Journal
PROGRESS IN NEUROBIOLOGY
Volume 73, Issue 6, Pages 379-396Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2004.06.004
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- NIMH NIH HHS [K01 MH001798-05, MH39683, R37 MH039683-23, KO1 MH01798] Funding Source: Medline
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This review addresses three principal questions about adenosine and sleep-wake regulation: (1) Is adenosine an endogenous sleep factor? (2) Are there specific brain regions/neuroanatomical targets and receptor subtypes through which adenosine mediates sleepiness? (3) What are the molecular mechanisms by which adenosine may mediate the long-term effects of sleep loss? Data suggest that adenosine is indeed an important endogenous, homeostatic sleep factor, likely mediating the sleepiness that follows prolonged wakefulness. The cholinergic basal forebrain is reviewed in detail as an essential area for mediating the sleep-inducing effects of adenosine by inhibition of wake-promoting neurons via the A, receptor. The A(2A) receptor in the subarachnoid space below the rostral forebrain may play a role in the prostaglandin D-2-mediated somnogenic effects of adenosine. Recent evidence indicates that a cascade of signal transduction induced by basal forebrain adenosine A, receptor activation in cholinergic neurons leads to increased transcription of the A, receptor; this may play a role in mediating the longer-term effects of sleep deprivation, often called sleep debt. Published by Elsevier Ltd.
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