title: Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of California, Irvine, CA 92697, USA.
authors.forename: Wang-Ping
authors.initials: WP
authors.lastname: Hu
authors.forename: Jia-Da
authors.initials: JD
authors.lastname: Li
authors.forename: Chengkang
authors.initials: C
authors.lastname: Zhang
authors.forename: Lisa
authors.initials: L
authors.lastname: Boehmer
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Siegel
authors.forename: Qun-Yong
authors.initials: QY
authors.lastname: Zhou
mesh_terms: 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
chemical_list: D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse