{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:14:35Z","timestamp":1791400475521,"version":"4.3.3"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,30]]},"abstract":"<jats:p>\n                    Narcolepsy-cataplexy is a neurological disorder associated with the inability to maintain wakefulness and abnormal intrusions of rapid eye movement sleep-related phenomena into wakefulness such as cataplexy. The vast majority of narcoleptic-cataplectic individuals have low or undetectable levels of orexin (hypocretin) neuropeptides in the cerebrospinal fluid, likely due to specific loss of the hypothalamic orexin-producing neurons. Currently available treatments for narcolepsy are only palliative, symptom-oriented pharmacotherapies. Here, we demonstrate rescue of the narcolepsy-cataplexy phenotype of orexin neuron-ablated mice by genetic and pharmacological means. Ectopic expression of a\n                    <jats:italic>prepro-orexin<\/jats:italic>\n                    transgene in the brain completely prevented cataplectic arrests and other abnormalities of rapid eye movement sleep in the absence of endogenous orexin neurons. Central administration of orexin-A acutely suppressed cataplectic behavioral arrests and increased wakefulness for 3 h. These results indicate that orexin neuron-ablated mice retain the ability to respond to orexin neuropeptides and that a temporally regulated and spatially targeted secretion of orexins is not necessary to prevent narcoleptic symptoms. Orexin receptor agonists would be of potential value for treating human narcolepsy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0400590101","type":"journal-article","created":{"date-parts":[[2004,3,30]],"date-time":"2004-03-30T14:58:04Z","timestamp":1080658684000},"page":"4649-4654","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":296,"title":["Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice"],"prefix":"10.1073","volume":"101","author":[{"given":"Michihiro","family":"Mieda","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Howard Hughes Medical Institute, and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050; Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan; and Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon T.","family":"Willie","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Howard Hughes Medical Institute, and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050; Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan; and Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Howard Hughes Medical Institute, and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050; Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan; and Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Sinton","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Howard Hughes Medical Institute, and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050; 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