Molecular mechanisms of (recovery) sleep: lessons from Drosophila Melanogaster

One of the key features of sleep is that if the duration of a waking period is prolonged, the following sleep period will be longer, including more slow-wave activity. This homeostasis is explained by production of sleep pressure that accumulates during the waking period. It is generally accepted that neuronal activity, in one way or other, is the driving force for accumulation of sleep pressure, both during spontaneous sleep-wake cycle and during prolonged wakefulness. Prolonged wakefulness is associated with increased energy consumption, production of danger signals and modulations in neural plasticity. Data derived from experiments with Drosophila melanogaster introduces a fascinating window to the basic mechanisms of sleep and sleep homeostasis, and undoubtedly sheds light to the mechanisms of sleep regulation also in humans. However, the existence of substantial cortex, which is regarded as a key actor in mammalian NREM sleep regulation, will add to the complexity of the regulatory circuits.Peer reviewe

Sleep quality, duration and behavioral symptoms among 5–6-year-old children

The objective of the present study was to examine whether parent-reported short sleep duration and sleeping difficulties are related to behavioral symptoms among pre-school aged children. The study is a cross-sectional survey of 297 families with 5–6-year-old children. The Sleep Disturbance Scale for children was used to measure sleep duration and sleeping difficulties, and the Child Behavior Checklist and Teacher’s Report Form were used to measure attention problems, and internalizing and externalizing symptoms. In multivariate logistic regression models, short sleep duration was according to parental reports related to inattention (adjusted odds ratio 4.70, 95% CI 1.58–14.00), internalizing (adjusted odds ratio 3.84, 95% CI 1.32–11.21), and total psychiatric symptoms (adjusted odds ratio 3.53, 95% CI 1.23–10.17) while according to teacher's reports it was almost significantly related to internalizing symptoms (adjusted odds ratio 4.20, 95% CI 0.86–20.51). Sleeping difficulties were strongly related to all subtypes of psychiatric symptoms according to parental reports (adjusted odds ratios ranging from 6.47 to 11.71) and to externalizing symptoms according to teachers’ reports (adjusted odds ratio 7.35, 95% CI 1.69–32.08). Both short sleep duration and sleeping difficulties are associated with children's behavioral symptoms. Intervention studies are needed to study whether childrens behavioral symptoms can be reduced by lengthening sleep duration or improving sleep quality

On the Role of Histamine Receptors in the Regulation of Circadian Rhythms

Several lines of evidence suggest a regulatory role of histamine in circadian rhythms, but little is known about signaling pathways that would be involved in such a putative role. The aim of this study was to examine whether histamine mediates its effects on the circadian system through Hrh1 or Hrh3 receptors. We assessed both diurnal and free-running locomotor activity rhythms of Hrh1(-/-) and Hrh3(-/-) mice. We also determined the expression of Per1, Per2 and Bmal1 genes in the suprachiasmatic nuclei, several areas of the cerebral cortex and striatum under symmetric 24 h light-dark cycle at zeitgeber times 14 and 6 by using radioactive in situ hybridization. We found no differences between Hrh1(-/-) and wild type mice in the length, amplitude and mesor of diurnal and free-running activity rhythms as well as in expression of Per1, Per2 and Bmal1 genes in any of the examined brain structures. The amplitude of free-running activity rhythm of the Hrh3(-/-) mice was significantly flattened, whereas the expression of the clock genes in Hrh3(-/-) mice was similar to the wild type animals in all of the assessed brain structures. Therefore, the knockout of Hrh1 receptor had no effects on the circadian rhythm of spontaneous locomotion, and a knockout of Hrh3 receptor caused a substantial reduction of free-running activity rhythm amplitude, but none of these knockout models affected the expression patterns of the core clock genes in any of the studied brain structures.Peer reviewe

Altered Electroencephalographic Activity Associated with Changes in the Sleep-Wakefulness Cycle of C57BL/6J Mice in Response to a Photoperiod Shortening

Aim: Under natural conditions diurnal rhythms of biological processes of the organism are synchronized with each other and to the environmental changes by means of the circadian system. Disturbances of the latter affect hormonal levels, sleep-wakefulness cycle and cognitive performance. To study mechanisms of such perturbations animal models subjected to artificial photoperiods are often used. The goal of current study was to understand the effects of circadian rhythm disruption, caused by a short light-dark cycle regime, on activity of the cerebral cortex in rodents. Methods: We used electroencephalogram to assess the distribution of vigilance states, perform spectral analysis, and estimate the homeostatic sleep drive. In addition, we analyzed spontaneous locomotion of C57BL/6J mice under symmetric, 22-, 21-, and 20-h-long light-dark cycles using video recording and tracking methods. Results and Conclusions: We found that shortening of photoperiod caused a significant increase of slow wave activity during non-rapid eye movement sleep suggesting an elevation of sleep pressure under such conditions. While the rhythm of spontaneous locomotion was completely entrained by all light-dark cycles tested, periodic changes in the power of the theta- and gamma-frequency ranges during wakefulness gradually disappeared under 22- and 21-h-long light-dark cycles. This was associated with a significant increase in the theta-gamma phase-amplitude coupling during wakefulness. Our results thus provide deeper understanding of the mechanisms underlying the impairment of learning and memory retention, which is associated with disturbed circadian regulation.Peer reviewe

Differential DNA methylation in recovery from shift work disorder

The human DNA methylome is responsive to our environment, but its dynamics remain underexplored. We investigated the temporal changes to DNA methylation (DNAme) in relation to recovery from a shift work disorder (SWD) by performing a paired epigenome-wide analysis in an occupational cohort of 32 shift workers (25 men, age=43.8 +/- 8.8 years, 21 SWD cases). We found that the effect of vacation on DNAme was more prominent in the SWD-group as compared to controls, with respect to the amount of significantly differentially methylated positions (DMPs; P-unadjPeer reviewe

The role of parental circadian preference in the onset of sleep difficulties in early childhood

Background: Chronotype is a construct contributing to individual differences in sleep-wake timing. Previous studies with children have found that evening-types exhibit greater sleep difficulties. Infant sleep quality can be modulated by several factors, such as parental characteristics. We examined the association between parental circadian preference and sleep in early childhood. Methods: This study was based on a longitudinal birth cohort, with several measurement points. We used information regarding parental questionnaires during pregnancy and children's sleep measures at three, eight, 18 and 24 months. In total, 1220 mothers, 1116 fathers, 993 infants at three months, 990 infants at eight months, 958 children at 18 months, and 777 children at 24 months were analyzed. Parental circadian preference was measured using the Horne-Ostberg Morningness-Eveningness Questionnaire. Concerning children's sleep, we used the Brief Infant Sleep Questionnaire (BISQ) and the Infant Sleep Questionnaire (ISQ) at each time point. Results: Maternal circadian preference was associated with infants' circadian rhythm development at three, eight, 18 and 24 months. Furthermore, increased maternal eveningness was also related to short sleep during daytime at three months, and nighttime at three and eight months, to long sleep-onset latency at three, 18 and 24 months, to late bedtime at three, eight and 18 months, and to sleep difficulties at eight and 24 months. Paternal circadian preference was not associated with any sleep variable at any time point. Conclusion: Maternal circadian preference is related to several sleep difficulties in early childhood, and it may be considered a potential risk factor for the onset of early sleeping problems. (c) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Development of sleep–wake rhythms during the first year of age

First published: 08 September 201

Intracerebral adenosine during sleep deprivation : A meta-analysis and new experimental data

Funding Information: The systematic review was funded by The Netherlands Organisation for Health Research and Development (ZonMW; 114024101); R2N, Federal State of Lower Saxony; and the DFG (FOR2591, BL 953/11-1). The microdialysis experiment was funded by Netherlands Organization for Scientific Research (NWO; 051-04-010, to Eus van Some-ren). The HPLC adenosine measurements were funded by the University of Helsinki sleep team and a travel grant from the European Sleep Research Society. Publisher Copyright: © 2018 Ubiquity Press. All rights reserved.The neuroregulator adenosine is involved in sleep-wake control. Basal forebrain (BF) adenosine levels increase during sleep deprivation. Only a few studies have addressed the effect of sleep deprivation on extracellular adenosine concentrations in other brain regions. In this paper, we describe a microdialysis experiment as well as a meta-analysis of published data. The 64 h microdialysis experiment determined the extracellular adenosine and adenosine monophosphate (AMP) concentrations in the medial prefrontal cortex of rats before, during and after 12 h of sleep deprivation by forced locomotion. The meta-analysis comprised published sleep deprivation animal experiments measuring adenosine by means of microdialysis. In the animal experiment, the overall median adenosine concentration was 0.36 nM and ranged from 0.004 nM to 27 nM. No significant differences were observed between the five conditions: 12 h of washout, baseline light phase, baseline dark phase, 12 h of sleep deprivation and 12 h of subsequent recovery. The overall median AMP concentration was 0.10 nM and ranged from 0.001 nM to 7.56 nM. Median AMP concentration increased during sleep deprivation (T = 47; p = 0.047) but normalised during subsequent recovery. The meta-analysis indicates that BF dialysate adenosine concentrations increase with 74.7% (95% CI: 54.1-95.3%) over baseline during sleep deprivation. Cortex dialysate adenosine concentrations during sleep deprivation were so far only reported by 2 publications. The increase in adenosine during sleep deprivation might be specific to the BF. At this stage, the evidence for adenosine levels in other brain regions is based on single experiments and insufficient for generalised conclusions. Further experiments are currently still warranted.Peer reviewe