Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline

Adam J Janowski; Kazuhiro Hayashi; Ashley N Plumb; Joseph B Lesnak; Angela F Smith; Lynn Rasmussen; Elizabeth Gross; Andrew A Post; Giovanni Berardi; Marguerita E Klein; Reid Brown; Heath Vignes; Eric B Taylor; Andrea G Nackley; Kathleen A Sluka

doi:10.1038/s41598-026-62864-x

Back

Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline

Journal article

Open access

Peer reviewed

Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline

Adam J Janowski, Kazuhiro Hayashi, Ashley N Plumb, Joseph B Lesnak, Angela F Smith, Lynn Rasmussen, Elizabeth Gross, Andrew A Post, Giovanni Berardi, Marguerita E Klein, …

Scientific reports

07/22/2026

DOI: 10.1038/s41598-026-62864-x

PMID: 42481658

Files and links (1)

url

https://doi.org/10.1038/s41598-026-62864-xView

Published (Version of record) Open Access

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.

Immune System

Metabolomics

Fatigue

Running wheel

Open field

Details

Title: Subtitle: Behavioral and molecular characterization of fatigue-like manifestations triggered by acute restraint stress and LPS or saline
Creators: Adam J Janowski - University of Iowa
Kazuhiro Hayashi - University of Iowa
Ashley N Plumb - University of Iowa
Joseph B Lesnak - University of Iowa
Angela F Smith - University of Iowa
Lynn Rasmussen - University of Iowa
Elizabeth Gross - University of Iowa
Andrew A Post - University of Iowa
Giovanni Berardi - University of Iowa
Marguerita E Klein - Duke University
Reid Brown - University of Iowa, Molecular Physiology and Biophysics
Heath Vignes - University of Iowa
Eric B Taylor - University of Iowa
Andrea G Nackley - Duke University
Kathleen A Sluka - University of Iowa
Resource Type: Journal article
Publication Details: Scientific reports
DOI: 10.1038/s41598-026-62864-x
PMID: 42481658
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: Springer Nature
Grant note: R01 AR073187 / NIAMS NIH HHS
Language: English
Electronic publication date: 07/22/2026
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9985183561802771

Metrics

1 Record Views