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Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF
A growing body of evidence supports the close relationship between major depressive disorder (MDD), a severe psychiatric disease more common among women than men, and alterations of the immune/inflammatory system. However, despite the large number of studies aimed at understanding the molecular base...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658805/ https://www.ncbi.nlm.nih.gov/pubmed/31379496 http://dx.doi.org/10.3389/fnmol.2019.00166 |
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author | Rossetti, Andrea Carlo Paladini, Maria Serena Trepci, Ada Mallien, Anne Riva, Marco Andrea Gass, Peter Molteni, Raffaella |
author_facet | Rossetti, Andrea Carlo Paladini, Maria Serena Trepci, Ada Mallien, Anne Riva, Marco Andrea Gass, Peter Molteni, Raffaella |
author_sort | Rossetti, Andrea Carlo |
collection | PubMed |
description | A growing body of evidence supports the close relationship between major depressive disorder (MDD), a severe psychiatric disease more common among women than men, and alterations of the immune/inflammatory system. However, despite the large number of studies aimed at understanding the molecular bases of this association, a lack of information exists on the potential cross-talk between systems known to be involved in depression and components of the inflammatory response, especially with respect to sex differences. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with a well-established role in MDD etiopathology: it is altered in depressed patients as well as in animal models of the disease and its changes are restored by antidepressant drugs. Interestingly, this neurotrophin is also involved in the inflammatory response. Indeed, it can be secreted by microglia, the primary innate immune cells in the central nervous system whose functions may be in turn regulated by BDNF. With these premises, in this study, we investigated the reciprocal impact of BDNF and the immune system by evaluating the neuroinflammatory response in male and female BDNF-heterozygous mutant mice acutely treated with the cytokine-inducer lipopolysaccharide (LPS). Specifically, we assessed the potential onset of an LPS-induced sickness behavior as well as changes of inflammatory mediators in the mouse hippocampus and frontal cortex, with respect to both genotype and sex. We found that the increased inflammatory response induced by LPS in the brain of male mice was independent of the genotype, whereas in the female, it was restricted to the heterozygous mice with no changes in the wild-type group, suggestive of a role for BDNF in the sex-dependent effect of the inflammatory challenge. Considering the involvement of both BDNF and neuroinflammation in several psychiatric diseases and the diverse incidence of such pathologies in males and females, a deeper investigation of the mechanisms underlying their interaction may have a critical translational relevance. |
format | Online Article Text |
id | pubmed-6658805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66588052019-08-02 Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF Rossetti, Andrea Carlo Paladini, Maria Serena Trepci, Ada Mallien, Anne Riva, Marco Andrea Gass, Peter Molteni, Raffaella Front Mol Neurosci Neuroscience A growing body of evidence supports the close relationship between major depressive disorder (MDD), a severe psychiatric disease more common among women than men, and alterations of the immune/inflammatory system. However, despite the large number of studies aimed at understanding the molecular bases of this association, a lack of information exists on the potential cross-talk between systems known to be involved in depression and components of the inflammatory response, especially with respect to sex differences. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with a well-established role in MDD etiopathology: it is altered in depressed patients as well as in animal models of the disease and its changes are restored by antidepressant drugs. Interestingly, this neurotrophin is also involved in the inflammatory response. Indeed, it can be secreted by microglia, the primary innate immune cells in the central nervous system whose functions may be in turn regulated by BDNF. With these premises, in this study, we investigated the reciprocal impact of BDNF and the immune system by evaluating the neuroinflammatory response in male and female BDNF-heterozygous mutant mice acutely treated with the cytokine-inducer lipopolysaccharide (LPS). Specifically, we assessed the potential onset of an LPS-induced sickness behavior as well as changes of inflammatory mediators in the mouse hippocampus and frontal cortex, with respect to both genotype and sex. We found that the increased inflammatory response induced by LPS in the brain of male mice was independent of the genotype, whereas in the female, it was restricted to the heterozygous mice with no changes in the wild-type group, suggestive of a role for BDNF in the sex-dependent effect of the inflammatory challenge. Considering the involvement of both BDNF and neuroinflammation in several psychiatric diseases and the diverse incidence of such pathologies in males and females, a deeper investigation of the mechanisms underlying their interaction may have a critical translational relevance. Frontiers Media S.A. 2019-07-17 /pmc/articles/PMC6658805/ /pubmed/31379496 http://dx.doi.org/10.3389/fnmol.2019.00166 Text en Copyright © 2019 Rossetti, Paladini, Trepci, Mallien, Riva, Gass and Molteni. 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 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 | Neuroscience Rossetti, Andrea Carlo Paladini, Maria Serena Trepci, Ada Mallien, Anne Riva, Marco Andrea Gass, Peter Molteni, Raffaella Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF |
title | Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF |
title_full | Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF |
title_fullStr | Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF |
title_full_unstemmed | Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF |
title_short | Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF |
title_sort | differential neuroinflammatory response in male and female mice: a role for bdnf |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658805/ https://www.ncbi.nlm.nih.gov/pubmed/31379496 http://dx.doi.org/10.3389/fnmol.2019.00166 |
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