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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (11): 1443-1452.doi: 10.12092/j.issn.1009-2501.2025.11.001

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Neural mechanisms of orexin regulating the sleep-wake cycle

HE Chao1, LUO Xinwei1, YU Qingsong2, LI Yadong2   

  1. 1Department of Physiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China; 2Songjiang Institute, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Emotional Brain Function and Intervention for Disorders, Shanghai 201699, China
  • Online:2025-11-26 Published:2025-12-04

Abstract:

The orexin (hypocretin) system is a hypothalamus-specific neuropeptidergic network that integrates metabolic, emotional, and environmental cues to regulate sleep-wake states. By activating arousal-promoting nuclei and inhibiting sleep-promoting regions through widespread downstream circuits, it plays a crucial role in the initiation and maintenance of wakefulness. Orexin system also plays a crucial role in regulation of rapid eye movement sleep. Loss of orexin function is closely associated with narcolepsy, characterized by fragmented wakefulness and emotionally triggered cataplexy. This review summarizes the current advances in the neural mechanisms underlying orexin-mediated regulation of the sleep-wake cycle, aiming to provide a theoretical basis for precision interventions in sleep disorders.

Key words: orexin, orexin receptors, sleep, REM sleep, wakefulness, neural circuits, insomnia, narcolepsy

CLC Number: