雌激素受体alpha亚基118位点丝氨酸的磷酸化在大脑海马性别分化中的作用及机制

项目名称： 雌激素受体alpha亚基118位点丝氨酸的磷酸化在大脑海马性别分化中的作用及机制

项目编号： No.31260244

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 许晓彬

作者单位： 南昌大学

项目金额： 55万元

中文摘要： 出生后早期是大脑性别分化的关键时期，脑内雌激素在这段时期的产生与否在大脑性别分化中起着重要的作用，但对其中的的神经机理仍知之甚少。申请人近期的研究表明，雌激素受体alpha亚基118位点的丝氨酸磷酸化（P-ERa-ser118）仅在性分化关键期一过性出现，而出生后摄入环境雌激素bisphenol A（BPA）则可明显下调该磷酸化，并引起海马的异常性分化-即雌性雄性化和雄性雌性化（Xu X, et al，Neurotoxicol and Terotol, 2011）。我们据此推测，P-ERa-ser118可能在海马的性别分化中发挥重要作用。在本课题中，申请人拟运用基因定点突变、质粒转染以及行为学等技术，观察雌雄小鼠脑内P-ERa-ser118水平与海马性分化的相关关系，分析干预该磷酸化对海马性分化的可能影响，并探讨潜在的分子机制。本研究对于阐明大脑性别分化的机制具有重要的生物学意义。

中文关键词： 双酚A；海马；雌激素；磷酸化；少突胶质细胞

英文摘要： During the critical period of sexual differentiation in the rodent brain, whether estradiol is synthesized within the brain is critical in organizing some of the most salient and reliable sex differences, but the mechanism remains elusive. Our recent research showed that perinatal exposure to bisphenol A (BPA) can induce feminization of males and masculinization of females in hippocampus. Furthermore, we found that in hippocampus estrogen receptor phosphorylation at serine118 residue (P-ERa-ser118), which was observed only within the critical period of brain sexual differentiation, was down-regulated by early postnatal BPA exposure. The fact implies that P-ERa-ser118 may play a pivotal role in the process of hippocampus sexual differentiation. The object of the present research is: 1) to analyze the sexual difference in P-ERa-ser118 expression level in developing hippocampus; 2) to examine whether blocking the phosphorylation of the 118 site can disturb the hippocampus sexual difference, and 3) to search for the molecular pathway by which estrogen and environmental estrogen influence the sexual differentiation. This research will help clarify the mechanism of sexual differentiation of the whole brain.

英文关键词： bisphenol A；hippocampus；estrogen receptor；phosphorylation；oligodendrocyte