Zonisamide-induced long-lasting recovery of dopaminergic neurons from MPTP-toxicity
Zonisamide-induced long-lasting recovery of dopaminergic neurons from MPTP-toxicity
复制标题
DOI：
10.1016/j.brainres.2011.02.017
复制
发表时间：
2011-04-12
期刊：
影响因子：
2.9
通讯作者：
Nomoto, Masahiro
中科院分区：
文献类型：
--
作者：
Choudhury, Mohammed Emamussalehin;Moritoyo, Takashi;Nomoto, Masahiro
唑尼沙胺是一种抗癫痫药物，也可以改善帕金森病的主要症状。本研究探讨唑尼沙胺对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）处理的小鼠多巴胺能神经元变性的影响。如下处理六组小鼠：1）生理盐水; 2）MPTP，15 mg/kg × 4，每2小时; 3）MPTP和唑尼沙胺，40 mg/kg × 1，最后一次MPTP剂量后1小时; 4）MPTP和唑尼沙胺，最后一次MPTP剂量后1天; 5）MPTP和唑尼沙胺，第一次MPTP剂量前1小时;和6）唑尼沙胺，40 mg/kg。MPTP处理后多巴胺含量降低，酪氨酸羟化酶（TH）阳性神经元的数量和面积减少。与唑尼沙胺和MPTP同时治疗的小鼠在治疗后1周没有表现出任何抑制MPTP对多巴胺含量的毒性作用，但与MPTP治疗组相比，其增加TH阳性神经元的数量和面积。存活的TH阳性神经元在几周后恢复了多巴胺的产生。此外，唑尼沙胺增加S100 β阳性和胶质细胞酸性蛋白（GFAP）阳性星形胶质细胞的数量和多巴胺周转。这些结果表明，唑尼沙胺作为一种神经保护剂，对MPTP诱导的多巴胺能神经元变性所示的TH阳性神经元的增加，这可能是介导的增加S100 β分泌。(C)2011 Elsevier B. V.保留所有权利。
Zonisamide is an antiepileptic drug that also improves the cardinal symptoms of Parkinson's disease. This study investigated the effects of zonisamide on dopaminergic neuronal degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Six groups of mice were treated as follows: 1) normal saline; 2) MPTP, 15 mg/kg x 4 every 2 h; 3) MPTP and zonisamide, 40 mg/kg x 1, 1 h after the last MPTP dose; 4) MPTP and zonisamide, 1 day after the last dose of MPTP; 5) MPTP and zonisamide, 1 h before the first MPTP dose; and 6) zonisamide, 40 mg/kg. MPTP-treatment decreased the contents of dopamine as well as the number and area of tyrosine hydroxylase (TH)-positive neurons. Concurrent treatment of mice with zonisamide and MPTP did not show any inhibition of the toxic effect of MPTP towards dopamine contents at 1 week after treatment but it increased the number and area of TH-positive neurons compared to the MPTP-treated group. Surviving TH-positive neurons had recovery of dopamine production after several weeks. Moreover, zonisamide increased the number of S100 beta-positive and glial fibrillary acidic protein (GFAP)-positive astrocytes and dopamine turnover. These results suggest that zonisamide acts as a neuro-protectant against MPTP-induced dopaminergic neuronal degeneration as shown by an increase of TH-positive neurons and this may be mediated by increased S100 beta secretion. (C) 2011 Elsevier B.V. All rights reserved.