Fermented gamma aminobutyric acid improves sleep behaviors in fruit flies and rodent models

Abstract

The aim of this study was to investigate the effect of Lactobacillus breves‐fermented γ‐ami-nobutyric acid (LB‐GABA) on sleep behaviors in invertebrate and vertebrate models. In Drosophila melanogaster, LB‐GABA‐treated group showed an 8–9%‐longer sleep duration than normal group did. LB‐GABA‐treated group also showed a 46.7% lower level of nighttime activity with a longer (11%) sleep duration under caffeine‐induced arousal conditions. The LB‐GABA‐mediated inhibition of activity was confirmed as a reduction of total movement of flies using a video tracking system. In the pentobarbital‐induced sleep test in mice, LB‐GABA (100 mg/kg) shortened the time of onset of sleep by 32.2% and extended sleeping time by 59%. In addition, mRNA and protein level of GA‐ BAergic/Serotonergic neurotransmitters were upregulated following treatment with LB‐GABA (2.0%). In particular, intestine‐ and brain‐derived GABAA protein levels were increased by sevenfold and fivefold, respectively. The electroencephalography (EEG) analysis in rats showed that LB‐ GABA significantly increased non‐rapid eye movement (NREM) (53%) with the increase in theta (θ, 59%) and delta (δ, 63%) waves, leading to longer sleep time (35%), under caffeine‐induced insomnia conditions. LB‐GABA showed a dose‐dependent agonist activity on human GABAA receptor with a half‐maximal effective concentration (EC50) of 3.44 μg/mL in human embryonic kidney 293 (HEK293) cells.