孤独症谱系障碍（ASD）是一种神经发育障碍疾病。神经免疫失衡和突触修剪的减少是可能的原因，但机制尚未明确。小胶质细胞（MC)是大脑重要的免疫细胞，髓样细胞触发受体2（TREM2）高表达于MC，与DAP12相互作用介导下游信号传导。TREM2/DAP12信号路在促进MC活化和突触修剪中起着重要的作用。最新研究显示ASD患者TREM2下降与ASD症状成负相关。本课题组前期研究显示孤独症样行为大鼠存在MC表型比例失衡，TREM2表达降低，提示TREM2/DAP12信号通路可能影响ASD的疾病进程。但调控TREM2/DAP12信号通路能否改变MC的表型从而减少ASD异常的神经免疫和突触修剪？目前尚无相关报道。因此本项目拟深入研究调控TREM2 /DAP12信号通路对MC介导的神经免疫和突触发育的影响及关键时间窗，有利于确定干预时间和位点，为预防或者治疗ASD的潜在可能性提供相应理论依据。

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. The possible reasons are the imbalance of neuroimmune and the decrease of synaptic pruning. But the mechanism is not clear yet. Microglial cell (MC) is an important immune cell in the brain. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed in MC and interacts with DAP12 to mediate downstream signal transduction. TREM2/ DAP12 signaling pathway plays an important role in promoting MC activation and synaptic pruning. The latest research shows that the decrease of TREM2 in ASD patients is negatively correlated with ASD symptoms. Our previous study showed that the proportion of MC phenotype was unbalanced and the expression of TREM2 was decreased in autism like behavior rats, suggesting that TREM2/ DAP12 signaling pathway may affect the disease progression of ASD. But can the regulation of TREM2/ DAP12 signal pathway change the phenotype of MC and reduce the abnormal neuroimmune and synaptic pruning of ASD? At present, there is no relevant report. Therefore, this project plans to further study the effect of regulation of TREM2/ DAP12 signaling pathway on MC mediated neuroimmune and synaptic development and the key time window, which is conducive to determine the intervention time and site, and provide the corresponding theoretical basis for the potential possibility of prevention or treatment of ASD.