Document Detail


Demethylation of specific Wnt/β-catenin pathway genes and its upregulation in rat brain induced by prenatal valproate exposure.
MedLine Citation:
PMID:  20734317     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Valproate (VPA) has been used for decades in the treatment of epilepsy and migraine. However, maternal administration of VPA during pregnancy increases susceptibility to autism spectrum disorders (ASDs) in the offspring. The aim of this study was to investigate the methylation modification and its effects on the activity of Wnt/β-catenin pathway in the rat brain prenatally exposed to VPA. We exposed the rats in early pregnancy to VPA and found that the prenatal VPA exposure, in comparison with the prenatal vehicle exposure, induced demethylation in the promoter regions of wnt1 and wnt2, but not in those of Wnt inhibitory factor-1 and Dickkopf 1, in the prefrontal cortexes and hippocampi of the offspring. Consequently, both mRNA and protein expression of wnt1 and wnt2 were increased. Furthermore, the activity of Wnt/β-catenin pathway was upregulated, as indicated by the increased levels of β-catenin, hence the growing expression of its target genes. This work suggested an epigenetic action via which VPA, when administered in early pregnancy, induced dysregulation of signaling pathway, further facilitating susceptibility to ASDs.
Authors:
Zhongping Wang; Li Xu; Xinping Zhu; Weigang Cui; Yan Sun; Hisao Nishijo; Yuwen Peng; Ruixi Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anatomical record (Hoboken, N.J. : 2007)     Volume:  293     ISSN:  1932-8494     ISO Abbreviation:  Anat Rec (Hoboken)     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101292775     Medline TA:  Anat Rec (Hoboken)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1947-53     Citation Subset:  IM    
Affiliation:
Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai, China.
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