CD40 activation induces NREM sleep and modulates genes associated with sleep homeostasis

The T-cell derived cytokine CD40 ligand is overexpressed in patients with autoimmune diseases. Through activation of its receptor, CD40 ligand leads to a tumor necrosis factor (TNF) receptor 1 (TNFR1) dependent impairment of locomotor activity in mice. Here we report that this effect is explained through a promotion of sleep, which was specific to non-rapid eye movement (NREM) sleep while REM sleep was suppressed. The increase in NREM sleep was accompanied by a decrease in EEG delta power during NREM sleep and by a decrease in the expression of transcripts in the cerebral cortex known to be associated with homeostatic sleep drive, such as Homer1a, Early growth response 2, Neuronal pentraxin 2, and Fos-like antigen 2. The effect of CD40 activation was mimicked by peripheral TNF injection and prevented by the TNF blocker etanercept. Our study indicates that sleep-wake dysregulation in autoimmune diseases may result from CD40 induced TNF:TNFR1 mediated alterations of molecular pathways, which regulate sleep-wake behavior.

Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus.

Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, their acute silencing (eNpHR3.0, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.

Sleepwalking, REM sleep behaviour disorder and overlap parasomnia in patients with Parkinson's disease

BACKGROUND/AIMS In a questionnaire survey, we identified 36 (9%) of 417 Parkinson's disease (PD) patients with sleepwalking (SW); 72% of them also had a history of REM sleep behaviour disorder (RBD). We aimed to assess the clinical and polysomnographic characteristics of SW in PD and to compare them to patients with PD with and without a history of RBD. METHODS We performed video-polysomnography and detailed clinical examination in 30 PD patients from the above-mentioned survey: 10 patients with a history of SW, 10 patients with a history of RBD, and 10 patients with no history of either SW or RBD. RESULTS PD patients with SW had higher depression, anxiety and Hoehn & Yahr scores and lower activities of daily living scores than patients without a history of RBD but did not differ from patients with RBD. Patients with SW and RBD also had more often dyskinesia and hallucinations. By polysomnography, RBD was observed in 8 patients with SW and in all patients with a history of RBD. A total of 5 patients without a history of either SW or RBD had REM sleep without atonia without behavioural peculiarities. CONCLUSION SW in PD is associated with depression, higher disease severity and functional disability. The simultaneous occurrence of SW and RBD (overlap parasomnia) in most patients suggests a common underlying disturbance of motor control during sleep in PD, with variable manifestations in different sleep stages.

Respiratory-related leg movements and their relationship with periodic leg movements during sleep

STUDY OBJECTIVES: To describe the time structure of leg movements (LM) in obstructive sleep apnea (OSA) syndrome, in order to advance understanding of their clinical significance. LOCATION: Sleep Research Centre, Oasi Institute (IRCCS), Troina, Italy. SETTING: Sleep laboratory. PATIENTS: Eighty-four patients (16 females, 68 males, mean age 55.1 y, range 29-74 y). METHODS: Respiratory-related leg movements (RRLM) and those unrelated to respiratory events (NRLM) were examined within diagnostic polysomnograms alone and together for their distributions within the sleep period and for their periodicity. MEASUREMENTS AND RESULTS: Patients with OSA and RRLM exhibited more periodic leg movements in sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM across the sleep period was observed in patients with RRLM. This pattern was less clear for RRLM. Frequency histograms of intermovement intervals of all LMs in patients with RRLM showed a prominent first peak at 4 sec, and a second peak at approximately 24 sec coincident with that of PLMS occurring in the absence of OSA. A third peak of lowest amplitude was the broadest with a maximum at approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single peak at 2-4 sec. A stepwise linear regression analysis showed that, after controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index, PLMS remained significantly associated with RRLM. CONCLUSION: The time structure of leg movements occurring in conjunction with respiratory events exhibit features of periodic leg movements in sleep occurring alone, only with a different and longer period. This brings into question the validity, both biologic and clinical, of scoring conventions with their a priori exclusion from consideration as periodic leg movements in sleep.

Adaption of cardio-respiratory balance during day-rest compared to deep sleep—An indicator for quality of life?

Heart rate and breathing rate fluctuations represent interacting physiological oscillations. These interactions are commonly studied using respiratory sinus arrhythmia (RSA) of heart rate variability (HRV) or analyzing cardiorespiratory synchronization. Earlier work has focused on a third type of relationship, the temporal ratio of respiration rate and heart rate (HRR). Each method seems to reveal a specific aspect of cardiorespiratory interaction and may be suitable for assessing states of arousal and relaxation of the organism. We used HRR in a study with 87 healthy subjects to determine the ability to relax during 5 day-resting periods in comparison to deep sleep relaxation. The degree to which a person during waking state could relax was compared to somatic complaints, health-related quality of life, anxiety and depression. Our results show, that HRR is barely connected to balance (LF/HF) in HRV, but significantly correlates to the perception of general health and mental well-being as well as to depression. If relaxation, as expressed in HRR, during day-resting is near to deep sleep relaxation, the subjects felt healthier, indicated better mental well-being and less depressive moods.

Lucid dreaming during NREM sleep: Two case reports

Lucid dreams – dreams in which the dreamer is aware that is dreaming – most frequently occur during REM sleep, yet there is some evidence suggesting that lucid dreaming can occur during NREM sleep as well. By conducting a sleep laboratory study on lucid dreams, we found two possible instances of lucidity during NREM sleep which are reported here. While lucid dreaming during NREM sleep seems to be much rarer and more difficult to achieve, it appears to be possible and is most likely to occur during N1 sleep, somewhat less likely during N2 sleep and yet to be observed during N3 sleep. Future studies should explore induction methods, underlying neural mechanisms and perceptual/dream content differences between REM and NREM lucid dreams. Furthermore, a consensus agreement is needed to define what is meant by lucid dreaming and create a vocabulary that is helpful in clarifying variable psychophysiological states that can support self-reflective awareness.

The effects of exercise on self-rated sleep among adults with chronic sleep complaints

Purpose The purpose of this study was to evaluate whether and to what extent the observed effects on self-rated sleep in a previous study using a combined treatment program with physical exercise and sleep education can be attributed by the physical activity (PA) component. Methods The present study reports supplementary analysis of an already described and published study. Data were provided by a nonclinical sample of 98 normal-active adults with chronic initiating and the maintaining of sleep complaints. The additional analysis included sleep log, exercise log, and daily pedometer data which were collected during a baseline week and 6-week of a combined intervention. Results The results indicate that the number of steps (p = 0.02) and the duration of PA (p = 0.01) is significantly related to the improvement in subjective sleep measures and therefore reveal an independent effect within this combined sleep program. Sleep diary data (recuperation of sleep, number of awakenings after sleep onset, and wake time after sleep onset time) improved significant (all p < 0.01) over the intervention program. About 50% of the participants stated that the PA had an effect on their improvement. Conclusion Improvements on subjective sleep quality after a combined intervention cannot be attributed to the cognitive component alone, but PA has an independent effect. Adults with chronic sleep complaints benefit from exercise. Therefore structured PA should be implemented in any sleep management programs.

Gender differences in disordered eating and weight dissatisfaction in Swiss adults: Which factors matter?

Background Research results from large, national population-based studies investigating gender differences in weight dissatisfaction and disordered eating across the adult life span are still limited. Gender is a significant factor in relation to weight dissatisfaction and disordered eating. However, the reasons for gender differences in these conditions are still poorly understood. The aim of this study was to examine gender differences in weight dissatisfaction and disordered eating in the general Swiss adult population and to identify gender-specific risk factors. Methods The study population consisted of 18156 Swiss adults who completed the population-based Swiss Health Survey 2007. Self-reported weight dissatisfaction, disordered eating and associated risk factors were assessed. In order to examine whether determinants of weight dissatisfaction and disordered eating (dieting to lose weight, binge eating, and irregular eating) differ in men and women, multivariate logistic regressions were applied separately for women and men. Results Although more men than women were overweight, more women than men reported weight dissatisfaction. Weight category, smoking status, education, and physical activity were significantly associated with weight dissatisfaction in men and women. In women, nationality and age were also significant factors. Gender-specific risk factors such as physical activity or weight category were identified for specific disordered eating behaviours. Conclusions The results suggest that gender specific associations between predictors and disordered eating behaviour should be considered in the development of effective prevention programs against disordered eating.

Developmental changes in sleep biology and potential effects on adolescent behavior and caffeine use

Adolescent development includes changes in the biological regulatory processes for the timing of sleep. Circadian rhythm changes and changes to the sleep-pressure system (sleep homeostasis) during adolescence both favor later timing of sleep. These changes, combined with prevailing social pressures, are responsible for most teens sleeping too late and too little; those who sleep least report consuming more caffeine. Although direct research findings are scarce, the likelihood of use and abuse of caffeine-laden products grows across the adolescent years due, in part, to excessive sleepiness