Sleep-anticipating effects of melatonin in the human brain

Gorfine, Tali; Assaf, Yaniv; Goshen‐Gottstein, Yonatan; Yeshurun, Yehezkel; Zisapel, Nava

doi:10.1016/j.neuroimage.2005.11.024

Cited by 66 publications

(75 citation statements)

References 57 publications

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“…Melatonin given in the afternoon to healthy young individuals attenuates activation in the precuneus, located at the rostro‐medial aspect of the occipital cortex (Figure 1A). These effects correlate with subjective measurements of fatigue (Gorfine et al, 2006). 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).…”

Section: Introductionsupporting

confidence: 52%

“…β‐blockers, clonidine, naloxone and non‐steroidal anti‐inflammatory drugs) abolish the nocturnal production of melatonin and are associated with impaired sleep. 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).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, melatonin acts at the default mode network (DMN) regions in the brain to promote fatigue and sleep‐like changes in activation of the precuneus (Gorfine et al, 2006; Gorfine and Zisapel, 2009). The DMN is a network of brain regions that is active during rest in the absence of task‐dependent performance (Raichle et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…The fMRI‐assessed visual search task related activation of brain networks (adapted from Gorfine et al, 2006; Gorfine and Zisapel, 2009). (A) The effect of exogenous melatonin administration at 16:00 h on task‐related activity.…”

Section: Introductionmentioning

confidence: 99%

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

Zisapel

2018

British J Pharmacology

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In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN‐activated, light‐inhibited production of melatonin conveys the message of darkness to the clock and induces night‐state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo‐controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm‐related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non‐restorative) sleep quality, non‐dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep‐anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build‐up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease.Linked ArticlesThis article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

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Section: Introductionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zisapel

2018

British J Pharmacology

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“…Indeed, exogenous melatonin is most effective when endogenous levels are low during the biological day. It elicits time-dependent soporific effects, which have been corroborated with electrophysiological mea sures of sleepiness such as (EEG) theta activity during wakefulness (Cajochen et al, 1997b) and with brain correlates of sleepiness in an fMRI study, which highlighted the role of melatonin in priming sleep-associated brain activation patterns in anticipation of sleep (Gorfine et al, 2006). In an experiment where we blocked the natural evening increase in heat loss, subjective sleepiness, and melatonin secretion by light exposure, we could show that melatonin replace ment (5 mg) acutely recovered the evening increase in heat loss, subjective sleepiness, and also theta activity in the waking EEG (Cajochen et al, 1998;Krä uchi et al, 1997).…”

Section: B Effects Of Exogenous Melatonin On Human Sleep and Wakefulmentioning

confidence: 65%

What Keeps Us Awake?—the Role of Clocks and Hourglasses, Light, and Melatonin

Cajochen

Chellappa

Schmidt

2010

International Review of Neurobiology

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Late evening brain activation patterns and their relation to the internal biological time, melatonin, and homeostatic sleep debt

Gorfine

Zisapel

2009

Human Brain Mapping

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Sleep propensity increases sharply at night. Some evidence implicates the pineal hormone melatonin in this process. Using functional magnetic resonance imaging, brain activation during a visual search task was examined at 22:00 h (when endogenous melatonin levels normally increase). The relationships between brain activation, endogenous melatonin (measured in saliva), and self-reported fatigue were assessed. Finally, the effects of exogenous melatonin administered at 22:00 h were studied in a double blind, placebo-controlled crossover manner. We show that brain activation patterns as well as the response to exogenous melatonin significantly differ at night from those seen in afternoon hours. Thus, activation in the rostro-medial and lateral aspects of the occipital cortex and the thalamus diminished at 22:00 h. Activation in the right parietal cortex increased at night and correlated with individual fatigue levels, whereas exogenous melatonin given at 22:00 h reduced activation in this area. The right dorsolateral prefrontal cortex, an area considered to reflect homeostatic sleep debt, demonstrated increased activation at 22:00 h. Surprisingly, this increase correlated with endogenous melatonin. These results demonstrate and partially differentiate circadian effects (whether mediated by melatonin or not) and homeostatic sleep debt modulation of human brain activity associated with everyday fatigue at night. Hum Brain

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Sleep-anticipating effects of melatonin in the human brain

Cited by 66 publications

References 57 publications

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

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

What Keeps Us Awake?—the Role of Clocks and Hourglasses, Light, and Melatonin

Late evening brain activation patterns and their relation to the internal biological time, melatonin, and homeostatic sleep debt

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