谷氨酸引起神经细胞的兴奋性中毒是许多神经系统疾病的共同发病机制和病理变化，如急性颅脑损伤、中风、多发性硬化症、癫痫、脊髓侧索多发性硬化症、老年痴呆病等。抑制过量的谷氨酸释放和降低细胞外过量的谷氨酸可以减少兴奋性中毒引起的神经细胞死亡。先前研究表明小胶质细胞(microglia, MG)通过缝隙连接释放的谷氨酸是病理情况下过量谷氨酸的最主要来源，抑制MG谷氨酸的释放可以减少神经元的死亡，对神经系统疾病起治疗作用。但是MG通过哪一种缝隙连接蛋白（connexin, Cx）组成的缝隙连接释放谷氨酸尚未明确。本课题组的先前研究表明，MG主要表达Cx32和Cx43两种缝隙连接蛋白。本课题将应用Cx32和Cx43的基因敲除小鼠，分别在体外细胞和体内动物实验对MG通过缝隙连接释放过量谷氨酸的机制进行探明，并将用脑缺血和多发性硬化症的两种小鼠动物模型来检验抑制MG的Cx表达是否对中枢神经系统疾病有治疗作用

Glutamate-induced excitotoxicity is considered as a major cause of neuronal death in various neurological disorders such as trauma, ischemia, multiple sclerosis, epilepsy,amyotrophic lateral sclerosis, Alzheimer's disease. Blockade of glutamate release or down-regulation of the extracelluar excessive glutamate could provent neuron from excitotoxicity. Priverous studies showed that the microglia release excessive glutamate through gap junction, and blockade of microglial gap junction could suppresses neurological disorders. However it is unclear which connxin (Cx) is involved to microglial glutamate release. Our priverous experiments showed that microglia express Cx32 and Cx43. This study is aim to demostrate which Cx is involoved to microglial glutamate release by using Cx32 and Cx43 knock out mouse. Moverover the animal models of ischemia and multiple sclerosis will be used to verify if silence the microglial Cx gene could reduce the clinicl score of neurological disorders.This study will re-conceptualize and open new opportunities to develop much needed therapies for fatal neurological disorders.