Neuroscience Center, University of Helsinki, Viikinkaari 4, Helsinki FIN-00014, Finland; Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China.
Axe Neurosciences, Centre de recherche du CHU de Québec, Québec, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt A):27-39. doi: 10.1016/j.pnpbp.2017.01.007. Epub 2017 Jan 15.
Mounting evidence indicates the importance of microglia for proper brain development and function, as well as in complex stress-related neuropsychiatric disorders and cognitive decline along the aging trajectory. Considering that microglia are resident immune cells of the brain, a homeostatic maintenance of their effector functions that impact neuronal circuitry, such as phagocytosis and secretion of inflammatory factors, is critical to prevent the onset and progression of these pathological conditions. However, the molecular mechanisms by which microglial functions can be properly regulated under healthy and pathological conditions are still largely unknown. We aim to summarize recent progress regarding the effects of psychosocial stress and oxidative stress on microglial phenotypes, leading to neuroinflammation and impaired microglia-synapse interactions, notably through our own studies of inbred mouse strains, and most importantly, to discuss about promising therapeutic strategies that take advantage of microglial functions to tackle such brain disorders in the context of adult psychosocial stress or aging-induced oxidative stress.
越来越多的证据表明，小胶质细胞在大脑的正常发育和功能中具有重要作用，在与复杂的应激相关的神经精神疾病和衰老过程中的认知能力下降中也具有重要作用。鉴于小胶质细胞是大脑的固有免疫细胞，它们的效应功能（如吞噬作用和炎症因子的分泌）的动态平衡对于预防这些病理状况的发生和进展至关重要。然而，在健康和病理条件下，小胶质细胞功能可以被适当调节的分子机制在很大程度上仍然未知。我们旨在总结关于心理社会应激和氧化应激对小胶质细胞表型的影响的最新进展，导致神经炎症和受损的小胶质细胞-突触相互作用，特别是通过我们对近交系小鼠品系的研究，并且最重要的是，讨论利用小胶质细胞功能来解决成年心理社会应激或衰老诱导的氧化应激背景下此类大脑疾病的有前途的治疗策略。
