Social Modulation of Microglia

描述(由申请人提供)：社会环境导致各种人类健康疾病的发病率和症状的个体差异，包括抑郁症、癌症、心血管疾病、脑血管疾病、伤口愈合和神经病理性疼痛。我们的实验室和其他人已经成功地在这些疾病的啮齿动物模型中总结了社交隔离对结果的恶化影响；每种情况的一个共同的生理特征是相对于社交饲养的动物，社交隔离动物的神经炎症增加。反过来，神经炎症与更高的生理和心理发病率有关，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，催产素是一种通过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。在这项提议中检验的特定假设是，催产素通过抑制小胶质细胞的激活来减少大脑中促炎症细胞因子的表达。通过体内和体外实验，将提供催产素调节小胶质细胞的聚合证据。作为这项提案的一部分，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。查明对健康产生潜在社会影响的生理因素可以促进制定治疗方法，改善社会环境贫困人口的健康措施。

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.