Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice

Introduction: The complex physiological and psychological responses to regular exercise are yet to be fully elucidated. Exercise strongly modulates the immune system, inducing a plethora of dynamic responses involving the innate immune cell function and inflammatory processes that contribute to both...

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Main Authors: I. Gálvez, M.C. Navarro, S. Torres-Piles, L. Martín-Cordero, M.D. Hinchado, E. Ortega
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Brain, Behavior, & Immunity - Health
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666354624001881
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author I. Gálvez
M.C. Navarro
S. Torres-Piles
L. Martín-Cordero
M.D. Hinchado
E. Ortega
author_facet I. Gálvez
M.C. Navarro
S. Torres-Piles
L. Martín-Cordero
M.D. Hinchado
E. Ortega
author_sort I. Gálvez
collection DOAJ
description Introduction: The complex physiological and psychological responses to regular exercise are yet to be fully elucidated. Exercise strongly modulates the immune system, inducing a plethora of dynamic responses involving the innate immune cell function and inflammatory processes that contribute to both potential health benefits and harmful side effects. Indeed, the relationship between physical exercise, stress, immunity, and metabolism serves as a paramount model of neuroimmunoendocrine interaction. Thus, the objective of this study was to conduct a comprehensive analysis of both systemic and local immunophysiological responses together with behavioral responses to a protocol of anxiety-inducing exercise. Material and methods: C57BL/6J mice were randomly allocated into sedentary or exercised groups, where the anxiety-inducing exercise protocol was based on a 14-day consecutive program of swimming in water at 38 °C. Anxiety-like behavior was corroborated through the elevated plus maze test. Systemic biomarkers of the stress response were assessed using ELISA technique and the expression of systemic inflammatory cytokines with Bio-Plex system. Phagocytic/microbicide activity, the expression of M1/M2 phenotype markers (CD11c, iNOS, CD206, ARG-1) and cytokines of the inflammatory response (MCP-1, IL-8, IL-6, TNF-α, TGF-β, IL-10) of peritoneal macrophages were determined via flow cytometry. Adipose tissue macrophage infiltration was studied through fluorescence immunohistochemistry. Results: Anxiety-like behavior, elevated circulating glucose concentrations, systemic stress and inflammatory responses, together with increased oxidative stress and inflammatory profile of peritoneal macrophages, and macrophage infiltration in white adipose tissue were observed in exercised animals. Conclusions: A protocol of exercise that induces anxiety is associated with a neuroimmunoendocrine dysregulation affecting the feedback between the inflammatory and the stress responses, together with detrimental metabolic effects in glucose modulation. Systemic inflammatory alterations are accompanied by detrimental inflammatory responses in tissue macrophage populations. Altogether, these results show that exercise associated with anxiety, stress, pro-inflammatory responses, and hyperglycaemia represents a model of ‘dangerous exercise’.
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spelling doaj-art-6be58ed43edf473b8c2c9494dc48311e2025-01-26T05:04:58ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-02-0143100910Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J miceI. Gálvez0M.C. Navarro1S. Torres-Piles2L. Martín-Cordero3M.D. Hinchado4E. Ortega5Immunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain; Immunophysiology Research Group, Nursing Department, Faculty of Medicine and Health Sciences, University of Extremadura, 06071, Badajoz, SpainImmunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain; Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071, Badajoz, Spain; Corresponding author. Immunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain.Immunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain; Immunophysiology Research Group, Department of Medical-Surgical Therapy, Faculty of Medicine, University of Extremadura, 06071, Badajoz, SpainImmunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain; Immunophysiology Research Group, Nursing Department, University Center of Plasencia, University of Extremadura, 10600, Plasencia, SpainImmunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain; Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071, Badajoz, SpainImmunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain; Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071, Badajoz, Spain; Corresponding author. Immunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071, Badajoz, Spain.Introduction: The complex physiological and psychological responses to regular exercise are yet to be fully elucidated. Exercise strongly modulates the immune system, inducing a plethora of dynamic responses involving the innate immune cell function and inflammatory processes that contribute to both potential health benefits and harmful side effects. Indeed, the relationship between physical exercise, stress, immunity, and metabolism serves as a paramount model of neuroimmunoendocrine interaction. Thus, the objective of this study was to conduct a comprehensive analysis of both systemic and local immunophysiological responses together with behavioral responses to a protocol of anxiety-inducing exercise. Material and methods: C57BL/6J mice were randomly allocated into sedentary or exercised groups, where the anxiety-inducing exercise protocol was based on a 14-day consecutive program of swimming in water at 38 °C. Anxiety-like behavior was corroborated through the elevated plus maze test. Systemic biomarkers of the stress response were assessed using ELISA technique and the expression of systemic inflammatory cytokines with Bio-Plex system. Phagocytic/microbicide activity, the expression of M1/M2 phenotype markers (CD11c, iNOS, CD206, ARG-1) and cytokines of the inflammatory response (MCP-1, IL-8, IL-6, TNF-α, TGF-β, IL-10) of peritoneal macrophages were determined via flow cytometry. Adipose tissue macrophage infiltration was studied through fluorescence immunohistochemistry. Results: Anxiety-like behavior, elevated circulating glucose concentrations, systemic stress and inflammatory responses, together with increased oxidative stress and inflammatory profile of peritoneal macrophages, and macrophage infiltration in white adipose tissue were observed in exercised animals. Conclusions: A protocol of exercise that induces anxiety is associated with a neuroimmunoendocrine dysregulation affecting the feedback between the inflammatory and the stress responses, together with detrimental metabolic effects in glucose modulation. Systemic inflammatory alterations are accompanied by detrimental inflammatory responses in tissue macrophage populations. Altogether, these results show that exercise associated with anxiety, stress, pro-inflammatory responses, and hyperglycaemia represents a model of ‘dangerous exercise’.http://www.sciencedirect.com/science/article/pii/S2666354624001881BehaviorRegular exerciseSwimmingCytokinesMacrophagesInflammation
spellingShingle I. Gálvez
M.C. Navarro
S. Torres-Piles
L. Martín-Cordero
M.D. Hinchado
E. Ortega
Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice
Brain, Behavior, & Immunity - Health
Behavior
Regular exercise
Swimming
Cytokines
Macrophages
Inflammation
title Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice
title_full Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice
title_fullStr Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice
title_full_unstemmed Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice
title_short Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice
title_sort exercise induced anxiety impairs local and systemic inflammatory response and glucose metabolism in c57bl 6j mice
topic Behavior
Regular exercise
Swimming
Cytokines
Macrophages
Inflammation
url http://www.sciencedirect.com/science/article/pii/S2666354624001881
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