title: Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain.
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.
authors.affiliation: Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Askew
authors.affiliation: Institute of Physiology II, University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Kaizhen
authors.initials: K
authors.lastname: Li
authors.affiliation: Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Olmos-Alonso
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PA, UK.
authors.forename: Fernando
authors.initials: F
authors.lastname: Garcia-Moreno
authors.affiliation: Institute of Physiology II, University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Philippa
authors.initials: P
authors.lastname: Richardson
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Tipton
authors.affiliation: Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Chapman
authors.affiliation: Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Riecken
authors.affiliation: Achucarro Basque Center for Neuroscience, Ikerbasque Foundation, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain.
authors.forename: Sol
authors.initials: S
authors.lastname: Beccari
authors.affiliation: Achucarro Basque Center for Neuroscience, Ikerbasque Foundation, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sierra
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PA, UK.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cragg
authors.affiliation: Institute of Physiology II, University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Garaschuk
authors.affiliation: Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
authors.affiliation: Biological Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. Electronic address: d.gomez-nicola@soton.ac.uk.
authors.forename: Diego
authors.initials: D
authors.lastname: Gomez-Nicola
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology*; D002452:Cell Count; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2
keywords: BrdU; CSF1R; CX3CR1; Macgreen; RNA-seq; Vav-Bcl2; self-renewal