Vezatin参与调控癫痫中CP-AMPAR所介导的神经元突触效应的分子机制研究

癫痫是一种发病机制十分复杂的慢性脑部疾病，目前其具体发病机制仍不清楚。本研究在前期实验中发现：突触调节蛋白Vezatin在颞叶癫痫患者脑组织与匹鲁卡品小鼠癫痫动物模型海马区的表达水平均明显上调；下调Vezatin在小鼠海马区的表达后明显降低了匹鲁卡品小鼠癫痫动物模型的癫痫发作易感性，同时也抑制了海马区神经元Ca2+-permeable AMPAR（CP-AMPAR）所介导的突触传递活动。该前期实验结果为癫痫发病机制的研究找到了关键切入点。本研究拟在前期实验基础上，从神经元突触效应的角度出发，通过动物实验与细胞实验深入研究与探讨Vezatin参与调控癫痫中海马区CP-AMPAR所介导的异常神经元突触效应的潜在分子机制，以期揭示并回答Vezatin影响癫痫发生、发展的具体分子机制，从而为癫痫发病机制的研究提供新的证据，并有助于加深我们对癫痫发病机制的理解与认识。

Epilepsy is a chronic brain disease with a complicated pathogenesis. Although recent studies have investigated the underlying mechanism of epilepsy, it remains largely unclear and deserves further investigation. Our preliminary study suggested an important role of Vezatin in epilepsy: Vezatin was up-regulated in epileptic foci of patients with temporal lobe epilepsy and hippocampus of pilocarpine (PILO)-induced mouse models of epilepsy. Moreover, Vezatin silencing in the hippocampus exerted an antiepileptic effect on PILO-induced mouse models of epilepsy and suppressed Ca2+-permeable AMPAR (CP-AMPAR)-mediated aberrant synaptic events. Based on our preliminary experimental results, we hypothesized that Vezatin may regulate epileptic seizures by controlling CP-AMPAR-mediated neuronal synaptic efficacy. Here, to verify this hypothesis, we aimed to explore the underlying molecular mechanism of Vezatin in regulating CP-AMPAR-mediated aberrant neuronal synaptic efficacy in epilepsy by conducting vivo and vitro experiments. This study will provide a new insight for the pathogenesis of epilepsy and improve our understanding of the pathogenesis of epilepsy.