Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter.
Experimental Neurology. 1999-02-01; 155(2): 268-273
DOI: 10.1006/exnr.1998.6995
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1. Exp Neurol. 1999 Feb;155(2):268-73.
Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter.
Bezard E(1), Gross CE, Fournier MC, Dovero S, Bloch B, Jaber M.
Author information:
(1)Basal Gang, CNRS UMR 5541, Laboratoire de Neurophysiologie, CNRS UMR 5543,
Université de Bordeaux II, 146 rue Leo Saignat, Bordeaux Cedex, 33076, France.
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.
Copyright 1999 Academic Press.
DOI: 10.1006/exnr.1998.6995
PMID: 10072302 [Indexed for MEDLINE]