神经精神狼疮（NPSLE）是系统性红斑狼疮（SLE）患者不良预后的重要因素。NPSLE症状多出现在系统性病理改变之前，提示脑内存在早发致病因素。C1q在脑内异常高表达不仅能激活小胶质细胞，而且与多种神经系统疾病中突触异常密切相关。因此，C1q对小胶质细胞突触修剪活性的调控是神经领域研究的热点之一。申请者前期研究发现MRL-lpr小鼠病程早期即出现神经精神行为学异常、脑内C1q表达升高、小胶质细胞活化伴突触蛋白密度降低；且C1q中和抗体能缓解SLE小鼠的行为学异常。但C1q如何调控小胶质细胞活性，进而介导NPSLE发病的机制仍不清楚。本项目拟在前期工作基础上，应用MRL-lpr自发NPSLE小鼠，在动物、细胞和分子水平研究脑内C1q对皮层、海马脑区小胶质细胞神经突触修剪功能的调节机制；阐明C1q在NPSLE中的作用。研究成果不仅有助于完善NPSLE病因学说，而且可为治疗NPSLE提供新思路。

Neuropsychiatric lupus (NPSLE) is an important factor for poor prognosis in patients with systemic lupus erythematosus (SLE). NPSLE symptoms often appear before systemic pathological changes, suggesting the existence of early onset pathogenic factors in the brain. The abnormal high expression of C1q in the brain not only activates microglia, but also is closely related to the abnormal synaptic structure in a variety of neurological diseases. Therefore, the regulation of C1q on microglial synaptic-pruning activity is one of the hotspots in the study of nervous system diseases. Our previous studies have found that neuropsychopathological abnormalities, increased C1q expression in the brain and microglial activation with decreased synaptic density occurred in SLE mice at the early stage of the disease. Moreover, C1q neutralizing antibody treatment can alleviate behavioral abnormalities in SLE mice. However, how C1q regulates microglia activity and thus mediates the pathogenesis of NPSLE remains unclear. In the present study, we intend to investigate the regulatory effects of C1q on microglia- mediated synaptic-pruning with MRL-lpr prone NPSLE mice in vivo and in vitro. We propose that C1q involves the pathogenesis of NPSLE via regulating microglia synaptic-pruning activation. These findings will give us an insight into the potential of C1q in the neuroprotection of NPSLE.