Lu Jianqing, Sun Feiyi, Ma Hong, Qing Hong, Deng Yulin
School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, People's Republic of China.
School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, People's Republic of China.
Biochem Biophys Res Commun. 2015 Sep 4;464(4):988-993. doi: 10.1016/j.bbrc.2015.07.007. Epub 2015 Jul 17.
Vector based over-expression of α-synuclein is a newly developed method to establish animal Parkinson's disease (PD) model. In this paper, we inject the rat brain with recombinant adeno-associated virus (rAAV) to express α-synuclein wild-type and A53T mutation, and compared the degeneration of dopaminergic neurons between them.
The rAAV vectors were injected into the substantia nigra pars compacta (SNpc) of rat brain. In different time point, immunohistochemistry was used to detect the expression of α-synuclein. The expression level was lower in the 3rd and 6th week and increased from the 9th week. α-synuclein spread around the neurons in SNpc in the 12th week. The loss of dopaminergic neurons was increasing along the expression of α-synuclein, and damage extent was more serious in the A53T group than the WT group. In the A53T group, there were more insoluble inclusions can be detected, and the phosphorylation of α-synuclein was also higher.
The result of comparison between the two types of α-synuclein showed that A53T mutated α-synuclein was more effective to establish PD model, and the model based A53T mutated α-synuclein was a suitable model to early-onset PD.
基于载体的α-突触核蛋白过表达是一种新开发的建立动物帕金森病(PD)模型的方法。在本文中,我们向大鼠脑内注射重组腺相关病毒(rAAV)以表达野生型和A53T突变型α-突触核蛋白,并比较二者之间多巴胺能神经元的退变情况。
将rAAV载体注射到大鼠脑黑质致密部(SNpc)。在不同时间点,采用免疫组织化学法检测α-突触核蛋白的表达。第3周和第6周时表达水平较低,从第9周开始升高。第12周时α-突触核蛋白在SNpc的神经元周围扩散。多巴胺能神经元的丢失随着α-突触核蛋白的表达而增加,且A53T组的损伤程度比野生型组更严重。在A53T组中,可检测到更多不溶性包涵体,且α-突触核蛋白的磷酸化水平也更高。
两种类型α-突触核蛋白的比较结果表明,A53T突变型α-突触核蛋白在建立PD模型方面更有效,基于A53T突变型α-突触核蛋白的模型适用于早发性PD。