星形胶质细胞异常引起突触发育障碍致力于自闭症的发生。我们前期研究发现星形胶质细胞中LXRβ缺失引起海马CA1区锥体神经元树突棘发育障碍、突触形成异常，并出现自闭症样的行为，提示星形胶质细胞LXRβ缺失可能通过抑制海马突触的形成而参与自闭症的发生。然而星形胶质细胞中LXRβ调控海马突触形成的途径与机制目前仍不明确。本课题将采用LXRβ条件敲除小鼠，结合基因转染、星形胶质细胞与神经元共培养、膜片钳记录和细胞移植等技术，检测星形胶质细胞中LXRβ调控海马内突触形成的途径；采用染色质免疫沉淀技术（ChIP）检测星形胶质细胞中LXRβ-STAT3复合体对突触形成关键分泌因子TSP1的转录调节，明确与TSP1启动子结合的区域。阐明星形胶质细胞中LXRβ缺失通过抑制海马内突触形成参与自闭症样行为发生的分子机制，为自闭症的预防与治疗提供新线索。

Abnormal synapse development induced by abnormal astrocyte is considered to be a key factor related to pathogenesis of autism. Our previous study revealed that astrocyte-specific LXRβ deletion induced developmental disorders in dendritic spines , synapse formation of CA1 pyramidal neurons, and the emergence of autism like behavior, suggesting that astrocytes lack LXRβ may inhibit hippocampal synaptic formation and participate in the occurrence of autism. However, the pathways and mechanisms of astrocytic LXRβ to regulate the formation of hippocampal synapses are still unclear. In the present study, the roles of astrocytic LXRβ in the hippocampal synapse formation will be investigated with astrocyte-specific LXRβ knockout mice, and combination with gene transfection, co cultured astrocytes and neurons, patch clamp recording and cell transplantation. A chromatin precipitation will be used to detect dynamic modulation of TSP1 by LXRβ-STAT3 transcription complex, and analyze binding region on the promoter. It will clarify the underlying mechanism of astrocyte-specific LXRβ deletion involved in the occurrence of autistic like behaviors through inhibiting synaptic formation in hippocampus, providing new clues for the prevention and treatment of autism.