Diurnal variation in CSF orexin-A in healthy male subjects.
OBJECTIVE
Orexin-A is hypothesized to promote wakefulness, and we examined whether cerebrospinal fluid (CSF) orexin-A levels are higher during the waking period in man.


METHODS
Within-subjects, repeated-measures design with balanced ordering of sampling at approximately 5 AM and 5 PM.


METHODS
Eight healthy young males. MESUREMENTS: CSF orexin-A levels and standard polysomnography.


RESULTS
Orexin-A levels during the sleep period were 4% higher than during the waking period (314.9 pg/ml versus 302.8 pg/ml, p < 0.03). Sleep period orexin-A levels were negatively correlated with REM sleep as a percentage of total sleep time (p < 0.05). The day and night levels of orexin-A were strongly correlated within subjects (r = 0.97; p < 0.0001) even though the samples were collected 1-2 weeks apart.


CONCLUSIONS
Orexin-A levels in lumbar CSF are slightly higher at 5 AM than at 5 PM. Because orexin release is thought to be highest during the waking period, this observation was unexpected and may reflect a long delay between the release of orexin and its appearance in lumbar CSF. Orexin-A levels vary moderately between subjects, but are quite consistent within the same subject. Thus, for the diagnostic evaluation of narcolepsy, the time of CSF collection should have little impact.
Portland Diabetes and Endocrinology Center, Portland, OR, USA.
Scott P
SP
Grady
Seiji
S
Nishino
Charles A
CA
Czeisler
David
D
Hepner
Thomas E
TE
Scammell
D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D006304:Health Status; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D009290:Narcolepsy / Q000134:cerebrospinal fluid; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D017286:Polysomnography; D012895:Sleep, REM / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins