SHANK3基因突变孤独症模型中枢兴奋抑制平衡变化的研究进展

Research progress on changes of central excitatory inhibitory balance in SHANK3 mutant model of ASD

编码SH3(Src homology domain 3)和多个锚蛋白重复结构域蛋白3(SHANK3)基因广泛分布于大脑的各个脑区,定位于兴奋性突触后致密部(postsynaptic density,PSD)。SHANK3基因不同位点突变的鼠类模型已被广泛构建,以模拟孤独症谱系障碍(autism spectrum disorder,ASD)的行为表现,探究异常行为背后的机制。各脑区的兴奋抑制平衡(E-I balance)是ASD的发生机制之一,与ASD的行为表现密切相关。SHANK3基因不同位点的突变可能会导致不同脑区E-I平衡的变化,从而产生ASD样行为。该文主要综述SHANK3基因不同位点突变ASD鼠类模型不同脑区E-I平衡的变化、与行为之间的联系及相关机制的研究进展,为SHANK3基因突变ASD鼠类模型的发病机制及干预的进一步深入研究提供借鉴。

The genes encoding SH3 and multiple anchor protein repeat domain protein 3(SHANK3)are widely distributed in various brain regions and are located in excitatory postsynaptic density(PSD).Mouse models of mutations at different loci of the SHANK3 gene have been extensively constructed to mimic the behavioral manifestations of autism spectrum disorder(ASD)and to explore the mechanisms behind abnormal behaviors.E-I balance is one of the mechanisms of ASD,which is closely related to the behavioral manifestations of ASD.Mutations at different sites in SHANK3 may lead to changes in the E-I balance in different brain regions,causing ASD-like behavior.In this paper,we reviewed the research progress on the changes of E-I balance in different brain regions,the relationship between E-I balance and behavior,and the related mechanisms in the mouse model of ASD with SHANK3 gene mutation at different sites,so as to provide reference for further in-depth studies on the pathogenesis and intervention of the mouse model of ASD with SHANK3 gene mutation.