Katharine Askew 1 , Kaizhen Li 2 , Adrian Olmos-Alonso 1 , Fernando Garcia-Moreno 3 , Yajie Liang 2 , Philippa Richardson 1 , Tom Tipton 4 , Mark A. Chapman 1 , Kristoffer Riecken 5 , Sol Beccari 6 , Amanda Sierra 6 , Zoltán Molnár 3 , Mark S. Cragg 4 , Olga Garaschuk 2 , V. Hugh Perry 1 , Diego Gomez-Nicola 1 , 7 , ∗
10 January 2017
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.
The microglial population is formed without the perinatal infiltration of monocytes
The microglial density remains remarkably stable over a mouse or human lifetime
In the mouse and human brain, microglia turn over several times during a lifetime
Microglia self-renewal is maintained by coupled proliferation and apoptosis
The mechanism or mechanisms underlying microglial homeostasis are unknown. Askew et al. show that microglia self-renewal is maintained by coupled proliferation and apoptosis, resulting in a stable microglia number over a mouse or human lifetime.