Neurobiology of Sleep and Circadian Rhythms最新文献

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.

The dorsal striatum forms part of the basal ganglia circuit that is a major regulator of voluntary motor behavior. Dysfunction in this circuit is a critical factor in the pathology of neurological (Parkinson's and Huntington's disease) as well as psychiatric disorders. In this study, we employed in vivo real-time monitoring of multiple unit neural activity (MUA) in the dorsal striatum of freely moving mice. We demonstrate that the striatum exhibits robust diurnal and circadian rhythms in MUA that peak in the night. These rhythms are dependent upon the central circadian clock located in the suprachiasmatic nucleus (SCN) as lesions of this structure caused the loss of rhythmicity measured in the striatum. Nonetheless, chronic treatment of methamphetamine (METH) makes circadian rhythms appear in MUA recorded from the striatum of SCN-lesioned mice. These data demonstrate that the physiological properties of neurons in the dorsal striatum are regulated by the circadian system and that METH drives circadian rhythms in striatal physiology in the absence of the SCN. The finding of SCN-driven circadian rhythms in striatal physiology has important implications for an understanding of the temporal regulation of motor control as well as revealing how disease processes may disrupt this regulation.

A better understanding of the spatial sensitivity of the human circadian system to photic stimulation can provide practical solutions for optimized circadian light exposures. Two psychophysical experiments, involving 25 adult participants in Experiment 1 (mean age = 34.0 years [SD 15.5]; 13 females) and 15 adult participants in Experiment 2 (mean age = 43.0 years [SD 12.6]; 12 females), were designed to investigate whether varying only the spatial distribution of luminous stimuli in the environment while maintaining a constant spectrally weighted irradiance at the eye could influence nocturnal melatonin suppression. Two spatial distributions were employed, one where the luminous stimulus was presented On-axis (along the line of sight) and one where two luminous stimuli were both presented Off-axis (laterally displaced at center by 14°). Two narrowband LED light sources, blue (λ_max = 451 nm) for first experiment and green (λ_max = 522 nm) for second experiment, were used in both the On-axis and the Off-axis spatial distributions. The blue luminous stimulus targeting the fovea and parafovea (On-axis) was about three times more effective for suppressing melatonin than the photometrically and spectrally matched stimulus targeting the more peripheral retina (Off-axis). The green luminous stimulus targeting the fovea and parafovea (On-axis) was about two times more effective for suppressing melatonin than the photometrically and spectrally matched stimulus targeting the more peripheral retina (Off-axis).

Night shift work is a risk factor for viral infection, suggesting that night shift schedules compromise host defense mechanisms. Prior studies have investigated changes in the temporal profiles of circulating cytokines important for priming and restraining the immune response to infectious challenges from night shift work, but not by way of a 24-h constant routine of continuous wakefulness devoid of behavioral or environmental influences. Hence the true endogenous pattern of cytokines, and the combined effect of sleep loss and circadian misalignment on these cytokines remains unknown. Here, 14 healthy young men and women underwent three days of either a simulated night shift or a simulated day shift schedule under dim light in a controlled in-laboratory environment. This was followed by a 24-h constant routine protocol during which venous blood was collected at 3-h intervals. Those who had been in the night shift schedule showed lower mean circulating TNF-α (t₁₃ = -6.03, p < 0.001), without any significant differences in IL-1β, IL-8 and IL-10, compared with those who had been in the day shift (i.e., control) schedule. Furthermore, circulating IL-6 increased with time awake in both shift work conditions (t₁₃ = 6.03, p < 0.001), such that temporal changes in IL-6 were markedly shifted relative to circadian clock time in the night shift condition. These results indicate that night shift work compromises host defense by creating cytokine conditions that initially impede anti-viral immunity (lower TNF-α) and may eventually promote autoimmunity (mistimed rise in IL-6).

The magnitude of the stimulus to the biological clock will depend upon the distribution of circadian phototransduction circuits across the retinae and the spatial distribution of luminous stimuli in the environment. The present study compared nocturnal melatonin suppression for light exposures to the superior, inferior, nasal, and temporal retina in one eye independent of shading from the brow and the nose. The stimulus was a 40° diameter luminous disc, half of which was blue light (LED, λ_peak = 470 nm) and the other amber light (LED, λ_peak = 590 nm). Experimentally, the orientation of the bipartite disc was rotated to each of the four cardinal points of the visual field. A full, 40° blue disc was also employed by replacing the amber half-disc with another blue half-disc. The blue full- and half-discs always produced 100 photopic lx at the cornea. As hypothesized, nocturnal melatonin suppression was statistically greatest when the blue half-disc was delivered to the nasal hemi-field (35%); the other three hemi-fields were equally affected by the blue half-disc (≈20%). Melatonin suppression for the full-disc was 24%, which was not statistically different than the average suppression for the four hemi-fields of 27%.

In this commentary, I play the Devil’s advocate and assume the title of High Contrarian. I intend to be provocative to challenge long-standing ideas about sleep. I blame all on Professor Craig Heller, who taught me to think this way as a graduate student in his laboratory. Scientists should fearlessly jump into the foaming edge of what we know, but also consider how safe are their intellectual harbors. There are many ideas we accept as ‘known’: that sleep is ubiquitous in the animal kingdom, that it serves vital functions, that it plays an essential role in brain plasticity. All of this could be wrong. As one example, I reexamine the idea that sleep is regulated by a mysterious ‘homeostat’ that determines sleep need based on prior wake time.