中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (9): 951-958.doi: 10.4103/1673-5374.133146

• 原著:退行性病与再生 • 上一篇    下一篇

敲除α-突触核蛋白减少甲基苯丙胺诱导多巴胺能神经元的凋亡神经毒性的保护作用

  

  • 收稿日期:2014-03-24 出版日期:2014-05-20 发布日期:2014-05-20
  • 基金资助:

    中国国家自然科学基金项目 (81072506)

Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons

Yunchun Tai 1, Ling Chen 1, Enping Huang 1, Chao Liu 1, 2, Xingyi Yang 1, Pingming Qiu 1, Huijun Wang 1   

  1. 1 Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China
    2 Guangzhou Forensic Science Institute, Guangzhou, Guangdong Province, China
  • Received:2014-03-24 Online:2014-05-20 Published:2014-05-20
  • Contact: Pingming Qiu, Ph.D., Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China, qiupm@163.com. Huijun Wang, Ph.D., Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China, hjwangcz@21cn.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81072506.

PDF

1044

摘要：

α-突触核蛋白过表达是甲基苯丙胺诱导的帕金森病模型中多巴胺能神经元死亡的主要因素。我们将α-syn-shRNA慢病毒立体定向注射到大鼠右侧纹状体中，2周后腹腔注射甲基苯丙胺建立帕金森病模型，发现右侧纹状体注射α-syn-shRNA慢病毒的大鼠右侧纹状体中α-syn mRNA和蛋白的表达显著下降，且这种敲除α-突触核蛋白的帕金森病模型大鼠食物摄入量和体质量增加，而水摄入量和刻板行为评分降低，纹状体中多巴胺水平和酪氨酸羟化酶及超氧化物歧化酶活性显著增加，但活性氧生成量、一氧化氮合酶活性、一氧化氮含量和丙二醛含量下降，同时纹状体中凋亡细胞的数量明显减少。结果提示α-突触核蛋白具有通过抑制氧化应激和改善多巴胺能系统功能减少甲基苯丙胺诱导纹状体多巴胺能神经元凋亡的作用。

关键词: 神经再生, α-突触核蛋白, 帕金森病, 甲基苯丙胺, 多巴胺能神经元, 神经毒性, 纹状体, 氧化应激, 细胞凋亡, NSFC grant

Abstract:

The over-expression of α-synuclein is a major factor in the death of dopaminergic neurons in a methamphetamine-induced model of Parkinson’s disease. In the present study, α-synuclein knockdown rats were created by injecting α-synuclein-shRNA lentivirus stereotaxically into the right striatum of experimental rats. At 2 weeks post-injection, the rats were injected intraperitoneally with methamphetamine to establish the model of Parkinson’s disease. Expression of α-synuclein mRNA and protein in the right striatum of the injected rats was significantly downregulated. Food intake and body weight were greater in α-synuclein knockdown rats, and water intake and stereotyped behavior score were lower than in model rats. Striatal dopamine and tyrosine hydroxylase levels were significantly elevated in α-synuclein knockdown rats. Moreover, superoxide dismutase activity was greater in α-synuclein knockdown rat striatum, but the levels of reactive oxygen species, malondialdehyde, nitric oxide synthase and nitrogen monoxide were lower compared with model rats. We also found that α-synuclein knockdown inhibited methamphetamine-induced neuronal apoptosis. These results suggest that α-synuclein has the capacity to reverse methamphetamine-induced apoptosis of dopaminergic neurons in the rat striatum by inhibiting oxidative stress and improving dopaminergic system function.

Key words: nerve regeneration, α-synuclein, Parkinson’s disease, methamphetamine, dopaminergic neurons, neurotoxicity, striatum, oxidative stress, apoptosis, NSFC grant, neural regeneration