Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline
5 affiliations
- 1Department of Physical Therapy & Rehabilitation Sciences, University of Iowa
- 2Department of Anesthesiology, Duke University School of Medicine
- 3Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa
- 4Flow Cytometry Core, Carver College of Medicine, University of Iowa
- 5Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa
Abstract
Fatigue is characterized as a feeling of exhaustion or lack of energy, is a common symptom of multiple chronic illnesses and interferes with daily activities and quality of life. There is a limited availability of animal models to examine potential underlying mechanisms, ultimately limiting development of potential therapeutic strategies. The primary purpose of this study was to develop a mouse model of persistent fatigue. A secondary purpose was to characterize potential measures of “fatigue-like” behaviors. An exploratory goal was to examine for immune and metabolic changes in the model. We examined voluntary wheel running and open field as measures of physical fatigue, and muscle and paw sensitivity as measures of pain. We also examined immune cell phenotype and plasma metabolite profiles after development of persistent fatigue. Acute stress paired with LPS or saline reduced wheel running compared to LPS alone or stress alone. Animals that received acute stress and LPS, showed a decreased ratio of T-helper to T-cytotoxic cells and reduced fatty acid metabolites 10 days after induction; there were no changes in the other groups. Thus, we characterized two unique methods, each requiring multiple stressors, to induce long-lasting fatigue-like behaviors that were associated with different mechanistic changes.
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BibTeX
@article{janowski2026behavioral,
title = {{Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline}},
author = {Adam J. Janowski and Kazuhiro Hayashi and Ashley N. Plumb and Joseph B. Lesnak and Angela F. Smith and Lynn Rasmussen and Elizabeth Gross and Andrew A. Post and Giovanni Berardi and Marguerita E. Klein and Reid Brown and Heath Vignes and Eric B. Taylor and Andrea G. Nackley and Kathleen A. Sluka},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62864-x},
url = {https://doi.org/10.1038/s41598-026-62864-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline
AU - Adam J. Janowski
AU - Kazuhiro Hayashi
AU - Ashley N. Plumb
AU - Joseph B. Lesnak
AU - Angela F. Smith
AU - Lynn Rasmussen
AU - Elizabeth Gross
AU - Andrew A. Post
AU - Giovanni Berardi
AU - Marguerita E. Klein
AU - Reid Brown
AU - Heath Vignes
AU - Eric B. Taylor
AU - Andrea G. Nackley
AU - Kathleen A. Sluka
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62864-x
UR - https://doi.org/10.1038/s41598-026-62864-x
AB - Fatigue is characterized as a feeling of exhaustion or lack of energy, is a common symptom of multiple chronic illnesses and interferes with daily activities and quality of life. There is a limited availability of animal models to examine potential underlying mechanisms, ultimately limiting development of potential therapeutic strategies. The primary purpose of this study was to develop a mouse model of persistent fatigue. A secondary purpose was to characterize potential measures of “fatigue-like” behaviors. An exploratory goal was to examine for immune and metabolic changes in the model. We examined voluntary wheel running and open field as measures of physical fatigue, and muscle and paw sensitivity as measures of pain. We also examined immune cell phenotype and plasma metabolite profiles after development of persistent fatigue. Acute stress paired with LPS or saline reduced wheel running compared to LPS alone or stress alone. Animals that received acute stress and LPS, showed a decreased ratio of T-helper to T-cytotoxic cells and reduced fatty acid metabolites 10 days after induction; there were no changes in the other groups. Thus, we characterized two unique methods, each requiring multiple stressors, to induce long-lasting fatigue-like behaviors that were associated with different mechanistic changes.
SN - 2045-2322
ER -