{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:31:42Z","timestamp":1792794702083,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T00:00:00Z","timestamp":1684540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100011076","name":"Simon Fougner Hartmanns Familiefond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R277-2018-260"],"award-info":[{"award-number":["R277-2018-260"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R344-2020-749"],"award-info":[{"award-number":["R344-2020-749"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Carlsberg Foundation Young Researcher Fellowship","id":[{"id":"https:\/\/ror.org\/01kpjmx04","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Narcolepsy type 1 (NT1) is a neurological disorder caused by disruption of hypocretin (HCRT; or orexin) neurotransmission leading to fragmented sleep\/wake states, excessive daytime sleepiness, and cataplexy (abrupt muscle atonia during wakefulness). Electroencephalography and electromyography (EEG\/EMG) monitoring is the gold standard to assess NT1 phenotypical features in both humans and mice. Here, we evaluated the digital ventilated home-cage (DVC\u00ae) activity system as an alternative to detect NT1 features in two NT1 mouse models: the genetic HCRT-knockout (-KO) model, and the inducible HCRT neuron-ablation hcrt-tTA;TetO-DTA (DTA) model, including both sexes. NT1 mice exhibited an altered dark phase activity profile and increased state transitions, compared to the wild-type (WT) phenotype. An inability to sustain activity periods &amp;gt;40 min represented a robust activity-based NT1 biomarker. These features were observable within the first weeks of HCRT neuron degeneration in DTA mice. We also created a nest-identification algorithm to differentiate between inactivity and activity, inside and outside the nest as a sleep and wake proxy, respectively, showing significant correlations with EEG\/EMG-assessed sleep\/wake behavior. Lastly, we tested the sensitivity of the activity system to detect behavioral changes in response to interventions such as repeated saline injection and chocolate. Surprisingly, daily consecutive saline injections significantly reduced activity and increased nest time of HCRT-WT mice. Chocolate increased total activity in all mice, and increased the frequency of short out-of-nest inactivity episodes in HCRT-KO mice. We conclude that the DVC\u00ae system provides a useful tool for non-invasive monitoring of NT1 phenotypical features, and has the potential to monitor drug effects in NT1 mice.<\/jats:p>","DOI":"10.1093\/sleep\/zsad144","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T23:25:41Z","timestamp":1684625141000},"source":"Crossref","is-referenced-by-count":17,"title":["Non-invasive detection of narcolepsy type I phenotypical features and disease progression by continuous home-cage monitoring of activity in two mouse models: the HCRT-KO and DTA model"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4585-5996","authenticated-orcid":false,"given":"Louise","family":"Piilgaard","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L","family":"Justinussen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille Gylling","family":"Hviid","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-4741","authenticated-orcid":false,"given":"Ren\u00e9","family":"Lemcke","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petrine","family":"Wellendorph","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-9451","authenticated-orcid":false,"given":"Birgitte Rahbek","family":"Kornum","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"issue":"9197","key":"2023090806293296000_CIT0001","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0140-6736(99)05582-8","article-title":"Hypocretin (orexin) deficiency in human narcolepsy","volume":"355","author":"Nishino","year":"2000","journal-title":"Lancet."},{"issue":"9","key":"2023090806293296000_CIT0002","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/79690","article-title":"A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains","volume":"6","author":"Peyron","year":"2000","journal-title":"Nat Med."},{"issue":"3","key":"2023090806293296000_CIT0003","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0896-6273(00)00058-1","article-title":"Reduced number of hypocretin neurons in human narcolepsy","volume":"27","author":"Thannickal","year":"2000","journal-title":"Neuron."},{"key":"2023090806293296000_CIT0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2016.100","article-title":"Narcolepsy","volume":"3","author":"Kornum","year":"2017","journal-title":"Nat Rev Dis Primer"},{"issue":"7","key":"2023090806293296000_CIT0005","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/14728222.2021.1969361","article-title":"Emerging therapeutic targets for narcolepsy","volume":"25","author":"Vringer","year":"2021","journal-title":"Expert Opin Ther Targets."},{"issue":"1","key":"2023090806293296000_CIT0006","doi-asserted-by":"crossref","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 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