Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy.

TitleLocalized loss of hypocretin (orexin) cells in narcolepsy without cataplexy.
Publication TypeJournal Article
Year of Publication2009
AuthorsThannickal TC, Nienhuis R, Siegel JM
Date Published2009 Aug
KeywordsAged, Aged, 80 and over, Brain Mapping, Cataplexy, Cell Count, Female, Glial Fibrillary Acidic Protein, Humans, Hypothalamic Hormones, Hypothalamus, Immunoenzyme Techniques, Intracellular Signaling Peptides and Proteins, Male, Melanins, Middle Aged, Narcolepsy, Neurons, Neuropeptides, Orexins, Pituitary Hormones

STUDY OBJECTIVES: Narcolepsy with cataplexy is characterized by a loss of approximately 90% of hypocretin (Hcrt) neurons. However, more than a quarter of narcoleptics do not have cataplexy and have normal levels of hypocretin in their cerebrospinal fluid, raising the possibility that their disease is caused by unrelated abnormalities. In this study we examined hypocretin pathology in narcolepsy without cataplexy.

DESIGN: We examined postmortem brain samples, including the hypothalamus of 5 narcolepsy with cataplexy patients; one narcolepsy without cataplexy patient whose complete hypothalamus was available (patient 1); one narcolepsy without cataplexy patient with anterior hypothalamus available (patient 2); and 6 normal brains. The hypothalamic tissue was immunostained for Hcrt-1, melanin-concentrating hormone (MCH), and glial fibrillary acidic protein (GFAP).

MEASUREMENTS AND RESULTS: Neither of the narcolepsy without cataplexy patients had a loss of Hcrt axons in the anterior hypothalamus. The narcolepsy without cataplexy patient whose entire brain was available for study had an overall loss of 33% of hypocretin cells compared to normals, with maximal cell loss in the posterior hypothalamus. We found elevated levels of gliosis with GFAP staining, with levels increased in the posterior hypothalamic nucleus by (295%), paraventricular (211%), periventricular (123%), arcuate (126%), and lateral (72%) hypothalamic nuclei, but not in the anterior, dorsomedial, or dorsal hypothalamus. There was no reduction in the number of MCH neurons in either patient.

CONCLUSIONS: Narcolepsy without cataplexy can be caused by a partial loss of hypocretin cells.

Alternate JournalSleep
PubMed ID19725250
PubMed Central IDPMC2717206
Grant ListHL41370 / HL / NHLBI NIH HHS / United States
MH64109 / MH / NIMH NIH HHS / United States
NS14610 / NS / NINDS NIH HHS / United States