Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

By Katharine E. Askew, Kaizhen Li, Adrian Olmos-Alonso, F. García-Moreno, Yajie Liang, Philippa Richardson, Thomas R. W. Tipton, M. Chapman, K. Riecken, S. Beccari and 6 more. Cell Reports, 2017

619 citations recorded by the source corpus.

Summary Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/5446310f78dede7e406452e2aa3cdeca6e9415dd

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Citations in the corpus

Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation (2019, background): “Unlike most peripheral tissue macrophages, MG and most CAMs such as pvMF and mMF arise from Linc-Kit erythromyeloid progenitors in the YS during embryonic development and are maintained throughout life by self-renewal (40, 47) independent of bone-marrow precursor cells (45, 48).”
Transcriptomic analysis of purified human cortical microglia reveals age-associated changes (2017, background): “A recent publication indicated that the microglial population in the brain is replaced approximately every 100 d in both mice and humans 46 .”
The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques (2019, background): “The cluster of CPMs did not display any selective enrichment for specific phenotypic groups (Figure 1C and S3A–S3D) and may represent a small pool of cycling microglia (Askew et al., 2017).”
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “59 The turnover rate of microglia differs in various regions of the brain in mice, with the olfactory bulb, hippocampus, and cortex in mice undergoing complete renewal in 8, 15, and 41 months, respectively.”