{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:45:00Z","timestamp":1794361500494,"version":"4.9.0"},"reference-count":51,"publisher":"Society for Neuroscience","issue":"19","license":[{"start":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T00:00:00Z","timestamp":1415318400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2014,5,7]]},"abstract":"<jats:p>The sleep disorder narcolepsy results from loss of hypothalamic orexin\/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin\/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertal<jats:italic>orexin-tTA;TetO DTA<\/jats:italic>mice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when \u223c5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin\/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep\/wake regulation, o<jats:italic>rexin-tTA; TetO DTA<\/jats:italic>mice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost.<\/jats:p>","DOI":"10.1523\/jneurosci.0073-14.2014","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T17:38:19Z","timestamp":1399484299000},"page":"6495-6509","source":"Crossref","is-referenced-by-count":214,"title":["Conditional Ablation of Orexin\/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function"],"prefix":"10.1523","volume":"34","author":[{"given":"Sawako","family":"Tabuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Tsunematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah W.","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tominaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyo","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Minokoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Kilduff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2014,5,7]]},"reference":[{"key":"2023041304104614000_34.19.6495.1","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1093\/sleep\/33.11.1457","article-title":"Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a retrospective study of 51 children","volume":"33","author":"Aran","year":"2010","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(76)90298-7"},{"key":"2023041304104614000_34.19.6495.3","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2442"},{"key":"2023041304104614000_34.19.6495.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0080-14.2014"},{"key":"2023041304104614000_34.19.6495.5","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01552.x"},{"key":"2023041304104614000_34.19.6495.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81973-X"},{"key":"2023041304104614000_34.19.6495.7","doi-asserted-by":"crossref","first-page":"RC168","DOI":"10.1523\/JNEUROSCI.21-19-j0003.2001","article-title":"Orexin (hypocretin) neurons contain dynorphin","volume":"21","author":"Chou","year":"2001","journal-title":"J Neurosci"},{"key":"2023041304104614000_34.19.6495.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.04.007"},{"key":"2023041304104614000_34.19.6495.9","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000101725.34089.1E"},{"key":"2023041304104614000_34.19.6495.10","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007762"},{"key":"2023041304104614000_34.19.6495.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.322"},{"key":"2023041304104614000_34.19.6495.12","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/sleep\/30.11.1417","article-title":"Running promotes wakefulness and increases cataplexy in orexin knockout mice","volume":"30","author":"Espa\u00f1a","year":"2007","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062391"},{"key":"2023041304104614000_34.19.6495.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00859-2"},{"key":"2023041304104614000_34.19.6495.15","doi-asserted-by":"publisher","DOI":"10.1038\/nn1997"},{"key":"2023041304104614000_34.19.6495.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00293-8"},{"key":"2023041304104614000_34.19.6495.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.01.046"},{"key":"2023041304104614000_34.19.6495.18","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-011-0137-6."},{"key":"2023041304104614000_34.19.6495.19","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/sleep\/9.1.254","article-title":"Increased frequency of non-insulin-dependent diabetes mellitus among narcoleptic patients","volume":"9","author":"Honda","year":"1986","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.20","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20808"},{"key":"2023041304104614000_34.19.6495.21","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23968"},{"key":"2023041304104614000_34.19.6495.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018697"},{"key":"2023041304104614000_34.19.6495.23","first-page":"A22","article-title":"Behavioral and polysomnographic characterization of orexin-1 receptor and orexin-2 receptor double knockout mice","volume":"24","author":"Kisanuki","year":"2001","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01884-3"},{"key":"2023041304104614000_34.19.6495.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.19.11371"},{"key":"2023041304104614000_34.19.6495.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81965-0"},{"key":"2023041304104614000_34.19.6495.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.04.013"},{"key":"2023041304104614000_34.19.6495.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8986.1995.tb02957.x"},{"key":"2023041304104614000_34.19.6495.29","first-page":"1012","article-title":"HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients","volume":"20","author":"Mignot","year":"1997","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.30","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1093\/sleep\/30.12.1705","article-title":"Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin","volume":"30","author":"Morgenthaler","year":"2007","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.31","doi-asserted-by":"publisher","DOI":"10.3390\/toxins3030294"},{"key":"2023041304104614000_34.19.6495.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(96)00070-6"},{"key":"2023041304104614000_34.19.6495.33","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1242\/jcs.113.17.3073","article-title":"Involvement of Iba1 in membrane ruffling and phagocytosis of macrophages\/microglia","volume":"113","author":"Ohsawa","year":"2000","journal-title":"J Cell Sci"},{"key":"2023041304104614000_34.19.6495.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0499-13.2013"},{"key":"2023041304104614000_34.19.6495.35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/sleep\/25.1.27","article-title":"Clinical aspects of narcolepsy-cataplexy across ethnic groups","volume":"25","author":"Okun","year":"2002","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.36","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10860"},{"key":"2023041304104614000_34.19.6495.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80949-6"},{"key":"2023041304104614000_34.19.6495.38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17771"},{"key":"2023041304104614000_34.19.6495.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2008.12.007"},{"key":"2023041304104614000_34.19.6495.40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.5665\/sleep\/32.1.111","article-title":"A consensus definition of cataplexy in mouse models of narcolepsy","volume":"32","author":"Scammell","year":"2009","journal-title":"Sleep"},{"key":"2023041304104614000_34.19.6495.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)74704-8"},{"key":"2023041304104614000_34.19.6495.42","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2972"},{"key":"2023041304104614000_34.19.6495.43","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1523\/JNEUROSCI.17-05-01869.1997","article-title":"Sleep and sleep regulation in normal and prion protein-deficient mice","volume":"17","author":"Tobler","year":"1997","journal-title":"J Neurosci"},{"key":"2023041304104614000_34.19.6495.44","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00238-0"},{"key":"2023041304104614000_34.19.6495.45","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3490-07.2008"},{"key":"2023041304104614000_34.19.6495.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2012.07.005"},{"key":"2023041304104614000_34.19.6495.47","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24019"},{"key":"2023041304104614000_34.19.6495.48","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt069"},{"key":"2023041304104614000_34.19.6495.49","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00330-1"},{"key":"2023041304104614000_34.19.6495.50","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6318"},{"key":"2023041304104614000_34.19.6495.51","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00331-3"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0073-14.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T22:05:11Z","timestamp":1681423511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0073-14.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,7]]},"references-count":51,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2014,5,7]]},"published-print":{"date-parts":[[2014,5,7]]}},"alternative-id":["10.1523\/JNEUROSCI.0073-14.2014"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0073-14.2014","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,7]]}}}