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Cell Rep. 2017 Jan 10;18(2):391-405. doi: 10.1016/j.celrep.2016.12.041.

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

Author information

1
Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
2
Institute of Physiology II, University of Tübingen, 72074 Tübingen, Germany.
3
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PA, UK.
4
Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Southampton SO16 6YD, UK.
5
Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
6
Achucarro Basque Center for Neuroscience, Ikerbasque Foundation, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain.
7
Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. Electronic address: d.gomez-nicola@soton.ac.uk.

Abstract

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.

KEYWORDS:

BrdU; CSF1R; CX3CR1; Macgreen; RNA-seq; Vav-Bcl2; self-renewal

PMID:
28076784
PMCID:
PMC5263237
DOI:
10.1016/j.celrep.2016.12.041
[Indexed for MEDLINE]
Free PMC Article

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