Bisht Kanchan, Sharma Kaushik, Tremblay Marie-Ève
Axe Neurosciences, CRCHU de Québec-Université Laval, Québec, QC, Canada.
Département de médecine moléculaire, Université Laval, Québec, QC, Canada.
Neurobiol Stress. 2018 May 19;9:9-21. doi: 10.1016/j.ynstr.2018.05.003. eCollection 2018 Nov.
Microglia are the predominant immune cells of the central nervous system (CNS) that exert key physiological roles required for maintaining CNS homeostasis, notably in response to chronic stress, as well as mediating synaptic plasticity, learning and memory. The repeated exposure to stress confers a higher risk of developing neurodegenerative diseases including sporadic Alzheimer's disease (AD). While microglia have been causally linked to amyloid beta (Aβ) accumulation, tau pathology, neurodegeneration, and synaptic loss in AD, they were also attributed beneficial roles, notably in the phagocytic elimination of Aβ. In this review, we discuss the interactions between chronic stress and AD pathology, overview the roles played by microglia in AD, especially focusing on chronic stress as an environmental risk factor modulating their function, and present recently-described microglial phenotypes associated with neuroprotection in AD. These microglial phenotypes observed under both chronic stress and AD pathology may provide novel opportunities for the development of better-targeted therapeutic interventions.
小胶质细胞是中枢神经系统（CNS）中的主要免疫细胞，在维持CNS稳态方面发挥着关键的生理作用，尤其是在应对慢性应激时，以及介导突触可塑性、学习和记忆。反复暴露于应激会增加患神经退行性疾病的风险，包括散发性阿尔茨海默病（AD）。虽然小胶质细胞与AD中的淀粉样β蛋白（Aβ）积累、tau病理、神经退行性变和突触丧失存在因果关系，但它们也具有有益作用，尤其是在吞噬清除Aβ方面。在这篇综述中，我们讨论了慢性应激与AD病理之间的相互作用，概述了小胶质细胞在AD中的作用，特别关注慢性应激作为调节其功能的环境风险因素，并介绍了最近描述的与AD神经保护相关的小胶质细胞表型。在慢性应激和AD病理情况下观察到的这些小胶质细胞表型可能为开发更具针对性的治疗干预措施提供新的机会。
