24-h Sleep Deprivation Research Articles

Isorhamnetin ameliorates sleep deprivation induced cognitive dysfunction by reducing oxidative stress, inflammation and neuronal apoptosis in mice

Sleep deprivation (SD) could cause a sequence of neurobehavioral deficits and physiological consequences. Isorhamnetin (ISOR) has been verified to have neuronal protective, anti‐inflammatory and anti‐oxidative effects. This article aimed to explore the mechanism under the neuroprotective effect of ISOR against 72h SD‐induced anxiety like behavior, oxidative stress, neuroinflammation in mice. The ameliorating effect of ISOR on SD‐induced learning and memory impairment was evaluated by Open field test (OFT) and Morris water maze tests (MWM). After the behavioral tests, antioxidant effects were detected by malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) assays. The level of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) both in serum and brain homogenates were detected by ELISA. Expressions of Bcl‐2, Bax were also detected along with JNK, P38 and ERK phosphorylation by western blot. HE staining and TUNEL assays were used to observe the neuron pathologic morphology and apoptosis caused by SD. The results suggest that ISOR could improve cognitive functions induced by 72h SD by reducing the anxiety like behavior, oxidative stress, neuroinflammation and the neuronal apoptosis.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China (Grant No.81102828, 81273037) and the Natural Science Foundation of Shandong province of China (No.2015ZRB14548)

Evidence That Homeostatic Sleep Regulation Depends on Ambient Lighting Conditions during Wakefulness.

We examined whether ambient lighting conditions during extended wakefulness modulate the homeostatic response to sleep loss as indexed by. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA) in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e., sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800 K), and once under either white light (WL: 250 lux, 2800 K) or blue-enriched white light (BL: 250 lux, 9000 K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.

Acute moderate-intensity exercise improves 24-h sleep deprivation-induced cognitive decline and cerebral oxygenation: A near-infrared spectroscopy study

We evaluated the effects of moderate-intensity exercise in improving the decline in cognitive performance induced by a 24-h period of acute sleep deprivation (SD). We hypothesized that the positive effect of exercise is mediated by increased oxygenation (measured using near-infrared spectroscopy) of the dorsolateral prefrontal cortex (DLPFC). Cognitive performance was measured using the reaction time and interference scores of the Stroop colour and word test, in 12 healthy adults (eight males, 21.1 ± 0.3 years-old), at pre- and post-exercise. Cognitive scores were compared under two conditions: rested wakefulness (RW) and 24-h SD. The exercise consisted of 20-min of ergometer cycling at an intensity of 60 % VO2peak. Oxygenation to the DLPFC increased, at 12 min after exercise onset, compared to the baseline and was maintained until the end of the exercise in both RW and SD conditions (P < 0.01). The change in RT correlated with sleepiness (P < 0.05), with no correlation for the interference score and oxygenation. Taken together, moderate-intensity exercise reverses SD-induced cognitive decline.

Sleep deprivation reduces the recovery of muscle injury induced by high-intensity exercise in a mouse model

Sleep is crucial to improve athlete performance and their circadian rhythm, but sleep patterns may be disturbed because athletes participate in several competitions. In addition, intensive training programs can cause muscle pain and psychological stress in athletes, resulting in a lack of sleep. Sleep also plays a critical role in the recovery of muscle injury induced by exercise. The current study evaluated the effect of sleep deprivation on the recovery of muscle injury induced by high-intensity exercise in a mouse model. In this study, 28 mice were randomly assigned to four groups (N = 7): control (Control), exercise (EX), sleep deprivation (SD), and sleep deprivation with exercise (EX+SD). The mice from the EX and EX+SD groups were subjected to high-intensity swimming. The results showed that 72-h sleep deprivation increased food intake and reduced body weight. However, the manipulation of 8-week exercise and/or 72-h sleep deprivation did not have any effect in the elevated plus maze task and tail suspension test. Interestingly, the EX+SD group exhibited improved memory performance in the Morris water maze and impaired motor activity in the open field test. According to the TNF-α level and aspartate aminotransferase (AST), and creatine phosphokinase (CK) activities, only the EX+SD group exhibited muscle impairment. Overall, high-intensity exercise may cause muscle injury, and adequate sleep can recover muscle damage. However, sleep deprivation reduces protein synthesis, which decreases the ability to restore muscle damage and aggravates the harmful effect of high-intensity exercise.

Sympathetic neural responsiveness to sleep deprivation in older adults: sex differences

Our laboratory has previously reported that total sleep deprivation (TSD) modifies muscle sympathetic neural activity (MSNA) differently in young men and women. Because postmenopausal women are among the highest risk for hypertension, this study compares MSNA responses with TSD in older men and women. We hypothesized that TSD would alter MSNA in older adults, with greater sympathoexcitation in postmenopausal women. Twenty-seven participants (14 men and 13 women) between the ages of 55 and 75 yr were tested twice, once after 24-h TSD and once after normal sleep (randomized, crossover design). Our primary outcome measure of MSNA (microneurography) was successful across both conditions in 20 participants (10 men and 10 women). Secondary outcome measures included seated blood pressure, heart rate, and fasting plasma testosterone, estradiol, and progesterone. Age (60 ± 1 vs. 61 ± 2 yr) and BMI (27 ± 1 vs. 26 ± 1 kg/m2) were not different between groups. TSD increased systolic blood pressure in both men (124 ± 5 to 130 ± 4 mmHg) and women (107 ± 5 to 116 ± 4 mmHg), but the increases were not different between groups (condition, P = 0.014; condition × sex, P > 0.05). In contrast, TSD elicited divergent MSNA responses in older men and women. Specifically, MSNA burst frequency increased in postmenopausal women (28 ± 3 to 34 ± 3 burst/min), but not older men (38 ± 3 to 35 ± 3 bursts/min; condition × sex, P = 0.032). In conclusion, TSD elicited sympathoexcitation in postmenopausal women but not age-matched men. These findings provide new mechanistic insight into reported links between sleep deprivation and hypertension.NEW & NOTEWORTHY Epidemiological studies report that sleep deprivation is more strongly associated with hypertension in women than in men. In the present study, 24-h total sleep deprivation (TSD) increased blood pressure in postmenopausal women and age-matched men. In contrast, only women demonstrated increases in muscle sympathetic nerve activity after TSD. The sympathoexcitation observed in postmenopausal women suggests a potential contributing mechanism for epidemiological observations and advances our understanding of the complex relations between sleep, sex, and hypertension.

MLC901 during sleep deprivation rescues fear memory disruption in rats.

Several lines of evidence suggest that sleep deprivation disrupts cognitive and emotional abilities and changes the expression of distinctive categories of genes in the brain. In the present study, saline- or MLC901 (a traditional Chinese medicine)-treated male Wistar rats were first submitted to a modified water box (for 24-h sleep deprivation) and then trained in contextual and tone fear conditioning tasks with the purpose to evaluate the effect of MLC901 during sleep deprivation on fear memory retention. Hippocampal mRNA measurement was performed by reverse transcription-polymerase chain reaction (RT-PCR). We found that the exposure of rats to 24h of sleep deprivation impaired contextual and tone fear memory retention, while administration of MLC901 (0.2, 0.4, and 0.8mg/kg, once/12h; i.p.) during sleep deprivation abolished memory deficits. Meanwhile, different doses of MLC901 alone had no effect on performance in both tasks. We observed that MLC901 increased the expression levels of pro-apoptotic BAD, anti-apoptotic Bcl-xL, and Tfam as an index of mitochondrial biogenesis compared to sleep-deprived rats, while MLC901 during sleep deprivation increased BAX, BAD, and Bcl-xL compared to the control group. Sleep deprivation decreased BAX and Tfam, by itself. MLC901 only decreased BAX and Tfam and increased BAD level compared to the non-sleep-deprived control group. It is suggested that MLC901 might be a therapeutic option for memory impairment during sleep deprivation.

Inhibited Endogenous H2S Generation and Excessive Autophagy in Hippocampus Contribute to Sleep Deprivation-Induced Cognitive Impairment.

Background and Aim: Sleep deprivation (SD) causes deficit of cognition, but the mechanisms remain to be fully established. Hydrogen sulfide (H2S) plays an important role in the formation of cognition, while excessive and prolonged autophagy in hippocampus triggers cognitive disorder. In this work, we proposed that disturbances in hippocampal endogenous H2S generation and autophagy might be involved in SD-induced cognitive impairment.Methods: After treatment of adult male wistar rats with 72-h SD, the Y-maze test, object location test (OLT), novel object recognition test (NORT) and the Morris water maze (MWM) test were performed to determine the cognitive function. The autophagosome formation was observed with electron microscope. Generation of endogenous H2S in the hippocampus of rats was detected using unisense H2S microsensor method. The expressions of cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), beclin-1, light chain LC3 II/LC3 I, and p62 in the hippocampus were assessed by western blotting.Results: The Y-maze, OLT, NORT, and MWM test demonstrated that SD-exposed rats exhibited cognitive dysfunction. SD triggered the elevation of hippocampal autophagy as evidenced by enhancement of autophagosome, up-regulations of beclin-1 and LC3 II/LC3 I, and down-regulation of p62. Meanwhile, the generation of endogenous H2S and the expressions of CBS and 3-MST (H2S producing enzyme) in the hippocampus of SD-treated rats were reduced.Conclusion: These results suggested that inhibition of endogenous H2S generation and excessiveness of autophagy in hippocampus are involved in SD-induced cognitive impairment.

Effect of preoperative sleep deprivation on hippocampal TLR4/NF-κB signaling pathway in aged mice with postoperative cognitive dysfunction

Objective To evaluate the effect of preoperative sleep deprivation on hippocampal Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)signaling pathway in aged mice with postoperative cognitive dysfunction. Methods Sixty clean-grade healthy male C57BL/6J mice, aged 16 months, weighing 28-36 g, were divided into 4 groups(n=15 each)using a random number table method: control group(group C), surgery group(group S), sleep deprivation group(group SD)and sleep deprivation plus surgery group(group SD+ S). Mice were fed a common diet in group C. Mice were sleep-deprived for 24 h in group SD. Tibial fracture internal fixation was performed in group S. Tibial fracture internal fixation was performed after 24-h sleep deprivation in group SD+ S. Cognitive function was assessed using the contextual fear conditioning test at days 3 and 7 after operation. The animals were sacrificed at day 7 after operation, brains were removed and hippocampi were isolated for determination of tumor necrosis factor-alpha(TNF-α)content(by enzyme-linked immunosorbent assay)and expression of TLR4 and p-NF-κB p65(by Western blot). Results Compared with group C, the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation, the content of TNF-α was increased, and the expression of TLR4 and p-NF-κB p65 was up-regulated in S, SD and SD+ S groups(P<0.05). Compared with group S and group SD, the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation, the content of TNF-α was increased, and the expression of TLR4 and p-NF-κB p65 was up-regulated in group SD+ S(P<0.05). Conclusion Preoperative sleep deprivation further accentuates postoperative cognitive dysfunction, and the mechanism is related to activating TLR4/NF-κB signaling pathway and inducing inflammatory responses of aged mice. Key words: Sleep deprivation; Aged; Cognition disorders; Hippocampus; Toll-like receptors; NF-kappa B

Effects of cannabinoid modulation on hypothalamic nesfatin-1 and insulin resistance.

Both nesfatin-1 and cannabinoid systems involved in the regulation of sleep, metabolism, and food intake. The relationship between cannabinoid system and nesfatin-1 levels remains to be elucidated. This study investigated nesfatin-1 and insulin resistance in 72-h rapid eye movement (REM) sleep-deprived mice under the effects of cannabinoid, and cannabinoid receptors CB1R and CB2R blocking. Sixty mice were exposed to 72-h sleep deprivation. Groups and drug administrations were as follows: Group 1 (control) received injection of vehicle. Group 2 received WIN 55,212,2. Group 3 received AM251 (CB1R antagonist) followed by WIN 55,212,2 injection. Group 4 received SR144528 (CB2R antagonist) followed by WIN 55,212,2 injection. Group 5 received only AM251. Group 6 received only SR144528. Blood samples were collected 1 h after drug administration and prepared for biochemical measurements. Glucose levels were measured by glucometer, whereas insulin and nesfatin-1 levels were measured by ELISA. Central nesfatin-1 was also assessed using immunohistochemistry. One-way analysis of variance together with post hoc Tukey's test was used for inter-group comparisons. Serum nesfatin-1 levels were comparable in all study groups. Brain nesfatin-1 immune-positive cell count was lower in WIN group compared to controls. The administration of CB1R or CB2R antagonist prevented reduction in nesfatin-1-positive cell count. Insulin resistance was higher in WINCB2 and CB2 groups than in control and WINCB1 groups. Cannabinoid treatment reduced nesfatin-1 immunoreactivity in the central nervous system and this effect was prevented by either CB1R or CB2R antagonist pretreatment. Insulin resistance might be related to CB2 receptor activation which was independent from central nesfatin-1 immunoreactivity.

Using emotion regulation strategies after sleep deprivation: ERP and behavioral findings.

Sleep deprivation is suggested to impact emotion regulation, but few studies have directly examined it. This study investigated the influence of sleep deprivation on three commonly used emotion regulation strategies (distraction, reappraisal, suppression) in Gross's (1998) process model of emotion regulation. Young healthy adults were randomly assigned to a sleep deprivation group (SD; n = 26, 13 males, age = 20.0 ± 1.7) or a sleep control group (SC; n = 25, 13 males, age = 20.2 ± 1.7). Following 24-h sleep deprivation or normal nighttime sleep, participants completed an emotion regulation task, in which they naturally viewed or applied a given emotion regulation strategy towards negative pictures, with electroencephalographic (EEG) recordings. A reduction in the centroparietal late positive potential (LPP) amplitudes towards negative pictures from the naturally viewing condition to a regulated condition was calculated as an index of regulatory effects. Comparisons between the two groups indicated that sleep deprivation significantly impaired the regulatory effects of distraction and reappraisal on LPP amplitudes. Suppression did not reduce LPP amplitudes in either group. In addition, habitual sleep quality moderated the effect of sleep deprivation on subjective perception of emotional stimuli, such that sleep deprivation only made good sleepers perceive negative pictures as more unpleasant and more arousing, but it had no significant effect on poor sleepers' perception of negative pictures. Altogether, this study provides the first evidence that sleep deprivation may impair the effectiveness of applying adaptive emotion regulation strategies (distraction and reappraisal), creating potentially undesirable consequences to emotional well-being.

Mania-like elevated mood in rats: Enhanced 50-kHz ultrasonic vocalizations after sleep deprivation

Mania is characterized by elevated drive and mood but animal models of mania have often neglected elevated mood. Ultrasonic vocalizations (USV) of 50-kHz emitted by rats are thought to index the subject's positive affective state. Fifty-kHz USV emission is increased by amphetamine, an effect blocked by lithium administration. Sleep deprivation (SD) is an environmental model of mania and the present study evaluated SD effects on behavioral activity and USV emission, together with the impact of lithium treatment. Adult rats were submitted to 24h or 72h SD, and locomotor activity and USV emission were assessed. To test their sensitivity to a standard antimanic drug, these behavioral parameters were also evaluated after acute administration of lithium carbonate (25, 50 or 100 mg/kg, i.p.). Striatal monoamine content was measured post-mortem. SD (24h and 72h) led to increased locomotor activity, rearing behavior and 50-kHz USV emission, together with a change in the call profile characterized by an increase in the percentage of frequency-modulated 50-kHz USV, which may indicate the mania-like consequences of SD. Importantly, all SD effects were reverted by lithium administration. SD also led to a decrease in dopamine content in the ventral striatum, while increasing dopamine turnover. In conclusion, SD increased 50-kHz USV emission, an effect prevented by acute lithium administration. This suggests 50-kHz USV as a new marker for mania-like elevated mood, which shows construct validity (associated with increased dopaminergic tone), face validity (reflecting increased positive affect) and predictive validity (high sensitivity to lithium treatment).

A Pilot Study Exploring the Effects of Sleep Deprivation on Analogue Measures of Pilot Competencies.

Sleep loss can result in cognitive, motor, and neurobehavioral impairments. In an aviation context, this can cause a serious threat to flight safety. Therefore, the study aimed to investigate the effects of 24-h sleep deprivation on mood, fatigue, and airline pilot competencies. Seven subjects attended two 24-h testing periods, one with an 8-h sleep opportunity, and the other with no sleep opportunity (i.e., sleep deprivation). Subjects were required to complete a battery of mood, fatigue, and analogue measures of pilot competency tasks every 8 h (0 h, 8 h, 16 h, 24 h) throughout each testing period. While total mood disturbance was found to significantly increase (83.42, SD = 25.7), both objective (352.71, SD = 42.00) and subjective (34.85, SD = 8.82) fatigue were found to significantly decrease following 24-h sleep deprivation. Cognitive flexibility (757.45, SD = 58.48) and hand-eye coordination (dominant hand only) (60.28, SD = 3.86) were also negatively impacted following 24-h sleep deprivation. However, working memory and situation awareness were not significantly negatively impacted by the bout of sleep deprivation. Some pilot-specific task-related factors such as subjective fatigue, cognitive flexibility, and working memory were found to be particularly susceptible to sleep loss, with significant declines in performance observed following 16-h continuous wakefulness, suggesting reductions in optimal functioning following this period of wakefulness. Further investigation using more regular testing time points, employing additional pilot competencies, and using more aviation-specific tasks is warranted.O'Hagan AD, Issartel J, McGinley E, Warrington G. A pilot study exploring the effects of sleep deprivation on analogue measures of pilot competencies. Aerosp Med Hum Perform. 2018; 89(7):609-615.

24-h sleep deprivation impairs early attentional modulation of neural processing: An event-related brain potential study

Prior research indicates sleep deprivation negatively impacts selective attention, although less is known about the neural bases of these effects. The present study used event-related brain potentials (ERPs) to examine whether the effects of total sleep deprivation could be traced to the earliest stages of sensory processing influenced by selective attention. Participants were randomly assigned either to a regular sleep or 24-h total sleep deprivation condition. Following either sleep deprivation or regular sleep, participants completed a dichotic listening selective attention task while ERPs were acquired. Well-rested participants showed typical attentional modulation of the N1 between 150 and 250 msec, with larger amplitude responses to attended relative to unattended auditory probes. In contrast, these effects were significantly reduced in sleep-deprived participants, who did not show significant effects of selective attention on early neural processing. Similar group differences were observed in the later processing negativity, from 300 to 450 msec. Taken together, these results indicate that 24-h total sleep deprivation can significantly reduce, or eliminate, early effects of selective attention on neural processing.

Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement

Sleepiness and cognitive function vary over the 24-h day due to circadian and sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks associated with these variations remain to be fully established. Using functional magnetic resonance imaging (fMRI), we investigated brain responses associated with circadian and homeostatic sleep-wake-driven dynamics of subjective sleepiness throughout day and night. Healthy volunteers regularly performed a psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep pressure). When sleep deprived, arousal-promoting thalamic activation during optimal PVT performance paralleled the time course of subjective sleepiness with peaks at night and troughs on the subsequent day. Conversely, task-related cortical activation decreased when sleepiness increased as a consequence of higher sleep debt. Under low sleep pressure, we did not observe any significant temporal association between PVT-related brain activation and subjective sleepiness. Thus, a circadian modulation in brain correlates of vigilant attention was only detectable under high sleep pressure conditions. Our data indicate that circadian and sleep homeostatic processes impact on vigilant attention via specific mechanisms; mirrored in a decline of cortical resources under high sleep pressure, opposed by a subcortical “rescuing” at adverse circadian times.

Hemodynamic, Autonomic, and Vascular Function Changes after Sleep Deprivation for 24, 28, and 32 Hours in Healthy Men.

This study aimed to analyze the impact of sleep deprivation (SD) on cardiac, hemodynamic, and endothelial parameters and to determine whether these are sustained with increased periods of SD. The study included 60 healthy men (mean: age 31.2±6.3 years; body mass index 24.6±2.6 kg/m2). Hemodynamic parameters, parameters of myocardial contractility, spectral analysis of heart rate (HR) and blood pressure (BP) variability, and the sensitivity of arterial baroreflex function were evaluated. Biochemical tests were performed to assess L-arginine (L-Arg) and asymmetric dimethylarginine (ADMA) levels in reflection of endothelial nitric oxide synthase ability. Measurements of cardiovascular system parameters were obtained at 9 a.m. (baseline) on the first day of the study and 9 a.m. (24-h SD), 1 p.m. (28-h SD), and 5 p.m. (32-h SD) on the second day. Blood samples for evaluating biochemical parameters were obtained at baseline and after 24-h SD. ANOVA Friedman's test revealed a significant effect for time in relation to HR (χ2=26.04, df=5, p=0.000), systolic BP (χ2=35.98, df=5, p=0.000), diastolic BP (χ2=18.01, df=5, p=0.003), and mean BP (χ2=28.32, df=5, p=0.000). L-Arg and ADMA levels changed from 78.2±12.9 and 0.3±0.1 at baseline to 68.8±10.2 and 0.4±0.1 after 24-hr SD, respectively (p=0.001, p=0.004). SD in healthy men is associated with increases in BP, which appear to occur after 24 hours of SD and are maintained over increasing periods of SD. The observed hemodynamic changes may have resulted due to disordered vascular endothelial function, as reflected in alterations in L-Arg and ADMA levels.

Dose-dependent and opposite effects of orexin A on prepulse inhibition response in sleep-deprived and non-sleep-deprived rats

Orexin is a novel neurotransmitter released from lateral hypothalamus, that is a crucial modulator in sleep/wakefulness system. Recent studies also suggest its possible role in the neurodevelopmental disorders, such as schizophrenia. Our study consists of two experiments, where we investigate the effect of orexin A (OXA), one of two isoforms of orexin that can pass blood brain barrier, on the prepulse inhibition of acoustic startle reflex. The first experiment tested the effect of OXA on PPI response of non-sleep-deprived rats via intraperitoneal injection 30min before testing. Our results show that 40μg/kg OXA attenuates PPI% at 78dB and 86dB prepulse intensities. The second experiment utilized 72-h REM sleep deprivation, as a model for sleep-deprivation-induced impairment of PPI response. Here, we tested the effect of OXA on PPI% of sleep-deprived rats via intraperitoneal injection at the last 30min of sleep deprivation, testing for PPI immediately afterwards. Our results showed that (1) sleep deprivation attenuates the PPI% at 74dB, 78dB and 86dB prepulse intensities and (2) 10μg/kg OXA completely restores the impaired PPI% at 78dB only, where the highest PPI% impairment was observed. These results suggest that orexin A modulates PPI response in rats in a dose-dependent manner, oppositely for non-sleep-deprived and sleep-deprived rats, and a more detailed investigation for the etiology of this effect should follow.

Sleep deprivation induces changes in 5-HT actions and 5-HT1A receptor expression in the rat hippocampus.

A 12h sleep deprivation enhances the expression of 5-hydroxytryptamine (5-HT) 1A receptors in rat hippocampus that recedes with 48h sleep recovery. The depressant effect of applied 5-HT on the field excitatory postsynaptic potentials recorded in the CA1 area, is also enhanced in hippocampi of SD rats. Following a 24 or 48h sleep recovery, the increase in the 5-HT effect subsided. These results have implications for therapeutics treating clinical depression.

Sleep Deprivation in Young and Healthy Subjects Is More Sensitively Identified by Higher Frequencies of Electrodermal Activity than by Skin Conductance Level Evaluated in the Time Domain.

We analyzed multiple measures of the autonomic nervous system (ANS) based on electrodermal activity (EDA) and heart rate variability (HRV) for young healthy subjects undergoing 24-h sleep deprivation. In this study, we have utilized the error awareness test (EAT) every 2 h (13 runs total), to evaluate the deterioration of performance. EAT consists of trials where the subject is presented words representing colors. Subjects are instructed to press a button (“Go” trials) or withhold the response if the word presented and the color of the word mismatch (“Stroop No-Go” trial), or the screen is repeated (“Repeat No-Go” trials). We measured subjects' (N = 10) reaction time to the “Go” trials, and accuracy to the “Stroop No-Go” and “Repeat No-Go” trials. Simultaneously, changes in EDA and HRV indices were evaluated. Furthermore, the relationship between reactiveness and vigilance measures and indices of sympathetic control based on HRV were analyzed. We found the performance improved to a stable level from 6 through 16 h of deprivation, with a subsequently sustained impairment after 18 h. Indices of higher frequencies of EDA related more to vigilance measures, whereas lower frequencies index (skin conductance leve, SCL) measured the reactiveness of the subject. We conclude that indices of EDA, including those of the higher frequencies, termed TVSymp, EDASymp, and NSSCRs, provide information to better understand the effect of sleep deprivation on subjects' autonomic response and performance.

Subjective Mood in Young Unmedicated Depressed Women under High and Low Sleep Pressure Conditions.

Diurnal mood variations are one of the core symptoms in depression, and total sleep deprivation (SD) can induce rapid, short-lasting clinical improvement in depressed patients. Here, we investigated if differential sleep pressure conditions impact on subjective mood levels in young women with major depressive disorder (MDD) without sleep disturbances, and in healthy controls. Eight healthy and eight MDD women underwent 40-h SD (high sleep pressure) and 40-h multiple NAP (low sleep pressure) protocols under constant routine conditions during which subjective mood was assessed every 30-min. MDD women rated overall significantly worse mood than controls, with minimal values for both groups during the biological night (ca. 4 a.m.), under high and low sleep pressure conditions. During SD, nighttime mood ratings in MDD women were lower than in controls and partially recovered during the second day of SD, but never attained control levels. The degree of this diurnal time-course in mood under SD correlated positively with sleep quality in MDD women. Our data indicate that MDD women without sleep disturbances did not exhibit a SD-induced antidepressant response, suggesting that the mood enhancement response to sleep deprivation might be related to the co-existence of sleep disturbances, which is an association that remains to be fully established.

Total sleep deprivation and pain perception during cold noxious stimuli in humans

Background and aimsA substantial portion of the population suffers from chronic pain leading to significant health care costs and lost productivity. Loss of sleep duration and quality are widely reported in patients suffering from a variety of acute or chronic pain conditions. Conversely, sleep loss has been known to elevate pain perception; thus a potential bi-directional relationship exists between sleep deprivation and pain. To date, the majority of studies examining the relationship between experimentally induced pain and sleep loss have focused on the measurement of pain threshold. Additionally, despite evidence of sex differences in ratings of perceived pain, previous studies examining pain following sleep loss have not probed for sex differences. We examined the effects of 24-h total sleep deprivation (TSD) on perceived pain during a 2-min cold pressor test (CPT). We hypothesized that TSD would augment perceived pain and that women would demonstrate an elevated pain response compared to men. MethodsTesting was carried out in 14 men and 13 women. All subjects reported to be nonsmokers with no history of cardiovascular disease, autonomic dysfunction, asthma, or diabetes. All female subjects were free of oral contraceptive use, and were tested during the early follicular phase of the menstrual cycle. Trial order was randomized and testing sessions (Normal sleep (NS) and TSD) were separated by approximately one month. Subjects immersed their left hand, up to the wrist, in an ice water bath (∼1°C), and perceived pain was recorded every 15s from a modified Borg scale (6–20 arbitrary units a.u.). ResultsPerceived pain responses during CPT were augmented following TSD (Δ1.2 a.u.; time×condition, p<0.05). The augmented pain response following TSD was noted when perceived pain was expressed as mean (NS Δ7.0±0.5 vs. TSD Δ8.2±0.5 a.u.; p<0.05) or peak (NS Δ8.9±0.6 vs. TSD Δ10.2±0.5 a.u.; p<0.05) perceived pain. The effects of TSD on perceived pain were similar in both men and women (condition×time×sex, p>0.05). Conclusions and implicationsWe conclude that TSD significantly augments perceived pain during CPT, but this response was not sex dependent. These findings support emerging evidence that adequate sleep represents a relevant, and cost effective, preventative/therapeutic strategy to reduce self-perceived pain in both men and women.