></name><article-title>An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction</article-title><source>Proc Natl Acad Sci U S A</source><year>2001</year><volume>98</volume><fpage>9271</fpage><lpage>9276</lpage><pub-id pub-id-type="pmid">11481487</pub-id></mixed-citation></ref><ref id="B23"><mixed-citation publication-type="journal"><name><surname>Royal</surname><given-names>W</given-names><suffix>3rd</suffix></name><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Guo</surname><given-names>M</given-names></name><name><surname>Jones</surname><given-names>O</given-names></name><name><surname>Davis</surname><given-names>H</given-names></name><name><surname>Bryant</surname><given-names>JL</given-names></name><article-title>Immune activation, viral gene product expression and neurotoxicity in the HIV-1 transgenic rat</article-title><source>J Neuroimmunol</source><year>2012</year><volume>247</volume><fpage>16</fpage><lpage>24</lpage><pub-id pub-id-type="pmid">22503372</pub-id></mixed-citation></ref><ref id="B24"><mixed-citation publication-type="journal"><name><surname>Hoang</surname><given-names>V</given-names></name><name><surname>Withers-Ward</surname><given-names>E</given-names></name><name><surname>Camerini</surname><given-names>D</given-names></name><article-title>Nonprimate models of HIV-1 infection and pathogenesis</article-title><source>Adv Pharmacol</source><year>2008</year><volume>56</volume><fpage>399</fpage><lpage>422</lpage><pub-id pub-id-type="pmid">18086419</pub-id></mixed-citation></ref><ref id="B25"><mixed-citation publication-type="journal"><name><surname>Dickie</surname><given-names>P</given-names></name><name><surname>Felser</surname><given-names>J</given-names></name><name><surname>Eckhaus</surname><given-names>M</given-names></name><name><surname>Bryant</surname><given-names>J</given-names></name><name><surname>Silver</surname><given-names>J</given-names></name><name><surname>Marinos</surname><given-names>N</given-names></name><name><surname>Notkins</surname><given-names>AL</given-names></name><article-title>HIV-associated nephropathy in transgenic mice expressing HIV-1 genes</article-title><source>Virology</source><year>1991</year><volume>185</volume><fpage>109</fpage><lpage>119</lpage><pub-id pub-id-type="pmid">1926769</pub-id></mixed-citation></ref><ref id="B26"><mixed-citation publication-type="journal"><name><surname>Wei</surname><given-names>P</given-names></name><name><surname>Garber</surname><given-names>ME</given-names></name><name><surname>Fang</surname><given-names>SM</given-names></name><name><surname>Fischer</surname><given-names>WH</given-names></name><name><surname>Jones</surname><given-names>KA</given-names></name><article-title>A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA</article-title><source>Cell</source><year>1998</year><volume>92</volume><fpage>451</fpage><lpage>462</lpage><pub-id pub-id-type="pmid">9491887</pub-id></mixed-citation></ref><ref id="B27"><mixed-citation publication-type="journal"><name><surname>Reid</surname><given-names>W</given-names></name><name><surname>Abdelwahab</surname><given-names>S</given-names></name><name><surname>Sadowska</surname><given-names>M</given-names></name><name><surname>Huso</surname><given-names>D</given-names></name><name><surname>Neal</surname><given-names>A</given-names></name><name><surname>Ahearn</surname><given-names>A</given-names></name><name><surname>Bryant</surname><given-names>J</given-names></name><name><surname>Gallo</surname><given-names>RC</given-names></name><name><surname>Lewis</surname><given-names>GK</given-names></name><name><surname>Reitz</surname><given-names>M</given-names></name><article-title>HIV-1 transgenic rats develop T cell abnormalities</article-title><source>Virology</source><year>2004</year><volume>321</volume><fpage>111</fpage><lpage>119</lpage><pub-id pub-id-type="pmid">15033570</pub-id></mixed-citation></ref><ref id="B28"><mixed-citation publication-type="journal"><name><surname>Subramanian</surname><given-names>A</given-names></name><name><surname>Tamayo</surname><given-names>P</given-names></name><name><surname>Mootha</surname><given-names>VK</given-names></name><name><surname>Mukherjee</surname><given-names>S</given-names></name><name><surname>Ebert</surname><given-names>BL</given-names></name><name><surname>Gillette</surname><given-names>MA</given-names></name><name><surname>Paulovich</surname><given-names>A</given-names></name><name><surname>Pomeroy</surname><given-names>SL</given-names></name><name><surname>Golub</surname><given-names>TR</given-names></name><name><surname>Lander</surname><given-names>ES</given-names></name><name><surname>Mesirov</surname><given-names>JP</given-names></name><article-title>Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles</article-title><source>Proc Natl Acad Sci USA</source><year>2005</year><volume>102</volume><fpage>15545</fpage><lpage>15550</lpage><pub-id pub-id-type="pmid">16199517</pub-id></mixed-citation></ref><ref id="B29"><mixed-citation publication-type="journal"><name><surname>Gerlai</surname><given-names>R</given-names></name><article-title>A new continuous alternation task in T-maze detects hippocampal dysfunction in mice. A strain comparison and lesion study</article-title><source>Behav Brain Res</source><year>1998</year><volume>95</volume><fpage>91</fpage><lpage>101</lpage><pub-id pub-id-type="pmid">9754881</pub-id></mixed-citation></ref><ref id="B30"><mixed-citation publication-type="journal"><name><surname>Gerlai</surname><given-names>R</given-names></name><name><surname>Shinsky</surname><given-names>N</given-names></name><name><surname>Shih</surname><given-names>A</given-names></name><name><surname>Williams</surname><given-names>P</given-names></name><name><surname>Winer</surname><given-names>J</given-names></name><name><surname>Armanini</surname><given-names>M</given-names></name><name><surname>Cairns</surname><given-names>B</given-names></name><name><surname>Winslow</surname><given-names>J</given-names></name><name><surname>Gao</surname><given-names>W</given-names></name><name><surname>Phillips</surname><given-names>HS</given-names></name><article-title>Regulation of learning by EphA receptors: a protein targeting study</article-title><source>J Neurosci off j Soc Neurosci</source><year>1999</year><volume>19</volume><fpage>9538</fpage><lpage>9549</lpage></mixed-citation></ref><ref id="B31"><mixed-citation publication-type="journal"><name><surname>Clark</surname><given-names>RE</given-names></name><name><surname>Zola</surname><given-names>SM</given-names></name><name><surname>Squire</surname><given-names>LR</given-names></name><article-title>Impaired recognition memory in rats after damage to the hippocampus</article-title><source>J Neurosci Off J Soci Neurosci</source><year>2000</year><volume>20</volume><fpage>8853</fpage><lpage>8860</lpage></mixed-citation></ref><ref id="B32"><mixed-citation publication-type="journal"><name><surname>Johnson</surname><given-names>CT</given-names></name><name><surname>Olton</surname><given-names>DS</given-names></name><name><surname>Gage</surname><given-names>FH</given-names><suffix>3rd</suffix></name><name><surname>Jenko</surname><given-names>PG</given-names></name><article-title>Damage to hippocampus and hippocampal connections: effects on DRL and spontaneous alternation</article-title><source>J Comp Physiol Psychol</source><year>1977</year><volume>91</volume><fpage>508</fpage><lpage>522</lpage><pub-id pub-id-type="pmid">874119</pub-id></mixed-citation></ref><ref id="B33"><mixed-citation publication-type="journal"><name><surname>Futter</surname><given-names>JE</given-names></name><name><surname>Aggleton</surname><given-names>JP</given-names></name><article-title>How rats perform spatial working memory tasks: limitations in the use of egocentric and idiothetic working memory</article-title><source>Q J Exp Psychol (Colchester)</source><year>2006</year><volume>59</volume><fpage>77</fpage><lpage>99</lpage></mixed-citation></ref><ref id="B34"><mixed-citation publication-type="journal"><name><surname>Stone</surname><given-names>WS</given-names></name><name><surname>Rudd</surname><given-names>RJ</given-names></name><name><surname>Parsons</surname><given-names>MW</given-names></name><name><surname>Gold</surname><given-names>PE</given-names></name><article-title>Memory scores in middle-aged rats predict later deficits in memory, paradoxical sleep, and blood glucose regulation in old age</article-title><source>Exp Aging Res</source><year>1997</year><volume>23</volume><fpage>287</fpage><lpage>300</lpage><pub-id pub-id-type="pmid">9248821</pub-id></mixed-citation></ref><ref id="B35"><mixed-citation publication-type="journal"><name><surname>Buhot</surname><given-names>MC</given-names></name><name><surname>Dubayle</surname><given-names>D</given-names></name><name><surname>Malleret</surname><given-names>G</given-names></name><name><surname>Javerzat</surname><given-names>S</given-names></name><name><surname>Segu</surname><given-names>L</given-names></name><article-title>Exploration, anxiety, and spatial memory in transgenic anophthalmic mice</article-title><source>Behav Neurosci</source><year>2001</year><volume>115</volume><fpage>455</fpage><lpage>467</lpage><pub-id pub-id-type="pmid">11345970</pub-id></mixed-citation></ref><ref id="B36"><mixed-citation publication-type="journal"><name><surname>Lashomb</surname><given-names>AL</given-names></name><name><surname>Vigorito</surname><given-names>M</given-names></name><name><surname>Chang</surname><given-names>SL</given-names></name><article-title>Further characterization of the spatial learning deficit in the human immunodeficiency virus-1 transgenic rat</article-title><source>J Neurovirol</source><year>2009</year><volume>15</volume><fpage>14</fpage><lpage>24</lpage><pub-id pub-id-type="pmid">19085205</pub-id></mixed-citation></ref><ref id="B37"><mixed-citation publication-type="journal"><name><surname>Vigorito</surname><given-names>M</given-names></name><name><surname>LaShomb</surname><given-names>AL</given-names></name><name><surname>Chang</surname><given-names>SL</given-names></name><article-title>Spatial learning and memory in HIV-1 transgenic rats</article-title><source>J Neuroimmune Pharmacol</source><year>2007</year><volume>2</volume><fpage>319</fpage><lpage>328</lpage><pub-id pub-id-type="pmid">18040850</pub-id></mixed-citation></ref><ref id="B38"><mixed-citation publication-type="journal"><name><surname>Fields</surname><given-names>J</given-names></name><name><surname>Dumaop</surname><given-names>W</given-names></name><name><surname>Adame</surname><given-names>A</given-names></name><name><surname>Ellis</surname><given-names>RJ</given-names></name><name><surname>Letendre</surname><given-names>S</given-names></name><name><surname>Grant</surname><given-names>I</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><article-title>Alterations in the Levels of Vesicular Trafficking Proteins Involved in HIV Replication in the Brains and CSF of Patients with HIV-associated Neurocognitive Disorders</article-title><source>J Neuroimmune Pharmacol</source><year>2013</year><volume>8</volume><issue>5</issue><fpage>1197</fpage><lpage>209</lpage><comment>doi:10.1007/s11481-013-9511-3.</comment><pub-id pub-id-type="pmid">24292993</pub-id></mixed-citation></ref><ref id="B39"><mixed-citation publication-type="journal"><name><surname>Wang</surname><given-names>RG</given-names></name><name><surname>Kaul</surname><given-names>M</given-names></name><name><surname>Zhang</surname><given-names>DX</given-names></name><article-title>Interferon-stimulated gene 15 as a general marker for acute and chronic neuronal injuries</article-title><source>Sheng Li Xue Bao</source><year>2012</year><volume>64</volume><fpage>577</fpage><lpage>583</lpage><pub-id pub-id-type="pmid">23090498</pub-id></mixed-citation></ref><ref id="B40"><mixed-citation publication-type="journal"><name><surname>Katsounas</surname><given-names>A</given-names></name><name><surname>Hubbard</surname><given-names>JJ</given-names></name><name><surname>Wang</surname><given-names>CH</given-names></name><name><surname>Zhang</surname><given-names>X</given-names></name><name><surname>Dou</surname><given-names>D</given-names></name><name><surname>Shivakumar</surname><given-names>B</given-names></name><name><surname>Winter</surname><given-names>S</given-names></name><name><surname>Schlaak</surname><given-names>JF</given-names></name><name><surname>Lempicki</surname><given-names>RA</given-names></name><name><surname>Masur</surname><given-names>H</given-names></name><name><surname>Polis</surname><given-names>M</given-names></name><name><surname>Kottilil</surname><given-names>S</given-names></name><name><surname>Osinusi</surname><given-names>A</given-names></name><article-title>High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV</article-title><source>J Med Virol</source><year>2013</year><volume>85</volume><fpage>959</fpage><lpage>963</lpage><pub-id pub-id-type="pmid">23588721</pub-id></mixed-citation></ref><ref id="B41"><mixed-citation publication-type="journal"><name><surname>Meeker</surname><given-names>RB</given-names></name><name><surname>Poulton</surname><given-names>W</given-names></name><name><surname>Markovic-Plese</surname><given-names>S</given-names></name><name><surname>Hall</surname><given-names>C</given-names></name><name><surname>Robertson</surname><given-names>K</given-names></name><article-title>Protein changes in CSF of HIV-infected patients: evidence for loss of neuroprotection</article-title><source>J Neurovirol</source><year>2011</year><volume>17</volume><fpage>258</fpage><lpage>273</lpage><pub-id pub-id-type="pmid">21556959</pub-id></mixed-citation></ref><ref id="B42"><mixed-citation publication-type="journal"><name><surname>Froldi</surname><given-names>M</given-names></name><name><surname>Castagna</surname><given-names>A</given-names></name><name><surname>Parma</surname><given-names>M</given-names></name><name><surname>Piona</surname><given-names>A</given-names></name><name><surname>Tedeschi</surname><given-names>A</given-names></name><name><surname>Miadonna</surname><given-names>A</given-names></name><name><surname>Lorini</surname><given-names>M</given-names></name><name><surname>Orazio</surname><given-names>EN</given-names></name><name><surname>Lazzarin</surname><given-names>A</given-names></name><article-title>Mediator release in cerebrospinal fluid of human immunodeficiency virus-positive patients with central nervous system involvement</article-title><source>J Neuroimmunol</source><year>1992</year><volume>38</volume><fpage>155</fpage><lpage>161</lpage><pub-id pub-id-type="pmid">1315794</pub-id></mixed-citation></ref><ref id="B43"><mixed-citation publication-type="journal"><name><surname>Masliah</surname><given-names>E</given-names></name><name><surname>Roberts</surname><given-names>ES</given-names></name><name><surname>Langford</surname><given-names>D</given-names></name><name><surname>Everall</surname><given-names>I</given-names></name><name><surname>Crews</surname><given-names>L</given-names></name><name><surname>Adame</surname><given-names>A</given-names></name><name><surname>Rockenstein</surname><given-names>E</given-names></name><name><surname>Fox</surname><given-names>HS</given-names></name><article-title>Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis</article-title><source>J Neuroimmunol</source><year>2004</year><volume>157</volume><fpage>163</fpage><lpage>175</lpage><pub-id pub-id-type="pmid">15579294</pub-id></mixed-citation></ref><ref id="B44"><mixed-citation publication-type="journal"><name><surname>Shaw</surname><given-names>KN</given-names></name><name><surname>Commins</surname><given-names>S</given-names></name><name><surname>O'Mara</surname><given-names>SM</given-names></name><article-title>Cyclooxygenase inhibition attenuates endotoxin-induced spatial learning deficits, but not an endotoxin-induced blockade of long-term potentiation</article-title><source>Brain Res</source><year>2005</year><volume>1038</volume><fpage>231</fpage><lpage>237</lpage><pub-id pub-id-type="pmid">15757639</pub-id></mixed-citation></ref><ref id="B45"><mixed-citation publication-type="journal"><name><surname>Basselin</surname><given-names>M</given-names></name><name><surname>Ramadan</surname><given-names>E</given-names></name><name><surname>Igarashi</surname><given-names>M</given-names></name><name><surname>Chang</surname><given-names>L</given-names></name><name><surname>Chen</surname><given-names>M</given-names></name><name><surname>Kraft</surname><given-names>AD</given-names></name><name><surname>Harry</surname><given-names>GJ</given-names></name><name><surname>Rapoport</surname><given-names>SI</given-names></name><article-title>Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats</article-title><source>J Cereb Blood Flow Metab</source><year>2011</year><volume>31</volume><fpage>486</fpage><lpage>493</lpage><pub-id pub-id-type="pmid">20664612</pub-id></mixed-citation></ref><ref id="B46"><mixed-citation publication-type="journal"><name><surname>Mohri</surname><given-names>I</given-names></name><name><surname>Taniike</surname><given-names>M</given-names></name><name><surname>Taniguchi</surname><given-names>H</given-names></name><name><surname>Kanekiyo</surname><given-names>T</given-names></name><name><surname>Aritake</surname><given-names>K</given-names></name><name><surname>Inui</surname><given-names>T</given-names></name><name><surname>Fukumoto</surname><given-names>N</given-names></name><name><surname>Eguchi</surname><given-names>N</given-names></name><name><surname>Kushi</surname><given-names>A</given-names></name><name><surname>Sasai</surname><given-names>H</given-names></name><name><surname>Kanaoka</surname><given-names>Y</given-names></name><name><surname>Ozono</surname><given-names>K</given-names></name><name><surname>Narumiya</surname><given-names>S</given-names></name><name><surname>Suzuki</surname><given-names>K</given-names></name><name><surname>Urade</surname><given-names>Y</given-names></name><article-title>Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher</article-title><source>J Neurosci Off J Soc Neurosci</source><year>2006</year><volume>26</volume><fpage>4383</fpage><lpage>4393</lpage></mixed-citation></ref><ref id="B47"><mixed-citation publication-type="journal"><name><surname>Kalaria</surname><given-names>RN</given-names></name><name><surname>Pax</surname><given-names>AB</given-names></name><article-title>Increased collagen content of cerebral microvessels in Alzheimer's disease</article-title><source>Brain Res</source><year>1995</year><volume>705</volume><fpage>349</fpage><lpage>352</lpage><pub-id pub-id-type="pmid">8821769</pub-id></mixed-citation></ref><ref id="B48"><mixed-citation publication-type="journal"><name><surname>van Horssen</surname><given-names>J</given-names></name><name><surname>Bo</surname><given-names>L</given-names></name><name><surname>Dijkstra</surname><given-names>CD</given-names></name><name><surname>de Vries</surname><given-names>HE</given-names></name><article-title>Extensive extracellular matrix depositions in active multiple sclerosis lesions</article-title><source>Neurobiol Dis</source><year>2006</year><volume>24</volume><fpage>484</fpage><lpage>491</lpage><pub-id pub-id-type="pmid">17005408</pub-id></mixed-citation></ref><ref id="B49"><mixed-citation publication-type="journal"><name><surname>Veznedaroglu</surname><given-names>E</given-names></name><name><surname>Van Bockstaele</surname><given-names>EJ</given-names></name><name><surname>O'Connor</surname><given-names>MJ</given-names></name><article-title>Extravascular collagen in the human epileptic brain: a potential substrate for aberrant cell migration in cases of temporal lobe epilepsy</article-title><source>J Neurosurg</source><year>2002</year><volume>97</volume><fpage>1125</fpage><lpage>1130</lpage><pub-id pub-id-type="pmid">12450035</pub-id></mixed-citation></ref><ref id="B50"><mixed-citation publication-type="journal"><name><surname>Gelman</surname><given-names>BB</given-names></name><name><surname>Chen</surname><given-names>T</given-names></name><name><surname>Lisinicchia</surname><given-names>JG</given-names></name><name><surname>Soukup</surname><given-names>VM</given-names></name><name><surname>Carmical</surname><given-names>JR</given-names></name><name><surname>Starkey</surname><given-names>JM</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><name><surname>Commins</surname><given-names>DL</given-names></name><name><surname>Brandt</surname><given-names>D</given-names></name><name><surname>Grant</surname><given-names>I</given-names></name><name><surname>Singer</surname><given-names>EJ</given-names></name><name><surname>Levine</surname><given-names>AJ</given-names></name><name><surname>Miller</surname><given-names>J</given-names></name><name><surname>Winkler</surname><given-names>JM</given-names></name><name><surname>Fox</surname><given-names>HS</given-names></name><name><surname>Luxon</surname><given-names>BA</given-names></name><name><surname>Morgello</surname><given-names>S</given-names></name><collab>National NeuroAIDS Tissue Consortium</collab><article-title>The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment</article-title><source>PLoS One</source><year>2012</year><volume>7</volume><fpage>e46178</fpage><pub-id pub-id-type="pmid">23049970</pub-id></mixed-citation></ref><ref id="B51"><mixed-citation publication-type="journal"><name><surname>Pocernich</surname><given-names>CB</given-names></name><name><surname>Poon</surname><given-names>HF</given-names></name><name><surname>Boyd-Kimball</surname><given-names>D</given-names></name><name><surname>Lynn</surname><given-names>BC</given-names></name><name><surname>Nath</surname><given-names>A</given-names></name><name><surname>Klein</surname><given-names>JB</given-names></name><name><surname>Butterfield</surname><given-names>DA</given-names></name><article-title>Proteomic analysis of oxidatively modified proteins induced by the mitochondrial toxin 3-nitropropionic acid in human astrocytes expressing the HIV protein tat</article-title><source>Brain Res Mol Brain Res</source><year>2005</year><volume>133</volume><fpage>299</fpage><lpage>306</lpage><pub-id pub-id-type="pmid">15710247</pub-id></mixed-citation></ref><ref id="B52"><mixed-citation publication-type="journal"><name><surname>Landi</surname><given-names>S</given-names></name><name><surname>Putignano</surname><given-names>E</given-names></name><name><surname>Boggio</surname><given-names>EM</given-names></name><name><surname>Giustetto</surname><given-names>M</given-names></name><name><surname>Pizzorusso</surname><given-names>T</given-names></name><name><surname>Ratto</surname><given-names>GM</given-names></name><article-title>The short-time structural plasticity of dendritic spines is altered in a model of Rett syndrome</article-title><source>Scientific Reports</source><year>2011</year><volume>1</volume><fpage>45</fpage><pub-id pub-id-type="pmid">22355564</pub-id></mixed-citation></ref><ref id="B53"><mixed-citation publication-type="journal"><name><surname>Barros</surname><given-names>CS</given-names></name><name><surname>Calabrese</surname><given-names>B</given-names></name><name><surname>Chamero</surname><given-names>P</given-names></name><name><surname>Roberts</surname><given-names>AJ</given-names></name><name><surname>Korzus</surname><given-names>E</given-names></name><name><surname>Lloyd</surname><given-names>K</given-names></name><name><surname>Stowers</surname><given-names>L</given-names></name><name><surname>Mayford</surname><given-names>M</given-names></name><name><surname>Halpain</surname><given-names>S</given-names></name><name><surname>Muller</surname><given-names>U</given-names></name><article-title>Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system</article-title><source>Proc Natl Acad Sci USA</source><year>2009</year><volume>106</volume><fpage>4507</fpage><lpage>4512</lpage><pub-id pub-id-type="pmid">19240213</pub-id></mixed-citation></ref><ref id="B54"><mixed-citation publication-type="journal"><name><surname>Grant</surname><given-names>A</given-names></name><name><surname>Hoops</surname><given-names>D</given-names></name><name><surname>Labelle-Dumais</surname><given-names>C</given-names></name><name><surname>Prevost</surname><given-names>M</given-names></name><name><surname>Rajabi</surname><given-names>H</given-names></name><name><surname>Kolb</surname><given-names>B</given-names></name><name><surname>Stewart</surname><given-names>J</given-names></name><name><surname>Arvanitogiannis</surname><given-names>A</given-names></name><name><surname>Flores</surname><given-names>C</given-names></name><article-title>Netrin-1 receptor-deficient mice show enhanced mesocortical dopamine transmission and blunted behavioural responses to amphetamine</article-title><source>Eur J Neurosci</source><year>2007</year><volume>26</volume><fpage>3215</fpage><lpage>3228</lpage><pub-id pub-id-type="pmid">18005074</pub-id></mixed-citation></ref><ref id="B55"><mixed-citation publication-type="journal"><name><surname>Benarroch</surname><given-names>EE</given-names></name><article-title>Insulin-like growth factors in the brain and their potential clinical implications</article-title><source>Neurology</source><year>2012</year><volume>79</volume><fpage>2148</fpage><lpage>2153</lpage><pub-id pub-id-type="pmid">23170013</pub-id></mixed-citation></ref><ref id="B56"><mixed-citation publication-type="journal"><name><surname>Szczesny</surname><given-names>E</given-names></name><name><surname>Slusarczyk</surname><given-names>J</given-names></name><name><surname>Glombik</surname><given-names>K</given-names></name><name><surname>Budziszewska</surname><given-names>B</given-names></name><name><surname>Kubera</surname><given-names>M</given-names></name><name><surname>Lason</surname><given-names>W</given-names></name><name><surname>Basta-Kaim</surname><given-names>A</given-names></name><article-title>Possible contribution of IGF-1 to depressive disorder</article-title><source>Pharmacol Reports PR</source><year>2013</year><volume>65</volume><fpage>1622</fpage><lpage>1631</lpage></mixed-citation></ref><ref id="B57"><mixed-citation publication-type="journal"><name><surname>Von Bohlen Und Halbach</surname><given-names>O</given-names></name><name><surname>Unsicker</surname><given-names>K</given-names></name><article-title>Neurotrophic support of midbrain dopaminergic neurons</article-title><source>Adv Exp Med Biol</source><year>2009</year><volume>651</volume><fpage>73</fpage><lpage>80</lpage><pub-id pub-id-type="pmid">19731552</pub-id></mixed-citation></ref><ref id="B58"><mixed-citation publication-type="journal"><name><surname>Clemmons</surname><given-names>DR</given-names></name><name><surname>Busby</surname><given-names>WH</given-names></name><name><surname>Arai</surname><given-names>T</given-names></name><name><surname>Nam</surname><given-names>TJ</given-names></name><name><surname>Clarke</surname><given-names>JB</given-names></name><name><surname>Jones</surname><given-names>JI</given-names></name><name><surname>Ankrapp</surname><given-names>DK</given-names></name><article-title>Role of insulin-like growth factor binding proteins in the control of IGF actions</article-title><source>Progress Growth Factor Res</source><year>1995</year><volume>6</volume><fpage>357</fpage><lpage>366</lpage></mixed-citation></ref><ref id="B59"><mixed-citation publication-type="journal"><name><surname>Clemmons</surname><given-names>DR</given-names></name><name><surname>Jones</surname><given-names>JI</given-names></name><name><surname>Busby</surname><given-names>WH</given-names></name><name><surname>Wright</surname><given-names>G</given-names></name><article-title>Role of insulin-like growth factor binding proteins in modifying IGF actions</article-title><source>Ann N Y Acad Sci</source><year>1993</year><volume>692</volume><fpage>10</fpage><lpage>21</lpage><pub-id pub-id-type="pmid">7692784</pub-id></mixed-citation></ref><ref id="B60"><mixed-citation publication-type="journal"><name><surname>Besset</surname><given-names>V</given-names></name><name><surname>Le Magueresse-Battistoni</surname><given-names>B</given-names></name><name><surname>Collette</surname><given-names>J</given-names></name><name><surname>Benahmed</surname><given-names>M</given-names></name><article-title>Tumor necrosis factor alpha stimulates insulin-like growth factor binding protein 3 expression in cultured porcine Sertoli cells</article-title><source>Endocrinology</source><year>1996</year><volume>137</volume><fpage>296</fpage><lpage>303</lpage><pub-id pub-id-type="pmid">8536626</pub-id></mixed-citation></ref><ref id="B61"><mixed-citation publication-type="journal"><name><surname>Scharla</surname><given-names>SH</given-names></name><name><surname>Strong</surname><given-names>DD</given-names></name><name><surname>Mohan</surname><given-names>S</given-names></name><name><surname>Chevalley</surname><given-names>T</given-names></name><name><surname>Linkhart</surname><given-names>TA</given-names></name><article-title>Effect of tumor necrosis factor-alpha on the expression of insulin-like growth factor I and insulin-like growth factor binding protein 4 in mouse osteoblasts</article-title><source>Eur J Endocrinol/Eur Federation Endocrine Societies</source><year>1994</year><volume>131</volume><fpage>293</fpage><lpage>301</lpage></mixed-citation></ref><ref id="B62"><mixed-citation publication-type="journal"><name><surname>Street</surname><given-names>ME</given-names></name><name><surname>Ziveri</surname><given-names>MA</given-names></name><name><surname>Spaggiari</surname><given-names>C</given-names></name><name><surname>Viani</surname><given-names>I</given-names></name><name><surname>Volta</surname><given-names>C</given-names></name><name><surname>Grzincich</surname><given-names>GL</given-names></name><name><surname>Virdis</surname><given-names>R</given-names></name><name><surname>Bernasconi</surname><given-names>S</given-names></name><article-title>Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis</article-title><source>Eur J Endocrinol / Eur Federation Endocrine Societies</source><year>2006</year><volume>154</volume><fpage>47</fpage><lpage>52</lpage></mixed-citation></ref><ref id="B63"><mixed-citation publication-type="journal"><name><surname>Tazearslan</surname><given-names>C</given-names></name><name><surname>Huang</surname><given-names>J</given-names></name><name><surname>Barzilai</surname><given-names>N</given-names></name><name><surname>Suh</surname><given-names>Y</given-names></name><article-title>Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles</article-title><source>Aging cell</source><year>2011</year><volume>10</volume><fpage>551</fpage><lpage>554</lpage><pub-id pub-id-type="pmid">21388493</pub-id></mixed-citation></ref><ref id="B64"><mixed-citation publication-type="journal"><name><surname>Xi</surname><given-names>ZQ</given-names></name><name><surname>Wang</surname><given-names>LY</given-names></name><name><surname>Sun</surname><given-names>JJ</given-names></name><name><surname>Liu</surname><given-names>XZ</given-names></name><name><surname>Zhu</surname><given-names>X</given-names></name><name><surname>Xiao</surname><given-names>F</given-names></name><name><surname>Guan</surname><given-names>LF</given-names></name><name><surname>Li</surname><given-names>JM</given-names></name><name><surname>Wang</surname><given-names>L</given-names></name><name><surname>Wang</surname><given-names>XF</given-names></name><article-title>TDAG51 in the anterior temporal neocortex of patients with intractable epilepsy</article-title><source>Neurosci Lett</source><year>2007</year><volume>425</volume><fpage>53</fpage><lpage>58</lpage><pub-id pub-id-type="pmid">17870236</pub-id></mixed-citation></ref><ref id="B65"><mixed-citation publication-type="journal"><name><surname>Basseri</surname><given-names>S</given-names></name><name><surname>Lhotak</surname><given-names>S</given-names></name><name><surname>Fullerton</surname><given-names>MD</given-names></name><name><surname>Palanivel</surname><given-names>R</given-names></name><name><surname>Jiang</surname><given-names>H</given-names></name><name><surname>Lynn</surname><given-names>EG</given-names></name><name><surname>Ford</surname><given-names>RJ</given-names></name><name><surname>Maclean</surname><given-names>KN</given-names></name><name><surname>Steinberg</surname><given-names>GR</given-names></name><name><surname>Austin</surname><given-names>RC</given-names></name><article-title>Loss of TDAG51 results in mature-onset obesity, hepatic steatosis, and insulin resistance by regulating lipogenesis</article-title><source>Diabetes</source><year>2013</year><volume>62</volume><fpage>158</fpage><lpage>169</lpage><pub-id pub-id-type="pmid">22961087</pub-id></mixed-citation></ref><ref id="B66"><mixed-citation publication-type="journal"><name><surname>Murata</surname><given-names>T</given-names></name><name><surname>Sato</surname><given-names>T</given-names></name><name><surname>Kamoda</surname><given-names>T</given-names></name><name><surname>Moriyama</surname><given-names>H</given-names></name><name><surname>Kumazawa</surname><given-names>Y</given-names></name><name><surname>Hanada</surname><given-names>N</given-names></name><article-title>Differential susceptibility to hydrogen sulfide-induced apoptosis between PHLDA1-overexpressing oral cancer cell lines and oral keratinocytes: Role of PHLDA1 as an apoptosis suppressor</article-title><source>Exp Cell Res</source><year>2014</year><volume>320</volume><fpage>247</fpage><lpage>257</lpage><pub-id pub-id-type="pmid">24270013</pub-id></mixed-citation></ref><ref id="B67"><mixed-citation publication-type="journal"><name><surname>Park</surname><given-names>ES</given-names></name><name><surname>Kim</surname><given-names>J</given-names></name><name><surname>Ha</surname><given-names>TU</given-names></name><name><surname>Choi</surname><given-names>JS</given-names></name><name><surname>Soo Hong</surname><given-names>K</given-names></name><name><surname>Rho</surname><given-names>J</given-names></name><article-title>TDAG51 deficiency promotes oxidative stress-induced apoptosis through the generation of reactive oxygen species in mouse embryonic fibroblasts</article-title><source>Exp Mol Med</source><year>2013</year><volume>45</volume><fpage>e35</fpage><pub-id pub-id-type="pmid">23928855</pub-id></mixed-citation></ref><ref id="B68"><mixed-citation publication-type="journal"><name><surname>Park</surname><given-names>CG</given-names></name><name><surname>Lee</surname><given-names>SY</given-names></name><name><surname>Kandala</surname><given-names>G</given-names></name><name><surname>Lee</surname><given-names>SY</given-names></name><name><surname>Choi</surname><given-names>Y</given-names></name><article-title>A novel gene product that couples TCR signaling to Fas(CD95) expression in activation-induced cell death</article-title><source>Immunity</source><year>1996</year><volume>4</volume><fpage>583</fpage><lpage>591</lpage><pub-id pub-id-type="pmid">8673705</pub-id></mixed-citation></ref><ref id="B69"><mixed-citation publication-type="journal"><name><surname>Mei</surname><given-names>L</given-names></name><name><surname>Xiong</surname><given-names>WC</given-names></name><article-title>Neuregulin 1 in neural development, synaptic plasticity and schizophrenia</article-title><source>Nat Rev Neurosci</source><year>2008</year><volume>9</volume><fpage>437</fpage><lpage>452</lpage><pub-id pub-id-type="pmid">18478032</pub-id></mixed-citation></ref><ref id="B70"><mixed-citation publication-type="journal"><name><surname>Lai Wing Sun</surname><given-names>K</given-names></name><name><surname>Correia</surname><given-names>JP</given-names></name><name><surname>Kennedy</surname><given-names>TE</given-names></name><article-title>Netrins: versatile extracellular cues with diverse functions</article-title><source>Development</source><year>2011</year><volume>138</volume><fpage>2153</fpage><lpage>2169</lpage><pub-id pub-id-type="pmid">21558366</pub-id></mixed-citation></ref><ref id="B71"><mixed-citation publication-type="journal"><name><surname>Horn</surname><given-names>KE</given-names></name><name><surname>Glasgow</surname><given-names>SD</given-names></name><name><surname>Gobert</surname><given-names>D</given-names></name><name><surname>Bull</surname><given-names>SJ</given-names></name><name><surname>Luk</surname><given-names>T</given-names></name><name><surname>Girgis</surname><given-names>J</given-names></name><name><surname>Tremblay</surname><given-names>ME</given-names></name><name><surname>McEachern</surname><given-names>D</given-names></name><name><surname>Bouchard</surname><given-names>JF</given-names></name><name><surname>Haber</surname><given-names>M</given-names></name><name><surname>Hamel</surname><given-names>E</given-names></name><name><surname>Krimpenfort</surname><given-names>P</given-names></name><name><surname>Murai</surname><given-names>KK</given-names></name><name><surname>Berns</surname><given-names>A</given-names></name><name><surname>Doucet</surname><given-names>G</given-names></name><name><surname>Chapman</surname><given-names>CA</given-names></name><name><surname>Ruthazer</surname><given-names>ES</given-names></name><name><surname>Kennedy</surname><given-names>TE</given-names></name><article-title>DCC expression by neurons regulates synaptic plasticity in the adult brain</article-title><source>Cell Rep</source><year>2013</year><volume>3</volume><fpage>173</fpage><lpage>185</lpage><pub-id pub-id-type="pmid">23291093</pub-id></mixed-citation></ref><ref id="B72"><mixed-citation publication-type="journal"><name><surname>Llambi</surname><given-names>F</given-names></name><name><surname>Lourenco</surname><given-names>FC</given-names></name><name><surname>Gozuacik</surname><given-names>D</given-names></name><name><surname>Guix</surname><given-names>C</given-names></name><name><surname>Pays</surname><given-names>L</given-names></name><name><surname>Del Rio</surname><given-names>G</given-names></name><name><surname>Kimchi</surname><given-names>A</given-names></name><name><surname>Mehlen</surname><given-names>P</given-names></name><article-title>The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase</article-title><source>EMBO J</source><year>2005</year><volume>24</volume><fpage>1192</fpage><lpage>1201</lpage><pub-id pub-id-type="pmid">15729359</pub-id></mixed-citation></ref><ref id="B73"><mixed-citation publication-type="journal"><name><surname>Barallobre</surname><given-names>MJ</given-names></name><name><surname>Pascual</surname><given-names>M</given-names></name><name><surname>Del Rio</surname><given-names>JA</given-names></name><name><surname>Soriano</surname><given-names>E</given-names></name><article-title>The Netrin family of guidance factors: emphasis on Netrin-1 signalling</article-title><source>Brain Res Brain Res Rev</source><year>2005</year><volume>49</volume><fpage>22</fpage><lpage>47</lpage><pub-id pub-id-type="pmid">15960985</pub-id></mixed-citation></ref><ref id="B74"><mixed-citation publication-type="journal"><name><surname>Bradford</surname><given-names>D</given-names></name><name><surname>Faull</surname><given-names>RL</given-names></name><name><surname>Curtis</surname><given-names>MA</given-names></name><name><surname>Cooper</surname><given-names>HM</given-names></name><article-title>Characterization of the netrin/RGMa receptor neogenin in neurogenic regions of the mouse and human adult forebrain</article-title><source>J Comp Neurol</source><year>2010</year><volume>518</volume><fpage>3237</fpage><lpage>3253</lpage><pub-id pub-id-type="pmid">20575069</pub-id></mixed-citation></ref><ref id="B75"><mixed-citation publication-type="journal"><name><surname>Staquicini</surname><given-names>FI</given-names></name><name><surname>Dias-Neto</surname><given-names>E</given-names></name><name><surname>Li</surname><given-names>J</given-names></name><name><surname>Snyder</surname><given-names>EY</given-names></name><name><surname>Sidman</surname><given-names>RL</given-names></name><name><surname>Pasqualini</surname><given-names>R</given-names></name><name><surname>Arap</surname><given-names>W</given-names></name><article-title>Discovery of a functional protein complex of netrin-4, laminin gamma1 chain, and integrin alpha6beta1 in mouse neural stem cells</article-title><source>Proc Natl Acad Sci U S A</source><year>2009</year><volume>106</volume><fpage>2903</fpage><lpage>2908</lpage><pub-id pub-id-type="pmid">19193855</pub-id></mixed-citation></ref><ref id="B76"><mixed-citation publication-type="journal"><name><surname>Cayre</surname><given-names>M</given-names></name><name><surname>Courtes</surname><given-names>S</given-names></name><name><surname>Martineau</surname><given-names>F</given-names></name><name><surname>Giordano</surname><given-names>M</given-names></name><name><surname>Arnaud</surname><given-names>K</given-names></name><name><surname>Zamaron</surname><given-names>A</given-names></name><name><surname>Durbec</surname><given-names>P</given-names></name><article-title>Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination</article-title><source>Development</source><year>2013</year><volume>140</volume><fpage>3107</fpage><lpage>3117</lpage><pub-id pub-id-type="pmid">23824572</pub-id></mixed-citation></ref><ref id="B77"><mixed-citation publication-type="journal"><name><surname>Peng</surname><given-names>H</given-names></name><name><surname>Sun</surname><given-names>L</given-names></name><name><surname>Jia</surname><given-names>B</given-names></name><name><surname>Lan</surname><given-names>X</given-names></name><name><surname>Zhu</surname><given-names>B</given-names></name><name><surname>Wu</surname><given-names>Y</given-names></name><name><surname>Zheng</surname><given-names>J</given-names></name><article-title>HIV-1-infected and immune-activated macrophages induce astrocytic differentiation of human cortical neural progenitor cells via the STAT3 pathway</article-title><source>PLoS One</source><year>2011</year><volume>6</volume><fpage>e19439</fpage><pub-id pub-id-type="pmid">21637744</pub-id></mixed-citation></ref><ref id="B78"><mixed-citation publication-type="journal"><name><surname>Swiech</surname><given-names>L</given-names></name><name><surname>Perycz</surname><given-names>M</given-names></name><name><surname>Malik</surname><given-names>A</given-names></name><name><surname>Jaworski</surname><given-names>J</given-names></name><article-title>Role of mTOR in physiology and pathology of the nervous system</article-title><source>Biochim Biophys Acta</source><year>2008</year><volume>1784</volume><fpage>116</fpage><lpage>132</lpage><pub-id pub-id-type="pmid">17913600</pub-id></mixed-citation></ref><ref id="B79"><mixed-citation publication-type="journal"><name><surname>Germain</surname><given-names>M</given-names></name><name><surname>Nguyen</surname><given-names>AP</given-names></name><name><surname>Khacho</surname><given-names>M</given-names></name><name><surname>Patten</surname><given-names>DA</given-names></name><name><surname>Screaton</surname><given-names>RA</given-names></name><name><surname>Park</surname><given-names>DS</given-names></name><name><surname>Slack</surname><given-names>RS</given-names></name><article-title>LKB1-regulated adaptive mechanisms are essential for neuronal survival following mitochondrial dysfunction</article-title><source>Hum Mol Genet</source><year>2013</year><volume>22</volume><fpage>952</fpage><lpage>962</lpage><pub-id pub-id-type="pmid">23187960</pub-id></mixed-citation></ref><ref id="B80"><mixed-citation publication-type="journal"><name><surname>Cross</surname><given-names>DA</given-names></name><name><surname>Alessi</surname><given-names>DR</given-names></name><name><surname>Cohen</surname><given-names>P</given-names></name><name><surname>Andjelkovich</surname><given-names>M</given-names></name><name><surname>Hemmings</surname><given-names>BA</given-names></name><article-title>Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B</article-title><source>Nature</source><year>1995</year><volume>378</volume><fpage>785</fpage><lpage>789</lpage><pub-id pub-id-type="pmid">8524413</pub-id></mixed-citation></ref><ref id="B81"><mixed-citation publication-type="journal"><name><surname>Mocchetti</surname><given-names>I</given-names></name><name><surname>Bachis</surname><given-names>A</given-names></name><name><surname>Campbell</surname><given-names>LA</given-names></name><name><surname>Avdoshina</surname><given-names>V</given-names></name><article-title>Implementing Neuronal Plasticity in NeuroAIDS: the Experience of Brain-derived Neurotrophic Factor and other Neurotrophic Factors</article-title><source>J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol</source><year>2013</year><volume>9</volume><issue>2</issue><fpage>80</fpage><lpage>91</lpage><comment>doi:10.1007/s11481-013-9488-y</comment></mixed-citation></ref><ref id="B82"><mixed-citation publication-type="journal"><name><surname>Woodbury</surname><given-names>ME</given-names></name><name><surname>Ikezu</surname><given-names>T</given-names></name><article-title>Fibroblast Growth Factor-2 Signaling in Neurogenesis and Neurodegeneration</article-title><source>J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol</source><year>2013</year><volume>9</volume><issue>2</issue><fpage>92</fpage><lpage>101</lpage><comment>doi:10.1007/s11481-013-9501-5</comment></mixed-citation></ref><ref id="B83"><mixed-citation publication-type="journal"><name><surname>Fields</surname><given-names>J</given-names></name><name><surname>Dumaop</surname><given-names>W</given-names></name><name><surname>Langford</surname><given-names>TD</given-names></name><name><surname>Rockenstein</surname><given-names>E</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><article-title>Role of Neurotrophic Factor Alterations in the Neurodegenerative Process in HIV Associated Neurocognitive Disorders</article-title><source>J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol</source><year>2014</year><volume>9</volume><issue>2</issue><fpage>102</fpage><lpage>116</lpage><comment>doi:10.1007/s11481-013-9520-2.</comment></mixed-citation></ref><ref id="B84"><mixed-citation publication-type="journal"><name><surname>Sanna</surname><given-names>PP</given-names></name><name><surname>Cammalleri</surname><given-names>M</given-names></name><name><surname>Berton</surname><given-names>F</given-names></name><name><surname>Simpson</surname><given-names>C</given-names></name><name><surname>Lutjens</surname><given-names>R</given-names></name><name><surname>Bloom</surname><given-names>FE</given-names></name><name><surname>Francesconi</surname><given-names>W</given-names></name><article-title>Phosphatidylinositol 3-kinase is required for the expression but not for the induction or the maintenance of long-term potentiation in the hippocampal CA1 region</article-title><source>J Neurosci Off J Soc for Neurosci</source><year>2002</year><volume>22</volume><fpage>3359</fpage><lpage>3365</lpage></mixed-citation></ref><ref id="B85"><mixed-citation publication-type="journal"><name><surname>Cammalleri</surname><given-names>M</given-names></name><name><surname>Lutjens</surname><given-names>R</given-names></name><name><surname>Berton</surname><given-names>F</given-names></name><name><surname>King</surname><given-names>AR</given-names></name><name><surname>Simpson</surname><given-names>C</given-names></name><name><surname>Francesconi</surname><given-names>W</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><article-title>Time-restricted role for dendritic activation of the mTOR-p70S6K pathway in the induction of late-phase long-term potentiation in the CA1</article-title><source>Proc Natl Acad Sci USA</source><year>2003</year><volume>100</volume><fpage>14368</fpage><lpage>14373</lpage><pub-id pub-id-type="pmid">14623952</pub-id></mixed-citation></ref><ref id="B86"><mixed-citation publication-type="journal"><name><surname>Tang</surname><given-names>SJ</given-names></name><name><surname>Reis</surname><given-names>G</given-names></name><name><surname>Kang</surname><given-names>H</given-names></name><name><surname>Gingras</surname><given-names>AC</given-names></name><name><surname>Sonenberg</surname><given-names>N</given-names></name><name><surname>Schuman</surname><given-names>EM</given-names></name><article-title>A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus</article-title><source>Proc Natl Acad Sci U S A</source><year>2002</year><volume>99</volume><fpage>467</fpage><lpage>472</lpage><pub-id pub-id-type="pmid">11756682</pub-id></mixed-citation></ref><ref id="B87"><mixed-citation publication-type="journal"><name><surname>Diaz-Ruiz</surname><given-names>O</given-names></name><name><surname>Navarro</surname><given-names>L</given-names></name><name><surname>Mendez-Diaz</surname><given-names>M</given-names></name><name><surname>Galicia</surname><given-names>O</given-names></name><name><surname>Elder</surname><given-names>JH</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><name><surname>Drucker-Colin</surname><given-names>R</given-names></name><name><surname>Prospero-Garcia</surname><given-names>O</given-names></name><article-title>Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase</article-title><source>Brain Res</source><year>2001</year><volume>913</volume><fpage>78</fpage><lpage>81</lpage><pub-id pub-id-type="pmid">11532249</pub-id></mixed-citation></ref><ref id="B88"><mixed-citation publication-type="journal"><name><surname>Van Veldhoven</surname><given-names>PP</given-names></name><article-title>Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism</article-title><source>J Lipid Res</source><year>2010</year><volume>51</volume><fpage>2863</fpage><lpage>2895</lpage><pub-id pub-id-type="pmid">20558530</pub-id></mixed-citation></ref><ref id="B89"><mixed-citation publication-type="journal"><name><surname>Ivashchenko</surname><given-names>O</given-names></name><name><surname>Van Veldhoven</surname><given-names>PP</given-names></name><name><surname>Brees</surname><given-names>C</given-names></name><name><surname>Ho</surname><given-names>YS</given-names></name><name><surname>Terlecky</surname><given-names>SR</given-names></name><name><surname>Fransen</surname><given-names>M</given-names></name><article-title>Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk</article-title><source>Mol Biol Cell</source><year>2011</year><volume>22</volume><fpage>1440</fpage><lpage>1451</lpage><pub-id pub-id-type="pmid">21372177</pub-id></mixed-citation></ref><ref id="B90"><mixed-citation publication-type="journal"><name><surname>Louboutin</surname><given-names>JP</given-names></name><name><surname>Agrawal</surname><given-names>L</given-names></name><name><surname>Reyes</surname><given-names>BA</given-names></name><name><surname>Van Bockstaele</surname><given-names>EJ</given-names></name><name><surname>Strayer</surname><given-names>DS</given-names></name><article-title>HIV-1 gp120-induced injury to the blood–brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress</article-title><source>J Neuropathol Exp Neurol</source><year>2010</year><volume>69</volume><fpage>801</fpage><lpage>816</lpage><pub-id pub-id-type="pmid">20613638</pub-id></mixed-citation></ref><ref id="B91"><mixed-citation publication-type="journal"><name><surname>Masliah</surname><given-names>E</given-names></name><name><surname>Ge</surname><given-names>N</given-names></name><name><surname>Mucke</surname><given-names>L</given-names></name><article-title>Pathogenesis of HIV-1 associated neurodegeneration</article-title><source>Crit Rev Neurobiol</source><year>1996</year><volume>10</volume><fpage>57</fpage><lpage>67</lpage><pub-id pub-id-type="pmid">8853954</pub-id></mixed-citation></ref><ref id="B92"><mixed-citation publication-type="journal"><name><surname>Cutler</surname><given-names>RG</given-names></name><name><surname>Haughey</surname><given-names>NJ</given-names></name><name><surname>Tammara</surname><given-names>A</given-names></name><name><surname>McArthur</surname><given-names>JC</given-names></name><name><surname>Nath</surname><given-names>A</given-names></name><name><surname>Reid</surname><given-names>R</given-names></name><name><surname>Vargas</surname><given-names>DL</given-names></name><name><surname>Pardo</surname><given-names>CA</given-names></name><name><surname>Mattson</surname><given-names>MP</given-names></name><article-title>Dysregulation of sphingolipid and sterol metabolism by ApoE4 in HIV dementia</article-title><source>Neurology</source><year>2004</year><volume>63</volume><fpage>626</fpage><lpage>630</lpage><pub-id pub-id-type="pmid">15326233</pub-id></mixed-citation></ref><ref id="B93"><mixed-citation publication-type="journal"><name><surname>Deicken</surname><given-names>RF</given-names></name><name><surname>Hubesch</surname><given-names>B</given-names></name><name><surname>Jensen</surname><given-names>PC</given-names></name><name><surname>Sappey-Marinier</surname><given-names>D</given-names></name><name><surname>Krell</surname><given-names>P</given-names></name><name><surname>Wisniewski</surname><given-names>A</given-names></name><name><surname>Vanderburg</surname><given-names>D</given-names></name><name><surname>Parks</surname><given-names>R</given-names></name><name><surname>Fein</surname><given-names>G</given-names></name><name><surname>Weiner</surname><given-names>MW</given-names></name><article-title>Alterations in brain phosphate metabolite concentrations in patients with human immunodeficiency virus infection</article-title><source>Arch Neurol</source><year>1991</year><volume>48</volume><fpage>203</fpage><lpage>209</lpage><pub-id pub-id-type="pmid">1993012</pub-id></mixed-citation></ref><ref id="B94"><mixed-citation publication-type="journal"><name><surname>Uzasci</surname><given-names>L</given-names></name><name><surname>Nath</surname><given-names>A</given-names></name><name><surname>Cotter</surname><given-names>R</given-names></name><article-title>Oxidative stress and the HIV-infected brain proteome</article-title><source>J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol</source><year>2013</year><volume>8</volume><fpage>1167</fpage><lpage>1180</lpage></mixed-citation></ref><ref id="B95"><mixed-citation publication-type="journal"><name><surname>Margottin</surname><given-names>F</given-names></name><name><surname>Bour</surname><given-names>SP</given-names></name><name><surname>Durand</surname><given-names>H</given-names></name><name><surname>Selig</surname><given-names>L</given-names></name><name><surname>Benichou</surname><given-names>S</given-names></name><name><surname>Richard</surname><given-names>V</given-names></name><name><surname>Thomas</surname><given-names>D</given-names></name><name><surname>Strebel</surname><given-names>K</given-names></name><name><surname>Benarous</surname><given-names>R</given-names></name><article-title>A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif</article-title><source>Mol Cell</source><year>1998</year><volume>1</volume><fpage>565</fpage><lpage>574</lpage><pub-id pub-id-type="pmid">9660940</pub-id></mixed-citation></ref><ref id="B96"><mixed-citation publication-type="journal"><name><surname>Li</surname><given-names>YP</given-names></name><article-title>Protein B23 is an important human factor for the nucleolar localization of the human immunodeficiency virus protein Tat</article-title><source>J Virol</source><year>1997</year><volume>71</volume><fpage>4098</fpage><lpage>4102</lpage><pub-id pub-id-type="pmid">9094689</pub-id></mixed-citation></ref><ref id="B97"><mixed-citation publication-type="journal"><name><surname>Bisikirska</surname><given-names>BC</given-names></name><name><surname>Adam</surname><given-names>SJ</given-names></name><name><surname>Alvarez</surname><given-names>MJ</given-names></name><name><surname>Rajbhandari</surname><given-names>P</given-names></name><name><surname>Cox</surname><given-names>R</given-names></name><name><surname>Lefebvre</surname><given-names>C</given-names></name><name><surname>Wang</surname><given-names>K</given-names></name><name><surname>Rieckhof</surname><given-names>GE</given-names></name><name><surname>Felsher</surname><given-names>DW</given-names></name><name><surname>Califano</surname><given-names>A</given-names></name><article-title>STK38 is a critical upstream regulator of MYC's oncogenic activity in human B-cell lymphoma</article-title><source>Oncogene</source><year>2013</year><volume>32</volume><fpage>5283</fpage><lpage>5291</lpage><pub-id pub-id-type="pmid">23178486</pub-id></mixed-citation></ref><ref id="B98"><mixed-citation publication-type="journal"><name><surname>Conti</surname><given-names>B</given-names></name><name><surname>Maier</surname><given-names>R</given-names></name><name><surname>Barr</surname><given-names>AM</given-names></name><name><surname>Morale</surname><given-names>MC</given-names></name><name><surname>Lu</surname><given-names>X</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><name><surname>Bilbe</surname><given-names>G</given-names></name><name><surname>Hoyer</surname><given-names>D</given-names></name><name><surname>Bartfai</surname><given-names>T</given-names></name><article-title>Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine</article-title><source>Mol Psychiatry</source><year>2006</year><volume>12</volume><issue>2</issue><fpage>167</fpage><lpage>189</lpage><pub-id pub-id-type="pmid">17033635</pub-id></mixed-citation></ref><ref id="B99"><mixed-citation publication-type="journal"><name><surname>Huang</surname><given-names>YC</given-names></name><article-title>The role of in vitro gene expression profiling in particulate matter health research</article-title><source>J Toxicol Environ Health B Crit Rev</source><year>2013</year><volume>16</volume><fpage>381</fpage><lpage>394</lpage><pub-id pub-id-type="pmid">24151968</pub-id></mixed-citation></ref><ref id="B100"><mixed-citation publication-type="journal"><name><surname>Letendre</surname><given-names>S</given-names></name><article-title>Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder</article-title><source>Top Antivir Med</source><year>2011</year><volume>19</volume><fpage>137</fpage><lpage>142</lpage><pub-id pub-id-type="pmid">22156215</pub-id></mixed-citation></ref><ref id="B101"><mixed-citation publication-type="journal"><name><surname>Nabha</surname><given-names>L</given-names></name><name><surname>Duong</surname><given-names>L</given-names></name><name><surname>Timpone</surname><given-names>J</given-names></name><article-title>HIV-associated neurocognitive disorders: perspective on management strategies</article-title><source>Drugs</source><year>2013</year><volume>73</volume><fpage>893</fpage><lpage>905</lpage><pub-id pub-id-type="pmid">23733447</pub-id></mixed-citation></ref><ref id="B102"><mixed-citation publication-type="journal"><name><surname>Schifitto</surname><given-names>G</given-names></name><name><surname>Navia</surname><given-names>BA</given-names></name><name><surname>Yiannoutsos</surname><given-names>CT</given-names></name><name><surname>Marra</surname><given-names>CM</given-names></name><name><surname>Chang</surname><given-names>L</given-names></name><name><surname>Ernst</surname><given-names>T</given-names></name><name><surname>Jarvik</surname><given-names>JG</given-names></name><name><surname>Miller</surname><given-names>EN</given-names></name><name><surname>Singer</surname><given-names>EJ</given-names></name><name><surname>Ellis</surname><given-names>RJ</given-names></name><name><surname>Kolson</surname><given-names>DL</given-names></name><name><surname>Simpson</surname><given-names>D</given-names></name><name><surname>Nath</surname><given-names>A</given-names></name><name><surname>Berger</surname><given-names>J</given-names></name><name><surname>Shriver</surname><given-names>SL</given-names></name><name><surname>Millar</surname><given-names>LL</given-names></name><name><surname>Colquhoun</surname><given-names>D</given-names></name><name><surname>Lenkinski</surname><given-names>R</given-names></name><name><surname>Gonzalez</surname><given-names>RG</given-names></name><name><surname>Lipton</surname><given-names>SA</given-names></name><collab>Adult AIDS Clinical Trial Group (ACTG) 301; 700 Teams; HIV MRS Consortium</collab><article-title>Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study</article-title><source>AIDS</source><year>2007</year><volume>21</volume><fpage>1877</fpage><lpage>1886</lpage><pub-id pub-id-type="pmid">17721095</pub-id></mixed-citation></ref><ref id="B103"><mixed-citation publication-type="journal"><name><surname>Zhao</surname><given-names>Y</given-names></name><name><surname>Navia</surname><given-names>BA</given-names></name><name><surname>Marra</surname><given-names>CM</given-names></name><name><surname>Singer</surname><given-names>EJ</given-names></name><name><surname>Chang</surname><given-names>L</given-names></name><name><surname>Berger</surname><given-names>J</given-names></name><name><surname>Ellis</surname><given-names>RJ</given-names></name><name><surname>Kolson</surname><given-names>DL</given-names></name><name><surname>Simpson</surname><given-names>D</given-names></name><name><surname>Miller</surname><given-names>EN</given-names></name><name><surname>Lipton</surname><given-names>SA</given-names></name><name><surname>Evans</surname><given-names>SR</given-names></name><name><surname>Schifitto</surname><given-names>G</given-names></name><collab>Adult Aids Clinical Trial Group (ACTG) 301 Team</collab><article-title>Memantine for AIDS dementia complex: open-label report of ACTG 301</article-title><source>HIV Clin Trials</source><year>2010</year><volume>11</volume><fpage>59</fpage><lpage>67</lpage><pub-id pub-id-type="pmid">20400412</pub-id></mixed-citation></ref><ref id="B104"><mixed-citation publication-type="journal"><name><surname>Fabbrini</surname><given-names>G</given-names></name><name><surname>Abbruzzese</surname><given-names>G</given-names></name><name><surname>Marconi</surname><given-names>S</given-names></name><name><surname>Zappia</surname><given-names>M</given-names></name><article-title>Selegiline: a reappraisal of its role in Parkinson disease</article-title><source>Clin Neuropharmacol</source><year>2012</year><volume>35</volume><fpage>134</fpage><lpage>140</lpage><pub-id pub-id-type="pmid">22592509</pub-id></mixed-citation></ref><ref id="B105"><mixed-citation publication-type="journal"><name><surname>Shulman</surname><given-names>KI</given-names></name><name><surname>Herrmann</surname><given-names>N</given-names></name><name><surname>Walker</surname><given-names>SE</given-names></name><article-title>Current place of monoamine oxidase inhibitors in the treatment of depression</article-title><source>CNS drugs</source><year>2013</year><volume>27</volume><fpage>789</fpage><lpage>797</lpage><pub-id pub-id-type="pmid">23934742</pub-id></mixed-citation></ref><ref id="B106"><mixed-citation publication-type="journal"><name><surname>Breitbart</surname><given-names>W</given-names></name><name><surname>Rosenfeld</surname><given-names>B</given-names></name><name><surname>Kaim</surname><given-names>M</given-names></name><name><surname>Funesti-Esch</surname><given-names>J</given-names></name><article-title>A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease</article-title><source>Arch Intern Med</source><year>2001</year><volume>161</volume><fpage>411</fpage><lpage>420</lpage><pub-id pub-id-type="pmid">11176767</pub-id></mixed-citation></ref><ref id="B107"><mixed-citation publication-type="journal"><name><surname>Fiala</surname><given-names>M</given-names></name><name><surname>Liu</surname><given-names>QN</given-names></name><name><surname>Sayre</surname><given-names>J</given-names></name><name><surname>Pop</surname><given-names>V</given-names></name><name><surname>Brahmandam</surname><given-names>V</given-names></name><name><surname>Graves</surname><given-names>MC</given-names></name><name><surname>Vinters</surname><given-names>HV</given-names></name><article-title>Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood–brain barrier</article-title><source>Eur J Clin Investig</source><year>2002</year><volume>32</volume><fpage>360</fpage><lpage>371</lpage><pub-id pub-id-type="pmid">12027877</pub-id></mixed-citation></ref><ref id="B108"><mixed-citation publication-type="journal"><name><surname>Graves</surname><given-names>MC</given-names></name><name><surname>Fiala</surname><given-names>M</given-names></name><name><surname>Dinglasan</surname><given-names>LA</given-names></name><name><surname>Liu</surname><given-names>NQ</given-names></name><name><surname>Sayre</surname><given-names>J</given-names></name><name><surname>Chiappelli</surname><given-names>F</given-names></name><name><surname>van Kooten</surname><given-names>C</given-names></name><name><surname>Vinters</surname><given-names>HV</given-names></name><article-title>nflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells</article-title><source>Amyotrop Lateral Sclerosis Motor Neuron Disorders Off Publ World Fed Neurol Res Group Motor Neuron Dis</source><year>2004</year><volume>5</volume><fpage>213</fpage><lpage>219</lpage></mixed-citation></ref><ref id="B109"><mixed-citation publication-type="journal"><name><surname>Pettersen</surname><given-names>FO</given-names></name><name><surname>Torheim</surname><given-names>EA</given-names></name><name><surname>Dahm</surname><given-names>AE</given-names></name><name><surname>Aaberge</surname><given-names>IS</given-names></name><name><surname>Lind</surname><given-names>A</given-names></name><name><surname>Holm</surname><given-names>M</given-names></name><name><surname>Aandahl</surname><given-names>EM</given-names></name><name><surname>Sandset</surname><given-names>PM</given-names></name><name><surname>Tasken</surname><given-names>K</given-names></name><name><surname>Kvale</surname><given-names>D</given-names></name><article-title>An exploratory trial of cyclooxygenase type 2 inhibitor in HIV-1 infection: downregulated immune activation and improved T cell-dependent vaccine responses</article-title><source>J Virol</source><year>2011</year><volume>85</volume><fpage>6557</fpage><lpage>6566</lpage><pub-id pub-id-type="pmid">21490090</pub-id></mixed-citation></ref><ref id="B110"><mixed-citation publication-type="journal"><name><surname>Ebert</surname><given-names>AD</given-names></name><name><surname>Beres</surname><given-names>AJ</given-names></name><name><surname>Barber</surname><given-names>AE</given-names></name><name><surname>Svendsen</surname><given-names>CN</given-names></name><article-title>Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease</article-title><source>Exp Neurol</source><year>2008</year><volume>209</volume><fpage>213</fpage><lpage>223</lpage><pub-id pub-id-type="pmid">18061591</pub-id></mixed-citation></ref><ref id="B111"><mixed-citation publication-type="journal"><name><surname>Quesada</surname><given-names>A</given-names></name><name><surname>Lee</surname><given-names>BY</given-names></name><name><surname>Micevych</surname><given-names>PE</given-names></name><article-title>PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease</article-title><source>Dev Neurobiol</source><year>2008</year><volume>68</volume><fpage>632</fpage><lpage>644</lpage><pub-id pub-id-type="pmid">18278798</pub-id></mixed-citation></ref><ref id="B112"><mixed-citation publication-type="journal"><name><surname>Carro</surname><given-names>E</given-names></name><name><surname>Trejo</surname><given-names>JL</given-names></name><name><surname>Gerber</surname><given-names>A</given-names></name><name><surname>Loetscher</surname><given-names>H</given-names></name><name><surname>Torrado</surname><given-names>J</given-names></name><name><surname>Metzger</surname><given-names>F</given-names></name><name><surname>Torres-Aleman</surname><given-names>I</given-names></name><article-title>Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis</article-title><source>Neurobiol Aging</source><year>2006</year><volume>27</volume><fpage>1250</fpage><lpage>1257</lpage><pub-id pub-id-type="pmid">16183170</pub-id></mixed-citation></ref><ref id="B113"><mixed-citation publication-type="journal"><name><surname>Carro</surname><given-names>E</given-names></name><name><surname>Trejo</surname><given-names>JL</given-names></name><name><surname>Gomez-Isla</surname><given-names>T</given-names></name><name><surname>LeRoith</surname><given-names>D</given-names></name><name><surname>Torres-Aleman</surname><given-names>I</given-names></name><article-title>Serum insulin-like growth factor I regulates brain amyloid-beta levels</article-title><source>Nat Med</source><year>2002</year><volume>8</volume><fpage>1390</fpage><lpage>1397</lpage><pub-id pub-id-type="pmid">12415260</pub-id></mixed-citation></ref><ref id="B114"><mixed-citation publication-type="journal"><name><surname>Bassil</surname><given-names>F</given-names></name><name><surname>Fernagut</surname><given-names>PO</given-names></name><name><surname>Bezard</surname><given-names>E</given-names></name><name><surname>Meissner</surname><given-names>WG</given-names></name><article-title>Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: Targets for disease modification?</article-title><source>Prog Neurobiol</source><year>2014</year><volume>118C</volume><fpage>1</fpage><lpage>18</lpage><comment>doi:10.1016/j.pneurobio.2014.02.005</comment><pub-id pub-id-type="pmid">24582776</pub-id></mixed-citation></ref><ref id="B115"><mixed-citation publication-type="journal"><name><surname>Kang</surname><given-names>YJ</given-names></name><name><surname>Digicaylioglu</surname><given-names>M</given-names></name><name><surname>Russo</surname><given-names>R</given-names></name><name><surname>Kaul</surname><given-names>M</given-names></name><name><surname>Achim</surname><given-names>CL</given-names></name><name><surname>Fletcher</surname><given-names>L</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><name><surname>Lipton</surname><given-names>SA</given-names></name><article-title>Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders</article-title><source>Ann Neurol</source><year>2010</year><volume>68</volume><fpage>342</fpage><lpage>352</lpage><pub-id pub-id-type="pmid">20818790</pub-id></mixed-citation></ref><ref id="B116"><mixed-citation publication-type="journal"><name><surname>Cabou</surname><given-names>C</given-names></name><name><surname>Campistron</surname><given-names>G</given-names></name><name><surname>Marsollier</surname><given-names>N</given-names></name><name><surname>Leloup</surname><given-names>C</given-names></name><name><surname>Cruciani-Guglielmacci</surname><given-names>C</given-names></name><name><surname>Penicaud</surname><given-names>L</given-names></name><name><surname>Drucker</surname><given-names>DJ</given-names></name><name><surname>Magnan</surname><given-names>C</given-names></name><name><surname>Burcelin</surname><given-names>R</given-names></name><article-title>Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity</article-title><source>Diabetes</source><year>2008</year><volume>57</volume><fpage>2577</fpage><lpage>2587</lpage><pub-id pub-id-type="pmid">18633100</pub-id></mixed-citation></ref><ref id="B117"><mixed-citation publication-type="journal"><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Duffy</surname><given-names>KB</given-names></name><name><surname>Ottinger</surname><given-names>MA</given-names></name><name><surname>Ray</surname><given-names>B</given-names></name><name><surname>Bailey</surname><given-names>JA</given-names></name><name><surname>Holloway</surname><given-names>HW</given-names></name><name><surname>Tweedie</surname><given-names>D</given-names></name><name><surname>Perry</surname><given-names>T</given-names></name><name><surname>Mattson</surname><given-names>MP</given-names></name><name><surname>Kapogiannis</surname><given-names>D</given-names></name><name><surname>Sambamurti</surname><given-names>K</given-names></name><name><surname>Lahiri</surname><given-names>DK</given-names></name><name><surname>Greig</surname><given-names>NH</given-names></name><article-title>GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease</article-title><source>J Alzheimer's Dis JAD</source><year>2010</year><volume>19</volume><fpage>1205</fpage><lpage>1219</lpage></mixed-citation></ref><ref id="B118"><mixed-citation publication-type="journal"><name><surname>Bertilsson</surname><given-names>G</given-names></name><name><surname>Patrone</surname><given-names>C</given-names></name><name><surname>Zachrisson</surname><given-names>O</given-names></name><name><surname>Andersson</surname><given-names>A</given-names></name><name><surname>Dannaeus</surname><given-names>K</given-names></name><name><surname>Heidrich</surname><given-names>J</given-names></name><name><surname>Kortesmaa</surname><given-names>J</given-names></name><name><surname>Mercer</surname><given-names>A</given-names></name><name><surname>Nielsen</surname><given-names>E</given-names></name><name><surname>Ronnholm</surname><given-names>H</given-names></name><name><surname>Wikstrom</surname><given-names>L</given-names></name><article-title>Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease</article-title><source>J Neurosci Res</source><year>2008</year><volume>86</volume><fpage>326</fpage><lpage>338</lpage><pub-id pub-id-type="pmid">17803225</pub-id></mixed-citation></ref><ref id="B119"><mixed-citation publication-type="journal"><name><surname>Harkavyi</surname><given-names>A</given-names></name><name><surname>Abuirmeileh</surname><given-names>A</given-names></name><name><surname>Lever</surname><given-names>R</given-names></name><name><surname>Kingsbury</surname><given-names>AE</given-names></name><name><surname>Biggs</surname><given-names>CS</given-names></name><name><surname>Whitton</surname><given-names>PS</given-names></name><article-title>Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease</article-title><source>J Neuroinflammation</source><year>2008</year><volume>5</volume><fpage>19</fpage><pub-id pub-id-type="pmid">18492290</pub-id></mixed-citation></ref><ref id="B120"><mixed-citation publication-type="journal"><name><surname>Gespach</surname><given-names>C</given-names></name><article-title>Guidance for life, cell death, and colorectal neoplasia by netrin dependence receptors</article-title><source>Adv Cancer Res</source><year>2012</year><volume>114</volume><fpage>87</fpage><lpage>186</lpage><pub-id pub-id-type="pmid">22588057</pub-id></mixed-citation></ref><ref id="B121"><mixed-citation publication-type="journal"><name><surname>Deng</surname><given-names>C</given-names></name><name><surname>Pan</surname><given-names>B</given-names></name><name><surname>Engel</surname><given-names>M</given-names></name><name><surname>Huang</surname><given-names>XF</given-names></name><article-title>Neuregulin-1 signalling and antipsychotic treatment: potential therapeutic targets in a schizophrenia candidate signalling pathway</article-title><source>Psychopharmacol</source><year>2013</year><volume>226</volume><fpage>201</fpage><lpage>215</lpage></mixed-citation></ref><ref id="B122"><mixed-citation publication-type="journal"><name><surname>Contreras</surname><given-names>X</given-names></name><name><surname>Barboric</surname><given-names>M</given-names></name><name><surname>Lenasi</surname><given-names>T</given-names></name><name><surname>Peterlin</surname><given-names>BM</given-names></name><article-title>HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription</article-title><source>PLoS Pathog</source><year>2007</year><volume>3</volume><fpage>1459</fpage><lpage>1469</lpage><pub-id pub-id-type="pmid">17937499</pub-id></mixed-citation></ref><ref id="B123"><mixed-citation publication-type="journal"><name><surname>Doyon</surname><given-names>G</given-names></name><name><surname>Sobolewski</surname><given-names>MD</given-names></name><name><surname>Huber</surname><given-names>K</given-names></name><name><surname>McMahon</surname><given-names>D</given-names></name><name><surname>Mellors</surname><given-names>JW</given-names></name><name><surname>Sluis-Cremer</surname><given-names>N</given-names></name><article-title>Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110alpha that reactivates latent HIV-1</article-title><source>PLoS One</source><year>2014</year><volume>9</volume><fpage>e84964</fpage><pub-id pub-id-type="pmid">24489654</pub-id></mixed-citation></ref><ref id="B124"><mixed-citation publication-type="journal"><name><surname>Patrick</surname><given-names>C</given-names></name><name><surname>Crews</surname><given-names>L</given-names></name><name><surname>Desplats</surname><given-names>P</given-names></name><name><surname>Dumaop</surname><given-names>W</given-names></name><name><surname>Rockenstein</surname><given-names>E</given-names></name><name><surname>Achim</surname><given-names>CL</given-names></name><name><surname>Everall</surname><given-names>IP</given-names></name><name><surname>Masliah</surname><given-names>E</given-names></name><article-title>Increased CDK5 expression in HIV encephalitis contributes to neurodegeneration via tau phosphorylation and is reversed with Roscovitine</article-title><source>Am J Pathol</source><year>2011</year><volume>178</volume><fpage>1646</fpage><lpage>1661</lpage><pub-id pub-id-type="pmid">21435449</pub-id></mixed-citation></ref><ref id="B125"><mixed-citation publication-type="journal"><name><surname>Ahmed</surname><given-names>SH</given-names></name><name><surname>Lutjens</surname><given-names>R</given-names></name><name><surname>van der Stap</surname><given-names>LD</given-names></name><name><surname>Lekic</surname><given-names>D</given-names></name><name><surname>Romano-Spica</surname><given-names>V</given-names></name><name><surname>Morales</surname><given-names>M</given-names></name><name><surname>Koob</surname><given-names>GF</given-names></name><name><surname>Repunte-Canonigo</surname><given-names>V</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><article-title>Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction</article-title><source>Proc Natl Acad Sci USA</source><year>2005</year><volume>102</volume><fpage>11533</fpage><lpage>11538</lpage><pub-id pub-id-type="pmid">16076954</pub-id></mixed-citation></ref><ref id="B126"><mixed-citation publication-type="journal"><name><surname>Repunte-Canonigo</surname><given-names>V</given-names></name><name><surname>van der Stap</surname><given-names>LD</given-names></name><name><surname>Chen</surname><given-names>J</given-names></name><name><surname>Sabino</surname><given-names>V</given-names></name><name><surname>Wagner</surname><given-names>U</given-names></name><name><surname>Zorrilla</surname><given-names>EP</given-names></name><name><surname>Schumann</surname><given-names>G</given-names></name><name><surname>Roberts</surname><given-names>AJ</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><article-title>Genome-wide gene expression analysis identifies K-ras as a regulator of alcohol intake</article-title><source>Brain Res</source><year>2010</year><volume>1339</volume><fpage>1</fpage><lpage>10</lpage><pub-id pub-id-type="pmid">20388501</pub-id></mixed-citation></ref><ref id="B127"><mixed-citation publication-type="journal"><name><surname>Repunte-Canonigo</surname><given-names>V</given-names></name><name><surname>Lutjens</surname><given-names>R</given-names></name><name><surname>van der Stap</surname><given-names>LD</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><article-title>Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure</article-title><source>Brain Res</source><year>2007</year><volume>1138</volume><fpage>48</fpage><lpage>56</lpage><pub-id pub-id-type="pmid">17270154</pub-id></mixed-citation></ref><ref id="B128"><mixed-citation publication-type="other"><name><surname>Repunte-Canonigo</surname><given-names>V</given-names></name><name><surname>Chen</surname><given-names>J</given-names></name><name><surname>Lefebvre</surname><given-names>C</given-names></name><name><surname>Kawamura</surname><given-names>T</given-names></name><name><surname>Kreifeldt</surname><given-names>M</given-names></name><name><surname>Basson</surname><given-names>O</given-names></name><name><surname>Roberts</surname><given-names>AJ</given-names></name><name><surname>Sanna</surname><given-names>PP</given-names></name><article-title>MeCP2 regulates ethanol sensitivity and intake</article-title><source>Addict Biol</source><year>2013</year><comment>doi:10.1111/adb.12047</comment></mixed-citation></ref><ref id="B129"><mixed-citation publication-type="journal"><name><surname>Livak</surname><given-names>KJ</given-names></name><name><surname>Schmittgen</surname><given-names>TD</given-names></name><article-title>Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method</article-title><source>Methods</source><year>2001</year><volume>25</volume><fpage>402</fpage><lpage>408</lpage><pub-id pub-id-type="pmid">11846609</pub-id></mixed-citation></ref><ref id="B130"><mixed-citation publication-type="journal"><name><surname>Douglas</surname><given-names>RJ</given-names></name><name><surname>Raphelson</surname><given-names>AC</given-names></name><article-title>Spontaneous alternation and septal lesions</article-title><source>J Comp Physiol Psychol</source><year>1966</year><volume>62</volume><fpage>320</fpage><lpage>322</lpage><pub-id pub-id-type="pmid">5338926</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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