KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Online Publication Date2015-04-01
Print Publication Date2015-04
Permanent link to this recordhttp://hdl.handle.net/10754/564135
MetadataShow full item record
AbstractStudy Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.
CitationBaud, M. O., Magistretti, P. J., & Petit, J.-M. (2015). Sustained Sleep Fragmentation Induces Sleep Homeostasis in Mice. Sleep, 38(4), 567–579. doi:10.5665/sleep.4572
SponsorsThis work was supported by a Swiss National Science Foundation grant (3100AO-108336/1) to Dr. Magistretti. Dr. Baud's work was directly supported by a Swiss National Science Foundation personal MD-PhD grant (323600-119351/1). The authors have indicated no financial conflicts of interest.
PublisherOxford University Press (OUP)
PubMed Central IDPMC4355896
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Regulation of Neuron-Astrocyte Metabolic Coupling across the Sleep-Wake CyclePetit, Jean-Marie; Magistretti, Pierre J. (Neuroscience, Elsevier BV, 2015-12-18) [Article]Over the last thirty years, a growing number of studies showed that astrocytes play a pivotal role in the energy support to synapses. More precisely, astrocytes adjust the energy production to the neuronal energy needs through different mechanisms grouped under the term “neurometabolic coupling” (NMC). In this review we describe these mechanisms of coupling and how they involve astrocytes. From a physiological point of view, these mechanisms of coupling are particularly important to ensure normal synaptic functioning when neurons undergo rapid and repetitive changes in firing rate such as during the sleep/wake transitions. Investigations on brain energy metabolism during the sleep/wake cycle have been mainly focused on glucose consumption and on glycogen metabolism. However, the recent development of substrate-specific biosensors allowed measurements of the variation in extracellular levels of glutamate, glucose and lactate with a time resolution compatible with sleep stage duration. Together with gene expression data these experiments allowed to better define the variations of energy metabolites regulation across the sleep/wake cycle. The aim of this review is to bring into perspective the role of astrocytes and neurometabolic coupling in the regulation of the sleep/wake cycle. The data reviewed also suggest an important role of the astrocytic network. In addition, the role of astrocytes in NMC mechanisms is consistent with the “local and use dependent” sleep hypothesis.
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