环境铅暴露所致神经系统损害一直是备受关注的公共卫生问题，其中大脑学习记忆损害过程机制最有吸引力和最具挑战性。本项目组根据国内外最新研究现状，结合自身长期铅神经毒性研究结果以及本项目前期研究预示，提出铅暴露可能作用于SIRT1/ERK，从而改变MEF2磷酸化和乙酰化的共价变构修饰引起突触生长障碍，进一步损害学习记忆的科学假设。拟采用qRT-PCR、蛋白印迹、免疫共沉淀等分子生物学技术以及膜片钳电生理技术等，在生命不同阶段，从不同水平上全面地研究铅暴露对 SIRT1/ERK-MEF2-Arc、synGAP通路的影响，从正向和反向研究SIRT1/ERK变构修饰MEF2对学习记忆有关基因表达的影响。期冀解决SIRT1/ERK变构修饰控制突触生长的MEF2在铅致学习记忆损害分子机制中作用的有关问题，为揭示铅暴露所致学习记忆损害分子机制提供新思路、新途径，为预防和干预铅暴露所致神经损害提供新靶点。

It has been concerned in the public health that environmental lead (Pb) exposure caused nervous system damages include intelligence developmental defects, children with ADHD, Alzheimer's disease and neurodegeneration. One of the brain damage processes of learning and memory mechanism is the most attractive and most challenging problems. According to latest research findings in neuroscience at domestic and overseas, combined with our own long-term research results of Pb-induced neurological damage and based on this project prophase research, we propose the scientific hypothesis that the effects of lead exposure on SIRT1 / ERK may change MEF2 phosphorylation and acetylated modification of covalent allosteric, subsequently induce synaptic growth disorder and cause further damage to the learning and memory. In this project, applying cellular and molecular techniques and patch clamp amplifier system, as well as morphologic quantitative analysis and so on, we will try to elucidate that the influence of lead exposure on SIRT1 / ERK - MEF2 - Arc, synGAP signaling pathways in integral, cellular and molecular level, and SIRT1 / ERK allosteric modified MEF2 affect on gene expression of learning and memory from reverse and forward. Our study will give additional information to reveal the lead neurotoxicity mechanism, provide new clues to discover the new target for lead intoxication prevention and treatment and offer new ideas to the further related researches on molecular mechanism of learning and memory impaired by heavy metals.