The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome.
BACKGROUND
Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like symptoms, such as sleep-onset rapid eye movement sleep and cataplexy, independent of obesity-related sleep disturbances, which suggests a disorder of the hypocretin neurons.


OBJECTIVE
We hypothesized that the narcolepsy-like symptoms in PWS are caused by a decline in the number of hypocretin neurons.


METHODS
We estimated the number of hypocretin neurons in postmortem hypothalami using immunocytochemistry and an image analysis system.


METHODS
This study was conducted at the Netherlands Institute for Brain Research.


METHODS
Eight PWS adults, three PWS infants, and 11 controls were studied.


METHODS
The total number of hypocretin neurons in the lateral hypothalamus was measured.


RESULTS
There was no significant difference in the total number of hypocretin-containing neurons among the seven PWS patients (in whom sufficient hypothalamic material was available to quantify total cell number) and seven age-matched controls, either in adults or in infants. A significant decline with age was found in adult PWS patients (r = -0.9; P = 0.037).


CONCLUSIONS
We conclude that a decrease in the number of hypocretin neurons does not play a major role in the occurrence of narcolepsy-like symptoms in PWS.
Netherlands Institute for Brain Research, Amsterdam, The Netherlands. r.fronczek@lumc.nl
Rolf
R
Fronczek
Gert Jan
GJ
Lammers
Rawien
R
Balesar
Unga A
UA
Unmehopa
Dick F
DF
Swaab
D000328:Adult; D000368:Aged; D000375:Aging; D016022:Case-Control Studies; D002452:Cell Count; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000150:complications; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D011218:Prader-Willi Syndrome / Q000150:complications / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins