α-Synuclein蛋白过表达对小鼠纹状体的影响  

Effects of α-Synuclein Protein Overexpression on Mice Striatum

作　　者：段晋燕[1] 刘可夫[1] 张永谦[1] 张彦彦[1] 庆宏[1] 邓玉林[1] 

机构地区：[1]北京理工大学生命学院,北京100081

出　　处：《科技导报》2014年第7期22-26,共5页Science & Technology Review

基　　金：国家科技重大专项(2012YQ040140)

摘　　要：帕金森病是世界第二大老年神经退行性疾病,致病机理极为复杂。α-synuclein(α-syn)是帕金森病主要病理特征的路易小体的主要组成成分,其突变基因α-syn A30P也与部分家族性帕金森相关。通过对过表达野生型人源α-syn WT及其突变体α-syn A30P蛋白的转基因小鼠的行为学检验、脑部纹状体中氧化应激水平以及儿茶酚胺异喹啉物质水平的检测,研究过表达α-syn蛋白对小鼠纹状体产生的影响。结果显示转基因小鼠模型与正常鼠相比,其协调能力明显下降,纹状体与全脑的比例显著降低。同时,模型鼠脑中的氧化应激水平与儿茶酚胺异喹啉物质的表达水平均显著升高。研究结果说明,α-syn蛋白及其突变体的过表达会引起小鼠脑部纹状体中氧化应激水平与儿茶酚异喹啉物质表达水平的升高,从而导致纹状体组织严重损伤。Parkinson＇s disease （PD） is a common progressive neurodegenerative syndrome. The α-synuclein （α-syn）is a major protein constituent of Lewy bodies, and the α-syn A30P mutant causes familial autosomal dominant PD. In the present study, we explored the effect of α-syn overexpression and its mutant α-syn A30P on mice striatum. The behavior of PDGF-h α-synucleinWT and PDGF-h α-synuclein^A30P transgenic mice was investigated, and the oxidative stress levels and the concentration of catecholamine isoquinolines （CAIQs） were determined in transgenic mice striatum, respectively. Compared to the control group, the coordination abilities of the two types of transgenic mice decreased. In addition, the level of oxidative stress and the concentration of CAIQs significantly increased in the overexpression of α-syn WT and α-syn A^30P mice striatum. Thus, it is concluded that overexpression of α-syn and its mutant α-syn A30P exhibit impairment in the striatum through increasing the level of oxidative stress and CAIQs.

关 键 词：帕金森病 α-synuclein蛋白 纹状体 氧化应激 儿茶酚异喹啉类物质 

分 类 号：R742.5[医药卫生—神经病学与精神病学]