Go, Hyo Sang Kim, Ki Chan Choi, Chang Soon Jeon, Se Jin Kwon, Kyung Ja Han, Seol-Heui Lee, Jongmin Cheong, Jae Hoon Ryu, Jong Hoon Kim, Chong-Hyun Ko, Kwang Ho Shin, Chan Young 2024-01-20T13:34:33Z 2024-01-20T13:34:33Z 2021-09-04 2012-11 0028-3908 https://pubs.kist.re.kr/handle/201004/128744 Autism is a spectrum of neurodevelopmental disorders characterized by social isolation and lack of interaction. Anatomically, autism patients often show macrocephaly and high neuronal density. To investigate the mechanism underlying the higher neuronal populations seen in ASD, we subcutaneously injected VPA (400 mg/kg) into pregnant Sprague-Dawley rats on E12, an animal model often used in ASD study. Alternatively, cultured rat neural progenitor cells were treated with VPA. Until E18, VPA induced NPC proliferation and delayed neurogenesis in fetal brain, but the subsequent differentiation of NPCs to neurons increased brain neuronal density afterward. Similar findings were observed with NPCs treated with VPA in vitro. At a molecular level, VPA enhanced Wnt1 expression and activated the GSK-3 beta/beta-catenin pathway. Furthermore, inhibition of this pathway attenuated the effects of VPA. The findings of this study suggest that an altered developmental process underlies the macrocephaly and abnormal brain structure observed in the autistic brain. (C) 2012 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD AUTISM SPECTRUM DISORDERS MOOD-STABILIZING DRUGS CEREBRAL CORTICAL SIZE PROTEIN-KINASE-C MINICOLUMNAR PATHOLOGY NEURITE OUTGROWTH PREFRONTAL CORTEX SIGNALING PATHWAY UP-REGULATION SELF-RENEWAL Prenatal exposure to valproic acid increases the neural progenitor cell pool and induces macrocephaly in rat brain via a mechanism involving the GSK-3 beta/beta-catenin pathway Article 10.1016/j.neuropharm.2012.07.028 1 NEUROPHARMACOLOGY, v.63, no.6, pp.1028 - 1041 NEUROPHARMACOLOGY 63 6 1028 1041 scie scopus 000309438600012 2-s2.0-84865268274 Neurosciences Pharmacology & Pharmacy Neurosciences & Neurology Pharmacology & Pharmacy Article AUTISM SPECTRUM DISORDERS MOOD-STABILIZING DRUGS CEREBRAL CORTICAL SIZE PROTEIN-KINASE-C MINICOLUMNAR PATHOLOGY NEURITE OUTGROWTH PREFRONTAL CORTEX SIGNALING PATHWAY UP-REGULATION SELF-RENEWAL Nestin GSK-3 beta beta-Catenin Macrocephaly Autism