Functions and mechanisms of adenosine and its receptors in sleep regulation

• Published in: Sleep medicine Vol. 115; pp. 210 - 217
• Main Authors: Huang, Lishan, Zhu, Wenwen, Li, Nanxi, Zhang, Bin, Dai, Wenbin, Li, Sen, Xu, Houping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2024
• Subjects: Adenosine; Adenosine receptors; Brain - physiology; Humans; Insomnia; Neurotransmitter Agents - physiology; Sleep - physiology; Sleep disorders; Sleep homeostasis; Sleep Initiation and Maintenance Disorders; Sleep-wake; Wakefulness - physiology; Sleep disorders; Sleep-wake; Adenosine; Adenosine receptors; Insomnia; Sleep homeostasis
• ISSN: 1389-9457; 1878-5506; 1878-5506
• DOI: 10.1016/j.sleep.2024.02.012

Sleep is a natural and recurring state of life. Long-term insomnia can lead to physical and mental fatigue, inattention, memory loss, anxiety, depression and other symptoms, imposing immense public health and economic burden worldwide. The sleep and awakening regulation system is composed of many nerve nuclei and neurotransmitters in the brain, and it forms a neural network that interacts and restricts each other to regulate the occurrence and maintenance of sleep-wake. Adenosine (AD) is a neurotransmitter in the central nervous system and a driver of sleep. Meanwhile, the functions and mechanisms underlying sleep-promoting effects of adenosine and its receptors are still not entirely clear. However, in recent years, the increasing evidence indicated that adenosine can promote sleep through inhibiting arousal system and activating sleep-promoting system. At the same time, astrocyte-derived adenosine in modulating sleep homeostasis and sleep loss-induced related cognitive and memory deficits plays an important role. This review, therefore, summarizes the current research on the functions and possible mechanisms of adenosine and its receptors in the regulation of sleep and homeostatic control of sleep. Understanding these aspects will provide us better ideas on clinical problems such as insomnia, hypersomnia and other sleep disorders. •The current article reviews the functions and mechanisms of adenosine and its receptors in sleep regulation and investigates the effects of adenosine receptors in different brain regions. We demonstrate regulation function of adenosine and its receptors from arousal system, sleep-promoting system, sleep homeostasis and circadian rhythm.•This article is suitable for the audience of Sleep Medicine, as adenosine is widely regarded as an endogenous sleep-regulatory substance nowadays.•This article could provide a valuable resource for researchers and clinicians seeking to better understand the role of adenosine and its receptors in sleep regulation and explore potential therapeutic targets.•We have presented several studies that show the sleep-promoting effects of Prostaglandin D2 or Nitric oxide partially depending on the adenosine system. However, the article would benefit from a more detailed discussion on animal models, human experiments, and even human subjects. And it will be of great significance for researchers and clinicians to provide more information about the current research situation in this field.•The article discusses the popular phytochemicals which exerted sedation and hypnosis action via adenosine receptors. As the demand for a new class of alternative natural products with sleep improving effects is still high, it may have good research value and broad prospects for insomnia treatment.