低剂量铅暴露在小胶质细胞对神经突触修饰中的作用及机制研究

项目名称： 低剂量铅暴露在小胶质细胞对神经突触修饰中的作用及机制研究

项目编号： No.81472942

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘明朝

作者单位： 中国人民解放军第四军医大学

项目金额： 65万元

中文摘要： 铅具有很强的神经毒性，在极低剂量时也可引起儿童认知缺陷。小胶质细胞是CNS免疫细胞，研究显示，小胶质细胞在生理状况下也不可或缺。如对冗余突触的修剪；促进新突触生成等。在铅暴露诱导认知损伤及正常突触功能障碍的过程中，小胶质细胞可能因铅暴露导致功能异常从而可能发挥了重要的作用。基于前期研究我们提出如下假设：①低剂量铅暴露可以产生神经毒性，导致学习记忆功能损害；②低剂量铅暴露对认知功能的损伤可能同时涉及到冗余突触修剪功能的障碍及新突触生成功能的障碍；而这一过程的异常可能是铅导致神经毒性及认知损伤的重要环节；③小胶质细胞在上述损伤过程中可能是低剂量铅暴露干扰了小胶质细胞对冗余突触的修剪以及对新突触生成的促进作用，从而最终导致学习记忆功能损害。若能够证实小胶质细胞功能异常在铅暴露所致神经毒性及学习记忆能力损伤中的作用，阐明其分子机制，将对进一步阐明铅对认知损伤的机制及防护措施具有重要意义。

中文关键词： 铅；海马；认知；突触可塑性；小胶质细胞

英文摘要： Studies have confirmed that lead is highly neurotoxic. It can cause brain damage and cognitive defects in children at very low doses. Microglia is a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system (CNS). Recent studies demonstrated that microglia paly more roles more than an immune cell in CNS, in physiological condition, microglia are conformed be a key role in synaptic stripping and formation. In the process of lead exposure-induced cognitive impairment and normal synaptic dysfunction, microglia may lose their normal function on synaptic caused by lead exposure and then play an important rolein this cognitive impairment and synaptic dysfunction. Based on preliminary studies we propose the following hypothesis: low dose lead exposure can produce neurotoxicity, resulting in learning and memory dysfunction; low doses of lead exposure on cognitive disfunction may both implicated with redundant synaptic pruning abnormal and new synaptic formation abnormal, while this process maybe a key point on lead induced neurotoxicity and cognitive impairment; microglia may be interfed by low-dose lead exposure and lose their normal function on synaptic stripping and formation in the process of lead induced neurotoxicity and cognitive impairment, which ultimately leads to learning and memory dysfunction. It will be benefit on further understanding the mechanism of lead induced cognitive disfunction and provide new protective methods if we can clarify the effect of microglia dysfunction on lead induced neurotoxicity and learning and memory injury and its molecular mechanism.

英文关键词： lead;hippocampus;cognition;synaptic plasticity;microglia