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Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI...

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Autores principales: Krukowski, Karen, Nolan, Amber, Becker, McKenna, Picard, Katherine, Vernoux, Nathalie, Frias, Elma S., Feng, Xi, Tremblay, Marie-Eve, Rosi, Susanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119574/
https://www.ncbi.nlm.nih.gov/pubmed/34403733
http://dx.doi.org/10.1016/j.bbi.2021.08.210
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author Krukowski, Karen
Nolan, Amber
Becker, McKenna
Picard, Katherine
Vernoux, Nathalie
Frias, Elma S.
Feng, Xi
Tremblay, Marie-Eve
Rosi, Susanna
author_facet Krukowski, Karen
Nolan, Amber
Becker, McKenna
Picard, Katherine
Vernoux, Nathalie
Frias, Elma S.
Feng, Xi
Tremblay, Marie-Eve
Rosi, Susanna
author_sort Krukowski, Karen
collection PubMed
description Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI-related pathologies. Following TBI, microglia, the brain resident immune cells, turn into a “reactive” state characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Utilizing multimodal, state-of-the-art techniques that widely span from ultrastructural analysis to optogenetic interrogation of circuit function, we investigated the reactive microglia phenotype one week after injury when learning and memory deficits are also measured. Microglia displayed increased: (i) phagocytic activity in vivo, (ii) synaptic engulfment, (iii) increased neuronal contact, including with dendrites and somata (termed ‘satellite microglia’). Functionally, satellite microglia might impact somatic inhibition as demonstrated by the associated reduction in inhibitory synaptic drive. Cumulatively, here we demonstrate novel microglia-mediated mechanisms that may contribute to synaptic loss and cognitive impairment after traumatic brain injury.
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spelling pubmed-91195742022-05-19 Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury Krukowski, Karen Nolan, Amber Becker, McKenna Picard, Katherine Vernoux, Nathalie Frias, Elma S. Feng, Xi Tremblay, Marie-Eve Rosi, Susanna Brain Behav Immun Article Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI-related pathologies. Following TBI, microglia, the brain resident immune cells, turn into a “reactive” state characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Utilizing multimodal, state-of-the-art techniques that widely span from ultrastructural analysis to optogenetic interrogation of circuit function, we investigated the reactive microglia phenotype one week after injury when learning and memory deficits are also measured. Microglia displayed increased: (i) phagocytic activity in vivo, (ii) synaptic engulfment, (iii) increased neuronal contact, including with dendrites and somata (termed ‘satellite microglia’). Functionally, satellite microglia might impact somatic inhibition as demonstrated by the associated reduction in inhibitory synaptic drive. Cumulatively, here we demonstrate novel microglia-mediated mechanisms that may contribute to synaptic loss and cognitive impairment after traumatic brain injury. 2021-11 2021-08-14 /pmc/articles/PMC9119574/ /pubmed/34403733 http://dx.doi.org/10.1016/j.bbi.2021.08.210 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Krukowski, Karen
Nolan, Amber
Becker, McKenna
Picard, Katherine
Vernoux, Nathalie
Frias, Elma S.
Feng, Xi
Tremblay, Marie-Eve
Rosi, Susanna
Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
title Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
title_full Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
title_fullStr Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
title_full_unstemmed Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
title_short Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
title_sort novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119574/
https://www.ncbi.nlm.nih.gov/pubmed/34403733
http://dx.doi.org/10.1016/j.bbi.2021.08.210
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