title: Altered Sleep Homeostasis in Rev-erbα Knockout Mice.
abstract: OBJECTIVE
  The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep.
  
  
  METHODS
  EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline.
  
  
  RESULTS
  Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain.
  
  
  CONCLUSIONS
  Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Géraldine M
authors.initials: GM
authors.lastname: Mang
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: La Spada
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Yann
authors.initials: Y
authors.lastname: Emmenegger
authors.affiliation: Faculty of Science, Department of Biology, Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chappuis
authors.affiliation: Faculty of Science, Department of Biology, Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Ripperger
authors.affiliation: Faculty of Science, Department of Biology, Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Albrecht
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Franken
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004569:Electroencephalography; D000071438:Fatty Acid-Binding Protein 7 / Q000235:genetics; D015870:Gene Expression; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D014851:Wakefulness / Q000235:genetics / Q000502:physiology
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D004298:Dopamine; D000071438:Fatty Acid-Binding Protein 7; D009419:Nerve Tissue Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C538961:Bmal1 protein, mouse; C086936:Fabp7 protein, mouse; C491259:Npas2 protein, mouse; C538944:Clock protein, mouse
keywords: Process S; clock genes; depression; mood; neurogenesis; slow wave activity.