Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.

Autor:	Ito H; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.; Japan Society for the Promotion of Science Research Fellowship for Young Scientists, Tokyo 102-0083, Japan., Fukatsu N; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan., Rahaman SM; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan., Mukai Y; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan., Izawa S; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan., Ono D; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan., Kilduff TS; Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA 94025., Yamanaka A; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.; Chinese Institute for Brain Research, Beijing 102206, China.; National Institute for Physiological Sciences, Aichi 444-8585, Japan.; National Institutes of Natural Sciences, Aichi 444-8585, Japan.; Division of Brain Sciences Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Oct 10; Vol. 120 (41), pp. e2301951120. Date of Electronic Publication: 2023 Oct 05.
DOI:	10.1073/pnas.2301951120
Abstrakt:	Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.
Databáze:	MEDLINE
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