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

A. Hyun Jeong, Jisu Hwang, Kyungae Jo, Singeun Kim, Yejin Ahn, Hyung Joo Suh, Hyeon Son Choi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3537
JournalInternational journal of molecular sciences
Volume22
Issue number7
DOIs
Publication statusPublished - 2021 Apr 1

Keywords

  • Dro-sophila melanogaster
  • GABA receptor
  • Non‐rapid eye movement
  • Rodents
  • Sleep promotion
  • γ‐aminobutyric acid

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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