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Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells

Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an anima...

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Autores principales: Ślusarczyk, Joanna, Trojan, Ewa, Głombik, Katarzyna, Budziszewska, Bogusława, Kubera, Marta, Lasoń, Władysław, Popiołek-Barczyk, Katarzyna, Mika, Joanna, Wędzony, Krzysztof, Basta-Kaim, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357262/
https://www.ncbi.nlm.nih.gov/pubmed/25814933
http://dx.doi.org/10.3389/fncel.2015.00082
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author Ślusarczyk, Joanna
Trojan, Ewa
Głombik, Katarzyna
Budziszewska, Bogusława
Kubera, Marta
Lasoń, Władysław
Popiołek-Barczyk, Katarzyna
Mika, Joanna
Wędzony, Krzysztof
Basta-Kaim, Agnieszka
author_facet Ślusarczyk, Joanna
Trojan, Ewa
Głombik, Katarzyna
Budziszewska, Bogusława
Kubera, Marta
Lasoń, Władysław
Popiołek-Barczyk, Katarzyna
Mika, Joanna
Wędzony, Krzysztof
Basta-Kaim, Agnieszka
author_sort Ślusarczyk, Joanna
collection PubMed
description Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression) as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test), the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive) in 3-month-old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1β, IL-18, IL-6, TNF-α, CCL2, CXCL12, CCR2, CXCR4) and beneficial (insulin-like growth factor-1 (IGF-1), brain derived neurotrophic factor (BDNF)) phenotypes in cultures of microglia obtained from the cortices of 1–2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like) disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1β, IL-18, TNF-α and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats. Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood.
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spelling pubmed-43572622015-03-26 Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells Ślusarczyk, Joanna Trojan, Ewa Głombik, Katarzyna Budziszewska, Bogusława Kubera, Marta Lasoń, Władysław Popiołek-Barczyk, Katarzyna Mika, Joanna Wędzony, Krzysztof Basta-Kaim, Agnieszka Front Cell Neurosci Neuroscience Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression) as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test), the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive) in 3-month-old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1β, IL-18, IL-6, TNF-α, CCL2, CXCL12, CCR2, CXCR4) and beneficial (insulin-like growth factor-1 (IGF-1), brain derived neurotrophic factor (BDNF)) phenotypes in cultures of microglia obtained from the cortices of 1–2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like) disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1β, IL-18, TNF-α and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats. Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood. Frontiers Media S.A. 2015-03-12 /pmc/articles/PMC4357262/ /pubmed/25814933 http://dx.doi.org/10.3389/fncel.2015.00082 Text en Copyright © 2015 Ślusarczyk, Trojan, Głombik, Budziszewska, Kubera, Lasoń, Popiołek-Barczyk, Mika, Wędzony and Basta-Kaim. http://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 and reproduction in other forums is permitted, provided the original author(s) or licensor 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 Neuroscience
Ślusarczyk, Joanna
Trojan, Ewa
Głombik, Katarzyna
Budziszewska, Bogusława
Kubera, Marta
Lasoń, Władysław
Popiołek-Barczyk, Katarzyna
Mika, Joanna
Wędzony, Krzysztof
Basta-Kaim, Agnieszka
Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
title Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
title_full Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
title_fullStr Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
title_full_unstemmed Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
title_short Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
title_sort prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357262/
https://www.ncbi.nlm.nih.gov/pubmed/25814933
http://dx.doi.org/10.3389/fncel.2015.00082
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