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Absence of MPTP-Induced Neuronal Death in Mice Lacking the Dopamine Transporter

Identifieur interne : 003E47 ( Main/Exploration ); précédent : 003E46; suivant : 003E48

Absence of MPTP-Induced Neuronal Death in Mice Lacking the Dopamine Transporter

Auteurs : Erwan Bezard [France] ; Christian E. Gross [France] ; Marie-Christine Fournier [France] ; Sandra Dovero [France] ; Bertrand Bloch [France] ; Mohamed Jaber [France]

Source :

Experimental Neurology [ 0014-4886 ] ; 1999.

RBID : ISTEX:D8B44DA2CDA43B53B63CDDC5D22DB7BCC2B115E7

Descripteurs français

Pascal (Inist)
- Animal, Dopamine, Déficit, Modèle animal, Mort cellulaire, Neurone dopaminergique, Neurotoxine, Parkinson maladie, Pathogénie, Pyridine(1-méthyl-4-phényl-1,2,3,6-tétrahydro), Souris, Transport biologique, Transporteur.
Wicri :
- topic : Déficit, Transporteur.

English descriptors

KwdEn :
- Animal, Animal model, Biological transport, Cell death, Conveyor, Deficiency, Dopamine, Dopaminergic neuron, MPTP, Mouse, Neurotoxin, Parkinson disease, Pathogenesis, dopamine transporter, immunohistochemistry, knock out., neurodegeneration, tyrosine hydroxylase.

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.

Url:

https://api.istex.fr/document/D8B44DA2CDA43B53B63CDDC5D22DB7BCC2B115E7/fulltext/pdf

DOI: 10.1006/exnr.1998.6995

Affiliations:

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<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+, 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>
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La maladie de Parkinson en France (serveur d'exploration)

Absence of MPTP-Induced Neuronal Death in Mice Lacking the Dopamine Transporter

Absence of MPTP-Induced Neuronal Death in Mice Lacking the Dopamine Transporter

Source :

Descripteurs français

English descriptors

Abstract

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

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

	La maladie de Parkinson en France (serveur d'exploration)
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