Sugama Shuei, Kakinuma Yoshihiko
Department of Physiology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8602, Japan.
Brain Behav Immun Health. 2020 Jul 23;7:100111. doi: 10.1016/j.bbih.2020.100111. eCollection 2020 Aug.
Stress has been well documented to bring about various clinical disorders, ranging from neurodegeneration, such as Parkinson's (PD) and Alzheimer's diseases (AD), to metabolic disorders including diabetes mellitus. Importantly, microglia, immunocompetent cells in the brain, have been shown to be involved in these clinical disorders. In the recent studies aiming to clarify the microglial responses, microglia are found to be quite responsive to stressful events, such as acute, subchronic, chronic stress, and social defeat stress. However, the mechanisms of these stress response on microglial activation have been not fully understood. In response to stress exposure, both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) are simultaneously activated, with the former inducing glucocorticoids (GCs) and the latter noradrenaline (NA), respectively. However, the effects of these stress-induced GCs and NA have not been consistent. The GCs, conventionally known to act on microglia as immunosuppressant, is also reported to act on it as stimulator. Similarly, the NA has been reported to act on microglia as stimulator or inhibitor depending on environmental conditions. Since any kinds of stress upregulate the HPA axis and SNS, with the levels of upregulation variable depending on the stress type, it is plausible that microglia is closely regulated by these two stress pathways. In this review, we discuss the microglial responses induced by various stresses as well as the possible mechanism by which stress induces microglial activation.
压力已被充分证明会引发各种临床疾病，范围从神经退行性疾病，如帕金森病（PD）和阿尔茨海默病（AD），到包括糖尿病在内的代谢紊乱。重要的是，小胶质细胞，即大脑中的免疫活性细胞，已被证明与这些临床疾病有关。在最近旨在阐明小胶质细胞反应的研究中，发现小胶质细胞对压力事件，如急性、亚慢性、慢性应激和社会挫败应激，反应相当灵敏。然而，这些应激反应对小胶质细胞激活的机制尚未完全了解。在应激暴露时，下丘脑-垂体-肾上腺（HPA）轴和交感神经系统（SNS）同时被激活，前者诱导糖皮质激素（GCs），后者诱导去甲肾上腺素（NA）。然而，这些应激诱导的GCs和NA的作用并不一致。传统上已知GCs作为免疫抑制剂作用于小胶质细胞，但也有报道称其作为刺激剂作用于小胶质细胞。同样，据报道NA根据环境条件作为刺激剂或抑制剂作用于小胶质细胞。由于任何类型的应激都会上调HPA轴和SNS，上调水平因应激类型而异，因此小胶质细胞很可能受到这两条应激途径的密切调节。在这篇综述中，我们讨论了各种应激诱导的小胶质细胞反应以及应激诱导小胶质细胞激活的可能机制。
