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首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease
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Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease

机译：唑尼沙胺可减轻帕金森氏病小鼠遗传模型中的黑纹状体多巴胺能神经变性

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摘要

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and consequent motor dysfunction. Zonisamide (1,2-benzisoxazole-3-methanesulfonamide), which was originally developed as an antiepileptic drug, has been found to have therapeutic benefits for PD. However, the pharmacological mechanisms behind the beneficial actions of zonisamide in PD are not fully understood. Here, we investigated the neuroprotective effects of zonisamide on nigrostriatal dopaminergic neurons of the Engrailed mutant mouse, a genetic model of PD. Chronic administration of zonisamide in Engrailed mutant mice was shown to improve the survival of nigrostriatal dopaminergic neurons compared with that under saline treatment. In addition, dopaminergic terminals in the striatum and the motor function were improved in zonisamide-treated Engrailed mutant mice to the levels of those in control mice. To clarify the mechanism behind the neuroprotective effects of zonisamide, the contents of neurotrophic factors were determined after chronic administration of zonisamide. Brain-derived neurotrophic factor content was increased in the striatum and ventral midbrain of the zonisamide-treated mice compared to saline-treated mice. These findings imply that zonisamide reduces nigrostriatal dopaminergic cell death through brain-derived neurotrophic factor signaling and may have similar beneficial effects in human parkinsonian patients as well.
机译：帕金森氏病（PD）是一种慢性神经退行性疾病，其特征是黑纹状体多巴胺能神经元的丧失和随之而来的运动功能障碍。唑尼沙胺（1,2-苯并恶唑-3-甲磺酰胺）最初是作为抗癫痫药开发的，已发现对帕金森氏症具有治疗作用。但是，尚不完全了解zonisamide在PD中有益作用的药理机制。在这里，我们研究了唑尼沙胺对Engrailed突变小鼠（PD的遗传模型）的黑质纹状体多巴胺能神经元的神经保护作用。与生理盐水处理相比，长期向已突变的突变小鼠中施用zonisamide可以改善黑纹状体多巴胺能神经元的存活。此外，用唑尼沙胺治疗的Engrailed突变小鼠的纹状体多巴胺能末端和运动功能得到了改善，达到了对照小鼠的水平。为了阐明唑尼沙胺神经保护作用背后的机制，在长期服用唑尼沙胺后测定了神经营养因子的含量。与盐水处理的小鼠相比，zonisamide处理的小鼠的纹状体和腹中脑的脑源性神经营养因子含量增加。这些发现暗示zonisamide可通过脑源性神经营养因子信号传导减少黑质纹状体多巴胺能细胞死亡，并且可能对人类帕金森病患者具有类似的有益作用。

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