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

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.

Hypothetical novel simulations to explain the evolutionary survival of the hypo-reproductive extreme tail in the complex human diversity.

Hierarchical structures which lie hidden between human complex conditions and reproductivity cannot be simple, and trends of each population component does not necessarily pertain to evolutionary theories. As an illustration, the fitness of individuals with heritable extreme conditions can be low across continuing generations in observational data. Autism and schizophrenia are characterized by such evolutionary paradox of survival and hypo-reproductivity in the complex human diversity. Theoretical mechanisms for the observational fact were evaluated using a simple formula which was established to simulate stochastic epistasis-mediated phenotypic diversity. The survival of the hypo-reproductive extreme tail could be imitated just by the predominant presence of stochastic epistasis mechanism, suggesting that stochastic epistasis might be a genetic prerequisite for the evolutionary paradox. As supplemental cofactors of stochastic epistasis, a random link of the extreme tail to both un- and hyper-reproductivity and group assortative mating were shown to be effective for the paradox. Especially, the mixed localization of un- and hyper-reproductivity in the tail of a generational population evidently induced the continuous survival of outliers and extremes. These hypothetical considerations and mathematical simulations may suggest the significance of stochastic epistasis as the essential genetic background of complex human diversity.