海马神经元细胞膜雄激素结合位点及其介导的雄激素对海马突触可塑性影响的研究

项目名称： 海马神经元细胞膜雄激素结合位点及其介导的雄激素对海马突触可塑性影响的研究

项目编号： No.31471145

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生理学与整合生物学

项目作者： 崔慧先

作者单位： 河北医科大学

项目金额： 85万元

中文摘要： 雄激素下降是老年男性患阿尔茨海默病的危险因素之一，雄激素经传统基因组途径发挥神经保护作用的研究较为充分，但是不依赖于传统基因组途径的非基因组效应尚不清楚。细胞膜上雄激素结合位点的确定是明确其非基因组效应的关键，在以往的研究工作中本课题组发现海马神经元雄激素膜受体存在的初步证据，在此基础上进一步验证海马神经元雄激素膜受体的存在、与胞内受体的异同点以及表达膜受体的神经元类型。之后，明确雄激素非基因组途径对海马神经元突触可塑性的影响，并阐明其作用机制，以期充分理解雄激素发挥生理作用的方式，为进一步推动雄激素神经保护机制的研究提供突触可塑性方面的依据，也为临床应用雄激素制剂防治老年性痴呆提供理论基础。

中文关键词： 突触可塑性；雄激素；非基因组效应；膜受体；信号转导

英文摘要： Androgen has been shown rapidly activate independent of the classical genomic model which can be considered non-genomic action though a membrane associated androgen receptor (mAR). Based on older men with low serum levels of circulating testosterone appear to be at a higher risk of developing AD compared to men with normal levels of this hormone, and the discoveries that the distribution of androgen receptor in hippocampal formation, as well as the hypothesis which androgen are synthesize from cholesterol locally in hippocampal neurons. Although the character of mAR is still unclear, it is possible to explore the existing evidence of mAR. This study will determine the presence and specificity of membrane androgen binding sites and visualize neurons, including both excitatory and inhibitory neurons, expressed membrane binding sites for androgen. Afterward, we will discuss the probably mechanism from molecular to cells level, and find the possible signal transduction pathways, to provide theoretical basis on synaptic plasticity for exploring the relationship between androgen and memory and learning. Further knowledge on the nature of mAR and its signaling pathways can be helpful for understanding the function of androgen and provide targets for development of brain selective androgen receptor modulators for prevention of neurodegenerative disease and provides a valuable theoretical basis for a discussion on synaptic plasticity.

英文关键词： synaptic plasticity;androgen;nongenomic effect;membrane receptor;signal transduction