The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
- University of Rochester Medical Center, United States
Abstract
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Antonio Ladron-de-Guevara
Funding
NIH Blueprint for Neuroscience Research (F99 NS108486-02)
- Monique Mendes
National Institute of Neurological Disorders and Stroke (R01 EY019277)
- Ania K Majewska
National Institute of Neurological Disorders and Stroke (RO1 NS114480)
- Ania K Majewska
National Institute of Neurological Disorders and Stroke (R21 NS099973)
- Ania K Majewska
National Science Foundation (1557971)
- Ania K Majewska
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal Experiments: All animal work was performed according to the approved guidelines from the University of Rochester, Institutional Animal Care and Use Committee and conformed to the National Institute of Health (NIH). Animals were housed in a 12-hour light/12-hour dark cycle with food ad libitum. Mice were housed in cages on a standard 12:12 hour light/dark cycle with food and water ad libitum. All animal experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Ethical approval number: UCAR: 2008-111; expires Dec. 1, 2023.
Reviewing Editor
- Sonia Garel, Ecole Normale Superieure, France
Publication history
- Preprint posted: March 6, 2020 (view preprint)
- Received: July 16, 2020
- Accepted: July 10, 2021
- Accepted Manuscript published: July 12, 2021 (version 1)
- Version of Record published: August 5, 2021 (version 2)
Copyright
© 2021, Mendes et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo
eLife 10:e61173.
https://doi.org/10.7554/eLife.61173
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