Release of hypocretin (orexin) during waking and sleep states.
Hypocretin (Hcrt or orexin) somas are located in the hypothalamus and project widely to forebrain and brainstem regions, densely innervating monoaminergic and cholinergic cells. Loss of Hcrt function results in the sleep disorder narcolepsy. However, the normal pattern of Hcrt release across the sleep-wake cycle is unknown. We monitored Hcrt-1 release in the basal forebrain, perifornical hypothalamus, and locus ceruleus (LC) across the sleep-wake cycle using microdialysis in freely moving cats and a sensitive solid phase radioimmunoassay. We found that the peptide concentration in dialysates from the hypothalamus was significantly higher during active waking (AW) than during slow-wave sleep (SWS). Moreover, Hcrt-1 release was significantly higher during rapid eye movement (REM) sleep than during SWS in the hypothalamus and basal forebrain. We did not detect a significant difference in release across sleep-waking states in the LC, perhaps because recovered levels of the peptide were lower at this site. Because there was a trend toward higher levels of Hcrt-1 release during AW compared with quiet waking (QW) in our 10 min dialysis samples, we compared Hcrt-1 levels in CSF in 2 hr AW and QW periods. Hcrt-1 release into CSF was 67% higher during AW than during QW. Elevated levels of Hcrt during REM sleep and AW are consistent with a role for Hcrt in the central programming of motor activity.
Kiyashchenko
Lyudmila I
LI
Department of Psychiatry and Biobehavioral Sciences and Brain Research Institute, University of California Los Angeles School of Medicine, North Hills, California 91343, USA.
Mileykovskiy
Boris Y
BY
Maidment
Nigel
N
Lam
Hoa A
HA
Wu
Ming-Fung
MF
John
Joshi
J
Peever
John
J
Siegel
Jerome M
JM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*; D002415:Cats; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*; D000068797:Orexins; D010507:Periodicity; D016548:Prosencephalon / Q000378:metabolism; D011863:Radioimmunoassay; D012890:Sleep; D014851:Wakefulness
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins