Altered Sleep Homeostasis in Rev-erba Knockout Mice

التفاصيل البيبلوغرافية
العنوان: Altered Sleep Homeostasis in Rev-erba Knockout Mice
المؤلفون: Sylvie Chappuis, Géraldine M. Mang, Paul Franken, Jürgen A. Ripperger, Urs Albrecht, Francesco La Spada, Yann Emmenegger
المصدر: SLEEP
Sleep, vol. 39, no. 3, pp. 589-601
Sleep
سنة النشر: 2016
مصطلحات موضوعية: 0301 basic medicine, Male, medicine.medical_specialty, clock genes, mood, depression, neurogenesis, Process S, slow wave activity, animal structures, Dopamine, CLOCK Proteins, Gene Expression, Nerve Tissue Proteins, Non-rapid eye movement sleep, 03 medical and health sciences, Mice, 0302 clinical medicine, Basic Science, Physiology (medical), Internal medicine, medicine, Basic Helix-Loop-Helix Transcription Factors, Animals, Homeostasis, Circadian rhythm, Wakefulness, Mice, Knockout, NPAS2, ARNTL Transcription Factors, Electroencephalography, Sleep in non-human animals, Circadian Rhythm, CLOCK, Sleep deprivation, 030104 developmental biology, Endocrinology, Nuclear Receptor Subfamily 1, Group D, Member 1, Neurology (clinical), medicine.symptom, Sleep onset, Psychology, Fatty Acid-Binding Protein 7, Sleep, 030217 neurology & neurosurgery, Signal Transduction
الوصف: Study Objectives: 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. Significance Although circadian clock genes are named for their role in driving circadian rhythms in gene expression, physiology, and behavior, they can fulfill other important functions. The clock gene and transcriptional repressor REV-ERBα plays a role in pathways affecting metabolism and central nervous functioning. Using mice lacking the gene encoding REV-ERBα, Nr1d1, we could extend these finding to include the homeostatic regulation of sleep. Because the activity of REV-ERBα is modulated by cellular redox state, we propose that this molecule can sense and respond to the metabolic imbalance imposed at the neuronal level by periods of extended wakefulness. Recently developed synthetic drugs targeting REV-ERBα could thus be useful in the treatment of both the circadian and homeostatic aspects of sleep-wake related disorders.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dfe8a6313522ed4458e59ae15cae505eTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763348Test/
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....dfe8a6313522ed4458e59ae15cae505e
قاعدة البيانات: OpenAIRE