Wnt/β-catenin信号通路对孤独症模型大鼠重复呆板样行为的影响

Effects of Wnt/β- catenin on repetitive/stereotypic- like movements in an autistic model induced by prenatal exposure to valproic acid

目的探讨Wnt/β-catenin信号通路对孤独症发生过程中重复呆板样行为的影响。方法利用丙戊酸(valproic acid,VPA)孤独症动物模型,检测了经典Wnt信号通路关键信号分子β-catenin及其负性调节因子GSK-3β在孤独症模型大鼠小脑脑区的表达变化;同时检测孤独症模型大鼠重复呆板样行为变化。Western blotting法检测GSK-3β、β-catenin总蛋白及磷酸化蛋白表达,运用旷场实验检测重复呆板样行为持续的时间、次数。结果与对照组相比,在小脑脑区模型组GSK-3β磷酸化蛋白表达增加,β-catenin磷酸化蛋白表达减少;重复呆板样行为持续的时间、次数均增加。结论孤独症大鼠小脑脑区经典wnt信号通路活性增加,运动亢进,提示经典Wnt信号通路活性增加可能导致重复呆板样行为变化,进而导致对孤独症的易感性增加。

Objective To investigate the effects of Wnt/β-catenin on repetitive/stereotypic-like movements in autism. Methods With an autistic model induced by prenatal exposure to valproic acid （VPA）, we detected the expression of GSK-3β, β-eatenin, the signaling molecules of the canonical Wnt pathway in the cerebellum of autistic rats. The expression levels of GSK-3β, phosphorylated GSK-3β, β- catenin, phosphorylated β-catenin were observed by Western blotting. The number of repetitive/stereotypic-like behaviors and time engag6d in repetitive/stereotypic-like movements were observed by open field. Results The phospholated protein levels of GSK-3β were higher, whereas those of β-catenin were lower in VPA-exposed group than those in the control group. In contrast, the number of repetitive/stereotypic-like behaviors and time engaged in repetitive/stereotypic-like movements were significantly higher in the animals treated with VPA than those in the control group. Conclusion Hyperkinetics and increased activity of the canonical Wnt pathway in cerebellum of autistic rats suggest that increased activity of the canonical Wnt pathway may result in repetitive/stereotypic-like mobility disorders and further contribute to the susceptibility to autism.