Recovery Sleep Research Articles

Model integration of circadian- and sleep-wake-driven contributions to rhythmic gene expression reveals distinct regulatory principles

Analyses of gene-expression dynamics in research on circadian rhythms and sleep homeostasis often describe these two processes using separate models. Rhythmically expressed genes are, however, likely to be influenced by both processes. We implemented a driven, damped harmonic oscillator model to estimate the contribution of circadian- and sleep-wake-driven influences on gene expression. The model reliably captured a wide range of dynamics in cortex, liver, and blood transcriptomes taken from mice and humans under various experimental conditions. Sleep-wake-driven factors outweighed circadian factors in driving gene expression in the cortex, whereas the opposite was observed in the liver and blood. Because of tissue- and gene-specific responses, sleep deprivation led to a long-lasting intra- and inter-tissue desynchronization. The model showed that recovery sleep contributed to these long-lasting changes. The results demonstrate that the analyses of the daily rhythms in gene expression must take the complex interactions between circadian and sleep-wake influences into account. A record of this paper's transparent peer review process is included in the supplemental information.

Improvement in sleep disturbance following arthroscopic rotator cuff repair

Approximately 90% of patients express concerns with sleep shortly after developing shoulder-related symptoms. Previous small cohort studies have demonstrated the impact of rotator cuff repair on sleep, but none have characterized the observed benefits. The purpose of this study is to evaluate sleep improvement after rotator cuff repair including the speed of sleep recovery, the time at which improvement plateaus, and the longer-term maintenance of improved sleep. A retrospective review of our institution's shoulder and elbow repository identified patients who underwent primary arthroscopic rotator cuff repair from 2012 - 2021 and reported sleep disturbance preoperatively. Patients were evaluated using sleep-related questions from the Simple Shoulder Test and American Shoulder and Elbow Surgeons score. Sleep outcomes were compared from a preoperative visit to 3-month, 6-month, 12-month, and most recent follow-ups to evaluate efficacy of treatment, speed of recovery and improvement plateaus. Among 677 RCR patients, 95.7% (648/677) reported sleep disturbance preoperatively. A total of 474 met inclusion criteria with median follow-up of 4.1 years (IQR, 2.1-6.1). At most recent follow-up, 81.8% were able to sleep comfortably and 65.7% were able to sleep on the affected side. A plateau in the ability to sleep comfortably was seen at 6 months while no plateau was observed in the ability to sleep on the affected side. More rapid improvement in the ability to sleep comfortably occurred during the first 3 months and from 3 - 6 months for the ability to sleep on the affected side. The majority of patients with sleep disturbance who undergo RCR, report significant, rapid, and lasting improvement in the ability to sleep comfortably and the ability to sleep on the affected side.

Isoflurane anesthesia and sleep deprivation trigger delayed and selective sleep alterations

Isoflurane anesthesia (IA) partially compensates NREM sleep (NREMS) and not REM sleep (REMS) requirement, eliciting post-anesthetic REMS rebound. Sleep deprivation triggers compensatory NREMS rebounds and REMS rebounds during recovery sleep as a result of the body’s homeostatic mechanisms. A combination of sleep deprivation and isoflurane anesthesia is common in clinical settings, especially prior to surgeries. This study investigates the effects of pre-anesthetic sleep deprivation on post-anesthetic sleep–wake architecture. The effects of isoflurane exposure (90 min) alone were compared with the effects of isoflurane exposure preceded by experimental sleep deprivation (6 h, gentle handling) on recovery sleep in adult mice by studying the architecture of post-anesthetic sleep for 3 consecutive post-anesthetic days. Effects of isoflurane anesthesia on recovery sleep developed only during the first dark period after anesthesia, the active phase in mice. During this time, mice irrespective of preceding sleep pressure, showed NREMS and REMS rebound and decreased wakefulness during recovery sleep. Additionally, sleep deprivation prior to isoflurane treatment caused a persistent reduction of theta power during post-anesthetic REMS at least for 3 post-anesthetic days. We showed that isoflurane causes NREMS rebound during recovery sleep which suggests that isoflurane may not fully compensate for natural NREMS. The study also reveals that isoflurane exposure preceded by sleep deprivation caused a persistent disruption of REMS quality. We suggest that preoperative sleep deprivation may impair postoperative recovery through lasting disruption in sleep quality.

Differential effects of sleep deprivation on sleepwalking: Role of demographic and clinical profiles

BackgroundAlthough sleepwalking is one of the most prevalent and potentially injurious of the NREM parasomnias, it is still diagnosed primarily based on the patient's clinical history. Early pilot work suggested that sleep deprivation protocols could help obtain a polysomnographically-based (PSG) diagnosis of sleepwalking, but larger studies remain lacking. MethodsWe compared baseline PSG recordings with those obtained after 25hrs of sleep deprivation in a cohort of 124 consecutively assessed adult sleepwalkers. ResultsWhen compared to baseline recordings, post-sleep deprivation PSG assessments resulted in nearly twice as many somnambulistic episodes being recorded in the laboratory and significantly increased the proportion of patients (from 48 % to 63 %) experiencing at least one lab-based episode. Moreover, while 17 % of patients experienced a sleepwalking event exclusively during recovery sleep, only 2 % of patients did so solely at baseline. Sleep deprivation had similar facilitating effects on patents’ somnambulistic events regardless of age of onset and positive versus negative family history for sleepwalking. Younger age and higher home episode frequency both predicted a positive response to sleep deprivation. A separate group of 17 patients with comorbid sleep disorders showed a similar increase in their proportion experiencing at least one episode during recovery sleep. ConclusionThe results from this large series of sleepwalkers provide strong support for the use of sleep deprivation in facilitating the occurrence of somnambulistic events in the sleep laboratory.

Sleep loss diminishes hippocampal reactivation and replay.

Memories benefit from sleep1, and the reactivation and replay of waking experiences during hippocampal sharp-wave ripples (SWRs) are considered to be crucial for this process2. However, little is known about how these patterns are impacted by sleep loss. Here we recorded CA1 neuronal activity over 12 h in rats across maze exploration, sleep and sleep deprivation, followed by recovery sleep. We found that SWRs showed sustained or higher rates during sleep deprivation but with lower power and higher frequency ripples. Pyramidal cells exhibited sustained firing during sleep deprivation and reduced firing during sleep, yet their firing rates were comparable during SWRs regardless of sleep state. Despite the robust firing and abundance of SWRs during sleep deprivation, we found that the reactivation and replay of neuronal firing patterns was diminished during these periods and, in some cases, completely abolished compared to ad libitum sleep. Reactivation partially rebounded after recovery sleep but failed to reach the levels found in natural sleep. These results delineate the adverse consequences of sleep loss on hippocampal function at the network level and reveal a dissociation between the many SWRs elicited during sleep deprivation and the few reactivations and replays that occur during these events.

Modafinil Subjectively Does Not Impair Sleep in Aviators After a Period of Extended Wakefulness.

INTRODUCTION: Modafinil is used as a countermeasure to limit the effects of fatigue in military aviation. However, literature is conflicting about its negative effects on subsequent sleep.METHODS: This randomized placebo-controlled trial conducted by the Center of Man in Aviation of the Royal Netherlands Airforce is part of a larger study. It included 32 subjects (mean age 35 yr old, 84% male) who followed a normal daily routine and stayed awake the subsequent night. At midnight, all subjects received either 300 mg caffeine, 200 mg modafinil, or placebo. At the end of the test night, subjects were awake for a median period of 26 h. Afterwards, sleep questionnaires containing qualitative (Groningen Sleep Quality Scale) and quantitative parameters of sleep for the subsequent day (recovery sleep) and consecutive night (post-test sleep) were completed and statistically analyzed using Friedman and Wilcoxon signed rank tests.RESULTS: A statistically significant difference in the reported recovery sleep was observed. The modafinil group slept 30% shorter than placebo, but sleep efficiency was not statistically different. Quantitatively post-test sleep did not vary statistically significantly between the three groups. However, Groningen Sleep Quality Scale scores were lower post-test than pre-test in the modafinil group, while this was not the case in the caffeine and placebo group.DISCUSSION:This study found that modafinil subjectively does not negatively impact recovery sleep or subsequent nighttime sleep after an extended period of wakefulness and suggests it may decrease the need for recovery sleep compared to placebo or caffeine.Wingelaar-Jagt YQ, Wingelaar TT, Riedel WJ, Ramaekers JG. Modafinil subjectively does not impair sleep in aviators after a period of extended wakefulness. Aerosp Med Hum Perform. 2024; 95(6):290-296.

Single-nucleus RNA-seq identifies one galanin neuronal subtype in mouse preoptic hypothalamus activated during recovery from sleep deprivation

The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation.

USE OF POST-EXERCISE RECOVERY STRATEGIES IN TEAM AND INDIVIDUAL SPORTS

INTRODUCTION The study aims to identify perceptions of recovery and actual post-exercise recovery utilized by team and individual athletes in Far North Queensland. METHODS The recovery techniques used by team and individual sport athletes of different competition levels was investigated by survey. Specifically, this study investigated if, when, why and how the following recovery strategies were used: active land-based recovery (ALB), active water-based recovery (AWB), stretching (STR), cold water immersion (CWI) and contrast water therapy (CWT). RESULTS Seventy-eight athletes (47 male: 31 female) mean age 25.59 ±8.48 yrs completed survey. Local competition was most represented (44%), followed by state (37%), regional (13%), national (5%) and international (1%). Rugby league/ruby union were the most represented team sport (42%), followed by soccer (16%), AFL (6%), netball (6%) and remaining team sports (8%). Individual sports (24%) included swimming, running, and ultra-marathon. A total of 84% of participants self-reported performing a recovery strategy following either competition, after pre-season training or after in-season training. Most popular recovery methods, stretch (28%), ice bath (26%), massage (14%) and sleep (10%). Stretching was the most effective recovery strategy, with 38% ‘always’ performing stretching after a game, 36% during pre-season training and 40% in season training. Self-report by athletes was suggestive of the more physiological being the most important, stating that the strategies helped speed up recovery, increase blood flow, decrease inflammation, swelling and soreness. CONCLUSION To date the survey data suggests athletes reporting why they believe recovery strategies are effective/ineffective are more aware of the physiological recovery aspects, and less so on psychological aspects. This suggests potential targeted education on psychological aspects of recovery and recovery related to heat and humidity aspects to assist in developing best practice guidelines and education for athletes and coaches.

Exploring the potential relationship between short sleep risks and cognitive function from the perspective of inflammatory biomarkers and cellular pathways: Insights from population-based and mice studies.

The molecular mechanism of short-sleep conditions on cognition remains largely unknown. This research aimed to investigate associations between short sleep, inflammatory biomarkers and cognitive function in the US population (NHANES data 2011-2014) and explore cellular mechanisms in mice. Systemic immune-inflammation index (SII) was calculated using blood-cell based biomarkers. Further, we employed integrated bioinformatics and single-cell transcriptomics (GSE137665) to examine how short sleep exposure influenced the molecular pathways associated with inflammation in the brain. To explore the signaling pathways and biological processes of sleep deprivation, we carried out enrichment analyses utilizing the GO and KEGG databases. Population results showed that, compared with normal sleep group, severe short sleep was associated with lower cognitive ability in all the four tests. Moreover, a higher SII level was correlated with lower scores of cognitive tests. In mice study, elevated activation of the inflammatory pathway was observed in cell subgroups of neurons within the sleep deprivation and recovery sleep cohorts. Additionally, heightened expression of oxidative stress and integrated stress response pathways was noted in GABAergic neurons during sleep deprivation. This study contributed to the understanding of the influence of short sleep on cognitive function and its cellular mechanisms.

0224 Sleep Deprivation and Recovery Sleep Impact Serum Biomarkers of Alzheimer's Disease in Retired Adults

0224 Sleep Deprivation and Recovery Sleep Impact Serum Biomarkers of Alzheimer's Disease in Retired Adults

The NFκB Dif is required for behavioral and molecular correlates of sleep homeostasis in Drosophila.

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, genetic studies of the role of specific NFκB transcription factors in sleep have been limited. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (Dif), and Relish. We previously found that loss of the Relish gene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep. Here we show that Dif regulates daily sleep and recovery sleep following prolonged wakefulness. Mutants of Dif showed reduced daily sleep and suppressed recovery in response to sleep deprivation. Pan-neuronal knockdown of Dif strongly suppressed daily sleep, indicating that in contrast to Relish, Dif functions from the central nervous system to regulate sleep. Based on the unique expression pattern of a Dif- GAL4 driver, we hypothesized that its effects on sleep were mediated by the pars intercerebralis (PI). While RNAi knock-down of Dif in the PI reduced daily sleep, it had no effect on the recovery response to sleep deprivation. However, recovery sleep was suppressed when RNAi knock-down of Dif was distributed across a wider range of neurons. Induction of the nemuri (nur) antimicrobial peptide by sleep deprivation was reduced in Dif mutants and pan-neuronal overexpression of nur also suppressed the Dif mutant phenotype by significantly increasing sleep and reducing nighttime arousability. Together, these findings indicate that Dif functions from brain to target nemuri and to promote deep sleep.

The dynamic responses of mood and sleep physiology to chronic sleep restriction and subsequent recovery sleep.

Healthy sleep of sufficient duration preserves mood and disturbed sleep is a risk factor for a range of psychiatric disorders. As adults commonly experience chronic sleep restriction (SR), an enhanced understanding of the dynamic relationship between sleep and mood is needed, including whether susceptibility to SR-induced mood disturbance differs between sexes. To address these gaps, data from N = 221 healthy adults who completed one of the two multi-day laboratory studies with identical 9-day SR protocols were analyzed. Participants randomized to the SR (n = 205) condition underwent 5 nights of SR to 4 hours of time-in-bed and were then randomized to one of the seven sleep doses that ranged from 0 to 12 hours in 2 hours increments; participants randomized to the control (n = 16) condition received 10 hours time-in-bed on all study nights. The Profile of Mood States (POMS) was used to assess mood every 2 hours during wakefulness and markers of sleep homeostasis (EEG slow-wave activity (SWA)) were derived via polysomnography. Mood progressively deteriorated across SR with marked disturbances in somatic mood components. Altered sleep physiology contributed to mood disturbance whereby increased EEG SWA was associated with increased POMS Total Mood Disturbance scores, a finding specific to males. The mood was restored in a dose-response fashion where improvements were greater with longer sleep doses. These findings suggest that when lifestyle and environmental factors are inhibited in the laboratory, the affective consequences of chronic sleep loss are primarily somatic mood disturbances. Altered sleep homeostasis may contribute to mood disturbance, yet sleep-dependent mechanisms may be sex-specific.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

The dynamics of neurobehavioral impairment and recovery sleep: improved biomathematical modeling for fatigue risk management in operational settings

Adequate sleep is essential for maintaining health, safety, and neurobehavioral functioning in 24/7 operational settings. Loss of sleep causes fatigue, which results in neurobehavioral impairment. Neurobehavioral impairment builds up disproportionately under conditions of total sleep deprivation compared to sustained sleep restriction; and recuperation due to recovery sleep is disproportionately fast after total sleep deprivation compared to sustained sleep restriction. These sleep schedule-dependent dynamics have been captured in a previously published, biomathematical model of fatigue, which includes positive feedback regulation of a relatively fast (hours to days) sleep/wake homeostatic process by a slower (days to weeks) allostatic process—a feature that suggests adenosinergic mechanisms are involved. However, the previously published model underestimates the rate of recuperation due to recovery sleep after acute total sleep deprivation as well as after consecutive days of sleep restriction. The objective of the present research is to modify the model to improve the accuracy of its predictions for recuperation due to recovery sleep. This can be accomplished by including in the model an additional, reciprocal feedback mechanism, presumed to be predominantly adenosinergic in nature, which provides feedback from the faster homeostatic process back onto the slower allostatic process. Adding a single new model parameter and refitting three existing model parameters significantly improves the predictions for recuperation due to recovery sleep after both acute total sleep deprivation and sustained sleep restriction. This model modification also improves the predictions of the build-up of neurobehavioral impairment across days of sustained sleep restriction, without adversely affecting the accuracy of the model in other scenarios including circadian misalignment and sleep inertia. The modified model preserves the previously developed capability to predict the differential dynamics of fatigue for objective performance impairment and subjective sleepiness. With the improved predictions for recuperation due to recovery sleep, the expanded model can be used to provide quantitative estimates for potentially impactful work scheduling decisions, such as the duration of time off needed before workers would be safe to return to the work floor. This enhances the usefulness of the model as a tool for predicting and managing neurobehavioral functioning and safety in 24/7 operational settings.

Sleeping for One Week on a Temperature-Controlled Mattress Cover Improves Sleep and Cardiovascular Recovery.

Body temperature should be tightly regulated for optimal sleep. However, various extrinsic and intrinsic factors can alter body temperature during sleep. In a free-living study, we examined how sleep and cardiovascular health metrics were affected by sleeping for one week with (Pod ON) vs. without (Pod OFF), an active temperature-controlled mattress cover (the Eight Sleep Pod). A total of 54 subjects wore a home sleep test device (HST) for eight nights: four nights each with Pod ON and OFF (>300 total HST nights). Nightly sleeping heart rate (HR) and heart rate variability (HRV) were collected. Compared to Pod OFF, men and women sleeping at cooler temperatures in the first half of the night significantly improved deep (+14 min; +22% mean change; p = 0.003) and REM (+9 min; +25% mean change; p = 0.033) sleep, respectively. Men sleeping at warm temperatures in the second half of the night significantly improved light sleep (+23 min; +19% mean change; p = 0.023). Overall, sleeping HR (-2% mean change) and HRV (+7% mean change) significantly improved with Pod ON (p < 0.01). To our knowledge, this is the first study to show a continuously temperature-regulated bed surface can (1) significantly modify time spent in specific sleep stages in certain parts of the night, and (2) enhance cardiovascular recovery during sleep.

Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice

BackgroundSleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients’ quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission. It has been linked to autism spectrum disorders and schizophrenia in humans, and deregulations of its expression were shown to cause epileptic-like hypersynchronized cerebral activity in rodents. Importantly, the absence of Nlgn2 (knockout: KO) was previously shown to alter sleep-wake duration and quality in mice, notably increasing slow-wave sleep (SWS) delta activity (1–4 Hz) and altering its 24-h dynamics. This type of brain oscillation is involved in memory consolidation, and is also a marker of homeostatic sleep pressure. Sleep deprivation (SD) is notably known to impair cognition and the physiological response to sleep loss involves GABAergic transmission.MethodsUsing electrocorticographic (ECoG) recordings, we here first aimed to verify how individual slow wave (SW; 0.5-4 Hz) density and properties (e.g., amplitude, slope, frequency) contribute to the higher SWS delta activity and altered 24-h dynamics observed in Nlgn2 KO mice. We further investigated the response of these animals to SD. Finally, we tested whether sleep loss affects the gene expression of Nlgn2 and related GABAergic transcripts in the cerebral cortex of wild-type mice using RNA sequencing.ResultsOur results show that Nlgn2 KO mice have both greater SW amplitude and density, and that SW density is the main property contributing to the altered 24-h dynamics. We also found the absence of Nlgn2 to accelerate paradoxical sleep recovery following SD, together with profound alterations in ECoG activity across vigilance states. Sleep loss, however, did not modify the 24-h distribution of the hypersynchronized ECoG events observed in these mice. Finally, RNA sequencing confirmed an overall decrease in cortical expression of Nlgn2 and related GABAergic transcripts following SD in wild-type mice.ConclusionsThis work brings further insight into potential mechanisms of sleep duration and quality deregulation in neurodevelopmental disorders, notably involving NLGN2 and GABAergic neurotransmission.

Chronic sleep fragmentation reduces left ventricular contractile function and alters gene expression related to innate immune response and circadian rhythm in the mouse heart

Sleep disorders have emerged as a widespread public health concern, primarily due to their association with an increased risk of developing cardiovascular diseases. Our previous research indicated a potential direct impact of insufficient sleep duration on cardiac remodeling in children and adolescents. Nevertheless, the underlying mechanisms behind the link between sleep fragmentation (SF) and cardiac abnormalities remain unclear. In this study, we aimed to investigate the effects of SF interventions at various life stages on cardiac structure and function, as well as to identify genes associated with SF-induced cardiac dysfunction. To achieve this, we established mouse models of chronic SF and two-week sleep recovery (SR). Our results revealed that chronic SF significantly compromised left ventricular contractile function across different life stages, leading to alterations in cardiac structure and ventricular remodeling, particularly during early life stages. Moreover, microarray analysis of mouse heart tissue identified two significant modules and nine hub genes (Ddx60, Irf9, Oasl2, Rnf213, Cmpk2, Stat2, Parp14, Gbp3, and Herc6) through protein–protein interaction analysis. Notably, the interactome predominantly involved innate immune responses. Importantly, all hub genes lost significance following SR. The second module primarily consisted of circadian clock genes, and real-time PCR validation demonstrated significant upregulation of Arntl, Dbp, and Cry1 after SF, while subsequent SR restored normal Arntl expression. Furthermore, the expression levels of four hub genes (Ddx60, Irf9, Oasl2, and Cmpk2) and three circadian clock genes (Arntl, Dbp, and Cry1) exhibited correlations with structural and functional echocardiographic parameters. Overall, our findings suggest that SF impairs left ventricular contractile function and ventricular remodeling during early life stages, and this may be mediated by modulation of the innate immune response and circadian rhythm. Importantly, our findings suggest that a short period of SR can alleviate the detrimental effects of SF on the cardiac immune response, while the influence of SF on circadian rhythm appears to be more persistent. These findings underscore the importance of good sleep for maintaining cardiac health, particularly during early life stages.

Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice

PurposeProstatitis is a highly prevalent condition that seriously affects men’s physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target.MethodsSleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated.ResultsSD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-β. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse.ConclusionsThe cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.

The effect of slow wave sleep deprivation on mood in adolescents with depressive symptoms: A pilot study

BackgroundThere is an urgent need for safe, rapid-acting treatment strategies for adolescent depression. In depressed adults, slow wave sleep deprivation (SWSD) improved next-day mood without disrupting sleep duration, but SWSD has not been tested in adolescents. In a pilot study, the aim was to assess the effect of SWSD on sleep physiology and mood outcomes (depression, rumination, anhedonia) among adolescents with depressive symptoms. MethodsSixteen adolescents (17.44 ± 1.46 yr, 12 female) completed three nights of polysomnographic sleep recording: Baseline, SWSD, and Recovery nights. Acoustic stimulation (tones of random pitch, duration, and volume) suppressed slow wave sleep (SWS) in real-time during SWSD. After each night, depression, rumination, and anhedonia severity were assessed. ResultsSWSD successfully suppressed SWS, increased N2, and had minimal impact on Rapid Eye Movement (REM), nocturnal awakenings, and total sleep time. While SWSD did not improve depression or anhedonia severity overall, lower baseline non-REM alpha activity and greater SWS rebound during recovery sleep correlated with SWSD-related reduction in clinician-rated depression severity. Next-day rumination severity decreased after SWSD, with sustained improvements following recovery sleep. However, rumination improvement was not associated with SWS suppression, but rather reduction in total sleep time and REM in exploratory correlation models. LimitationsSmall sample size and large proportion of females. ConclusionSWSD did not improve depression in adolescents overall but a subset with low non-REM alpha activity and intact homeostatic sleep regulation may benefit from this approach. Findings from this pilot study also suggest that partial sleep deprivation may be a beneficial therapeutic strategy for rumination in adolescents.

Sleep- and sleep deprivation-related changes of vertex auditory evoked potentials during the estrus cycle in female rats

The estrus cycle in female rodents has been shown to affect a variety of physiological functions. However, little is known about its presumably thorough effect on auditory processing during the sleep–wake cycle and sleep deprivation. Vertex auditory evoked potentials (vAEPs) were evoked by single click tone stimulation and recorded during different stages of the estrus cycle and sleep deprivation performed in metestrus and proestrus in female rats. vAEPs showed a strong sleep-dependency, with the largest amplitudes present during slow wave sleep while the smallest ones during wakefulness. Higher amplitudes and longer latencies were seen in the light phase during all vigilance stages. The largest amplitudes were found during proestrus (light phase) while the shortest latencies were seen during estrus (dark phase) compared to the 2nd day diestrus baseline. High-amplitude responses without latency changes were also seen during metestrus with increased homeostatic sleep drive. More intense and faster processing of auditory information during proestrus and estrus suggesting a more effective perception of relevant environmental cues presumably in preparation for sexual receptivity. A 4-h sleep deprivation resulted in more pronounced sleep recovery in metestrus compared to proestrus without difference in delta power replacement suggesting a better tolerance of sleep deprivation in proestrus. Sleep deprivation decreased neuronal excitability and responsiveness in a similar manner both during metestrus and proestrus, suggesting that the negative consequences of sleep deprivation on auditory processing may have a limited correlation with the estrus cycle stage.