Absence of MPTP-lnduced neuronal death in mice lacking the dopamine transporter
Identifieur interne : 004682 ( Main/Merge ); précédent : 004681; suivant : 004683Absence of MPTP-lnduced neuronal death in mice lacking the dopamine transporter
Auteurs : E. Bezard [France] ; C. E. Gross [France] ; M.-C. Fournier [France] ; S. Dovero [France] ; B. Bloch [France] ; M. Jaber [France]Source :
- Experimental neurology [ 0014-4886 ] ; 1999.
Descripteurs français
- Pascal (Inist)
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- topic : Déficit, Transporteur.
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Abstract
MPTP has been shown to induce parkinsonism both in human and in nonhuman primates. The precise mechanism of dopaminergic cell death induced following MPTP treatment is still subject to intense debate. MPP+, which is the oxidation product of MPTP, is actively transported into presynaptic dopaminergic nerve terminals through the plasma membrane dopamine transporter (DAT). In this study, we used mice lacking the DAT by homologous recombination and demonstrated that the MPTP-induced dopaminergic cell loss is dependent on the presence of the DAT. For this we have used tyrosine hydroxylase immunoreactivity (TH-IR) labeling of dopamine cells of the substantia nigra compacta in wild-type, heterozygote, and homozygote mice that were given either saline or MPTP treatments (two ip injections of 30 mg/kg, 10 h apart). Our results show a significant loss of TH-IR in wild type (34.4%), less loss in heterozygotes (22.5%), and no loss in homozygote animals. Thus dopamine cell loss is related to levels of the DAT. These results shed light on the degenerative process of dopamine neurons and suggest that individual differences in developing Parkinson's disease in human may be related to differences of uptake through the DAT of a yet unidentified neurotoxin.
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Bezard</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543</s1><s2>33076 Bordeaux</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Gross, C E" sort="Gross, C E" uniqKey="Gross C" first="C. E." last="Gross">C. E. Gross</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543</s1><s2>33076 Bordeaux</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Fournier, M C" sort="Fournier, M C" uniqKey="Fournier M" first="M.-C." last="Fournier">M.-C. Fournier</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>CNRS UMR 5541, Université de Bordeaux II, 146 rue Leo Saignat</s1><s2>33076 Bordeaux</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Dovero, S" sort="Dovero, S" uniqKey="Dovero S" first="S." last="Dovero">S. Dovero</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543</s1><s2>33076 Bordeaux</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Bloch, B" sort="Bloch, B" uniqKey="Bloch B" first="B." last="Bloch">B. Bloch</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>CNRS UMR 5541, Université de Bordeaux II, 146 rue Leo Saignat</s1><s2>33076 Bordeaux</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Jaber, M" sort="Jaber, M" uniqKey="Jaber M" first="M." last="Jaber">M. Jaber</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>CNRS UMR 5541, Université de Bordeaux II, 146 rue Leo Saignat</s1><s2>33076 Bordeaux</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Experimental neurology</title><title level="j" type="abbreviated">Exp. neurol.</title><idno type="ISSN">0014-4886</idno><imprint><date when="1999">1999</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Experimental neurology</title><title level="j" type="abbreviated">Exp. neurol.</title><idno type="ISSN">0014-4886</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Animal model</term><term>Biological transport</term><term>Cell death</term><term>Conveyor</term><term>Deficiency</term><term>Dopamine</term><term>Dopaminergic neuron</term><term>Mouse</term><term>Neurotoxin</term><term>Parkinson disease</term><term>Pathogenesis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Déficit</term><term>Transporteur</term><term>Dopamine</term><term>Transport biologique</term><term>Parkinson maladie</term><term>Neurone dopaminergique</term><term>Neurotoxine</term><term>Pyridine(1-méthyl-4-phényl-1,2,3,6-tétrahydro)</term><term>Pathogénie</term><term>Modèle animal</term><term>Animal</term><term>Souris</term><term>Mort cellulaire</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Déficit</term><term>Transporteur</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">MPTP has been shown to induce parkinsonism both in human and in nonhuman primates. The precise mechanism of dopaminergic cell death induced following MPTP treatment is still subject to intense debate. MPP<sup>+</sup>, which is the oxidation product of MPTP, is actively transported into presynaptic dopaminergic nerve terminals through the plasma membrane dopamine transporter (DAT). In this study, we used mice lacking the DAT by homologous recombination and demonstrated that the MPTP-induced dopaminergic cell loss is dependent on the presence of the DAT. For this we have used tyrosine hydroxylase immunoreactivity (TH-IR) labeling of dopamine cells of the substantia nigra compacta in wild-type, heterozygote, and homozygote mice that were given either saline or MPTP treatments (two ip injections of 30 mg/kg, 10 h apart). Our results show a significant loss of TH-IR in wild type (34.4%), less loss in heterozygotes (22.5%), and no loss in homozygote animals. Thus dopamine cell loss is related to levels of the DAT. These results shed light on the degenerative process of dopamine neurons and suggest that individual differences in developing Parkinson's disease in human may be related to differences of uptake through the DAT of a yet unidentified neurotoxin.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Aquitaine</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Bordeaux</li></settlement></list><tree><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Bezard, E" sort="Bezard, E" uniqKey="Bezard E" first="E." last="Bezard">E. Bezard</name></region><name sortKey="Bloch, B" sort="Bloch, B" uniqKey="Bloch B" first="B." last="Bloch">B. Bloch</name><name sortKey="Dovero, S" sort="Dovero, S" uniqKey="Dovero S" first="S." last="Dovero">S. Dovero</name><name sortKey="Fournier, M C" sort="Fournier, M C" uniqKey="Fournier M" first="M.-C." last="Fournier">M.-C. Fournier</name><name sortKey="Gross, C E" sort="Gross, C E" uniqKey="Gross C" first="C. E." last="Gross">C. E. Gross</name><name sortKey="Jaber, M" sort="Jaber, M" uniqKey="Jaber M" first="M." last="Jaber">M. Jaber</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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