Sleep Restriction Group Research Articles

Effects of sleep restriction during pregnancy on the mother and fetuses in rats

The present study aimed to analyze the effects of sleep restriction (SR) during pregnancy in rats. The following three groups were studied: home cage (HC pregnant females remained in their home cage), Sham (females were placed in tanks similar to the SR group but with sawdust) and SR (females were submitted to the multiple platform method for 20h per day from gestational days (GD) 14 to 20). Plasma corticosterone after 6days of SR was not different among the groups. However, the relative adrenal weight was higher in the SR group compared with the HC group, which suggests possible stress impact. SR during pregnancy reduces the body weight of the female but no changes in liver glycogen, cholesterol and triglycerides, and muscle glycogen were detected. On GD 20, the fetuses of the females submitted to SR exhibited increased brain derived neurotrophic factor (BDNF) in the hippocampus, which indicates that sleep restriction of mothers during the final week of gestation may affect neuronal growth factors in a fetal brain structure, in which active neurogenesis occurs during the deprivation period. However, no changes in the total reactive oxygen species (ROS) in the cortex, hippocampus, or cerebellum of the fetuses were detected. SR females showed no major change in the maternal behavior, and the pups' preference for the mother's odor on postpartum day (PPD) 7 was not altered. On GD 20, the SR females exhibited increased plasma prolactin (PRL) and oxytocin (OT) compared with the HC and Sham groups. The negative outcomes of sleep restriction during delivery could be related, in part, to this hormonal imbalance. Sleep restriction during pregnancy induces different changes compared with the changes described in males and affects both the mother and offspring.

Efficacy of physical activity counseling plus sleep restriction therapy on the patients with chronic insomnia.

ObjectiveLack of physical activity (PA) is common in patients with chronic insomnia. Studies to increase PA and decrease sedentary behavior in those patients are limited. Therefore, we investigated the efficacy of “PA counseling combined with sleep restriction (SR) therapy (PASR)” vs only SR in the patients with chronic insomnia.MethodsSeventy-one outpatients were assigned to either PASR (n=35), consisting of four weekly PA counseling sessions based on 5A model (assess, advise, agree, assist, and arrange) + SR, or SR (n=36), consisting of four weekly SR. International Physical Activity Questionnaire (Chinese version) and pedometer-based daily steps were evaluated as the primary endpoints. Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep Diary were evaluated as the secondary endpoints.ResultsThe results showed that the patients in the PASR group gained more benefits than the SR group in terms of PA level and pedometer-based daily steps (all P<0.05). Better improvements of the study group were also shown in Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep efficiency (all P<0.05).ConclusionWe conclude that PA counseling based on 5A model combined with SR cannot only effectively increase the PA levels but also improve the sleep quality for patients with chronic insomnia.

Effect of Repeated Exposure to Sleep Restriction on Interleukin 6 Levels in Humans

Repeated exposures to sleep restriction with short in‐between periods of recovery sleep are increasingly common in society, in particular for individuals with irregular work schedules. Short periods of experimental sleep restriction have been shown to elevate inflammatory markers, such as interleukin 6 (IL‐6) which has been suggested to increase the risk for cardiometabolic diseases. However, the effect of repeated exposure to sleep restriction on IL‐6 is unknown. Forty‐three healthy participants (age 32+2 yrs; BMI 24+1 kg/m2; 21 men and 22 women) were randomized to a 22‐day study of repeated cycles of sleep restriction (4hr sleep/night for 3 nights followed by one recovery sleep, 4 cycles) or routine sleep (8hr sleep/night). Blood was sampled from fasting recumbent participants in the morning after awakening, during baseline, third day of each sleep restriction or control cycle, and following recovery sleep. Plasma concentrations of IL‐6 were measured using high sensitivity immunosorbent assay (R&amp;D Systems ELISA). The sleep restriction group showed a significant increase in IL‐6 levels during the first sleep restriction cycle, exceeding control levels by 30% (p&lt;0.05). These levels did not return to baseline in the remaining sleep restriction cycles when compared with the control group. IL‐6 levels return to baseline levels after recovery sleep. In conclusion, these findings suggest that repeated patterns of sleep restriction elevate circulating levels of IL‐6 which may contribute to the development of risk for cardiovascular and cardiometabolic diseases. Supported by NIH (HL‐106782).

Impairment of male reproductive function after sleep deprivation

To evaluate the influence of sleep loss on sexual behavior, hormone levels, sperm parameters, and testis-specific gene expression in male rats. Experimental research. Animal laboratory. Male adult Wistar-Hannover rats. Sexually experienced rats were subjected to paradoxic sleep deprivation (PSD) for 96hours or sleep restriction (SR) for 21days or kept in their home cage as control (CTRL). Sexual behavior, hormone levels, sperm parameters and expression of stress and nitric oxide-related genes were evaluated. PSD significantly decreased sexual behavior compared with the CTRL group, whereas SR had no effect. The PSD group had significantly lower testosterone levels than the CTRL group. Both PSD and SR groups had lower sperm viabilities than the CTRL group. The decrease in the number of live sperm compared with the CTRL group was larger in the PSD group than in the SR group. Regarding testicular gene expression, both PSD and SR led to an increase of iNOS and hydroxysteroid 11β-dehydrogenase 1 expressions compared with the CTRL group. These changes were more pronounced in the PSD group. A significant increase in endothelial nitric oxide synthase expression was observed in the PSD groups compared with the CTRL group. No changes were observed in dimethylarginine dimethylaminohydrolase 1 and casein kinase 2β-polypeptide expressions. Sleep loss can promote marked changes in the male reproductive system of rats, particularly affecting spermatic function in part by interfering in the testicular nitric oxide pathway.

Sleep restriction during simulated wildfire suppression: effect on physical task performance.

ObjectivesTo examine the effects of sleep restriction on firefighters’ physical task performance during simulated wildfire suppression.MethodsThirty-five firefighters were matched and randomly allocated to either a control condition (8-hour sleep opportunity, n = 18) or a sleep restricted condition (4-hour sleep opportunity, n = 17). Performance on physical work tasks was evaluated across three days. In addition, heart rate, core temperature, and worker activity were measured continuously. Rate of perceived and exertion and effort sensation were evaluated during the physical work periods.ResultsThere were no differences between the sleep-restricted and control groups in firefighters’ task performance, heart rate, core temperature, or perceptual responses during self-paced simulated firefighting work tasks. However, the sleep-restricted group were less active during periods of non-physical work compared to the control group.ConclusionsUnder self-paced work conditions, 4 h of sleep restriction did not adversely affect firefighters’ performance on physical work tasks. However, the sleep-restricted group were less physically active throughout the simulation. This may indicate that sleep-restricted participants adapted their behaviour to conserve effort during rest periods, to subsequently ensure they were able to maintain performance during the firefighter work tasks. This work contributes new knowledge to inform fire agencies of firefighters’ operational capabilities when their sleep is restricted during multi-day wildfire events. The work also highlights the need for further research to explore how sleep restriction affects physical performance during tasks of varying duration, intensity, and complexity.

Prolonged REM sleep restriction induces metabolic syndrome-related changes: Mediation by pro-inflammatory cytokines.

Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (p<0.001), of leptin plasma levels and hypothalamic leptin receptors. Conversely, increased levels of TNF-α and IL-6 and expression of phosphorylated NFκ-β in the RPAT of SR21 compared to CTL rats (p<0.01, for all parameters). SR21 rats also displayed reduced glucose clearance and IRS-1 expression than CTL rats (p<0.01). The present results indicated that 21days of sleep restriction by the platform method induced metabolic syndrome-related alterations that may be mediated by inflammation of the RPAT.

Heart rate variability for evaluating vigilant attention in partial chronic sleep restriction.

Examine the use of spectral heart rate variability (HRV) metrics in measuring sleepiness under chronic partial sleep restriction, and identify underlying relationships between HRV, Karolinska Sleepiness Scale ratings (KSS), and performance on the Psychomotor Vigilance Task (PVT). Controlled laboratory study. Experimental laboratory of the Brain Work Research Centre of the Finnish Institute of Occupational Health, Helsinki, Finland. Twenty-three healthy young males (mean age ± SD = 23.77 ± 2.29). A sleep restriction group (N = 15) was subjected to chronic partial sleep restriction with 4 h sleep for 5 nights. A control group (N = 8) had 8 h sleep on all nights. Based on a search over all HRV frequency bands in the range [0.00, 0.40] Hz, the band [0.01, 0.08] Hz showed the highest correlation for HRV-PVT (0.60, 95% confidence interval [0.49, 0.69]) and HRV-KSS (0.33, 95% confidence interval [0.16, 0.46]) for the sleep restriction group; no correlation was found for the control group. We studied the fraction of variance in PVT explained by HRV and a 3-component alertness model, containing circadian and homeostatic processes coupled with sleep inertia, respectively. HRV alone explained 33% of PVT variance. The findings suggest that HRV spectral power reflects vigilant attention in subjects exposed to partial chronic sleep restriction. Henelius A, Sallinen M, Huotilainen M, Müller K, Virkkala J, Puolamäki K. Heart rate variability for evaluating vigilant attention in partial chronic sleep restriction.

Augmented hemodynamic response to insufficient sleep in women: response to a novel repetitive sleep restriction challenge (1171.4)

Recent epidemiological studies demonstrate a consistent association between short sleep (i.e. self‐reported) and higher risk of hypertension. While this association seems to be stronger in women compared to men, the evidence from laboratory‐controlled studies is lacking. Thirty‐four healthy subjects (age 32±2 yrs; BMI 24±1 kg/m2; 18 men and 16 women) participated in a 22‐day in hospital study. Following 3 nights of adaptation sleep of 8h/night, subjects were randomly assigned to 4 cycles of repeated sleep restriction (4h of sleep/night for 3 nights followed by a night of 8h of sleep, repeated 4 times), or an 8h sleep control group. Blood pressure (BP) and heart rate (HR) were measured every morning at 8:30am and evening at 10pm in a seated position for 5 times over a 15min period. Morning BPs were not significantly different between sleep restriction and control groups in men or women (p&gt;0.05). In contrast, women had significantly increased evening BP (i.e. up to 10±2mmHg in systolic BP, 5±2mmHg in diastolic BP) on the sleep restriction days compared to control (p=0.003 and 0.023 for systolic and diastolic BP, respectively). Moreover, repeated sleep restriction induced an increase in morning HR compared to control in women (p=0.005). Women show a pronounced pressor response to repeated challenges of sleep restriction, in a well‐controlled study.Grant Funding Source: Supported by NIH (HL‐106782)

The role of sleep and sildenafil in the progression of chronic kidney disease: A new therapeutic approach

Introduction The prevalence of chronic kidney disease (CKD) is increasing rapidly throughout the world. Also, CKD is associated with comorbidities such as sexual dysfunction and sleep disorders which may impact the patients’ quality of life. Although sleep loss is inherent to the lifestyle of people suffering from CKD, its effects on the disease progression are unknown. Moreover, there are few studies evaluating potential alternative treatments that could attenuate some CKD comorbidities. Thus, the aim of this study was to evaluate the outcomes of a chronic treatment with sildenafil in an animal model of CKD subjected to sleep restriction (SR). Materials and methods The study was performed using 140 male adult Wistar rats distributed into 4 groups: sham treated with vehicle (SHAM + V), sham treated with sildenafil (SHAM + S), CKD treated with vehicle (CKD + V) and CKD treated with sildenafil (CKD + S). After 46 days, all groups were sub distributed in sleep control (SC) and SR. Blood pressure and heart rate was assessed once a week. In the end, we performed the evaluation of the sexual behavior followed by euthanasia and collection of blood. Results Sildenafil was able to prevent the disease progression, demonstrated by higher levels of serum creatinine in CKD + V + SC compared to SHAM + V + SC and CKD + S + SC groups. Nevertheless, creatinine levels of CKD + S + SR was significantly higher than SHAM + S + SR group. Moreover, sildenafil prevented the development of systemic hypertension, although this was not sustained after SR. Heart rate was only affected by disease and SR, both contributing to tachycardia. Sildenafil treatment also reduced the excessive body weight loss, the iron deficit, the dyslipidemia, the decrease of serum testosterone and LH and the increase of proinflammatory cytokines IL-1 α , TNF α e IL-17. However, many of these effects were attenuated or abolished by SR. Regarding the sexual behavior, CKD + V + SC group had lower sexual activity index than SHAM + V + SC and CKD + S + SC. Overall, SR had a stimulant-like effect on sexual behavior by increasing the sexual motivation and performance in the animals. This effect was also followed by increased corticosterone, progesterone and FSH levels. Conclusion The early chronic treatment with sildenafil in CKD plays a role as possible adjuvant in the therapy for CKD and its comorbidities. Importantly, its effectiveness demands the maintenance of the sleep quality. Acknowledgements This work was supported by grants from AFIP , FAPESP , CAPES and CNPq .

How much one sleeps at night affects napping effects on emotional memory consolidation

Sleep schedule of participants were regulated and varied across experiments, so it remains unclear if nighttime sleep and daytime nap play a different role in memory consolidation thus yielding conflicting results about the effect of sleep on consolidation of emotional memory. This study explored the interactive effect of habitual sleep duration and daytime nap on consolidation. Sixty-three young adults (Mean age = 20.38, SD = 1.39, 63.5%male) were randomly assigned to either the Nap or the Wake group with no significant group differences in age, sex, body mass index, habitual sleep duration and sleep quality. Average baseline sleep duration (SLEEP) was calculated from sleep diaries completed five days before the lab day. Participants were instructed to rate the valence of eyes stimuli adopted from ¡¥¡¥Reading the Mind in the Eyes test. The Nap group then obtained a 90-min polysomnograph-monitored sleep opportunity, when the Wake group remained awake. An incidental recognition test of the stimuli was administered after the Nap/Wake period. Memory discriminability of stimuli of positive, neutral and negative valence, was compared using two-way analysis of variance with CONDITION (Nap&Wake) and SLEEP (<5 h, 5–6.5 h, >6.5–8 h & >8 h) as between-subject factors. For neutral memory, there were significant main effect of CONDITION with the Nap group performing better (p = .009) and main effect of SLEEP (p = .003) with worse performance in those with <5 h sleep. There was significant CONDITION*SLEEP interaction, p = .016. Post-hoc tests indicated that the nap group performed better in the <5 h sleep group (p < .05) but not in the other three groups (ps > .05). For negative memory, a significant main effect of CONDITION was found with better performance in the Nap group (p = .004). No main effect of SLEEP but significant CONDITION*SLEEP interaction was found (p=.045). Post-hoc tests indicated that better performance in the Nap group was found among those with <5 h, 5–6.5 h and >6.5–8 h sleep (ps < .05), but not those with >8 h sleep (ps > .05). For positive memory, no main or interaction effects were found. Our results showed that a nap strengthened memory of neutral valence in only the most sleep-restricted group, but the napping effects on memory of negative valence were present in groups of all sleep duration, except for the most sleep-satiated. This study provided the first evidence on the interaction between habitual sleep duration and a daytime nap on emotional memory. This work was supported by HKU Seed Funding Program for Basic Research.

Interconnectivity of sympathetic and sleep networks is mediated through reduction of gamma aminobutyric acidergic inhibition in the paraventricular nucleus

Chronic short sleep duration has been linked to sympathoexcitation and increased risk of cardiovascular disease. The central nervous system plays an important role in the regulation of sympathetic activity. Thus, the present study evaluates the pre-autonomic neurones in the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla after sleep restriction using various protein expression measurements and electrophysiological approaches. Wistar male rats were assigned randomly to two experimental groups: control or sleep restriction for 14days. Sleep restriction was defined as 20h of paradoxical sleep deprivation followed by a 4h sleep permission period using the modified multiple platform method. Micropunches of the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla were dissected to evaluate the protein expression of angiotensin II receptor, type 1 (AT1), AT2, gamma aminobutyric acidA ) (N-methyl-d-aspartate receptor1) and neuronal nitric oxide synthase neuronal nitric oxide synthase isoform through immunoblotting. Sleep restriction induced a down-regulation of the gamma aminobutyric acidA receptor in the paraventricular nucleus of the hypothalamus. Microinjection of bicuculline, a gamma aminobutyric acid receptor blocker, into the paraventricular nucleus of the hypothalamus increased renal sympathetic activity renal sympathetic nerve activity, mean arterial pressure and heart rate in anaesthetized control rats. However, the amplitude and frequency of renal sympathetic nerve activity was higher in the sleep restriction group. These findings suggest that gamma aminobutyric acidergic inhibition within the paraventricular nucleus of the hypothalamus is involved in sympathoexcitation induced by sleep restriction.

Effects of Experimental Sleep Restriction on Caloric Intake and Activity Energy Expenditure

Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P=.006) and decreased in the control group by -118 kcal/d (SD, 386 kcal/d, P=.51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P=.014). Sleep restriction was not associated with changes in activity energy expenditure (P=.62). No change was seen in levels of leptin (P=.27) or ghrelin (P=.21). Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. ClinicalTrials.gov; No.: NCT01334788; URL: www.clinicaltrials.gov.

A novel model of chronic sleep restriction reveals an increase in the perceived incentive reward value of cocaine in high drug-taking rats

Substance abuse and sleep deprivation are major problems in our society. Clinical studies suggest that measures of poor sleep quality effectively predict relapse to substance abuse. Previously, our laboratory has shown that acute sleep deprivation increases the rate and efficiency (i.e., the goal-directed nature of responding) of cocaine self-administration using a progressive ratio (PR) schedule of reinforcement. However, the problem of sleep deprivation in our nation is largely one of chronicity. Therefore, the current study used a rodent model of chronic sleep restriction more akin to that experienced by humans (approximately 25% reduction in baseline sleep over the course of 8days) to assess the impact of chronic sleep deprivation on cocaine-seeking and cocaine-taking behaviors in rats early during acquisition of self-administration. While low drug-taking rats were unaffected by chronic sleep restriction, high drug-takers in the chronic sleep restriction (CSR) group exhibited enhanced fixed ratio (FR) responding by the fourth day of FR training and significantly higher PR breakpoints than their non-sleep restriction (NSR) counterparts. This study is the first to directly assess the impact of chronic sleep deprivation on drug self-administration. These results show that chronic sleep deprivation early during acquisition of self-administration has a significant effect on the perceived incentive reward value of cocaine in high drug-takers, as indicated by both increased FR responding and an increased willingness to work for drug. Thus, it is important to be mindful of such factors in clinical settings designed for treatment of addiction and relapse prevention.

Effects of cumulative sleep restriction on self‐perceptions while multitasking

This study addressed a rarely studied question of self-perceptions of performance and overall functional state during cumulative sleep restriction and the ensuing recovery period. Twenty healthy male volunteers, aged 19-29years, were divided into a sleep restriction group (n=13) and a control group (n=7). On the first 2 nights, the sleep restriction group had an 8-h sleep opportunity that was restricted to 4h for the next 5 nights, and then restored to 8h for the last 2nights. The control group had an 8-h sleep opportunity each night. Each day participants accomplished 50-min multitask sessions and gave self-ratings in their connection. Similar to our previous findings on multitasking performance, self-perceived task performance, sleepiness and mental fatigue impaired during the sleep restriction and returned to baseline during the recovery phase. Self-perceived mental effort, tension, task difficulty and task pace showed no sensitivity to the sleep restriction. We concluded that sleep-restricted individuals can probably make use of some self-perceptions when assessing their 'fitness for duty'. However, at the individual level these measures seem to be inaccurate in revealing actual performance impairments.

Pain–autonomic interaction after work‐induced sleep restriction

Poor sleep is commonly associated with alterations in pain perception. However, there is a lack of studies that address work-associated sleep restriction (SR) and changes in non-nociceptive perception and autonomic responses after work-induced SR. This study was performed with 19 medical students after a normal-sleep night (NS phase) and after a night shift at the local emergency room (SR phase). We performed clinical assessment, quantitative sensory testing for electrical and temperature sensation, RR interval analysis, and recorded sudomotor skin responses (SSRs). The total mean duration of sleep was 436 ± 18 min in the NS group and 120 ± 28 min in the SR group (P<0.001). The anxiety scores were higher following the SR phase compared with those after the NS phase (P<0.01). After SR, there was a decrease in heat-pain threshold, but neither warm nor electrical thresholds were affected. Following SR, subjects showed higher SSR amplitudes and an increased number of double responses at an interstimulus interval of 2 s. We also observed a moderate inverse correlation between heat-pain thresholds and SSR amplitude (r= -0.46; P<0.01). However, there was no correlation between anxiety scores and SSR parameters. The effects of SR in the context of work stress on pain are specific and appear unrelated to general changes in sensory perception. Hyperalgesia was associated with abnormal autonomic responses, but not with increased anxiety, which suggests an association between the nociceptive and autonomic nervous systems that is independent of the emotional state.

Sleep Restriction Masks the Influence of the Circadian Process on Sleep Propensity

Previous forced desynchrony studies have highlighted the close relationship between the circadian rhythms of core body temperature (CBT) and sleep propensity. In particular, these studies have shown that a “forbidden zone” for sleep exists on the rising limb of the CBT rhythm. In these previous studies, the length of the experimental day was either ultrashort (90 min), short (20 h), or long (28 h), and the ratio of sleep to wake was normal (i.e., 1:2). The aim of the current study was to examine the relative effects of the circadian and homeostatic processes on sleep propensity using a 28-h forced desynchrony protocol in which the ratio of sleep to wake was substantially lower than normal (i.e., 1:5). Twenty-seven healthy males lived in a time-isolation sleep laboratory for 11 consecutive days. Participants completed either a control (n = 13) or sleep restriction (n = 14) condition. In both conditions, the protocol consisted of 2 × 24-h baseline days followed by 8 × 28-h forced desynchrony days. On forced desynchrony days, the control group had 9.3 h in bed and 18.7 h of wake, and the sleep restriction group had 4.7 h in bed and 23.3 h of wake. For all participants, each 30-s epoch of time in bed was scored as sleep or wake based on standard polysomnography recordings, and was also assigned a circadian phase (360° = 24 h) based on a cosine equation fitted to continuously recorded CBT data. For each circadian phase (i.e., 72 × 5° bins), sleep propensity was calculated as the percentage of epochs spent in bed scored as sleep. For the control group, there was a clear circadian rhythm in sleep propensity, with a peak of 98.5% at 5° (∼05:20 h), a trough of 64.9% at 245° (∼21:20 h), and an average of 82.3%. In contrast, sleep propensity for the sleep restriction group was relatively high at all circadian phases, with an average of 96.7%. For this group, the highest sleep propensity (99.0%) occurred at 60° (∼09:00 h), and the lowest sleep propensity (91.3%) occurred at 265° (∼22:40 h). As has been shown previously, these current data indicate that with a normal sleep-to-wake ratio, the effect of the circadian process on sleep propensity is pronounced, such that a forbidden zone for sleep exists at a phase equivalent to evening time for a normally entrained individual. However, these current data also indicate that when the ratio of sleep to wake is substantially lower than normal, this circadian effect is masked. In particular, sleep propensity is very high at all circadian phases, including those that coincide with the forbidden zone for sleep. This finding suggests that if the homeostatic pressure for sleep is sufficiently high, then the circadian drive for wakefulness can be overridden. In future studies, it will be important to determine whether or not this masking effect occurs with less severe sleep restriction, e.g., with a sleep-to-wake ratio of 1:3. (Author correspondence: charli.sargent@cqu.edu.au)

Chronic partial sleep deprivation reduces brain sensitivity to glutamate N‐methyl‐d‐aspartate receptor‐mediated neurotoxicity

It has been hypothesized that insufficient sleep may compromise neuronal function and contribute to neurodegenerative processes. While sleep loss by itself may not lead to cell death directly, it may affect the sensitivity to a subsequent neurodegenerative insult. Here we examined the effects of chronic sleep restriction (SR) on the vulnerability of the brain to N-methyl-d-aspartate (NMDA)-induced excitotoxicity. Animals were kept awake 20 h per day and were only allowed to rest during the first 4 h of the light phase, i.e. their normal circadian resting phase. After 30 days of SR all rats received a unilateral injection with a neurotoxic dose of NMDA into the nucleus basalis magnocellularis (NBM). Brains were collected for assessment of damage. In the intact non-injected hemisphere, the number of cholinergic cells in the NBM and the density of their projections in the cortex were not affected by SR. In the injected hemisphere, NMDA caused a significant loss of cholinergic NBM cells and cortical fibres in all animals. However, the loss of cholinergic cells was attenuated in the SR group as compared with the controls. These data suggest that, if anything, SR reduces the sensitivity to a subsequent excitotoxic insult. Chronic SR may constitute a mild threat to the brain that does not lead to neurodegeneration by itself but prepares the brain for subsequent neurotoxic challenges. These results do not support the hypothesis that sleep loss increases the sensitivity to neurodegenerative processes.

Association of methamidophos and sleep loss on reproductive toxicity of male mice

This study investigated the effects of organophosphate exposure on the male reproductive system of mice submitted to chronic sleep loss condition. Adult Swiss mice were distributed into 4 groups: control; methamidophos (MTP); sleep restriction (SR); and MTP + SR. The dose of methamidophos was 0.002 mg kg −1 day −1 (half of the Acceptable Daily Intake). Sleep restriction condition was 21 h day −1 during 15 days. In relation to control group, MTP treatment induced a significant reduction of 12% on morphologically normal spermatozoa in both MTP and MTP + SR groups. In addition, the absolute and relative weights of the seminal vesicles were decreased (MTP, −34%; MTP + SR, −45%). Epididymal fat was reduced in SR groups (SR, −64%; MTP + SR, −58%). Plasma testosterone levels were significantly decreased in MTP and SR groups, and progesterone levels were increased 8 times in MTP + SR in comparison with the control group. The corticosterone levels were unaffected by MTP or SR conditions. Thus, low dose MTP exposure resulted in deleterious effects on the male reproductive system. Sleep loss associated with MTP potentiated the effect on steroidogenesis, mainly in terms of progesterone levels.

Differential sympathetic activation induced by intermittent hypoxia and sleep loss in rats: Action of angiotensin (1–7)

The present study attempted to evaluate the effects of chronic intermittent hypoxia (CIH) associated with sleep restriction in hemodynamic parameters and the plasma renin–angiotensin system. Wistar–Hannover rats were submitted to isolated CIH exposure (1000–1600h), sleep restriction (1600–1000h), defined as 18-h paradoxical sleep deprivation followed by 6-h sleep permission period and CIH associated to sleep restriction for 21days. The CIH and sleep restriction group showed a preferential increase in renal sympathetic nervous system (rSNA) associated with a reduction in plasma angiotensin (1–7) concentrations. However, CIH-sleep restriction rats did not modify rSNA and showed a higher angiotensin (1–7) concentration when compared to isolated CIH and sleep restriction. These results suggest that CIH and sleep restriction impaired the cardiovascular system, and its association to sleep loss can modify these effects by partially restoring circulating angiotensin (1–7).

Impact of sex on hyperalgesia induced by sleep loss

This study evaluated the impact of sex on the short term consequences of different periods of sleep deprivation and the effect of the respective sleep recovery periods on nociceptive responses. Male and female C57BL/6J mice were assigned to the following groups: paradoxical sleep deprived (PSD) for 72h, sleep restricted (SR) for 15days, exposed to respective recovery periods for 24h, or untreated home-cage controls (CTRL). Mice were submitted to a noxious thermal stimulus to evaluate their nociceptive response after PSD, SR, or recovery periods. Blood was collected for hormonal analysis. The nociceptive response was significantly lower in PSD and SR mice compared to CTRL animals, regardless of the sex. However, SR females had a lower paw withdrawal threshold than males. Sleep recovery was able to restore normal nociceptive sensitivity after PSD in both sexes. The hyperalgesia induced by SR was not reversed by sleep rebound. In females, low concentrations of estradiol were found after SR, and these concentrations continued to decrease after 24hours of sleep recovery. The PSD male mice exhibited higher concentrations of corticosterone than the CTRL and SR male mice. Corticosterone levels were not affected by SR. Our study revealed that PSD and SR induce hyperalgesia in mice. The SR groups showed marked changes in the nociceptive response, and the females were more sensitive to these alterations. This finding indicates that, although different periods of sleep deprivation change the nociceptive sensitivity in male and female mice, sex could influence hyperalgesia induced by chronic sleep loss.