丙戊酸孤独症大鼠脑中经典Wnt信号通路的变化  

Changes of canonical Wnt signaling pathway in brains of rats with autism induced by prenatal exposure to valproic acid

作　　者：张应花[1] 邓晓慧[1] 王中平[2,3] 崔卫刚[1,2] 文小军[1] 李瑞锡[2] 

机构地区：[1]新乡医学院解剖教研室,河南新乡453003 [2]复旦大学上海医学院人体解剖与组织胚胎学系,上海200032 [3]九江学院基础医学院生理学与病理生理学教研室,江西九江332000

出　　处：《中国病理生理杂志》2014年第8期1394-1399,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81301174;No.81260211);新乡医学院博士科研启动基金资助项目(No.505003)

摘　　要：目的:探讨经典Wnt信号通路在孤独症发病中的作用。方法:利用丙戊酸孤独症大鼠模型,检测经典Wnt信号通路信号分子在孤独症大鼠前额叶皮质及海马脑区的表达。Western blotting法检测糖原合成酶激酶3β(glycogen synthase kinase 3β,GSK-3β)、磷酸化GSK-3β、β-catenin和磷酸化β-catenin表达,半定量RT-PCR法检测GSK-3β、β-catenin、c-Myc和cyclin D1 mRNA表达。结果:与对照组相比,在丙戊酸孤独症大鼠前额叶皮质及海马脑区,失活的GSK-3β磷酸化表达显著增加,抑制性的β-catenin磷酸化表达显著减少;GSK-3βmRNA表达减少,β-catenin mRNA表达增加,下游c-Myc和cyclin D1 mRNA表达增加。结论:前额叶皮质及海马中经典Wnt信号通路活性增加可能促进了机体对孤独症的易感性。[ABSTRACT]AIM：ToinvestigatetherolesofthecanonicalWntpathwayinautism.METHODS：Usinganau-tistic model induced by prenatal exposure to valproic acid （ VPA） , we detected the expression of the signaling molecules of the canonical Wnt pathway in the prefrontal cortex （PFC） and hippocampus formation （HF） of autistic rats.The expres-sion levels of glycogen synthase kinase 3β（ GSK-3β） , phosphorylated GSK-3β, β-catenin and phosphorylated β-catenin were observed by Western blotting .The mRNA expression of GSK-3β, β-catenin, c-Myc and cyclin D1 was assessed by semi-quantitative RT-PCR.RESULTS：The results of Western blotting showed that inactivated GSK-3β（Ser9） phospho-rylation was significantly increased , and inhibitory β-catenin （ Ser33/37/Thr41 ） phosphorylation was obviously decreased compared with control group .The results of RT-PCR showed that the mRNA levels of β-catenin, c-Myc and cyclin D1 in-creased, and GSK-3βwas significantly enhanced in VPA-exposed rats compared with the controls .CONCLUSION： In-creased activity of canonical Wnt pathway in the PFC and HF of autistic rats may contribute to the susceptibility to autism .

关 键 词：孤独症 WNT信号通路 丙戊酸 

分 类 号：R363[医药卫生—病理学]