{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:49:27Z","timestamp":1755218967021,"version":"3.43.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Sleep"],"abstract":"<jats:p>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 <jats:italic>CHD8<\/jats:italic>, 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 <jats:italic>Chd8<\/jats:italic> heterozygous knockout mice of both sexes, an established ASD model, using electroencephalography (EEG)\/electromyography (EMG) recordings. <jats:italic>Chd8<\/jats:italic> 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., &amp;lt;150 seconds) during the light phase. <jats:italic>Chd8<\/jats:italic> knockout also showed reduced locomotor activity at night. These findings provide new insights into the sleep phenotypes associated with <jats:italic>CHD8<\/jats:italic>-related ASD and may help elucidate the underlying neurobiological mechanisms of sleep disturbances in this condition.<\/jats:p>","DOI":"10.3389\/frsle.2025.1614100","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T14:33:51Z","timestamp":1754490831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation"],"prefix":"10.3389","volume":"4","author":[{"given":"Jiahui","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norie","family":"Deki-Arima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki C.","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Furutani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichi I.","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasutaka","family":"Niwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arisa","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/aur.1707","article-title":"Hyperactivity and male-specific sleep deficits in the 16p11.2 deletion mouse model of autism","volume":"10","author":"Angelakos","year":"2017","journal-title":"Autism Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3389\/fnins.2015.00477","article-title":"Mutations and modeling of the chromatin remodeler CHD8 define an emerging autism etiology","volume":"9","author":"Barnard","year":"2015","journal-title":"Front. Neuro. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.cell.2014.06.017","article-title":"Disruptive CHD8 mutations define a subtype of autism early in development","volume":"158","author":"Bernier","year":"2014","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1212\/WNL.0000000000009033","article-title":"Practice guideline: treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: report of the guideline development, dissemination, and implementation subcommittee of the american academy of neurology","volume":"94","author":"Buckley","year":"2020","journal-title":"Neurology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1186\/s12888-021-03405-w","article-title":"Sleep problems in children with autism spectrum disorder: a multicenter survey","volume":"21","author":"Chen","year":"2021","journal-title":"BMC Psychiatry"},{"key":"B6","doi-asserted-by":"publisher","first-page":"16763","DOI":"10.1523\/JNEUROSCI.1885-12.2012","article-title":"The lateral hypothalamic area controls paradoxical (REM) sleep by means of descending projections to brainstem GABAergic neurons","volume":"32","author":"Cl\u00e9ment","year":"2012","journal-title":"J. Neuro. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1866-1955-6-44","article-title":"The relationship between sleep and behavior in autism spectrum disorder (ASD): a review","volume":"6","author":"Cohen","year":"2014","journal-title":"J. Neurodev. Disord"},{"key":"B8","doi-asserted-by":"publisher","first-page":"eabe2626","DOI":"10.1126\/sciadv.abe2626","article-title":"The CHD8\/CHD7\/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects","volume":"7","author":"Coll-Tan\u00e9","year":"2021","journal-title":"Sci. Adv."},{"key":"B9","doi-asserted-by":"publisher","first-page":"22425","DOI":"10.1038\/s41598-022-23614-x","article-title":"The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1","volume":"12","author":"Derafshi","year":"2022","journal-title":"Sci. Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/nature20142","article-title":"Forward-genetics analysis of sleep in randomly mutagenized mice","volume":"539","author":"Funato","year":"2016","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3080","DOI":"10.1038\/s41598-024-74008-0","article-title":"Utility of complexity analysis in electroencephalography and electromyography for automated classification of sleep-wake states in mice","volume":"15","author":"Furutani","year":"2025","journal-title":"Sci. Rep"},{"key":"B12","doi-asserted-by":"publisher","first-page":"736696","DOI":"10.3389\/fpsyt.2022.736696","article-title":"Sleep disturbances in children affected by autism spectrum disorder","volume":"13","author":"Galli","year":"2022","journal-title":"Front. Psychiatry"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.rasd.2011.01.010","article-title":"Sleep is associated with problem behaviors in children and adolescents with Autism Spectrum Disorders","volume":"5","author":"Goldman","year":"2011","journal-title":"Res. Autism Spectr. Disord"},{"key":"B14","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s10803-011-1270-5","article-title":"Parental sleep concerns in autism spectrum disorders: variations from childhood to adolescence","volume":"42","author":"Goldman","year":"2012","journal-title":"J. Autism Dev. Disord"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1016\/j.ridd.2014.03.037","article-title":"Sleep patterns in children with and without autism spectrum disorders: Developmental comparisons","volume":"35","author":"Hodge","year":"2014","journal-title":"Res. Dev. Disabil"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e42819","DOI":"10.7554\/eLife.42819","article-title":"Shank3 modulates sleep and expression of circadian transcription factors","volume":"8","author":"Ingiosi","year":"2019","journal-title":"eLife"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1126\/science.aax9238","article-title":"REM sleep\u2013active MCH neurons are involved in forgetting hippocampus-dependent memories","volume":"365","author":"Izawa","year":"2019","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41392-022-01081-0","article-title":"Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications","volume":"7","author":"Jiang","year":"2022","journal-title":"Signal Transduct. Target. Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3389\/fnsys.2014.00118","article-title":"Twenty-four hour quantitative-EEG and in-vivo glutamate biosensor detects activity and circadian rhythm dependent biomarkers of pathogenesis in Mecp2 null mice","volume":"8","author":"Johnston","year":"2014","journal-title":"Front. Syst. Neuro. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.nbd.2015.02.016","article-title":"Sleep impairment and reduced interneuron excitability in a mouse model of Dravet Syndrome. Neurobiol","volume":"77","author":"Kalume","year":"2015","journal-title":"Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/nature19357","article-title":"CHD8 haploinsufficiency results in autistic-like phenotypes in mice","volume":"537","author":"Katayama","year":"2016","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"zsac273","DOI":"10.1093\/sleep\/zsac273","article-title":"Sleep architecture is associated with core symptom severity in autism spectrum disorder","volume":"46","author":"Kawai","year":"2022","journal-title":"Sleep"},{"key":"B23","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41572-019-0138-4","article-title":"Autism spectrum disorder","volume":"6","author":"Lord","year":"2020","journal-title":"Nat. Rev. Dis. Prim"},{"key":"B24","doi-asserted-by":"publisher","first-page":"zsy253","DOI":"10.1093\/sleep\/zsy253","article-title":"Altered sleep architecture, rapid eye movement sleep, and neural oscillation in a mouse model of human chromosome 16p11.2 microdeletion","volume":"42","author":"Lu","year":"2018","journal-title":"Sleep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12964-021-00741-y","article-title":"Types of nuclear localization signals and mechanisms of protein import into the nucleus","volume":"19","author":"Lu","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.5665\/sleep.3192","article-title":"Role of MCH neurons in paradoxical (REM) sleep control","volume":"36","author":"Luppi","year":"2013","journal-title":"Sleep"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1007\/s10803-011-1418-3","article-title":"Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes","volume":"42","author":"Malow","year":"2012","journal-title":"J. Autism Dev. Disord"},{"key":"B28","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/9780470942390.mo110126","article-title":"Sleep and EEG phenotyping in mice","volume":"2","author":"Mang","year":"2012","journal-title":"Curr. Protoc. Mouse Biol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s40489-013-0009-y","article-title":"Sleep problems in autism spectrum disorder: a literature review","volume":"1","author":"Mannion","year":"2014","journal-title":"Rev. J. Autism Dev. Disord"},{"key":"B30","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1080\/19315860801988210","article-title":"Sleep disturbances in adults with autism spectrum disorders and severe intellectual impairments","volume":"1","author":"Matson","year":"2008","journal-title":"J. Ment. Heal. Res. Intellect. Disabil"},{"key":"B31","doi-asserted-by":"publisher","first-page":"100095","DOI":"10.1016\/j.nbscr.2023.100095","article-title":"Sleep disturbances in autism spectrum disorder: animal models, neural mechanisms, and therapeutics","volume":"14","author":"Maurer","year":"2023","journal-title":"Neurobiol. Sleep Circadian Rhythm"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1002\/jnr.25119","article-title":"Shank3 influences mammalian sleep development","volume":"100","author":"Medina","year":"2022","journal-title":"J. Neuro. Sci. Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"722","DOI":"10.47102\/annals-acadmedsg.V37N8p722","article-title":"Behavioural sleep disorders in children and adolescents","volume":"37","author":"Mindell","year":"2008","journal-title":"Ann. Acad. Med. Singap"},{"key":"B34","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11011","article-title":"Patterns and rates of exonic de novo mutations in autism spectrum disorders","volume":"485","author":"Neale","year":"2012","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/ncb1831","article-title":"CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis","volume":"11","author":"Nishiyama","year":"2009","journal-title":"Nat. Cell Biol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1128\/MCB.06409-11","article-title":"Histone H1 recruitment by CHD8 is essential for suppression of the Wnt\u2013\u03b2-Catenin signaling pathway","volume":"32","author":"Nishiyama","year":"2012","journal-title":"Mol. Cell. Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1126\/science.1227764","article-title":"Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders","volume":"338","author":"O'Roak","year":"","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/nature10989","article-title":"Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations","volume":"485","author":"O'Roak","year":"","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1111\/epi.12060","article-title":"Altered sleep regulation in a mouse model of SCN1A-derived genetic epilepsy with febrile seizures plus (GEFS+)","volume":"54","author":"Papale","year":"2013","journal-title":"Epilepsia"},{"key":"B40","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.pcl.2011.03.009","article-title":"Sleep and autism spectrum disorders","volume":"58","author":"Reynolds","year":"2011","journal-title":"Pediatr. Clin. North Am"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e46316","DOI":"10.1371\/journal.pone.0046316","article-title":"Chromodomain helicase binding protein 8 (Chd8) is a novel a-kinase anchoring protein expressed during rat cardiac development","volume":"7","author":"Shanks","year":"2012","journal-title":"PLoS ONE"},{"key":"B42","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"515","author":"Study","year":"2014","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neubiorev.2019.04.012","article-title":"Behavioral neuroscience of autism","volume":"110","author":"Takumi","year":"2020","journal-title":"Neuro. Sci. Biobehav. Rev"},{"key":"B44","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.cell.2012.03.028","article-title":"Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries","volume":"149","author":"Talkowski","year":"2012","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neuron.2016.02.032","article-title":"Involvement of Ca2+-Dependent hyperpolarization in sleep duration in mammals","volume":"90","author":"Tatsuki","year":"2016","journal-title":"Neuron"},{"key":"B46","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00401-017-1736-4","article-title":"Autism spectrum disorder: neuropathology and animal models","volume":"134","author":"Varghese","year":"2017","journal-title":"Acta Neuropathol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1866-1955-5-24","article-title":"Resting state EEG abnormalities in autism spectrum disorders","volume":"5","author":"Wang","year":"2013","journal-title":"J. Neurodev. Disord"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.3390\/genes12081133","article-title":"The mechanisms of CHD8 in neurodevelopment and autism spectrum disorders","volume":"12","author":"Weissberg","year":"2021","journal-title":"Genes"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1002\/jnr.24619","article-title":"Sleep, brain development, and autism spectrum disorders: Insights from animal models","volume":"98","author":"Wintler","year":"2020","journal-title":"J. Neuro. Sci. Res"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e12852","DOI":"10.1111\/gbb.12852","article-title":"Melatonin ameliorates sleep\u2013wake disturbances and autism-like behaviors in the Ctnnd2 knock out mouse model of autism spectrum disorders","volume":"22","author":"Xu","year":"2023","journal-title":"Genes, Brain Behav"},{"key":"B51","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/aur.2696","article-title":"Global prevalence of autism: a systematic review update","volume":"15","author":"Zeidan","year":"2022","journal-title":"Autism Res"},{"key":"B52","doi-asserted-by":"publisher","first-page":"785","DOI":"10.5665\/sleep.3590","article-title":"The circadian clock gene csnk1e regulates rapid eye movement sleep amount, and nonrapid eye movement sleep architecture in mice","volume":"37","author":"Zhou","year":"2014","journal-title":"Sleep"}],"container-title":["Frontiers in Sleep"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frsle.2025.1614100\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T14:33:52Z","timestamp":1754490832000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frsle.2025.1614100\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":52,"alternative-id":["10.3389\/frsle.2025.1614100"],"URL":"https:\/\/doi.org\/10.3389\/frsle.2025.1614100","relation":{},"ISSN":["2813-2890"],"issn-type":[{"type":"electronic","value":"2813-2890"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"article-number":"1614100"}}