Biomol Ther  
Administration of Alphas1-Casein Hydrolysate Increases Sleep and Modulates GABAA Receptor Subunit Expression
Taddesse Yayeh1, Yea-Hyun Leem1, Kyung-Mi Kim2, Jae-Chul Jung2, Jessica Schwarz3, Ki-Wan Oh4 and Seikwan Oh1,*
1Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University, Seoul 07985,
2Life Science Research Institute, Novarex Co., Ltd, Ochang, Cheongwon 28126, Republic of Korea,
3Ingredia SA, 51 Av. Lobbedez, 62033 Arras Cedex, France,
4Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea
E-mail: skoh@ewha.ac.kr
Tel: +82-2-2650-5749, Fax: +82-2-2643-0634
Received: April 6, 2017; Revised: August 29, 2017; Accepted: September 19, 2017; Published online: January 9, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Sleep is the most basic and essential physiological requirement for mental health, and sleep disorders pose potential risks of metabolic and neurodegenerative diseases. Tryptic hydrolysate of αS1-casein (αS1-CH) has been shown to possess stress relieving and sleep promoting effects. However, the differential effects of αS1-CH on electroencephalographic wave patterns and its effects on the protein levels of γ-aminobutyric acid A (GABAA) receptor subtypes in hypothalamic neurons are not well understood. We found αS1-CH (120, 240 mg/kg) increased sleep duration in mice and reduced sleep-wake cycle numbers in rats. While αS1- CH (300 mg/kg) increased total sleeping time in rats, it significantly decreased wakefulness. In addition, electroencephalographic theta (θ) power densities were increased whereas alpha (α) power densities were decreased by αS1-CH (300 mg/kg) during sleep-wake cycles. Furthermore, protein expressions of GABAA receptor β1 subtypes were elevated in rat hypothalamus by αS1-CH. These results suggest αS1-CH, through GABAA receptor modulation, might be useful for treating sleep disorders.
Keywords: Sleep, αS1-CH, Electroencephalogram, GABAA receptor


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