Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells

Journal of Biomedical Science

Research

Hae Rang Bak¹  Hyo Sang Go¹  Kwang Ho Ko¹  So Min Han¹  Ki Chan Kim¹  Pitna Kim²  Seol-Heui Han²  Chang Soon Choi²  Chan Young Shin²  Inha Choi² 

[1] Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, Korea;School of Medicine and Center for Neuroscience Research, IBST, Konkuk University, Korea;

关键词: Neuronal Differentiation;    Fetal Alcohol Spectrum Disorder;    Fetal Alcohol Spectrum Disorder;    Ethanol Treatment;    Fluorescent Activate Cell Sort Analysis;   

DOI  :  10.1186/1423-0127-17-85

 received in 2010-08-03, accepted in 2010-11-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPrenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD). The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC) and in vivo FASD models.MethodsNeural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4 g/kg/day) diluted with normal saline from E7 to E16 for in vivo FASD animal models. Expression level of proteins was investigated by western blot analysis and immunocytochemical assays. MTT was used for cell viability. Proliferative activity of NPCs was identified by BrdU incorporation, immunocytochemistry and FACS analysis.ResultsReduced proliferation of NPCs by ethanol was demonstrated using BrdU incorporation, immunocytochemistry and FACS analysis. In addition, ethanol induced the imbalance between glutamatergic and GABAergic neuronal differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD with concomitant decrease in the expression of Mash1. Similar pattern of expression of those transcription factors was observed using an in vivo model of FASD as well as the increased expression of PSD-95 and decreased expression of GAD67.ConclusionsThese results suggest that ethanol induces hyper-differentiation of glutamatergic neuron through Pax6 pathway, which may underlie the hyper-excitability phenotype such as hyperactivity or seizure susceptibility in FASD patients.

【 授权许可】

Unknown   
© Kim et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.