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Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder
Increasing evidence supports the notion that neuroinflammation plays a critical role in the etiology of major depressive disorder (MDD), at least in a subset of patients. By virtue of their capacity to transform into reactive states in response to inflammatory insults, microglia, the brain’s residen...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245023/ https://www.ncbi.nlm.nih.gov/pubmed/35782423 http://dx.doi.org/10.3389/fpsyt.2022.871997 |
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author | Rahimian, Reza Belliveau, Claudia Chen, Rebecca Mechawar, Naguib |
author_facet | Rahimian, Reza Belliveau, Claudia Chen, Rebecca Mechawar, Naguib |
author_sort | Rahimian, Reza |
collection | PubMed |
description | Increasing evidence supports the notion that neuroinflammation plays a critical role in the etiology of major depressive disorder (MDD), at least in a subset of patients. By virtue of their capacity to transform into reactive states in response to inflammatory insults, microglia, the brain’s resident immune cells, play a pivotal role in the induction of neuroinflammation. Experimental studies have demonstrated the ability of microglia to recognize pathogens or damaged cells, leading to the activation of a cytotoxic response that exacerbates damage to brain cells. However, microglia display a wide range of responses to injury and may also promote resolution stages of inflammation and tissue regeneration. MDD has been associated with chronic priming of microglia. Recent studies suggest that altered microglial morphology and function, caused either by intense inflammatory activation or by senescence, may contribute to depression and associated impairments in neuroplasticity. In this context, modifying microglia phenotype by tuning inflammatory pathways might have important translational relevance to harness neuroinflammation in MDD. Interestingly, it was recently shown that different microglial phenotypes are associated with distinct metabolic pathways and analysis of the underlying molecular mechanisms points to an instrumental role for energy metabolism in shaping microglial functions. Here, we review various canonical pro-inflammatory, anti-inflammatory and metabolic pathways in microglia that may provide new therapeutic opportunities to control neuroinflammation in brain disorders, with a strong focus on MDD. |
format | Online Article Text |
id | pubmed-9245023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92450232022-07-01 Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder Rahimian, Reza Belliveau, Claudia Chen, Rebecca Mechawar, Naguib Front Psychiatry Psychiatry Increasing evidence supports the notion that neuroinflammation plays a critical role in the etiology of major depressive disorder (MDD), at least in a subset of patients. By virtue of their capacity to transform into reactive states in response to inflammatory insults, microglia, the brain’s resident immune cells, play a pivotal role in the induction of neuroinflammation. Experimental studies have demonstrated the ability of microglia to recognize pathogens or damaged cells, leading to the activation of a cytotoxic response that exacerbates damage to brain cells. However, microglia display a wide range of responses to injury and may also promote resolution stages of inflammation and tissue regeneration. MDD has been associated with chronic priming of microglia. Recent studies suggest that altered microglial morphology and function, caused either by intense inflammatory activation or by senescence, may contribute to depression and associated impairments in neuroplasticity. In this context, modifying microglia phenotype by tuning inflammatory pathways might have important translational relevance to harness neuroinflammation in MDD. Interestingly, it was recently shown that different microglial phenotypes are associated with distinct metabolic pathways and analysis of the underlying molecular mechanisms points to an instrumental role for energy metabolism in shaping microglial functions. Here, we review various canonical pro-inflammatory, anti-inflammatory and metabolic pathways in microglia that may provide new therapeutic opportunities to control neuroinflammation in brain disorders, with a strong focus on MDD. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9245023/ /pubmed/35782423 http://dx.doi.org/10.3389/fpsyt.2022.871997 Text en Copyright © 2022 Rahimian, Belliveau, Chen and Mechawar. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Rahimian, Reza Belliveau, Claudia Chen, Rebecca Mechawar, Naguib Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder |
title | Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder |
title_full | Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder |
title_fullStr | Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder |
title_full_unstemmed | Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder |
title_short | Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder |
title_sort | microglial inflammatory-metabolic pathways and their potential therapeutic implication in major depressive disorder |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245023/ https://www.ncbi.nlm.nih.gov/pubmed/35782423 http://dx.doi.org/10.3389/fpsyt.2022.871997 |
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