Voluntary wheel running promotes resilience to the behavioral effects of unpredictable chronic mild stress in male and female mice

Abstract

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. Physiological and behavioral evaluations were conducted throughout the stress paradigm to determine if exercise blunts the effects of UCMS. Chronic stress induced voluntary wheel running (VWR) and weight loss in male and female mice. Compared to males, increased VWR was reported in females who also regained their weight lost by the end of the UCMS protocol. Exercise promoted resilience to stress-induced hyponeophagia in the novelty-suppressed feeding test and increased sucrose consumption. Exercise induced a sex-specific reduction in immobility and avoidance behavior in the tail suspension and open field tests and increased exploratory behavior in the light-dark test. These results indicate that exercise can promote resilience to the behavioral effects of chronic stress in males and females, and can affect behavior independent of chronic stress.

Keywords:

• Exercise
• chronic
• stress
• sex
• behavior
• resilience

Author contributions

EE: conceptualization; formal analysis; investigation; writing-original draft; and visualization. AYZ: Formal analysis; investigation; and writing-original draft. AGW: Formal analysis; investigation; and writing-original draft. MJP: Formal analysis and investigation. MTM: conceptualization; formal analysis; investigation; writing- review and editing; supervision; and project administration.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was funded by startup funds granted to Melissa Manners from St. Joseph’s University.

Notes on contributors

Elias Elias

Elias Elias received his undergraduate degree in Biology and his Master’s degree in Molecular Biology from the Lebanese American University. His research experience expands from cancer in vitro pharmacology to in vivo neurobiology. He is currently pursuing his PhD in Cell and Molecular Biology at Saint Joseph’s University in the laboratory of Dr. Melissa T. Manners conducting research on neuroinflammation and mechanisms of resilience to chronic stress.

Ariel Y. Zhang

Ariel Y. Zhang received her undergraduate degree in Integrative Neuroscience from Fordham University, and her master’s degree in Biomedical Science from Geisinger Commonwealth School of Medicine. She is currently pursuing a PhD in Cell and Molecular Biology from Saint Joseph’s University in the laboratory of Dr. Melissa T. Manners. Her graduate work focuses on chronic stress and neuroinflammation.

Abigail G. White

Abigail Grace White received her Bachelor of Science degree in Neuroscience from the University of the Sciences, now Saint Joseph’s University. During her undergraduate training she investigated the molecular and behavioral effects of chronic stress in the laboratory of Dr. Manners.

Matthew J. Pyle

Matthew J. Pyle received his Bachelor of Science degree in Biology from the University of the Sciences, now Saint Joseph’s University, where he conducted neurobiology research in the Manners Lab.

Melissa T. Manners

Melissa Taft Manners received her undergraduate degree in Biology from Rutgers University, and her PhD in Pharmacology and Physiology from Drexel University College of Medicine. She developed research expertise in stress neurobiology during her postdoctoral training in the laboratory of Dr. Julie Blendy at the University of Pennsylvania. Her laboratory has been conducting stress research since 2019 at University of the Sciences, now Saint Joseph’s University, and is continuing this research focus at Rowan University.