Sleep Restriction Period Research Articles

Acute and chronic sleep restriction differentially modify maternal behavior and milk macronutrient composition in the postpartum rat

BackgroundsSleep restriction is considered a stressful condition itself, causing a wide variety of physiological alterations, from cognitive and hormonal to immunological status. In addition, it is established that stress in mother rats can modify milk ejection, milk composition, and maternal care of the pups. Also, sleep disturbances during the early stages of motherhood are a common feature of all studied species. In this context, while the impacts of sleep disruption in non-lactating animals were extensively investigated, its repercussions during the initial phases of motherhood have been poorly explored. Therefore, we wonder if maternal behavior, milk ejection and its macronutrient composition would be disrupted when mother rats are subjected to an additional acute or chronic sleep restriction to the already existing sleep disturbances. MethodsLactating rats were implanted with unilateral electrodes for polysomnographic recordings and for deep brain electrical stimulation into mesopontine waking-promoting area (for sleep deprivation). During the early postpartum period (postpartum day 5–9), mother rats were randomly assigned into one of three groups: chronic sleep restriction group (CSR; 6 h of sleep deprivation/day for five consecutive days), acute sleep restriction group (ASR; 6 h of sleep deprivation only for one day), or undisturbed group (control group). Active maternal behaviors (retrievals of the pups into the nest, mouthing, lickings [corporal and anogenital] and sniffing the pups) and passive maternal behaviors (kyphotic and supine nursing postures) were evaluated during a 30 min period without sleep restriction immediately after the sleep restriction or control period. The litter weight gain was assessed every day, and on the last experimental session mothers were milked for posterior macronutrients analysis (protein, carbohydrates and fat). ResultsWhen compared to control group, CSR decreased the amount of milk ejected in the middle days of the sleep restriction period, while ASR did not affect this parameter. Moreover, ASR reduced milk protein content compared to control and CSR groups. Finally, compared to the control group, CSR reduced active maternal behaviors towards the end of the treatment days. ConclusionsWe demonstrated that not only acute but also chronic sleep restriction impacts on the postpartum period, each one affecting different aspects of maternal behavior and lactation. Our results suggest the existence of a homeostatic recovery mechanism in breastfeeding during CSR, possibly ensuring the survival of the litter, while the decline in active maternal behaviors appears to be cumulative.

Long-term influence of sleep/wake history on the dynamic neurobehavioural response to sustained sleep restriction.

Chronic sleep restriction, common in today's 24/7 society, causes cumulative neurobehavioural impairment, but the dynamics of the build-up and dissipation of this impairment have not been fully elucidated. We addressed this knowledge gap in a laboratory study involving two, 5-day periods of sleep restriction to 4 hr per day, separated by a 1-day dose-response intervention sleep opportunity. We measured sleep physiological and waking neurobehavioural responses in 70 healthy adults, each randomized to one of seven dose-response intervention sleep doses ranging from 0 to 12 hr, or a non-sleep-restricted control group. As anticipated, sleep physiological markers showed homeostatic dynamics throughout the study, and waking neurobehavioural impairment accumulated across the two sleep restriction periods. Unexpectedly, there was only a slight and short-lived effect of the 1-day dose-response intervention sleep opportunity. Whether the dose-response intervention sleep opportunity involved extension, further restriction or total deprivation of sleep, neurobehavioural functioning during the subsequent second sleep restriction period was dominated by prior sleep-wake history. Our findings revealed a profound and enduring influence of long-term sleep-wake history as a fundamental aspect of the dynamic regulation of the neurobehavioural response to sleep loss.

Assessing the impact of sleep restriction on the attention and executive functions of medical students: a prospective cohort study.

To compare the performance of medical students regarding attention and executive functions during a period of sleep restriction (insufficient sleep; period of classes) and a period of free sleep (sufficient sleep; vacation period). Sleep deprivation is associated with poor academic outcomes. Few studies have assessed the cognitive changes associated with sleep deprivation due to insufficient sleep syndrome in students and how they occur in real-life situations. This was a prospective cohort study. Medical students were assessed at two moments (class and vacation). The interval between assessments was 30days. The Pittsburgh Sleep Quality Index, the Consensus Sleep Diary, the Montreal Cognitive Assessment, the Psychomotor Vigilance Test (PVT) and the Wisconsin Sorting Cards Test were used. Forty-one students were assessed, 49% were female, with a median age of 21 (20; 23) years. There was a lower number of hours slept (5.75 (5.4; 7.0) vs 7.33 (6.0; 8.0) hours; p = 0.037), and a significantly poorer performance in the PVT (mean reaction time, p = 0.005; Minor lapses, p = 0.009) during the period of classes when compared to the vacation period. There was a correlation between the variation in hours of sleep of the two assessments and a variation in minor lapses in the two assessments (Ro: -0.395; p = 0.011; Spearman's correlation). Students had fewer hours of sleep and more reduced attention during the period of classes than during the vacation period. This decrease in sleeping hours was correlated with more impaired attention.

Impact of sleep restriction in B-1 cells activation and differentiation

B-1 lymphocytes are a subtype of B cells with functional and phenotypic features that differ from conventional B lymphocytes. These cells are mainly located in mice’s pleural and peritoneal cavities and express unconventional B cell surface markers. B-1 cells participate in immunity by producing antibodies, cytokines, and chemokines and physically interacting with other immune cells. In addition, B-1 cells can differentiate into mononuclear phagocyte-like cells and phagocytize several pathogens. However, the activation and differentiation of B-1 cells are not entirely understood. It is known that several factors can influence B-1 cells, such as pathogens components and the immune response. This work aimed to evaluate the influence of chronic stress on B-1 cell activation and differentiation into phagocytes. The experimental sleep restriction was used as a stress model since the sleep alteration alters several immune cells' functions. Thus, mice were submitted to sleep restriction for 21 consecutive days, and the activation and differentiation of B-1 cells were analyzed. Our results demonstrated that B-1 cells initiated the differentiation process into mononuclear phagocytes after the period of sleep restriction. In addition, we detected a significant decrease in lymphoid lineage commitment factors (EBF, E2A, Blnk) (*P < 0.05) and an increase in the G-CSFR gene (related to the myeloid lineage commitment factor) (****P < 0.0001), as compared to control mice no submitted to sleep restriction. An increase in the co-stimulatory molecules CD80 and CD86 (**P < 0.01 and *P < 0.05, respectively) and a higher production of nitric oxide (NO) (*P < 0.05) and reactive oxygen species (ROS) (*P < 0.05) were also observed in B-1 cells from mice submitted to sleep restriction. Nevertheless, B-1 cells from sleep-restricted mice showed a significant reduction in the Toll-like receptors (TLR)-2, −6, and −9, and interleukine-10 (IL-10) cytokine expression (***P < 0.001) as compared to control. Sleep-restricted mice intraperitoneally infected withL. amazonensispromastigotes showed a reduction in the average internalized parasites (*P < 0.05) by B-1 cells. These findings suggest that sleep restriction interferes with B-1 lymphocyte activation and differentiation. In addition, b-1 cells assumed a more myeloid profile but with a lower phagocytic capacity in this stress condition.

The Effect of Sleep Restriction, With or Without Exercise, on Skeletal Muscle Transcriptomic Profiles in Healthy Young Males.

BackgroundInadequate sleep is associated with many detrimental health effects, including increased risk of developing insulin resistance and type 2 diabetes. These effects have been associated with changes to the skeletal muscle transcriptome, although this has not been characterised in response to a period of sleep restriction. Exercise induces a beneficial transcriptional response within skeletal muscle that may counteract some of the negative effects associated with sleep restriction. We hypothesised that sleep restriction would down-regulate transcriptional pathways associated with glucose metabolism, but that performing exercise would mitigate these effects.Methods20 healthy young males were allocated to one of three experimental groups: a Normal Sleep (NS) group (8 h time in bed per night (TIB), for five nights (11 pm – 7 am)), a Sleep Restriction (SR) group (4 h TIB, for five nights (3 am – 7 am)), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB, for five nights (3 am – 7 am) and three high-intensity interval exercise (HIIE) sessions (performed at 10 am)). RNA sequencing was performed on muscle samples collected pre- and post-intervention. Our data was then compared to skeletal muscle transcriptomic data previously reported following sleep deprivation (24 h without sleep).ResultsGene set enrichment analysis (GSEA) indicated there was an increased enrichment of inflammatory and immune response related pathways in the SR group post-intervention. However, in the SR+EX group the direction of enrichment in these same pathways occurred in the opposite directions. Despite this, there were no significant changes at the individual gene level from pre- to post-intervention. A set of genes previously shown to be decreased with sleep deprivation was also decreased in the SR group, but increased in the SR+EX group.ConclusionThe alterations to inflammatory and immune related pathways in skeletal muscle, following five nights of sleep restriction, provide insight regarding the transcriptional changes that underpin the detrimental effects associated with sleep loss. Performing three sessions of HIIE during sleep restriction attenuated some of these transcriptional changes. Overall, the transcriptional alterations observed with a moderate period of sleep restriction were less evident than previously reported changes following a period of sleep deprivation.

Abstract P042: Impact Of Mild Sleep Restriction On Lipid Profile: Influence Of Inflammatory Markers

Introduction: Short sleep duration is associated with an increased risk of cardiovascular disease (CVD). Dyslipidemia is one of the main risk factors for CVD but the influence of sleep duration on this risk factor is, for the moment, inconclusive. Objective: The goal of this study is to test the impact of mild sleep restriction (SR), sustained for 6 wk, on the lipid profile of participants at risk of CVD. Methods: A randomized crossover study was carried out in 64 adults (68% women) aged 20-73 y with a BMI between 19.2-29.9 kg/m 2 . Participants habitually slept ≥7 h/night, verified by 2 wk of wrist actigraphy during screening. Participants underwent 2 sleep conditions of 6 wk each: AS and SR (a reduction of 1.5 h/night relative to AS). Lipid profile was determined from fasted blood samples collected at baseline, wk 3, wk 4 and wk 6 of each phase. In a subset of 34 women, we analyzed inflammatory markers: interleukin- 6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor α (TNF-α). Linear mixed models were used to test the influence of sleep condition on change in lipid profile over time. We further performed Pearson correlations between change in inflammatory markers over each of the the 6-wk phases with lipids measures assessed at endpoint of the respective condition. Results: No effect of sleep condition on change in total cholesterol and triglyceride concentrations (β=0.40±1.80; p=0.83; β=0.43±2.38; p=0.86, respectively) was observed. LDL-C decreased over time, and this was more pronounced in SR compared to AS (β=-3.75±1.59; p=0.019). Similarly, HDL-C decreased over time, and this was less pronounced in SR compared to AS (β=1.78±0.64; p=0.006). Findings were similar in sub-group analyses by sex and menopausal status. Correlation analyses revealed trends for inverse correlations between IL-6 and total cholesterol (r=-0.299; p= 0.096), and LDL-C (r=-0.344; p=0.054) during SR. Also, a decrease in CRP during SR was correlated with higher HDL-C levels at endpoint (r=-0.545; p= 0.002). Conversely, in AS, we only detected a positive correlation between change in CRP and LDL-C at endpoint (r=0.354; p= 0.037). Conclusions: Six weeks of mild sleep restriction does not adversely impact lipid profile. However, this may be a maladaptive response to increases in inflammatory markers after a period of mild sleep restriction. Further studies are needed to confirm these findings.

112 Chronic sleep restriction disrupts slow-wave sleep homeostatic regulation and damages monoaminergic structures in the rat brain

Abstract Introduction The neurophysiological mechanisms underlying long-term neurological and cognitive disorders associated with chronic sleep restriction (CSR) are not fully understood. Here we evaluated how the sleep-wake cycle changes during and after a period of sleep restriction in rats, and whether CSR results in neurodegeneration in monoaminergic brain structures. Methods For CSR, 7-8-month-old Wistar rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 5 days on the orbital shaker. Telemetric sleep recordings were made before, during, and after CSR. Neurodegeneration in brain monoaminergic structures was assessed immunohistochemically. Results During SD, wakefulness comprised 85% of the total registration time; the remaining time was represented by drowsiness with low EEG delta power. Rapid eye movement sleep (REMS) was absent. During CSR, slow-wave sleep (SWS) and REMS were reduced by 62% and 57%. Total SWS time during SO periods increased on the first CSR day, but decreased to the baseline by the fifth CSR day. SWS EEG delta power (a measure of sleep intensity) decreased gradually from the first to the fifth CSR day. REMS total time remained elevated during all SO periods. During the first recovery day after CSR, SWS did not change, but REMS increased by 30%. No changes in total sleep time were found on the second recovery day but sleep intensity was decreased. In 14 days after CSR, all sleep parameters returned to the baseline. We revealed a loss of 24% of noradrenergic locus coeruleus neurons, 29% and 17% of dopaminergic neurons in the substantia nigra, the ventral tegmental area as well as in their striatal terminals. Conclusion We consider CSR as a damaging factor leading to a gradual suppression of homeostatic mechanisms governing sleep recovery. CSR can provoke neurodegeneration in monoaminergic structures involved in the regulation of emotional behavior, sleep, and autonomic functions. Support (if any) Ministry of Science and Higher Education of the Russian Federation grant (No. 075-15-2020-916 dated November 13, 2020) for the establishment and development of the Pavlovsky Center “Integrative Physiology for Medicine, High-Tech Healthcare and Stress Resilience Technologies”.

Modeling of chronic sleep restriction for translational studies

To develop of a chronic sleep restriction model in rats by repeated sleep deprivation using an orbital shaker and to determine whether this model leads to disturbances in sleep homeostatic mechanisms. Male Wistar rats (7-8 months old) underwent sleep restriction for five consecutive days: 3 h of sleep deprivation and 1 h of sleep opportunity repeating throughout each day. Polysomnograms were recorded telemetrically throughout the day before sleep restriction (baseline), on the 1st, 3rd, 5th day of sleep restriction and 2 days after the end of sleep restriction (recovery period). During the period of sleep restriction, the total amount of slow-wave sleep (SWS) and rapid eye movement (REM) sleep decreased by 61% and 55%, respectively, compared to baseline. On the first day of recovery, amount of SWS increased mainly in the dark (active) phase of the day, while REM sleep increased in both light and dark phases; there was no marked rebound of daily SWS amount, while REM sleep increased by 30% from baseline. On the first day of recovery, an elevation of EEG beta and sigma power in sleep states was observed mainly in the light phase of the day. The loss of deep SWS throughout the sleep restriction period increased from 50% on 1st day to 75% on 5th day. The level of deep SWS remained below the baseline by 15-20% on the two subsequent days of recovery. The findings suggest that homeostatic mechanisms of SWS are persistently impaired after 5-day chronic sleep restriction. Besides, a decline of wakefulness accompanied by an increase of SWS in the active phase of the recovery period indicates a disruption in circadian rhythm. The proposed model leads to the disruption of sleep homeostatic mechanisms, which, in turn, impede compensation of SWS loss caused by chronic insufficient sleep.

Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms

ObjectiveSleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Because exercise improves glucose tolerance and mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep. MethodsTo minimize between-group differences of baseline characteristics, 24 healthy young males were allocated into one of the three experimental groups: a Normal Sleep (NS) group (8 h time in bed (TIB) per night, for five nights), a Sleep Restriction (SR) group (4 h TIB per night, for five nights), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB per night, for five nights and three high-intensity interval exercise (HIIE) sessions). Glucose tolerance, mitochondrial respiratory function, sarcoplasmic protein synthesis (SarcPS), and diurnal measures of peripheral skin temperature were assessed pre- and post-intervention. ResultsWe report that the SR group had reduced glucose tolerance post-intervention (mean change ± SD, P value, SR glucose AUC: 149 ± 115 A.U., P = 0.002), which was also associated with reductions in mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O2.s−1.mg−1, P = 0.001), a lower rate of SarcPS (FSR%/day SR: 1.11 ± 0.25%, P < 0.001), and reduced amplitude of diurnal rhythms. These effects were not observed when incorporating three sessions of HIIE during this period (SR+EX: glucose AUC 67 ± 57, P = 0.239, mitochondrial respiratory function: 0.6 ± 11.8 pmol O2.s−1.mg−1, P = 0.997, and SarcPS (FSR%/day): 1.77 ± 0.22%, P = 0.971). ConclusionsA five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance. We provide novel data demonstrating that these same detrimental effects are not observed when HIIE is performed during the period of sleep restriction. These data therefore provide evidence in support of the use of HIIE as an intervention to mitigate the detrimental physiological effects of sleep loss.

0290 Caffeine Efficacy Varies as a Function of Individual Vulnerability to Sleep Restriction

Abstract Introduction We previously showed that relative to placebo (PL), caffeine (CAF) significantly improved psychomotor vigilance task (PVT) reaction time (RT) during the first 2 days (ACUTE phase), but not during the last 3 days (CHRONIC phase) of sleep restriction (SR) (Doty et al., 2018). However, while individual differences in RT during sleep deprivation have been previously documented, the interaction between CAF and individual vulnerability (VUL) during SR on PVT-RT is not well-known. Methods For statistical analysis, we computed trends in RTs (SLOPE) as follows; baseline, 1st and the 2nd SR days to represent ACUTE phase, and the 2nd, 3rd, 4th and 5th SR days for CHRONIC phase. Participants in each GROUP (CAF or PL) were split into 2 for VUL; high vulnerable (HIGHVUL), and low vulnerable (LOWVUL), depending on the number of minor lapses made during SR. We used 3-way ANOVA model with independent measures (2x2x2; GROUPxVULxPHASE) and a dependent measure (SLOPE). Results We found a main effect of VUL (F=12.69, p&amp;lt;0.001), an interaction between GROUP and PHASE (F=12.95, p&amp;lt;0.001) and an interaction between VUL, GROUP, and PHASE (F=8.04, p&amp;lt;.01). Resolving this 3-way interaction for ACUTE revealed a main effect of VUL (F=9.34, p&amp;lt;.005), a main effect of GROUP (F=5.96, p&amp;lt;.05). Although the interaction between VUL and GROUP failed to achieve significance (F=3.46, p=0.073), only for the LOWVUL, PL participants were significantly higher than CAF, p&amp;lt;0.01)). Resolving the 3-way interaction for CHRONIC revealed a main effect of GROUP (F=8.95, p&amp;lt;0.01), no significant of VUL (F=3.36, p=0.077) and an interaction between VUL and GROUP (F=6.11, p&amp;lt;0.05). Resolving this interaction showed that only for the LOWVUL participants in CAF, the slope was higher than PL (p&amp;lt;.001). Conclusion Performance enhancing effects of caffeine were only evident for low vulnerability participants, and for only the first few days of sleep restriction. At the tested dose level, caffeine did not result in meaningful improvements in performance in highly vulnerable participants during the sleep restriction period. Support Department of Defense Military Operational Medicine Research Program (MOMRP)

Effects of sleep restriction on subjective and physiological variables in middle-aged Korean adults: an intervention study

BackgroundAdequate sleep is crucial for normal functioning. However, most people, including middle-aged adults of reproductive age, show a marked reduction in their sleep duration. Thus, sleep is a major issue that should be addressed in health management. We investigated the effects of short-term sleep restriction on subjective parameters (sleepiness, stress, fatigue) and physiological parameters (cortisol, thyrotropin [TSH], thyroxine [T4], triiodothyronine [T3], C-reactive protein [CRP]) in middle-aged adults, the recovery of these parameters after rest, and the associations between parameters. MethodsA total of 118 healthy adults (59 men, 59 women), aged 35–44 years, and without sleep problems, were enrolled. Participants underwent a 4-h sleep restriction per day for 3 day at a hospital, and then returned to their daily lives to take four days of rest. A questionnaire and blood test were administered before and after sleep restriction, and after the recovery period, to assess subjective and physiological parameters. ResultsAfter sleep restriction, sleepiness, fatigue, and stress significantly increased compared to baseline. Cortisol and TSH were elevated after sleep restriction, while T4, T3, and CRP were reduced compared to baseline. After the recovery phase, all parameters were restored to levels similar to baseline levels. Changes in each parameter were mutually associated; fatigue and sleepiness had the strongest association. ConclusionOur results suggest that even a short period of sleep restriction can have an adverse impact on psychological and physiological stress parameters in middle-aged adults, and that adequate rest and sleep are needed to restore them to normal levels.

Long-duration spaceflight adversely affects post-landing operator proficiency

Performance of astronaut pilots during space shuttle landing was degraded after a few weeks of microgravity exposure, and longer-term exposure has the potential to impact operator proficiency during critical landing and post-landing operations for exploration-class missions. Full-motion simulations of operationally-relevant tasks were utilized to assess the impact of long-duration spaceflight on operator proficiency in a group of 8 astronauts assigned to the International Space Station, as well as a battery of cognitive/sensorimotor tests to determine the underlying cause of any post-flight performance decrements. A ground control group (N = 12) and a sleep restriction cohort (N = 9) were also tested to control for non-spaceflight factors such as lack of practice between pre- and post-flight testing and fatigue. On the day of return after 6 months aboard the space station, astronauts exhibited significant deficits in manual dexterity, dual-tasking and motion perception, and a striking degradation in the ability to operate a vehicle. These deficits were not primarily due to fatigue; performance on the same tasks was unaffected after a 30-h period of sleep restriction. Astronauts experienced a general post-flight malaise in motor function and motion perception, and a lack of cognitive reserve apparent only when faced with dual tasks, which had recovered to baseline by four days after landing.

Cellular and Molecular Mechanisms of REM Sleep Homeostatic Drive: A Plausible Component for Behavioral Plasticity.

Homeostatic regulation of REM sleep drive, as measured by an increase in the number of REM sleep transitions, plays a key role in neuronal and behavioral plasticity (i.e., learning and memory). Deficits in REM sleep homeostatic drive (RSHD) are implicated in the development of many neuropsychiatric disorders. Yet, the cellular and molecular mechanisms underlying this RSHD remain to be incomplete. To further our understanding of this mechanism, the current study was performed on freely moving rats to test a hypothesis that a positive interaction between extracellular-signal-regulated kinase 1 and 2 (ERK1/2) activity and brain-derived neurotrophic factor (BDNF) signaling in the pedunculopontine tegmentum (PPT) is a causal factor for the development of RSHD. Behavioral results of this study demonstrated that a short period (<90 min) of selective REM sleep restriction (RSR) exhibited a strong RSHD. Molecular analyses revealed that this increased RSHD increased phosphorylation and activation of ERK1/2 and BDNF expression in the PPT. Additionally, pharmacological results demonstrated that the application of the ERK1/2 activation inhibitor U0126 into the PPT prevented RSHD and suppressed BDNF expression in the PPT. These results, for the first time, suggest that the positive interaction between ERK1/2 and BDNF in the PPT is a casual factor for the development of RSHD. These findings provide a novel direction in understanding how RSHD-associated specific molecular changes can facilitate neuronal plasticity and memory processing.

Impact of sleep restriction on local immune response and skin barrier restoration with and without "multinutrient" nutrition intervention.

Systemic immune function is impaired by sleep restriction. However, the impact of sleep restriction on local immune responses and to what extent any impairment can be mitigated by nutritional supplementation is unknown. We assessed the effect of 72-h sleep restriction (2-h nightly sleep) on local immune function and skin barrier restoration of an experimental wound, and determined the influence of habitual protein intake (1.5 g·kg-1·day-1) supplemented with arginine, glutamine, zinc sulfate, vitamin C, vitamin D3, and omega-3 fatty acids compared with lower protein intake (0.8 g·kg-1·day-1) without supplemental nutrients on these outcomes. Wounds were created in healthy adults by removing the top layer of less than or equal to eight forearm blisters induced via suction, after adequate sleep (AS) or 48 h of a 72-h sleep restriction period (SR; 2-h nightly sleep). A subset of participants undergoing sleep restriction received supplemental nutrients during and after sleep restriction (SR+). Wound fluid was serially sampled 48 h postblistering to assess local cytokine responses. The IL-8 response of wound fluid was higher for AS compared with SR [area-under-the-curve (log10), 5.1 ± 0.2 and 4.9 ± 0.2 pg/ml, respectively; P = 0.03]; and both IL-6 and IL-8 concentrations were higher for SR+ compared with SR ( P < 0.0001), suggestive of a potentially enhanced early wound healing response. Skin barrier recovery was shorter for AS (4.2 ± 0.9 days) compared with SR (5.0 ± 0.9 days) ( P = 0.02) but did not differ between SR and SR+ ( P = 0.18). Relatively modest sleep disruption delays wound healing. Supplemental nutrition may mitigate some decrements in local immune responses, without detectable effects on wound healing rate. NEW & NOTEWORTHY The data herein characterizes immune function in response to sleep restriction in healthy volunteers with and without nutrition supplementation. We used a unique skin wound model to show that sleep restriction delays skin barrier recovery, and nutrition supplementation attenuates decrements in local immune responses produced by sleep restriction. These findings support the beneficial effects of adequate sleep on immune function. Additional studies are necessary to characterize practical implications for populations where sleep restriction is unavoidable.

Supplemental Protein and Multi‐Nutrient Beverage Improve Immune Response at Experimental Wound Site during 72‐h Sleep Restriction

The suctionblister model creates experimental skin wounds and permits evaluation of local immune response and wound healing. Sleep restriction negatively affects immune function at the wound site and delays skin barrier restoration; however, the impact of nutrition intervention on local immune response and skin barrier restoration of experimental wounds concomitant with sleep restriction is not known. This study assessed the effect of a high protein diet and multi‐nutrient beverage on cytokine concentrations of wound exudate and skin barrier restoration of experimental wounds in participants who underwent 72‐h of sleep restriction. The experimental group (EXP), compared to the control group (CON), consumed additional protein (~1.5 versus 0.8 g/kg bodyweight/d, respectively) and a multi‐nutrient beverage administered twice daily during the 3‐d sleep restriction period and five days afterwards. The beverage contained L‐arginine (20 g· d−1), L‐glutamine (30 g· d−1), omega‐3 fatty acids (1 g· d−1), zinc sulfate (24 mg· d−1), vitamin D3 (800 IU· d−1) and vitamin C (400 mg· d−1). On the second day of a 3‐d sleep restriction period (monitored in laboratory with ~2‐h sleep per night), up to 8 blisters (~30 mm2) were induced via suction on participant's forearm, and top layer of blisters was removed to reveal wounds. Wound exudate was sampled at 4, 7, 24 and 48‐h post blistering to assess cytokine response via multiplex assay and area‐under‐the‐curve with respect to baseline cytokine concentrations (AUCi) was calculated. Skin barrier restoration was assessed by transepidermal water loss, measured daily until values were within 90% of unbroken skin. Data was analyzed with mixed models analysis of variance and independent samples t‐tests. Twenty participants in each group (CON, 21 ± 4 years [mean±SD]and EXP, 21 ± 3 years) completed the study. Sleep duration in the 5‐days leading up to either the sleep restriction period was not different between CON and EXP (7.71 ± 0.67 hrs· d−1and 7.64 ± 0.5 hrs· d−1, respectively, p = 0.71). Wound exudate concentrations of IL6, IL8, MIP1α, MIP1β and TNFα significantly increased over time for both groups (p&lt;0.05);and, concentrations of IL6, IL8 and MIP1β were higher for (EXP) compared to (CON)at various time‐points (p &lt; 0.05). The AUCi was higher for (EXP) compared to (CON) with regard to IL6 (log10,5.7 ±0.3 and 5.3 ± 0.3, respectively, p &lt; 0.0001) and IL8 (log10,6.3 ±0.5 and 5.6 ± 0.1, respectively, p &lt; 0.0001). Skin barrier restoration was not significantly different between (CON) and (EXP): 5.0 ± 0.9 days and 4.6± 0.8 days (P = 0.18). These data indicate that local immune function is positively impacted by additional protein and a multi‐nutrient beverage during and after 72‐h sleep restriction, but no between‐group differences in skin barrier restoration were detected. A cross‐over study to confirm the findings is warranted.DisclaimerThe views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government.Support or Funding InformationFunded by the Medical Research and Materiel Command, Aberdeen Proving Ground, Maryland.

Cardiac autonomic control and complexity during sleep are preserved after chronic sleep restriction in healthy subjects.

Acute sleep deprivation (SD) alters cardiovascular autonomic control (CAC) and is associated with an increased risk of cardiovascular disorders. However, the effects of partial SD on CAC are unclear. Thus, we aimed to investigate the effects of partial SD on CAC during sleep. We randomized seventeen healthy subjects to a restriction group (RES, n = 8, subjects slept two‐thirds of normal sleep time based on individual habitual sleep duration for 8 days and 8 nights) or a Control group (CON, n = 9, subjects were allowed to sleep their usual sleep time). Attended polysomnographic (PSG) studies were performed every night; a subset of them was selected for the analysis at baseline (day 3‐D3), the first night after sleep restriction (day 5‐D5), at the end of sleep restriction period (day 11‐D11), and at the end of recovery phase (day 14‐D14). We extracted electrocardiogram (ECG) and respiration from the PSG and divided into wakefulness (W), nonrapid eye movements (REM) sleep (N2 and N3) and REM sleep. CAC was evaluated by means of linear spectral analysis, nonlinear symbolic analysis and complexity indexes. In both RES and CON groups, sympathetic modulation decreased and parasympathetic modulation increased during N2 and N3 compared to W and REM at D3, D5, D11, D14. Complexity analysis revealed a reduction in complexity during REM compared to NREM sleep in both DEP and CON. After 8 days of moderate SD, cardiac autonomic dynamics, characterized by decreased sympathetic, and increased parasympathetic modulation, and higher cardiac complexity during NREM sleep, compared to W and REM, are preserved.

Neurobehavioral Impact of Successive Cycles of Sleep Restriction With and Without Naps in Adolescents.

Study Objectives:To characterize adolescents’ neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction.Methods:Fifty-seven healthy adolescents (aged 15–19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00–06:00) and recovery (9-hr TIB for two nights per cycle; 23:00–08:00) intended to simulate the weekday sleep loss and weekend attempt to “catch up” on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day.Results:Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study.Conclusions:Adolescents’ neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend “catch-up sleep,” even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night.

Sleep restriction can attenuate prioritization benefits on declarative memory consolidation.

SummaryAs chronic sleep restriction is a widespread problem among adolescents, the present study investigated the effects of a 1‐week sleep restriction (SR) versus control period on the consolidation of long‐term memory for prose passages. We also determined whether the benefit of prioritization on memory is modulated by adequate sleep occurring during consolidation. Fifty‐six healthy adolescents (25 male, aged 15–19 years) were instructed to remember a prose passage in which half of the content was highlighted (prioritized), and were told that they would receive an additional bonus for remembering highlighted content. Following an initial free recall test, participants underwent a 7‐night period in which they received either a 5‐h (SR) or 9‐h (control) nightly sleep opportunity, monitored by polysomnography on selected nights. Free recall of the passage was tested at the end of the sleep manipulation period (1 week after encoding), and again 6 weeks after encoding. Recall of highlighted content was superior to that of non‐highlighted content at all three time‐points (initial, 1 week, 6 weeks). This beneficial effect of prioritization on memory was stronger 1 week relative to a few minutes after encoding for the control, but not the SR group. N3 duration was similar in the control and SR groups. Overall, the present study shows that the benefits of prioritization on memory are enhanced over time, requiring time and sleep to unfold fully. Partial sleep deprivation (i.e. 5‐h nocturnal sleep opportunity) may attenuate such benefits, but this may be offset by preservation of N3 sleep duration.

The effects of sleep restriction and altered sleep timing on energy intake and energy expenditure

Experimental evidence suggests that sleep restriction increases energy intake (EI) and may alter energy expenditure (EE). However, it is unknown whether the timing of a sleep restriction period impacts EI and EE the following day. Hence, we examined the effects of sleep restriction with an advanced wake-time or delayed bedtime on next day EI and EE. Twelve men and 6 women (age: 23±4years, body fat: 18.8±10.1%) participated in 3 randomized crossover sessions: control (habitual bed- and wake-times), 50% sleep restriction with an advanced wake-time and 50% sleep restriction with a delayed bedtime. Outcome variables included sleep architecture (polysomnography), EI (food menu), total EE and activity times (accelerometry). Carbohydrate intake was greater on day 2 in the delayed bedtime vs. control session (1386±513 vs. 1579±571kcal; P=0.03). Relative moderate-intensity physical activity (PA) time was greater in the delayed bedtime session vs. control and advanced wake-time sessions on day 1 (26.6±19.9 vs. 16.1±10.6 and 17.5±11.8%; P=0.01), whereas vigorous-intensity PA time was greater following advanced wake-time vs. delayed bedtime on day 1 (2.7±3.0 vs. 1.3±2.4%; P=0.004). Greater stage 1 sleep (β=110kcal, 95% CI for β=42 to 177kcal; P=0.004), and a trend for lower REM sleep (β=−20kcal, 95% CI for β=−41 to 2kcal; P=0.07), durations were associated with greater EI between sleep restriction sessions. These findings suggest that the timing of a sleep restriction period impacts energy balance parameters. Additional studies are needed to corroborate these findings, given the increasing prevalence of shift workers and incidences of sleep disorders and voluntary sleep restriction.

Restriction of rapid eye movement sleep during adolescence increases energy gain and metabolic efficiency in young adult rats.

What is the central question of this study? Sleep curtailment in infancy and adolescence may lead to long-term risk for obesity, but the mechanisms involved have not yet been determined. This study examined the immediate and long-term metabolic effects produced by sleep restriction in young rats. What is the main finding and its importance? Prolonged sleep restriction reduced weight gain (body fat stores) in young animals. After prolonged recovery, sleep-restricted rats tended to save more energy and to store more fat, possibly owing to increased gross food efficiency. This could be the first step to understand this association. Sleep curtailment is associated with obesity and metabolic changes in adults and children. The aim of the present study was to evaluate the immediate and long-term metabolic alterations produced by sleep restriction in pubertal male rats. Male Wistar rats (28 days old) were allocated to a control (CTL) group or a sleep-restricted (SR) group. This was accomplished by the single platform technique for 18 h per day for 21 days. These groups were subdivided into the following four time points for assessment: sleep restriction and 1, 2 and 4 months of recovery. Body weight and food intake were monitored throughout the experiment. At the end of each time period, blood was collected for metabolic profiling, and the carcasses were processed for measurement of body composition and energy balance. During the period of sleep restriction, SR animals consumed less food in the home cages. This group also displayed lower body weight, body fat, triglycerides and glucose levels than CTL rats. At the end of the first month of recovery, despite eating as much as CTL rats, SR animals showed greater energy and body weight gain, increased gross food efficiency and decreased energy expenditure. At the end of the second and fourth months of recovery, the groups were no longer different, except for energy gain and gross food efficiency, which remained higher in SR animals. In conclusion, sleep restriction affected weight gain of young animals, owing to reduction of fat stores. Two months were sufficient to recover this deficit and to reveal that SR rats tended to save more energy and to store more fat.