Sleep and sleep disturbances: biological basis and clinical implications

Abstract

Sleep is a neurochemical process involving sleep promoting and arousal centers in the brain. Sleep performs an essential restorative function and facilitates memory consolidation in humans. The remarkably standardized bouts of consolidated sleep at night and daytime wakefulness reflect an interaction between the homeostatic sleep need that is manifested by increase in sleep propensity after sleep deprivation and decrease during sleep and the circadian pacemaker. Melatonin, the hormone produced nocturnally by the pineal gland, serves as a time cue and sleep-anticipating signal. A close interaction exists between the sleep-wake, melatonin, core temperature, blood pressure, immune and hormonal rhythms leading to optimization of the internal temporal order. With age the robustness of the circadian system decreases and the prevalence of sleep disorders, particularly insomnia, increases. Deviant sleep patterns are associated with increased risks of morbidity, poor quality of life and mortality. Current sleep pharmacotherapies treat insufficient sleep quantity, but fail to improve daytime functioning. New treatment modalities for sleep disorders that will also improve daytime functioning remain a scientific and medical challenge.

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

“…Melatonin therapy is a rational approach for N24HSWD in the totally blind population (Zisapel, 2007; Emens and Eastman, 2017). The administration of immediate release (IR) melatonin to totally blind individuals with N24HSWD (0.5–10 mg, once daily in the evening for 1 day up to several months) facilitated phase advances and entrainment to the societal sleep/wake norms and reportedly entrained endogenous melatonin and cortisol rhythms to the 24 h cycle.…”

“…Sleep propensity depends on the amount of sleep deprivation (homeostatic component) and on time of day (circadian clock component). The interaction between these processes forms the basis of a remarkably standardized bout of sleep at night and a consolidated bout of wakefulness throughout the day (reviewed in Zisapel, 2007). The duration of wakefulness predicts the amount of SWS regardless of the circadian phase.…”

“…The sharp increase in sleep propensity at night usually occurs 2 h after the onset of endogenous melatonin production in humans (Lavie, 1997; Zisapel, 2007); in addition, the duration of nocturnal melatonin relays night length information to the brain and various organs, including the SCN itself. The circadian melatonin rhythm is closely associated with the sleep rhythm in both normal and blind subjects (Zisapel, 2001).…”

“…Administration of melatonin during daytime (when it is not present endogenously) results in the induction of fatigue and sleepiness in humans (Gorfine et al, 2006). Importantly, melatonin is not sedating: in nocturnally‐active animals, melatonin is associated with awake, not sleep, periods and in humans, its sleep‐promoting effects become significant about 2 h after intake similar to the physiological sequence at night (Zisapel, 2007). The effects of exogenous melatonin can be best demonstrated when endogenous melatonin levels are low (e.g.…”

“…However, activation of this brain area is decreased concomitantly with the endogenous rise of melatonin, so that administration of exogenous melatonin at night does not have a further notable effect (Figure 1B,C). Because melatonin does not increase the amount of SWS (Arbon et al, 2015), which is considered a marker of the homeostatic sleep pressure (Zisapel, 2007), the sleep promoting effects of melatonin may be mostly ascribed to the circadian component of sleep regulation.…”