Uemura Maiko T, Asano Takeshi, Hikawa Rie, Yamakado Hodaka, Takahashi Ryosuke
Department of Neurology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Neurology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Neurosci Res. 2017 Nov;124:25-32. doi: 10.1016/j.neures.2017.05.008. Epub 2017 Jun 15.
Zonisamide (ZNS) is an effective drug for not only motor symptoms but also non-motor symptoms in Parkinson's disease. However, the actions of ZNS as an anti-Parkinsonian drug are not well understood. To clarify the actions of ZNS in vivo, we administered ZNS to mice and examined the effects on neurotransmitter metabolism and behaviors, focusing on motor and non-motor symptoms. Administration of ZNS decreased dopamine (DA) turnover in various brain regions, including the striatum. In behavioral tests, ZNS enhanced locomotor activity and novelty seeking in the open field test, light-dark transition test, and the social interaction test. Consistent with these results of DA metabolism in ZNS-treated mice, monoamine oxidase activity was significantly inhibited by ZNS in primary neurons and astrocytes. Collectively, these data suggest that ZNS inhibits monoamine oxidase activity and decreases DA turnover, which increases locomotor activity and novelty seeking in mice. ZNS is potentially useful to improve not only motor symptoms but also neuropsychiatric non-motor symptoms such as apathy in PD.
唑尼沙胺（ZNS）不仅是治疗帕金森病运动症状的有效药物，也是治疗非运动症状的有效药物。然而，ZNS作为抗帕金森病药物的作用尚未完全明确。为了阐明ZNS在体内的作用，我们给小鼠服用ZNS，并研究其对神经递质代谢和行为的影响，重点关注运动和非运动症状。服用ZNS可降低包括纹状体在内的各个脑区的多巴胺（DA）周转率。在行为测试中，ZNS在旷场试验、明暗转换试验和社交互动试验中增强了运动活动和新奇探索行为。与ZNS处理小鼠的DA代谢结果一致，ZNS在原代神经元和星形胶质细胞中显著抑制单胺氧化酶活性。总体而言，这些数据表明，ZNS抑制单胺氧化酶活性并降低DA周转率，从而增加小鼠的运动活动和新奇探索行为。ZNS不仅可能有助于改善帕金森病的运动症状，还可能有助于改善神经精神性非运动症状，如冷漠。
