- 作者: Ki Chan Kim; Hyo Sang Go; Hae Rang Bak; Chang Soon Choi; Inha Choi; Pitna Kim; Seol-Heui Han; So Min Han; Chan Young Shin; Kwang Ho Ko
- 作者服務機構: Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, Korea
- 中文摘要: --
- 英文摘要:
Background: Prenatal 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.
Methods: Neural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice
and rats were treated with ethanol (2 or 4g/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.
Results: Reduced 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. Conclusions: These 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. - 中文關鍵字: --
- 英文關鍵字: --