title: Concomitant loss of dynorphin, NARP, and orexin in narcolepsy.
abstract: BACKGROUND
  Narcolepsy with cataplexy is associated with a loss of orexin/hypocretin. It is speculated that an autoimmune process kills the orexin-producing neurons, but these cells may survive yet fail to produce orexin.
  
  
  OBJECTIVE
  To examine whether other markers of the orexin neurons are lost in narcolepsy with cataplexy.
  
  
  METHODS
  We used immunohistochemistry and in situ hybridization to examine the expression of orexin, neuronal activity-regulated pentraxin (NARP), and prodynorphin in hypothalami from five control and two narcoleptic individuals.
  
  
  RESULTS
  In the control hypothalami, at least 80% of the orexin-producing neurons also contained prodynorphin mRNA and NARP. In the patients with narcolepsy, the number of cells producing these markers was reduced to about 5 to 10% of normal.
  
  
  CONCLUSIONS
  Narcolepsy with cataplexy is likely caused by a loss of the orexin-producing neurons. In addition, loss of dynorphin and neuronal activity-regulated pentraxin may contribute to the symptoms of narcolepsy.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Crocker
authors.forename: R A
authors.initials: RA
authors.lastname: España
authors.forename: M
authors.initials: M
authors.lastname: Papadopoulou
authors.forename: C B
authors.initials: CB
authors.lastname: Saper
authors.forename: J
authors.initials: J
authors.lastname: Faraco
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: E
authors.initials: E
authors.lastname: Mignot
authors.forename: T E
authors.initials: TE
authors.lastname: Scammell
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D020274:Autoimmune Diseases of the Nervous System / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D004399:Dynorphins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D000068797:Orexins; D012333:RNA, Messenger / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D001323:Autoantibodies; D002097:C-Reactive Protein; D004399:Dynorphins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D000099153:Pentraxins