Neurobiology of Sleep and Circadian Rhythms最新文献

Many physiological functions with approximately 24-h rhythmicity (circadian rhythms) are generated by an internal time-measuring system of the circadian clock. While sleep/wake cycles, feeding patterns, and body temperature are the most widely known physiological functions under the regulation of the circadian clock, physiological regulation by the circadian clock extends to higher brain functions. Accumulating evidence suggests strong associations between the circadian clock and mood disorders such as depression, but the underlying mechanisms of the functional relationship between them are obscure. This review overviews rodent models with disrupted circadian rhythms on depression-related responses. The animal models with circadian disturbances (by clock gene mutations and artifactual interventions) will help understand the causal link between the circadian clock and depression.

Shift work (work outside of standard daylight hours) is common throughout the Western world. However, there are notable health consequences to shift work, including increased prevalence of mental health and sleep disorders in shift worker populations. Therefore, the health and wellbeing of shift workers is a public health concern that needs to be addressed. Here we investigate the effects of two separate light induced shift work-like patterns on male and female mouse behaviour (anxiety-like, exploration, marble burying, startle reflex and circadian rhythms). After 6 weeks of shift-like disruptions patterns, animals displayed no behavioral differences in exploration, marble burying and startle reflex. Interestingly however, we identified sex specific and disruption specific effects in light aversion and wheel running activities. Notably, analysis of the activity patterns of animals in disruptive conditions demonstrated that they maintained a degree of rhythmicity through the disruption period, which may explain the lack of behavioral differences in most behavioral tests.

Background

Machado-Joseph Disease (MJD), or Spinocerebellar Ataxia Type 3 (SCA3), is a genetic disorder that causes progressive muscle weakness, loss of motor control, ataxia and permanent physical disability. Sleep disturbances are associated with MJD but remain poorly understood.

Objective

To investigate frequency and characteristics of sleep disorders and their association with health-related quality of life and psychosocial wellbeing for Aboriginal Australians living with MJD.

Methods

A convenience sample of MJD participants n = 24 participated in a semi-attended, ambulatory diagnostic sleep study to capture polysomnography, actigraphy and sleep diary data. Self-report measures collected were the Pittsburgh Sleep Quality Index (PSQI), STOP-BANG Questionnaire for Obstructive Sleep Apnoea (OSA), International Restless Legs Syndrome Study Group rating scale (IRLS), Kessler-5 (K5) and EuroQoL-5 Dimension (EQ5D). Caregivers (n = 22) reported EQ-5D, K5 and bed partners’ sleep behaviour (Mayo Sleep Questionnaire-Informant). Environmental factors were measured.

Results

We observed Nocturia, Sleep Related Leg Cramps, OSA, REM Behaviour Disorder, and RLS, respectively in 100%, 71%, 47%, 43%, and 33% of participants with a significant positive correlation between Body mass index (BMI) and Apnoea hypopnea index (AHI). The majority of sleep was spent in non-rapid eye movement sleep (NREM)-N2 stage (77.8% (67.7, 81.6)). Overcrowding (92%) and overnight care needs (42%) interrupted sleep. MJD participants and caregivers reported high psychological distress (K5 median 12.5 IQR 7, 16.5 & 8 IQR 6, 12 respectively).

Conclusion

Poor sleep quality and sleep disturbances are prevalent among this cohort. Disease manifestations and environmental factors are driving factors. Larger sample sizes are required to predict risk factors and confirm observed associations.

Sleep is required for the full expression of plasticity during the visual critical period (CP). However, the precise role of rapid-eye-movement (REM) sleep in this process is undetermined. Previous studies in rodents indicate that REM sleep weakens cortical circuits following MD, but this has been explored in only one class of cortical neuron (layer 5 apical dendrites). We investigated the role of REM sleep in ocular dominance plasticity (ODP) in layer 2/3 neurons using 2-photon calcium imaging in awake CP mice. In contrast to findings in layer 5 neurons, we find that REM sleep promotes changes consistent with synaptic strengthening and weakening. This supports recent suggestions that the effects of sleep on plasticity are highly dependent upon the type of circuit and preceding waking experience.

Objective

In pregnancy melatonin regulates circadian rhythms, induce sleep, and has a neuroprotective positive effect on fetal development. Artificial blue light in the evening delays and suppresses melatonin production. Thus, we investigated the effect of blocking blue light on the melatonin profile.

Methods

A randomized controlled trial (n=30 blue-blocking glasses vs. n=30 control glasses with partial blue-blocking effect) including healthy nulliparous pregnant women in the beginning of the third trimester. Salivary melatonin and subjective sleep were measured before and after two weeks of intervention/control condition. Saliva was sampled at 30-min intervals from 3 h before normal bedtime. Melatonin onset was set at 4.0 pg/ml.

Results

Due to missing data melatonin onset was estimated for 47 participants. At posttreatment, melatonin onset advanced by 28 min in the blue-blocking group compared with the control condition (p=.019). Melatonin levels were significantly higher, favoring the blue-blocking glass condition, at clock time 20:00, 21:00 and 22:00 h, and for sample number 3 and 4. The phase angle (time interval) between melatonin onset and sleep bedtime and sleep onset time increased within the blue blocking group (+45 min and +41 min, respectively), but did not reach statistical significance compared to control condition (+13 min and +26 min, respectively).

Conclusion

Blocking blue light in the evening had a positive effect on the circadian system with an earlier onset and rise of melatonin levels in healthy nulliparous pregnant women. This demonstrated the effectiveness and feasibility of a simple non-pharmacological chronobiological intervention during pregnancy.

Sleep deprivation can generate inflammatory responses in the central nervous system. In turn, this inflammation increases sleep drive, leading to a rebound in sleep duration. Microglia, the innate immune cells found exclusively in the CNS, have previously been found to release inflammatory signals and exhibit altered characteristics in response to sleep deprivation. Together, this suggests that microglia may be partially responsible for the brain's response to sleep deprivation through their inflammatory activity. In this study, we ablated microglia from the mouse brain and assessed resulting sleep, circadian, and sleep deprivation phenotypes. We find that microglia are dispensable for both homeostatic sleep and circadian function and the sleep rebound response to sleep deprivation. However, we uncover a phenomenon by which microglia appear to be essential for the protection of fear-conditioning memories formed during the recovery sleep period following a period of sleep deprivation. This phenomenon occurs potentially through the upregulation of synaptic-homeostasis related genes to protect nascent dendritic spines that may be otherwise removed or downscaled during recovery sleep. These findings further expand the list of known functions for microglia in synaptic modulation.

Military veterans with posttraumatic stress disorder often complain of non-restful sleep, which further exacerbates their symptoms. Our previous study showed a deficit in Lo Deep sleep, or slow oscillations, in the PTSD population compared to healthy control sleepers. Because Lo Deep sleep is likely a stage when the brain eliminates protein debris, it is critical to find the cause and effective therapeutics to reverse Lo Deep deficiency. The current study aims to replicate and extend this finding by examining several physiological and medication factors that may be responsible for the Lo Deep deficiency. We recorded overnight sleep electroencephalogram (EEG) via a 2-channel headband device on 69 veterans in a residential treatment facility. Dried urine samples were collected at 4 time points during one day to measure melatonin, cortisol, norepinephrine and other factors. EEG data were transformed into frequency power and submitted to an automated sleep scoring algorithm. The scoring corresponds to clear spectral patterns in the overnight spectrogram but does not align exactly with traditional visual scoring stages. As expected, veterans showed decreased Lo Deep (activity < 1 Hz) and more Hi Deep sleep (1–3 Hz activity) than healthy controls, replicating our previous study. Multiple linear regressions showed that melatonin dose and morning urine melatonin correlated with more Lo Deep sleep. Buspirone dose also correlated with more Lo Deep, but only 6 subjects were taking buspirone. Also replicating the findings from our last study were independent reductions of REM sleep with prazosin and sertraline. Other findings included decreased Lo and increased Hi Deep sleep with higher caffeine dose, and less Hi Deep percentage with higher testosterone. Finally, evening cortisol levels correlated with a higher percentage of Wake after sleep onset. These results confirm Lo Deep deficiency in this PTSD population and suggests melatonin as a possible therapeutic to reverse Lo Deep deficiency. This is a critical first step to establishing a systematic sleep assessment and treatment program in this and potentially other populations to prevent future brain pathology.

Development of non-pharmacological interventions to improve disrupted rest-activity patterns and disturbed behavior in people with dementia is an important research goal. Here we report a proof-of-concept study which evaluates the effect and applicability of a dynamic light intervention to improve rest-activity patterns in cognitively impaired, institutionalized, older adults. The study was a randomized, open-label, proof-of-concept trial of limited sample size conducted at a nursing home for older adults in a non-metropolitan area in Denmark. Participants were 24 older nursing home residents with cognitive deficiencies. Equipment for delivery of a specialized dynamic light intervention was installed in the private apartments (within the nursing home) of the residents in the experimental group (N = 12). Study duration was four weeks. The control group (N = 12) was exposed to conventional lighting. We measured activity and rest using actigraphy, functional disability, behavioral disturbances, and time in bed We performed regression analyses to examine differences between the intervention groups. Participants in the experimental group partially improved on one of three diurnal rhythm variables, but otherwise no differences were observed between the two intervention groups. The improvement was found for the intradaily variability during the first part of the intervention period indicating a more stable and less fragmented 24-h rest-activity rhythm. However, availability of staff assistance in response to impaired physical mobility of the residents seemed to be a stronger determinant of activity level and pattern. The examined intervention showed promising results but did not consistently alter circadian rest-activity patterns in older nursing home residents given the current sample size. Future studies in the field need to consider real-life applicability of the experimental intervention and the interaction and importance of other important zeitgebers than light.

Sleep is a vital part of our lives as it is required to maintain health and optimal cognition. In humans, sex differences are relatively well-established for many sleep phenotypes. However, precise differences in sleep phenotypes between male and female rodents are less documented. The main goal of this article is to review sex differences in sleep architecture and electroencephalographic (EEG) activity during wakefulness and sleep in rodents. The effects of acute sleep deprivation on sleep duration and EEG activity in male and female rodents will also be covered, in addition to sex differences in specific circadian phenotypes. When possible, the contribution of the female estrous cycle to the observed differences between males and females will be described. In general, male rodents spend more time in non-rapid eye movement sleep (NREMS) in comparison to females, while other differences between sexes in sleep phenotypes are species- and estrous cycle phase-dependent. Altogether, the review illustrates the need for a sex-based perspective in basic sleep and circadian research, including the consideration of sex chromosomes and gonadal hormones in sleep and circadian phenotypes.

It is well established that certain alteration of sleep disorders occur in patients with wake-up stroke (WUS) such as sleep disordered breathing, periodic limb movements and sleep duration. However, the data are lacking about the microarchitecture of different sleep stages among those patients.

Aim of work

To compare the polysomnographic microarchitecture of rapid eye movement (REM) sleep between WUS and daytime stroke (DTS).

Methods

A cross-sectional polysomnographic study was conducted on 20 patients with WUS and 20 patients with DTS, with analysis of REM sleep microarchitecture in specific.

Results

Patients with WUS had significantly shorter REM stage (11.76 ± 5.48% in WUS versus 16.59 ± 5.33% in DTS, P = 0.008), longer early morning REM was (25.70 ± 13.13 min in WUS versus 4.15 ± 4.69 min in DTS, P=<0.001), higher apnea-hypopnea index (AHI) during REM (6.29 ± 10.18 in WUS versus 1.10 ± 4.57 in DTS, P = 0.009), and lower mean Oxygen saturation during REM (92.70 ± 3.63 WUS versus 95.45 ± 1.35 DTS, P = 0.012). The OR of early morning REM duration was 1.8 (CI 1.099–3.130, p = 0.021) for WUS.

Conclusion

The microarchitecture of REM sleep is disrupted in patients with wake-up stroke.