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Hypothalamic orexins/hypocretins as regulators of breathing

Published online by Cambridge University Press:  02 October 2008

Rhîannan H. Williams*
Affiliation:
Department of Pharmacology, University of Cambridge, Cambridge, UK.
Denis Burdakov
Affiliation:
Department of Pharmacology, University of Cambridge, Cambridge, UK.
*
*Corresponding author: Rhîannan Williams, University of Cambridge, Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, UK. Tel: +44 (0)1223 334000; Fax: +44 (0)1223 334100; E-mail: [email protected]

Abstract

It was suggested half a century ago that electrical impulses from the lateral hypothalamic area stimulate breathing. It is now emerging that these effects may be mediated, at least in part, by neurons containing orexin neuropeptides (also known as hypocretins). These cells promote wakefulness and consciousness, and their loss results in narcolepsy. Recent data also show that orexin neurons directly project to respiratory centres in the brainstem, which express orexin receptors, and where injection of orexin stimulates breathing. Because orexin neurons receive inputs that signal metabolic, sleep/wake and emotional states, it is tempting to speculate that they may regulate breathing according to these parameters. Knockout of the orexin gene in mice reduces CO2-induced increases in breathing by ∼50% and increases the frequency of spontaneous sleep apneas. The relationship between orexins and breathing may be bidirectional: the rate of breathing controls acid and CO2 levels, and these signals alter the electrical activity of orexin neurons in vitro. Overall, these findings suggest that orexins are important for the regulation of breathing and may potentially play a role in the pathophysiology and medical treatment of respiratory disorders.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

Patient-support websites on sleep-related disorders and narcolepsy can be found at:

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