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 .
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