Fermented Gamma Aminobutyric Acid Improves Sleep Behaviors in Fruit Flies and Rodent Models.
A-Hyun JeongJisu HwangKyungae JoSingeun KimYejin AhnHyung-Joo SuhHyeon-Son ChoiPublished in: International journal of molecular sciences (2021)
The aim of this study was to investigate the effect of Lactobacillus brevis-fermented γ-aminobutyric 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 GABAergic/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.
Keyphrases
- sleep quality
- endothelial cells
- high glucose
- drosophila melanogaster
- physical activity
- diabetic rats
- binding protein
- working memory
- drug induced
- induced apoptosis
- depressive symptoms
- oxidative stress
- induced pluripotent stem cells
- small molecule
- functional connectivity
- signaling pathway
- metabolic syndrome
- white matter
- newly diagnosed
- cell death
- heart rate
- brain injury
- skeletal muscle
- replacement therapy
- subarachnoid hemorrhage
- pi k akt