Impact of chronic sleep deprivation on male reproductive health: Insights from testicular and epididymal responses in mice.

BACKGROUND: Sleep deprivation (SD) can cause damage to the male reproductive system. However, the duration required for such damage and the specific sequence and severity of damage to the testis and epididymis remain unclear. OBJECTIVE: To investigate the effects of different durations of SD on different parts of the testis and epididymis caput, corpus, and cauda. METHODS: Adult ICR mice were randomly assigned to five groups: the SD group (SD for 18 h/day for 1, 2, 3, or 4 weeks), the SD + Vit E group (supplemented with Vit E 50 mg/kg/d during 4 weeks of SD, the SD+NS group (saline supplementation during 4 weeks of SD), the SD + RS group (5 weeks of recovery sleep after 4 weeks of SD), and a normal sleep control (Ctrl) group. Following the interventions, sperm parameters, testicular and epididymal histopathology, inflammatory response, and oxidative stress markers were compared between the groups. RESULTS: Compared to the Ctrl group, the SD group showed a decrease in sperm motility and concentration from SD 2 W and SD 3 W, respectively. Decreases in sperm concentration and motility were more pronounced in the cauda compared to the caput and corpus. Pathological damage was less severe in the epididymis caput than in the corpus and cauda. After 4 weeks of SD, inflammation and oxidative stress increased in both testes and epididymis. Both sleep recovery and vitamin E supplementation showed significant improvements, though they did not fully reach the level of the Ctrl group. CONCLUSION: Chronic SD for more than 2 weeks causes varying degrees of damage to the testis, epididymis caput, corpus, and cauda in male mice. This damage is not fully reversible after 5 weeks of sleep recovery and antioxidant stress treatment. These findings help us to identify and prevent SD damage to the male reproduction at an early stage.

Effects of low-dose acetylsalicylic acid on the inflammatory response to experimental sleep restriction in healthy humans.

BACKGROUND: Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction. METHODS: 46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models. RESULTS: Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition). CONCLUSION: This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03377543.

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.

Neurobehavioral functions during recurrent periods of sleep restriction: effects of intra-individual variability in sleep duration.

STUDY OBJECTIVES: To investigate whether neurobehavioral impairments are exacerbated during successive cycles of sleep restriction and recovery in young adults, and whether a variable short sleep schedule can mitigate these impairments relative to a stable one. METHODS: Fifty-two healthy young adults (25 males, aged: 21-28) were randomly assigned to the stable short sleep group, the variable short sleep group, or the control group in this laboratory-based study. They underwent two baseline nights of 8-hour time-in-bed (TIB), followed by two cycles of "weekday" sleep opportunity manipulation and "weekend" recovery (8-hour TIB). During each manipulation period, the stable short sleep and the control groups received 6- and 8-hour TIBs each night respectively, while the variable short sleep group received 8-hour, 4-hour, 8-hour, 4-hour, and 6-hour TIBs from the first to the fifth night. Neurobehavioral functions were assessed five times each day. RESULTS: The stable short sleep group showed faster vigilance deterioration in the second week of sleep restriction as compared to the first. This effect was not observed in the variable short sleep group. Subjective alertness and practice-based improvement in processing speed were attenuated in both short sleep groups. CONCLUSIONS: In young adults, more variable short sleep schedules incorporating days of prophylactic or recovery sleep might mitigate compounding vigilance deficits resulting from recurrent cycles of sleep restriction. However, processing speed and subjective sleepiness were still impaired in both short sleep schedules. Getting sufficient sleep consistently is the only way to ensure optimal neurobehavioral functioning. CLINICAL TRIAL: Performance, Mood, and Brain and Metabolic Functions During Different Sleep Schedules (STAVAR), https://www.clinicaltrials.gov/study/NCT04731662, NCT04731662.

Decrease in the P2 Amplitude of Object Working Memory after 8 h-Recovery Sleep Following 36 h-Total Sleep Deprivation: An ERP Study.

The impact of sleep deprivation on working memory can only be reversed by recovery sleep (RS). However, there are limited electrophysiological studies on the effect of RS on the improvement in working memory after sleep deprivation, and the changes in the early components of event-related potentials (ERPs) before and after RS are still unclear. Therefore, this study aims to explore the effects of RS on the earlier ERP components related to object working memory following 36 h of total sleep deprivation (TSD). Twenty healthy male participants performed an object working memory task after 36 h of TSD and after 8 h of RS. Electroencephalogram data were recorded accordingly while the task was performed. Repeated ANOVA showed that P2 amplitudes related to object working memory decreased significantly after 8 h of RS compared to after a 36 h period of TSD, but there was no significant difference from baseline (BS), which indicates a trend of recovery to the baseline state. An 8 h RS can partially improve impaired object working memory caused by TSD. However, a longer period of RS is needed for the complete recovery of cognitive function after a long period of TSD.

The Effects of Commercially-Relevant Disturbances on Sleep Behaviour in Laying Hens.

Ensuring the welfare of commercially kept animals is a legal and ethical responsibility. Sleep behaviour can be sensitive to environmental perturbations and may be useful in assessing welfare state. The objective of this study was to use behavioural and electrophysiological (EEG) measures to observe the effects of 24 h stressors followed by periods of no stressors on laying hen sleep behaviour, and to investigate the use of sleep behaviour as a means of welfare assessment in commercial poultry. Ten laying hens surgically implanted with EEG devices to record their brain activity over four batches were used. Hens were subjected to undisturbed, disturbed and recovery periods for 24 h. Disturbed periods consisted of either feed deprivation, increased ambient temperature (28 °C) or simulated footpad pain via injection of Freund's adjuvant into the footpad. Sleep state was scored using behaviour data from infrared cameras and EEG data. Over all periods, hens engaged in both SWS (average 60%) and REM sleep (average 12%) during the lights-off period. Feed deprivation and footpad pain had little to no effect on sleep states, while increased ambient temperature significantly reduced REM sleep (to near elimination, p < 0.001) and SWS (p = 0.017). During the lights-on period, footpad pain increased the proportion of time spent resting (p = 0.008) and in SWS (p < 0.001), with feed deprivation or increased ambient temperature (p > 0.05) having no effect. Increasing ambient temperatures are likely to affect sleep and welfare in commercially-kept laying hens in the face of global climate change.

Heart rate and heart rate variability following sleep deprivation in retired night shift workers and retired day workers.

Shift workers experience poor sleep and dysregulated cardiac autonomic function during sleep. However, it is unknown if this dysregulation persists into retirement, potentially accelerating the age-associated risk for adverse cardiovascular outcomes. Using sleep deprivation as a physiological challenge to cardiovascular autonomic function, we compared heart rate (HR) and high-frequency heart rate variability (HF-HRV) during baseline and recovery sleep following sleep deprivation between retired night shift and day workers. Participants were retired night shift (N = 33) and day workers (N = 37) equated on age (mean [standard deviation] = 68.0 [5.6] years), sex (47% female), race/ethnicity (86% White), and body mass index. Participants completed a 60-h lab protocol including one night of baseline polysomnography-monitored sleep, followed by 36 h of sleep deprivation and one night of recovery sleep. Continuously recorded HR was used to calculate HF-HRV. Linear mixed models compared HR and HF-HRV during non-rapid eye movement (NREM) and REM sleep between groups during baseline and recovery nights. Groups did not differ on HR or HF-HRV during NREM or REM sleep (ps > .05) and did not show differential responses to sleep deprivation. In the full sample, HR increased and HF-HRV decreased from baseline to recovery during NREM (ps < .05) and REM (ps < .01). Both groups exhibited cardiovascular autonomic changes during recovery sleep following 36 h of sleep deprivation. Sleep deprivation appears to induce cardiovascular autonomic changes that persist into recovery sleep in older adults, regardless of shift work history.

Prolonged experimental sleep disturbance affects the inflammatory resolution pathways in healthy humans.

BACKGROUND: Sleep disturbances, as manifested in insomnia symptoms of difficulties falling asleep or frequent nighttime awakenings, are a strong risk factor for a diverse range of diseases involving immunopathology. Low-grade systemic inflammation has been frequently found associated with sleep disturbances and may mechanistically contribute to increased disease risk. Effects of sleep disturbances on inflammation have been observed to be long lasting and remain after recovery sleep has been obtained, suggesting that sleep disturbances may not only affect inflammatory mediators, but also the so-called specialized pro-resolving mediators (SPMs) that actively resolve inflammation. The goal of this investigation was to test for the first time whether the omega-3 fatty acid-derived D- (RvD) and E-series (RvE) resolvins are impacted by prolonged experimental sleep disturbance (ESD). METHODS: Twenty-four healthy participants (12 F, age 20-42 years) underwent two 19-day in-hospital protocols (ESD/control), separated by > 2 months. The ESD protocol consisted of repeated nights of short and disrupted sleep with intermittent nights of undisturbed sleep, followed by three nights of recovery sleep at the end of the protocol. Under the control sleep condition, participants had an undisturbed sleep opportunity of 8 h/night throughout the protocol. The D- and E-series resolvins were measured in plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The precursor of the D-series resolvins, 17-HDHA, was downregulated in the ESD compared to the control sleep condition (p <.001 for condition), and this effect remained after the third night of recovery sleep has been obtained. This effect was also observed for the resolvins RvD3, RvD4, and RvD5 (p <.001 for condition), while RvD1 was higher in the ESD compared to the control sleep condition (p <.01 for condition) and RvD2 showed a mixed effect of a decrease during disturbed sleep followed by an increase during recovery sleep in the ESD condition (p <.001 for condition*day interaction). The precursor of E-series resolvins, 18-HEPE, was downregulated in the ESD compared to the control sleep condition (p <.01 for condition) and remained low after recovery sleep has been obtained. This effect of downregulation was also observed for RvE2 (p <.01 for condition), while there was no effect for RvE1 (p >.05 for condition or condition*day interaction). Sex-differential effects were found for two of the D-series resolvins, i.e., RvD2 and RvD4. CONCLUSION: This first investigation on the effects of experimental sleep disturbance on inflammatory resolution processes shows that SPMs, particularly resolvins of the D-series, are profoundly downregulated by sleep disturbances and remain downregulated after recovery sleep has been obtained, suggesting a longer lasting impact of sleep disturbances on these mediators. These findings also suggest that sleep disturbances contribute to the development and progression of a wide range of diseases characterized by immunopathology by interfering with processes that actively resolve inflammation. Pharmacological interventions aimed at promoting inflammatory resolution physiology may help to prevent future disease risk as a common consequence of sleep disturbances. TRIAL REGISTRATION: ClinicalTrials.gov NCT02484742.

Dynamics of recovery sleep from chronic sleep restriction.

Sleep loss is common in our 24/7 society with many people routinely sleeping less than they need. Sleep debt is a term describing the difference between the amount of sleep needed, and the amount of sleep obtained. Sleep debt can accumulate over time, resulting in poor cognitive performance, increased sleepiness, poor mood, and a higher risk for accidents. Over the last 30 years, the sleep field has increasingly focused attention on recovery sleep and the ways we can recover from a sleep debt faster and more effectively. While there are still many unanswered questions and debates about the nature of recovery sleep, such as the exact components of sleep important for recovery of function, the amount of sleep needed to recover and the impacts of prior sleep history on recovery, recent research has revealed several important attributes about recovery sleep: (1) the dynamics of the recovery process is impacted by the type of sleep loss (acute versus chronic), (2) mood, sleepiness, and other aspects of cognitive performance recover at different rates, and (3) the recovery process is complex and dependent on the length of recovery sleep and the number of recovery opportunities available. This review will summarize the current state of the literature on recovery sleep, from specific studies of recovery sleep dynamics to napping, "banking" sleep and shiftwork, and will suggest the next steps for research in this field. This paper is part of the David F. Dinges Festschrift Collection. This collection is sponsored by Pulsar Informatics and the Department of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania.

Recovery sleep attenuates impairments in working memory following total sleep deprivation.

Introduction: The detrimental effects of sleep deprivation (SD) on cognitive function and quality of life are well known, and sleep disturbances are a major physical and mental health issue worldwide. Working memory plays an important role in many complex cognitive processes. Therefore, it is necessary to identify strategies that can effectively counteract the negative effects of SD on working memory. Methods: In the present study, we utilized event-related potentials (ERPs) to investigate the restorative effects of 8 h of recovery sleep (RS) on working memory impairments induced by total sleep deprivation for 36 h. We analyzed ERP data from 42 healthy male participants who were randomly assigned to two groups. The nocturnal sleep (NS) group completed a 2-back working memory task before and after normal sleep for 8 h. The sleep deprivation (SD) group completed a 2-back working memory task before and after 36 h of total sleep deprivation (TSD) and after 8 h of RS. Electroencephalographic data were recorded during each task. Results: The N2 and P3 components-which are related to working memory-exhibited low-amplitude and slow-wave characteristics after 36 h of TSD. Additionally, we observed a significant decrease in N2 latency after 8 h of RS. RS also induced significant increases in the amplitude of the P3 component and in the behavioral indicators. Discussion: Overall, 8 h of RS attenuated the decrease in working memory performance caused by 36 h of TSD. However, the effects of RS appear to be limited.

The Effects of Mild Disturbances on Sleep Behaviour in Laying Hens.

The positive welfare of commercial animals presents many benefits, making the accurate assessment of welfare important. Assessments frequently use behaviour to determine welfare state; however, nighttime behaviours are often ignored. Sleep behaviour may offer new insights into welfare assessments. This study aimed to establish a baseline for sleep behaviour in laying hens and to then apply mild short-term disturbances and observe the subsequent effects. Twelve laying hens were divided into four batches and were surgically implanted with electroencephalogram (EEG) devices to record their brain activity. The batches were subjected to undisturbed, disturbed and recovery types of nights. Disturbed nights consisted of systematic sequences of disturbance application (wind, 90 dB noise or 20 lux light) applied one at a time for 5 min every 30 min from 21:00 to 03:00 (lights off period: 19:00-05:00). Sleep state was scored using EEG data and behaviour data from infrared cameras. Over all the types of night hens engaged in both SWS (58%) and REM sleep (18%) during lights off. When applied, the disturbances were effective at altering the amounts of wakefulness and SWS (Time × Type of Night, p < 0.001, p = 0.017, respectively), whereas REM sleep was unaltered (p = 0.540). There was no evidence of carry-over effects over the following day or night. Laying hens may be resilient to short-term sleep disruption by compensating for this in the same night, suggesting that these disturbances do not impact their long-term welfare (i.e., over days). Sleep behaviour potentially offers a unique means of assessing an aspect of animal welfare that, to date, has been poorly studied.

The Effects of Recovery Sleep on Experimental Pain.

Recent research suggests that recovery sleep (RS) has the potential to restore pain sensitivity and modulation after hyperalgesia due to preceding sleep deprivation. However, it has not yet been systematically examined whether the restoration of these pain parameters is driven by sleep characteristics of RS. Thus, the present study assessed changes in experimental pain during RS after total sleep deprivation (TSD) to test whether RS parameters predicted the restoration of the pain system. Thirty healthy participants completed one night of habitual sleep, one night of TSD and a subsequent recovery night. At-home sleep during baseline and recovery was assessed using portable polysomnography and a questionnaire. Before and after each night pressure pain thresholds (PPTs), temporal pain summation (TSP) and conditioned pain modulation (CPM) were assessed. PPTs decreased after TSD and increased following RS, indicating a restoration of pain sensitivity after hyperalgesia. RS characteristics did not predict this restoration, suggesting other mechanisms (eg, changes in serotonergic activity) underlying the observed pain changes. TSP indicated a lack of effect of experimental sleep manipulations on excitatory processes whereas CPM lacked sufficient reliability to investigate inhibitory processes. Thus, results indicate moderate effects of sleep manipulations on pain sensitivity, but not on pain modulation. PERSPECTIVE: This article highlights the potential of recovery sleep to let pain thresholds return to normal following their decrease after a night of total sleep deprivation. In contrast, endogenous pain modulation (temporal pain summation, conditioned pain modulation) was not affected by sleep deprivation and recovery sleep.

One night of 10-h sleep restores vigilance after total sleep deprivation: the role of delta and theta power during recovery sleep.

A series of studies have demonstrated that impaired vigilance performance caused by total sleep deprivation could restore to baseline when recovery sleep is longer than the habitual sleep. However, it is unclear which factors on the recovery night affected the restoration of vigilance performance impaired by sleep deprivation. 22 participant's sleep electroencephalograms were recorded with polysomnography in 8-h baseline sleep and one-night 10-h recovery sleep following 36-h sleep deprivation. Participants completed a 10-min psychomotor vigilance task and subjective ratings after baseline and recovery sleep the following day. Objective vigilance and subjective ratings were impaired by sleep deprivation and recovered to baseline after one-night 10-h recovery sleep. Compared with baseline sleep, sleep depth increased with enhanced delta and theta power density, and sleep duration was also prolonged during recovery sleep. The vigilance performance difference between recovery and baseline sleep was taken as a behavioral index of the restoration of vigilance. The restoration of vigilance was correlated with the delta and theta power density of stage N3 in the frontal and central region during the recovery sleep. These findings indicated that one-night 10-h recovery sleep could restore the impaired objective vigilance and subjective ratings caused by sleep deprivation. The recuperative effect of vigilance relies on individual differences in sleep intensity. Individuals with higher sleep intensity in recovery sleep obtained better vigilance recovery.

Recovery Sleep Immediately after Prolonged Sleep Deprivation Stimulates the Transcription of Integrated Stress Response-Related Genes in the Liver of Male Rats.

Sleep loss induces performance impairment and fatigue. The reactivation of human herpesvirus-6, which is related to the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), is one candidate for use as an objective biomarker of fatigue. Phosphorylated eIF2α is a key regulator in integrated stress response (ISR), an intracellular stress response system. However, the relation between sleep/sleep loss and ISR is unclear. The purpose of the current study was to evaluate the effect of prolonged sleep deprivation and recovery sleep on ISR-related gene expression in rat liver. Eight-week-old male Sprague-Dawley rats were subjected to a 96-hour sleep deprivation using a flowerpot technique. The rats were sacrificed, and the liver was collected immediately or 6 or 72 h after the end of the sleep deprivation. RT-qPCR was used to analyze the expression levels of ISR-related gene transcripts in the rat liver. The transcript levels of the Atf3, Ddit3, Hmox-1, and Ppp15a1r genes were markedly increased early in the recovery sleep period after the termination of sleep deprivation. These results indicate that both activation and inactivation of ISRs in the rat liver occur simultaneously in the early phase of recovery sleep.

Sleep deprivation and recovery sleep affect healthy male resident's pain sensitivity and oxidative stress markers: The medial prefrontal cortex may play a role in sleep deprivation model.

Sleep is essential for the body's repair and recovery, including supplementation with antioxidants to maintain the balance of the body's redox state. Changes in sleep patterns have been reported to alter this repair function, leading to changes in disease susceptibility or behavior. Here, we recruited healthy male physicians and measured the extent of the effect of overnight sleep deprivation (SD) and recovery sleep (RS) on nociceptive thresholds and systemic (plasma-derived) redox metabolism, namely, the major antioxidants glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD). Twenty subjects underwent morning measurements before and after overnight total SD and RS. We found that one night of SD can lead to increased nociceptive hypersensitivity and the pain scores of the Numerical Rating Scale (NRS) and that one night of RS can reverse this change. Pre- and post-SD biochemical assays showed an increase in MDA levels and CAT activity and a decrease in GSH levels and SOD activity after overnight SD. Biochemical assays before and after RS showed a partial recovery of MDA levels and a basic recovery of CAT activity to baseline levels. An animal study showed that SD can cause a significant decrease in the paw withdrawal threshold and paw withdrawal latency in rats, and after 4 days of unrestricted sleep, pain thresholds can be restored to normal. We performed proteomics in the rat medial prefrontal cortex (mPFC) and showed that 37 proteins were significantly altered after 6 days of SD. Current findings showed that SD causes nociceptive hyperalgesia and oxidative stress, and RS can restore pain thresholds and repair oxidative stress damage in the body. However, one night of RS is not enough for repairing oxidative stress damage in the human body.

Bone Turnover Markers After Six Nights of Insufficient Sleep and Subsequent Recovery Sleep in Healthy Men.

PURPOSE: The goal of this study was to determine the bone turnover marker (BTM) response to insufficient and subsequent recovery sleep, independent of changes in posture, body weight, and physical activity. METHODS: Healthy men (N = 12) who habitually slept 7-9 h/night were admitted to an inpatient sleep laboratory for a baseline 8 h/night sleep opportunity followed by six nights of insufficient sleep (5 h/night). Diet, physical activity, and posture were controlled. Serum markers of bone formation (osteocalcin, PINP) and resorption (ß-CTX) were obtained over 24 h at baseline and on the last night of sleep restriction, and on fasted samples obtained daily while inpatient and five times after discharge over 3 weeks. Maximum likelihood estimates in a repeated measures model were used to assess the effect of insufficient and subsequent recovery sleep on BTM levels. RESULTS: There was no statistically or clinically significant change in PINP (p = 0.53), osteocalcin (p = 0.66), or ß-CTX (p = 0.10) in response to six nights of insufficient sleep. There were no significant changes in BTMs from the inpatient stay through 3 weeks of recovery sleep (all p [Formula: see text] 0.63). On average, body weight was stable during the inpatient stay (Δweight = - 0.55 ± 0.91 kg, p = 0.06). CONCLUSION: No significant changes in serum BTMs were observed after six nights of insufficient or subsequent recovery sleep in young healthy men. Changes in weight and physical activity may be required to observe significant BTM change in response to sleep and circadian disruptions. Clinical Trials Registration Registered at ClinicalTrials.gov (NCT03733483) on November 7, 2018.

Staying vigilant during recurrent sleep restriction: dose-response effects of time-in-bed and benefits of daytime napping.

STUDY OBJECTIVES: We characterized vigilance deterioration with increasing time-on-task (ToT) during recurrent sleep restriction of different extents on simulated weekdays and recovery sleep on weekends, and tested the effectiveness of afternoon napping in ameliorating ToT-related deficits. METHODS: In the Need for Sleep studies, 194 adolescents (age = 15-19 years) underwent two baseline nights of 9-h time-in-bed (TIB), followed by two cycles of weekday manipulation nights and weekend recovery nights (9-h TIB). They were allocated 9 h, 8 h, 6.5 h, or 5 h of TIB for nocturnal sleep on weekdays. Three additional groups with 5 h or 6.5 h TIB were given an afternoon nap opportunity (5 h + 1 h, 5 h + 1.5 h, and 6.5 h + 1.5 h). ToT effects were quantified by performance change from the first 2 min to the last 2 min in a 10-min Psychomotor Vigilance Task administered daily. RESULTS: The 9 h and the 8 h groups showed comparable ToT effects that remained at baseline levels throughout the protocol. ToT-related deficits were greater among the 5 h and the 6.5 h groups, increased prominently in the second week of sleep restriction despite partial recuperation during the intervening recovery period and diverged between these two groups from the fifth sleep-restricted night. Daytime napping attenuated ToT effects when nocturnal sleep restriction was severe (i.e. 5-h TIB/night), and held steady at baseline levels for a milder dose of nocturnal sleep restriction when total TIB across 24 h was within the age-specific recommended sleep duration (i.e. 6.5 h + 1.5 h). CONCLUSIONS: Reducing TIB beyond the recommended duration significantly increases ToT-associated vigilance impairment, particularly during recurrent periods of sleep restriction. Daytime napping is effective in ameliorating such decrement. CLINICAL TRIAL REGISTRATION: NCT02838095, NCT03333512, and NCT04044885.

Assessment of effects of total sleep deprivation and subsequent recovery sleep: a methodological strategy feasible without sleep laboratory.

BACKGROUND: Sleep is critical for maintaining homeostasis in bodily and neurobehavioral functions. This homeostasis can be disturbed by sleep interruption and restored to normal by subsequent recovery sleep. Most research regarding recovery sleep (RS) effects has been conducted in specialized sleep laboratories, whereas small, less-well equipped research units may lack the possibilities to run studies in this area. Hence, the aims of the present study were to develop and validate an experimental protocol, which allows a thorough assessment of at-home recovery sleep after sleep deprivation. METHODS: The experimental protocol, comprising one night of baseline sleep (BL) at home, one night of monitored total sleep deprivation and a subsequent recovery night at home, was tested in a sample of 30 healthy participants. Subjects' fatigue and alertness were assessed prior to and after each night. Sleep at home (BL, RS) was objectively assessed using portable polysomnography. To check whether our at-home sleep assessments yielded results that are comparable to those conducted in sleep laboratories, we compared the sleep data assessed in our study with sleep data assessed in laboratory studies. RESULTS: Sleep parameters assessed during RS exhibited changes as expected (prolonged total sleep time, better sleep efficiency, slow wave sleep rebound). Sleep parameters of BL and RS were in line with parameters assessed in previous studies examining sleep in a laboratory setting. Fatigue normalized after one night of RS; alertness partly recovered. CONCLUSIONS: Our results suggest a successful implementation of our new experimental protocol, emphasizing it as a useful tool for future studies on RS outside of well-equipped sleep laboratories.

Trait Interindividual Differences in the Magnitude of Subjective Sleepiness from Sleep Inertia.

In shift work settings and on-call operations, workers may be at risk of sleep inertia when called to action immediately after awakening from sleep. However, individuals may differ substantially in their susceptibility to sleep inertia. We investigated this using data from a laboratory study in which 20 healthy young adults were each exposed to 36 h of total sleep deprivation, preceded by a baseline sleep period and followed by a recovery sleep period, on three separate occasions. In the week prior to each laboratory session and on the corresponding baseline night in the laboratory, participants either extended their sleep period to 12 h/day or restricted it to 6 h/day. During periods of wakefulness in the laboratory, starting right after scheduled awakening, participants completed neurobehavioral tests every 2 h. Testing included the Karolinska Sleepiness Scale to measure subjective sleepiness, for which the data were analyzed with nonlinear mixed-effects regression to quantify sleep inertia. This revealed considerable interindividual differences in the magnitude of sleep inertia, which were highly stable within individuals after both baseline and recovery sleep periods, regardless of study condition. Our results demonstrate that interindividual differences in subjective sleepiness due to sleep inertia are substantial and constitute a trait.

Bone turnover marker responses to sleep restriction and weekend recovery sleep.

BACKGROUND: Prior data demonstrated three weeks of sleep restriction and concurrent circadian disruption uncoupled bone turnover markers (BTMs), indicating decreased bone formation and no change or increased bone resorption. The effect of insufficient sleep with or without ad libitum weekend recovery sleep on BTMs is unknown. METHODS: BTMs were measured in stored serum from 20 healthy adults randomized to one of three study groups consisting of a control group (N = 3 men; 9 h/night) or one of two nocturnal sleep restriction groups in an inpatient laboratory environment. One Sleep Restriction group ("SR"; N = 9; 4 women) had 5 h sleep opportunity per night for nine nights. The other sleep restriction group had an opportunity for ad libitum Weekend Recovery sleep ("WR"; N = 8; 4 women) after four nights of 5 h sleep opportunity per night. Food intake was energy balanced at baseline and ad libitum thereafter. Fasted morning BTM levels and hourly 24 h melatonin levels were obtained on study days 3 (baseline), 5 (after 1 night of sleep restriction for WR and SR), and 11 (after a sleep restricted workweek with weekend recovery sleep in WR or 7 nights of sleep restriction in SR). Linear mixed-effects modeling was used to examine the effect of study duration (e.g., change over time), study condition, age, and sex on BTMs. Pearson correlations were used to determine associations between changes in BTMs and changes in weight and morning circadian misalignment (i.e., duration of high melatonin levels after wake time). RESULTS: There was no significant difference between the three study groups in change over time (p ≥ 0.4 for interaction between assigned group and time for all BTMs), adjusted for age and sex. There was no significant change in N-terminal propeptide of procollagen type I (P1NP), osteocalcin, or C-telopeptide of type I collagen (CTX) from baseline to day 11 (all p ≥ 0.3). In women <25 years old, there was a non-significant decline in P1NP from day 3 to day 5 (= -15.74 ± 7.80 ng/mL; p = 0.06). Change in weight and morning circadian misalignment from baseline to day 11 were correlated with statistically non-significant changes in BTMs (all p ≤ 0.05). CONCLUSION: In this small secondary analysis, we showed that nine nights of prescribed sleep restriction with or without weekend recovery sleep and ad libitum food intake did not alter BTMs. It is possible that age, sex, weight change and morning circadian misalignment modify the effects of sleep restriction on bone metabolism.