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Metab Brain Dis. 2003 Jun;18(2):139-46.

Role of dopamine transporter against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice.

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1
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan.

Abstract

We investigated the alterations of dopamine transporter (DAT)-immunopositive cells against MPTP neurotoxicity, in comparison with tyrosine hydroxylase (TH)-immunopositive neurons and glial fibrillary acidic protein (GFAP)-immunopositive cells. This study showed that DAT and TH immunoreactivity was decreased gradually in the striatum and substantia nigra of mice after MPTP treatment. The patterns of the intense TH-immunoreactive fibers and cell bodies were similar to those of DAT-immunoreactive fibers and cell bodies in the striatum and substantia nigra of mice after MPTP treatment. In contrast, GFAP immunoreactivity was increased gradually in the striatum and substantia nigra after MPTP treatment. In our double-labeled immunostaining with anti-DAT and anti-GFAP antibodies, DAT immunoreactivity was observed only in the nigral dopaminergic neurons, but not in the reactive astrocytes. The present results provide further evidence that the functional damage of DAT may precede dopaminergic neuronal death after MPTP treatment, although the decrease in the number of TH-immunopositive neurons was more pronounced than that in the number of DAT-immunopositive neurons. Furthermore, our findings demonstrate that MPTP can selectively injure the dopaminergic neurons which DAT proteins are predominantly distributed on the striatum and substantia nigra. The results provide beneficial information for MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.

PMID:
12822832
DOI:
10.1023/a:1023863003093
[Indexed for MEDLINE]

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