Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A 2A receptors.

Autor: Roy K; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Zhou X; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.; Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China., Otani R; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Yuan PC; Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Joint International Research Laboratory of Sleep, Fudan University, Shanghai, China.; School of Pharmacy, Wannan Medical College, Wuhu, China., Ioka S; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Vogt KE; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Kondo T; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Farag NHT; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Ijiri H; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.; PhD Program in Humanics, University of Tsukuba, Tsukuba, Ibaraki, Japan., Wu Z; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China., Chitose Y; Department of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University Research Center for Photo-Drug-Delivery Systems (HiU-P-DDS), Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan., Amezawa M; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Uygun DS; Department of Psychiatry, Veterans Administration Boston Healthcare System and Harvard Medical School, West Roxbury, MA, USA., Cherasse Y; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Nagase H; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Li Y; New Cornerstone Science Laboratory, State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China., Yanagisawa M; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Abe M; Department of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University Research Center for Photo-Drug-Delivery Systems (HiU-P-DDS), Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan., Basheer R; Department of Psychiatry, Veterans Administration Boston Healthcare System and Harvard Medical School, West Roxbury, MA, USA., Wang YQ; Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Joint International Research Laboratory of Sleep, Fudan University, Shanghai, China. yiqunwang@fudan.edu.cn., Saitoh T; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan. saito.tsuyoshi.gf@u.tsukuba.ac.jp.; Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. saito.tsuyoshi.gf@u.tsukuba.ac.jp., Lazarus M; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan. lazarus.michael.ka@u.tsukuba.ac.jp.; Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. lazarus.michael.ka@u.tsukuba.ac.jp.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 30; Vol. 15 (1), pp. 3661. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1038/s41467-024-47964-4
Abstrakt: Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli. Adenosine emerges as a promising candidate molecule for activating indirect pathway neurons of the NAc expressing adenosine A 2A receptors (A 2A Rs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A 2A Rs (A 2A R PAM) that can be rapidly photoactivated with visible light (λ > 400 nm) and used it optoallosterically to induce SWS in the NAc of freely behaving male mice by increasing the activity of extracellular adenosine derived from astrocytic and neuronal activity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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