Valproate induces upregulation of Wnt/β-catenin pathway through DNA demethylation in primary cultured neurons

Wang Zhongping; Chen Mingjun; Xu Li; Li Ruixi

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Valproate induces upregulation of Wnt/β-catenin pathway through DNA demethylation in primary cultured neurons

Wang Zhongping,Chen Mingjun,Xu Li,Li Ruixi *

Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University

*Correspondence author

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Funding: Sponsored by the Ministry of Education of China （No.No. 20070246184）

Opened online: 1 February 2011

Accepted by: none

Citation: Wang Zhongping,Chen Mingjun,Xu Li.Valproate induces upregulation of Wnt/β-catenin pathway through DNA demethylation in primary cultured neurons[OL]. [ 1 February 2011] http://en.paper.edu.cn/en_releasepaper/content/4407902

Valproate (valproic acid, VPA) has been well used in treatment of the epilepsy. However, maternal administration of VPA early in pregnancy will remarkably increase susceptibility in the offspring to autism spectrum disorders (ASDs). It is proposed that dysregulation of Wnt/β-catenin pathway is an underlying mechanism. In the present study we observed that VPA treatment in primary cultured neurons significantly induced demethylation in the promoter region of the gene of wnt1 but not Wnt inhibitory factor -1 (WIF-1). Wnt1 mRNA expression was concomitantly increased, displaying correlation with the promoter region demethylation level. Furthermore, western blot showed significant overexpression of Wnt1 and β-catenin in the VPA treated neurons compared with control. We also observed that VPA treatment promoted neuronal growth, manifesting as significant increment of number of neurite branches and total neurite length in comparison with control neurons. We concluded that VPA induced upregulation of Wnt/β-catenin pathway through DNA demethylation in primary cultured neurons and further promotes neuronal neurite complexity.

Keywords:cultured neuron;Wnt pathway;autism

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