{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:51:05Z","timestamp":1791337865750,"version":"4.3.1"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T00:00:00Z","timestamp":1390262400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["32003B_125504"],"award-info":[{"award-number":["32003B_125504"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wake Up Narcolepsy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Narcolepsy is caused by loss of the hypothalamic neurons producing the orexin\/hypocretin neuropeptides. One key target of the orexin system is the histaminergic neurons of the tuberomammillary nucleus (TMN), an essential wake\u2010promoting system. As cerebrospinal fluid histamine levels may be low in patients with narcolepsy, we examined histaminergic neurons in patients with narcolepsy and in 2 mouse models of narcolepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We counted the number of hypothalamic neurons producing orexin, melanin\u2010concentrating hormone, and histamine in 7 narcolepsy patients and 12 control subjects using stereological techniques. We identified histaminergic neurons using immunostaining for histidine decarboxylase. We also examined these systems in 6 wild\u2010type mice, 6 orexin\/ataxin\u20103 transgenic mice, and 5 orexin ligand knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to controls, narcolepsy patients had 94% more histaminergic TMN neurons (233,572\u2009\u00b1\u200949,476 vs 120,455\u2009\u00b1\u200910,665, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). This increase was higher in 5 narcolepsy patients with &gt;90% orexin neuron loss than in 2 patients with \u226475% orexin neuron loss (252,279\u2009\u00b1\u200946,264 vs 186,804\u2009\u00b1\u20091,256, <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Similarly, the number of histaminergic TMN neurons was increased 53% in orexin ligand knockout mice compared to wild\u2010type mice, whereas orexin\/ataxin\u20103 transgenic mice showed an intermediate 28% increase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This surprising increase in histaminergic neurons in narcolepsy may be a compensatory response to loss of excitatory drive from the orexin neurons and may contribute to some of the symptoms of narcolepsy such as preserved consciousness during cataplexy and fragmented nighttime sleep. In addition, this finding may have therapeutic implications, as medications that enhance histamine signaling are now under development. Ann Neurol 2013;74:794\u2013804<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24019","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T11:10:54Z","timestamp":1378379454000},"page":"794-804","source":"Crossref","is-referenced-by-count":154,"title":["Increase of histaminergic tuberomammillary neurons in narcolepsy"],"prefix":"10.1002","volume":"74","author":[{"given":"Philipp O.","family":"Valko","sequence":"first","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center Boston MA"},{"name":"Department of Neurology University Hospital of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury V.","family":"Gavrilov","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center Boston MA"},{"name":"Department of Neurology University Hospital of Zurich Zurich Switzerland"},{"name":"Department of General Pathology and Pathological Physiology 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CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian R.","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center Boston MA"},{"name":"Department of Neurology University Hospital of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Scammell","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center Boston 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