Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation

Wei-Xiang Ma; Ping-Chuan Yuan; Hui Zhang; Ling-Xi Kong; Michael Lazarus; Wei-Min Qu; Yi-Qun Wang; Zhi-Li Huang

doi:10.3389/fphar.2023.1098976

Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation

Front Pharmacol. 2023 Mar 10:14:1098976. doi: 10.3389/fphar.2023.1098976. eCollection 2023.

Authors

Wei-Xiang Ma¹, Ping-Chuan Yuan², Hui Zhang², Ling-Xi Kong¹, Michael Lazarus³, Wei-Min Qu¹, Yi-Qun Wang¹, Zhi-Li Huang¹

Affiliations

¹ State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Department of Pharmacology, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China.
² Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, School of Pharmacy, Wannan Medical College, Wuhu, China.
³ International Institute for Integrative Sleep Medicine (WPI-IIIS) and Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Abstract

Sleep, torpor, and hibernation are three distinct hypometabolic states. However, they have some similar physiological features, such as decreased core body temperature and slowing heart rate. In addition, the accumulation of adenosine seems to be a common feature before entry into these three states, suggesting that adenosine and its receptors, also known as P1 receptors, may mediate the initiation and maintenance of these states. This review, therefore, summarizes the current research on the roles and possible neurobiological mechanisms of adenosine and P1 receptors in sleep, torpor, and hibernation. Understanding these aspects will give us better prospects in sleep disorders, therapeutic hypothermia, and aerospace medicine.

Keywords: P1 receptors; adenosine; hibernation; sleep; torpor.

Publication types

Review

Grants and funding

This study was supported by the STI 2030-major project (2021ZD0203400 to Z-LH), the China National Key R&D Program; National Key Research and Development Program (2022YFA1604504 to Y-QW), the National Natural Science Foundation of China (82171479, 81871037 to Y-QW; 82020108014 and 32070984 to Z-LH), the Shanghai Science and Technology Innovation Action Plan Laboratory Animal Research Project (201409001800 to Z-LH), Program for Shanghai Outstanding Academic Leaders (to Z-LH), the Shanghai Municipal Science and Technology Major Project, and ZJ Lab, and Shanghai Center for Brain Science and Brain-inspired Technology (2018SHZDZX01 to Z-LH), Japan Society for the Promotion of Science [Grants-in-Aid for Scientific Research B (grant number 21H02802) and RECONNECT Initiative (grant number JP22K21351) to ML]; the Japan Science and Technology Agency [CREST (grant number JPMJCR1655) to ML]; Japan Agency for Medical Research and Development (AMED) [Moonshot Program (grant number JP21zf0127005) to ML]; the project “Social Application of Mobility Innovation and Future Social Engineering Research Phase IV (grant number CRI04006),” a joint research project between Toyota Motor Corporation and the University of Tsukuba to ML; and the World Premier International Research Center Initiative (WPI) from MEXT to ML.