{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:01:44Z","timestamp":1792101704008,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,8,23]],"date-time":"2010-08-23T00:00:00Z","timestamp":1282521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\/\u03b2\u2010catenin 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 <jats:italic>wnt1<\/jats:italic> and <jats:italic>wnt2<\/jats:italic>, but not in those of Wnt inhibitory factor\u20101 and <jats:italic>Dickkopf 1<\/jats:italic>, in the prefrontal cortexes and hippocampi of the offspring. Consequently, both mRNA and protein expression of <jats:italic>wnt1<\/jats:italic> and <jats:italic>wnt2<\/jats:italic> were increased. Furthermore, the activity of Wnt\/\u03b2\u2010catenin pathway was upregulated, as indicated by the increased levels of \u03b2\u2010catenin, 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. Anat Rec, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ar.21232","type":"journal-article","created":{"date-parts":[[2010,8,29]],"date-time":"2010-08-29T00:11:17Z","timestamp":1283040677000},"page":"1947-1953","source":"Crossref","is-referenced-by-count":48,"title":["Demethylation of Specific Wnt\/\u03b2\u2010Catenin Pathway Genes and its Upregulation in Rat Brain Induced by Prenatal Valproate 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