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Sleep homeostasis: a role for adenosine in humans?


Landolt, H P (2008). Sleep homeostasis: a role for adenosine in humans? Biochemical Pharmacology, 75(11):2070-2079.

Abstract

Sleep is not the mere absence of wakefulness, but an active state which is finely regulated. The homeostatic facet of sleep-wake regulation is keeping track of changes in 'sleep propensity' (or 'sleep need'), which increases during wakefulness and decreases during sleep. Increased sleep propensity following extended prior wakefulness (sleep deprivation) is counteracted by prolonged sleep duration, but also by enhanced non-rapid-eye-movement (nonREM) sleep intensity as measured by electroencephalographic (EEG) slow-wave activity (SWA, power within approximately 1-4 Hz). This highly reliable regulatory feature of nonREM sleep may be the most important aspect of sleep in relation to its function. The neurochemical mechanisms underlying nonREM sleep homeostasis are poorly understood. Here we provide compelling and convergent evidence that adenosinergic neurotransmission plays a role in nonREM sleep homeostasis in humans. Specifically, a functional polymorphism in the adenosine metabolizing enzyme, adenosine deaminase, contributes to the high inter-individual variability in deep slow-wave sleep duration and intensity. Moreover, the adenosine receptor antagonist, caffeine, potently attenuates the EEG markers of nonREM sleep homeostasis during sleep, as well as during wakefulness. Finally, adenosinergic mechanisms modulate individual vulnerability to the detrimental effects of sleep deprivation on neurobehavioral performance, and EEG indices of disturbed sleep after caffeine consumption. While these convergent findings strongly support an important contribution of adenosine and adenosine receptors to nonREM sleep homeostasis, further research is needed to elucidate the underlying mechanisms that mediate the actions of adenosine on sleep and the sleep EEG.

Abstract

Sleep is not the mere absence of wakefulness, but an active state which is finely regulated. The homeostatic facet of sleep-wake regulation is keeping track of changes in 'sleep propensity' (or 'sleep need'), which increases during wakefulness and decreases during sleep. Increased sleep propensity following extended prior wakefulness (sleep deprivation) is counteracted by prolonged sleep duration, but also by enhanced non-rapid-eye-movement (nonREM) sleep intensity as measured by electroencephalographic (EEG) slow-wave activity (SWA, power within approximately 1-4 Hz). This highly reliable regulatory feature of nonREM sleep may be the most important aspect of sleep in relation to its function. The neurochemical mechanisms underlying nonREM sleep homeostasis are poorly understood. Here we provide compelling and convergent evidence that adenosinergic neurotransmission plays a role in nonREM sleep homeostasis in humans. Specifically, a functional polymorphism in the adenosine metabolizing enzyme, adenosine deaminase, contributes to the high inter-individual variability in deep slow-wave sleep duration and intensity. Moreover, the adenosine receptor antagonist, caffeine, potently attenuates the EEG markers of nonREM sleep homeostasis during sleep, as well as during wakefulness. Finally, adenosinergic mechanisms modulate individual vulnerability to the detrimental effects of sleep deprivation on neurobehavioral performance, and EEG indices of disturbed sleep after caffeine consumption. While these convergent findings strongly support an important contribution of adenosine and adenosine receptors to nonREM sleep homeostasis, further research is needed to elucidate the underlying mechanisms that mediate the actions of adenosine on sleep and the sleep EEG.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 June 2008
Deposited On:18 Dec 2008 09:47
Last Modified:05 Apr 2016 12:36
Publisher:Elsevier
ISSN:0006-2952
Publisher DOI:https://doi.org/10.1016/j.bcp.2008.02.024
PubMed ID:18384754

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