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Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels
Psychological chronic stress is an important risk factor for major depressive disorder, of which consequences have been widely studied in rodent models. This work aimed at describing a pig model of chronic stress based on social isolation, environmental impoverishment and unpredictability. Three gro...
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/PMC6646532/ https://www.ncbi.nlm.nih.gov/pubmed/31379533 http://dx.doi.org/10.3389/fnbeh.2019.00161 |
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author | Menneson, Sophie Ménicot, Samuel Ferret-Bernard, Stéphanie Guérin, Sylvie Romé, Véronique Le Normand, Laurence Randuineau, Gwénaëlle Gambarota, Giulio Noirot, Virginie Etienne, Pierre Coquery, Nicolas Val-Laillet, David |
author_facet | Menneson, Sophie Ménicot, Samuel Ferret-Bernard, Stéphanie Guérin, Sylvie Romé, Véronique Le Normand, Laurence Randuineau, Gwénaëlle Gambarota, Giulio Noirot, Virginie Etienne, Pierre Coquery, Nicolas Val-Laillet, David |
author_sort | Menneson, Sophie |
collection | PubMed |
description | Psychological chronic stress is an important risk factor for major depressive disorder, of which consequences have been widely studied in rodent models. This work aimed at describing a pig model of chronic stress based on social isolation, environmental impoverishment and unpredictability. Three groups of animals of both sexes were constituted. Two were exposed to the psychosocial stressors while receiving (SF, n = 12) or not (SC, n = 22) the antidepressant fluoxetine, and a third group (NSC, n = 22) remained unstressed. Animals were observed in home pens and during dedicated tests to assess resignation and anxiety-like behaviors. Brain structure and function were evaluated via proton MRS and fMRI. Hippocampal molecular biology and immunodetection of cellular proliferation (Ki67(+)) and neuron maturation (DCX(+)) in the dentate gyrus were also performed. Salivary cortisol, fecal short-chain fatty acids (SCFAs), and various plasmatic and intestinal biomarkers were analyzed. Compared to NSC, SC animals showed more resignation (p = 0.019) and had a higher level of salivary cortisol (p = 0.020). SC brain responses to stimulation by a novel odor were lower, similarly to their hippocampal neuronal density (p = 0.015), cellular proliferation (p = 0.030), and hippocampal levels of BDNF and 5-HT(1A)R (p = 0.056 and p = 0.007, respectively). However, the number of DCX(+) cells was higher in the ventral dentate gyrus in this group (p = 0.025). In addition, HOMA-IR was also higher (p < 0.001) and microbiota fermentation activity was lower (SCFAs, SC/NSC: p < 0.01) in SC animals. Fluoxetine partially or totally reversed several of these effects. Exposure to psychosocial stressors in the pig model induced effects consistent with the human and rodent literature, including resignation behavior and alterations of the HPA axis and hippocampus. This model opens the way to innovative translational research exploring the mechanisms of chronic stress and testing intervention strategies with good face validity related to human. |
format | Online Article Text |
id | pubmed-6646532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66465322019-08-02 Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels Menneson, Sophie Ménicot, Samuel Ferret-Bernard, Stéphanie Guérin, Sylvie Romé, Véronique Le Normand, Laurence Randuineau, Gwénaëlle Gambarota, Giulio Noirot, Virginie Etienne, Pierre Coquery, Nicolas Val-Laillet, David Front Behav Neurosci Neuroscience Psychological chronic stress is an important risk factor for major depressive disorder, of which consequences have been widely studied in rodent models. This work aimed at describing a pig model of chronic stress based on social isolation, environmental impoverishment and unpredictability. Three groups of animals of both sexes were constituted. Two were exposed to the psychosocial stressors while receiving (SF, n = 12) or not (SC, n = 22) the antidepressant fluoxetine, and a third group (NSC, n = 22) remained unstressed. Animals were observed in home pens and during dedicated tests to assess resignation and anxiety-like behaviors. Brain structure and function were evaluated via proton MRS and fMRI. Hippocampal molecular biology and immunodetection of cellular proliferation (Ki67(+)) and neuron maturation (DCX(+)) in the dentate gyrus were also performed. Salivary cortisol, fecal short-chain fatty acids (SCFAs), and various plasmatic and intestinal biomarkers were analyzed. Compared to NSC, SC animals showed more resignation (p = 0.019) and had a higher level of salivary cortisol (p = 0.020). SC brain responses to stimulation by a novel odor were lower, similarly to their hippocampal neuronal density (p = 0.015), cellular proliferation (p = 0.030), and hippocampal levels of BDNF and 5-HT(1A)R (p = 0.056 and p = 0.007, respectively). However, the number of DCX(+) cells was higher in the ventral dentate gyrus in this group (p = 0.025). In addition, HOMA-IR was also higher (p < 0.001) and microbiota fermentation activity was lower (SCFAs, SC/NSC: p < 0.01) in SC animals. Fluoxetine partially or totally reversed several of these effects. Exposure to psychosocial stressors in the pig model induced effects consistent with the human and rodent literature, including resignation behavior and alterations of the HPA axis and hippocampus. This model opens the way to innovative translational research exploring the mechanisms of chronic stress and testing intervention strategies with good face validity related to human. Frontiers Media S.A. 2019-07-16 /pmc/articles/PMC6646532/ /pubmed/31379533 http://dx.doi.org/10.3389/fnbeh.2019.00161 Text en Copyright © 2019 Menneson, Ménicot, Ferret-Bernard, Guérin, Romé, Le Normand, Randuineau, Gambarota, Noirot, Etienne, Coquery and Val-Laillet. 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 Menneson, Sophie Ménicot, Samuel Ferret-Bernard, Stéphanie Guérin, Sylvie Romé, Véronique Le Normand, Laurence Randuineau, Gwénaëlle Gambarota, Giulio Noirot, Virginie Etienne, Pierre Coquery, Nicolas Val-Laillet, David Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels |
title | Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels |
title_full | Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels |
title_fullStr | Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels |
title_full_unstemmed | Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels |
title_short | Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels |
title_sort | validation of a psychosocial chronic stress model in the pig using a multidisciplinary approach at the gut-brain and behavior levels |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646532/ https://www.ncbi.nlm.nih.gov/pubmed/31379533 http://dx.doi.org/10.3389/fnbeh.2019.00161 |
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