Role of dopamine transporter against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice
Role of dopamine transporter against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice
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DOI：
10.1023/a:1023863003093
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发表时间：
2003-06-01
影响因子：
3.6
通讯作者：
Araki, T
中科院分区：
文献类型：
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作者：
Kurosaki, R;Muramatsu, Y;Araki, T
我们研究了多巴胺转运蛋白（DAT）免疫阳性细胞对MPTP神经毒性的变化，与酪氨酸羟化酶（TH）免疫阳性神经元和胶质细胞酸性蛋白（GFAP）免疫阳性细胞相比。本研究表明，MPTP处理后，小鼠纹状体和黑质的DAT和TH免疫反应性逐渐降低。MPTP处理后，小鼠纹状体和黑质内TH免疫反应阳性纤维和胞体的分布与DAT免疫反应阳性纤维和胞体的分布相似。MPTP处理后，纹状体和黑质GFAP免疫反应逐渐增强。在我们的双标记的免疫染色与抗DAT和抗GFAP抗体，DAT免疫反应只观察到在黑质多巴胺能神经元，但没有在反应性星形胶质细胞。本研究结果提供了进一步的证据表明，DAT的功能损害可能先于多巴胺能神经元死亡后MPTP处理，虽然TH-免疫阳性神经元的数量的减少比DAT-免疫阳性神经元的数量更明显。此外，我们的研究结果表明，MPTP可以选择性地损害多巴胺能神经元，DAT蛋白主要分布在纹状体和黑质。这些结果为MPTP诱导的黑质纹状体多巴胺能神经元通路的神经变性提供了有益的信息。
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.