Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)neurotoxicity in mice
Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)neurotoxicity in mice
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DOI：
10.1007/s11011-010-9191-0
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发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Araki, Tsutomu
中科院分区：
文献类型：
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作者：
Yokoyama, Hironori;Yano, Ryohei;Araki, Tsutomu
采用免疫印迹、免疫组化和行为学方法研究唑尼沙胺对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）神经毒性的治疗作用。我们的蛋白质印迹分析和免疫组织化学研究表明，唑尼沙胺后处理可显着防止多巴胺能细胞损伤、酪氨酸羟化酶（TH）蛋白水平的耗尽以及纹状体和/或黑质中小胶质细胞的增殖MPTP处理后8天。此外，我们的行为学研究表明，唑尼沙胺后处理MPTP治疗后7天的运动障碍显着减弱。这些结果表明唑尼沙胺对小鼠帕金森病（PD）MPTP模型具有治疗作用。我们的研究还证明了唑尼沙胺对小鼠MPTP治疗后多巴胺能细胞损伤的神经保护作用。因此，我们目前的研究结果表明，治疗策略针对TH蛋白的激活和/或抑制小胶质细胞的激活唑尼沙胺可能提供一个巨大的潜力，恢复幸存的多巴胺能神经元的功能能力与PD患者。
We investigated the therapeutic effect of zonisamide against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, using Western blot analysis, immunohistochemistry and behavioral test. Our Western blot analysis and immunohistochemical study showed that the post-treatment with zonisamide prevented significantly dopaminergic cell damage, the depletion of tyrosine-hydroxylase (TH) protein levels and the proliferation of microglia in the striatum and/or substantia nigra 8 days after MPTP treatment. Furthermore, our behavioral study showed that the post-treatment with zonisamide attenuated significantly the motor deficits 7 days after MPTP treatment. These results show that zonisamide has the therapeutic effect in the MPTP model of Parkinson's disease (PD) in mice. Our study also demonstrates the neuroprotective effect of zonisamide against dopaminergic cell damage after MPTP treatment in mice. Thus our present findings suggest that therapeutic strategies targeted to the activation of TH protein and/or the inhibition of microglial activation with zonisamide may offer a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with PD.