Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Adv Neurobiol. 2024;37:445-456. doi: 10.1007/978-3-031-55529-9_25.
Multiple sclerosis (MS) is a devastating autoimmune disease that leads to profound disability. This disability arises from the stochastic, regional loss of myelin-the insulating sheath surrounding neurons-in the central nervous system (CNS). The demyelinated regions are dominated by the brain's resident macrophages: microglia. Microglia perform a variety of functions in MS and are thought to initiate and perpetuate demyelination through their interactions with peripheral immune cells that traffic into the brain. However, microglia are also likely essential for recruiting and promoting the differentiation of cells that can restore lost myelin in a process known as remyelination. Given these seemingly opposing functions, an overarching beneficial or detrimental role is yet to be ascribed to these immune cells. In this chapter, we will discuss microglia dynamics throughout the MS disease course and probe the apparent dichotomy of microglia as the drivers of both demyelination and remyelination.
多发性硬化症(MS)是一种破坏性的自身免疫性疾病,可导致严重残疾。这种残疾是由于中枢神经系统(CNS)中髓鞘的随机、区域性丧失而引起的,髓鞘是围绕神经元的绝缘鞘。脱髓鞘区域主要由大脑常驻巨噬细胞:小胶质细胞主导。小胶质细胞在 MS 中具有多种功能,并且被认为通过与进入大脑的外周免疫细胞相互作用来引发和持续脱髓鞘。然而,小胶质细胞对于招募和促进能够恢复丢失髓鞘的细胞的分化也是必不可少的,这个过程被称为髓鞘再生。鉴于这些看似相反的功能,这些免疫细胞的总体有益或有害作用尚未确定。在本章中,我们将讨论 MS 病程中小胶质细胞的动态变化,并探讨小胶质细胞作为脱髓鞘和髓鞘再生双重驱动者的明显二分法。