Olmedillas Maria, Brawek Bianca, Li Kaizhen, Richter Cris, Garaschuk Olga
Department of Neurophysiology, Institute of Physiology, Eberhard Karls University of Tübingen, Tübingen, Germany.
Glia. 2023 Dec;71(12):2884-2901. doi: 10.1002/glia.24458. Epub 2023 Aug 19.
Microglia, the major immune cells of the brain, are functionally heterogeneous but in vivo functional properties of these cells are rarely studied at single-cell resolution. By using microRNA-9 regulated viral vectors for multicolor labeling and longitudinal in vivo monitoring of individual microglia, we followed their fate in the cortex of healthy adult mice and at the onset of amyloidosis in a mouse model of Alzheimer's disease. In wild-type mice, microglia were rather mobile (16% of the cells migrated at least once in 10-20 days) but had a low turnover as documented by low division and death rates. Half of the migratory events were tightly associated with blood vessels. Surprisingly, basic migration properties of microglia (i.e., fraction of migrating cells, saltatory migration pattern, speed of migration, translocation distance, and strong association with blood vessels) were preserved in amyloid-depositing brains, despite amyloid plaques becoming the major destination of migration. Besides, amyloid deposition significantly increased microglial division and death rates. Moreover, the plaque vicinity became a hotspot of microglial turnover, harboring 33% of all migration, 70% of death and 54% of division events.
小胶质细胞是大脑中的主要免疫细胞，功能具有异质性，但这些细胞在体内的功能特性很少在单细胞分辨率下进行研究。通过使用微小RNA-9调控的病毒载体对单个小胶质细胞进行多色标记和纵向体内监测，我们追踪了它们在健康成年小鼠皮质以及阿尔茨海默病小鼠模型淀粉样变性发作时的命运。在野生型小鼠中，小胶质细胞相当活跃（16%的细胞在10 - 20天内至少迁移一次），但如低分裂率和死亡率所示，其更新率较低。一半的迁移事件与血管紧密相关。令人惊讶的是，尽管淀粉样斑块成为迁移的主要目的地，但在淀粉样蛋白沉积的大脑中，小胶质细胞的基本迁移特性（即迁移细胞的比例、跳跃式迁移模式、迁移速度、易位距离以及与血管的紧密关联）得以保留。此外，淀粉样蛋白沉积显著增加了小胶质细胞的分裂率和死亡率。而且，斑块附近成为小胶质细胞更新的热点区域，所有迁移事件的33%、死亡事件的70%和分裂事件的54%都发生在此处。
