环境重金属污染是影响人们身心健康的突出环境问题之一。目前一般人群体内均可检测到一定剂量的铅、镉、汞等有害重金属，但在此剂量下的健康风险尚不明确。大脑对环境因素极敏感，任何时候接触环境有害重金属都可能导致神经结构或功能异常。本项目以我们长期研究的大脑最基本、最重要功能和特性之一的 “突触可塑性”为关键点；基于前期实验，拟从“神经元主动去甲基化”研究前沿切入，围绕“低剂量环境重金属暴露通过Tet的DNA去甲基化通路，调控AMPARs及其C末端调节蛋白的基因特异性表达，进而改变AMPARs膜转位，引起突触可塑性异常，导致认知障碍”的科学假说开展研究。拟采用甲基化特异性PCR、氧化重亚硫酸盐测序、免疫共沉淀、激光共聚焦、膜片钳、细胞定量分析等先进技术，从细胞、器官和整体动物水平，研究回答本项目所提出的关键科学问题，为防控环境重金属污染所致神经系统损害和疾病提供新思路，为寻找新的防治措施提供新途径。

Environmental heavy metal pollution is one of the prominent environmental problems that affect people's physical and mental health. At present, a certain dose of harmful heavy metals such as lead, cadmium and mercury can be detected in the general population, but the health risks at this dose are still not clear. The brain is extremely sensitive to environmental factors, and exposure to harmful heavy metals in the environment at any time can lead to structural or functional abnormalities in the brain. This project takes the synaptic plasticity, one of the most basic and important functions and characteristics of the brain that we have studied for a long time, as the key point. Based on previous experiments, we intend to cut into the frontier of “active demethylation in post-mitotic neurons” as a starting point, then conduct research around the scientific hypothesis about “low-dose environmental heavy metal exposure through Tet's DNA demethylation pathway, regulating the gene-specific expression of AMPARs and its C-terminal regulatory proteins, and thus changing the membrane translocation of AMPARs, causing abnormalities in synaptic plasticity, leading to cognitive impairment.” Advanced technologies such as methylation-specific PCR, oxidative bisulfite sequencing, immunoprecipidation, laser confocal, patch clamp and cell quantitative analysis will be applied to answer the key scientific questions raised in this project from the level of cells, organs and whole animals. Our research will provide new ideas for preventing and controlling nervous system damage and diseases caused by heavy metal pollution in the environment, and provide new ways to find new control measures.