Cortical miR-709 links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner.

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD) altered; while the rapid-eye-movement sleep (REMS) rebound was compromised in both, the increase in EEG delta (1 to 4 Hz) power during non-REMS (NREMS) was smaller in cKO mice and larger in icKO mice compared to controls. We subsequently investigated the effects of SD on the forebrain miRNA transcriptome and found that the expression of 48 miRNAs was affected, and in particular that of the activity-dependent miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75 to 1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates genes involved in glutamatergic neurotransmission. A subset of these genes was also affected in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal activity during wakefulness to brain synchrony during sleep through the regulation of glutamatergic signaling

Reductions in negative automatic thoughts in students attending mindfulness tutorials predicts increased life satisfaction

University education confronts students with stressful developmental challenges that can lead to mental health problems. Innovative programs must address an increasing prevalence of these problems but are impeded by the high costs involved. In this study, thirty-nine undergraduate students attended weekly one hour mindfulness meditation tutorials during a single (14 week) semester. Tutorials involved 40 minutes of guided meditation, followed by open-ended discussions on mindfulness and related scientific research. Multiple regression analysis tested associations between self-reported changes in mindfulness, in negative automatic thoughts and in satisfaction with life.Reductions in automatic thoughts accounted for a significant proportion of variance in life satisfaction and decreases in automatic thoughts were associated with an increased life satisfaction. This finding suggests guided meditation tutorials merit consideration in promoting student mental health on university campuses.Social Sciences and Humanities Research Council (SSHRC

Consequences of the Timing of Menarche on Female Adolescent Sleep Phase Preference

Most parents experience their children's puberty as a dramatic change in family life. This is not surprising considering the dynamics of physical and psychosocial maturation which occur during adolescence. A reasonable question, particularly from the parents' perspective, is: when does this vibrant episode end and adulthood finally start? The aim of the present study was to assess the relationship between puberty and the changes in sleep phase preferences during female maturation and adulthood by a cross-sectional survey. The results from 1'187 females aged 5 to 51 years based on self-report measures of sleep preferences on weekdays and on free days as well as the occurrence of menarche, show that in contrast to prepubertal children, adolescent females exhibit a striking progression in delaying their sleep phase preference until 5 years after menarche. Thereafter, the sleep phase preference switches to advancing. The current study provides evidence that a clear shift in sleep-wake cycles temporally linked to menarche heralds the beginning of “adult-like” sleep-wake behaviour in women and can be used as a (chrono)biological marker for the onset of adulthood

Circadian Preference Modulates the Neural Substrate of Conflict Processing across the Day

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions

Embodying compassion: A virtual reality paradigm for overcoming excessive self-criticism

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions.N/

Daily rhythms of the sleep-wake cycle

The amount and timing of sleep and sleep architecture (sleep stages) are determined by several factors, important among which are the environment, circadian rhythms and time awake. Separating the roles played by these factors requires specific protocols, including the constant routine and altered sleep-wake schedules. Results from such protocols have led to the discovery of the factors that determine the amounts and distribution of slow wave and rapid eye movement sleep as well as to the development of models to determine the amount and timing of sleep. One successful model postulates two processes. The first is process S, which is due to sleep pressure (and increases with time awake) and is attributed to a 'sleep homeostat'. Process S reverses during slow wave sleep (when it is called process S'). The second is process C, which shows a daily rhythm that is parallel to the rhythm of core temperature. Processes S and C combine approximately additively to determine the times of sleep onset and waking. The model has proved useful in describing normal sleep in adults. Current work aims to identify the detailed nature of processes S and C. The model can also be applied to circumstances when the sleep-wake cycle is different from the norm in some way. These circumstances include: those who are poor sleepers or short sleepers; the role an individual's chronotype (a measure of how the timing of the individual's preferred sleep-wake cycle compares with the average for a population); and changes in the sleep-wake cycle with age, particularly in adolescence and aging, since individuals tend to prefer to go to sleep later during adolescence and earlier in old age. In all circumstances, the evidence that sleep times and architecture are altered and the possible causes of these changes (including altered S, S' and C processes) are examined

Modelling the impact of atherosclerosis on drug release and distribution from coronary stents

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES. Such work has identified the physical phenomena determining the transport of drug from the stent and through tissue, and has highlighted the importance of stent coatings and drug physical properties to this process. However, there is limited information regarding the precise role that the atherosclerotic lesion has in determining the uptake and distribution of drug. In this review, we start by discussing the various models that have been used in this research area, highlighting the different types of information they can provide. We then go on to describe more recent methods that incorporate the impact of atherosclerotic lesions

Cross-translational studies in human and Drosophila identify markers of sleep loss

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss