Reduced number of hypocretin neurons in human narcolepsy.
Murine and canine narcolepsy can be caused by mutations of the hypocretin (Hcrt) (orexin) precursor or Hcrt receptor genes. In contrast to these animal models, most human narcolepsy is not familial, is discordant in identical twins, and has not been linked to mutations of the Hcrt system. Thus, the cause of human narcolepsy remains unknown. Here we show that human narcoleptics have an 85%-95% reduction in the number of Hcrt neurons. Melanin-concentrating hormone (MCH) neurons, which are intermixed with Hcrt cells in the normal brain, are not reduced in number, indicating that cell loss is relatively specific for Hcrt neurons. The presence of gliosis in the hypocretin cell region is consistent with a degenerative process being the cause of the Hcrt cell loss in narcolepsy.
Thannickal
T C
TC
Department of Psychiatry and Brain Research Institute, University of California, Los Angeles, USA.
Moore
R Y
RY
Nienhuis
R
R
Ramanathan
L
L
Gulyani
S
S
Aldrich
M
M
Cornford
M
M
Siegel
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins; D002452:Cell Count; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006801:Humans; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008543:Melanins / Q000378:metabolism; D008875:Middle Aged; D009290:Narcolepsy / Q000209:etiology / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000378:metabolism*; D000068797:Orexins; D010907:Pituitary Hormones / Q000378:metabolism
D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone