PPARγ依赖的小胶质细胞免疫调控对早期应激致个体神经可塑性的机制研究

个体发育早期所经历的心理应激是造成其后期精神异常的重要因素。研究表明小胶质细胞表型改变及其对中枢神经系统内环境的调控是早期应激影响情绪及认知的重要生理基础，而其在神经系统发育早期的形成的长期免疫调控机制并不明确。基于小胶质细胞的免疫调控功能和精神疾病的神经免疫特征，结合转录组测序和表观遗传修饰检测，本研究进一步探索早期心理应激所致小胶质细胞长期免疫记忆形成的分子基础。通过建立体内和体外的PPARγ表达调控体系，广泛分析这一分子信号对小胶质细胞表型和细胞因子的长期调节作用。结合神经元体外稀疏培养和神经电生理技术，检测小胶质细胞特异性PPARγ表达调控对神经元形态与功能可塑性的影响。研究旨在阐明依赖于PPARγ的小胶质细胞先天免疫记忆对早期应激致子代行为异常调控的生理机制，增进对小胶质细胞早期发育过程的认识并探寻基于这一途径的精神病理研究和治疗的新策略。

The psychological stress experiences in early life stage are important factors that caused mental disorders in offspring later lives. A large number of studies have shown that the changes of microglia phenotype and internal environment of offspring central nervous system (CNS) are important physiological basis for early life stress (ELS) induced aberrant emotion and cognition. However, its long-term regulation mechanism is not completely clear. Based on the inflammatory regulation of microglia and the neuroimmune characteristics of mental disease, combined with transcriptome and epigenetic modification sequencing, we further explore the genetic basis of microglia specific immune memory caused by early psychological stress. The PPARγ expression regulation system in vivo and vitro were established to extensively analyze the changes of microglia phenotypes and endocrine factors by regulating PPARγ signal. Then combined with neuron sparse culture in vitro and electrophysiological techniques, examined the influence of specific PPARγ regulation of microglia on the neuron morphological and functional plasticity. This study reveals the molecular and cellular mechanisms of PPARγ dependent microglia phenotypic on the regulation of emotional in ELS offspring, increase the recognition on the early development of microglia, and explore the new strategies for psychopathology research and treatment.