Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid
Identifieur interne : 002510 ( Main/Exploration ); précédent : 002509; suivant : 002511Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid
Auteurs : Daniel Alvarez-Fischer [France] ; Serge Guerreiro [France] ; Stephane Hunot [France] ; Francoise Saurini [France] ; Marc Marien [France] ; Pierre Sokoloff [France] ; Etienne C. Hirsch [France] ; Andreas Hartmann [France] ; Patrick P. Michel [France]Source :
- Journal of neurochemistry [ 0022-3042 ] ; 2008.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histological features of the disease such as Lewy body like inclusions and long-term inflammatory changes are lacking. Fornai et al. [Proc. Natl Acad. Sci. USA 102 (2005), 3413] suggested that continuous delivery of MPTP with Alzet osmotic minipumps may possibly circumvent these problems. Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable.
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type="wicri:Area/Main/Curation">002510</idno><idno type="wicri:Area/Main/Exploration">002510</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid</title><author><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Guerreiro, Serge" sort="Guerreiro, Serge" uniqKey="Guerreiro S" first="Serge" last="Guerreiro">Serge Guerreiro</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Saurini, Francoise" sort="Saurini, Francoise" uniqKey="Saurini F" first="Francoise" last="Saurini">Francoise Saurini</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>INSERM, Unité Mixte de Recherche S677</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Marien, Marc" sort="Marien, Marc" uniqKey="Marien M" first="Marc" last="Marien">Marc Marien</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Centre de Recherche Pierre Fabre</s1><s2>Castres</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Castres</settlement></placeName></affiliation></author><author><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Centre de Recherche Pierre Fabre</s1><s2>Castres</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Castres</settlement></placeName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Assistance Publique-Hôpitaux de Paris, Hôpital de la Salpêtrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Université Pierre et Marie Curie-Paris 6</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Centre de Recherche Pierre Fabre</s1><s2>Castres</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Castres</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal model</term><term>Cell death</term><term>Coronary heart disease</term><term>Corpus striatum</term><term>Depletion</term><term>Dopamine</term><term>Dopaminergic neuron</term><term>Graft vascular disease</term><term>Locus niger</term><term>Long term</term><term>Parkinson disease</term><term>Poisoning</term><term>Toxin</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Modèle animal</term><term>Mort cellulaire</term><term>Long terme</term><term>Artériosclérose de greffe</term><term>Cardiopathie coronaire</term><term>Déplétion</term><term>Corps strié</term><term>Dopamine</term><term>Intoxication</term><term>Locus niger</term><term>Toxine</term><term>Maladie de Parkinson</term><term>Neurone dopaminergique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histological features of the disease such as Lewy body like inclusions and long-term inflammatory changes are lacking. Fornai et al. [Proc. Natl Acad. Sci. USA 102 (2005), 3413] suggested that continuous delivery of MPTP with Alzet osmotic minipumps may possibly circumvent these problems. Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Île-de-France</li></region><settlement><li>Castres</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name></region><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name><name sortKey="Guerreiro, Serge" sort="Guerreiro, Serge" uniqKey="Guerreiro S" first="Serge" last="Guerreiro">Serge Guerreiro</name><name sortKey="Guerreiro, Serge" sort="Guerreiro, Serge" uniqKey="Guerreiro S" first="Serge" last="Guerreiro">Serge Guerreiro</name><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><name sortKey="Marien, Marc" sort="Marien, Marc" uniqKey="Marien M" first="Marc" last="Marien">Marc Marien</name><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><name sortKey="Saurini, Francoise" sort="Saurini, Francoise" uniqKey="Saurini F" first="Francoise" last="Saurini">Francoise Saurini</name><name sortKey="Saurini, Francoise" sort="Saurini, Francoise" uniqKey="Saurini F" first="Francoise" last="Saurini">Francoise Saurini</name><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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