Adenosine-independent regulation of the sleep-wake cycle by astrocyte activity PMID: 36746933

ADC Targets in Oncology

2026-04-10

Adenosine-independent regulation of the sleep-wake cycle by astrocyte activity

Cell Discov. 2023 Feb 7;9(1):16. doi: 10.1038/s41421-022-00498-9.

Wanling Peng ^# ¹ ² , Xiaotong Liu ^# ³ ⁴ , Guofen Ma ^# ⁵ ⁶ , Zhaofa Wu ⁷ ⁸ , Ziyue Wang ⁵ ⁶ , Xiang Fei ³ ⁴ , Meiling Qin ³ , Lizhao Wang ⁵ ⁶ , Yulong Li ⁷ ⁸ ⁹ , Siyu Zhang ¹⁰ ¹¹ , Min Xu ¹² ¹³ ¹⁴

Affiliations

1. Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. [email protected].
2. University of Chinese Academy of Sciences, Beijing, China. [email protected].
3. Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
4. University of Chinese Academy of Sciences, Beijing, China.
5. Center for Brain Science of Shanghai Children's Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
6. Songjiang Institute and Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
7. State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.
8. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
9. PKU-IDG/McGovern Institute for Brain Research, Beijing, China.
10. Center for Brain Science of Shanghai Children's Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
11. Songjiang Institute and Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
12. Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. [email protected].
13. University of Chinese Academy of Sciences, Beijing, China. [email protected].
14. Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shangha, China. [email protected].
# Contributed equally.

Abstract

Astrocytes play a crucial role in regulating sleep-wake behavior, and adenosine signaling is generally thought to be involved. Here we show multiple lines of evidence supporting that modulation of the sleep-wake behavior by astrocyte CA²⁺ activity could occur without adenosine signaling. In the basal forebrain and the brainstem, two brain regions that are known to be essential for sleep-wake regulation, chemogenetically-induced astrocyte CA²⁺ elevation significantly modulated the sleep-wake cycle. Although astrocyte CA²⁺ level positively correlated with the amount of extracellular adenosine, as revealed by a genetically encoded adenosine sensor, we found no detectable change in adenosine level after suppressing astrocyte CA²⁺ elevation, and transgenic mice lacking one of the major extracellular ATP-adenosine conversion Enzymes showed similar extracellular adenosine level and astrocyte CA²⁺-induced sleep modulation. Furthermore, astrocyte CA²⁺ is dependent primarily on local neuronal activity, causing brain region-specific regulation of the sleep-wake cycle. Thus, neural activity-dependent astrocyte activity could regulate the sleep-wake behavior independent of adenosine signaling.