CRMP-1调控神经元骨架蛋白重构在癫痫发作中的机制研究

项目名称： CRMP-1调控神经元骨架蛋白重构在癫痫发作中的机制研究

项目编号： No.81501122

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 罗晶

作者单位： 重庆医科大学

项目金额： 17.5万元

中文摘要： 大多数癫痫发作都具有遗传元素背景，对癫痫进行的表观遗传学研究发现DNA甲基化参与了癫痫的发生发展，并逐渐成为癫痫研究的新领域。通过全基因组DNA甲基化芯片扫描，课题组发现参与调节轴突导向的坍塌反应调节蛋白（CRMP-1）在癫痫患者脑组织中甲基化程度增高，点燃动物模型中也发现类似结果。本项目拟在国家自然科学基金委前期资助项目《调控沉默基因及突触激活的miRNA在耐药性癫痫形成中的作用》研究基础上，继续利用课题组建立的由300多例耐药性癫痫患者手术后脑组织组成的脑库和4种癫痫动物模型，通过对点燃癫痫动物模型脑内CRMP-1基因进行敲除、过表达干预，结合在体多通道脑电监测，同时采用转染、细胞骨架蛋白染色、全细胞膜片钳等技术从基因表达、功能、机制三个层面进一步探索CRMP-1在癫痫发作中的作用及其信号通路，建立基因-靶点-疾病链，以揭示其调控癫痫发生的可能机制，为癫痫的防治提供新思维和路径。

中文关键词： CRMP-1；基因调控；发病机制；癫痫

英文摘要： A current accepted concept is that most epileptic seizures due to genetics background, study of epigenetic mechanisms in epilepsy has found that DNA methylation may plays an important part in epileptogenesis. By DNA methylation screening in the brain of refractory epilepsy and theoretical bioinformatics analysis of differentially expressed genes, we have found that the mythylation level of collapse response regulatory proteins(CRMP-1) in regulating axon guidance is higher in epileptic brain than control brain, and the same result was found in animal model. Under the support of National Natural Science Foundation of China, we have finished the project of: The role of miRNAs in regulating genes silecne and synaptic activation in the formation of drug-resistant epilepys. We have found a brain tissue bank which contains more than 300 cases of brain tissues from patients who received surgery for intractable epilepsy and we also successfully established many kinds of epilepsy animal models. Using the in vivo multi-channel recording methods for EEG with methods of transfection, fluorescent staining of the actin cytoskeleton and electrophysiology (patch-clamp), to evaluated weather the CRMP-1 can modifying the epileptic seizure and epileptiform discharge of rat models through gene knock-down and over-expression.This study will investigate the role of CRMP-1 in epileptogenesis and explore their effects on downstream signaling, aimed to establish a regulating gene-target-disease chain, and uncover their potential mechanisms in epileptogenesis.

英文关键词： CRMP-1; gene regulation ; pathogenesis ;epilepsy