Social Modulation of Microglia

描述（由申请人提供）：社会环境导致多种人类健康状况的发病率和病理学的个体差异，包括抑郁症、癌症、心血管疾病、脑血管疾病、伤口愈合和神经性疼痛。我们的实验室和其他实验室已经成功地概括了社会隔离对这些疾病的啮齿动物模型结果的加剧作用;这些疾病中每一种的共同生理特征是社会隔离动物相对于社会圈养动物的神经炎症增加。反过来，神经炎症与更大的身体和心理发病率有关，尽管社会行为和神经炎症之间的生理联系尚不清楚。我们认为，催产素，一种由社会互动释放的激素，通过抑制小胶质细胞的激活来提供保护功能。在这个提议中测试的特定假设是催产素通过抑制小胶质细胞活化来减少脑中促炎细胞因子的表达。缩宫素调节小胶质细胞的证据将通过体内和体外实验提供。作为该提案的一部分收集的数据将增加我们对社会环境变化如何影响健康的理解。确定社会对健康影响的生理因素，可以促进治疗方法的发展，改善贫困社会环境中的人的健康措施。

DESCRIPTION (provided by applicant): Social environment contributes to individual differences in the incidence and symptomology of a wide range of human health conditions, including depression, cancer, cardiovascular disease, cerebrovascular disease, wound healing, and neuropathic pain. Our laboratory and others have successfully recapitulated the exacerbating effects of social isolation on outcome in rodent models of these disorders; a common physiological feature of each of these conditions is increased neuroinflammation among socially isolated animals relative to socially housed animals. In turn, neuroinflammation is associated with greater physical and psychological morbidity, although the physiological link between social behavior and neuroinflammation is not known. We propose that oxytocin, a hormone that is released by social interaction, provides a protective function by suppressing the activation of microglia. The specific hypothesis tested in this proposal is that oxytocin reduces the expression of proinflammatory cytokines in the brain by suppressing microglial activation. Converging evidence of oxytocin modulation of microglia will be provided through in vivo and in vitro experiments. The data collected as part of this proposal will increase our understanding of how variation in social environment can impact health. Identification of the physiological factors underlying social influences on health could facilitate the development of therapeutic approaches that improve health measures among people with impoverished social environments.