Administration of Alpha(s1)-Casein Hydrolysate Increases Sleep and Modulates GABA(A) Receptor Subunit Expression

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 α(S1)-casein (α(S1)-CH) has been shown to possess stress relieving and sleep promoting effects. However, the differential effects of α(S1)-CH on electroencephalographic wave patterns and its effects on the protein levels of γ-aminobutyric acid A (GABA(A)) receptor subtypes in hypothalamic neurons are not well understood. We found α(S1)-CH (120, 240 mg/kg) increased sleep duration in mice and reduced sleep-wake cycle numbers in rats. While α(S1)-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 α(S1)-CH (300 mg/kg) during sleep-wake cycles. Furthermore, protein expressions of GABA(A) receptor β(1) subtypes were elevated in rat hypothalamus by α(S1)-CH. These results suggest α(S1)-CH, through GABA(A) receptor modulation, might be useful for treating sleep disorders.