Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice.
OBJECTIVE
Sleep is regulated by circadian and homeostatic processes. Recent studies with mutant mice have indicated that circadian-related genes regulate sleep amount, as well as the timing of sleep. Thus a direct link between circadian and homeostatic regulation of sleep may exist, at least at the molecular level. Prokineticin 2 (PK2), which oscillates daily with high amplitude in the suprachiasmatic nuclei (SCN), has been postulated to be an SCN output molecule. In particular, mice lacking the PK2 gene (PK2-/-) have been shown to display significantly reduced rhythmicity for a variety of circadian physiological and behavioral parameters. We investigated the role of PK2 in sleep regulation.


METHODS
EEG/EMG sleep-wake patterns were recorded in PK2-/- mice and their wild-type littermate controls under baseline and challenged conditions.


RESULTS
PK2-/- mice exhibited reduced total sleep time under entrained light-dark and constant darkness conditions. The reduced sleep time in PK2-/- mice occurred predominantly during the light period and was entirely due to a decrease in non-rapid eye movement (NREM) sleep time. However, PK2-/- mice showed increased rapid eye movement (REM) sleep time in both light and dark periods. After sleep deprivation, compensatory rebound in NREM sleep, REM sleep, and EEG delta power was attenuated in PK2-/- mice. In addition, PK2-/- mice had an impaired response to sleep disturbance caused by cage change in the light phase.


CONCLUSIONS
These results indicate that PK2 plays roles in both circadian and homeostatic regulation of sleep. PK2 may also be involved in maintaining the awake state in the presence of behavioral challenges.
Hu
Wang-Ping
WP
Department of Pharmacology, University of California, Irvine, CA 92697, USA.
Li
Jia-Da
JD
Zhang
Chengkang
C
Boehmer
Lisa
L
Siegel
Jerome M
JM
Zhou
Qun-Yong
QY
D000818:Animals; D001143:Arousal / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D004569:Electroencephalography; D004576:Electromyography; D005768:Gastrointestinal Hormones / Q000172:deficiency* / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics*; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D012894:Sleep Stages / Q000235:genetics* / Q000502:physiology; D012931:Social Environment; D013493:Suprachiasmatic Nucleus / Q000503:physiopathology; D014851:Wakefulness / Q000235:genetics / Q000502:physiology
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse