Theanine, Antistress Amino Acid in Tea Leaves, Causes Hippocampal Metabolic Changes and Antidepressant Effects in Stress-Loaded Mice.

Keiko Unno,Yoriyuki Nakamura,Koichi Inoue,Kyoko Taguchi,Tomokazu Konishi,Atsuyoshi Shimada,Sanae Hasegawa-Ishii,Yoshio Muguruma

doi:10.3390/ijms22010193

Abstract

By comprehensively measuring changes in metabolites in the hippocampus of stress-loaded mice, we investigated the reasons for stress vulnerability and the effect of theanine, i.e., an abundant amino acid in tea leaves, on the metabolism. Stress sensitivity was higher in senescence-accelerated mouse prone 10 (SAMP10) mice than in normal ddY mice when these mice were loaded with stress on the basis of territorial consciousness in males. Group housing was used as the low-stress condition reference. Among the statistically altered metabolites, depression-related kynurenine and excitability-related histamine were significantly higher in SAMP10 mice than in ddY mice. In contrast, carnosine, which has antidepressant-like activity, and ornithine, which has antistress effects, were significantly lower in SAMP10 mice than in ddY mice. The ingestion of theanine, an excellent antistress amino acid, modulated the levels of kynurenine, histamine, and carnosine only in the stress-loaded SAMP10 mice and not in the group-housing mice. Depression-like behavior was suppressed in mice that had ingested theanine only under stress loading. Taken together, changes in these metabolites, such as kynurenine, histamine, carnosine, and ornithine, were suggested to be associated with the stress vulnerability and depression-like behavior of stressed SAMP10 mice. It was also shown that theanine action appears in the metabolism of mice only under stress loading.

Highlights

Under similar circumstances, the stress response is heterogeneous in both humans and experimental animals
The stress was based on territorial consciousness as follows: After two male mice were housed in a partitioned cage for one month to establish territorial consciousness, the partition was removed to expose the mice to psychosocial confrontational stress, and the two mice subsequently cohabited in the same cage
The partition was removed to expose the mice to confrontational stress, and the two mice subsequently cohabited in the same cage for one month (Figure 1)

Summary

Introduction

The stress response is heterogeneous in both humans and experimental animals. SAMP10 mice are known to display age-related characteristic brain atrophy and depression-like behavior [1,2]. Volumetric brain changes induced by psychosocial stress have been observed one month after confrontational housing in SAMP10 mice, and atrophy continued thereafter [4]. Significant adrenal hypertrophy, a typical stress response, has been observed at least one week after confrontational housing in ddY mice [5], and it was considered that SAMP10 and ddY mice felt similar psychosocial stress by confrontational housing. We investigated changes in gene expression in the hippocampus on the third day of stress loading, and clarified the difference between SAMP10 and ddY mice, that is, the expression levels of neuronal PAS domain protein 4 (Npas4) and lipocalin

Methods

Results

Conclusion