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Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy
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 unders...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576136/ https://www.ncbi.nlm.nih.gov/pubmed/37796986 http://dx.doi.org/10.1073/pnas.2301951120 |
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author | Ito, Hiroto Fukatsu, Noriaki Rahaman, Sheikh Mizanur Mukai, Yasutaka Izawa, Shuntaro Ono, Daisuke Kilduff, Thomas S. Yamanaka, Akihiro |
author_facet | Ito, Hiroto Fukatsu, Noriaki Rahaman, Sheikh Mizanur Mukai, Yasutaka Izawa, Shuntaro Ono, Daisuke Kilduff, Thomas S. Yamanaka, Akihiro |
author_sort | Ito, Hiroto |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10576136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-105761362023-10-15 Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy Ito, Hiroto Fukatsu, Noriaki Rahaman, Sheikh Mizanur Mukai, Yasutaka Izawa, Shuntaro Ono, Daisuke Kilduff, Thomas S. Yamanaka, Akihiro Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-10-05 2023-10-10 /pmc/articles/PMC10576136/ /pubmed/37796986 http://dx.doi.org/10.1073/pnas.2301951120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Ito, Hiroto Fukatsu, Noriaki Rahaman, Sheikh Mizanur Mukai, Yasutaka Izawa, Shuntaro Ono, Daisuke Kilduff, Thomas S. Yamanaka, Akihiro Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy |
title | Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy |
title_full | Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy |
title_fullStr | Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy |
title_full_unstemmed | Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy |
title_short | Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy |
title_sort | deficiency of orexin signaling during sleep is involved in abnormal rem sleep architecture in narcolepsy |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576136/ https://www.ncbi.nlm.nih.gov/pubmed/37796986 http://dx.doi.org/10.1073/pnas.2301951120 |
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