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Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk

Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive...

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Detalles Bibliográficos
Autores principales: Carloni, Elisa, Ramos, Adriana, Hayes, Lindsay N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657756/
https://www.ncbi.nlm.nih.gov/pubmed/34884841
http://dx.doi.org/10.3390/ijms222313035
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author Carloni, Elisa
Ramos, Adriana
Hayes, Lindsay N.
author_facet Carloni, Elisa
Ramos, Adriana
Hayes, Lindsay N.
author_sort Carloni, Elisa
collection PubMed
description Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting. Immune activation is a shared pathophysiology across several different developmental stressors and may thus be a targetable treatment to mitigate the later behavioral deficits. In this review, we explore different types of prenatal and perinatal stressors and their contribution to disease risk and underlying molecular mechanisms. We highlight the impact of developmental stressors on microglia biology because of their early infiltration into the brain, their critical role in brain development and function, and their long-lived status in the brain throughout life. Furthermore, we introduce innate immune memory as a potential underlying mechanism for developmental stressors’ impact on disease. Finally, we highlight the molecular and epigenetic reprogramming that is known to underlie innate immune memory and explain how similar molecular mechanisms may be at work for cells to retain a long-term perturbation after exposure to developmental stressors.
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spelling pubmed-86577562021-12-10 Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk Carloni, Elisa Ramos, Adriana Hayes, Lindsay N. Int J Mol Sci Review Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting. Immune activation is a shared pathophysiology across several different developmental stressors and may thus be a targetable treatment to mitigate the later behavioral deficits. In this review, we explore different types of prenatal and perinatal stressors and their contribution to disease risk and underlying molecular mechanisms. We highlight the impact of developmental stressors on microglia biology because of their early infiltration into the brain, their critical role in brain development and function, and their long-lived status in the brain throughout life. Furthermore, we introduce innate immune memory as a potential underlying mechanism for developmental stressors’ impact on disease. Finally, we highlight the molecular and epigenetic reprogramming that is known to underlie innate immune memory and explain how similar molecular mechanisms may be at work for cells to retain a long-term perturbation after exposure to developmental stressors. MDPI 2021-12-02 /pmc/articles/PMC8657756/ /pubmed/34884841 http://dx.doi.org/10.3390/ijms222313035 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Carloni, Elisa
Ramos, Adriana
Hayes, Lindsay N.
Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
title Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
title_full Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
title_fullStr Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
title_full_unstemmed Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
title_short Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
title_sort developmental stressors induce innate immune memory in microglia and contribute to disease risk
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657756/
https://www.ncbi.nlm.nih.gov/pubmed/34884841
http://dx.doi.org/10.3390/ijms222313035
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