Administration of Alpha_s1-Casein Hydrolysate Increases Sleep and Modulates GABA_A Receptor Subunit Expression

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 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 β₁ 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.