发育关键期双酚A暴露对神经突触功能的影响及机理研究

项目名称： 发育关键期双酚A暴露对神经突触功能的影响及机理研究

项目编号： No.21307024

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 环境科学、安全科学

项目作者： 胡繁

作者单位： 合肥工业大学

项目金额： 25万元

中文摘要： 在日常生活中广泛使用的化工原料双酚A是一种内分泌扰乱剂，会引起多种疾病发病率的增高。近年来研究发现，双酚A暴露导致幼年大鼠学习记忆能力的下降和多动症的发生，但对于内在生理变化基础以及分子机理知之甚少。本项目拟以发育关键期大鼠和离体海马神经元为实验对象，采用膜片钳记录、双光子显微成像等实验方法，从以下几个方面较为系统地研究双酚A导致中枢神经系统损伤的机制：1、研究双酚A对海马神经元电生理反应特性的影响，特别是对兴奋性和抑制性突触传递的影响，探索造成这些变化的可能机制，为相关行为特征改变提供生理学证据；2、研究不同时程双酚A暴露对树突形态的影响，验证电生理特性变化的结构基础；3、利用分子生物学手段，探索双酚A引起树突形态改变的可能分子途径。本研究将为双酚A安全剂量标准的制定提供参考依据，也为临床分析和防治双酚A对儿童中枢系统的影响提供重要的生理基础和实验依据。

中文关键词： 双酚A；海马；前额叶；认知能力；突触

英文摘要： Bisphenol A, a kind of endocrine disrupter, always causes side-effect on human several system due to its extensivly enviornmental exposure. Recently, lots of studies showed that Bisphenol A exposure could induce the hyperactivity and decrease of memory ability on the juvenile rodents, but its physiological change and underlying mechanism are almost unknown. The present study will explore whether developmental Bisphenol A exposure induces synaptic alteration and clarify its underlying mechanisms by patch-clamp technology,two-photo micrscopic imaging and morphological staining methods. Firstly, the change of electrophysiological properties, especially,the excitatory and inhibitory synaptic transmission will be detected after low dose Bisphenol A exposure by patch-clamp recording. It will provide physiologcial evidence to explain the Bisphenol-A related behavior change. Secondly,the morphological alteration of neurons will be examined by two-photon and laser confocal microscopic imaging technology in real-time observation and thus explain the structural basis of the physiological functions change.It also could disovle the debate on the alteration of spine density after Bisphenol-A exposure. Thirdly, the alteration expression or activity of proteins, which could regulate the remodeling of synaptic str

英文关键词： Bisphenol A；hippocampus；mPFC；cognitive ability；synapse