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Changes of canonical Wnt signaling pathway in brains of rats with autism induced by prenatal exposure to valproic acid
Authors:ZHANG Ying-hua  DENG Xiao-hui  WANG Zhong-ping  CUI Wei-gang  WEN Xiao-jun  LI Rui-xi
Institution:1.Department of Human Anatomy, Xinxiang Medical University, Xinxiang 453003, China;2.Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 200032, China;3.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Jiujiang University, Jiujiang 332000, China.
Abstract:AIM:To investigate the roles of the canonical Wnt pathway in autism. METHODS:Using an autistic 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 expression 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) phosphorylation 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 increased, and GSK-3β was significantly enhanced in VPA-exposed rats compared with the controls. CONCLUSION:Increased activity of canonical Wnt pathway in the PFC and HF of autistic rats may contribute to the susceptibility to autism.
Keywords:Autism  Wnt signaling pathway  Valproic acid  
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