【作者】 张越； 张立娟； 张进强； 韩岳； 林文娟； 游自立；

【Author】 Zhang Yue;Zhang Lijuan;Zhang Jingqiang;Han Yue;Lin Wenjuan;You Zili;School of Life Science and Technology,University of Electronic Science and Technology of China;CAS Key Laboratory of Mental Health,Institute of Psychology,Chinese Academy of Sciences;

【机构】 电子科技大学生命科学与技术学院； 中国科学院心理研究所心理健康重点实验室；

【摘要】 髓系来源的小胶质细胞是中枢神经系统的主要免疫细胞,它通过监测(sensing)、自稳(housekeeping)和防御(defensing)等措施,参与生理调节与病理变化。越来越多的证据表明小胶质细胞在应激所致的认知与行为损伤中发挥重要作用,神经发生的变化是其重要实现途径。白细胞介素10(IL-10)是一种抗炎性细胞因子,可诱导小胶质细胞呈现神经保护表型。在我们的研究中发现,应激易感小鼠神经发生缺失,并与小胶质细胞激活标志物相关;构建AAV-GFAP-IL10表达载体可在小鼠海马稳定表达,并诱导小胶质细胞从炎性激活状态向促神经发生表型转变;IL-10过表达小鼠可逆转应激所致的新生神经元减少,增强动物抗应激能力;小胶质细胞促神经发生效应与其吞噬凋亡神经前体细胞相关;清除小胶质细胞、敲低小胶质细胞IL-10受体、阻断促神经发生等措施可消除IL-10介导的抗应激作用。研究工作表明成年神经发生可能缓冲应激的病理损害,依赖于小胶质细胞促神经发生作用减缓抑郁样行为。近年来,学术界对曾经"沉寂"的小胶质细胞给予了极大的关注,探索其在健康和病理状态下的形态和功能的动态变化,丰富了"认识脑、保护脑、开发脑"的科学内涵。着眼于小胶质细胞对神经发生的调节作用,在治疗情感障碍中具有重要意义。更多还原

【Abstract】 Microglia, arising from yolk sac macrophages, are the main immune cells in the central nervous system. Microglia have three essential functions--sensing, housekeeping, and defensing, depending on which microglia participate in the regulating physiology state and pathological changes. Increasing evidences showed that microglia playing a pivotal role in cognitive and behavioral impairments under stress, associated with neurogenesis deficits. Interleukin 10(IL-10), an anti-inflammatory cytokine, can induce microglia from inflammatory phenotype towards neuroprotective phenotype. In our study, we’ve found that there are neurogenesis impairments in the mice vulnerable to stress, which is related to microglial activation markers. Overexpression IL-10 in the hippocampus of mice was archived with an AAV-GFAP-IL10 express vector, which drives microglial phenotypes changing from inflammatory activation to a neuroprotective one. AAV-GFAP-IL10-treated mice showed neurogenesis improvement and stress resilience when exposed to chronic mild stress. Microglial pro-neurogenesis effect is correlated to the phagocytosis of apoptotic neural progenitor cells. After eliminating microglia, knockdown IL-10 receptors on microglia, or blocking pro-neurogenesis, the antidepressant effects of IL-10 were blocked. Our results indicated that adult neurogenesis could ease the pathological damage of stress, which is relied on microglial pro-neurogenesis effects. In recent years, academia has been paying great attention to the once ‘ignored’ microglia, exploring the morphological and functional dynamics under health and disease, that immensely enriched the scientific intension of ‘Understand the brain, Protect the brain, Develop the brain’. Focusing on how microglia regulate neurogenesis, will be of vital importance in treating mental disorders.更多还原