Guest EditorialMelatonin, sleep, and circadian rhythms
Section snippets
Melatonin regulation
In mammals, melatonin plasma levels are high during darkness at night and low during the day. Even in an environment free of time cues and in constant dim light, melatonin continues to express its circadian (or ‘approximately 24-h’) rhythm. This endogenous circadian rhythm is driven by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN), via a multi-synaptic pathway involving the spinal cord and the sympathetic nervous system.1, 2 Light exposure during the night
Melatonin as a chronobiotic
Melatonin has been shown to phase-shift and entrain the circadian timing system in a variety of species. This has been shown in an in vitro slice preparation of the rodent SCN,11 in vivo in rodents under constant conditions,12 and in humans under more and less stringent conditions.13 The influence of melatonin as a chronobiotic in humans is discussed in detail by Arendt and Skene5. In designing future studies to investigate the phase-shifting and entraining potential of melatonin in humans,
Species-dependent effects of melatonin
The statement that melatonin has a sleep-promoting effect should be placed in the context of the species under investigation. In humans and other day-active mammals, melatonin is high during their resting/sleep phase, whereas in night-active mammals, melatonin is high during their activity/wake phase. Indeed, it has thus been argued that melatonin is ‘a hormone of darkness’5, 6, 15, 22 rather than a ‘sleep hormone’. In line with this, melatonin might even be wake–promoting rather than
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2022, Seminars in Cell and Developmental BiologyCitation Excerpt :In a landmark study by Silver et al., researchers demonstrated that SCN grafts housed in a semi-permeable capsule that prevented axonal outgrowth were able to restore behavioral circadian rhythmicity in SCN-lesioned animals, suggesting that diffusible factors play a key role in circadian sleep regulation [98]. The rhythmic release of the pineal hormone melatonin also plays a role in the timing of sleep in mammals [99]. The SCN regulates the timing of melatonin release via a multisynaptic projection connecting the PVN and the superior cervical ganglion of the spinal cord, and terminating in the pineal gland (Fig. 1).
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Dr. CA Czeisler is a consultant for Cephalon, Hypnion, Pfizer, Respironics, Takeda Pharmaceuticals, and Vanda Pharmaceuticals