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The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo

Microglia are the brain’s resident immune cells with a tremendous capacity to autonomously self-renew. Because microglial self-renewal has largely been studied using static tools, its mechanisms and kinetics are not well understood. Using chronic in vivo two-photon imaging in awake mice, we confirm...

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Autores principales: Mendes, Monique S, Le, Linh, Atlas, Jason, Brehm, Zachary, Ladron-de-Guevara, Antonio, Matei, Evelyn, Lamantia, Cassandra, McCall, Matthew N, Majewska, Ania K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341987/
https://www.ncbi.nlm.nih.gov/pubmed/34250902
http://dx.doi.org/10.7554/eLife.61173
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author Mendes, Monique S
Le, Linh
Atlas, Jason
Brehm, Zachary
Ladron-de-Guevara, Antonio
Matei, Evelyn
Lamantia, Cassandra
McCall, Matthew N
Majewska, Ania K
author_facet Mendes, Monique S
Le, Linh
Atlas, Jason
Brehm, Zachary
Ladron-de-Guevara, Antonio
Matei, Evelyn
Lamantia, Cassandra
McCall, Matthew N
Majewska, Ania K
author_sort Mendes, Monique S
collection PubMed
description Microglia are the brain’s resident immune cells with a tremendous capacity to autonomously self-renew. Because microglial self-renewal has largely been studied using static tools, its mechanisms and kinetics are not well understood. Using chronic in vivo two-photon imaging in awake mice, we confirm that cortical microglia show limited turnover and migration under basal conditions. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of remaining microglia, in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly born microglia resemble mature microglia within days of repopulation, although morphological maturation is different in newly born microglia in P2Y12 knock out mice. Our work suggests that microglia rapidly locally and that newly born microglia do not recapitulate the slow maturation seen in development but instead take on mature roles in the CNS.
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spelling pubmed-83419872021-08-09 The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo Mendes, Monique S Le, Linh Atlas, Jason Brehm, Zachary Ladron-de-Guevara, Antonio Matei, Evelyn Lamantia, Cassandra McCall, Matthew N Majewska, Ania K eLife Neuroscience Microglia are the brain’s resident immune cells with a tremendous capacity to autonomously self-renew. Because microglial self-renewal has largely been studied using static tools, its mechanisms and kinetics are not well understood. Using chronic in vivo two-photon imaging in awake mice, we confirm that cortical microglia show limited turnover and migration under basal conditions. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of remaining microglia, in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly born microglia resemble mature microglia within days of repopulation, although morphological maturation is different in newly born microglia in P2Y12 knock out mice. Our work suggests that microglia rapidly locally and that newly born microglia do not recapitulate the slow maturation seen in development but instead take on mature roles in the CNS. eLife Sciences Publications, Ltd 2021-07-12 /pmc/articles/PMC8341987/ /pubmed/34250902 http://dx.doi.org/10.7554/eLife.61173 Text en © 2021, Mendes et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Mendes, Monique S
Le, Linh
Atlas, Jason
Brehm, Zachary
Ladron-de-Guevara, Antonio
Matei, Evelyn
Lamantia, Cassandra
McCall, Matthew N
Majewska, Ania K
The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
title The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
title_full The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
title_fullStr The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
title_full_unstemmed The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
title_short The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
title_sort role of p2y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341987/
https://www.ncbi.nlm.nih.gov/pubmed/34250902
http://dx.doi.org/10.7554/eLife.61173
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