Hypocretins and adenosine in the regulation of sleep

[EN] Aims. To review the recent discovery of hypocretins (orexins) and their link to the pathophysiology of narcolepsy and the role of adenosine in the integration of brain metabolism and sleep. Development. The importance of the functions carried out by the hypothalamus in the regulation of sleep a...

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Bibliographic Details
Author: Salín-Pascual, Rafael J.
Format: article
Status:Published version
Publication Date:2004
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/396910
Online Access:http://hdl.handle.net/10261/396910
https://api.elsevier.com/content/abstract/scopus_id/4744371954
Access Level:Open access
Keyword:Adenosine
Aging
Caffeine
Hypocretin
Narcolepsy
Sleep
Description
Summary:[EN] Aims. To review the recent discovery of hypocretins (orexins) and their link to the pathophysiology of narcolepsy and the role of adenosine in the integration of brain metabolism and sleep. Development. The importance of the functions carried out by the hypothalamus in the regulation of sleep and the waking state has been consolidated by the discovery of hypocretins and the role played by cerebral adenosine. Hypocretins are two peptides made up of 33 and 28 amino acids whose neurons are located predominantly in the lateral hypothalamus and surrounding regions. In the Doberman canine narcolepsy model, in which this disease is presented with an autosomal recessive pattern, a mutation was detected in one of the receptors involved in the hypocretin system, namely the hypocretin-2 receptor. Failures in the hypocretin system have been confirmed as a key factor in narcolepsy by other findings in laboratory animals and humans. Adenosine, on the other hand, is accumulated during the waking state as a result of neuronal metabolism and this in turn is related to drowsiness. Sleep episodes lower the levels of this substance in the brain. Adenosine receptor antagonists increase wakefulness (e.g. caffeine), while the agonists promote slow-wave sleep. Conclusions. Hypocretins and adenosine from the hypothalamus perform functions involving the regulation of sleep and wakefulness. Understanding these two systems can have repercussions on clinical problems such as insomnia, hypersomnia and other neuropsychiatric disorders.