铅暴露导致突触异常可能是铅损害学习和记忆行为的重要机制之一，铅暴露可导致NMDA、SV2C、BDNF、Syn和SNAP-25这些在维持突触形态和功能中起关键作用蛋白的mRNA水平下调。铅可通过干扰转录因子的转录活性来改变其调控的下游基因的转录。神经元限制性沉默因子（NRSF）是一个锌指蛋白转录抑制因子，它对含NRSE作用元件的基因产生抑制作用，根据生物信息学发现NMDA、SV2C、BDNF、Syn和SNAP-25启动子区含有NRSE作用元件，因此本项目在预实验基础上将进一步研究铅暴露对NRSF的表达和转录活性影响。明确铅是否通过影响NRSF的转录活性来调控NMDA、SV2C、BDNF、Syn和SNAP-25的转录水平，干扰NRSF表达是否能逆转铅对其转录水平的影响，这将进一步阐明铅的神经毒性分子机制和寻找新的治疗铅中毒药物有重要的理论和实际指导意义。

Lead exposure leads to synaptic abnormalities may be one of the important mechanism of Lead damage to learning and memory behavior. Lead exposure can lead to NMDA, SV2C,BDNF， Syn and SNAP-25 which play an important role in maintenance of synaptic morphology and function mRNA levels decrease. Lead can interfere the transcriptional activity of transcription factors and regulate downstream gene transcription. Neuron restrictive silencer factor (NRSF) is a zinc finger protein transcriptional repressor factor that represses or silences genes by recruitment to its cognate the neuron restrictive silencer element (NRSE) regulator sites.Using bioinformatics analysis, we found that NMDA, SV2C, BDNF, Syn and SNAP-25 promoters contained a NRSE regulator site. so based on the Preliminary experiments. we will explore that the effects of Lead on the expression and transcription activity of NRSF. We will ivestigate whether Lead regulates NMDA, SV2C, BDNF, Syn and SNAP-25 the transcriptional level through affectting NRSF transcription activity, Interfering NRSF expression whether can restore effect of Lead on the transcription level of NMDA, SV2C, BDNF, Syn and SNAP-25. This will further clarify the neurotoxicity of Lead molecular mechanisms and provide important theoretical and practical significance in looking for new treatment of Lead poisoning drugs.