Summary: The turn over of microglia cells is at least ten times faster than previously predicted, allowing for entire renewal of microglia a number of times during ones lifetime, a new study reports.
Source: University of Southampton.
A study, led by the University of Southampton and published in Cell Reports, shows that the turnover of the cells, called Microglia, is 10 times faster, allowing the whole population of Microglia cells to be renewed several times during a lifetime.
“Microglia are constantly scanning the brain to find and fix issues – you could call them the housekeepers of the brain,” said Dr Diego Gomez-Nicola, of the University of Southampton, who supervised the study. “We previously thought that microglia would renew themselves so slowly that a whole lifetime would not suffice to renew the whole population. But now we can talk about up to six renewal cycles in a lifetime. We now need to reinterpret how they interact and regulate the function of other brain cells to understand their full potential.”
The study, led by PhD student, Katharine Askew, assessed the proliferation of microglia, from both mouse and human brain, using staining of sections with specific antibodies alongside live imaging of the cells.
It also found that the number of microglial cells remains relatively unchanged from birth until ageing and is maintained by the spatial and temporal coupling of cell division and cell death.
The research was carried out in collaboration with researchers at the University of Tubingen (Germany), University of Oxford, University of Hamburg (Germany) and Achucarro Basque Center for Neuroscience (Spain).
The Southampton team believe this new research will help the understanding of Microglia’s behaviour in diseases like Alzheimer’s Disease. In Alzheimer’s microglia contribute to the person’s cognitive decline.
Dr Diego Gomez-Nicola added: “This finding provides a basic piece of cell biology, needed to understand the functions of microglia and their interaction with other cells in the brain. Understanding the clockwork of microglia will help understand their behaviour in psychiatric and neurodegenerative diseases of the brain like Alzheimer’s.”
Source: Becky Attwood – University of Southampton
Image Source: NeuroscienceNews.com image is credited to University of Southampton.
Original Research: Full open access research for “Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain” by Katharine Askew, Kaizhen Li, Adrian Olmos-Alonso, Fernando Garcia-Moreno, Yajie Liang, Philippa Richardson, Tom Tipton, Mark A. Chapman, Kristoffer Riecken, Sol Beccari, Amanda Sierra, Zoltán Molnár, Mark S. Cragg, Olga Garaschuk, V. Hugh Perry, Diego Gomez-Nicola in Cell Reports. Published online January 10 2017 doi:10.1016/j.celrep.2016.12.041
Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain
•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
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.
“Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain” by Katharine Askew, Kaizhen Li, Adrian Olmos-Alonso, Fernando Garcia-Moreno, Yajie Liang, Philippa Richardson, Tom Tipton, Mark A. Chapman, Kristoffer Riecken, Sol Beccari, Amanda Sierra, Zoltán Molnár, Mark S. Cragg, Olga Garaschuk, V. Hugh Perry, Diego Gomez-Nicola in Cell Reports. Published online January 10 2017 doi:10.1016/j.celrep.2016.12.041