Physiology

Waking Up to Orexin

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Science  01 Feb 2008:
Vol. 319, Issue 5863, pp. 549
DOI: 10.1126/science.319.5863.549c

What do narcolepsy and anesthesia have in common? Almost a decade ago, a mouse model for human narcolepsy was developed on the basis of results demonstrating that the neuropeptide orexin promoted wakefulness and that genetic ablation of orexinergic neurons yielded mice with behavioral and physiological symptoms remarkably like those of narcoleptic humans. Anesthesia, on the other hand, can be induced by a wide variety of agents such as isoflurane or sevoflurane but has resisted efforts to identify its neural loci of action.

In their mouse model, Kelz et al. find that the neural systems innervated by orexinergic neurons are central in the emergence from (though not the induction of) an anesthetized state. Both isoflurane and sevoflurane reduced the percentage of active orexin neurons to the levels seen during non-rapid eye movement sleep, yet an orexin receptor antagonist surprisingly did not change the rate of entry into anesthesia. Nevertheless, the same antagonist did markedly delay recovery from an anesthetized state, and a similar delay was observed in orexin-deficient mice and also is seen in some human narcoleptic patients. — GJC

Proc. Natl. Acad. Sci. U.S.A. 105, 10.1073/pnas.0707146105 (2008).

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