MovDisordV3, Pmc, Curation, bibRecord, 000461

Living on the edge with too many mouths to feed: Why dopamine neurons die

Identifieur interne : 000461 ( Pmc/Curation ); précédent : 000460; suivant : 000462

Living on the edge with too many mouths to feed: Why dopamine neurons die

Auteurs : J Paul Bolam [Royaume-Uni] ; Eleftheria K. Pissadaki [Royaume-Uni, Grèce]

Source :

Movement Disorders [ 0885-3185 ] ; 2012.

RBID : PMC:3504389

Abstract

Although genes, protein aggregates, environmental toxins, and other factors associated with Parkinson’s disease (PD) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of PD is the exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What is it about these neurons, among all other neurons in the brain, that makes them so susceptible in PD? We hypothesize that a major contributory factor is the unique cellular architecture of SNc DA neuron axons. Their large, complex axonal arbour puts them under such a tight energy budget that it makes them particularly susceptible to factors that contribute to cell death, including unique molecular characteristics associated with SNc DA neurons and nonspecific, nervous-system–wide factors. © 2012 Movement Disorder Society

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504389

DOI: 10.1002/mds.25135
PubMed: 23008164
PubMed Central: 3504389

Links toward previous steps (curation, corpus...)

to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000461

Links to Exploration step

PMC:3504389

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Living on the edge with too many mouths to feed: Why dopamine neurons die</title>
<author><name sortKey="Bolam, J Paul" sort="Bolam, J Paul" uniqKey="Bolam J" first="J Paul" last="Bolam">J Paul Bolam</name>
<affiliation wicri:level="1"><nlm:aff id="au1"><institution>Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson’s Disease Centre,</institution>
<addr-line>University of Oxford, Oxford, UK</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Oxford, Oxford</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pissadaki, Eleftheria K" sort="Pissadaki, Eleftheria K" uniqKey="Pissadaki E" first="Eleftheria K" last="Pissadaki">Eleftheria K. Pissadaki</name>
<affiliation wicri:level="1"><nlm:aff id="au1"><institution>Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson’s Disease Centre,</institution>
<addr-line>University of Oxford, Oxford, UK</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Oxford, Oxford</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="au2"><institution>Department of Basic Sciences, Faculty of Medicine,</institution>
<addr-line>University of Crete, Heraklion, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>University of Crete, Heraklion</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23008164</idno>
<idno type="pmc">3504389</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504389</idno>
<idno type="RBID">PMC:3504389</idno>
<idno type="doi">10.1002/mds.25135</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000461</idno>
<idno type="wicri:Area/Pmc/Curation">000461</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Living on the edge with too many mouths to feed: Why dopamine neurons die</title>
<author><name sortKey="Bolam, J Paul" sort="Bolam, J Paul" uniqKey="Bolam J" first="J Paul" last="Bolam">J Paul Bolam</name>
<affiliation wicri:level="1"><nlm:aff id="au1"><institution>Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson’s Disease Centre,</institution>
<addr-line>University of Oxford, Oxford, UK</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Oxford, Oxford</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pissadaki, Eleftheria K" sort="Pissadaki, Eleftheria K" uniqKey="Pissadaki E" first="Eleftheria K" last="Pissadaki">Eleftheria K. Pissadaki</name>
<affiliation wicri:level="1"><nlm:aff id="au1"><institution>Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson’s Disease Centre,</institution>
<addr-line>University of Oxford, Oxford, UK</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Oxford, Oxford</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="au2"><institution>Department of Basic Sciences, Faculty of Medicine,</institution>
<addr-line>University of Crete, Heraklion, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>University of Crete, Heraklion</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement Disorders</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Although genes, protein aggregates, environmental toxins, and other factors associated with Parkinson’s disease (PD) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of PD is the exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What is it about these neurons, among all other neurons in the brain, that makes them so susceptible in PD? We hypothesize that a major contributory factor is the unique cellular architecture of SNc DA neuron axons. Their large, complex axonal arbour puts them under such a tight energy budget that it makes them particularly susceptible to factors that contribute to cell death, including unique molecular characteristics associated with SNc DA neurons and nonspecific, nervous-system–wide factors. © 2012 Movement Disorder Society</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Martin, I" uniqKey="Martin I">I Martin</name>
</author>
<author><name sortKey="Dawson, Vl" uniqKey="Dawson V">VL Dawson</name>
</author>
<author><name sortKey="Dawson, Tm" uniqKey="Dawson T">TM Dawson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schapira, Ah" uniqKey="Schapira A">AH Schapira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D Sulzer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gasser, T" uniqKey="Gasser T">T Gasser</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Obeso, Ja" uniqKey="Obeso J">JA Obeso</name>
</author>
<author><name sortKey="Rodriguez Oroz, Mc" uniqKey="Rodriguez Oroz M">MC Rodriguez-Oroz</name>
</author>
<author><name sortKey="Goetz, Cg" uniqKey="Goetz C">CG Goetz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Surmeier, Dj" uniqKey="Surmeier D">DJ Surmeier</name>
</author>
<author><name sortKey="Guzman, Jn" uniqKey="Guzman J">JN Guzman</name>
</author>
<author><name sortKey="Sanchez Padilla, J" uniqKey="Sanchez Padilla J">J Sanchez-Padilla</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Guzman, Jn" uniqKey="Guzman J">JN Guzman</name>
</author>
<author><name sortKey="Sanchez Padilla, J" uniqKey="Sanchez Padilla J">J Sanchez-Padilla</name>
</author>
<author><name sortKey="Wokosin, D" uniqKey="Wokosin D">D Wokosin</name>
</author>
<author><name sortKey="Kondapalli, J" uniqKey="Kondapalli J">J Kondapalli</name>
</author>
<author><name sortKey="Ilijic, E" uniqKey="Ilijic E">E Ilijic</name>
</author>
<author><name sortKey="Schumacker, Pt" uniqKey="Schumacker P">PT Schumacker</name>
</author>
<author><name sortKey="Surmeier, Dj" uniqKey="Surmeier D">DJ Surmeier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Surmeier, Dj" uniqKey="Surmeier D">DJ Surmeier</name>
</author>
<author><name sortKey="Guzman, Jn" uniqKey="Guzman J">JN Guzman</name>
</author>
<author><name sortKey="Sanchez Padilla, J" uniqKey="Sanchez Padilla J">J Sanchez-Padilla</name>
</author>
<author><name sortKey="Goldberg, Ja" uniqKey="Goldberg J">JA Goldberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chan, Cs" uniqKey="Chan C">CS Chan</name>
</author>
<author><name sortKey="Guzman, Jn" uniqKey="Guzman J">JN Guzman</name>
</author>
<author><name sortKey="Ilijic, E" uniqKey="Ilijic E">E Ilijic</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Laar, Vs" uniqKey="Van Laar V">VS Van Laar</name>
</author>
<author><name sortKey="Dukes, Aa" uniqKey="Dukes A">AA Dukes</name>
</author>
<author><name sortKey="Cascio, M" uniqKey="Cascio M">M Cascio</name>
</author>
<author><name sortKey="Hastings, Tg" uniqKey="Hastings T">TG Hastings</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Laar, Vs" uniqKey="Van Laar V">VS Van Laar</name>
</author>
<author><name sortKey="Mishizen, Aj" uniqKey="Mishizen A">AJ Mishizen</name>
</author>
<author><name sortKey="Cascio, M" uniqKey="Cascio M">M Cascio</name>
</author>
<author><name sortKey="Hastings, Tg" uniqKey="Hastings T">TG Hastings</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Berman Sb Hastings, Tg" uniqKey="Berman Sb Hastings T">TG Berman SB Hastings</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hirsch, E" uniqKey="Hirsch E">E Hirsch</name>
</author>
<author><name sortKey="Graybiel, Am" uniqKey="Graybiel A">AM Graybiel</name>
</author>
<author><name sortKey="Agid, Ya" uniqKey="Agid Y">YA Agid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gesi, M" uniqKey="Gesi M">M Gesi</name>
</author>
<author><name sortKey="Soldani, P" uniqKey="Soldani P">P Soldani</name>
</author>
<author><name sortKey="Giorgi, Fs" uniqKey="Giorgi F">FS Giorgi</name>
</author>
<author><name sortKey="Santinami, A" uniqKey="Santinami A">A Santinami</name>
</author>
<author><name sortKey="Bonaccorsi, I" uniqKey="Bonaccorsi I">I Bonaccorsi</name>
</author>
<author><name sortKey="Fornai, F" uniqKey="Fornai F">F Fornai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Braak, H" uniqKey="Braak H">H Braak</name>
</author>
<author><name sortKey="Ghebremedhin, E" uniqKey="Ghebremedhin E">E Ghebremedhin</name>
</author>
<author><name sortKey="Rub, U" uniqKey="Rub U">U Rub</name>
</author>
<author><name sortKey="Bratzke, H" uniqKey="Bratzke H">H Bratzke</name>
</author>
<author><name sortKey="Del Tredici, K" uniqKey="Del Tredici K">K Del Tredici</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Braak, H" uniqKey="Braak H">H Braak</name>
</author>
<author><name sortKey="Del Tredici, K" uniqKey="Del Tredici K">K Del Tredici</name>
</author>
<author><name sortKey="Bratzke, H" uniqKey="Bratzke H">H Bratzke</name>
</author>
<author><name sortKey="Hamm Clement, J" uniqKey="Hamm Clement J">J Hamm-Clement</name>
</author>
<author><name sortKey="Sandmann Keil, D" uniqKey="Sandmann Keil D">D Sandmann-Keil</name>
</author>
<author><name sortKey="Rub, U" uniqKey="Rub U">U Rub</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meredith, Ge" uniqKey="Meredith G">GE Meredith</name>
</author>
<author><name sortKey="Halliday, Gm" uniqKey="Halliday G">GM Halliday</name>
</author>
<author><name sortKey="Totterdell, S" uniqKey="Totterdell S">S Totterdell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Langston, Jw" uniqKey="Langston J">JW Langston</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lammel, S" uniqKey="Lammel S">S Lammel</name>
</author>
<author><name sortKey="Hetzel, A" uniqKey="Hetzel A">A Hetzel</name>
</author>
<author><name sortKey="Hackel, O" uniqKey="Hackel O">O Hackel</name>
</author>
<author><name sortKey="Jones, I" uniqKey="Jones I">I Jones</name>
</author>
<author><name sortKey="Liss, B" uniqKey="Liss B">B Liss</name>
</author>
<author><name sortKey="Roeper, J" uniqKey="Roeper J">J Roeper</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sherer, Tb" uniqKey="Sherer T">TB Sherer</name>
</author>
<author><name sortKey="Kim, Jh" uniqKey="Kim J">JH Kim</name>
</author>
<author><name sortKey="Betarbet, R" uniqKey="Betarbet R">R Betarbet</name>
</author>
<author><name sortKey="Greenamyre, Jt" uniqKey="Greenamyre J">JT Greenamyre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Drolet, Re" uniqKey="Drolet R">RE Drolet</name>
</author>
<author><name sortKey="Cannon, Jr" uniqKey="Cannon J">JR Cannon</name>
</author>
<author><name sortKey="Montero, L" uniqKey="Montero L">L Montero</name>
</author>
<author><name sortKey="Greenamyre, Jt" uniqKey="Greenamyre J">JT Greenamyre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Betarbet, R" uniqKey="Betarbet R">R Betarbet</name>
</author>
<author><name sortKey="Sherer, Tb" uniqKey="Sherer T">TB Sherer</name>
</author>
<author><name sortKey="Mackenzie, G" uniqKey="Mackenzie G">G MacKenzie</name>
</author>
<author><name sortKey="Garcia Osuna, M" uniqKey="Garcia Osuna M">M Garcia-Osuna</name>
</author>
<author><name sortKey="Panov, Av" uniqKey="Panov A">AV Panov</name>
</author>
<author><name sortKey="Greenamyre, Jt" uniqKey="Greenamyre J">JT Greenamyre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moss, J" uniqKey="Moss J">J Moss</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moss, J" uniqKey="Moss J">J Moss</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matsuda, W" uniqKey="Matsuda W">W Matsuda</name>
</author>
<author><name sortKey="Furuta, T" uniqKey="Furuta T">T Furuta</name>
</author>
<author><name sortKey="Nakamura, Kc" uniqKey="Nakamura K">KC Nakamura</name>
</author>
<author><name sortKey="Hioki, H" uniqKey="Hioki H">H Hioki</name>
</author>
<author><name sortKey="Fujiyama, F" uniqKey="Fujiyama F">F Fujiyama</name>
</author>
<author><name sortKey="Arai, R" uniqKey="Arai R">R Arai</name>
</author>
<author><name sortKey="Kaneko, T" uniqKey="Kaneko T">T Kaneko</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anden, Ne" uniqKey="Anden N">NE Andén</name>
</author>
<author><name sortKey="Fuxe, K" uniqKey="Fuxe K">K Fuxe</name>
</author>
<author><name sortKey="Hamberger, B" uniqKey="Hamberger B">B Hamberger</name>
</author>
<author><name sortKey="Hokfelt, T" uniqKey="Hokfelt T">T Hökfelt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bjorklund, A" uniqKey="Bjorklund A">A Björklund</name>
</author>
<author><name sortKey="Lindvall, O" uniqKey="Lindvall O">O Lindvall</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wickens, J" uniqKey="Wickens J">J Wickens</name>
</author>
<author><name sortKey="Arbuthnott, Gw" uniqKey="Arbuthnott G">GW Arbuthnott</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nair Roberts, Rg" uniqKey="Nair Roberts R">RG Nair-Roberts</name>
</author>
<author><name sortKey="Chatelain Badie, Sd" uniqKey="Chatelain Badie S">SD Chatelain-Badie</name>
</author>
<author><name sortKey="Benson, E" uniqKey="Benson E">E Benson</name>
</author>
<author><name sortKey="White Cooper, H" uniqKey="White Cooper H">H White-Cooper</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</name>
</author>
<author><name sortKey="Ungless, Ma" uniqKey="Ungless M">MA Ungless</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Oorschot, De" uniqKey="Oorschot D">DE Oorschot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bevan, Md" uniqKey="Bevan M">MD Bevan</name>
</author>
<author><name sortKey="Booth, Pac" uniqKey="Booth P">PAC Booth</name>
</author>
<author><name sortKey="Eaton, Sa" uniqKey="Eaton S">SA Eaton</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kawaguchi, Y" uniqKey="Kawaguchi Y">Y Kawaguchi</name>
</author>
<author><name sortKey="Wilson, Cj" uniqKey="Wilson C">CJ Wilson</name>
</author>
<author><name sortKey="Emson, Pc" uniqKey="Emson P">PC Emson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kita, H" uniqKey="Kita H">H Kita</name>
</author>
<author><name sortKey="Kitai, St" uniqKey="Kitai S">ST Kitai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tepper, Jm" uniqKey="Tepper J">JM Tepper</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name>
</author>
<author><name sortKey="Richard, S" uniqKey="Richard S">S Richard</name>
</author>
<author><name sortKey="Parent, A" uniqKey="Parent A">A Parent</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Furuta, T" uniqKey="Furuta T">T Furuta</name>
</author>
<author><name sortKey="Tomioka, R" uniqKey="Tomioka R">R Tomioka</name>
</author>
<author><name sortKey="Taki, K" uniqKey="Taki K">K Taki</name>
</author>
<author><name sortKey="Nakamura, K" uniqKey="Nakamura K">K Nakamura</name>
</author>
<author><name sortKey="Tamamaki, N" uniqKey="Tamamaki N">N Tamamaki</name>
</author>
<author><name sortKey="Kaneko, T" uniqKey="Kaneko T">T Kaneko</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fujiyama, F" uniqKey="Fujiyama F">F Fujiyama</name>
</author>
<author><name sortKey="Sohn, J" uniqKey="Sohn J">J Sohn</name>
</author>
<author><name sortKey="Nakano, T" uniqKey="Nakano T">T Nakano</name>
</author>
<author><name sortKey="Furuta, T" uniqKey="Furuta T">T Furuta</name>
</author>
<author><name sortKey="Nakamura, Kc" uniqKey="Nakamura K">KC Nakamura</name>
</author>
<author><name sortKey="Matsuda, W" uniqKey="Matsuda W">W Matsuda</name>
</author>
<author><name sortKey="Kaneko, T" uniqKey="Kaneko T">T Kaneko</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ohno, S" uniqKey="Ohno S">S Ohno</name>
</author>
<author><name sortKey="Kuramoto, E" uniqKey="Kuramoto E">E Kuramoto</name>
</author>
<author><name sortKey="Furuta, T" uniqKey="Furuta T">T Furuta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Prensa, L" uniqKey="Prensa L">L Prensa</name>
</author>
<author><name sortKey="Parent, A" uniqKey="Parent A">A Parent</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Attwell, D" uniqKey="Attwell D">D Attwell</name>
</author>
<author><name sortKey="Laughlin, Sb" uniqKey="Laughlin S">SB Laughlin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Damier, P" uniqKey="Damier P">P Damier</name>
</author>
<author><name sortKey="Hirsch, Ec" uniqKey="Hirsch E">EC Hirsch</name>
</author>
<author><name sortKey="Agid, Y" uniqKey="Agid Y">Y Agid</name>
</author>
<author><name sortKey="Graybiel, Am" uniqKey="Graybiel A">AM Graybiel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Khaliq, Zm" uniqKey="Khaliq Z">ZM Khaliq</name>
</author>
<author><name sortKey="Bean, Bp" uniqKey="Bean B">BP Bean</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yin, D" uniqKey="Yin D">D Yin</name>
</author>
<author><name sortKey="Valles, Fe" uniqKey="Valles F">FE Valles</name>
</author>
<author><name sortKey="Fiandaca, Ms" uniqKey="Fiandaca M">MS Fiandaca</name>
</author>
<author><name sortKey="Forsayeth, J" uniqKey="Forsayeth J">J Forsayeth</name>
</author>
<author><name sortKey="Larson, P" uniqKey="Larson P">P Larson</name>
</author>
<author><name sortKey="Starr, P" uniqKey="Starr P">P Starr</name>
</author>
<author><name sortKey="Bankiewicz, Ks" uniqKey="Bankiewicz K">KS Bankiewicz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hardman, Cd" uniqKey="Hardman C">CD Hardman</name>
</author>
<author><name sortKey="Henderson, Jm" uniqKey="Henderson J">JM Henderson</name>
</author>
<author><name sortKey="Finkelstein, Di" uniqKey="Finkelstein D">DI Finkelstein</name>
</author>
<author><name sortKey="Horne, Mk" uniqKey="Horne M">MK Horne</name>
</author>
<author><name sortKey="Paxinos, G" uniqKey="Paxinos G">G Paxinos</name>
</author>
<author><name sortKey="Halliday, Gm" uniqKey="Halliday G">GM Halliday</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Berger, B" uniqKey="Berger B">B Berger</name>
</author>
<author><name sortKey="Gaspar, P" uniqKey="Gaspar P">P Gaspar</name>
</author>
<author><name sortKey="Verney, C" uniqKey="Verney C">C Verney</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Garcia Cabezas, Ma" uniqKey="Garcia Cabezas M">MA Garcia-Cabezas</name>
</author>
<author><name sortKey="Martinez Sanchez, P" uniqKey="Martinez Sanchez P">P Martinez-Sanchez</name>
</author>
<author><name sortKey="Sanchez Gonzalez, Ma" uniqKey="Sanchez Gonzalez M">MA Sanchez-Gonzalez</name>
</author>
<author><name sortKey="Garzon, M" uniqKey="Garzon M">M Garzon</name>
</author>
<author><name sortKey="Cavada, C" uniqKey="Cavada C">C Cavada</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pissadaki, Ek" uniqKey="Pissadaki E">EK Pissadaki</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Elstner, M" uniqKey="Elstner M">M Elstner</name>
</author>
<author><name sortKey="Morris, Cm" uniqKey="Morris C">CM Morris</name>
</author>
<author><name sortKey="Heim, K" uniqKey="Heim K">K Heim</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wellstead, P" uniqKey="Wellstead P">P Wellstead</name>
</author>
<author><name sortKey="Cloutier, M" uniqKey="Cloutier M">M Cloutier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kim Han, Js" uniqKey="Kim Han J">JS Kim-Han</name>
</author>
<author><name sortKey="Antenor Dorsey, Ja" uniqKey="Antenor Dorsey J">JA Antenor-Dorsey</name>
</author>
<author><name sortKey="O Alley, Kl" uniqKey="O Alley K">KL O’Malley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burke, Re" uniqKey="Burke R">RE Burke</name>
</author>
<author><name sortKey="O Alley, K" uniqKey="O Alley K">K O’Malley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patel, Nk" uniqKey="Patel N">NK Patel</name>
</author>
<author><name sortKey="Gill, Ss" uniqKey="Gill S">SS Gill</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rosenblad, C" uniqKey="Rosenblad C">C Rosenblad</name>
</author>
<author><name sortKey="Kirik, D" uniqKey="Kirik D">D Kirik</name>
</author>
<author><name sortKey="Bjorklund, A" uniqKey="Bjorklund A">A Björklund</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rosenblad, C" uniqKey="Rosenblad C">C Rosenblad</name>
</author>
<author><name sortKey="Kirik, D" uniqKey="Kirik D">D Kirik</name>
</author>
<author><name sortKey="Devaux, B" uniqKey="Devaux B">B Devaux</name>
</author>
<author><name sortKey="Moffat, B" uniqKey="Moffat B">B Moffat</name>
</author>
<author><name sortKey="Phillips, Hs" uniqKey="Phillips H">HS Phillips</name>
</author>
<author><name sortKey="Bjorklund, A" uniqKey="Bjorklund A">A Björklund</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Welberg, L" uniqKey="Welberg L">L Welberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kincaid, Ae" uniqKey="Kincaid A">AE Kincaid</name>
</author>
<author><name sortKey="Zheng, T" uniqKey="Zheng T">T Zheng</name>
</author>
<author><name sortKey="Wilson, Cj" uniqKey="Wilson C">CJ Wilson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lacey, Cj" uniqKey="Lacey C">CJ Lacey</name>
</author>
<author><name sortKey="Boyes, J" uniqKey="Boyes J">J Boyes</name>
</author>
<author><name sortKey="Gerlach, O" uniqKey="Gerlach O">O Gerlach</name>
</author>
<author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name>
</author>
<author><name sortKey="Magill, Pj" uniqKey="Magill P">PJ Magill</name>
</author>
<author><name sortKey="Bolam, Jp" uniqKey="Bolam J">JP Bolam</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">Mov Disord</journal-id>
<journal-id journal-id-type="iso-abbrev">Mov. Disord</journal-id>
<journal-id journal-id-type="publisher-id">mds</journal-id>
<journal-title-group><journal-title>Movement Disorders</journal-title>
</journal-title-group>
<issn pub-type="ppub">0885-3185</issn>
<issn pub-type="epub">1531-8257</issn>
<publisher><publisher-name>Wiley Subscription Services, Inc., A Wiley Company</publisher-name>
<publisher-loc>Hoboken</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23008164</article-id>
<article-id pub-id-type="pmc">3504389</article-id>
<article-id pub-id-type="doi">10.1002/mds.25135</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Viewpoints</subject>
</subj-group>
</article-categories>
<title-group><article-title>Living on the edge with too many mouths to feed: Why dopamine neurons die</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bolam</surname>
<given-names>J Paul</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pissadaki</surname>
<given-names>Eleftheria K</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<aff id="au1"><label>1</label>
<institution>Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson’s Disease Centre,</institution>
<addr-line>University of Oxford, Oxford, UK</addr-line>
</aff>
<aff id="au2"><label>2</label>
<institution>Department of Basic Sciences, Faculty of Medicine,</institution>
<addr-line>University of Crete, Heraklion, Greece</addr-line>
</aff>
</contrib-group>
<author-notes><corresp id="cor1">*Dr. J. Paul Bolam, MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3TH, United Kingdom; <email>paul.bolam@pharm.ox.ac.uk</email>
</corresp>
<fn><p><bold>Funding agencies</bold>
: The authors’ own work described in this article was supported by the Medical Research Council, UK (grant no.: U138164490), Parkinson’s UK (grant nos.: G-0601 and K-1103), and the European Community (FP7: HEALTH-F2-2008-201716).</p>
</fn>
<fn><p><bold>Relevant conflicts of interest/financial disclosures</bold>
: Nothing to report.</p>
</fn>
<fn><p>Full financial disclosures and author roles may be found in the online version of this article.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>9</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><month>10</month>
<year>2012</year>
</pub-date>
<volume>27</volume>
<issue>12</issue>
<fpage>1478</fpage>
<lpage>1483</lpage>
<history><date date-type="received"><day>24</day>
<month>4</month>
<year>2012</year>
</date>
<date date-type="rev-recd"><day>2</day>
<month>7</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>17</day>
<month>7</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012 Movement Disorder Society</copyright-statement>
<copyright-year>2012</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.5/"><license-p>Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.</license-p>
</license>
</permissions>
<abstract><p>Although genes, protein aggregates, environmental toxins, and other factors associated with Parkinson’s disease (PD) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of PD is the exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What is it about these neurons, among all other neurons in the brain, that makes them so susceptible in PD? We hypothesize that a major contributory factor is the unique cellular architecture of SNc DA neuron axons. Their large, complex axonal arbour puts them under such a tight energy budget that it makes them particularly susceptible to factors that contribute to cell death, including unique molecular characteristics associated with SNc DA neurons and nonspecific, nervous-system–wide factors. © 2012 Movement Disorder Society</p>
</abstract>
<kwd-group><kwd>Parkinson’s</kwd>
<kwd>dopamine neurons</kwd>
<kwd>energy</kwd>
<kwd>neurodegeneration</kwd>
</kwd-group>
</article-meta>
</front>
<body><p>The causes of Parkinson’s disease (PD) are varied and complex and include a variety of genetic and environmental factors, but the majority of cases are idiopathic. Selective degeneration of dopamine (DA) neurons of the SNc is responsible for the principal motor symptoms of PD. Factors that contribute to their cell death are many and varied and include protein mishandling, oxidative stress, inflammation, calcium dynamics, toxicity of DA metabolites, and, frequently, mitochondrial dysfunction.1–12 The loss of neurons in PD is, however, not confined to the substantia nigra. It has long been known that cell death occurs at many levels of the nervous system; for instance, there is a marked loss of cholinergic neurons in the pedunculopontine nucleus<xref ref-type="bibr" rid="b13">13</xref>
 and noradrenergic neurons in the locus coeruleus.<xref ref-type="bibr" rid="b14">14</xref>
 Indeed, cell death is associated with neurons that possess long axons that are unmyelinated in their region of aborization at least.<xref ref-type="bibr" rid="b15">15</xref>
, <xref ref-type="bibr" rid="b16">16</xref>
 Furthermore, it has recently been proposed that PD is a dynamic, widespread disease. Lewy body pathology and cell death is first identified in the brain stem (or possibly even the enteric nervous system) and there is a slow progression to the forebrain; when the wave of pathology reaches the midbrain DA neurons, then the cardinal motor symptoms of PD are expressed.<xref ref-type="bibr" rid="b15">15</xref>
, <xref ref-type="bibr" rid="b16">16</xref>
</p>
<p>Factors considered to contribute to cell death in PD (see above) are also found widely distributed in the nervous system,1–3 but the consistent feature of both idiopathic and genetic forms of PD is the selective, and exceptional, vulnerability of DA neurons of the SNc.<xref ref-type="bibr" rid="b3">3</xref>
 This is one of the most critical issues in the field of PD research: Why is it that DA neurons of the SNc, above all other neurons in the brain, and indeed above other classes of DA neuron, show such selective vulnerability in PD and in models of PD? The explanation is relatively straightforward when one considers toxins such as 6-hydroxydopamine and MPTP and its active metabolite, 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>
), both of which are used to create animal models of PD.<xref ref-type="bibr" rid="b17">17</xref>
 Their selectivity for DA neurons is because their access to the intracellular compartment is dependent on the DA transporter, which is only expressed by DA neurons and, interestingly, at lower levels in DA neurons of the ventral tegmental area (VTA), which are less susceptible to toxins and PD.<xref ref-type="bibr" rid="b19">19</xref>
 However, the explanation is more complex when one considers general mitochondrial poisons, such as rotenone (mitochondrial complex I inhibitor), which, when used at appropriate doses, leads to selective, dramatic loss of DA neurons in the SNc.20–22 Similarly, when one considers genetic variants of PD, it is usually the case that the mutated proteins are expressed widely in the brain (e.g., LRRK2<xref ref-type="bibr" rid="b1">1</xref>
, <xref ref-type="bibr" rid="b2">2</xref>
, <xref ref-type="bibr" rid="b4">4</xref>
, <xref ref-type="bibr" rid="b5">5</xref>
 and do not show selectivity for DA neurons). Furthermore, in idiopathic PD (iPD), mitochondrial dysfunction that has been identified postmortem in the substantia nigra is not confined to this area, but is evident in many brain regions and in other tissues, including skeletal muscle and platelets.<xref ref-type="bibr" rid="b2">2</xref>
 Why, in these situations, is it that DA neurons of the SNc show such selective vulnerability?</p>
<p>In this article, we will not address the molecular characteristics of SNc DA neurons that have been proposed to contribute to their selective vulnerability (see reviews above), but we suggest that a major contributory factor that underlies their selective vulnerability is their uniquely massive, unmyelinated axonal arbor. Axons of DA neurons of the SNc give rise to a massive number of synapses and a massive axonal field.23–25 The extreme bioenergetic demands of maintaining these unique morphological features and of maintaining neuronal signaling puts SNc DA neurons energetically “on the edge”—they are at a marked disadvantage in that they simply have “too many mouths to feed,” thus making them especially vulnerable to stressors of any sort, including environmental and genetic factors, whose effects are widely distributed in the body, and factors that are specific to DA neurons.</p>
<sec><title>Axonal Arbor of DA Neurons</title>
<p>It is well recognized that DA neurons provide a massive, and importantly unmyelinated, innervation of the forebrain, a fact that was evident even in the earliest histofluorescence studies of DA neurons<xref ref-type="bibr" rid="b26">26</xref>
 and, by analysis of sections of the forebrain (of any mammalian species) stained to reveal markers of DA neurons (e.g., tyrosine hydroxylase; see, for instance, Björklund and Lindvall<xref ref-type="bibr" rid="b27">27</xref>
), the synthetic enzyme of catecholamines. Quantitative analyses of the numbers of DA neurons in the midbrain and their innervation of the forebrain in rats have revealed the true nature of this innervation<xref ref-type="bibr" rid="b23">23</xref>
, <xref ref-type="bibr" rid="b27">27</xref>
, <xref ref-type="bibr" rid="b28">28</xref>
 (<xref ref-type="table" rid="tbl1">Table 1</xref>
). Rat SNc contains approximately 12,000 DA neurons,<xref ref-type="bibr" rid="b29">29</xref>
, <xref ref-type="bibr" rid="b30">30</xref>
 which provide the dense innervation of the striatum. Because we know the number of neurons in the striatum and SNc in rats, as well as quantitative details about the precise synaptic relationship between dopaminergic axons and the principal neuron of the striatum, the medium spiny neuron (MSN),<xref ref-type="bibr" rid="b23">23</xref>
 we can estimate that, in rats, the axon of a single SNc DA neuron gives rise to between 102,165 and 245,103 synapses (<xref ref-type="table" rid="tbl1">Table 1</xref>
) at the level of the striatum. Our estimate is in the same order of magnitude as other studies in rats; estimates of the number of axonal varicosities (putative synapses) of a single DA neuron by Andén et al.<xref ref-type="bibr" rid="b26">26</xref>
 (250,000 varicosities per neuron; recalculated by Björklund and Lindvall<xref ref-type="bibr" rid="b2">27</xref>
) and the estimate of the number of synapses by Wickens and Arbuthnott (369,881 synapses per neuron<xref ref-type="bibr" rid="b28">28</xref>
) that was based on the density of synapses in the striatum.</p>
<table-wrap id="tbl1" position="float"><label>Table 1</label>
<caption><p>Estimation of the number of synapses formed by a single DA neuron with MSNs in the rat striatum</p>
</caption>
<table frame="hsides" rules="groups"><tbody><tr><td align="left" rowspan="1" colspan="1">1. Average number of dendritic spines on one MSN</td>
<td align="left" rowspan="1" colspan="1">6,250 to 15,000<xref ref-type="bibr" rid="b56">56</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">2. Percentage of axospinous synapses that involve cortical and thalamic terminals</td>
<td align="left" rowspan="1" colspan="1">64.8%<xref ref-type="bibr" rid="b57">57</xref>
<xref ref-type="table-fn" rid="tf1-1">a</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">3. Average number of dendritic spines postsynaptic to cortical or thalamic terminals on one MSN (value 1) × (value 2)</td>
<td align="left" rowspan="1" colspan="1">4,050 to 9,720</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">4. Proportion of these dendritic spines in synaptic contact with a DA terminal</td>
<td align="left" rowspan="1" colspan="1">0.06666<xref ref-type="bibr" rid="b23">23</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">5. Number of these dendritic spines on one MSN in synaptic contact with a dopamine terminal (value 3) × (value 4)</td>
<td align="left" rowspan="1" colspan="1">270 to 648</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">6. Percentage of DA terminals that contact dendritic spines (not shafts or cell bodies)</td>
<td align="left" rowspan="1" colspan="1">61.3%<xref ref-type="bibr" rid="b23">23</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">7. Multiplying factor to incorporate synapses with dendritic shafts and cell bodies; reciprocal of 0.613 (value 6)</td>
<td align="left" rowspan="1" colspan="1">1.632</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">8. Number of DA terminals forming synapses with one MSN (value 5) × (value 7)</td>
<td align="left" rowspan="1" colspan="1">441 to 1,058</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">9. Number of MSNs in the striatum (one hemisphere)</td>
<td align="left" rowspan="1" colspan="1">2,780,000<xref ref-type="bibr" rid="b30">30</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">10. Number of DA terminals forming synapses with all MSNs in one hemisphere (value 8) × (value 9)</td>
<td align="left" rowspan="1" colspan="1">1,225,980,000 to 2,941,240,000</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">11. Number of DA neurons in the SNc (one hemisphere) of rat</td>
<td align="left" rowspan="1" colspan="1">12,000<xref ref-type="bibr" rid="b29">29</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">12. Number of synapses formed by one DA neuron in the rat striatum (value 10)/(value 11)</td>
<td align="left" rowspan="1" colspan="1">102,165 to 245,103</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tf1-1"><p>Note that to arrive at the number of dopaminergic synapses in contact with an individual MSN, quantitative data from spines that are postsynaptic to cortical or thalamic terminals was used.<xref ref-type="bibr" rid="b23">23</xref>
 This will introduce error (i.e., an underestimate of the number of synapses) because dopaminergic terminals may contact other spines. Table is modified from Moss and Bolam.<xref ref-type="bibr" rid="b24">24</xref>
</p>
</fn>
<fn><p><sup>a</sup>
This figure represents the percentage of axospinous synapses involving VGluT1-positive (cortical) and VGluT2-positive (thalamic) terminals. It is likely to be an underestimate as a result of false-negative labeling of terminals.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>The figure of hundreds of thousands of synapses can be put into perspective when one considers the axons of other types of neurons in the basal ganglia of the rat. Based on the analysis of single cells and counts of axonal varicosities, the principal type of neuron in the globus pallidus (external) gives rise to approximately 2,000 synapses, an MSN gives rise to 300–500 synapses, and a fast-spiking GABA interneuron in the striatum gives rise to approximately 5,000 synapses.31–35 Thus, SNc DA neurons possess at least two orders of magnitude more synapses than other neurons in the basal ganglia.</p>
<p>Estimates of such a large number of synapses of SNc dopaminergic neurons are consistent with the findings of Matsuda et al.<xref ref-type="bibr" rid="b25">25</xref>
 These investigators used a viral vector based upon a Sindbis virus designed to express green fluorescent protein that labels infected neurons in a Golgi-like manner,36–38 an approach that is necessary to get good labeling of dopaminergic axons. They demonstrated that the axons of single DA neurons of the SNc labeled <italic>in vivo</italic>
 in the rat occupy up to approximately 6% of the volume of the striatum, with a total length of all the axonal branches of up to 78 cm (average total length = 46.6 cm) that branches frequently (mean interbranch interval of ∼31 μm) and gives rise to a highly tortuous axonal arbor. Note that this figure is remarkably close to the estimate of 30 cm, based on the analysis of histofluorescently labeled axons in the striatum (Andén el al.<xref ref-type="bibr" rid="b26">26</xref>
; recalculated by Björklund and Lindvall<xref ref-type="bibr" rid="b27">27</xref>
). It should be noted that the observations of Matsusda et al.<xref ref-type="bibr" rid="b25">25</xref>
 reveal much larger axonal arbors than reported on by Prensa and Parent,<xref ref-type="bibr" rid="b39">39</xref>
 who used extracellular deposits of biotinylated dextran amine (BDA) to label axons. Although this study provided critical qualitative information about the collateralization of the axons of DA neurons, the sizes of the axonal fields were not quantified. Calculations, based on representations of the BDA-labeled axons and estimates of the number of synapses/varicosities formed by the axon of an individual SNc dopaminergic neuron, suggest that the use of nonreplicating markers leads to underestimates of the size of axonal arbors (see Supporting Materials).</p>
<p>What are the likely consequences of such an extensive unmyelinated axonal field and large number of synapses? One can predict that such a large neuronal architecture would put the neuron under a phenomenal energy demand not just to maintain healthy cell biological functions (e.g., protein synthesis, cytoskeleton maintenance, axonal transport, and so forth), but also in the maintenance of the membrane potential, the propagation of action potentials, and in synaptic transmission. These neuron-specific aspects of cell function are energetically expensive, particularly if the axon is not myelinated,<xref ref-type="bibr" rid="b40">40</xref>
 as is the case for DA neurons. We propose that the tight energy budget that this unique axonal architecture imposes on SNc DA neurons is a critical factor in their susceptibility in PD and animal models of PD. They are under a bioenergetic demand that is so extreme that they are energetically on the edge. Under normal circumstances, there is no effect of this high energy demand on the neurons. However, any situation that perturbs the balance between energy production and demand—such as mitochondrial dysfunction or oxidative stress—would “tip them over the edge,” such that energy demand exceeds supply. A negative energy balance would lead to many detrimental consequences within a neuron, including further oxidative stress, further mitochondrial dysfunction, inability to deal with protein turnover, impaired autophagy, and so on, all factors considered to contribute to cell death in PD (for references, see above). A negative energy balance would thus lead to functional failure and, eventually, cell death.</p>
<p>Any theory that accounts for the loss of SNc DA neurons in PD must include an explanation as to why DA neurons of the VTA, or indeed calbindin-positive SNc DA neurons, are relatively spared in PD or models of PD.<xref ref-type="bibr" rid="b13">13</xref>
, <xref ref-type="bibr" rid="b41">41</xref>
 It is clear that they have different molecular and physiological characteristics that contribute to the differential susceptibility<xref ref-type="bibr" rid="b3">3</xref>
, <xref ref-type="bibr" rid="b19">19</xref>
, <xref ref-type="bibr" rid="b42">42</xref>
; however, they also have strikingly different morphological characteristics. In contrast to DA neurons of the SNc, DA neurons of the VTA are likely to give rise to far fewer synapses. We estimate that a DA neuron in the VTA of rats gives rise to 12,000 to 30,000 synapses.<xref ref-type="bibr" rid="b24">24</xref>
 This figure is based on the fact that approximately twice as many DA neurons in the VTA<xref ref-type="bibr" rid="b29">29</xref>
 innervate the ventral striatum, which has a volume of approximately one fifth of that of the dorsal striatum (<xref ref-type="table" rid="tbl2">Table 2</xref>
). This estimate assumes that the pattern and density of innervation of the ventral striatum (nucleus accumbens) by VTA neurons is similar to the pattern and density of innervation of the dorsal striatum by SNc DA neurons. Thus, those DA neurons that are less susceptible in PD in humans and in animal models of PD have an order of magnitude fewer synapses and much smaller axonal arbors and thus a bioenergetic demand to maintain their structural and functional properties that is far less than that of SNc DA neurons. We do not have an estimate of the number of synapses formed by calbindin-positive DA neurons in the SNc that also innervate the striatum, but our hypothesis predicts that they give rise to a far smaller number of synapses.</p>
<table-wrap id="tbl2" position="float"><label>Table 2</label>
<caption><p>Estimation of the number of synapses formed by a single VTA DA neuron in the ventral striatum of the rat</p>
</caption>
<table frame="hsides" rules="groups"><tbody><tr><td align="left" rowspan="1" colspan="1">Number of DA neurons in the SNc (one hemisphere)</td>
<td align="left" rowspan="1" colspan="1">12,000<xref ref-type="bibr" rid="b29">29</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Volume of striatum (mm<sup>3</sup>
)</td>
<td align="left" rowspan="1" colspan="1">19.9<xref ref-type="bibr" rid="b30">30</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Volume of (dorsal) striatum per SNc DA neuron (mm<sup>3</sup>
)</td>
<td align="left" rowspan="1" colspan="1">0.001658 (19.9/12,000)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Number of DA neurons in the VTA (one hemisphere)</td>
<td align="left" rowspan="1" colspan="1">20,000<xref ref-type="bibr" rid="b29">29</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Volume of ventral striatum (mm<sup>3</sup>
) (approximately one fifth of size of striatum)</td>
<td align="left" rowspan="1" colspan="1">∼ 4 (19.9/5)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Volume of ventral striatum per VTA DA neuron (mm<sup>3</sup>
)</td>
<td align="left" rowspan="1" colspan="1">0.0002 (4/20,000)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Ratio of ventral versus dorsal striatum volume per DA neuron</td>
<td align="left" rowspan="1" colspan="1">0.121 (0.0002/0.001658)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Number of synapses formed by one DA neuron in the ventral striatum</td>
<td align="left" rowspan="1" colspan="1">12,351 to 29,644 (0.121 × 102,165<xref ref-type="table-fn" rid="tf2-1">a</xref>
) to (0.121 × 245,103<xref ref-type="table-fn" rid="tf2-1">a</xref>
)</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tf2-1"><p><sup>a</sup>
Estimated number of synapses formed by one SNc DA neuron in the striatum in the rat (see <xref ref-type="table" rid="tbl1">Table 1</xref>
).</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec><title>Characteristics of Axons of Human DA Neurons</title>
<p>All of the detailed quantitative analyses of the axons of DA neurons have been carried out in rats; however, rats do not spontaneously develop PD, whereas humans do. There are a number of explanations for this. One of the strongest risk factors for PD is age. However, comparative anatomy and quantitative analyses reveal that the bioenergetic demand on SNc DA neurons in humans is likely to be much greater than in rats (<xref ref-type="table" rid="tbl3">Table 3</xref>
). The volume of the striatum has increased by approximately 300-fold from rats (19.9 mm<sup>3</sup>
) to humans (6,280 mm<sup>3</sup>
),<xref ref-type="bibr" rid="b30">30</xref>
, <xref ref-type="bibr" rid="b43">43</xref>
 but the number of DA neurons in the SNc has increased by only 32-fold (rats, 12,000; humans, 382,000).<xref ref-type="bibr" rid="b29">29</xref>
, <xref ref-type="bibr" rid="b44">44</xref>
 If we assume that the density and pattern of innervation of the striatum by DA neurons in humans is similar to that in rats, then an individual SNc DA neuron in humans should give rise to 10 times the number of synapses in rats—that is, a single SNc DA neuron in humans is estimated to give rise to between 1 and 2.4 million synapses at the level of the striatum (<xref ref-type="table" rid="tbl3">Table 3</xref>
). Furthermore, if the branching patterns of DA neuron axons are similar in rats and humans, then we can estimate that the average total length of the axon of an individual SNc DA neuron is in the region of 4.5 meters with—assuming a similar interbranch interval to that in rats—an arborization of incredible complexity. Thus, the bioenergetic demand to maintain the structure and functionality of SNc DA neurons in humans is likely to be an order of magnitude greater than that required for rat SNc DA neurons. This, together with longevity, may account for why humans, and not rats, get PD.</p>
<table-wrap id="tbl3" position="float"><label>Table 3</label>
<caption><p>Estimation of the number of synapses formed by a single DA neuron in the striatum in humans</p>
</caption>
<table frame="hsides" rules="groups"><tbody><tr><td align="left" rowspan="1" colspan="1">Number of DA in the SNc (one hemisphere)</td>
<td align="left" rowspan="1" colspan="1">382,000<xref ref-type="bibr" rid="b44">44</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Volume of striatum (mm<sup>3</sup>
)</td>
<td align="left" rowspan="1" colspan="1">6,280<xref ref-type="bibr" rid="b43">43</xref>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Volume of striatum per SNc DA neuron (mm<sup>3</sup>
)</td>
<td align="left" rowspan="1" colspan="1">0.01644 (6,280/382,000)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Ratio human versus rat of striatum volume per DA neuron</td>
<td align="left" rowspan="1" colspan="1">9.916 (0.01644 /0.001658<xref ref-type="table-fn" rid="tf3-1">a</xref>
)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Number of synapses formed by one DA neuron in the human striatum</td>
<td align="left" rowspan="1" colspan="1">1,013,068 to 2,430,441 (9.916 × 102,165<xref ref-type="table-fn" rid="tf3-2">b</xref>
) to (9.916 × 245,103<xref ref-type="table-fn" rid="tf3-2">b</xref>
)</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tf3-1"><p><sup>a</sup>
Volume of striatum per SNc DA neuron in rat (see <xref ref-type="table" rid="tbl1">Table 1</xref>
).</p>
</fn>
<fn id="tf3-2"><p><sup>b</sup>
 Estimated number of synapses formed by one SNc DA neuron in the striatum in the rat (see <xref ref-type="table" rid="tbl1">Table 1</xref>
).</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>It should be noted that although the innervation of the striatum by DA axons far exceeds that in other regions of the brain, our estimates of numbers of synapses do not take into account the innervation of extrastriatal regions by SNc or VTA neurons nor the differences in the density of innervation of these regions across species.<xref ref-type="bibr" rid="b45">45</xref>
, <xref ref-type="bibr" rid="b46">46</xref>
 Although this is likely to lead to underestimates of the numbers of synapses, the orders of magnitude are likely to be similar.</p>
<p>We have begun to address the hypothesis by the creation of a biology-based computational model of the axons of DA neurons. Data derived from the model suggests that the energy cost of the propagation of action potentials and recovery of membrane potential grows as a power law with respect to the size and complexity of the axonal arbor.<xref ref-type="bibr" rid="b47">47</xref>
 Thus, DA neurons of the SNc not only have disproportionately large, complex axonal arbors, compared with other dopamine neurons and other neurons in the brain, but the very nature of the size and complexity means that the energy cost of signal propagation is disproportionately greater.</p>
</sec>
<sec><title>Implications for Treatment and Understanding of PD</title>
<p>What are the implications of this hypothesis for PD and its treatment? The idea put forward in this article suggests that DA neuron death in iPD, and probably other forms of PD, is ultimately a consequence of energy supply—iPD is not specific for DA neurons, it is just that SNc DA show the greatest susceptibility when energy metabolism is perturbed, whether the cause be a specific deficit in DA neurons or a nonspecific insult.<xref ref-type="bibr" rid="b48">48</xref>
 This is not a new idea in itself, because it is well recognized that mitochondrial dysfunction is associated with idiopathic and other forms of PD.<xref ref-type="bibr" rid="b2">2</xref>
 Indeed, it has recently been proposed by Wellstead and Cloutier, on the basis of a systems biology approach, that PD is a disease of energy metabolism.<xref ref-type="bibr" rid="b49">49</xref>
 Furthermore, mitochondria in DA axons are smaller and transported more slowly than other neurons,<xref ref-type="bibr" rid="b50">50</xref>
 and consistent with the hypothesis, it has been proposed that axons preferentially degenerate in PD.<xref ref-type="bibr" rid="b51">51</xref>
 Our hypothesis, however, offers an explanation as to why it is that SNc DA neurons are particularly susceptible to impaired energy metabolism and/or supply.</p>
<p>One might suggest that a novel approach to the treatment of PD could be to enhance energy supply to DA neurons, whether this be by genetic or molecular means. The use of growth factors<xref ref-type="bibr" rid="b52">52</xref>
 at the level of the striatum, which promote the growth and “sprouting” of the axons of surviving DA neurons,<xref ref-type="bibr" rid="b53">53</xref>
, <xref ref-type="bibr" rid="b54">54</xref>
 may be counterproductive, in that it would increase the energy demand on individual neurons and hence their susceptibility. Because the sprouting of the axons of surviving DA neurons occurs once degeneration has begun, perhaps cell-based therapies, such as deposits of fetal DA neurons or, in the future, stem cells should be initiated early in the progression of the disease before such sprouting has occurred.</p>
<p>Whatever the implications for disease treatment, we suggest that the unique axonal architectural features and unmyelinated nature of the axons of DA neurons of the SNc, especially in humans, render these neurons particularly sensitive to DA-neuron–specific and –nonspecific stressors. This suggests that iPD is a nonspecific disease—it is simply the case that the very nature of the structure of SNc DA neurons means that these neurons fall into a negative energy balance, and ultimately die, as a consequence of longevity coinciding with DA-neuron–specific and/or –nonspecific stressors in the nervous system. Thus, the Achilles heel of SNc DA neurons<xref ref-type="bibr" rid="b55">55</xref>
 includes not only their unique molecular characteristics, but also their unique morphological features.</p>
</sec>
</body>
<back><ack><p>The authors thank Tim Greenamyre, Terri Hastings, Pablo Henny, Jon Moss, and Peter Mgill for their helpful discussions.</p>
</ack>
<ref-list><title>References</title>
<ref id="b1"><label>1</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martin</surname>
<given-names>I</given-names>
</name>
<name><surname>Dawson</surname>
<given-names>VL</given-names>
</name>
<name><surname>Dawson</surname>
<given-names>TM</given-names>
</name>
</person-group>
<article-title>The impact of genetic research on our understanding of Parkinson’s disease</article-title>
<source>Prog Brain Res</source>
<year>2010</year>
<volume>183</volume>
<fpage>21</fpage>
<lpage>41</lpage>
<pub-id pub-id-type="pmid">20696313</pub-id>
</element-citation>
</ref>
<ref id="b2"><label>2</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schapira</surname>
<given-names>AH</given-names>
</name>
</person-group>
<article-title>Mitochondria in the aetiology and pathogenesis of Parkinson’s disease</article-title>
<source>Lancet Neurol</source>
<year>2008</year>
<volume>7</volume>
<fpage>97</fpage>
<lpage>109</lpage>
<pub-id pub-id-type="pmid">18093566</pub-id>
</element-citation>
</ref>
<ref id="b3"><label>3</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sulzer</surname>
<given-names>D</given-names>
</name>
</person-group>
<article-title>Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease</article-title>
<source>Trends Neurosci</source>
<year>2007</year>
<volume>30</volume>
<fpage>244</fpage>
<lpage>250</lpage>
<pub-id pub-id-type="pmid">17418429</pub-id>
</element-citation>
</ref>
<ref id="b4"><label>4</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gasser</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Identifying PD-causing genes and genetic susceptibility factors: current approaches and future prospects</article-title>
<source>Prog Brain Res</source>
<year>2010</year>
<volume>183</volume>
<fpage>3</fpage>
<lpage>20</lpage>
<pub-id pub-id-type="pmid">20696312</pub-id>
</element-citation>
</ref>
<ref id="b5"><label>5</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Obeso</surname>
<given-names>JA</given-names>
</name>
<name><surname>Rodriguez-Oroz</surname>
<given-names>MC</given-names>
</name>
<name><surname>Goetz</surname>
<given-names>CG</given-names>
</name>
</person-group>
<article-title>Missing pieces in the Parkinson’s disease puzzle</article-title>
<source>Nat Med</source>
<year>2010</year>
<volume>16</volume>
<fpage>653</fpage>
<lpage>661</lpage>
<pub-id pub-id-type="pmid">20495568</pub-id>
</element-citation>
</ref>
<ref id="b6"><label>6</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Surmeier</surname>
<given-names>DJ</given-names>
</name>
<name><surname>Guzman</surname>
<given-names>JN</given-names>
</name>
<name><surname>Sanchez-Padilla</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Calcium, cellular aging, and selective neuronal vulnerability in Parkinson’s disease</article-title>
<source>Cell Calcium</source>
<year>2010</year>
<volume>47</volume>
<fpage>175</fpage>
<lpage>182</lpage>
<pub-id pub-id-type="pmid">20053445</pub-id>
</element-citation>
</ref>
<ref id="b7"><label>7</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guzman</surname>
<given-names>JN</given-names>
</name>
<name><surname>Sanchez-Padilla</surname>
<given-names>J</given-names>
</name>
<name><surname>Wokosin</surname>
<given-names>D</given-names>
</name>
<name><surname>Kondapalli</surname>
<given-names>J</given-names>
</name>
<name><surname>Ilijic</surname>
<given-names>E</given-names>
</name>
<name><surname>Schumacker</surname>
<given-names>PT</given-names>
</name>
<name><surname>Surmeier</surname>
<given-names>DJ</given-names>
</name>
</person-group>
<article-title>Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1</article-title>
<source>Nature</source>
<year>2010</year>
<volume>468</volume>
<fpage>696</fpage>
<lpage>700</lpage>
<pub-id pub-id-type="pmid">21068725</pub-id>
</element-citation>
</ref>
<ref id="b8"><label>8</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Surmeier</surname>
<given-names>DJ</given-names>
</name>
<name><surname>Guzman</surname>
<given-names>JN</given-names>
</name>
<name><surname>Sanchez-Padilla</surname>
<given-names>J</given-names>
</name>
<name><surname>Goldberg</surname>
<given-names>JA</given-names>
</name>
</person-group>
<article-title>What causes the death of dopaminergic neurons in Parkinson’s disease?</article-title>
<source>Prog Brain Res</source>
<year>2010</year>
<volume>183</volume>
<fpage>59</fpage>
<lpage>77</lpage>
<pub-id pub-id-type="pmid">20696315</pub-id>
</element-citation>
</ref>
<ref id="b9"><label>9</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chan</surname>
<given-names>CS</given-names>
</name>
<name><surname>Guzman</surname>
<given-names>JN</given-names>
</name>
<name><surname>Ilijic</surname>
<given-names>E</given-names>
</name>
</person-group>
<article-title>‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease</article-title>
<source>Nature</source>
<year>2007</year>
<volume>447</volume>
<fpage>1081</fpage>
<lpage>1086</lpage>
<pub-id pub-id-type="pmid">17558391</pub-id>
</element-citation>
</ref>
<ref id="b10"><label>10</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Laar</surname>
<given-names>VS</given-names>
</name>
<name><surname>Dukes</surname>
<given-names>AA</given-names>
</name>
<name><surname>Cascio</surname>
<given-names>M</given-names>
</name>
<name><surname>Hastings</surname>
<given-names>TG</given-names>
</name>
</person-group>
<article-title>Proteomic analysis of rat brain mitochondria following exposure to dopamine quinone: implications for Parkinson disease</article-title>
<source>Neurobiol Dis</source>
<year>2008</year>
<volume>29</volume>
<fpage>477</fpage>
<lpage>489</lpage>
<pub-id pub-id-type="pmid">18226537</pub-id>
</element-citation>
</ref>
<ref id="b11"><label>11</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Laar</surname>
<given-names>VS</given-names>
</name>
<name><surname>Mishizen</surname>
<given-names>AJ</given-names>
</name>
<name><surname>Cascio</surname>
<given-names>M</given-names>
</name>
<name><surname>Hastings</surname>
<given-names>TG</given-names>
</name>
</person-group>
<article-title>Proteomic identification of dopamine-conjugated proteins from isolated rat brain mitochondria and SH-SY5Y cells</article-title>
<source>Neurobiol Dis</source>
<year>2009</year>
<volume>34</volume>
<fpage>487</fpage>
<lpage>500</lpage>
<pub-id pub-id-type="pmid">19332121</pub-id>
</element-citation>
</ref>
<ref id="b12"><label>12</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berman SB Hastings</surname>
<given-names>TG</given-names>
</name>
</person-group>
<article-title>Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease</article-title>
<source>J Neurochem</source>
<year>1999</year>
<volume>73</volume>
<fpage>1127</fpage>
<lpage>1137</lpage>
<pub-id pub-id-type="pmid">10461904</pub-id>
</element-citation>
</ref>
<ref id="b13"><label>13</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hirsch</surname>
<given-names>E</given-names>
</name>
<name><surname>Graybiel</surname>
<given-names>AM</given-names>
</name>
<name><surname>Agid</surname>
<given-names>YA</given-names>
</name>
</person-group>
<article-title>Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease</article-title>
<source>Nature</source>
<year>1988</year>
<volume>334</volume>
<fpage>345</fpage>
<lpage>348</lpage>
<pub-id pub-id-type="pmid">2899295</pub-id>
</element-citation>
</ref>
<ref id="b14"><label>14</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gesi</surname>
<given-names>M</given-names>
</name>
<name><surname>Soldani</surname>
<given-names>P</given-names>
</name>
<name><surname>Giorgi</surname>
<given-names>FS</given-names>
</name>
<name><surname>Santinami</surname>
<given-names>A</given-names>
</name>
<name><surname>Bonaccorsi</surname>
<given-names>I</given-names>
</name>
<name><surname>Fornai</surname>
<given-names>F</given-names>
</name>
</person-group>
<article-title>The role of the locus coeruleus in the development of Parkinson’s disease</article-title>
<source>Neurosci Biobehav Rev</source>
<year>2000</year>
<volume>24</volume>
<fpage>655</fpage>
<lpage>668</lpage>
<pub-id pub-id-type="pmid">10940440</pub-id>
</element-citation>
</ref>
<ref id="b15"><label>15</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Braak</surname>
<given-names>H</given-names>
</name>
<name><surname>Ghebremedhin</surname>
<given-names>E</given-names>
</name>
<name><surname>Rub</surname>
<given-names>U</given-names>
</name>
<name><surname>Bratzke</surname>
<given-names>H</given-names>
</name>
<name><surname>Del Tredici</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Stages in the development of Parkinson’s disease-related pathology</article-title>
<source>Cell Tissue Res</source>
<year>2004</year>
<volume>318</volume>
<fpage>121</fpage>
<lpage>134</lpage>
<pub-id pub-id-type="pmid">15338272</pub-id>
</element-citation>
</ref>
<ref id="b16"><label>16</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Braak</surname>
<given-names>H</given-names>
</name>
<name><surname>Del Tredici</surname>
<given-names>K</given-names>
</name>
<name><surname>Bratzke</surname>
<given-names>H</given-names>
</name>
<name><surname>Hamm-Clement</surname>
<given-names>J</given-names>
</name>
<name><surname>Sandmann-Keil</surname>
<given-names>D</given-names>
</name>
<name><surname>Rub</surname>
<given-names>U</given-names>
</name>
</person-group>
<article-title>Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages)</article-title>
<source>J Neurol</source>
<year>2002</year>
<volume>249</volume>
<issue>Suppl 3</issue>
<fpage>III/1</fpage>
<lpage>5</lpage>
</element-citation>
</ref>
<ref id="b17"><label>17</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Meredith</surname>
<given-names>GE</given-names>
</name>
<name><surname>Halliday</surname>
<given-names>GM</given-names>
</name>
<name><surname>Totterdell</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>A critical review of the development and importance of proteinaceous aggregates in animal models of Parkinson’s disease: new insights into Lewy body formation</article-title>
<source>Parkinsonism Relat Disord</source>
<year>2004</year>
<volume>10</volume>
<fpage>191</fpage>
<lpage>202</lpage>
<pub-id pub-id-type="pmid">15120093</pub-id>
</element-citation>
</ref>
<ref id="b18"><label>18</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Langston</surname>
<given-names>JW</given-names>
</name>
</person-group>
<article-title>MPTP neurotoxicity: an overview and characterization of phases of toxicity</article-title>
<source>Life Sci</source>
<year>1985</year>
<volume>36</volume>
<fpage>201</fpage>
<lpage>206</lpage>
<pub-id pub-id-type="pmid">2857048</pub-id>
</element-citation>
</ref>
<ref id="b19"><label>19</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lammel</surname>
<given-names>S</given-names>
</name>
<name><surname>Hetzel</surname>
<given-names>A</given-names>
</name>
<name><surname>Hackel</surname>
<given-names>O</given-names>
</name>
<name><surname>Jones</surname>
<given-names>I</given-names>
</name>
<name><surname>Liss</surname>
<given-names>B</given-names>
</name>
<name><surname>Roeper</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system</article-title>
<source>Neuron</source>
<year>2008</year>
<volume>57</volume>
<fpage>760</fpage>
<lpage>773</lpage>
<pub-id pub-id-type="pmid">18341995</pub-id>
</element-citation>
</ref>
<ref id="b20"><label>20</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sherer</surname>
<given-names>TB</given-names>
</name>
<name><surname>Kim</surname>
<given-names>JH</given-names>
</name>
<name><surname>Betarbet</surname>
<given-names>R</given-names>
</name>
<name><surname>Greenamyre</surname>
<given-names>JT</given-names>
</name>
</person-group>
<article-title>Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation</article-title>
<source>Exp Neurol</source>
<year>2003</year>
<volume>179</volume>
<fpage>9</fpage>
<lpage>16</lpage>
<pub-id pub-id-type="pmid">12504863</pub-id>
</element-citation>
</ref>
<ref id="b21"><label>21</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Drolet</surname>
<given-names>RE</given-names>
</name>
<name><surname>Cannon</surname>
<given-names>JR</given-names>
</name>
<name><surname>Montero</surname>
<given-names>L</given-names>
</name>
<name><surname>Greenamyre</surname>
<given-names>JT</given-names>
</name>
</person-group>
<article-title>Chronic rotenone exposure reproduces Parkinson’s disease gastrointestinal neuropathology</article-title>
<source>Neurobiol Dis</source>
<year>2009</year>
<volume>36</volume>
<fpage>96</fpage>
<lpage>102</lpage>
<pub-id pub-id-type="pmid">19595768</pub-id>
</element-citation>
</ref>
<ref id="b22"><label>22</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Betarbet</surname>
<given-names>R</given-names>
</name>
<name><surname>Sherer</surname>
<given-names>TB</given-names>
</name>
<name><surname>MacKenzie</surname>
<given-names>G</given-names>
</name>
<name><surname>Garcia-Osuna</surname>
<given-names>M</given-names>
</name>
<name><surname>Panov</surname>
<given-names>AV</given-names>
</name>
<name><surname>Greenamyre</surname>
<given-names>JT</given-names>
</name>
</person-group>
<article-title>Chronic systemic pesticide exposure reproduces features of Parkinson’s disease</article-title>
<source>Nat Neurosci</source>
<year>2000</year>
<volume>3</volume>
<fpage>1301</fpage>
<lpage>1306</lpage>
<pub-id pub-id-type="pmid">11100151</pub-id>
</element-citation>
</ref>
<ref id="b23"><label>23</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moss</surname>
<given-names>J</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
</person-group>
<article-title>A dopaminergic axon lattice in the striatum and its relationship with cortical and thalamic terminals</article-title>
<source>J Neurosci</source>
<year>2008</year>
<volume>28</volume>
<fpage>11221</fpage>
<lpage>11230</lpage>
<pub-id pub-id-type="pmid">18971464</pub-id>
</element-citation>
</ref>
<ref id="b24"><label>24</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Moss</surname>
<given-names>J</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
</person-group>
<person-group person-group-type="editor"><name><surname>Iversen</surname>
<given-names>LL</given-names>
</name>
<name><surname>Iversen</surname>
<given-names>SD</given-names>
</name>
<name><surname>Dunnett</surname>
<given-names>SB</given-names>
</name>
<name><surname>Björklund</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>The relationship between dopaminergic axons and glutamatergic synapses in the striatum: structural considerations</article-title>
<source>Dopamine Handbook New York Oxford University Press</source>
<year>2010</year>
<fpage>49</fpage>
<lpage>59</lpage>
</element-citation>
</ref>
<ref id="b25"><label>25</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsuda</surname>
<given-names>W</given-names>
</name>
<name><surname>Furuta</surname>
<given-names>T</given-names>
</name>
<name><surname>Nakamura</surname>
<given-names>KC</given-names>
</name>
<name><surname>Hioki</surname>
<given-names>H</given-names>
</name>
<name><surname>Fujiyama</surname>
<given-names>F</given-names>
</name>
<name><surname>Arai</surname>
<given-names>R</given-names>
</name>
<name><surname>Kaneko</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum</article-title>
<source>J Neurosci</source>
<year>2009</year>
<volume>29</volume>
<fpage>444</fpage>
<lpage>453</lpage>
<pub-id pub-id-type="pmid">19144844</pub-id>
</element-citation>
</ref>
<ref id="b26"><label>26</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Andén</surname>
<given-names>NE</given-names>
</name>
<name><surname>Fuxe</surname>
<given-names>K</given-names>
</name>
<name><surname>Hamberger</surname>
<given-names>B</given-names>
</name>
<name><surname>Hökfelt</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>A quantitative study on the nigro-neostriatal dopamine neuron system in the rat</article-title>
<source>Acta Physiol Scand</source>
<year>1966</year>
<volume>67</volume>
<fpage>306</fpage>
<lpage>312</lpage>
<pub-id pub-id-type="pmid">5967596</pub-id>
</element-citation>
</ref>
<ref id="b27"><label>27</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Björklund</surname>
<given-names>A</given-names>
</name>
<name><surname>Lindvall</surname>
<given-names>O</given-names>
</name>
</person-group>
<person-group person-group-type="editor"><name><surname>Björklund</surname>
<given-names>A</given-names>
</name>
<name><surname>Hökfelt</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Dopamine-containing sytems in the CNS</article-title>
<source>Handbook of Chemical Neuroanatomy Amsterdam Elsevier</source>
<year>1984</year>
<fpage>55</fpage>
<lpage>122</lpage>
</element-citation>
</ref>
<ref id="b28"><label>28</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Wickens</surname>
<given-names>J</given-names>
</name>
<name><surname>Arbuthnott</surname>
<given-names>GW</given-names>
</name>
</person-group>
<person-group person-group-type="editor"><name><surname>Dunnett</surname>
<given-names>SB</given-names>
</name>
<name><surname>Bentivoglio</surname>
<given-names>M</given-names>
</name>
<name><surname>Björklund</surname>
<given-names>A</given-names>
</name>
<name><surname>Hökfelt</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Strutural and functional interactions in the striatum at the receptor level</article-title>
<source>Handbook of Chemical Neuroanatomy Amsterdam Elsevier</source>
<year>2005</year>
<fpage>199</fpage>
<lpage>236</lpage>
</element-citation>
</ref>
<ref id="b29"><label>29</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nair-Roberts</surname>
<given-names>RG</given-names>
</name>
<name><surname>Chatelain-Badie</surname>
<given-names>SD</given-names>
</name>
<name><surname>Benson</surname>
<given-names>E</given-names>
</name>
<name><surname>White-Cooper</surname>
<given-names>H</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
<name><surname>Ungless</surname>
<given-names>MA</given-names>
</name>
</person-group>
<article-title>Stereological estimates of dopaminergic, GABAergic, and glutamatergic neurons in the ventral tegmental area, substantia nigra, and retrorubral field in the rat</article-title>
<source>Neuroscience</source>
<year>2008</year>
<volume>152</volume>
<fpage>1024</fpage>
<lpage>1031</lpage>
<pub-id pub-id-type="pmid">18355970</pub-id>
</element-citation>
</ref>
<ref id="b30"><label>30</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oorschot</surname>
<given-names>DE</given-names>
</name>
</person-group>
<article-title>Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: a stereological study using the cavalieri and optical disector methods</article-title>
<source>J Comp Neurol</source>
<year>1996</year>
<volume>366</volume>
<fpage>580</fpage>
<lpage>599</lpage>
<pub-id pub-id-type="pmid">8833111</pub-id>
</element-citation>
</ref>
<ref id="b31"><label>31</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bevan</surname>
<given-names>MD</given-names>
</name>
<name><surname>Booth</surname>
<given-names>PAC</given-names>
</name>
<name><surname>Eaton</surname>
<given-names>SA</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
</person-group>
<article-title>Selective innervation of neostriatal interneurons by a subclass of neuron in the globus pallidus of the rat</article-title>
<source>J Neurosci</source>
<year>1998</year>
<volume>18</volume>
<fpage>9438</fpage>
<lpage>9452</lpage>
<pub-id pub-id-type="pmid">9801382</pub-id>
</element-citation>
</ref>
<ref id="b32"><label>32</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kawaguchi</surname>
<given-names>Y</given-names>
</name>
<name><surname>Wilson</surname>
<given-names>CJ</given-names>
</name>
<name><surname>Emson</surname>
<given-names>PC</given-names>
</name>
</person-group>
<article-title>Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin</article-title>
<source>J Neurosci</source>
<year>1990</year>
<volume>10</volume>
<fpage>3421</fpage>
<lpage>3438</lpage>
<pub-id pub-id-type="pmid">1698947</pub-id>
</element-citation>
</ref>
<ref id="b33"><label>33</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kita</surname>
<given-names>H</given-names>
</name>
<name><surname>Kitai</surname>
<given-names>ST</given-names>
</name>
</person-group>
<article-title>The morphology of globus pallidus projection neurons in the rat: an intracellular staining study</article-title>
<source>Brain Res</source>
<year>1994</year>
<volume>636</volume>
<fpage>308</fpage>
<lpage>319</lpage>
<pub-id pub-id-type="pmid">8012814</pub-id>
</element-citation>
</ref>
<ref id="b34"><label>34</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tepper</surname>
<given-names>JM</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
</person-group>
<article-title>Functional diversity and specificity of neostriatal interneurons</article-title>
<source>Curr Opin Neurobiol</source>
<year>2004</year>
<volume>14</volume>
<fpage>685</fpage>
<lpage>692</lpage>
<pub-id pub-id-type="pmid">15582369</pub-id>
</element-citation>
</ref>
<ref id="b35"><label>35</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname>
<given-names>Y</given-names>
</name>
<name><surname>Richard</surname>
<given-names>S</given-names>
</name>
<name><surname>Parent</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>The organization of the striatal output system: a single-cell juxtacellular labeling study in the rat</article-title>
<source>Neurosci Res</source>
<year>2000</year>
<volume>38</volume>
<fpage>49</fpage>
<lpage>62</lpage>
<pub-id pub-id-type="pmid">10997578</pub-id>
</element-citation>
</ref>
<ref id="b36"><label>36</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Furuta</surname>
<given-names>T</given-names>
</name>
<name><surname>Tomioka</surname>
<given-names>R</given-names>
</name>
<name><surname>Taki</surname>
<given-names>K</given-names>
</name>
<name><surname>Nakamura</surname>
<given-names>K</given-names>
</name>
<name><surname>Tamamaki</surname>
<given-names>N</given-names>
</name>
<name><surname>Kaneko</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title><italic>In vivo</italic>
 transduction of central neurons using recombinant Sindbis virus: Golgi-like labeling of dendrites and axons with membrane-targeted fluorescent proteins</article-title>
<source>J Histochem Cytochem</source>
<year>2001</year>
<volume>9</volume>
<fpage>1497</fpage>
<lpage>1508</lpage>
<pub-id pub-id-type="pmid">11724897</pub-id>
</element-citation>
</ref>
<ref id="b37"><label>37</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fujiyama</surname>
<given-names>F</given-names>
</name>
<name><surname>Sohn</surname>
<given-names>J</given-names>
</name>
<name><surname>Nakano</surname>
<given-names>T</given-names>
</name>
<name><surname>Furuta</surname>
<given-names>T</given-names>
</name>
<name><surname>Nakamura</surname>
<given-names>KC</given-names>
</name>
<name><surname>Matsuda</surname>
<given-names>W</given-names>
</name>
<name><surname>Kaneko</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Exclusive and common targets of neostriatofugal projections of rat striosome neurons: a single neuron-tracing study using a viral vector</article-title>
<source>Eur J Neurosci</source>
<year>2011</year>
<volume>33</volume>
<fpage>668</fpage>
<lpage>677</lpage>
<pub-id pub-id-type="pmid">21314848</pub-id>
</element-citation>
</ref>
<ref id="b38"><label>38</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ohno</surname>
<given-names>S</given-names>
</name>
<name><surname>Kuramoto</surname>
<given-names>E</given-names>
</name>
<name><surname>Furuta</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>A morphological analysis of thalamocortical axon fibers of rat posterior thalamic nuclei: a single neuron tracing study with viral vectors</article-title>
<source>Cerebral Cortex</source>
<year>2011</year>
<comment>Dec 20. doi: 10.1093/cercor/bhr356</comment>
</element-citation>
</ref>
<ref id="b39"><label>39</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prensa</surname>
<given-names>L</given-names>
</name>
<name><surname>Parent</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>The nigrostriatal pathway in the rat: a single-axon study of the relationship between dorsal and ventral tier nigral neurons and the striosome/matrix striatal compartments</article-title>
<source>J Neurosci</source>
<year>2001</year>
<volume>21</volume>
<fpage>7247</fpage>
<lpage>7260</lpage>
<pub-id pub-id-type="pmid">11549735</pub-id>
</element-citation>
</ref>
<ref id="b40"><label>40</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Attwell</surname>
<given-names>D</given-names>
</name>
<name><surname>Laughlin</surname>
<given-names>SB</given-names>
</name>
</person-group>
<article-title>An energy budget for signaling in the grey matter of the brain</article-title>
<source>J Cereb Blood Flow Metab</source>
<year>2001</year>
<volume>21</volume>
<fpage>1133</fpage>
<lpage>1145</lpage>
<pub-id pub-id-type="pmid">11598490</pub-id>
</element-citation>
</ref>
<ref id="b41"><label>41</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Damier</surname>
<given-names>P</given-names>
</name>
<name><surname>Hirsch</surname>
<given-names>EC</given-names>
</name>
<name><surname>Agid</surname>
<given-names>Y</given-names>
</name>
<name><surname>Graybiel</surname>
<given-names>AM</given-names>
</name>
</person-group>
<article-title>The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease</article-title>
<source>Brain</source>
<year>1999</year>
<volume>122</volume>
<fpage>1437</fpage>
<lpage>1448</lpage>
<pub-id pub-id-type="pmid">10430830</pub-id>
</element-citation>
</ref>
<ref id="b42"><label>42</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khaliq</surname>
<given-names>ZM</given-names>
</name>
<name><surname>Bean</surname>
<given-names>BP</given-names>
</name>
</person-group>
<article-title>Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances</article-title>
<source>J Neurosci</source>
<year>2010</year>
<volume>30</volume>
<fpage>7401</fpage>
<lpage>7413</lpage>
<pub-id pub-id-type="pmid">20505107</pub-id>
</element-citation>
</ref>
<ref id="b43"><label>43</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yin</surname>
<given-names>D</given-names>
</name>
<name><surname>Valles</surname>
<given-names>FE</given-names>
</name>
<name><surname>Fiandaca</surname>
<given-names>MS</given-names>
</name>
<name><surname>Forsayeth</surname>
<given-names>J</given-names>
</name>
<name><surname>Larson</surname>
<given-names>P</given-names>
</name>
<name><surname>Starr</surname>
<given-names>P</given-names>
</name>
<name><surname>Bankiewicz</surname>
<given-names>KS</given-names>
</name>
</person-group>
<article-title>Striatal volume differences between non-human and human primates</article-title>
<source>J Neurosci Methods</source>
<year>2009</year>
<volume>176</volume>
<fpage>200</fpage>
<lpage>205</lpage>
<pub-id pub-id-type="pmid">18809434</pub-id>
</element-citation>
</ref>
<ref id="b44"><label>44</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hardman</surname>
<given-names>CD</given-names>
</name>
<name><surname>Henderson</surname>
<given-names>JM</given-names>
</name>
<name><surname>Finkelstein</surname>
<given-names>DI</given-names>
</name>
<name><surname>Horne</surname>
<given-names>MK</given-names>
</name>
<name><surname>Paxinos</surname>
<given-names>G</given-names>
</name>
<name><surname>Halliday</surname>
<given-names>GM</given-names>
</name>
</person-group>
<article-title>Comparison of the basal ganglia in rats, marmosets, macaques, baboons, and humans: volume and neuronal number for the output, internal relay, and striatal modulating nuclei</article-title>
<source>J Comp Neurol</source>
<year>2002</year>
<volume>445</volume>
<fpage>238</fpage>
<lpage>255</lpage>
<pub-id pub-id-type="pmid">11920704</pub-id>
</element-citation>
</ref>
<ref id="b45"><label>45</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berger</surname>
<given-names>B</given-names>
</name>
<name><surname>Gaspar</surname>
<given-names>P</given-names>
</name>
<name><surname>Verney</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates</article-title>
<source>Trends Neurosci</source>
<year>1991</year>
<volume>14</volume>
<fpage>21</fpage>
<lpage>27</lpage>
<pub-id pub-id-type="pmid">1709528</pub-id>
</element-citation>
</ref>
<ref id="b46"><label>46</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garcia-Cabezas</surname>
<given-names>MA</given-names>
</name>
<name><surname>Martinez-Sanchez</surname>
<given-names>P</given-names>
</name>
<name><surname>Sanchez-Gonzalez</surname>
<given-names>MA</given-names>
</name>
<name><surname>Garzon</surname>
<given-names>M</given-names>
</name>
<name><surname>Cavada</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Dopamine innervation in the thalamus: monkey versus rat</article-title>
<source>Cereb Cortex</source>
<year>2009</year>
<volume>19</volume>
<fpage>424</fpage>
<lpage>434</lpage>
<pub-id pub-id-type="pmid">18550594</pub-id>
</element-citation>
</ref>
<ref id="b47"><label>47</label>
<element-citation publication-type="other"><person-group person-group-type="author"><name><surname>Pissadaki</surname>
<given-names>EK</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
</person-group>
<source>Signal propagation and metabolic efficiency in the axons of SNc dopamine neurons</source>
<comment>IBAGS X June 20–24, 2010, Long Branch, NJ</comment>
</element-citation>
</ref>
<ref id="b48"><label>48</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elstner</surname>
<given-names>M</given-names>
</name>
<name><surname>Morris</surname>
<given-names>CM</given-names>
</name>
<name><surname>Heim</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Expression analysis of dopaminergic neurons in Parkinson’s disease and aging links transcriptional dysregulation of energy metabolism to cell death</article-title>
<source>Acta Neuropath</source>
<year>2011</year>
<volume>122</volume>
<fpage>75</fpage>
<lpage>86</lpage>
<pub-id pub-id-type="pmid">21541762</pub-id>
</element-citation>
</ref>
<ref id="b49"><label>49</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wellstead</surname>
<given-names>P</given-names>
</name>
<name><surname>Cloutier</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>An energy systems approach to Parkinson’s disease</article-title>
<source>Wiley Interdiscip Rev Syst Biol Med</source>
<year>2011</year>
<volume>3</volume>
<fpage>1</fpage>
<lpage>6</lpage>
<pub-id pub-id-type="pmid">21061310</pub-id>
</element-citation>
</ref>
<ref id="b50"><label>50</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim-Han</surname>
<given-names>JS</given-names>
</name>
<name><surname>Antenor-Dorsey</surname>
<given-names>JA</given-names>
</name>
<name><surname>O’Malley</surname>
<given-names>KL</given-names>
</name>
</person-group>
<article-title>The Parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons</article-title>
<source>J Neurosci</source>
<year>2011</year>
<volume>31</volume>
<fpage>7212</fpage>
<lpage>7221</lpage>
<pub-id pub-id-type="pmid">21562285</pub-id>
</element-citation>
</ref>
<ref id="b51"><label>51</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burke</surname>
<given-names>RE</given-names>
</name>
<name><surname>O’Malley</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Axon degeneration in Parkinson’s disease</article-title>
<source>Exp Neurol</source>
<year>2012</year>
<comment>Jan 18. doi: 10.1016/j.expneurol.2012.01.011</comment>
</element-citation>
</ref>
<ref id="b52"><label>52</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname>
<given-names>NK</given-names>
</name>
<name><surname>Gill</surname>
<given-names>SS</given-names>
</name>
</person-group>
<article-title>GDNF delivery for Parkinson’s disease</article-title>
<source>Acta Neurochir Suppl</source>
<year>2007</year>
<volume>97</volume>
<fpage>135</fpage>
<lpage>154</lpage>
<pub-id pub-id-type="pmid">17691299</pub-id>
</element-citation>
</ref>
<ref id="b53"><label>53</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rosenblad</surname>
<given-names>C</given-names>
</name>
<name><surname>Kirik</surname>
<given-names>D</given-names>
</name>
<name><surname>Björklund</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Sequential administration of GDNF into the substantia nigra and striatum promotes dopamine neuron survival and axonal sprouting but not striatal reinnervation or functional recovery in the partial 6-OHDA lesion model</article-title>
<source>Exp Neurol</source>
<year>2000</year>
<volume>161</volume>
<fpage>503</fpage>
<lpage>516</lpage>
<pub-id pub-id-type="pmid">10686072</pub-id>
</element-citation>
</ref>
<ref id="b54"><label>54</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rosenblad</surname>
<given-names>C</given-names>
</name>
<name><surname>Kirik</surname>
<given-names>D</given-names>
</name>
<name><surname>Devaux</surname>
<given-names>B</given-names>
</name>
<name><surname>Moffat</surname>
<given-names>B</given-names>
</name>
<name><surname>Phillips</surname>
<given-names>HS</given-names>
</name>
<name><surname>Björklund</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson’s disease after administration into the striatum or the lateral ventricle</article-title>
<source>Eur J Neurosci</source>
<year>1999</year>
<volume>11</volume>
<fpage>1554</fpage>
<lpage>1566</lpage>
<pub-id pub-id-type="pmid">10215908</pub-id>
</element-citation>
</ref>
<ref id="b55"><label>55</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Welberg</surname>
<given-names>L</given-names>
</name>
</person-group>
<article-title>SNc neurons’ Achilles heel</article-title>
<source>Nature Rev Neurosci</source>
<year>2011</year>
<volume>12</volume>
<fpage>6</fpage>
<lpage>7</lpage>
<pub-id pub-id-type="pmid">21218575</pub-id>
</element-citation>
</ref>
<ref id="b56"><label>56</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kincaid</surname>
<given-names>AE</given-names>
</name>
<name><surname>Zheng</surname>
<given-names>T</given-names>
</name>
<name><surname>Wilson</surname>
<given-names>CJ</given-names>
</name>
</person-group>
<article-title>Connectivity and convergence of single corticostriatal axons</article-title>
<source>J Neurosci</source>
<year>1998</year>
<volume>18</volume>
<fpage>4722</fpage>
<lpage>4731</lpage>
<pub-id pub-id-type="pmid">9614246</pub-id>
</element-citation>
</ref>
<ref id="b57"><label>57</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lacey</surname>
<given-names>CJ</given-names>
</name>
<name><surname>Boyes</surname>
<given-names>J</given-names>
</name>
<name><surname>Gerlach</surname>
<given-names>O</given-names>
</name>
<name><surname>Chen</surname>
<given-names>L</given-names>
</name>
<name><surname>Magill</surname>
<given-names>PJ</given-names>
</name>
<name><surname>Bolam</surname>
<given-names>JP</given-names>
</name>
</person-group>
<article-title>GABA(B) receptors at glutamatergic synapses in the rat striatum</article-title>
<source>Neuroscience</source>
<year>2005</year>
<volume>136</volume>
<fpage>1083</fpage>
<lpage>1095</lpage>
<pub-id pub-id-type="pmid">16226840</pub-id>
</element-citation>
</ref>
</ref-list>
<sec sec-type="supplementary-material"><title>Supporting Information</title>
<p>Additional Supporting Information may be found in the online version of this article.</p>
<supplementary-material content-type="local-data" id="SD1"><media xlink:href="mds0027-1478-SD1.doc" xlink:type="simple" id="d34e2639" position="anchor" mimetype="application" mime-subtype="msword"></media>
</supplementary-material>
</sec>
</back>
</pmc>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/Pmc/Curation

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000461 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000461 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Santé
   |area=    MovDisordV3
   |flux=    Pmc
   |étape=   Curation
   |type=    RBID
   |clé=     PMC:3504389
   |texte=   Living on the edge with too many mouths to feed: Why dopamine neurons die
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i   -Sk "pubmed:23008164" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd   \
       | NlmPubMed2Wicri -a MovDisordV3

This area was generated with Dilib version V0.6.23.
Data generation: Sun Jul 3 12:29:32 2016. Site generation: Wed Feb 14 10:52:30 2024

	Movement Disorders (revue)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Movement Disorders (revue)

Living on the edge with too many mouths to feed: Why dopamine neurons die

Living on the edge with too many mouths to feed: Why dopamine neurons die

Source :

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki