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Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain

Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain
Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain
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.
2211-1247
391-405
Askew, Katharine
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Li, Kaizhen
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Olmos Alonso, Adrian
c52c3bd9-2cf0-4b55-9214-cb549449db75
Garcia-Moreno, Fernando
ecd62243-4db3-48f6-94c3-f8d0d636319e
Liang, Yajie
9f9476f7-a4ac-4b3a-87fc-2dd83ee1af16
Richardson, Philippa
19973be6-08e7-487a-8276-ac5861c5e0c3
Tipton, Thomas
a0a94b14-7d09-4411-b988-84c9d39eb0d6
Chapman, Mark
8bac4a92-bfa7-4c3c-af29-9af852ef6383
Riecken, Kristoffer
0eca316e-6c54-4cda-80e0-92c571263996
Beccari, Sol
df8b2d6b-6085-4e1a-b0c5-1ad98457e838
Sierra, Amanda
b44cfc91-1fd2-44de-a3a3-2df1b360df8f
Molnar, Zoltan
9b15b8da-6939-43c6-946f-6c7f213baaf7
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Garaschuk, Olga
f751209b-b876-41b8-9d83-b999f3ce1f82
Perry, Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Askew, Katharine
ffc96fb4-f94c-4cb7-8479-e9f0b2dae0c7
Li, Kaizhen
49fd8b31-e763-4b28-946f-e78fcd74fd7a
Olmos Alonso, Adrian
c52c3bd9-2cf0-4b55-9214-cb549449db75
Garcia-Moreno, Fernando
ecd62243-4db3-48f6-94c3-f8d0d636319e
Liang, Yajie
9f9476f7-a4ac-4b3a-87fc-2dd83ee1af16
Richardson, Philippa
19973be6-08e7-487a-8276-ac5861c5e0c3
Tipton, Thomas
a0a94b14-7d09-4411-b988-84c9d39eb0d6
Chapman, Mark
8bac4a92-bfa7-4c3c-af29-9af852ef6383
Riecken, Kristoffer
0eca316e-6c54-4cda-80e0-92c571263996
Beccari, Sol
df8b2d6b-6085-4e1a-b0c5-1ad98457e838
Sierra, Amanda
b44cfc91-1fd2-44de-a3a3-2df1b360df8f
Molnar, Zoltan
9b15b8da-6939-43c6-946f-6c7f213baaf7
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Garaschuk, Olga
f751209b-b876-41b8-9d83-b999f3ce1f82
Perry, Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5

Askew, Katharine, Li, Kaizhen, Olmos Alonso, Adrian, Garcia-Moreno, Fernando, Liang, Yajie, Richardson, Philippa, Tipton, Thomas, Chapman, Mark, Riecken, Kristoffer, Beccari, Sol, Sierra, Amanda, Molnar, Zoltan, Cragg, Mark S., Garaschuk, Olga, Perry, Hugh and Gomez-Nicola, Diego (2017) Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain. Cell Reports, 18 (2), 391-405. (doi:10.1016/j.celrep.2016.12.041).

Record type: Article

Abstract

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.

Text Askew et al Cell Rep 2016.pdf - Accepted Manuscript
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Text PIIS2211124716317466.pdf - Version of Record
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More information

Accepted/In Press date: 13 December 2016
e-pub ahead of print date: 10 January 2017
Published date: 10 January 2017
Organisations: Cancer Sciences, Biomedicine
Learn more about Biological Sciences research

Identifiers

Local EPrints ID: 403985
URI: https://eprints.soton.ac.uk/id/eprint/403985
DOI: doi:10.1016/j.celrep.2016.12.041
ISSN: 2211-1247
PURE UUID: a3159248-6623-464d-b247-4993fcdceb5d
ORCID for Mark Chapman: ORCID iD orcid.org/0000-0002-7151-723X
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 19 Dec 2016 12:06
Last modified: 26 Jul 2018 00:34

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Contributors

Author: Katharine Askew
Author: Kaizhen Li
Author: Adrian Olmos Alonso
Author: Fernando Garcia-Moreno
Author: Yajie Liang
Author: Philippa Richardson
Author: Thomas Tipton
Author: Mark Chapman ORCID iD
Author: Kristoffer Riecken
Author: Sol Beccari
Author: Amanda Sierra
Author: Zoltan Molnar
Author: Mark S. Cragg ORCID iD
Author: Olga Garaschuk
Author: Hugh Perry
Author: Diego Gomez-Nicola ORCID iD

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