Zonisamide ameliorates levodopa-induced dyskinesia and reduces expression of striatal genes in Parkinson model rats
Zonisamide ameliorates levodopa-induced dyskinesia and reduces expression of striatal genes in Parkinson model rats
复制标题
DOI：
10.1016/j.neures.2017.04.003
复制
发表时间：
2017-09-01
影响因子：
2.9
通讯作者：
Kusaka, Hirofumi
中科院分区：
文献类型：
--
作者：
Oki, Mitsuaki;Kaneko, Satoshi;Kusaka, Hirofumi
为了研究左旋多巴给药方式和唑尼沙胺 (ZNS) 作用的结果差异，我们分析了帕金森模型大鼠纹状体中多巴胺能和非多巴胺能受体的 mRNA 表达与左旋多巴诱导的运动障碍 (LID) 发生的关系。将单侧帕金森模型大鼠分为4组：不用药（N组）、持续左旋多巴输注（C组）、间歇性左旋多巴注射（I组）、间歇性左旋多巴联合ZNS注射（Z组）。治疗两周后，I、Z组出现LID，Z组较轻。I、Z组D1、D2受体mRNA表达均升高，C组仅D2受体mRNA表达升高。仅I组腺苷A2A受体mRNA表达升高。N、C、I组内源性大麻素CB1受体mRNA表达升高，Z组无升高。 注射左旋多巴引起 LID，与 D1 和 A2A 受体表达升高有关。 ZNS 改善 LID 的发展并抑制 A2A 和 CB1 受体的上调。这些受体的调节可能会导致运动障碍的治疗方法。 (C) 2017 Elsevier Ireland Ltd 和日本神经科学学会。版权所有。
To investigate the difference in results according to the mode of levodopa administration and the effect of zonisamide (ZNS), we analyzed the mRNA expression of dopaminergic and non-dopaminergic receptors in the striatum of Parkinson model rats in relation to the development of levodopa-induced dyskinesia (LID). Unilateral Parkinson model rats were subdivided into 4 groups and treated as follows: no medication (group N), continuous levodopa infusion (group C), intermittent levodopa injection (group I), and intermittent levodopa and ZNS injection (group Z). Two weeks after the treatment, LID was observed in group I and Z, but less severe in group Z. The level of both D1 and D2 receptor mRNAs was elevated in groups I and Z, but only D2 receptor mRNA expression was elevated in group C. Adenosine A2A receptor mRNA showed increased expression only in group I. The level of endocannabinoid CB1 receptor mRNA was elevated in groups N, C, and I, but not in group Z. Intermittent injection of levodopa caused LID, in association with elevated expression of D1 and A2A receptors. ZNS ameliorated the development of LID and inhibited up-regulation of A2A and CB1 receptors. Modulation of these receptors may lead to therapeutic approaches for dyskinesia. (C) 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.