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Reduced Glutathione Regulates Sleep in Unrestrained
Rats by Producing Oxidized Glutathione
Kazuki Honda, Ph.D., Masami Sagara, M.Sc., Masayuki Ikeda,
*
Ph.D., and
Shojiro Inou , D.Sc.
The present study was conducted to examine whether reduced glutathione (GSH), a
naturally occurring tripeptide in the brain, exert somnogenic activity in freely behaving
rats, since its dimer oxidized glutathione (GSSG) is a potent endogenous sleep-promoting
substance. Nocturnal 10-h intracerebroventricular (icv) infusion of 50 nmol
GSH increased amount of non-rapid-eye-movement (nonREM) sleep during the 12-h
dark period (maximally 21 % above the baseline). Dose-response relations exhibited a
bell shape at 4 different doses in a range 10-100 nmol. However, inhibition of GSH
biosynthesis by diurnal 10-h icv infusion of a GSH peroxidase inhibitor, N-ethylmaleimide
(NEM), at 4 different doses in a range 0.01-10 mol, dose-dependently brought about
suppression of both nonREM and REM sleep. These results indicate that GSSG
biosynthesized from GSH is actually responsible for the GSH-induced enhancement of
sleep. (Sleep and Hypnosis 2000;1:26-30)
Keywords: glutathione, GSH peroxidase inhibitor, intracerebroventricular infusion,
N-ethylmaleimide, neuronal detoxification, nonREM sleep, sleep-promoting substance |
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