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Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo
Although microglia possess the unique ability to migrate, whether mobility is evident in all microglia, is sex dependent, and what molecular mechanisms drive this, is not well understood in the adult brain. Using longitudinal in vivo two-photon imaging of sparsely labeled microglia, we find a relati...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629543/ https://www.ncbi.nlm.nih.gov/pubmed/37428916 http://dx.doi.org/10.1073/pnas.2302892120 |
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author | Boghozian, Roobina Sharma, Sorabh Narayana, Kamal Cheema, Manjinder Brown, Craig E. |
author_facet | Boghozian, Roobina Sharma, Sorabh Narayana, Kamal Cheema, Manjinder Brown, Craig E. |
author_sort | Boghozian, Roobina |
collection | PubMed |
description | Although microglia possess the unique ability to migrate, whether mobility is evident in all microglia, is sex dependent, and what molecular mechanisms drive this, is not well understood in the adult brain. Using longitudinal in vivo two-photon imaging of sparsely labeled microglia, we find a relatively small population of microglia (~5%) are mobile under normal conditions. Following injury (microbleed), the fraction of mobile microglia increased in a sex-dependent manner, with male microglia migrating significantly greater distances toward the microbleed relative to their female counterparts. To understand the signaling pathways involved, we interrogated the role of interferon gamma (IFNγ). Our data show that in male mice, stimulating microglia with IFNγ promotes migration whereas inhibiting IFNγ receptor 1 signaling inhibits them. By contrast, female microglia were generally unaffected by these manipulations. These findings highlight the diversity of microglia migratory responses to injury, its dependence on sex and the signaling mechanisms that modulate this behavior. |
format | Online Article Text |
id | pubmed-10629543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-106295432023-11-08 Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo Boghozian, Roobina Sharma, Sorabh Narayana, Kamal Cheema, Manjinder Brown, Craig E. Proc Natl Acad Sci U S A Biological Sciences Although microglia possess the unique ability to migrate, whether mobility is evident in all microglia, is sex dependent, and what molecular mechanisms drive this, is not well understood in the adult brain. Using longitudinal in vivo two-photon imaging of sparsely labeled microglia, we find a relatively small population of microglia (~5%) are mobile under normal conditions. Following injury (microbleed), the fraction of mobile microglia increased in a sex-dependent manner, with male microglia migrating significantly greater distances toward the microbleed relative to their female counterparts. To understand the signaling pathways involved, we interrogated the role of interferon gamma (IFNγ). Our data show that in male mice, stimulating microglia with IFNγ promotes migration whereas inhibiting IFNγ receptor 1 signaling inhibits them. By contrast, female microglia were generally unaffected by these manipulations. These findings highlight the diversity of microglia migratory responses to injury, its dependence on sex and the signaling mechanisms that modulate this behavior. National Academy of Sciences 2023-07-10 2023-07-18 /pmc/articles/PMC10629543/ /pubmed/37428916 http://dx.doi.org/10.1073/pnas.2302892120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Boghozian, Roobina Sharma, Sorabh Narayana, Kamal Cheema, Manjinder Brown, Craig E. Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
title | Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
title_full | Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
title_fullStr | Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
title_full_unstemmed | Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
title_short | Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
title_sort | sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629543/ https://www.ncbi.nlm.nih.gov/pubmed/37428916 http://dx.doi.org/10.1073/pnas.2302892120 |
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