{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:53:56Z","timestamp":1782132836719,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS056872"],"award-info":[{"award-number":["R01 NS056872"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R56 NS115978"],"award-info":[{"award-number":["R56 NS115978"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD103525"],"award-info":[{"award-number":["P50 HD103525"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH\u201022\u20101\u20100227"],"award-info":[{"award-number":["W81XWH\u201022\u20101\u20100227"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A strong bidirectional relationship exists between epilepsy and sleep, with seizures often occurring more frequently in sleep and, in turn, sleep being disrupted by seizures. However, the mechanistic basis of seizure\u2013sleep interactions is poorly understood. In this study, we characterized the relationship between seizures and sleep in a mouse model of the genetic disorder tuberous sclerosis complex (TSC) and investigated potential mechanisms underlying seizure\u2013sleep interactions related to hypothalamic orexin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Tsc1<\/jats:italic>\n                      <jats:sup>GFAP<\/jats:sup>\n                      CKO mice were used to investigate the relationship between seizures and sleep with video, electroencephalographic (EEG), and electromyographic analysis, including the dependence of seizure frequency on vigilance state (awake, rapid eye movement [REM], non\u2010REM) and the effect of seizures on the wake\u2013sleep cycle. Orexin expression in hypothalamus was assessed by immunohistochemistry in relation to seizure frequency. The effect of orexin antagonists on sleep and seizures was tested by video\u2010EEG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall seizures occurred most commonly in non\u2010REM sleep in\n                      <jats:italic>Tsc1<\/jats:italic>\n                      <jats:sup>GFAP<\/jats:sup>\n                      CKO mice but had the highest seizure frequency in REM sleep after normalizing for amount of time spent in each vigilance state. Conversely, seizures were associated with disruptions in the sleep\u2013wake cycle, particularly a decrease in REM sleep.\n                      <jats:italic>Tsc1<\/jats:italic>\n                      <jats:sup>GFAP<\/jats:sup>\n                      CKO mice with seizures had increased orexin expression compared with control mice or\n                      <jats:italic>Tsc1<\/jats:italic>\n                      <jats:sup>GFAP<\/jats:sup>\n                      CKO mice without seizures. The orexin antagonist suvorexant reversed the decrease in REM sleep but had no significant effect on seizures in\n                      <jats:italic>Tsc1<\/jats:italic>\n                      <jats:sup>GFAP<\/jats:sup>\n                      CKO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>A bidirectional relationship between seizures and sleep was demonstrated in a mouse model of TSC, with relative seizure frequency surprisingly being highest in REM sleep and seizures causing a disruption of REM sleep. Hypothalamic orexin may partly mediate these seizure\u2013sleep interactions, and orexin antagonists may represent rational therapies for sleep disorders in TSC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70151","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:15:42Z","timestamp":1770909342000},"page":"3108-3121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bidirectional sleep\u2010seizure interactions and orexin in a mouse model of tuberous sclerosis complex\u2010related epilepsy"],"prefix":"10.1002","volume":"67","author":[{"given":"Nicholas R.","family":"Rensing","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology 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