Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease
Identifieur interne : 001564 ( Ncbi/Merge ); précédent : 001563; suivant : 001565Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease
Auteurs : Stéphanie Bissonnette [Canada] ; Mylène Vaillancourt [Canada] ; Sébastien S. Hébert [Canada] ; Guy Drolet [Canada] ; Pershia Samadi [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
The reduction of pre-enkephalin (pENK) mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington’s disease (HD), due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing) neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2)-containing green fluorescence protein (GFP)-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.
Url:
DOI: 10.1371/journal.pone.0075099
PubMed: 24040390
PubMed Central: 3770591
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000A95
- to stream Pmc, to step Curation: 000A95
- to stream Pmc, to step Checkpoint: 000577
Links to Exploration step
PMC:3770591Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease</title><author><name sortKey="Bissonnette, Stephanie" sort="Bissonnette, Stephanie" uniqKey="Bissonnette S" first="Stéphanie" last="Bissonnette">Stéphanie Bissonnette</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Vaillancourt, Mylene" sort="Vaillancourt, Mylene" uniqKey="Vaillancourt M" first="Mylène" last="Vaillancourt">Mylène Vaillancourt</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hébert">Sébastien S. Hébert</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de psychiatrie et de neurosciences, Université Laval, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Drolet, Guy" sort="Drolet, Guy" uniqKey="Drolet G" first="Guy" last="Drolet">Guy Drolet</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de psychiatrie et de neurosciences, Université Laval, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de psychiatrie et de neurosciences, Université Laval, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24040390</idno><idno type="pmc">3770591</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770591</idno><idno type="RBID">PMC:3770591</idno><idno type="doi">10.1371/journal.pone.0075099</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000A95</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A95</idno><idno type="wicri:Area/Pmc/Curation">000A95</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A95</idno><idno type="wicri:Area/Pmc/Checkpoint">000577</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000577</idno><idno type="wicri:Area/Ncbi/Merge">001564</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease</title><author><name sortKey="Bissonnette, Stephanie" sort="Bissonnette, Stephanie" uniqKey="Bissonnette S" first="Stéphanie" last="Bissonnette">Stéphanie Bissonnette</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Vaillancourt, Mylene" sort="Vaillancourt, Mylene" uniqKey="Vaillancourt M" first="Mylène" last="Vaillancourt">Mylène Vaillancourt</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hébert">Sébastien S. Hébert</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de psychiatrie et de neurosciences, Université Laval, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Drolet, Guy" sort="Drolet, Guy" uniqKey="Drolet G" first="Guy" last="Drolet">Guy Drolet</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de psychiatrie et de neurosciences, Université Laval, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de psychiatrie et de neurosciences, Université Laval, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The reduction of pre-enkephalin (pENK) mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington’s disease (HD), due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing) neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2)-containing green fluorescence protein (GFP)-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Ross, Ca" uniqKey="Ross C">CA Ross</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saudou, F" uniqKey="Saudou F">F Saudou</name></author><author><name sortKey="Finkbeiner, S" uniqKey="Finkbeiner S">S Finkbeiner</name></author><author><name sortKey="Devys, D" uniqKey="Devys D">D Devys</name></author><author><name sortKey="Greenberg, Me" uniqKey="Greenberg M">ME Greenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Sh" uniqKey="Li S">SH Li</name></author><author><name sortKey="Schilling, G" uniqKey="Schilling G">G Schilling</name></author><author><name sortKey="Young, Ws" uniqKey="Young W">WS Young</name></author><author><name sortKey="Li, Xj" uniqKey="Li X">XJ Li</name></author><author><name sortKey="Margolis, Rl" uniqKey="Margolis R">RL Margolis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fusco, Fr" uniqKey="Fusco F">FR Fusco</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author><author><name sortKey="Lamoreaux, Wj" uniqKey="Lamoreaux W">WJ Lamoreaux</name></author><author><name sortKey="Figueredo Cardenas, G" uniqKey="Figueredo Cardenas G">G Figueredo-Cardenas</name></author><author><name sortKey="Jiao, Y" uniqKey="Jiao Y">Y Jiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reiner, A" uniqKey="Reiner A">A Reiner</name></author><author><name sortKey="Albin, Rl" uniqKey="Albin R">RL Albin</name></author><author><name sortKey="Anderson, Kd" uniqKey="Anderson K">KD Anderson</name></author><author><name sortKey="D Amato, Cj" uniqKey="D Amato C">CJ D'Amato</name></author><author><name sortKey="Penney, Jb" uniqKey="Penney J">JB Penney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bodnar, Rj" uniqKey="Bodnar R">RJ Bodnar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peckys, D" uniqKey="Peckys D">D Peckys</name></author><author><name sortKey="Landwehrmeyer, Gb" uniqKey="Landwehrmeyer G">GB Landwehrmeyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Williams, Jt" uniqKey="Williams J">JT Williams</name></author><author><name sortKey="Christie, Mj" uniqKey="Christie M">MJ Christie</name></author><author><name sortKey="Manzoni, O" uniqKey="Manzoni O">O Manzoni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bezard, E" uniqKey="Bezard E">E Bezard</name></author><author><name sortKey="Ravenscroft, P" uniqKey="Ravenscroft P">P Ravenscroft</name></author><author><name sortKey="Gross, Ce" uniqKey="Gross C">CE Gross</name></author><author><name sortKey="Crossman, Ar" uniqKey="Crossman A">AR Crossman</name></author><author><name sortKey="Brotchie, Jm" uniqKey="Brotchie J">JM Brotchie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bezard, E" uniqKey="Bezard E">E Bezard</name></author><author><name sortKey="Gross, Ce" uniqKey="Gross C">CE Gross</name></author><author><name sortKey="Brotchie, Jm" uniqKey="Brotchie J">JM Brotchie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samadi, P" uniqKey="Samadi P">P Samadi</name></author><author><name sortKey="Gregoire, L" uniqKey="Gregoire L">L Gregoire</name></author><author><name sortKey="Hadj, Ta" uniqKey="Hadj T">TA Hadj</name></author><author><name sortKey="Di Paolo, T" uniqKey="Di Paolo T">T Di Paolo</name></author><author><name sortKey="Rouillard, C" uniqKey="Rouillard C">C Rouillard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samadi, P" uniqKey="Samadi P">P Samadi</name></author><author><name sortKey="Bedard, Pj" uniqKey="Bedard P">PJ Bedard</name></author><author><name sortKey="Rouillard, C" uniqKey="Rouillard C">C Rouillard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barry, U" uniqKey="Barry U">U Barry</name></author><author><name sortKey="Zuo, Z" uniqKey="Zuo Z">Z Zuo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Xia, X" uniqKey="Xia X">X Xia</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Su, Ds" uniqKey="Su D">DS Su</name></author><author><name sortKey="Wang, Zh" uniqKey="Wang Z">ZH Wang</name></author><author><name sortKey="Zheng, Yj" uniqKey="Zheng Y">YJ Zheng</name></author><author><name sortKey="Zhao, Yh" uniqKey="Zhao Y">YH Zhao</name></author><author><name sortKey="Wang, Xr" uniqKey="Wang X">XR Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, Mc" uniqKey="Ma M">MC Ma</name></author><author><name sortKey="Qian, H" uniqKey="Qian H">H Qian</name></author><author><name sortKey="Ghassemi, F" uniqKey="Ghassemi F">F Ghassemi</name></author><author><name sortKey="Zhao, P" uniqKey="Zhao P">P Zhao</name></author><author><name sortKey="Xia, Y" uniqKey="Xia Y">Y Xia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, S" uniqKey="Wang S">S Wang</name></author><author><name sortKey="Duan, Y" uniqKey="Duan Y">Y Duan</name></author><author><name sortKey="Su, D" uniqKey="Su D">D Su</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Tan, J" uniqKey="Tan J">J Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, L" uniqKey="Qin L">L Qin</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Qian, X" uniqKey="Qian X">X Qian</name></author><author><name sortKey="Hong, Js" uniqKey="Hong J">JS Hong</name></author><author><name sortKey="Block, Ml" uniqKey="Block M">ML Block</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Polakiewicz, Rd" uniqKey="Polakiewicz R">RD Polakiewicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Borlongan, Cv" uniqKey="Borlongan C">CV Borlongan</name></author><author><name sortKey="Su, Tp" uniqKey="Su T">TP Su</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Sm" uniqKey="Johnson S">SM Johnson</name></author><author><name sortKey="Turner, Sm" uniqKey="Turner S">SM Turner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, M" uniqKey="Zhu M">M Zhu</name></author><author><name sortKey="Li, Mw" uniqKey="Li M">MW Li</name></author><author><name sortKey="Tian, Xs" uniqKey="Tian X">XS Tian</name></author><author><name sortKey="Ou, Xm" uniqKey="Ou X">XM Ou</name></author><author><name sortKey="Zhu, Cq" uniqKey="Zhu C">CQ Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Borlongan, Cv" uniqKey="Borlongan C">CV Borlongan</name></author><author><name sortKey="Su, Tp" uniqKey="Su T">TP Su</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menalled, L" uniqKey="Menalled L">L Menalled</name></author><author><name sortKey="Zanjani, H" uniqKey="Zanjani H">H Zanjani</name></author><author><name sortKey="Mackenzie, L" uniqKey="Mackenzie L">L MacKenzie</name></author><author><name sortKey="Koppel, A" uniqKey="Koppel A">A Koppel</name></author><author><name sortKey="Carpenter, E" uniqKey="Carpenter E">E Carpenter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z Sun</name></author><author><name sortKey="Del Mar, N" uniqKey="Del Mar N">N Del Mar</name></author><author><name sortKey="Meade, C" uniqKey="Meade C">C Meade</name></author><author><name sortKey="Goldowitz, D" uniqKey="Goldowitz D">D Goldowitz</name></author><author><name sortKey="Reiner, A" uniqKey="Reiner A">A Reiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Albin, Rl" uniqKey="Albin R">RL Albin</name></author><author><name sortKey="Qin, Y" uniqKey="Qin Y">Y Qin</name></author><author><name sortKey="Young, Ab" uniqKey="Young A">AB Young</name></author><author><name sortKey="Penney, Jb" uniqKey="Penney J">JB Penney</name></author><author><name sortKey="Chesselet, Mf" uniqKey="Chesselet M">MF Chesselet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, Yp" uniqKey="Deng Y">YP Deng</name></author><author><name sortKey="Albin, Rl" uniqKey="Albin R">RL Albin</name></author><author><name sortKey="Penney, Jb" uniqKey="Penney J">JB Penney</name></author><author><name sortKey="Young, Ab" uniqKey="Young A">AB Young</name></author><author><name sortKey="Anderson, Kd" uniqKey="Anderson K">KD Anderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crook, Zr" uniqKey="Crook Z">ZR Crook</name></author><author><name sortKey="Housman, D" uniqKey="Housman D">D Housman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samadi, P" uniqKey="Samadi P">P Samadi</name></author><author><name sortKey="Boutet, A" uniqKey="Boutet A">A Boutet</name></author><author><name sortKey="Rymar, Vv" uniqKey="Rymar V">VV Rymar</name></author><author><name sortKey="Rawal, K" uniqKey="Rawal K">K Rawal</name></author><author><name sortKey="Maheux, J" uniqKey="Maheux J">J Maheux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stack, Ec" uniqKey="Stack E">EC Stack</name></author><author><name sortKey="Kubilus, Jk" uniqKey="Kubilus J">JK Kubilus</name></author><author><name sortKey="Smith, K" uniqKey="Smith K">K Smith</name></author><author><name sortKey="Cormier, K" uniqKey="Cormier K">K Cormier</name></author><author><name sortKey="Del Signore, Sj" uniqKey="Del Signore S">SJ Del Signore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Tc" uniqKey="He T">TC He</name></author><author><name sortKey="Zhou, S" uniqKey="Zhou S">S Zhou</name></author><author><name sortKey="Da Costa, Lt" uniqKey="Da Costa L">LT da Costa</name></author><author><name sortKey="Yu, J" uniqKey="Yu J">J Yu</name></author><author><name sortKey="Kinzler, Kw" uniqKey="Kinzler K">KW Kinzler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zolotukhin, S" uniqKey="Zolotukhin S">S Zolotukhin</name></author><author><name sortKey="Potter, M" uniqKey="Potter M">M Potter</name></author><author><name sortKey="Zolotukhin, I" uniqKey="Zolotukhin I">I Zolotukhin</name></author><author><name sortKey="Sakai, Y" uniqKey="Sakai Y">Y Sakai</name></author><author><name sortKey="Loiler, S" uniqKey="Loiler S">S Loiler</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bailoo, Jd" uniqKey="Bailoo J">JD Bailoo</name></author><author><name sortKey="Bohlen, Mo" uniqKey="Bohlen M">MO Bohlen</name></author><author><name sortKey="Wahlsten, D" uniqKey="Wahlsten D">D Wahlsten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mathis, C" uniqKey="Mathis C">C Mathis</name></author><author><name sortKey="Bott, Jb" uniqKey="Bott J">JB Bott</name></author><author><name sortKey="Candusso, Mp" uniqKey="Candusso M">MP Candusso</name></author><author><name sortKey="Simonin, F" uniqKey="Simonin F">F Simonin</name></author><author><name sortKey="Cassel, Jc" uniqKey="Cassel J">JC Cassel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drouin Ouellet, J" uniqKey="Drouin Ouellet J">J Drouin-Ouellet</name></author><author><name sortKey="Lebel, M" uniqKey="Lebel M">M LeBel</name></author><author><name sortKey="Filali, M" uniqKey="Filali M">M Filali</name></author><author><name sortKey="Cicchetti, F" uniqKey="Cicchetti F">F Cicchetti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshikawa, K" uniqKey="Yoshikawa K">K Yoshikawa</name></author><author><name sortKey="Williams, C" uniqKey="Williams C">C Williams</name></author><author><name sortKey="Sabol, Sl" uniqKey="Sabol S">SL Sabol</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Beaudry, G" uniqKey="Beaudry G">G Beaudry</name></author><author><name sortKey="Langlois, Mc" uniqKey="Langlois M">MC Langlois</name></author><author><name sortKey="Weppe, I" uniqKey="Weppe I">I Weppe</name></author><author><name sortKey="Rouillard, C" uniqKey="Rouillard C">C Rouillard</name></author><author><name sortKey="Levesque, D" uniqKey="Levesque D">D Levesque</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baydyuk, M" uniqKey="Baydyuk M">M Baydyuk</name></author><author><name sortKey="Russell, T" uniqKey="Russell T">T Russell</name></author><author><name sortKey="Liao, Gy" uniqKey="Liao G">GY Liao</name></author><author><name sortKey="Zang, K" uniqKey="Zang K">K Zang</name></author><author><name sortKey="An, Jj" uniqKey="An J">JJ An</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sadikot, Af" uniqKey="Sadikot A">AF Sadikot</name></author><author><name sortKey="Sasseville, R" uniqKey="Sasseville R">R Sasseville</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="File, Se" uniqKey="File S">SE File</name></author><author><name sortKey="Mahal, A" uniqKey="Mahal A">A Mahal</name></author><author><name sortKey="Mangiarini, L" uniqKey="Mangiarini L">L Mangiarini</name></author><author><name sortKey="Bates, Gp" uniqKey="Bates G">GP Bates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Raamsdonk, Jm" uniqKey="Van Raamsdonk J">JM Van Raamsdonk</name></author><author><name sortKey="Pearson, J" uniqKey="Pearson J">J Pearson</name></author><author><name sortKey="Slow, Ej" uniqKey="Slow E">EJ Slow</name></author><author><name sortKey="Hossain, Sm" uniqKey="Hossain S">SM Hossain</name></author><author><name sortKey="Leavitt, Br" uniqKey="Leavitt B">BR Leavitt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lemiere, J" uniqKey="Lemiere J">J Lemiere</name></author><author><name sortKey="Decruyenaere, M" uniqKey="Decruyenaere M">M Decruyenaere</name></author><author><name sortKey="Evers Kiebooms, G" uniqKey="Evers Kiebooms G">G Evers-Kiebooms</name></author><author><name sortKey="Vandenbussche, E" uniqKey="Vandenbussche E">E Vandenbussche</name></author><author><name sortKey="Dom, R" uniqKey="Dom R">R Dom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cepeda, C" uniqKey="Cepeda C">C Cepeda</name></author><author><name sortKey="Wu, N" uniqKey="Wu N">N Wu</name></author><author><name sortKey="Andre, Vm" uniqKey="Andre V">VM Andre</name></author><author><name sortKey="Cummings, Dm" uniqKey="Cummings D">DM Cummings</name></author><author><name sortKey="Levine, Ms" uniqKey="Levine M">MS Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lei, W" uniqKey="Lei W">W Lei</name></author><author><name sortKey="Jiao, Y" uniqKey="Jiao Y">Y Jiao</name></author><author><name sortKey="Del Mar, N" uniqKey="Del Mar N">N Del Mar</name></author><author><name sortKey="Reiner, A" uniqKey="Reiner A">A Reiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fusco, Fr" uniqKey="Fusco F">FR Fusco</name></author><author><name sortKey="Martorana, A" uniqKey="Martorana A">A Martorana</name></author><author><name sortKey="De, Mz" uniqKey="De M">MZ De</name></author><author><name sortKey="Viscomi, Mt" uniqKey="Viscomi M">MT Viscomi</name></author><author><name sortKey="Sancesario, G" uniqKey="Sancesario G">G Sancesario</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Milnerwood, Aj" uniqKey="Milnerwood A">AJ Milnerwood</name></author><author><name sortKey="Raymond, La" uniqKey="Raymond L">LA Raymond</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andre, Vm" uniqKey="Andre V">VM Andre</name></author><author><name sortKey="Cepeda, C" uniqKey="Cepeda C">C Cepeda</name></author><author><name sortKey="Levine, Ms" uniqKey="Levine M">MS Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Milnerwood, Aj" uniqKey="Milnerwood A">AJ Milnerwood</name></author><author><name sortKey="Gladding, Cm" uniqKey="Gladding C">CM Gladding</name></author><author><name sortKey="Pouladi, Ma" uniqKey="Pouladi M">MA Pouladi</name></author><author><name sortKey="Kaufman, Am" uniqKey="Kaufman A">AM Kaufman</name></author><author><name sortKey="Hines, Rm" uniqKey="Hines R">RM Hines</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, Br" uniqKey="Miller B">BR Miller</name></author><author><name sortKey="Dorner, Jl" uniqKey="Dorner J">JL Dorner</name></author><author><name sortKey="Shou, M" uniqKey="Shou M">M Shou</name></author><author><name sortKey="Sari, Y" uniqKey="Sari Y">Y Sari</name></author><author><name sortKey="Barton, Sj" uniqKey="Barton S">SJ Barton</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Stack, Ec" uniqKey="Stack E">EC Stack</name></author><author><name sortKey="Dedeoglu, A" uniqKey="Dedeoglu A">A Dedeoglu</name></author><author><name sortKey="Smith, Km" uniqKey="Smith K">KM Smith</name></author><author><name sortKey="Cormier, K" uniqKey="Cormier K">K Cormier</name></author><author><name sortKey="Kubilus, Jk" uniqKey="Kubilus J">JK Kubilus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, Zg" uniqKey="Jiang Z">ZG Jiang</name></author><author><name sortKey="North, Ra" uniqKey="North R">RA North</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Pickel, Vm" uniqKey="Pickel V">VM Pickel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Parent, A" uniqKey="Parent A">A Parent</name></author><author><name sortKey="Sato, F" uniqKey="Sato F">F Sato</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name></author><author><name sortKey="Gauthier, J" uniqKey="Gauthier J">J Gauthier</name></author><author><name sortKey="Levesque, M" uniqKey="Levesque M">M Levesque</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yin, Hh" uniqKey="Yin H">HH Yin</name></author><author><name sortKey="Knowlton, Bj" uniqKey="Knowlton B">BJ Knowlton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wei, Cj" uniqKey="Wei C">CJ Wei</name></author><author><name sortKey="Singer, P" uniqKey="Singer P">P Singer</name></author><author><name sortKey="Coelho, J" uniqKey="Coelho J">J Coelho</name></author><author><name sortKey="Boison, D" uniqKey="Boison D">D Boison</name></author><author><name sortKey="Feldon, J" uniqKey="Feldon J">J Feldon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giralt, A" uniqKey="Giralt A">A Giralt</name></author><author><name sortKey="Saavedra, A" uniqKey="Saavedra A">A Saavedra</name></author><author><name sortKey="Carreton, O" uniqKey="Carreton O">O Carreton</name></author><author><name sortKey="Xifro, X" uniqKey="Xifro X">X Xifro</name></author><author><name sortKey="Alberch, J" uniqKey="Alberch J">J Alberch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ariano, Ma" uniqKey="Ariano M">MA Ariano</name></author><author><name sortKey="Aronin, N" uniqKey="Aronin N">N Aronin</name></author><author><name sortKey="Difiglia, M" uniqKey="Difiglia M">M Difiglia</name></author><author><name sortKey="Tagle, Da" uniqKey="Tagle D">DA Tagle</name></author><author><name sortKey="Sibley, Dr" uniqKey="Sibley D">DR Sibley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Torres Peraza, Jf" uniqKey="Torres Peraza J">JF Torres-Peraza</name></author><author><name sortKey="Giralt, A" uniqKey="Giralt A">A Giralt</name></author><author><name sortKey="Garcia Martinez, Jm" uniqKey="Garcia Martinez J">JM Garcia-Martinez</name></author><author><name sortKey="Pedrosa, E" uniqKey="Pedrosa E">E Pedrosa</name></author><author><name sortKey="Canals, Jm" uniqKey="Canals J">JM Canals</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waldhoer, M" uniqKey="Waldhoer M">M Waldhoer</name></author><author><name sortKey="Bartlett, Se" uniqKey="Bartlett S">SE Bartlett</name></author><author><name sortKey="Whistler, Jl" uniqKey="Whistler J">JL Whistler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Cs" uniqKey="Chan C">CS Chan</name></author><author><name sortKey="Gertler, Ts" uniqKey="Gertler T">TS Gertler</name></author><author><name sortKey="Surmeier, Dj" uniqKey="Surmeier D">DJ Surmeier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Day, M" uniqKey="Day M">M Day</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Ding, J" uniqKey="Ding J">J Ding</name></author><author><name sortKey="An, X" uniqKey="An X">X An</name></author><author><name sortKey="Ingham, Ca" uniqKey="Ingham C">CA Ingham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mosharov, Ev" uniqKey="Mosharov E">EV Mosharov</name></author><author><name sortKey="Larsen, Ke" uniqKey="Larsen K">KE Larsen</name></author><author><name sortKey="Kanter, E" uniqKey="Kanter E">E Kanter</name></author><author><name sortKey="Phillips, Ka" uniqKey="Phillips K">KA Phillips</name></author><author><name sortKey="Wilson, K" uniqKey="Wilson K">K Wilson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dai, Y" uniqKey="Dai Y">Y Dai</name></author><author><name sortKey="Dudek, Nl" uniqKey="Dudek N">NL Dudek</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q Li</name></author><author><name sortKey="Fowler, Sc" uniqKey="Fowler S">SC Fowler</name></author><author><name sortKey="Muma, Na" uniqKey="Muma N">NA Muma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ayalon, L" uniqKey="Ayalon L">L Ayalon</name></author><author><name sortKey="Doron, R" uniqKey="Doron R">R Doron</name></author><author><name sortKey="Weiner, I" uniqKey="Weiner I">I Weiner</name></author><author><name sortKey="Joel, D" uniqKey="Joel D">D Joel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reiner, A" uniqKey="Reiner A">A Reiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beal, Mf" uniqKey="Beal M">MF Beal</name></author><author><name sortKey="Ferrante, Rj" uniqKey="Ferrante R">RJ Ferrante</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vlamings, R" uniqKey="Vlamings R">R Vlamings</name></author><author><name sortKey="Benazzouz, A" uniqKey="Benazzouz A">A Benazzouz</name></author><author><name sortKey="Chetrit, J" uniqKey="Chetrit J">J Chetrit</name></author><author><name sortKey="Janssen, Ml" uniqKey="Janssen M">ML Janssen</name></author><author><name sortKey="Kozan, R" uniqKey="Kozan R">R Kozan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Temel, Y" uniqKey="Temel Y">Y Temel</name></author><author><name sortKey="Cao, C" uniqKey="Cao C">C Cao</name></author><author><name sortKey="Vlamings, R" uniqKey="Vlamings R">R Vlamings</name></author><author><name sortKey="Blokland, A" uniqKey="Blokland A">A Blokland</name></author><author><name sortKey="Ozen, H" uniqKey="Ozen H">H Ozen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Sk" uniqKey="Tan S">SK Tan</name></author><author><name sortKey="Vlamings, R" uniqKey="Vlamings R">R Vlamings</name></author><author><name sortKey="Lim, L" uniqKey="Lim L">L Lim</name></author><author><name sortKey="Sesia, T" uniqKey="Sesia T">T Sesia</name></author><author><name sortKey="Janssen, Ml" uniqKey="Janssen M">ML Janssen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nambu, A" uniqKey="Nambu A">A Nambu</name></author><author><name sortKey="Llinas, R" uniqKey="Llinas R">R Llinas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ogura, M" uniqKey="Ogura M">M Ogura</name></author><author><name sortKey="Kita, H" uniqKey="Kita H">H Kita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abou Khalil, B" uniqKey="Abou Khalil B">B Abou-Khalil</name></author><author><name sortKey="Young, Ab" uniqKey="Young A">AB Young</name></author><author><name sortKey="Penney, Jb" uniqKey="Penney J">JB Penney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tokuno, H" uniqKey="Tokuno H">H Tokuno</name></author><author><name sortKey="Chiken, S" uniqKey="Chiken S">S Chiken</name></author><author><name sortKey="Kametani, K" uniqKey="Kametani K">K Kametani</name></author><author><name sortKey="Moriizumi, T" uniqKey="Moriizumi T">T Moriizumi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delfs, Jm" uniqKey="Delfs J">JM Delfs</name></author><author><name sortKey="Kong, H" uniqKey="Kong H">H Kong</name></author><author><name sortKey="Mestek, A" uniqKey="Mestek A">A Mestek</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Yu, L" uniqKey="Yu L">L Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhai, W" uniqKey="Zhai W">W Zhai</name></author><author><name sortKey="Jeong, H" uniqKey="Jeong H">H Jeong</name></author><author><name sortKey="Cui, L" uniqKey="Cui L">L Cui</name></author><author><name sortKey="Krainc, D" uniqKey="Krainc D">D Krainc</name></author><author><name sortKey="Tjian, R" uniqKey="Tjian R">R Tjian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bruce, Aw" uniqKey="Bruce A">AW Bruce</name></author><author><name sortKey="Donaldson, Ij" uniqKey="Donaldson I">IJ Donaldson</name></author><author><name sortKey="Wood, Ic" uniqKey="Wood I">IC Wood</name></author><author><name sortKey="Yerbury, Sa" uniqKey="Yerbury S">SA Yerbury</name></author><author><name sortKey="Sadowski, Mi" uniqKey="Sadowski M">MI Sadowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rigamonti, D" uniqKey="Rigamonti D">D Rigamonti</name></author><author><name sortKey="Bolognini, D" uniqKey="Bolognini D">D Bolognini</name></author><author><name sortKey="Mutti, C" uniqKey="Mutti C">C Mutti</name></author><author><name sortKey="Zuccato, C" uniqKey="Zuccato C">C Zuccato</name></author><author><name sortKey="Tartari, M" uniqKey="Tartari M">M Tartari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weeks, Ra" uniqKey="Weeks R">RA Weeks</name></author><author><name sortKey="Cunningham, Vj" uniqKey="Cunningham V">VJ Cunningham</name></author><author><name sortKey="Piccini, P" uniqKey="Piccini P">P Piccini</name></author><author><name sortKey="Waters, S" uniqKey="Waters S">S Waters</name></author><author><name sortKey="Harding, Ae" uniqKey="Harding A">AE Harding</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24040390</article-id><article-id pub-id-type="pmc">3770591</article-id><article-id pub-id-type="publisher-id">PONE-D-13-25636</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0075099</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease</article-title><alt-title alt-title-type="running-head">Pre-Enkephalin and Huntington's Disease</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bissonnette</surname><given-names>Stéphanie</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vaillancourt</surname><given-names>Mylène</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hébert</surname><given-names>Sébastien S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Drolet</surname><given-names>Guy</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Samadi</surname><given-names>Pershia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Axe Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, Canada</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Département de psychiatrie et de neurosciences, Université Laval, Québec, Canada</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Kahle</surname><given-names>Philipp J.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Germany</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>Pershia.samadi@fmed.ulaval.ca</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: PS. Performed the experiments: SB MV. Analyzed the data: SB PS. Contributed reagents/materials/analysis tools: SSH GD PS. Wrote the paper: PS. Revised the paper: SSH GD PS.</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>11</day><month>9</month><year>2013</year></pub-date><volume>8</volume><issue>9</issue><elocation-id>e75099</elocation-id><history><date date-type="received"><day>20</day><month>6</month><year>2013</year></date><date date-type="accepted"><day>9</day><month>8</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Bissonnette et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>The reduction of pre-enkephalin (pENK) mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington’s disease (HD), due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing) neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2)-containing green fluorescence protein (GFP)-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.</p></abstract><funding-group><funding-statement>This work was supported by start-up grant from CHUQ, and faculty of medicine at Laval University to PS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="16"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Bissonnette, Stephanie" sort="Bissonnette, Stephanie" uniqKey="Bissonnette S" first="Stéphanie" last="Bissonnette">Stéphanie Bissonnette</name></noRegion><name sortKey="Drolet, Guy" sort="Drolet, Guy" uniqKey="Drolet G" first="Guy" last="Drolet">Guy Drolet</name><name sortKey="Drolet, Guy" sort="Drolet, Guy" uniqKey="Drolet G" first="Guy" last="Drolet">Guy Drolet</name><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hébert">Sébastien S. Hébert</name><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hébert">Sébastien S. Hébert</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><name sortKey="Vaillancourt, Mylene" sort="Vaillancourt, Mylene" uniqKey="Vaillancourt M" first="Mylène" last="Vaillancourt">Mylène Vaillancourt</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001564 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 001564 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:3770591
|texte= Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:24040390" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |