Author
Listed:
- Koustav Roy
(University of Tsukuba)
- Xuzhao Zhou
(University of Tsukuba
Wenzhou Medical University)
- Rintaro Otani
(University of Tsukuba)
- Ping-Chuan Yuan
(Fudan University
Wannan Medical College)
- Shuji Ioka
(University of Tsukuba)
- Kaspar E. Vogt
(University of Tsukuba)
- Tamae Kondo
(University of Tsukuba)
- Nouran H. T. Farag
(University of Tsukuba)
- Haruto Ijiri
(University of Tsukuba
University of Tsukuba)
- Zhaofa Wu
(Chinese Academy of Sciences)
- Youhei Chitose
(Hiroshima University)
- Mao Amezawa
(University of Tsukuba)
- David S. Uygun
(Veterans Administration Boston Healthcare System and Harvard Medical School)
- Yoan Cherasse
(University of Tsukuba)
- Hiroshi Nagase
(University of Tsukuba)
- Yulong Li
(Peking University)
- Masashi Yanagisawa
(University of Tsukuba)
- Manabu Abe
(Hiroshima University)
- Radhika Basheer
(Veterans Administration Boston Healthcare System and Harvard Medical School)
- Yi-Qun Wang
(Fudan University)
- Tsuyoshi Saitoh
(University of Tsukuba
University of Tsukuba)
- Michael Lazarus
(University of Tsukuba
University of Tsukuba)
Abstract
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 A2A receptors (A2ARs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A2ARs (A2AR 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.
Suggested Citation
Koustav Roy & Xuzhao Zhou & Rintaro Otani & Ping-Chuan Yuan & Shuji Ioka & Kaspar E. Vogt & Tamae Kondo & Nouran H. T. Farag & Haruto Ijiri & Zhaofa Wu & Youhei Chitose & Mao Amezawa & David S. Uygun , 2024.
"Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
Handle:
RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47964-4
DOI: 10.1038/s41467-024-47964-4
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