2. Academic Validation
  3. Adenosine-independent regulation of the sleep-wake cycle by astrocyte activity

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

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. wlpeng@ion.ac.cn.
  • 2 University of Chinese Academy of Sciences, Beijing, China. wlpeng@ion.ac.cn.
  • 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. zhang_siyu@sjtu.edu.cn.
  • 11 Songjiang Institute and Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhang_siyu@sjtu.edu.cn.
  • 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. mxu@ion.ac.cn.
  • 13 University of Chinese Academy of Sciences, Beijing, China. mxu@ion.ac.cn.
  • 14 Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shangha, China. mxu@ion.ac.cn.
  • # Contributed equally.
PMID: 36746933 DOI: 10.1038/s41421-022-00498-9
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.

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