精神分裂症（SZ）神经炎症假说引起学术界广泛重视，既往研究提示活化的小胶质细胞致使突触过度修剪是SZ突触损伤的原因之一，其中补体系统可能协同活化的小胶质细胞参与突触过度修剪，但具体机制不明。本课题组前期研究发现高水平吲哚胺2，3-双加氧酶（IDO）导致动物出现SZ样行为，引起小胶质细胞活化和补体增加，并造成突触损伤，但IDO、小胶质细胞活化和补体增加以及突触损伤之间的关系不明。本项目以IDO为切入点，选取孕期感染子代SZ大鼠模型为研究对象，探讨小胶质细胞活化和补体增加对突触损伤的可能机制，具体开展以下两方面工作：1.通过调控IDO表达或活性，探究孕期感染子代SZ大鼠模型IDO与SZ样行为、活化小胶质细胞损伤突触以及补体激活的相关性；2.通过调控补体组分的表达，分析补体在IDO致使活化的小胶质细胞损伤突触的作用。本项目有助于阐释IDO参与SZ的发病机理，为丰富SZ神经炎症假说提供实验证据。

The neuroinflammation hypothesis of schizophrenia (SZ) has attracted extensive attention. Previous studies have shown that the overpruning of synapses by activated microglia is one of the causes of synaptic injury in schizophrenia (SZ), in which the complement system may synergistically perform function. However, the specific mechanism is unknown. Our previous study found that high level of indoleamine 2, 3-dioxygenase (IDO) can lead to SZ-like behavior, synaptic injury and induce the activation of complement systerm and microglia cell. However, the relationships among IDO and synaptic injury and enhanced complement systerm and activated microglia are not clear. This work will focus on IDO and explore whether synaptic damage in SZ is resulted from complement-dependent microglia phagocytosis. The following studies will be carried on. 1st, the expression or activation of IDO will be regulated by virus or inhibitor to explore the correlation between IDO and SZ-like behavior, and to make sure whether IDO enhance the process of sypnase injury induced by acivated microglia phagocytosis in maternal immune activation SZ rat model, and to analyse the role of IDO in complement activation; 2nd, the expression or activation of complement components, C3b, will be regulated by virus to assess the role of complement systerm in the process of IDO-enhanced synaptic injury mediated by microglia phagocytosis. The expected results would contribute to understanding the relationships between IDO and SZ, and enriching the neuroinflammation hypothesis of SZ.