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Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice

BACKGROUND: Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically s...

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Autores principales: Couch, Yvonne, Trofimov, Alexander, Markova, Natalyia, Nikolenko, Vladimir, Steinbusch, Harry W., Chekhonin, Vladimir, Schroeter, Careen, Lesch, Klaus-Peter, Anthony, Daniel C., Strekalova, Tatyana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867526/
https://www.ncbi.nlm.nih.gov/pubmed/27184538
http://dx.doi.org/10.1186/s12974-016-0572-0
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author Couch, Yvonne
Trofimov, Alexander
Markova, Natalyia
Nikolenko, Vladimir
Steinbusch, Harry W.
Chekhonin, Vladimir
Schroeter, Careen
Lesch, Klaus-Peter
Anthony, Daniel C.
Strekalova, Tatyana
author_facet Couch, Yvonne
Trofimov, Alexander
Markova, Natalyia
Nikolenko, Vladimir
Steinbusch, Harry W.
Chekhonin, Vladimir
Schroeter, Careen
Lesch, Klaus-Peter
Anthony, Daniel C.
Strekalova, Tatyana
author_sort Couch, Yvonne
collection PubMed
description BACKGROUND: Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive. METHODS: Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress. RESULTS: When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1β and region-specific 5-HT(2A) mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1β levels. CONCLUSIONS: It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0572-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-48675262016-05-17 Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice Couch, Yvonne Trofimov, Alexander Markova, Natalyia Nikolenko, Vladimir Steinbusch, Harry W. Chekhonin, Vladimir Schroeter, Careen Lesch, Klaus-Peter Anthony, Daniel C. Strekalova, Tatyana J Neuroinflammation Research BACKGROUND: Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive. METHODS: Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress. RESULTS: When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1β and region-specific 5-HT(2A) mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1β levels. CONCLUSIONS: It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0572-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-16 /pmc/articles/PMC4867526/ /pubmed/27184538 http://dx.doi.org/10.1186/s12974-016-0572-0 Text en © Couch et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Couch, Yvonne
Trofimov, Alexander
Markova, Natalyia
Nikolenko, Vladimir
Steinbusch, Harry W.
Chekhonin, Vladimir
Schroeter, Careen
Lesch, Klaus-Peter
Anthony, Daniel C.
Strekalova, Tatyana
Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
title Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
title_full Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
title_fullStr Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
title_full_unstemmed Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
title_short Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
title_sort low-dose lipopolysaccharide (lps) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867526/
https://www.ncbi.nlm.nih.gov/pubmed/27184538
http://dx.doi.org/10.1186/s12974-016-0572-0
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