Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783733993741484032 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8341987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mendesmoniques theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT lelinh theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT atlasjason theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT brehmzachary theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT ladrondeguevaraantonio theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT mateievelyn theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT lamantiacassandra theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT mccallmatthewn theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT majewskaaniak theroleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT mendesmoniques roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT lelinh roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT atlasjason roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT brehmzachary roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT ladrondeguevaraantonio roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT mateievelyn roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT lamantiacassandra roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT mccallmatthewn roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo AT majewskaaniak roleofp2y12inthekineticsofmicroglialselfrenewalandmaturationintheadultvisualcortexinvivo |