@article{3e33de8e6827423f9c963e7397b9d780,
title = "Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors",
abstract = "Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms.",
keywords = "adenosine A2a receptor knockout mice, capillary, cerebral blood flow, rapid-eye-movement (REM) sleep, sleep homeostasis, two-photon microscopy",
author = "Tsai, {Chia Jung} and Takeshi Nagata and Liu, {Chih Yao} and Takaya Suganuma and Takeshi Kanda and Takehiro Miyazaki and Kai Liu and Tsuyoshi Saitoh and Hiroshi Nagase and Michael Lazarus and Vogt, {Kaspar E.} and Masashi Yanagisawa and Yu Hayashi",
note = "Funding Information: We thank Chika Miyoshi for technical advice, Jiang-Fan Chen for the A2aR-KO mice, and Mojtaba Bandarabadi and Antoine Adamantidis for the MATLAB scripts. This work was supported by AMED under grant nos. JP19gm1110008 and JP21wm0425018 (to Y.H.) and JP19lm0203023 (to M.L.); JSPS KAKENHI under grant nos. JP20H03353, JP20K21456, and JP21F21109; MEXT KAKENHI under grant nos. JP21H00199 and JP21H00414; JST under grant no. JPMJPR13AC; the MEXT WPI program; the Cell Science Research Foundation; the Asahi Glass Foundation; the Astellas Foundation for Research on Metabolic Disorders; the Daiichi Sankyo Foundation of Life Science (to Y.H.); and the Japan Foundation for Applied Enzymology (TMFC, to Y.H. and T. Saitoh). Conceptualization, C.-J.T. and Y.H.; investigation, C.-J.T. C.-Y.L. and T. Suganuma; software, C.-J.T. T.N. and K.L.; formal analysis, C.-J.T. C.-Y.L, and T. Suganuma; resources, T.K. T.M. K.E.V. and M.Y. (for the experimental platform for simultaneous 2PM and EEG/EMG recording) and T. Saitoh, H.N. and M.L. (for synthetized and provided A2AR PAM-1); writing ? original draft, C.-J.T. and Y.H.; writing ? review & editing, C.-J.T. and Y.H.; supervision, Y.H. K.E.V. and M.Y. The authors declare no competing interests. T.N. is an employee of Mizuho Research & Technologies. T. Suganuma is an employee of Kao Corporation. We worked to ensure sex balance in the selection of non-human subjects. Funding Information: We thank Chika Miyoshi for technical advice, Jiang-Fan Chen for the A2aR-KO mice, and Mojtaba Bandarabadi and Antoine Adamantidis for the MATLAB scripts. This work was supported by AMED under grant nos. JP19gm1110008 and JP21wm0425018 (to Y.H.) and JP19lm0203023 (to M.L.); JSPS KAKENHI under grant nos. JP20H03353 , JP20K21456 , and JP21F21109 ; MEXT KAKENHI under grant nos. JP21H00199 and JP21H00414 ; JST under grant no. JPMJPR13AC ; the MEXT WPI program ; the Cell Science Research Foundation ; the Asahi Glass Foundation ; the Astellas Foundation for Research on Metabolic Disorders ; the Daiichi Sankyo Foundation of Life Science (to Y.H.); and the Japan Foundation for Applied Enzymology (TMFC, to Y.H. and T. Saitoh). Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = aug,
day = "17",
doi = "10.1016/j.celrep.2021.109558",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}