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Acute repeated cage exchange stress modifies urinary stress and plasma metabolic profiles in male mice

PLOS ONE · 9 authors, 3 centres

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TL;DR

A/J mice subjected to repeated cage exchange (four times over 8 h) showed increased urinary catecholamines and corticosterone, greater anxiety-like behavior, lower plasma glucose, and higher levels of branched-chain amino acids and phenylalanine compared with control mice.

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A/J mice, a strain prone to stress, underwent four cage exchanges at 2-h intervals over 8 h to model novel-environment stress. Body temperature was measured via implanted microchip; urinary catecholamines, corticosterone, and plasma metabolites (glucose, free fatty acids, amino acids) were quantified. CE mice showed increased body temperature with each exchange, greater body weight reduction, and higher water intake. Urinary norepinephrine, epinephrine, and corticosterone levels were elevated in CE mice, and anxiety-like behavior scores were worse in the elevated plus maze. Plasma glucose was significantly lower, while branched-chain amino acids (isoleucine, leucine, valine) and phenylalanine were significantly higher in CE mice. Free fatty acids and several amino acids decreased from baseline in both groups without between-group differences. Limitations include use of only male mice of a single strain, one behavioral test, and inability to disentangle stress effects from physical activity. The findings suggest potential for nutritional intervention in novel-environment stress.

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preclinical research

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ORIGINAL PAPER

PMC10564260

Acute repeated cage exchange stress modifies urinary stress and plasma metabolic profiles in male mice

PLOS ONE

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ABSTRACT

Exposure to a novel environment is psychologically and physically stressful for humans and animals. The response has been reported to involve enhanced sympathetic nervous system activity, but changes in nutrient levels under stress are not fully understood. As a form of exposure to a novel environment, repeated cage exchange (CE, four times at 2-h intervals for 8 h from 08:00 h) during the light phase with no restraint on movement was applied to A/J mice, a strain particularly prone to stress. Body temperature was measured with a temperature-sensing microchip implanted in the interscapular region. The stress conditions and anxiety level were evaluated by measuring urinary catecholamines and corticosterone and by performing an anxiety-like behavior test, respectively. Major nutrients such as glucose, fatty acids, and amino acids in the plasma were also examined. CE mice showed a significant increase in body temperature with each CE. They also showed a significantly greater reduction of body weight change, more water intake, and higher levels of urinary catecholamines and corticosterone and anxiety-like behavior score than control mice. The model revealed a significantly lower plasma glucose level and higher levels of several essential amino acids, such as branched-chain amino acids and phenylalanine, than those of control mice. Meanwhile, free fatty acids and several amino acids such as arginine, aspartic acid, proline, threonine, and tryptophan in both sets of mice were significantly decreased from the corresponding levels at 08:00 h, while similar plasma levels were exhibited between mice with and without CE. In conclusion, repeated CE stress was associated with changes in glucose and amino acids in plasma. Although further study is needed to clarify how these changes are specifically linked to anxiety-like behavior, this study suggests the potential for nutritional intervention to counter stress in humans exposed to novel environments.

CITATION EXPORT

Sayuri Fushuku, Miharu Ushikai, Emi Arimura et al.. Acute repeated cage exchange stress modifies urinary stress and plasma metabolic profiles in male mice. PLOS ONE. (2023). https://doi.org/10.1371/journal.pone.0292649

AUTHORS

9 · 3 CENTRES

Sayuri Fushuku, Miharu Ushikai, Emi Arimura, Yuga Komaki, Masahisa Horiuchi, Yukiori Goto, Yukiori Goto, Yukiori Goto, Yukiori Goto

1 Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
2 Major in Food and Nutrition, Department of Life and Environmental Science, Kagoshima Prefectural College, Kagoshima, Japan
Kyoto University Graduate School of Informatics: Kyoto Daigaku Daigakuin Johogaku Kenkyuka, JAPAN

EDITOR / REVIEWER

Yukiori Goto