Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease</title><author><name sortKey="Farmer, Kyle" sort="Farmer, Kyle" uniqKey="Farmer K" first="Kyle" last="Farmer">Kyle Farmer</name><affiliation><nlm:aff id="af1-ijms-16-18865">Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</nlm:aff></affiliation></author><author><name sortKey="Smith, Catherine A" sort="Smith, Catherine A" uniqKey="Smith C" first="Catherine A." last="Smith">Catherine A. Smith</name><affiliation><nlm:aff id="af1-ijms-16-18865">Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</nlm:aff></affiliation></author><author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><affiliation><nlm:aff id="af1-ijms-16-18865">Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</nlm:aff></affiliation></author><author><name sortKey="Smith, Jeffrey" sort="Smith, Jeffrey" uniqKey="Smith J" first="Jeffrey" last="Smith">Jeffrey Smith</name><affiliation><nlm:aff id="af2-ijms-16-18865">Carleton University Department of Chemistry and Institute of Biochemistry, 1125 Colonel By Drive, Steacie Building, Ottawa, ON K1S 5B6, Canada; E-Mail:<email>jeff_smith@carleton.ca</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26274953</idno><idno type="pmc">4581276</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581276</idno><idno type="RBID">PMC:4581276</idno><idno type="doi">10.3390/ijms160818865</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000064</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000064</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease</title><author><name sortKey="Farmer, Kyle" sort="Farmer, Kyle" uniqKey="Farmer K" first="Kyle" last="Farmer">Kyle Farmer</name><affiliation><nlm:aff id="af1-ijms-16-18865">Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</nlm:aff></affiliation></author><author><name sortKey="Smith, Catherine A" sort="Smith, Catherine A" uniqKey="Smith C" first="Catherine A." last="Smith">Catherine A. Smith</name><affiliation><nlm:aff id="af1-ijms-16-18865">Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</nlm:aff></affiliation></author><author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><affiliation><nlm:aff id="af1-ijms-16-18865">Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</nlm:aff></affiliation></author><author><name sortKey="Smith, Jeffrey" sort="Smith, Jeffrey" uniqKey="Smith J" first="Jeffrey" last="Smith">Jeffrey Smith</name><affiliation><nlm:aff id="af2-ijms-16-18865">Carleton University Department of Chemistry and Institute of Biochemistry, 1125 Colonel By Drive, Steacie Building, Ottawa, ON K1S 5B6, Canada; E-Mail:<email>jeff_smith@carleton.ca</email></nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bernheimer, H" uniqKey="Bernheimer H">H. Bernheimer</name></author><author><name sortKey="Birkmayer, W" uniqKey="Birkmayer W">W. Birkmayer</name></author><author><name sortKey="Hornykiewicz, O" uniqKey="Hornykiewicz O">O. Hornykiewicz</name></author><author><name sortKey="Jellinger, K" uniqKey="Jellinger K">K. Jellinger</name></author><author><name sortKey="Seitelberger, F" uniqKey="Seitelberger F">F. Seitelberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klockgether, T" uniqKey="Klockgether T">T. Klockgether</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menza, M" uniqKey="Menza M">M. Menza</name></author><author><name sortKey="Donkin, R" uniqKey="Donkin R">R. Donkin</name></author><author><name sortKey="Marin, H" uniqKey="Marin H">H. Marin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marie, R" uniqKey="Marie R">R. Marié</name></author><author><name sortKey="Barre, L" uniqKey="Barre L">L. Barré</name></author><author><name sortKey="Dupuy, B" uniqKey="Dupuy B">B. Dupuy</name></author><author><name sortKey="Viader, F" uniqKey="Viader F">F. Viader</name></author><author><name sortKey="Defer, G" uniqKey="Defer G">G. Defer</name></author><author><name sortKey="Baron, J" uniqKey="Baron J">J. Baron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Farmer, K" uniqKey="Farmer K">K. Farmer</name></author><author><name sortKey="Rudyk, C" uniqKey="Rudyk C">C. Rudyk</name></author><author><name sortKey="Prowse, N A" uniqKey="Prowse N">N.A. Prowse</name></author><author><name sortKey="Hayley, S" uniqKey="Hayley S">S. Hayley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perier, C" uniqKey="Perier C">C. Perier</name></author><author><name sortKey="Bove, J" uniqKey="Bove J">J. Bové</name></author><author><name sortKey="Wu, D C" uniqKey="Wu D">D.-C. Wu</name></author><author><name sortKey="Dehay, B" uniqKey="Dehay B">B. Dehay</name></author><author><name sortKey="Choi, D K" uniqKey="Choi D">D.-K. Choi</name></author><author><name sortKey="Jackson Lewis, V" uniqKey="Jackson Lewis V">V. Jackson-Lewis</name></author><author><name sortKey="Rathke Hartlieb, S" uniqKey="Rathke Hartlieb S">S. Rathke-Hartlieb</name></author><author><name sortKey="Bouillet, P" uniqKey="Bouillet P">P. Bouillet</name></author><author><name sortKey="Strasser, A" uniqKey="Strasser A">A. Strasser</name></author><author><name sortKey="Schulz, J B" uniqKey="Schulz J">J.B. Schulz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, B" uniqKey="Zheng B">B. Zheng</name></author><author><name sortKey="Liao, Z" uniqKey="Liao Z">Z. Liao</name></author><author><name sortKey="Locascio, J J" uniqKey="Locascio J">J.J. Locascio</name></author><author><name sortKey="Lesniak, K A" uniqKey="Lesniak K">K.A. Lesniak</name></author><author><name sortKey="Roderick, S S" uniqKey="Roderick S">S.S. Roderick</name></author><author><name sortKey="Watt, M L" uniqKey="Watt M">M.L. Watt</name></author><author><name sortKey="Eklund, A C" uniqKey="Eklund A">A.C. Eklund</name></author><author><name sortKey="Zhang James, Y" uniqKey="Zhang James Y">Y. Zhang-James</name></author><author><name sortKey="Kim, P D" uniqKey="Kim P">P.D. Kim</name></author><author><name sortKey="Hauser, M A" uniqKey="Hauser M">M.A. Hauser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Winklhofer, K F" uniqKey="Winklhofer K">K.F. Winklhofer</name></author><author><name sortKey="Haass, C" uniqKey="Haass C">C. Haass</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hagenah, J M" uniqKey="Hagenah J">J.M. Hagenah</name></author><author><name sortKey="Konig, I R" uniqKey="Konig I">I.R. König</name></author><author><name sortKey="Becker, B" uniqKey="Becker B">B. Becker</name></author><author><name sortKey="Hilker, R" uniqKey="Hilker R">R. Hilker</name></author><author><name sortKey="Kasten, M" uniqKey="Kasten M">M. Kasten</name></author><author><name sortKey="Hedrich, K" uniqKey="Hedrich K">K. Hedrich</name></author><author><name sortKey="Pramstaller, P P" uniqKey="Pramstaller P">P.P. Pramstaller</name></author><author><name sortKey="Klein, C" uniqKey="Klein C">C. Klein</name></author><author><name sortKey="Seidel, G" uniqKey="Seidel G">G. Seidel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schweitzer, K J" uniqKey="Schweitzer K">K.J. Schweitzer</name></author><author><name sortKey="Brussel, T" uniqKey="Brussel T">T. Brüssel</name></author><author><name sortKey="Leitner, P" uniqKey="Leitner P">P. Leitner</name></author><author><name sortKey="Kruger, R" uniqKey="Kruger R">R. Krüger</name></author><author><name sortKey="Bauer, P" uniqKey="Bauer P">P. Bauer</name></author><author><name sortKey="Woitalla, D" uniqKey="Woitalla D">D. Woitalla</name></author><author><name sortKey="Tomiuk, J" uniqKey="Tomiuk J">J. Tomiuk</name></author><author><name sortKey="Gasser, T" uniqKey="Gasser T">T. Gasser</name></author><author><name sortKey="Berg, D" uniqKey="Berg D">D. Berg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prasad, K" uniqKey="Prasad K">K. Prasad</name></author><author><name sortKey="Winnik, B" uniqKey="Winnik B">B. Winnik</name></author><author><name sortKey="Thiruchelvam, M J" uniqKey="Thiruchelvam M">M.J. Thiruchelvam</name></author><author><name sortKey="Buckley, B" uniqKey="Buckley B">B. Buckley</name></author><author><name sortKey="Mirochnitchenko, O" uniqKey="Mirochnitchenko O">O. Mirochnitchenko</name></author><author><name sortKey="Richfield, E K" uniqKey="Richfield E">E.K. Richfield</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goonesinghe, A" uniqKey="Goonesinghe A">A. Goonesinghe</name></author><author><name sortKey="Mundy, E S" uniqKey="Mundy E">E.S. Mundy</name></author><author><name sortKey="Smith, M" uniqKey="Smith M">M. Smith</name></author><author><name sortKey="Khosravi Far, R" uniqKey="Khosravi Far R">R. Khosravi-Far</name></author><author><name sortKey="Martinou, J C" uniqKey="Martinou J">J.-C. Martinou</name></author><author><name sortKey="Esposti, M D" uniqKey="Esposti M">M.D. Esposti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, Z" uniqKey="Qin Z">Z. Qin</name></author><author><name sortKey="Zhu, H" uniqKey="Zhu H">H. Zhu</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giussani, P" uniqKey="Giussani P">P. Giussani</name></author><author><name sortKey="Tringali, C" uniqKey="Tringali C">C. Tringali</name></author><author><name sortKey="Riboni, L" uniqKey="Riboni L">L. Riboni</name></author><author><name sortKey="Viani, P" uniqKey="Viani P">P. Viani</name></author><author><name sortKey="Venerando, B" uniqKey="Venerando B">B. Venerando</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wright, M M" uniqKey="Wright M">M.M. Wright</name></author><author><name sortKey="Howe, A G" uniqKey="Howe A">A.G. Howe</name></author><author><name sortKey="Zaremberg, V" uniqKey="Zaremberg V">V. Zaremberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gulshan, K" uniqKey="Gulshan K">K. Gulshan</name></author><author><name sortKey="Moye Rowley, W S" uniqKey="Moye Rowley W">W.S. Moye-Rowley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Treede, I" uniqKey="Treede I">I. Treede</name></author><author><name sortKey="Braun, A" uniqKey="Braun A">A. Braun</name></author><author><name sortKey="Sparla, R" uniqKey="Sparla R">R. Sparla</name></author><author><name sortKey="Kuhnel, M" uniqKey="Kuhnel M">M. Kühnel</name></author><author><name sortKey="Giese, T" uniqKey="Giese T">T. Giese</name></author><author><name sortKey="Turner, J R" uniqKey="Turner J">J.R. Turner</name></author><author><name sortKey="Anes, E" uniqKey="Anes E">E. Anes</name></author><author><name sortKey="Kulaksiz, H" uniqKey="Kulaksiz H">H. Kulaksiz</name></author><author><name sortKey="Fullekrug, J" uniqKey="Fullekrug J">J. Füllekrug</name></author><author><name sortKey="Stremmel, W" uniqKey="Stremmel W">W. Stremmel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marinova Mutafchieva, L" uniqKey="Marinova Mutafchieva L">L. Marinova-Mutafchieva</name></author><author><name sortKey="Sadeghian, M" uniqKey="Sadeghian M">M. Sadeghian</name></author><author><name sortKey="Broom, L" uniqKey="Broom L">L. Broom</name></author><author><name sortKey="Davis, J B" uniqKey="Davis J">J.B. Davis</name></author><author><name sortKey="Medhurst, A D" uniqKey="Medhurst A">A.D. Medhurst</name></author><author><name sortKey="Dexter, D T" uniqKey="Dexter D">D.T. Dexter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stott, S R W" uniqKey="Stott S">S.R.W. Stott</name></author><author><name sortKey="Barker, R A" uniqKey="Barker R">R.A. Barker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choudhury, M E" uniqKey="Choudhury M">M.E. Choudhury</name></author><author><name sortKey="Sugimoto, K" uniqKey="Sugimoto K">K. Sugimoto</name></author><author><name sortKey="Kubo, M" uniqKey="Kubo M">M. Kubo</name></author><author><name sortKey="Nagai, M" uniqKey="Nagai M">M. Nagai</name></author><author><name sortKey="Nomoto, M" uniqKey="Nomoto M">M. Nomoto</name></author><author><name sortKey="Takahashi, H" uniqKey="Takahashi H">H. Takahashi</name></author><author><name sortKey="Yano, H" uniqKey="Yano H">H. Yano</name></author><author><name sortKey="Tanaka, J" uniqKey="Tanaka J">J. Tanaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernandes, M S" uniqKey="Hernandes M">M.S. Hernandes</name></author><author><name sortKey="Santos, G D R" uniqKey="Santos G">G.D.R. Santos</name></author><author><name sortKey="Cafe Mendes, C C" uniqKey="Cafe Mendes C">C.C. Café-Mendes</name></author><author><name sortKey="Lima, L S" uniqKey="Lima L">L.S. Lima</name></author><author><name sortKey="Scavone, C" uniqKey="Scavone C">C. Scavone</name></author><author><name sortKey="Munhoz, C D" uniqKey="Munhoz C">C.D. Munhoz</name></author><author><name sortKey="Britto, L R G" uniqKey="Britto L">L.R.G. Britto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goes, A T R" uniqKey="Goes A">A.T.R. Goes</name></author><author><name sortKey="Souza, L C" uniqKey="Souza L">L.C. Souza</name></author><author><name sortKey="Filho, C B" uniqKey="Filho C">C.B. Filho</name></author><author><name sortKey="Del Fabbro, L" uniqKey="Del Fabbro L">L. del Fabbro</name></author><author><name sortKey="De Gomes, M G" uniqKey="De Gomes M">M.G. de Gomes</name></author><author><name sortKey="Boeira, S P" uniqKey="Boeira S">S.P. Boeira</name></author><author><name sortKey="Jesse, C R" uniqKey="Jesse C">C.R. Jesse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanrott, K" uniqKey="Hanrott K">K. Hanrott</name></author><author><name sortKey="Gudmunsen, L" uniqKey="Gudmunsen L">L. Gudmunsen</name></author><author><name sortKey="O Eill, M J" uniqKey="O Eill M">M.J. O’Neill</name></author><author><name sortKey="Wonnacott, S" uniqKey="Wonnacott S">S. Wonnacott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Argaud, L" uniqKey="Argaud L">L. Argaud</name></author><author><name sortKey="Prigent, A F" uniqKey="Prigent A">A.-F. Prigent</name></author><author><name sortKey="Chalabreysse, L" uniqKey="Chalabreysse L">L. Chalabreysse</name></author><author><name sortKey="Loufouat, J" uniqKey="Loufouat J">J. Loufouat</name></author><author><name sortKey="Lagarde, M" uniqKey="Lagarde M">M. Lagarde</name></author><author><name sortKey="Ovize, M" uniqKey="Ovize M">M. Ovize</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wright, M M" uniqKey="Wright M">M.M. Wright</name></author><author><name sortKey="Mcmaster, C R" uniqKey="Mcmaster C">C.R. McMaster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hayakawa, T" uniqKey="Hayakawa T">T. Hayakawa</name></author><author><name sortKey="Chang, M C J" uniqKey="Chang M">M.C.J. Chang</name></author><author><name sortKey="Bell, J M" uniqKey="Bell J">J.M. Bell</name></author><author><name sortKey="Seeman, R" uniqKey="Seeman R">R. Seeman</name></author><author><name sortKey="Rapoport, S I" uniqKey="Rapoport S">S.I. Rapoport</name></author><author><name sortKey="Appel, N M" uniqKey="Appel N">N.M. Appel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, H J" uniqKey="Lee H">H.-J. Lee</name></author><author><name sortKey="Bazinet, R P" uniqKey="Bazinet R">R.P. Bazinet</name></author><author><name sortKey="Rapoport, S I" uniqKey="Rapoport S">S.I. Rapoport</name></author><author><name sortKey="Bhattacharjee, A K" uniqKey="Bhattacharjee A">A.K. Bhattacharjee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, S J" uniqKey="Kim S">S.J. Kim</name></author><author><name sortKey="Gershov, D" uniqKey="Gershov D">D. Gershov</name></author><author><name sortKey="Ma, X" uniqKey="Ma X">X. Ma</name></author><author><name sortKey="Brot, N" uniqKey="Brot N">N. Brot</name></author><author><name sortKey="Elkon, K B" uniqKey="Elkon K">K.B. Elkon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaattela, M" uniqKey="Jaattela M">M. Jaattela</name></author><author><name sortKey="Benedict, M" uniqKey="Benedict M">M. Benedict</name></author><author><name sortKey="Tewari, M" uniqKey="Tewari M">M. Tewari</name></author><author><name sortKey="Shayman, J A" uniqKey="Shayman J">J.A. Shayman</name></author><author><name sortKey="Dixit, V M" uniqKey="Dixit V">V.M. Dixit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahmad, A S" uniqKey="Ahmad A">A.S. Ahmad</name></author><author><name sortKey="Maruyama, T" uniqKey="Maruyama T">T. Maruyama</name></author><author><name sortKey="Narumiya, S" uniqKey="Narumiya S">S. Narumiya</name></author><author><name sortKey="Dore, S" uniqKey="Dore S">S. Doré</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kreisler, A" uniqKey="Kreisler A">A. Kreisler</name></author><author><name sortKey="Gele, P" uniqKey="Gele P">P. Gelé</name></author><author><name sortKey="Wiart, J F" uniqKey="Wiart J">J.-F. Wiart</name></author><author><name sortKey="Lhermitte, M" uniqKey="Lhermitte M">M. Lhermitte</name></author><author><name sortKey="Destee, A" uniqKey="Destee A">A. Destée</name></author><author><name sortKey="Bordet, R" uniqKey="Bordet R">R. Bordet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ravnsjkjaer, K" uniqKey="Ravnsjkjaer K">K. Ravnsjkjaer</name></author><author><name sortKey="Frigerio, F" uniqKey="Frigerio F">F. Frigerio</name></author><author><name sortKey="Boegesen, M" uniqKey="Boegesen M">M. Boegesen</name></author><author><name sortKey="Nielsen, T" uniqKey="Nielsen T">T. Nielsen</name></author><author><name sortKey="Maechler, P" uniqKey="Maechler P">P. Maechler</name></author><author><name sortKey="Mandrup, S" uniqKey="Mandrup S">S. Mandrup</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kupsch, A" uniqKey="Kupsch A">A. Kupsch</name></author><author><name sortKey="Schmidt, W" uniqKey="Schmidt W">W. Schmidt</name></author><author><name sortKey="Gizatullina, Z" uniqKey="Gizatullina Z">Z. Gizatullina</name></author><author><name sortKey="Debska Vielhaber, G" uniqKey="Debska Vielhaber G">G. Debska-Vielhaber</name></author><author><name sortKey="Voges, J" uniqKey="Voges J">J. Voges</name></author><author><name sortKey="Striggow, F" uniqKey="Striggow F">F. Striggow</name></author><author><name sortKey="Panther, P" uniqKey="Panther P">P. Panther</name></author><author><name sortKey="Schwegler, H" uniqKey="Schwegler H">H. Schwegler</name></author><author><name sortKey="Heinze, H J" uniqKey="Heinze H">H.-J. Heinze</name></author><author><name sortKey="Vielhaber, S" uniqKey="Vielhaber S">S. Vielhaber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, S Y" uniqKey="Park S">S.Y. Park</name></author><author><name sortKey="Kim, D Y" uniqKey="Kim D">D.Y. Kim</name></author><author><name sortKey="Kang, J K" uniqKey="Kang J">J.-K. Kang</name></author><author><name sortKey="Park, G" uniqKey="Park G">G. Park</name></author><author><name sortKey="Choi, Y W" uniqKey="Choi Y">Y.-W. Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khan, M M" uniqKey="Khan M">M.M. Khan</name></author><author><name sortKey="Ahmad, A" uniqKey="Ahmad A">A. Ahmad</name></author><author><name sortKey="Ishrat, T" uniqKey="Ishrat T">T. Ishrat</name></author><author><name sortKey="Khan, M B" uniqKey="Khan M">M.B. Khan</name></author><author><name sortKey="Hoda, M N" uniqKey="Hoda M">M.N. Hoda</name></author><author><name sortKey="Khuwaja, G" uniqKey="Khuwaja G">G. Khuwaja</name></author><author><name sortKey="Raza, S S" uniqKey="Raza S">S.S. Raza</name></author><author><name sortKey="Khan, A" uniqKey="Khan A">A. Khan</name></author><author><name sortKey="Javed, H" uniqKey="Javed H">H. Javed</name></author><author><name sortKey="Vaibhav, K" uniqKey="Vaibhav K">K. Vaibhav</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Asaithambi, A" uniqKey="Asaithambi A">A. Asaithambi</name></author><author><name sortKey="Ay, M" uniqKey="Ay M">M. Ay</name></author><author><name sortKey="Jin, H" uniqKey="Jin H">H. Jin</name></author><author><name sortKey="Gosh, A" uniqKey="Gosh A">A. Gosh</name></author><author><name sortKey="Anantharam, V" uniqKey="Anantharam V">V. Anantharam</name></author><author><name sortKey="Kanthasamy, A" uniqKey="Kanthasamy A">A. Kanthasamy</name></author><author><name sortKey="Kanthasamy, A G" uniqKey="Kanthasamy A">A.G. Kanthasamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cunningham, T J" uniqKey="Cunningham T">T.J. Cunningham</name></author><author><name sortKey="Yao, L" uniqKey="Yao L">L. Yao</name></author><author><name sortKey="Lucena, A" uniqKey="Lucena A">A. Lucena</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu Wu, Y" uniqKey="Liu Wu Y">Y. Liu-Wu</name></author><author><name sortKey="Hurt Camejo, E" uniqKey="Hurt Camejo E">E. Hurt-Camejo</name></author><author><name sortKey="Wiklund, O" uniqKey="Wiklund O">O. Wiklund</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goncalves, I" uniqKey="Goncalves I">I. Gonçalves</name></author><author><name sortKey="Edsfeldt, A" uniqKey="Edsfeldt A">A. Edsfeldt</name></author><author><name sortKey="Ko, N Y" uniqKey="Ko N">N.Y. Ko</name></author><author><name sortKey="Grufman, H" uniqKey="Grufman H">H. Grufman</name></author><author><name sortKey="Berg, K" uniqKey="Berg K">K. Berg</name></author><author><name sortKey="Bjorkbacka, H" uniqKey="Bjorkbacka H">H. Björkbacka</name></author><author><name sortKey="Nitulescu, M" uniqKey="Nitulescu M">M. Nitulescu</name></author><author><name sortKey="Persson, A" uniqKey="Persson A">A. Persson</name></author><author><name sortKey="Nilsson, M" uniqKey="Nilsson M">M. Nilsson</name></author><author><name sortKey="Prehn, C" uniqKey="Prehn C">C. Prehn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ryborg, A K" uniqKey="Ryborg A">A.K. Ryborg</name></author><author><name sortKey="Deleuran, B" uniqKey="Deleuran B">B. Deleuran</name></author><author><name sortKey="Thestrup Pedersen, K" uniqKey="Thestrup Pedersen K">K. Thestrup-Pedersen</name></author><author><name sortKey="Kragballe, K" uniqKey="Kragballe K">K. Kragballe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcmurray, H F" uniqKey="Mcmurray H">H.F. McMurray</name></author><author><name sortKey="Parthasarathy, S" uniqKey="Parthasarathy S">S. Parthasarathy</name></author><author><name sortKey="Steinberg, D" uniqKey="Steinberg D">D. Steinberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quinn, M T" uniqKey="Quinn M">M.T. Quinn</name></author><author><name sortKey="Parthasarathy, S" uniqKey="Parthasarathy S">S. Parthasarathy</name></author><author><name sortKey="Steinberg, D" uniqKey="Steinberg D">D. Steinberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fabelo, N" uniqKey="Fabelo N">N. Fabelo</name></author><author><name sortKey="Martin, V" uniqKey="Martin V">V. Martín</name></author><author><name sortKey="Santpere, G" uniqKey="Santpere G">G. Santpere</name></author><author><name sortKey="Marin, R" uniqKey="Marin R">R. Marín</name></author><author><name sortKey="Torrent, L" uniqKey="Torrent L">L. Torrent</name></author><author><name sortKey="Ferrer, I" uniqKey="Ferrer I">I. Ferrer</name></author><author><name sortKey="Diaz, M" uniqKey="Diaz M">M. Díaz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Braverman, N E" uniqKey="Braverman N">N.E. Braverman</name></author><author><name sortKey="Moser, A B" uniqKey="Moser A">A.B. Moser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lohmeyer, M" uniqKey="Lohmeyer M">M. Lohmeyer</name></author><author><name sortKey="Bittman, R" uniqKey="Bittman R">R. Bittman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dave, P C" uniqKey="Dave P">P.C. Dave</name></author><author><name sortKey="Billington, E" uniqKey="Billington E">E. Billington</name></author><author><name sortKey="Pan, Y L" uniqKey="Pan Y">Y.-L. Pan</name></author><author><name sortKey="Straus, S K" uniqKey="Straus S">S.K. Straus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Putten, H" uniqKey="Van Der Putten H">H. Van der Putten</name></author><author><name sortKey="Wiederhold, K H" uniqKey="Wiederhold K">K.H. Wiederhold</name></author><author><name sortKey="Probst, A" uniqKey="Probst A">A. Probst</name></author><author><name sortKey="Barbieri, S" uniqKey="Barbieri S">S. Barbieri</name></author><author><name sortKey="Mistl, C" uniqKey="Mistl C">C. Mistl</name></author><author><name sortKey="Danner, S" uniqKey="Danner S">S. Danner</name></author><author><name sortKey="Kauffmann, S" uniqKey="Kauffmann S">S. Kauffmann</name></author><author><name sortKey="Hofele, K" uniqKey="Hofele K">K. Hofele</name></author><author><name sortKey="Spooren, W P" uniqKey="Spooren W">W.P. Spooren</name></author><author><name sortKey="Ruegg, M A" uniqKey="Ruegg M">M.A. Ruegg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lotharius, J" uniqKey="Lotharius J">J. Lotharius</name></author><author><name sortKey="Brundin, P" uniqKey="Brundin P">P. Brundin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Galvin, J E" uniqKey="Galvin J">J.E. Galvin</name></author><author><name sortKey="Uryu, K" uniqKey="Uryu K">K. Uryu</name></author><author><name sortKey="Lee, V M" uniqKey="Lee V">V.M. Lee</name></author><author><name sortKey="Trojanowski, J Q" uniqKey="Trojanowski J">J.Q. Trojanowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheng, H" uniqKey="Cheng H">H. Cheng</name></author><author><name sortKey="Ulane, C" uniqKey="Ulane C">C. Ulane</name></author><author><name sortKey="Burke, R" uniqKey="Burke R">R. Burke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blandini, F" uniqKey="Blandini F">F. Blandini</name></author><author><name sortKey="Armentero, M T" uniqKey="Armentero M">M.T. Armentero</name></author><author><name sortKey="Martignoni, E" uniqKey="Martignoni E">E. Martignoni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sauer, H" uniqKey="Sauer H">H. Sauer</name></author><author><name sortKey="Oertel, W H" uniqKey="Oertel W">W.H. Oertel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernandes, M S" uniqKey="Hernandes M">M.S. Hernandes</name></author><author><name sortKey="Cafe Mendes, C C" uniqKey="Cafe Mendes C">C.C. Café-Mendes</name></author><author><name sortKey="Britto, L R G" uniqKey="Britto L">L.R.G. Britto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Segura Aguilar, J" uniqKey="Segura Aguilar J">J. Segura-Aguilar</name></author><author><name sortKey="Kostrzewa, R M" uniqKey="Kostrzewa R">R.M. Kostrzewa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mielke, M M" uniqKey="Mielke M">M.M. Mielke</name></author><author><name sortKey="Maetzler, W" uniqKey="Maetzler W">W. Maetzler</name></author><author><name sortKey="Haughey, N J" uniqKey="Haughey N">N.J. Haughey</name></author><author><name sortKey="Bandaru, V V R" uniqKey="Bandaru V">V.V.R. Bandaru</name></author><author><name sortKey="Savica, R" uniqKey="Savica R">R. Savica</name></author><author><name sortKey="Deuschle, C" uniqKey="Deuschle C">C. Deuschle</name></author><author><name sortKey="Gasser, T" uniqKey="Gasser T">T. Gasser</name></author><author><name sortKey="Hauser, A K" uniqKey="Hauser A">A.-K. Hauser</name></author><author><name sortKey="Gr Ber Sultan, S" uniqKey="Gr Ber Sultan S">S. Gräber-Sultan</name></author><author><name sortKey="Schleicher, E" uniqKey="Schleicher E">E. Schleicher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mapstone, M" uniqKey="Mapstone M">M. Mapstone</name></author><author><name sortKey="Cheema, A K" uniqKey="Cheema A">A.K. Cheema</name></author><author><name sortKey="Fiandaca, M S" uniqKey="Fiandaca M">M.S. Fiandaca</name></author><author><name sortKey="Zhong, X" uniqKey="Zhong X">X. Zhong</name></author><author><name sortKey="Mhyre, T R" uniqKey="Mhyre T">T.R. Mhyre</name></author><author><name sortKey="Macarthur, L H" uniqKey="Macarthur L">L.H. MacArthur</name></author><author><name sortKey="Hall, W J" uniqKey="Hall W">W.J. Hall</name></author><author><name sortKey="Fisher, S G" uniqKey="Fisher S">S.G. Fisher</name></author><author><name sortKey="Peterson, D R" uniqKey="Peterson D">D.R. Peterson</name></author><author><name sortKey="Haley, J M" uniqKey="Haley J">J.M. Haley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paxinos, G" uniqKey="Paxinos G">G. Paxinos</name></author><author><name sortKey="Watson, C" uniqKey="Watson C">C. Watson</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">Int J Mol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id><journal-id journal-id-type="publisher-id">ijms</journal-id><journal-title-group><journal-title>International Journal of Molecular Sciences</journal-title></journal-title-group><issn pub-type="epub">1422-0067</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26274953</article-id><article-id pub-id-type="pmc">4581276</article-id><article-id pub-id-type="doi">10.3390/ijms160818865</article-id><article-id pub-id-type="publisher-id">ijms-16-18865</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Farmer</surname><given-names>Kyle</given-names></name><xref ref-type="aff" rid="af1-ijms-16-18865">1</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Catherine A.</given-names></name><xref ref-type="aff" rid="af1-ijms-16-18865">1</xref></contrib><contrib contrib-type="author"><name><surname>Hayley</surname><given-names>Shawn</given-names></name><xref ref-type="aff" rid="af1-ijms-16-18865">1</xref><xref rid="c1-ijms-16-18865" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Jeffrey</given-names></name><xref ref-type="aff" rid="af2-ijms-16-18865">2</xref></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Harry</surname><given-names>G. Jean</given-names></name><role>Academic Editor</role></contrib></contrib-group><aff id="af1-ijms-16-18865"><label>1</label>Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada; E-Mails:<email>kyle_farmer@carleton.ca</email> (K.F.);<email>csmith@connect.carleton.ca</email> (C.A.S.)</aff><aff id="af2-ijms-16-18865"><label>2</label>Carleton University Department of Chemistry and Institute of Biochemistry, 1125 Colonel By Drive, Steacie Building, Ottawa, ON K1S 5B6, Canada; E-Mail:<email>jeff_smith@carleton.ca</email></aff><author-notes><corresp id="c1-ijms-16-18865"><label>*</label>Author to whom correspondence should be addressed; E-Mail: <email>shawn_hayley@carleton.ca</email>; Tel.: +1-613-520-2600 (ext. 6314); Fax: +1-613-520-4052.</corresp></author-notes><pub-date pub-type="epub"><day>12</day><month>8</month><year>2015</year></pub-date><pub-date pub-type="collection"><month>8</month><year>2015</year></pub-date><volume>16</volume><issue>8</issue><fpage>18865</fpage><lpage>18877</lpage><history><date date-type="received"><day>18</day><month>6</month><year>2015</year></date><date date-type="accepted"><day>06</day><month>8</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 by the authors; licensee MDPI, Basel, Switzerland.</copyright-statement><copyright-year>2015</copyright-year><license><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This article is an open access article distributed under the terms and conditions 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>).</license-p></license></permissions><abstract><p>Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.</p></abstract><kwd-group><kwd>lipidomic profile</kwd><kwd>Parkinson’s disease</kwd><kwd>early stage model</kwd><kwd>6-hydroxydopamine</kwd><kwd>HPLC-ESI-MS/MS</kwd></kwd-group></article-meta></front><body><sec><title>1. Introduction</title><p>Parkinson’s disease (PD) is a progressive neurodegenerative disease which affects the dopaminergic nigrostriatal pathway, a brain region critical in the initiation and control of motor behaviour. The degeneration, which occurs over many decades [<xref rid="B1-ijms-16-18865" ref-type="bibr">1</xref>] eventually causes severe motor and cognitive deficits [<xref rid="B2-ijms-16-18865" ref-type="bibr">2</xref>,<xref rid="B3-ijms-16-18865" ref-type="bibr">3</xref>,<xref rid="B4-ijms-16-18865" ref-type="bibr">4</xref>]. The primary symptoms of PD are muscle tremors and rigidity within the distal limbs, bradykinesia (slowed movements), and general gait disturbances. Typically PD patients do not begin to manifest primary symptoms until 50%–80% of the nigrostriatum has degenerated [<xref rid="B1-ijms-16-18865" ref-type="bibr">1</xref>], resulting in delayed treatments and an overall poorer prognosis. Therefore, identifying early neuronal changes which characterize the early phase of PD (early stage of disease that precedes the manifestation of full blown primary symptoms) is of great importance. Indeed, identifying biomarkers that could help classify the trajectory of illness in PD would greatly aid in the treatment process, as well as provide potential novel targets for the development of future therapeutics.</p><p>We have recently utilized a low dose of the specific neurotoxin 6-hydroxydopamine (6-OHDA) to induce a prodromal-like PD state. Specifically, an infusion of 6-OHDA into the dorsal striatum resulted in a modest partial lesion which encompassed 10% and 15% of the striatal volume at two and four weeks after toxin administration, respectively [<xref rid="B5-ijms-16-18865" ref-type="bibr">5</xref>]. We also found that our model resulted in no difference in the number of neurons within the substantia nigra (SNc); however, as would be expected in the early stages of PD, many of the neurons had morphology typically seen in unhealthy cells, specifically increased vacuolization, decreased dendritic projections, and an overall decreased cell volume [<xref rid="B5-ijms-16-18865" ref-type="bibr">5</xref>]. Additionally, numerous other reports have indicated that pro-death oxidative and mitochondrial stress pathways are likely involved in the early stages of PD, and that pro-inflammatory factors also arise to contribute to primary or secondary pathological processes active in the disease [<xref rid="B6-ijms-16-18865" ref-type="bibr">6</xref>,<xref rid="B7-ijms-16-18865" ref-type="bibr">7</xref>,<xref rid="B8-ijms-16-18865" ref-type="bibr">8</xref>]. At the same time, certain genetic mutations (e.g., LRRK2, Parkin, PINK1) can lead to a familial form of PD or increase the vulnerability to a host of environmental insults, such as pesticides and heavy metals [<xref rid="B9-ijms-16-18865" ref-type="bibr">9</xref>,<xref rid="B10-ijms-16-18865" ref-type="bibr">10</xref>]. Surprisingly however, scant evidence exists regarding the potential importance of lipid alterations in PD. This is particularly surprising given that many of the toxicants implicated in PD are highly lipid soluble and in fact, accumulate to a substantial degree in brain lipid membranes [<xref rid="B11-ijms-16-18865" ref-type="bibr">11</xref>].</p><p>Recent attention has focused on lipids and their role in both cell-signalling pathways that govern survival or neurodegeneration. Lysophosphotidylcholines (lysoPC), for example, have been associated with pro-apoptotic processes by activating various deleterious signalling cascades, such as activation of the Bid BH3 protein and caspase-3 [<xref rid="B12-ijms-16-18865" ref-type="bibr">12</xref>]. LysoPC species have also been shown to cause decreased expression of the anti-apoptotic TNF receptor-associated factor (TRAF) 2 [<xref rid="B13-ijms-16-18865" ref-type="bibr">13</xref>]. Comparatively, sphingolipids (SP) have an interesting dichotomous effect, such that they can act as both a pro-apoptotic and anti-apoptotic second messenger, wherein the difference between the two signalling pathways appears to be dependent on the site of lipid cleavage [<xref rid="B14-ijms-16-18865" ref-type="bibr">14</xref>]. Both SP and lysoPC lipid species are derived from phosphatidylcholines (PC), a lipid class which is an important mediator in various structural and signalling roles, having previously been implicated in numerous processes, such as cellular growth and survival [<xref rid="B15-ijms-16-18865" ref-type="bibr">15</xref>]. Yet, in many cases it is still unclear as to whether the effects are due to direct signalling by the lipids themselves as second messengers, or due to hyper- or hypoactivity of their associated enzymes [<xref rid="B14-ijms-16-18865" ref-type="bibr">14</xref>,<xref rid="B15-ijms-16-18865" ref-type="bibr">15</xref>].</p><p>In the present investigation, we analyzed the lipid profiles evident in the substantia nigra region of rats subjected to our 6-OHDA early stage model of PD. We then compared the relative quantity and structure of PC, lysoPC and SP using HPLC-ESI-MS/MS. Importantly, we employed a novel HPLC solvent methodology to separate and identify the different lipids according to their individual mass to charge (<italic>m</italic>/<italic>z</italic>) ratio. It is our belief that this broad lipidomics profile can be used as a starting point to investigate the role of lipidomic signaling in the etiology and progression of PD, as well as to further expand research directed at identifying detectable biomarkers of the neurodegenerative condition.</p></sec><sec><title>2. Results and Discussion</title><sec><title>2.1. Results</title><p>Our lipidomics profile scan identified 115 different lipid species, of these, 19 (16.5%) were significantly changed in the 6-OHDA treated animals. We found that 17 (89.5%) of these significantly altered lipids were down-regulated and only 2 (10.5%) were up-regulated. PC species were primarily affected accounting for 63.2% of all significantly altered lipids (12/19), and were found to be entirely down-regulated (<xref ref-type="fig" rid="ijms-16-18865-f001">Figure 1</xref>). Similarly, we found that lysoPC species were mainly down-regulated (<xref ref-type="fig" rid="ijms-16-18865-f002">Figure 2</xref>); however two notable lysoPC lipids were up-regulated; LPC (16:0) and LPC (18:1). The two upregulated lysoPC lipids were also found to be in the highest relative concentrations, with normalized peak area values in the 6-OHDA treated animals being 379 and 294 for LPC (16:0) and (18:1) respectively. Comparatively, the average normalized peak area for all other lysoPC lipids is 1.84, and 1.90 for PC lipids. Finally, we found that 36.8% of the significantly altered lipids contained ether-linked acyl chains. A summary of our findings can be found in <xref ref-type="table" rid="ijms-16-18865-t001">Table 1</xref>.</p><table-wrap id="ijms-16-18865-t001" position="float"><object-id pub-id-type="pii">ijms-16-18865-t001_Table 1</object-id><label>Table 1</label><caption><p>Summary table of lipidomic findings. The class of lipids was determined using the LIPID MAPS MS Prediction Tool.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Category</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>N</italic></th></tr></thead><tbody><tr><td align="left" valign="middle" style="border:none" rowspan="1" colspan="1">Lipids Identified</td><td align="center" valign="middle" style="border:none" rowspan="1" colspan="1">115</td></tr><tr><td align="left" valign="middle" style="border:none" rowspan="1" colspan="1">Lipids with Significant Changes</td><td align="center" valign="middle" style="border:none" rowspan="1" colspan="1">19</td></tr><tr><td align="left" valign="middle" style="border:none" rowspan="1" colspan="1">Lipids up-regulated in 6-OHDA Animals</td><td align="center" valign="middle" style="border:none" rowspan="1" colspan="1">2</td></tr><tr><td align="left" valign="middle" style="border:none" rowspan="1" colspan="1">Lipids down-regulated in 6-OHDA Animals</td><td align="center" valign="middle" style="border:none" rowspan="1" colspan="1">17</td></tr><tr><td align="left" valign="middle" style="border:none" rowspan="1" colspan="1">Phosphatidylcholines with Significant Changes</td><td align="center" valign="middle" style="border:none" rowspan="1" colspan="1">12</td></tr><tr><td align="left" valign="middle" style="border:none;border-bottom:solid thin" rowspan="1" colspan="1">Lysophosphatidylcholines with Significant Changes</td><td align="center" valign="middle" style="border:none;border-bottom:solid thin" rowspan="1" colspan="1">7</td></tr></tbody></table></table-wrap><fig id="ijms-16-18865-f001" position="float"><label>Figure 1</label><caption><p>The relative abundance of phosphatidylcholine species in the substantia nigra of animals treated with either 6-OHDA (20 µg) or saline vehicle into the right anterior dorsal striatum, as determined by HPLC-ESI-MS/MS measurements. All measurements were run in triplicate and the error bars represent the standard error. Only species displaying significant differences between treatment and control groups are shown. Significance was determined by independent sample <italic>t</italic>-test. The relative fold change of phosphatidylcholine species is represented along the X-axis in the form of a color heat map.</p></caption><graphic xlink:href="ijms-16-18865-g001"></graphic></fig><fig id="ijms-16-18865-f002" position="float"><label>Figure 2</label><caption><p>The relative abundance of lysophosphotidylcholine species in the substantia nigra of animals treated with either 6-OHDA (20 µg) or saline vehicle into the right anterior dorsal striatum, as determined by HPLC-ESI-MS/MS measurements. All measurements were run in triplicate and the error bars represent the standard error. Only species that were significantly differences between treatment and control groups are shown. Significance was determined by independent sample <italic>t</italic>-test. The relative fold change of lysophosphotidylcholine species is represented along the X-axis in the form of a color heat map.</p></caption><graphic xlink:href="ijms-16-18865-g002"></graphic></fig></sec><sec><title>2.2. Discussion</title><p>In this study we used a relatively low dose of 6-OHDA to induce a partial nigrostriatal lesion, which we believe may partially model a prodromal-like PD state. We have recently found that this animal model causes modest striatal lesions, coupled with morphological abnormalities of surviving neurons [<xref rid="B5-ijms-16-18865" ref-type="bibr">5</xref>]. In the present study, we found that PC lipid species were markedly altered in animals treated with 6-OHDA. By far, PC species were the most affected and were generally down-regulated in all cases. Importantly, PC lipids are major components of many cell structures [<xref rid="B15-ijms-16-18865" ref-type="bibr">15</xref>], including being present with exceptionally high levels in vacuole membranes [<xref rid="B16-ijms-16-18865" ref-type="bibr">16</xref>]. The possibility exists that the decrease of PC lipids in 6-OHDA treated mice reflects some degree of structural rearrangement. In effect, as neurons develop PD like pathology (e.g., decreased dendritic projections, decreased cell volume and cell death) the cell may simply require significantly lower PC lipid concentrations.</p><p>In addition to structural support, PC lipids may also contribute to functional aspects of neuronal processes by influencing various signalling pathways. For instance, previous studies have reported that PC lipids modulate anti-inflammatory signaling [<xref rid="B17-ijms-16-18865" ref-type="bibr">17</xref>]. Moreover, it is known that 6-OHDA can induce microglial reactivity [<xref rid="B5-ijms-16-18865" ref-type="bibr">5</xref>,<xref rid="B18-ijms-16-18865" ref-type="bibr">18</xref>,<xref rid="B19-ijms-16-18865" ref-type="bibr">19</xref>] and elevations of pro-inflammatory cytokines [<xref rid="B20-ijms-16-18865" ref-type="bibr">20</xref>,<xref rid="B21-ijms-16-18865" ref-type="bibr">21</xref>,<xref rid="B22-ijms-16-18865" ref-type="bibr">22</xref>]. Thus, the decrease in PC lipids currently observed may influence cell survival in the context of 6-OHAD treatment by influencing inflammatory processes.</p><p>Although 6-OHDA can provoke pro-apoptotic effects through the protein kinase Cδ (PKCδ) complex system [<xref rid="B23-ijms-16-18865" ref-type="bibr">23</xref>], this same system can also impart anti-apoptotic consequences through diacylglycerol (DAG) molecules, which are primary PC lipid metabolites [<xref rid="B24-ijms-16-18865" ref-type="bibr">24</xref>,<xref rid="B25-ijms-16-18865" ref-type="bibr">25</xref>]. This raises the possibility that the array of lipids modulated by 6-OHDA are likely engaged in a sort of cellular “tug of war” concerning neuronal survival pathways. Another potential source of anti-apoptotic DAG is via sphingomyelin synthase, an enzyme that combines a ceramide and PC lipid to cause the synthesis of a SP and DAG molecule [<xref rid="B15-ijms-16-18865" ref-type="bibr">15</xref>]. Although our findings did not show any significant changes in SP lipids, we did find trends in which up-regulations of sphingosine and sphinganine approached significance.</p><p>Similar to our PC results, we found an overall decrease in lysoPC species among 6-OHDA treated animals. However, there were two notable exceptions, such that LPC (16:0) and (18:1) were greatly increased in 6-OHDA treated animals. LysoPC are lipids synthesized from PCs via the enzyme phospholipase A2 (PLA2). 6-OHDA has been reported to induce PLA2 enzymatic activity within the nigrostriatal tract [<xref rid="B26-ijms-16-18865" ref-type="bibr">26</xref>,<xref rid="B27-ijms-16-18865" ref-type="bibr">27</xref>]. Interestingly, increased PLA2 activity has been repeatedly associated with apoptotic effects [<xref rid="B28-ijms-16-18865" ref-type="bibr">28</xref>,<xref rid="B29-ijms-16-18865" ref-type="bibr">29</xref>] including 6-OHDA induced apoptosis [<xref rid="B30-ijms-16-18865" ref-type="bibr">30</xref>]. However the role of PLA2 is exceedingly complex, as the enzyme has also been implicated in anti-apoptotic pathways, primarily via the arachidonic acid and peroxisome proliferator-activated receptor (PPAR) signalling pathway [<xref rid="B31-ijms-16-18865" ref-type="bibr">31</xref>]. Arachidonic acid and PPAR system activation has also been shown to reduce oxidative stress and normalize mitochondrial dysfunction [<xref rid="B31-ijms-16-18865" ref-type="bibr">31</xref>,<xref rid="B32-ijms-16-18865" ref-type="bibr">32</xref>]; both of which are affected by 6-OHDA [<xref rid="B33-ijms-16-18865" ref-type="bibr">33</xref>,<xref rid="B34-ijms-16-18865" ref-type="bibr">34</xref>,<xref rid="B35-ijms-16-18865" ref-type="bibr">35</xref>,<xref rid="B36-ijms-16-18865" ref-type="bibr">36</xref>]. Interestingly, both LPC (16:0) and LPC (18:1) have been shown to play major roles in regulating PLA2 enzyme activity by acting as an uncompetitive inhibitor [<xref rid="B37-ijms-16-18865" ref-type="bibr">37</xref>]. Alternatively, the accumulation of these LPC species could be related to impairment of other enzymes in the PC re-acylation or de-acylation processes. However, as the literature is lacking on the role of these other enzymes in PD and PD-like pathology, with further enzymology follow up studies required.</p><p>It is also possible that the observed increase in LysoPC species (16:0) and (18:1) is unrelated to altered 6-OHDA induced PLA2 enzymatic activity, and instead could be increased to serve a very specific and targeted role by acting as immune signalling mediators. In this regard, it has been shown that LysoPC (16:0) and (18:1) play a major role in inflammatory signaling [<xref rid="B37-ijms-16-18865" ref-type="bibr">37</xref>], including the release of various cytokines (interlukin-1β, interlukin-6, chemokine ligand 2, chemokine ligand 4, and tumor necrosis factor alpha) [<xref rid="B38-ijms-16-18865" ref-type="bibr">38</xref>,<xref rid="B39-ijms-16-18865" ref-type="bibr">39</xref>]. Importantly, the two LPC species have also have potent chemotactic abilities, being able to induce and recruit macrophages and T-lymphocytes to injured tissue [<xref rid="B38-ijms-16-18865" ref-type="bibr">38</xref>,<xref rid="B40-ijms-16-18865" ref-type="bibr">40</xref>,<xref rid="B41-ijms-16-18865" ref-type="bibr">41</xref>,<xref rid="B42-ijms-16-18865" ref-type="bibr">42</xref>]. Given these findings, it is possible that the overall decrease of lysoPC species, as a class of lipids, is related to changes in PLA2 activity, whereas, the dramatic increase in LysoPC (16:0) and (18:1) may arise from their involvement in inflammatory processes induced by 6-OHDA. Finally, it is important to point out that we currently report relative differences between the various species rather than absolute lipid levels. Indeed, we are most interested in lipid profile changes that might be characteristic of early stages PD.</p><p>In addition to “typical” PC and lysoPC species, we identified numerous “atypical” ether linked forms of these species; all of which were down-regulated. In agreement with our current findings, it has also been reported that PD patients had significantly decreased levels of ether-linked lipids [<xref rid="B43-ijms-16-18865" ref-type="bibr">43</xref>]. Ether linked lipids are known to generally be platelet activating factors, and have been shown to be heavily involved in the neuroinflammatory responses [<xref rid="B44-ijms-16-18865" ref-type="bibr">44</xref>]. Importantly, drugs that antagonize ether-linked phospholipids have potential clinical relevance given their reported neuroprotective and anti-tumorigenic effects [<xref rid="B45-ijms-16-18865" ref-type="bibr">45</xref>,<xref rid="B46-ijms-16-18865" ref-type="bibr">46</xref>].</p><p>It is of considerable importance to underscore that we currently assessed lipid levels in the SNc, which normally sends projections “downstream” to the striatum to modulate basal ganglia activity. Thus, the observed lipid changes are presumably upstream from the neurotoxin-injected striatum, indicating that they likely stem from retrograde signalling pathways. Indeed, the view is widely held that PD begins with a loss of function and degeneration of the axon terminals in the striatum, which then progresses back to the cell bodies in the SNc [<xref rid="B47-ijms-16-18865" ref-type="bibr">47</xref>,<xref rid="B48-ijms-16-18865" ref-type="bibr">48</xref>,<xref rid="B49-ijms-16-18865" ref-type="bibr">49</xref>,<xref rid="B50-ijms-16-18865" ref-type="bibr">50</xref>]. Further to this point, the intra-striatal 6-OHDA model of PD is also known to induce progressive neuronal degeneration over numerous weeks [<xref rid="B51-ijms-16-18865" ref-type="bibr">51</xref>,<xref rid="B52-ijms-16-18865" ref-type="bibr">52</xref>] and causes increased neuroinflammatory responses [<xref rid="B20-ijms-16-18865" ref-type="bibr">20</xref>,<xref rid="B22-ijms-16-18865" ref-type="bibr">22</xref>,<xref rid="B53-ijms-16-18865" ref-type="bibr">53</xref>]. Additionally, we used a low dose of 6-OHDA which we have recently reported to cause a modest but significant loss of dopamine (DA) striatal terminals, but does not significantly affect the number of neurons within SNc [<xref rid="B5-ijms-16-18865" ref-type="bibr">5</xref>]. Taken together, these findings suggest that the intra-striatal 6-OHDA model of PD can be an important tool for the investigation of the early stages of PD as it mimics the human condition in many key aspects.</p><p>Mitochondrial dysfunction is an important contributor to PD pathology, and indeed 6-OHDA acts primarily via disruption of mitochondrial processes, resulting in the generation of reactive oxygen species [<xref rid="B33-ijms-16-18865" ref-type="bibr">33</xref>,<xref rid="B54-ijms-16-18865" ref-type="bibr">54</xref>]. It is important to note, however, that our assay results in the extraction of general cellular and not specific mitochondrial lipids <italic>per se</italic>. Methods to isolate mitochondrial lipids in a manner that renders them amenable to MS analysis are difficult to perform and introduce a great deal of variability.</p><p>In the current study, we can only identify the general structure of the various lipid species. Identifying the full fatty acid composition can be achieved with further MS2 analysis using either lithium or acetate adduction methods. However, these methods pose significant limitations, as they are effective for standards, but can be problematic when using complex tissue samples (as they become difficult to separate chromatographically). Both adduction methods are also substantially less sensitive than those involving the production of protonated phosphocholine fragment ions, such as the precursor <italic>m</italic>/<italic>z</italic> 184 scan in positive ion mode (as outlined in the detailed methods section) was used in the current study.</p><p>Besides identifying novel lipids that could be mechanistically involved in PD, the present findings could conceivably have implications for the development of biomarkers. Of course, for a molecule to be a useful biomarker it must be readily detectable in peripheral tissue and/or fluids. In this regard, a recent study detected increases in 9 ceramide class lipids in the plasma of PD patients [<xref rid="B55-ijms-16-18865" ref-type="bibr">55</xref>]. Moreover, several PC and lysoPC lipid alterations were found in the plasma of patients with Alzheimer’s disease [<xref rid="B56-ijms-16-18865" ref-type="bibr">56</xref>]. Future studies are required to assess whether 6-OHDA induces peripheral lipid changes that parallel the presently observed brain lipid changes. However, current evidence is promising and the use of lipidomics screens as a potential tool for early diagnosis of PD may play an important role in the future.</p></sec></sec><sec><title>3. Experimental Section</title><sec><title>3.1. Animals</title><p>Six male Sprague Dawley rats (Charles River), weighing between 250–280 g on arrival were used in the current experiments. The animals were individually housed in a standard polypropylene cage (27 × 48 × 20 cm) and maintained a 12-h light/dark cycle. Tap water and food (Harlan Rat Chow, Somerville, NJ, USA) was provided ad libitum, while room temperature and humidity were maintained at 20 °C and 50%, respectively. All aspects of this experiment were approved by the Carleton University Committee for Animal Care (P10-28, 3 January 2013) and adhered to the guidelines outlined by the Canadian Council for the Use and Care of Animals in Research.</p></sec><sec><title>3.2. Surgery</title><p>The animals were anaesthetized using variable flow isoflurane inhalational anesthetic (isoflurane volume of 2%–3% in pure O<sub>2</sub>). Animals were then placed in a Kopf instruments Model 940 stereotaxic frame (Kopf Instruments, Tujunga, CA, USA) with the incisor bar positioned 3.3 mm below the incisor line. An L-shaped PlasticsOne 328OP Osmotic Pump Cannula was implanted in the right striatum at the coordinates 1.0 mm anterior, 3.0 mm lateral and 5.0 mm ventral relative to bregma and skull surface. A single infusion of 20 μg of 6-hydroxydopamine (Sigma, St. Louis, MO, USA; purchased as a hydrochloride salt, <italic>n</italic> = 3) in 0.9% injectable saline (containing 0.02% ascorbic acid), or vehicle solution (<italic>n</italic> = 3), was given at a rate of 1 μL/min using a Hamilton 25 μL syringe with a 22 gauge needle attached to a Harvard Apparatus PicoPlus 11 Pump (Harvard Apparatus, Holliston, MA, USA). The vehicle solution was made fresh daily and the 6-hydroxydopamine hydrochloride salt was mixed immediately before the infusion. After the infusion the cannula remained in place for an additional 5 min before being removed to ensure maximal diffusion of the 6-hydroxydopamine solution. BoneWax<sup>®</sup> (Stoelting, Wood Dale, IL, USA) was placed over the drill hole in the skull and the incision site was clipped using EZclip<sup>®</sup> surgical staples (Stoelting, Wood Dale, IL, USA). A single application of 2% lidocaine hydrochloride topical anaesthetic jelly (Xylocaine, AstraZeneca, CDMV, Saint-Hyacinthe, QC, Canada) was applied to the incision site.</p></sec><sec><title>3.3. Euthanasia</title><p>Animals were deeply anesthetized with an injection of sodium pentobarbital and subsequently euthanized via transcardial perfusion using a chilled 0.9% saline solution 21 days after the surgical infusion. The ipsilateral substantia nigra (SNc) was isolated from the extracted brain by dissecting the appropriate coronal section using a Kopf Instruments rat blocker obtaining a 2 mm slice approximately −4.3 to −6.3 mm with respect to bregma using the Paxinos and Watson rat atlas [<xref rid="B57-ijms-16-18865" ref-type="bibr">57</xref>]. The coronal slice was then further dissected manually using a clean razor blade so as to isolate only the region of tissue containing the substantia nigra. The extracted tissue was immediately flash frozen using 100% ethanol on dry ice. All samples were stored at −80 °C until ready for lipid extraction.</p></sec><sec><title>3.4. Lipid Extraction</title><p>All samples were individually weighed using an analytical balance, measured in grams and accurate to 5 decimal places, to be used later in the data analysis. The extracted tissue was then homogenized via sonication in a solution containing 3.2 mL 0.1 M sodium acetate, 4 mL acidified methanol (2% acetic acid), and 41.3 µL of 10 µM C13:0 LPC (internal standard). Lipids where extracted via liquid–liquid extraction using 3.8 mL of chloroform, centrifuged at 3000 RPM for 2 min at 4 °C. Chloroform extraction was repeated 3 more times using 2 mL chloroform, each replicate being centrifuged at 2000 RPM for 2 min at 4 °C to ensure extraction of all lipids from the original homogenate solution. The extracted chloroform layers were evaporated using ultrapure nitrogen gas, and lipids were subsequently re-suspended in 300 µL absolute ethanol. Lipid samples were stored at −20 °C, and were analyzed via HPLC-ESI-MS/MS within 48 h of being extracted.</p></sec><sec><title>3.5. HPLC-ESI-MS/MS</title><p>Fifteen centimeter lengths of 200 μm inner diameter fused silica (PolymicroTechnologies, Phoenix, AZ, USA) were dipped in a 3:1 solution of Kasil 1678 potassium silicate and formamide (Promega, Madison, WI, USA) to make a column frit on one end. The columns were allowed to dry for 24 h, were shortened to 10 cm, and subsequently packed with 5 cm of 5 μm ReproSil-Pur C4 stationary phase beads (Dr. Maisch GmbH, Ammerbuch, Germany) in acetone using a nitrogen pressure vessel. A PicoFrit Emitter (New Objective, Woburn, MA, USA) was filled in a similar manner, however only 1 cm of ReproSil-Pur C4 beads were used.</p><p>Test samples were prepared immediately before each run (1 μL of concentrated lipid sample, 5 μL of absolute ethanol, and 34 μL of deionized water). Samples were placed into a Dionex UltiMate 3000 autosampler (Thermo Fisher Scientific, Waltham, MA, USA) maintained at 4 °C and loaded onto the chromatography column using a Dionex UltiMate 3000 pump (Thermo Fisher Scientific, Waltham, MA, USA, 20 µL total volume). All mobile phases were prepared using HPLC grade solvents: (A) 30% methanol in 10 mM ammonium acetate; (B) isopropanol with 10 mM ammonium acetate and (C) hexane. Each lipid mass analysis was 60 min in length and began with a 100% A mobile phase. Four min later solvent B was gradually increased until the mobile phase became 100% B at the 45.5 min mark where is remained at 100% B for 1 min. At the 46.6 min mark solvent C gradually increased until the mobile phase became 100% C where it remained until the end of the run.</p><p>Chromatographically separated lipids were directly analyzed using an AB Sciex 4000 QTRAP ESI-MS/MS Hybrid Triple Quadrupole/Linear Ion Trap (AB Sciex, Framingham, MA, USA). The QTRAP was run in positive ion mode, with the ESI nanospray voltage set at 3 kV, curtain gas at 20 and declustering potential at 25 V. A precursor ion scan and an enhanced mass spectrum (EMS) were conducted using a mass range of 250–1500 Da. The precursor ion scan was set to analyze precursors of <italic>m</italic>/<italic>z</italic> 184 with a collision energy of 40.0 eV and collision cell exit potential of 10 V.</p><p>Immediately after each lipid sample was analyzed, a 140 min hexane wash was run (90% C and 10% B). Towards the end of the wash at the 130 min mark the mobile phase switched to 100% B and before switching to 100% A at 137 min. A 40 min blank was run immediately following the wash cycle to ensure there was no carry over. The mobile phase began with 100% A before gradually switching to 100% B at starting a 4 min and ending at 28 min. The mobile phase remained at 100% B for another minute before returning to 100% A until the end of the run. All samples were run in triplicate.</p></sec><sec><title>3.6. Data Analysis</title><p>Mass spectra were analyzed using Analyst Software version 1.5.1 (AB Sciex, Concord, ON, Canada). The precursor <italic>m</italic>/<italic>z</italic> 184 scan was manually analyzed to generate a list of phosphatidylcholine and sphingolipid <italic>m</italic>/<italic>z</italic>-values. The <italic>m</italic>/<italic>z</italic>-values (±0.2 Da) were then entered into MultiQuant 2.1.1 (AB Sciex, Concord, ON, Canada). All desired peaks were integrated and an output containing a variety of parameters, such as peak area and retention time, was generated. The peak area of each lipid was divided by the peak area of the internal standard C13:0 LPC (<italic>m</italic>/<italic>z</italic> 454), and then again by the total weight of the substantia nigra. The triplicate data was averaged for each animal providing a biological <italic>n</italic> of 3 per treatment group. LIPID MAPS MS Prediction Tool (LIPID MAPS, San Diego, CA, USA) was then used to determine the classification and to predict the structure of all lipid masses identified in the precursor <italic>m</italic>/<italic>z</italic> 184 scan. Statistical significance between treatment groups for each lipid species was determined using independent-samples <italic>t</italic>-tests.</p></sec></sec><sec><title>4. Conclusions</title><p>We report that 21 days after an intrastriatal infusion of a low dose of 6-OHDA there are significant decreases in PC and lysoPC within the SNc. Two lipids, LysoPC (16:0) and (18:1) stood out in that they greatly upregulated by 6-OHDA. Although speculative, these observed lipid changes may contribute to structural reconfiguration, immune system signalling, and pro- and anti-apoptotic pathways. This broad lipidomic profile is novel and might be used to further investigate the role of specific lipid species in the etiology and progression of PD, as well as providing potential biomarkers for PD progression. Of course, to be ultimately useful in this capacity, future work will be required to determine whether peripheral lipid species change in parallel with the presently observed SNc variations. Finally, it is particularly noteworthy that the series of marked lipid changes occurred within the SNc, which is of course, up-stream of the 6-OHDA injected striatum. Thus, our findings clearly indicate that retrograde signals likely emanated from the partially lesioned striatum to modulate lipid composition within the SNc cell soma.</p></sec></body><back><ack><title>Acknowledgments</title><p>Shawn Hayley was supported by funds from Canadian Institutes of Health Research, Natural Sciences and Engineering Research Counsil and Parkinson’s Society of Canada. Jeffrey Smith was supported by funds from Natural Sciences and Engineering Research Council, Canadian Foundation for Innovation, Ontario Research Fund, Canadian Institutes of Health Research and Carleton University.</p></ack><notes><title>Author Contributions</title><p>Kyle Farmer, Shawn Hayley, and Jeffrey Smith conceived and designed the study. Kyle Farmer completed all <italic>in vivo</italic> procedures. Kyle Farmer and Catherine A. Smith completed all <italic>ex vivo</italic> procedures. Kyle Farmer completed data and statistical analysis. Kyle Farmer, Shawn Hayley, and Jeffrey Smith wrote the manuscript. All authors have read an approved this manuscript.</p></notes><notes><title>Conflicts of Interest</title><p>The authors declare no conflict of interest.</p></notes><ref-list><title>References</title><ref id="B1-ijms-16-18865"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bernheimer</surname><given-names>H.</given-names></name><name><surname>Birkmayer</surname><given-names>W.</given-names></name><name><surname>Hornykiewicz</surname><given-names>O.</given-names></name><name><surname>Jellinger</surname><given-names>K.</given-names></name><name><surname>Seitelberger</surname><given-names>F.</given-names></name></person-group><article-title>Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations</article-title><source>J. Neurol. Sci.</source><year>1973</year><volume>20</volume><fpage>415</fpage><lpage>455</lpage><pub-id pub-id-type="doi">10.1016/0022-510X(73)90175-5</pub-id><pub-id pub-id-type="pmid">4272516</pub-id></element-citation></ref><ref id="B2-ijms-16-18865"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klockgether</surname><given-names>T.</given-names></name></person-group><article-title>Parkinson’s disease: Clinical aspects</article-title><source>Cell Tissue Res.</source><year>2004</year><volume>318</volume><fpage>115</fpage><lpage>120</lpage><pub-id pub-id-type="doi">10.1007/s00441-004-0975-6</pub-id><pub-id pub-id-type="pmid">15365814</pub-id></element-citation></ref><ref id="B3-ijms-16-18865"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Menza</surname><given-names>M.</given-names></name><name><surname>Donkin</surname><given-names>R.</given-names></name><name><surname>Marin</surname><given-names>H.</given-names></name></person-group><article-title>Treatment of depression in Parkinson’s disease</article-title><source>Curr. Psychiatry Rep.</source><year>2006</year><volume>8</volume><fpage>234</fpage><lpage>240</lpage><pub-id pub-id-type="doi">10.1007/s11920-006-0029-8</pub-id><pub-id pub-id-type="pmid">19817075</pub-id></element-citation></ref><ref id="B4-ijms-16-18865"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marié</surname><given-names>R.</given-names></name><name><surname>Barré</surname><given-names>L.</given-names></name><name><surname>Dupuy</surname><given-names>B.</given-names></name><name><surname>Viader</surname><given-names>F.</given-names></name><name><surname>Defer</surname><given-names>G.</given-names></name><name><surname>Baron</surname><given-names>J.</given-names></name></person-group><article-title>Relationships between striatal dopamine denervation and frontal executive tests in Parkinson’s disease</article-title><source>Neurosci. Lett.</source><year>1999</year><volume>260</volume><fpage>77</fpage><lpage>80</lpage><pub-id pub-id-type="doi">10.1016/S0304-3940(98)00928-8</pub-id><pub-id pub-id-type="pmid">10025703</pub-id></element-citation></ref><ref id="B5-ijms-16-18865"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Farmer</surname><given-names>K.</given-names></name><name><surname>Rudyk</surname><given-names>C.</given-names></name><name><surname>Prowse</surname><given-names>N.A.</given-names></name><name><surname>Hayley</surname><given-names>S.</given-names></name></person-group><article-title>Hematopoietic cytokines as therapeutic players in early stages Parkinson’s disease</article-title><source>Front. Aging Neurosci.</source><year>2015</year><volume>7</volume><fpage>126</fpage><pub-id pub-id-type="doi">10.3389/fnagi.2015.00126</pub-id><pub-id pub-id-type="pmid">26191001</pub-id></element-citation></ref><ref id="B6-ijms-16-18865"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Perier</surname><given-names>C.</given-names></name><name><surname>Bové</surname><given-names>J.</given-names></name><name><surname>Wu</surname><given-names>D.-C.</given-names></name><name><surname>Dehay</surname><given-names>B.</given-names></name><name><surname>Choi</surname><given-names>D.-K.</given-names></name><name><surname>Jackson-Lewis</surname><given-names>V.</given-names></name><name><surname>Rathke-Hartlieb</surname><given-names>S.</given-names></name><name><surname>Bouillet</surname><given-names>P.</given-names></name><name><surname>Strasser</surname><given-names>A.</given-names></name><name><surname>Schulz</surname><given-names>J.B.</given-names></name><etal></etal></person-group><article-title>Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson’s disease</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2007</year><volume>104</volume><fpage>8161</fpage><lpage>8166</lpage><pub-id pub-id-type="doi">10.1073/pnas.0609874104</pub-id><pub-id pub-id-type="pmid">17483459</pub-id></element-citation></ref><ref id="B7-ijms-16-18865"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zheng</surname><given-names>B.</given-names></name><name><surname>Liao</surname><given-names>Z.</given-names></name><name><surname>Locascio</surname><given-names>J.J.</given-names></name><name><surname>Lesniak</surname><given-names>K.A.</given-names></name><name><surname>Roderick</surname><given-names>S.S.</given-names></name><name><surname>Watt</surname><given-names>M.L.</given-names></name><name><surname>Eklund</surname><given-names>A.C.</given-names></name><name><surname>Zhang-James</surname><given-names>Y.</given-names></name><name><surname>Kim</surname><given-names>P.D.</given-names></name><name><surname>Hauser</surname><given-names>M.A.</given-names></name><etal></etal></person-group><article-title>PGC-1α, a potential therapeutic target for early intervention in Parkinson’s disease</article-title><source>Sci. Transl. Med.</source><year>2010</year><volume>2</volume><fpage>52</fpage><lpage>73</lpage><pub-id pub-id-type="doi">10.1126/scitranslmed.3001059</pub-id><pub-id pub-id-type="pmid">20926834</pub-id></element-citation></ref><ref id="B8-ijms-16-18865"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Winklhofer</surname><given-names>K.F.</given-names></name><name><surname>Haass</surname><given-names>C.</given-names></name></person-group><article-title>Mitochondrial dysfunction in Parkinson’s disease</article-title><source>Biochim. Biophys. Acta</source><year>2010</year><volume>1802</volume><fpage>29</fpage><lpage>44</lpage><pub-id pub-id-type="doi">10.1016/j.bbadis.2009.08.013</pub-id><pub-id pub-id-type="pmid">19733240</pub-id></element-citation></ref><ref id="B9-ijms-16-18865"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hagenah</surname><given-names>J.M.</given-names></name><name><surname>König</surname><given-names>I.R.</given-names></name><name><surname>Becker</surname><given-names>B.</given-names></name><name><surname>Hilker</surname><given-names>R.</given-names></name><name><surname>Kasten</surname><given-names>M.</given-names></name><name><surname>Hedrich</surname><given-names>K.</given-names></name><name><surname>Pramstaller</surname><given-names>P.P.</given-names></name><name><surname>Klein</surname><given-names>C.</given-names></name><name><surname>Seidel</surname><given-names>G.</given-names></name></person-group><article-title>Substantia nigra hyperechogenicity correlates with clinical status and number of Parkin mutated alleles</article-title><source>J. Neurol.</source><year>2007</year><volume>254</volume><fpage>1407</fpage><lpage>1413</lpage><pub-id pub-id-type="doi">10.1007/s00415-007-0567-y</pub-id><pub-id pub-id-type="pmid">17934880</pub-id></element-citation></ref><ref id="B10-ijms-16-18865"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schweitzer</surname><given-names>K.J.</given-names></name><name><surname>Brüssel</surname><given-names>T.</given-names></name><name><surname>Leitner</surname><given-names>P.</given-names></name><name><surname>Krüger</surname><given-names>R.</given-names></name><name><surname>Bauer</surname><given-names>P.</given-names></name><name><surname>Woitalla</surname><given-names>D.</given-names></name><name><surname>Tomiuk</surname><given-names>J.</given-names></name><name><surname>Gasser</surname><given-names>T.</given-names></name><name><surname>Berg</surname><given-names>D.</given-names></name></person-group><article-title>Transcranial ultrasound in different monogenetic subtypes of Parkinson’s disease</article-title><source>J. Neurol.</source><year>2007</year><volume>254</volume><fpage>613</fpage><lpage>616</lpage><pub-id pub-id-type="doi">10.1007/s00415-006-0369-7</pub-id><pub-id pub-id-type="pmid">17415511</pub-id></element-citation></ref><ref id="B11-ijms-16-18865"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prasad</surname><given-names>K.</given-names></name><name><surname>Winnik</surname><given-names>B.</given-names></name><name><surname>Thiruchelvam</surname><given-names>M.J.</given-names></name><name><surname>Buckley</surname><given-names>B.</given-names></name><name><surname>Mirochnitchenko</surname><given-names>O.</given-names></name><name><surname>Richfield</surname><given-names>E.K.</given-names></name></person-group><article-title>Prolonged toxicokinetics and toxicodynamics of paraquat in mouse brain</article-title><source>Environ. Health Perspect.</source><year>2007</year><volume>115</volume><fpage>1448</fpage><lpage>1453</lpage><pub-id pub-id-type="doi">10.1289/ehp.9932</pub-id><pub-id pub-id-type="pmid">17938734</pub-id></element-citation></ref><ref id="B12-ijms-16-18865"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goonesinghe</surname><given-names>A.</given-names></name><name><surname>Mundy</surname><given-names>E.S.</given-names></name><name><surname>Smith</surname><given-names>M.</given-names></name><name><surname>Khosravi-Far</surname><given-names>R.</given-names></name><name><surname>Martinou</surname><given-names>J.-C.</given-names></name><name><surname>Esposti</surname><given-names>M.D.</given-names></name></person-group><article-title>Pro-apoptotic Bid induces membrane perturbation by inserting selected lysolipids into the bilayer</article-title><source>Biochem. J.</source><year>2005</year><volume>387</volume><fpage>109</fpage><lpage>118</lpage><pub-id pub-id-type="doi">10.1042/BJ20041389</pub-id><pub-id pub-id-type="pmid">15500442</pub-id></element-citation></ref><ref id="B13-ijms-16-18865"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qin</surname><given-names>Z.</given-names></name><name><surname>Zhu</surname><given-names>H.</given-names></name><name><surname>Hu</surname><given-names>Y.</given-names></name></person-group><article-title>Effects of lysophosphatidylcholine on β-amyloid-induced neuronal apoptosis</article-title><source>Acta Pharmacol. Sin.</source><year>2009</year><volume>30</volume><fpage>388</fpage><lpage>395</lpage><pub-id pub-id-type="doi">10.1038/aps.2009.25</pub-id><pub-id pub-id-type="pmid">19343059</pub-id></element-citation></ref><ref id="B14-ijms-16-18865"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Giussani</surname><given-names>P.</given-names></name><name><surname>Tringali</surname><given-names>C.</given-names></name><name><surname>Riboni</surname><given-names>L.</given-names></name><name><surname>Viani</surname><given-names>P.</given-names></name><name><surname>Venerando</surname><given-names>B.</given-names></name></person-group><article-title>Sphingolipids: Key regulators of apoptosis and pivotal players in cancer drug resistance</article-title><source>Int. J. Mol. Sci.</source><year>2014</year><volume>15</volume><fpage>4356</fpage><lpage>4392</lpage><pub-id pub-id-type="doi">10.3390/ijms15034356</pub-id><pub-id pub-id-type="pmid">24625663</pub-id></element-citation></ref><ref id="B15-ijms-16-18865"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wright</surname><given-names>M.M.</given-names></name><name><surname>Howe</surname><given-names>A.G.</given-names></name><name><surname>Zaremberg</surname><given-names>V.</given-names></name></person-group><article-title>Cell membranes and apoptosis: Role of cardiolipin, phosphatidylcholine, and anticancer lipid</article-title><source>Biochem. Cell Biol.</source><year>2004</year><volume>26</volume><fpage>18</fpage><lpage>26</lpage><pub-id pub-id-type="doi">10.1139/o03-092</pub-id><pub-id pub-id-type="pmid">15052325</pub-id></element-citation></ref><ref id="B16-ijms-16-18865"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gulshan</surname><given-names>K.</given-names></name><name><surname>Moye-Rowley</surname><given-names>W.S.</given-names></name></person-group><article-title>Vacuolar import of phosphatidylcholine requires the ATP-binding cassette transporter Ybt1</article-title><source>Traffic</source><year>2011</year><volume>12</volume><fpage>1257</fpage><lpage>1268</lpage><pub-id pub-id-type="doi">10.1111/j.1600-0854.2011.01228.x</pub-id><pub-id pub-id-type="pmid">21649806</pub-id></element-citation></ref><ref id="B17-ijms-16-18865"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Treede</surname><given-names>I.</given-names></name><name><surname>Braun</surname><given-names>A.</given-names></name><name><surname>Sparla</surname><given-names>R.</given-names></name><name><surname>Kühnel</surname><given-names>M.</given-names></name><name><surname>Giese</surname><given-names>T.</given-names></name><name><surname>Turner</surname><given-names>J.R.</given-names></name><name><surname>Anes</surname><given-names>E.</given-names></name><name><surname>Kulaksiz</surname><given-names>H.</given-names></name><name><surname>Füllekrug</surname><given-names>J.</given-names></name><name><surname>Stremmel</surname><given-names>W.</given-names></name><etal></etal></person-group><article-title>Anti-inflammatory effects of phosphatidylcholine</article-title><source>J. Biol. Chem.</source><year>2007</year><volume>282</volume><fpage>27155</fpage><lpage>27164</lpage><pub-id pub-id-type="doi">10.1074/jbc.M704408200</pub-id><pub-id pub-id-type="pmid">17636253</pub-id></element-citation></ref><ref id="B18-ijms-16-18865"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marinova-Mutafchieva</surname><given-names>L.</given-names></name><name><surname>Sadeghian</surname><given-names>M.</given-names></name><name><surname>Broom</surname><given-names>L.</given-names></name><name><surname>Davis</surname><given-names>J.B.</given-names></name><name><surname>Medhurst</surname><given-names>A.D.</given-names></name><name><surname>Dexter</surname><given-names>D.T.</given-names></name></person-group><article-title>Relationship between microglial activation and dopaminergic neuronal loss in the substantia nigra: A time course study in a 6-hydroxydopamine model of Parkinson’s disease</article-title><source>J. Neurochem.</source><year>2009</year><volume>110</volume><fpage>966</fpage><lpage>975</lpage><pub-id pub-id-type="doi">10.1111/j.1471-4159.2009.06189.x</pub-id><pub-id pub-id-type="pmid">19549006</pub-id></element-citation></ref><ref id="B19-ijms-16-18865"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stott</surname><given-names>S.R.W.</given-names></name><name><surname>Barker</surname><given-names>R.A.</given-names></name></person-group><article-title>Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson’s disease</article-title><source>Eur. J. Neurosci.</source><year>2014</year><volume>39</volume><fpage>1042</fpage><lpage>1056</lpage><pub-id pub-id-type="doi">10.1111/ejn.12459</pub-id><pub-id pub-id-type="pmid">24372914</pub-id></element-citation></ref><ref id="B20-ijms-16-18865"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Choudhury</surname><given-names>M.E.</given-names></name><name><surname>Sugimoto</surname><given-names>K.</given-names></name><name><surname>Kubo</surname><given-names>M.</given-names></name><name><surname>Nagai</surname><given-names>M.</given-names></name><name><surname>Nomoto</surname><given-names>M.</given-names></name><name><surname>Takahashi</surname><given-names>H.</given-names></name><name><surname>Yano</surname><given-names>H.</given-names></name><name><surname>Tanaka</surname><given-names>J.</given-names></name></person-group><article-title>A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats</article-title><source>Brain Behav.</source><year>2011</year><volume>1</volume><fpage>26</fpage><lpage>43</lpage><pub-id pub-id-type="doi">10.1002/brb3.11</pub-id><pub-id pub-id-type="pmid">22398979</pub-id></element-citation></ref><ref id="B21-ijms-16-18865"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hernandes</surname><given-names>M.S.</given-names></name><name><surname>Santos</surname><given-names>G.D.R.</given-names></name><name><surname>Café-Mendes</surname><given-names>C.C.</given-names></name><name><surname>Lima</surname><given-names>L.S.</given-names></name><name><surname>Scavone</surname><given-names>C.</given-names></name><name><surname>Munhoz</surname><given-names>C.D.</given-names></name><name><surname>Britto</surname><given-names>L.R.G.</given-names></name></person-group><article-title>Microglial cells are involved in the susceptibility of NADPH oxidase knockout mice to 6-hydroxy-dopamine-induced neurodegeneration</article-title><source>PLoS ONE</source><year>2013</year><volume>8</volume><fpage>e75532</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0075532</pub-id><pub-id pub-id-type="pmid">24086556</pub-id></element-citation></ref><ref id="B22-ijms-16-18865"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goes</surname><given-names>A.T.R.</given-names></name><name><surname>Souza</surname><given-names>L.C.</given-names></name><name><surname>Filho</surname><given-names>C.B.</given-names></name><name><surname>del Fabbro</surname><given-names>L.</given-names></name><name><surname>de Gomes</surname><given-names>M.G.</given-names></name><name><surname>Boeira</surname><given-names>S.P.</given-names></name><name><surname>Jesse</surname><given-names>C.R.</given-names></name></person-group><article-title>Neuroprotective effects of swimming training in a mouse model of Parkinson’s disease induced by 6-hydroxydopamine</article-title><source>Neuroscience</source><year>2013</year><volume>256</volume><fpage>61</fpage><lpage>71</lpage><pub-id pub-id-type="doi">10.1016/j.neuroscience.2013.09.042</pub-id><pub-id pub-id-type="pmid">24090962</pub-id></element-citation></ref><ref id="B23-ijms-16-18865"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hanrott</surname><given-names>K.</given-names></name><name><surname>Gudmunsen</surname><given-names>L.</given-names></name><name><surname>O’Neill</surname><given-names>M.J.</given-names></name><name><surname>Wonnacott</surname><given-names>S.</given-names></name></person-group><article-title>6-hydroxydopamine-induced apoptosis is mediated via extracellular auto-oxidation and caspase 3-dependent activation of protein kinase Cdelta</article-title><source>J. Biol. Chem.</source><year>2006</year><volume>281</volume><fpage>5373</fpage><lpage>5382</lpage><pub-id pub-id-type="doi">10.1074/jbc.M511560200</pub-id><pub-id pub-id-type="pmid">16361258</pub-id></element-citation></ref><ref id="B24-ijms-16-18865"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Argaud</surname><given-names>L.</given-names></name><name><surname>Prigent</surname><given-names>A.-F.</given-names></name><name><surname>Chalabreysse</surname><given-names>L.</given-names></name><name><surname>Loufouat</surname><given-names>J.</given-names></name><name><surname>Lagarde</surname><given-names>M.</given-names></name><name><surname>Ovize</surname><given-names>M.</given-names></name></person-group><article-title>Ceramide in the antiapoptotic effect of ischemic preconditioning</article-title><source>Am. J. Physiol. Heart Circ. Physiol.</source><year>2004</year><volume>286</volume><fpage>H246</fpage><lpage>H251</lpage><pub-id pub-id-type="doi">10.1152/ajpheart.00638.2003</pub-id><pub-id pub-id-type="pmid">14512282</pub-id></element-citation></ref><ref id="B25-ijms-16-18865"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wright</surname><given-names>M.M.</given-names></name><name><surname>McMaster</surname><given-names>C.R.</given-names></name></person-group><article-title>Phospholipid synthesis, diacylglycerol compartmentation, and apoptosis</article-title><source>Biol. Res.</source><year>2002</year><volume>35</volume><fpage>223</fpage><lpage>229</lpage><pub-id pub-id-type="doi">10.4067/S0716-97602002000200014</pub-id><pub-id pub-id-type="pmid">12415740</pub-id></element-citation></ref><ref id="B26-ijms-16-18865"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hayakawa</surname><given-names>T.</given-names></name><name><surname>Chang</surname><given-names>M.C.J.</given-names></name><name><surname>Bell</surname><given-names>J.M.</given-names></name><name><surname>Seeman</surname><given-names>R.</given-names></name><name><surname>Rapoport</surname><given-names>S.I.</given-names></name><name><surname>Appel</surname><given-names>N.M.</given-names></name></person-group><article-title>Fatty acid incorporation depicts brain activity in a rat model of Parkinson’s disease</article-title><source>Brain Res.</source><year>1998</year><volume>807</volume><fpage>177</fpage><lpage>181</lpage><pub-id pub-id-type="doi">10.1016/S0006-8993(98)00751-3</pub-id><pub-id pub-id-type="pmid">9757030</pub-id></element-citation></ref><ref id="B27-ijms-16-18865"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>H.-J.</given-names></name><name><surname>Bazinet</surname><given-names>R.P.</given-names></name><name><surname>Rapoport</surname><given-names>S.I.</given-names></name><name><surname>Bhattacharjee</surname><given-names>A.K.</given-names></name></person-group><article-title>Brain arachidonic acid cascade enzymes are up-regulated in a rat model of unilateral parkinson disease</article-title><source>Neurochem. Res.</source><year>2010</year><volume>35</volume><fpage>613</fpage><lpage>619</lpage><pub-id pub-id-type="doi">10.1007/s11064-009-0106-6</pub-id><pub-id pub-id-type="pmid">19997776</pub-id></element-citation></ref><ref id="B28-ijms-16-18865"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>S.J.</given-names></name><name><surname>Gershov</surname><given-names>D.</given-names></name><name><surname>Ma</surname><given-names>X.</given-names></name><name><surname>Brot</surname><given-names>N.</given-names></name><name><surname>Elkon</surname><given-names>K.B.</given-names></name></person-group><article-title>I-PLA2 Activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation</article-title><source>J. Exp. Med.</source><year>2002</year><volume>196</volume><fpage>655</fpage><lpage>665</lpage><pub-id pub-id-type="doi">10.1084/jem.20020542</pub-id><pub-id pub-id-type="pmid">12208880</pub-id></element-citation></ref><ref id="B29-ijms-16-18865"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jaattela</surname><given-names>M.</given-names></name><name><surname>Benedict</surname><given-names>M.</given-names></name><name><surname>Tewari</surname><given-names>M.</given-names></name><name><surname>Shayman</surname><given-names>J.A.</given-names></name><name><surname>Dixit</surname><given-names>V.M.</given-names></name></person-group><article-title>Bcl-x and Bcl-2 inhibit TN and Fas-induced apoptosis and activation of phospholipase A1 in breast carcinoma cells</article-title><source>Oncogene</source><year>1995</year><volume>10</volume><fpage>2297</fpage><lpage>2305</lpage><pub-id pub-id-type="pmid">7540278</pub-id></element-citation></ref><ref id="B30-ijms-16-18865"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ahmad</surname><given-names>A.S.</given-names></name><name><surname>Maruyama</surname><given-names>T.</given-names></name><name><surname>Narumiya</surname><given-names>S.</given-names></name><name><surname>Doré</surname><given-names>S.</given-names></name></person-group><article-title>PGE2 EP1 receptor deletion attenuates 6-OHDA-induced Parkinsonism in mice: Old switch, new target</article-title><source>Neurotox. Res.</source><year>2013</year><volume>23</volume><fpage>260</fpage><lpage>266</lpage><pub-id pub-id-type="doi">10.1007/s12640-013-9381-8</pub-id><pub-id pub-id-type="pmid">23385625</pub-id></element-citation></ref><ref id="B31-ijms-16-18865"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kreisler</surname><given-names>A.</given-names></name><name><surname>Gelé</surname><given-names>P.</given-names></name><name><surname>Wiart</surname><given-names>J.-F.</given-names></name><name><surname>Lhermitte</surname><given-names>M.</given-names></name><name><surname>Destée</surname><given-names>A.</given-names></name><name><surname>Bordet</surname><given-names>R.</given-names></name></person-group><article-title>Lipid-lowering drugs in the MPTP mouse model of Parkinson’s disease: Fenofibrate has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase inhibitors do not</article-title><source>Brain Res.</source><year>2007</year><volume>1135</volume><fpage>77</fpage><lpage>84</lpage><pub-id pub-id-type="doi">10.1016/j.brainres.2006.12.011</pub-id><pub-id pub-id-type="pmid">17196944</pub-id></element-citation></ref><ref id="B32-ijms-16-18865"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ravnsjkjaer</surname><given-names>K.</given-names></name><name><surname>Frigerio</surname><given-names>F.</given-names></name><name><surname>Boegesen</surname><given-names>M.</given-names></name><name><surname>Nielsen</surname><given-names>T.</given-names></name><name><surname>Maechler</surname><given-names>P.</given-names></name><name><surname>Mandrup</surname><given-names>S.</given-names></name></person-group><article-title>PPAR-γ is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction</article-title><source>J. Lipid Res.</source><year>2014</year><volume>51</volume><fpage>1370</fpage><lpage>1379</lpage><pub-id pub-id-type="doi">10.1194/jlr.M001123</pub-id><pub-id pub-id-type="pmid">19965574</pub-id></element-citation></ref><ref id="B33-ijms-16-18865"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kupsch</surname><given-names>A.</given-names></name><name><surname>Schmidt</surname><given-names>W.</given-names></name><name><surname>Gizatullina</surname><given-names>Z.</given-names></name><name><surname>Debska-Vielhaber</surname><given-names>G.</given-names></name><name><surname>Voges</surname><given-names>J.</given-names></name><name><surname>Striggow</surname><given-names>F.</given-names></name><name><surname>Panther</surname><given-names>P.</given-names></name><name><surname>Schwegler</surname><given-names>H.</given-names></name><name><surname>Heinze</surname><given-names>H.-J.</given-names></name><name><surname>Vielhaber</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>6-Hydroxydopamine impairs mitochondrial function in the rat model of Parkinson’s disease: Respirometric, histological, and behavioral analyses</article-title><source>J. Neural Transm.</source><year>2014</year><volume>121</volume><fpage>1245</fpage><lpage>1257</lpage><pub-id pub-id-type="doi">10.1007/s00702-014-1185-3</pub-id><pub-id pub-id-type="pmid">24627045</pub-id></element-citation></ref><ref id="B34-ijms-16-18865"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Park</surname><given-names>S.Y.</given-names></name><name><surname>Kim</surname><given-names>D.Y.</given-names></name><name><surname>Kang</surname><given-names>J.-K.</given-names></name><name><surname>Park</surname><given-names>G.</given-names></name><name><surname>Choi</surname><given-names>Y.-W.</given-names></name></person-group><article-title>Involvement of activation of the Nrf2/ARE pathway in protection against 6-OHDA-induced SH-SY5Y cell death by α-iso-cubebenol</article-title><source>Neurotoxicology</source><year>2014</year><volume>44</volume><fpage>160</fpage><lpage>180</lpage><pub-id pub-id-type="doi">10.1016/j.neuro.2014.06.011</pub-id><pub-id pub-id-type="pmid">24997245</pub-id></element-citation></ref><ref id="B35-ijms-16-18865"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khan</surname><given-names>M.M.</given-names></name><name><surname>Ahmad</surname><given-names>A.</given-names></name><name><surname>Ishrat</surname><given-names>T.</given-names></name><name><surname>Khan</surname><given-names>M.B.</given-names></name><name><surname>Hoda</surname><given-names>M.N.</given-names></name><name><surname>Khuwaja</surname><given-names>G.</given-names></name><name><surname>Raza</surname><given-names>S.S.</given-names></name><name><surname>Khan</surname><given-names>A.</given-names></name><name><surname>Javed</surname><given-names>H.</given-names></name><name><surname>Vaibhav</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson’s disease</article-title><source>Brain Res.</source><year>2010</year><volume>1328</volume><fpage>139</fpage><lpage>151</lpage><pub-id pub-id-type="doi">10.1016/j.brainres.2010.02.031</pub-id><pub-id pub-id-type="pmid">20167206</pub-id></element-citation></ref><ref id="B36-ijms-16-18865"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Asaithambi</surname><given-names>A.</given-names></name><name><surname>Ay</surname><given-names>M.</given-names></name><name><surname>Jin</surname><given-names>H.</given-names></name><name><surname>Gosh</surname><given-names>A.</given-names></name><name><surname>Anantharam</surname><given-names>V.</given-names></name><name><surname>Kanthasamy</surname><given-names>A.</given-names></name><name><surname>Kanthasamy</surname><given-names>A.G.</given-names></name></person-group><article-title>Protein kinase D1 (PKD1) phosphorylation promotes dopaminergic neuronal survival during 6-OHDA-induced oxidative stress</article-title><source>PLoS ONE</source><year>2014</year><volume>9</volume><fpage>e96947</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0096947</pub-id><pub-id pub-id-type="pmid">24806360</pub-id></element-citation></ref><ref id="B37-ijms-16-18865"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cunningham</surname><given-names>T.J.</given-names></name><name><surname>Yao</surname><given-names>L.</given-names></name><name><surname>Lucena</surname><given-names>A.</given-names></name></person-group><article-title>Product inhibition of secreted phospholipase A2 may explain lysophosphatidylcholines’ unexpected therapeutic properties</article-title><source>J. Inflamm.</source><year>2008</year><volume>5</volume><fpage>17</fpage><pub-id pub-id-type="doi">10.1186/1476-9255-5-17</pub-id><pub-id pub-id-type="pmid">18945345</pub-id></element-citation></ref><ref id="B38-ijms-16-18865"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu-Wu</surname><given-names>Y.</given-names></name><name><surname>Hurt-Camejo</surname><given-names>E.</given-names></name><name><surname>Wiklund</surname><given-names>O.</given-names></name></person-group><article-title>Lysophosphatidylcholine induces the production of IL-1β by human monocytes</article-title><source>Atherosclerosis</source><year>1998</year><volume>137</volume><fpage>351</fpage><lpage>357</lpage><pub-id pub-id-type="doi">10.1016/S0021-9150(97)00295-5</pub-id><pub-id pub-id-type="pmid">9622278</pub-id></element-citation></ref><ref id="B39-ijms-16-18865"><label>39.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gonçalves</surname><given-names>I.</given-names></name><name><surname>Edsfeldt</surname><given-names>A.</given-names></name><name><surname>Ko</surname><given-names>N.Y.</given-names></name><name><surname>Grufman</surname><given-names>H.</given-names></name><name><surname>Berg</surname><given-names>K.</given-names></name><name><surname>Björkbacka</surname><given-names>H.</given-names></name><name><surname>Nitulescu</surname><given-names>M.</given-names></name><name><surname>Persson</surname><given-names>A.</given-names></name><name><surname>Nilsson</surname><given-names>M.</given-names></name><name><surname>Prehn</surname><given-names>C.</given-names></name><etal></etal></person-group><article-title>Evidence supporting a key role of Lp-PLA2-generated lysophosphatidylcholine in human atherosclerotic plaque inflammation</article-title><source>Arterioscler. Thromb. Vasc. Biol.</source><year>2012</year><volume>32</volume><fpage>1505</fpage><lpage>1512</lpage><pub-id pub-id-type="doi">10.1161/ATVBAHA.112.249854</pub-id><pub-id pub-id-type="pmid">22499993</pub-id></element-citation></ref><ref id="B40-ijms-16-18865"><label>40.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ryborg</surname><given-names>A.K.</given-names></name><name><surname>Deleuran</surname><given-names>B.</given-names></name><name><surname>Thestrup-Pedersen</surname><given-names>K.</given-names></name><name><surname>Kragballe</surname><given-names>K.</given-names></name></person-group><article-title>Lysophosphatidylcholine: A chemoattractant to human T lymphocytes</article-title><source>Arch. Dermatol. Res.</source><year>1994</year><volume>286</volume><fpage>462</fpage><lpage>465</lpage><pub-id pub-id-type="doi">10.1007/BF00371572</pub-id><pub-id pub-id-type="pmid">7864659</pub-id></element-citation></ref><ref id="B41-ijms-16-18865"><label>41.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McMurray</surname><given-names>H.F.</given-names></name><name><surname>Parthasarathy</surname><given-names>S.</given-names></name><name><surname>Steinberg</surname><given-names>D.</given-names></name></person-group><article-title>Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes</article-title><source>J. Clin. Investig.</source><year>1993</year><volume>92</volume><fpage>1004</fpage><lpage>1008</lpage><pub-id pub-id-type="doi">10.1172/JCI116605</pub-id><pub-id pub-id-type="pmid">8349785</pub-id></element-citation></ref><ref id="B42-ijms-16-18865"><label>42.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quinn</surname><given-names>M.T.</given-names></name><name><surname>Parthasarathy</surname><given-names>S.</given-names></name><name><surname>Steinberg</surname><given-names>D.</given-names></name></person-group><article-title>Lysophosphatidylcholine: A chemotactic factor for human monocytes and its potential role in atherogenesis</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>1988</year><volume>85</volume><fpage>2805</fpage><lpage>2809</lpage><pub-id pub-id-type="doi">10.1073/pnas.85.8.2805</pub-id><pub-id pub-id-type="pmid">3357891</pub-id></element-citation></ref><ref id="B43-ijms-16-18865"><label>43.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fabelo</surname><given-names>N.</given-names></name><name><surname>Martín</surname><given-names>V.</given-names></name><name><surname>Santpere</surname><given-names>G.</given-names></name><name><surname>Marín</surname><given-names>R.</given-names></name><name><surname>Torrent</surname><given-names>L.</given-names></name><name><surname>Ferrer</surname><given-names>I.</given-names></name><name><surname>Díaz</surname><given-names>M.</given-names></name></person-group><article-title>Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease</article-title><source>Mol. Med.</source><year>2011</year><volume>17</volume><fpage>1107</fpage><lpage>1118</lpage><pub-id pub-id-type="doi">10.2119/molmed.2011.00119</pub-id><pub-id pub-id-type="pmid">21717034</pub-id></element-citation></ref><ref id="B44-ijms-16-18865"><label>44.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Braverman</surname><given-names>N.E.</given-names></name><name><surname>Moser</surname><given-names>A.B.</given-names></name></person-group><article-title>Functions of plasmalogen lipids in health and disease</article-title><source>Biochim. Biophys. Acta</source><year>2012</year><volume>1822</volume><fpage>1442</fpage><lpage>1452</lpage><pub-id pub-id-type="doi">10.1016/j.bbadis.2012.05.008</pub-id><pub-id pub-id-type="pmid">22627108</pub-id></element-citation></ref><ref id="B45-ijms-16-18865"><label>45.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lohmeyer</surname><given-names>M.</given-names></name><name><surname>Bittman</surname><given-names>R.</given-names></name></person-group><article-title>Antitumore ether lipids and alkylphosphocholines</article-title><source>Drugs Future</source><year>1994</year><volume>19</volume><fpage>1021</fpage><lpage>1037</lpage><pub-id pub-id-type="doi">10.1358/dof.1994.019.11.595800</pub-id></element-citation></ref><ref id="B46-ijms-16-18865"><label>46.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dave</surname><given-names>P.C.</given-names></name><name><surname>Billington</surname><given-names>E.</given-names></name><name><surname>Pan</surname><given-names>Y.-L.</given-names></name><name><surname>Straus</surname><given-names>S.K.</given-names></name></person-group><article-title>Interaction of alamethicin with ether-linked phospholipid bilayers: Oriented circular dichroism, 31P solid-state NMR, and differential scanning calorimetry studies</article-title><source>Biophys. J.</source><year>2005</year><volume>89</volume><fpage>2434</fpage><lpage>2442</lpage><pub-id pub-id-type="doi">10.1529/biophysj.105.067678</pub-id><pub-id pub-id-type="pmid">16055546</pub-id></element-citation></ref><ref id="B47-ijms-16-18865"><label>47.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van der Putten</surname><given-names>H.</given-names></name><name><surname>Wiederhold</surname><given-names>K.H.</given-names></name><name><surname>Probst</surname><given-names>A.</given-names></name><name><surname>Barbieri</surname><given-names>S.</given-names></name><name><surname>Mistl</surname><given-names>C.</given-names></name><name><surname>Danner</surname><given-names>S.</given-names></name><name><surname>Kauffmann</surname><given-names>S.</given-names></name><name><surname>Hofele</surname><given-names>K.</given-names></name><name><surname>Spooren</surname><given-names>W.P.</given-names></name><name><surname>Ruegg</surname><given-names>M.A.</given-names></name><etal></etal></person-group><article-title>Neuropathology in mice expressing human α-synuclein</article-title><source>J. Neurosci.</source><year>2000</year><volume>20</volume><fpage>6021</fpage><lpage>6029</lpage><pub-id pub-id-type="pmid">10934251</pub-id></element-citation></ref><ref id="B48-ijms-16-18865"><label>48.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lotharius</surname><given-names>J.</given-names></name><name><surname>Brundin</surname><given-names>P.</given-names></name></person-group><article-title>Pathogenesis of Parkinson’s disease: Dopamine, vesicles and α-synuclein</article-title><source>Nat. Rev. Neurosci.</source><year>2002</year><volume>3</volume><fpage>932</fpage><lpage>942</lpage><pub-id pub-id-type="doi">10.1038/nrn983</pub-id><pub-id pub-id-type="pmid">12461550</pub-id></element-citation></ref><ref id="B49-ijms-16-18865"><label>49.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Galvin</surname><given-names>J.E.</given-names></name><name><surname>Uryu</surname><given-names>K.</given-names></name><name><surname>Lee</surname><given-names>V.M.</given-names></name><name><surname>Trojanowski</surname><given-names>J.Q.</given-names></name></person-group><article-title>Axon pathology in Parkinson ’ s disease and Lewy body dementia hippocampus contains α-, β- and γ-synuclein</article-title><source>PNAS</source><year>1999</year><volume>96</volume><fpage>13450</fpage><lpage>13455</lpage><pub-id pub-id-type="doi">10.1073/pnas.96.23.13450</pub-id><pub-id pub-id-type="pmid">10557341</pub-id></element-citation></ref><ref id="B50-ijms-16-18865"><label>50.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheng</surname><given-names>H.</given-names></name><name><surname>Ulane</surname><given-names>C.</given-names></name><name><surname>Burke</surname><given-names>R.</given-names></name></person-group><article-title>Clinical progression in Parkinson’s disease and the neurobiology of axons</article-title><source>Ann. Neurol.</source><year>2010</year><volume>67</volume><fpage>715</fpage><lpage>725</lpage><pub-id pub-id-type="doi">10.1002/ana.21995</pub-id><pub-id pub-id-type="pmid">20517933</pub-id></element-citation></ref><ref id="B51-ijms-16-18865"><label>51.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blandini</surname><given-names>F.</given-names></name><name><surname>Armentero</surname><given-names>M.T.</given-names></name><name><surname>Martignoni</surname><given-names>E.</given-names></name></person-group><article-title>The 6-hydroxydopamine model: News from the past</article-title><source>Parkinsonism Relat. Disord.</source><year>2008</year><volume>14</volume><issue>Suppl. 2</issue><fpage>S124</fpage><lpage>S129</lpage><pub-id pub-id-type="doi">10.1016/j.parkreldis.2008.04.015</pub-id><pub-id pub-id-type="pmid">18595767</pub-id></element-citation></ref><ref id="B52-ijms-16-18865"><label>52.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sauer</surname><given-names>H.</given-names></name><name><surname>Oertel</surname><given-names>W.H.</given-names></name></person-group><article-title>Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: A combined retrograde tracing and immunocytochemical study in the rat</article-title><source>Neuroscience</source><year>1994</year><volume>59</volume><fpage>401</fpage><lpage>415</lpage><pub-id pub-id-type="doi">10.1016/0306-4522(94)90605-X</pub-id><pub-id pub-id-type="pmid">7516500</pub-id></element-citation></ref><ref id="B53-ijms-16-18865"><label>53.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hernandes</surname><given-names>M.S.</given-names></name><name><surname>Café-Mendes</surname><given-names>C.C.</given-names></name><name><surname>Britto</surname><given-names>L.R.G.</given-names></name></person-group><article-title>NADPH oxidase and the degeneration of dopaminergic neurons in parkinsonian mice</article-title><source>Oxid. Med. Cell. Longev.</source><year>2013</year><volume>2013</volume><fpage>157857</fpage><pub-id pub-id-type="doi">10.1155/2013/157857</pub-id><pub-id pub-id-type="pmid">24379900</pub-id></element-citation></ref><ref id="B54-ijms-16-18865"><label>54.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Segura-Aguilar</surname><given-names>J.</given-names></name><name><surname>Kostrzewa</surname><given-names>R.M.</given-names></name></person-group><article-title>Neurotoxin mechanisms and processes relevant to Parkinson’s disease: An update</article-title><source>Neurotox. Res.</source><year>2015</year><volume>27</volume><fpage>328</fpage><lpage>354</lpage><pub-id pub-id-type="doi">10.1007/s12640-015-9519-y</pub-id><pub-id pub-id-type="pmid">25631236</pub-id></element-citation></ref><ref id="B55-ijms-16-18865"><label>55.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mielke</surname><given-names>M.M.</given-names></name><name><surname>Maetzler</surname><given-names>W.</given-names></name><name><surname>Haughey</surname><given-names>N.J.</given-names></name><name><surname>Bandaru</surname><given-names>V.V.R.</given-names></name><name><surname>Savica</surname><given-names>R.</given-names></name><name><surname>Deuschle</surname><given-names>C.</given-names></name><name><surname>Gasser</surname><given-names>T.</given-names></name><name><surname>Hauser</surname><given-names>A.-K.</given-names></name><name><surname>Gräber-Sultan</surname><given-names>S.</given-names></name><name><surname>Schleicher</surname><given-names>E.</given-names></name><etal></etal></person-group><article-title>Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson’s disease and associated with cognitive impairment: A pilot study</article-title><source>PLoS ONE</source><year>2013</year><volume>8</volume><fpage>e73094</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0073094</pub-id><pub-id pub-id-type="pmid">24058461</pub-id></element-citation></ref><ref id="B56-ijms-16-18865"><label>56.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mapstone</surname><given-names>M.</given-names></name><name><surname>Cheema</surname><given-names>A.K.</given-names></name><name><surname>Fiandaca</surname><given-names>M.S.</given-names></name><name><surname>Zhong</surname><given-names>X.</given-names></name><name><surname>Mhyre</surname><given-names>T.R.</given-names></name><name><surname>MacArthur</surname><given-names>L.H.</given-names></name><name><surname>Hall</surname><given-names>W.J.</given-names></name><name><surname>Fisher</surname><given-names>S.G.</given-names></name><name><surname>Peterson</surname><given-names>D.R.</given-names></name><name><surname>Haley</surname><given-names>J.M.</given-names></name><etal></etal></person-group><article-title>Plasma phospholipids identify antecedent memory impairment in older adults</article-title><source>Nat. Med.</source><year>2014</year><volume>20</volume><fpage>415</fpage><lpage>418</lpage><pub-id pub-id-type="doi">10.1038/nm.3466</pub-id><pub-id pub-id-type="pmid">24608097</pub-id></element-citation></ref><ref id="B57-ijms-16-18865"><label>57.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Paxinos</surname><given-names>G.</given-names></name><name><surname>Watson</surname><given-names>C.</given-names></name></person-group><source>The Rat Brain in Stereotaxic Coordinates</source><publisher-name>Academic Press</publisher-name><publisher-loc>San Diego, CA, USA</publisher-loc><year>1998</year><fpage>1</fpage><lpage>75</lpage></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000064 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000064 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.29. |  |