Abstract

Chronic stress can impair the health of human brains. An important strategy that may prevent the accumulation of stress may be the consumption of functional foods. When senescence-accelerated mice prone 10 (SAMP10), a stress-sensitive strain, were loaded with stress using imposed male mouse territoriality, brain volume decreased. However, in mice that ingested theanine (6 mg/kg), the main amino acid in tea leaves, brain atrophy was suppressed, even under stress. On the other hand, brain atrophy was not clearly observed in a mouse strain that aged normally (Slc:ddY). The expression level of the transcription factor Npas4 (neuronal PAS domain protein 4), which regulates the formation and maintenance of inhibitory synapses in response to excitatory synaptic activity, decreased in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but increased in mice that ingested theanine. Lipocalin 2 (Lcn2), the expression of which increased in response to stress, was significantly high in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but not in mice that ingested theanine. These data suggest that Npas4 and Lcn2 are involved in the brain atrophy and stress vulnerability of SAMP10 mice, which are prevented by the consumption of theanine, causing changes in the expression of these genes.

Highlights

  • It is well established that stress—especially chronic stress—seriously perturbs physiological and/or psychological homeostasis and affects cognitive function and brain structure, including thatNutrients 2020, 12, 174; doi:10.3390/nu12010174 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 174 of the hippocampus, prefrontal cortex and amygdala [1,2]

  • Each image was visually inspected for any possible artifacts, and a total of 237 mouse brain images (n = 122 for senescence-accelerated mice prone 10 (SAMP10) mice and n = 115 for ddY mice) were used for the analysis

  • Each image was visually inspected for any possible artifacts, and a total of 237 mouse brain images (n = 122 for SAMP10 and n = 115 for ddY)

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Summary

Introduction

It is well established that stress—especially chronic stress—seriously perturbs physiological and/or psychological homeostasis and affects cognitive function and brain structure, including thatNutrients 2020, 12, 174; doi:10.3390/nu12010174 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 174 of the hippocampus, prefrontal cortex and amygdala [1,2]. In humans, the cumulative exposure to adverse life events is associated with a smaller gray matter volume in the prefrontal and limbic regions which are involved in stress [3]. Animal models and human neuroimaging studies have suggested that stress-associated changes are mediated in part by glucocorticoids that are released from the adrenal gland in response to stressors, while circadian glucocorticoid oscillations are disrupted by chronic stress [5,6,7]. The maintenance of a balance between inhibitory and excitatory elements in the brain is believed to be important for synaptic plasticity and cognitive function [12,13], and the regulation of inhibitory neuronal activation may be especially important in the hippocampus during chronic stress [14,15,16,17]

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