Narcolepsy increased L-PGDS (beta-trace) levels correlate with excessive daytime sleepiness but not with cataplexy.
OBJECTIVE
Alterations in the prostaglandin-D-system have been found in animal sleep experiments and disorders that present with hypersomnia or sleep disturbances. The recently demonstrated involvement of the leptomeningeal lipocalin-type prostaglandin-Dsynthase (L-PGDS) (beta-trace) in human physiological sleep encouraged us to investigate its role in the pathophysiology of narcolepsy.


METHODS
In a pilot study, serum LPGDS and melatonin concentrations were assessed in 14 narcoleptic patients during undisturbed sleep and total sleep deprivation, compared with those from 14 healthy controls during undisturbed sleep. Excessive daytime sleepiness was measured by a standardized questionnaire (Epworth sleepiness scale, ESS).


RESULTS
In narcoleptic patients, markedly increased baseline L-PGDS levels were significantly correlated with the ESS score, but not with the degree of cataplexy. Serum L-PGDS concentrations in patients as well as in controls followed a time-dependent fluctuation with evening increases, highest values during the night and in the morning. Compared with controls, patients exhibited significant/increased amplitude of circulating L-PGDS without any suppression by total sleep deprivation.


CONCLUSIONS
These findings indicate that the prostaglandin-D-system contributes to the pathophysiology of narcolepsy, e. g. the regulation of excessive daytime sleepiness. Since it has been suggested that L-PGDS is also involved in neurodegenerative disorders, there may be a more specific role of the prostaglandin- D-system in narcoleptic aetiogenesis. Moreover, its linkage with the immune system as well as with human sleep regulation offers a direct access for investigating both systems.
Jordan
Wolfgang
W
Dept. of Psychiatry and Psychotherapy, Georg-August-University of Göttingen, von Sieboldstr. 5, 37075 Göttingen, Germany. wjordan@gwdg.de
Tumani
Hayrettin
H
Cohrs
Stefan
S
Rodenbeck
Andrea
A
Rüther
Eckart
E
Bechthold
Jens
J
Mayer
Geert
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D054834:Lipocalins; D008297:Male; D008550:Melatonin / Q000097:blood; D008875:Middle Aged; D009290:Narcolepsy / Q000097:blood* / Q000503:physiopathology*; D010865:Pilot Projects
D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D008550:Melatonin