Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation

Individuals with autism spectrum disorder (ASD) frequently experience sleep disturbances, including difficulties in sleep initiation, reduced total sleep time, and excessive daytime sleepiness. Among them, those carrying mutations in the CHD8, a high-penetrance ASD risk gene, often exhibit both core...

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Main Authors: Jiahui Yu, Norie Deki-Arima, Yuki C. Saito, Naoki Furutani, Masaaki Nishiyama, Keiichi I. Nakayama, Yasutaka Niwa, Arisa Hirano, Takeshi Sakurai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Sleep
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Online Access:https://www.frontiersin.org/articles/10.3389/frsle.2025.1614100/full
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author Jiahui Yu
Jiahui Yu
Jiahui Yu
Norie Deki-Arima
Norie Deki-Arima
Yuki C. Saito
Yuki C. Saito
Naoki Furutani
Masaaki Nishiyama
Masaaki Nishiyama
Keiichi I. Nakayama
Yasutaka Niwa
Arisa Hirano
Arisa Hirano
Takeshi Sakurai
Takeshi Sakurai
Takeshi Sakurai
author_facet Jiahui Yu
Jiahui Yu
Jiahui Yu
Norie Deki-Arima
Norie Deki-Arima
Yuki C. Saito
Yuki C. Saito
Naoki Furutani
Masaaki Nishiyama
Masaaki Nishiyama
Keiichi I. Nakayama
Yasutaka Niwa
Arisa Hirano
Arisa Hirano
Takeshi Sakurai
Takeshi Sakurai
Takeshi Sakurai
author_sort Jiahui Yu
collection DOAJ
description Individuals with autism spectrum disorder (ASD) frequently experience sleep disturbances, including difficulties in sleep initiation, reduced total sleep time, and excessive daytime sleepiness. Among them, those carrying mutations in the CHD8, a high-penetrance ASD risk gene, often exhibit both core ASD symptoms and pronounced sleep abnormalities. However, detailed evaluations of sleep architecture and circadian activity in this population remain limited. In this study, we characterized the daily sleep patterns of Chd8 heterozygous knockout mice of both sexes, an established ASD model, using electroencephalography (EEG)/electromyography (EMG) recordings. Chd8 knockout mice exhibited reduced wakefulness and increased rapid eye movement (REM) sleep duration during the dark phase, along with disruption of normal daily REM sleep fluctuations. Furthermore, analysis of REM latency distributions revealed a reduction in short-latency REM bouts (i.e., <150 seconds) during the light phase. Chd8 knockout also showed reduced locomotor activity at night. These findings provide new insights into the sleep phenotypes associated with CHD8-related ASD and may help elucidate the underlying neurobiological mechanisms of sleep disturbances in this condition.
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spelling doaj-art-08f8580daae749169a7d0799dffa1a222025-08-20T02:57:35ZengFrontiers Media S.A.Frontiers in Sleep2813-28902025-08-01410.3389/frsle.2025.16141001614100Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutationJiahui Yu0Jiahui Yu1Jiahui Yu2Norie Deki-Arima3Norie Deki-Arima4Yuki C. Saito5Yuki C. Saito6Naoki Furutani7Masaaki Nishiyama8Masaaki Nishiyama9Keiichi I. Nakayama10Yasutaka Niwa11Arisa Hirano12Arisa Hirano13Takeshi Sakurai14Takeshi Sakurai15Takeshi Sakurai16International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Ibaraki, JapanDegree Program in Comprehensive Human Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki, JapanInstitute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Ibaraki, JapanInstitute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Ibaraki, JapanInstitute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, JapanDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanSocial Brain Development Research Unit, Next Generation Medical Development Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa, JapanDepartment of Histology and Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, JapanAnticancer Strategies Laboratory, Advanced Research Initiative, Institute of Science Tokyo, Tokyo, JapanDepartment of Pharmacology, Biomedical Research Center, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Ibaraki, JapanInstitute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Ibaraki, JapanInstitute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, JapanLife Science Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, JapanIndividuals with autism spectrum disorder (ASD) frequently experience sleep disturbances, including difficulties in sleep initiation, reduced total sleep time, and excessive daytime sleepiness. Among them, those carrying mutations in the CHD8, a high-penetrance ASD risk gene, often exhibit both core ASD symptoms and pronounced sleep abnormalities. However, detailed evaluations of sleep architecture and circadian activity in this population remain limited. In this study, we characterized the daily sleep patterns of Chd8 heterozygous knockout mice of both sexes, an established ASD model, using electroencephalography (EEG)/electromyography (EMG) recordings. Chd8 knockout mice exhibited reduced wakefulness and increased rapid eye movement (REM) sleep duration during the dark phase, along with disruption of normal daily REM sleep fluctuations. Furthermore, analysis of REM latency distributions revealed a reduction in short-latency REM bouts (i.e., <150 seconds) during the light phase. Chd8 knockout also showed reduced locomotor activity at night. These findings provide new insights into the sleep phenotypes associated with CHD8-related ASD and may help elucidate the underlying neurobiological mechanisms of sleep disturbances in this condition.https://www.frontiersin.org/articles/10.3389/frsle.2025.1614100/fullautism spectrum disorder (ASD)sleepEEGCHD8Chd8 knockout mice
spellingShingle Jiahui Yu
Jiahui Yu
Jiahui Yu
Norie Deki-Arima
Norie Deki-Arima
Yuki C. Saito
Yuki C. Saito
Naoki Furutani
Masaaki Nishiyama
Masaaki Nishiyama
Keiichi I. Nakayama
Yasutaka Niwa
Arisa Hirano
Arisa Hirano
Takeshi Sakurai
Takeshi Sakurai
Takeshi Sakurai
Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation
Frontiers in Sleep
autism spectrum disorder (ASD)
sleep
EEG
CHD8
Chd8 knockout mice
title Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation
title_full Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation
title_fullStr Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation
title_full_unstemmed Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation
title_short Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation
title_sort circadian activity and sleep architecture in autism spectrum disorder mouse model with chd8 mutation
topic autism spectrum disorder (ASD)
sleep
EEG
CHD8
Chd8 knockout mice
url https://www.frontiersin.org/articles/10.3389/frsle.2025.1614100/full
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