Days Of Sleep Deprivation Research Articles

Prolonged Sleep Deprivation Induces a Reprogramming of Circadian Rhythmicity with the Hepatic Metabolic Transcriptomic Profile.

Sleep disturbances can disrupt the overall circadian rhythm. However, the impact of sleep deprivation on the circadian rhythm of the liver and its underlying mechanisms still requires further exploration. In this study, we subjected male mice to 5 days of sleep deprivation and performed liver transcriptome sequencing analysis at various time points within a 24-h period. Subsequently, we monitored the autonomic activity and food intake in these male mice for six days post-sleep deprivation. We observed alterations in sleep-wake and feeding rhythms in the first two days following sleep deprivation. Additionally, we also observed a decrease in 24-h serum-glucose levels. Liver transcriptome sequencing has shown that sleep deprivation induces the rhythmic transcription of a large number of genes, or alters the rhythmic properties of genes, which were then significantly enriched in the carbohydrate, lipid, and protein metabolism pathways. Our findings suggest that under conditions of prolonged sleep deprivation, the expression of metabolic-related genes in the liver was reset, leading to changes in the organism's metabolic state to ensure energy supply to sustain prolonged wakefulness.

Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus.

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro-inflammatory cytokines and Sirt1/miR-134 pathway-related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1β, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.

Melatonin protects against body weight gain induced by sleep deprivation in mice

Sleep deprivation is an epidemic phenomenon in modern society. Lack of sleep has been shown to result in metabolic and endocrine disorders that predispose to obesity and other chronic metabolic diseases. Melatonin is a sleep-related neurohormone and affected by the circadian rhythm and light/dark cycles. Melatonin has recently been used to ameliorate diet-induced or night light-induced energy metabolic imbalance. However, the effect of melatonin on sleep deprivation-induced obesity has been poorly characterized. This study focuses on the protective effects of melatonin on lipid metabolism and body weight homeostasis in sleep-deprived mice. Mice subjected to sleep deprivation had significantly decreased plasma melatonin content and increased food intake and body weight gain compared to that of control. Meanwhile, the transcription factor PPARγ protein in liver increased, but there were no significant changes in hepatic circadian proteins BMAL1 and REV-ERBα after 10 consecutive days of sleep deprivation. Moreover, melatonin supplementation increased liver AMPKα/PPARα signaling pathway activity, which leads to lipid catabolism and reduced fat accumulation. These findings suggested that melatonin may be a potential agent for protecting against sleep deprivation-induced obesity.

Sleep Deprivation Influences Trial-to-Trial Transfer but Not Task Performance.

Previous research has shown that sleep deprivation can affect emotions and some cognitive functions. However, research on how sleep deprivation influences the visuomotor memory have rarely been reported. In the current study, a Fitts’ Law task was used to investigate how movement and the visuomotor memory are affected under the condition of sleep deprivation. Experiment 1 had 36 participants (15 males, mean age = 21.61 years) complete the same Fitts’ Law task 10 days apart under standard conditions. Experiment 2 had five participants (three males, mean age = 27.2 years) complete the task after 7 days of sleep deprivation, then complete it again after 10 days without sleep deprivation. Experiment 1 demonstrated the stability of the trial-to-trial effects. Experiment 2 showed that the previous trial (n) exerted no effect on the current trial (n + 1) under the conditions of sleep deprivation (p = 0.672). However, the effect was observed after 10 days without sleep deprivation (p = 0.013). This suggests that sleep deprivation did not affect task performance but influenced the transfer of the trial history. Future studies are required to investigate the effect of sleep deprivation with more participants.

Sleep deprivation leads to further impairment of hippocampal synaptic plasticity by suppressing melatonin secretion in the pineal gland of chronically unpredictable stress rats

There has been ample research showing that insomnia is a potential trigger of depression as well as a symptom of depression. These two factors contribute to behavioural problems and are closely related to the plasticity of hippocampal synapses. Although depression and insomnia impair hippocampal synaptic plasticity, the mechanism by which this happens remains a mystery. This study aimed to investigate the pathogenesis of insomnia comorbidity in depression and the regulatory effect of venlafaxine combined with melatonin on hippocampal synaptic plasticity in chronic unpredictable mild stress (CUMS) with sleep deprivation (SD) rats. Thus, rats were subjected to 14 days of chronic mild unpredictable stress, gradually acclimated to sleep deprivation on days 12–14. Followed by 21 consecutive days of sleep deprivation, 18 h per day, with daily gavage of venlafaxine (13.5 mg/kg) + melatonin (72 mg/kg) on days 15–36. Venlafaxine + melatonin treatment improves depression-like behaviour, pentobarbital sodium experimental sleep latency, and sleep duration in CUMS +SD rats. In addition to improving depressive-like behaviors, sleep deprivation also upregulates the expression of caspase-specific cysteine protein 3 (Caspase 3) in the pineal glial cells of chronic mild rats, as well as in hippocampal microglia. Expression of ionic calcium-binding adaptor 1 (iba-1), downregulates the secretion of several synaptic plasticity-related proteins, notably cAMP response element binding protein (CREB), glial cell line-derived neurotrophic factor (GDNF), and the synaptic scaffolding protein Spinophiline (Spinophiline). Hematoxylin-eosin staining showed that the structure of the pineal gland and hippocampus was damaged, and Golgi staining showed that the dendrites and spines in the DG area of the hippocampus were destroyed, vaguely aggregated or even disappeared, and the connection network could not be established. Western blot analysis further revealed a positive correlation between low melatonin levels and reduced Spinophiline protein. Interestingly, venlafaxine + melatonin reversed these events by promoting hippocampal synaptic plasticity by regulating melatonin secretion from the pineal gland. Therefore, it exerted an antidepressant effect in sleep deprivation combined with CUMS model rats. Overall, the results of this study suggest that the pathophysiology of depressive insomnia comorbidity is mediated by impaired pineal melatonin secretion and impaired hippocampal synaptic plasticity. In addition, these responses are associated with melatonin secretion from the pineal gland.

Acute sleep deprivation increases inflammation and aggravates heart failure after myocardial infarction.

Sleep disorders have been observed among patients with heart failure. The aim of this study was to investigate whether acute sleep deprivation (SD) aggravates left heart function. Male C57B/L6 mice were assigned to four experimental groups. Ligation of the left anterior descending branch (LAD) caused myocardial infarction (MI) in mice in the LAD group and the LAD+SD group, while mice in the sham and sham+SD groups underwent the same surgery without ligation. Echocardiography was performed before and 8 weeks after ligation of the LAD to evaluate the left ventricular internal diameter at diastole (LVIDd), left ventricular internal diameter at systole (LVIDs), ejection fraction (EF), and fractional shortening (FS). Seven days of sleep deprivation induced using the modified single platform method resulted in a lower EF and FS and a higher LVIDd and LVIDs, as well as increased expression of the IL-1β, IL-18, and IL-10 mRNAs in the left ventricular tissue of MI mice. ELISA also indicated higher levels of IL-1β and IL-10 in the LAD+SD group. It was concluded that acute sleep deprivation induced cardiovascular alterations in cardiac structure and function in HF mice, accompanied by increased levels of inflammatory cytokines.

Xiaoyao Pill Improves the Affective Dysregulation of Sleep-deprived Female Mice by Inhibiting Brain Injury and Regulating the Content of Monoamine Neurotransmitter.

Sleep curtailment is a serious problem in many societies. Clinical evidence has shown that sleep deprivation is associated with mood dysregulation, formation of false memory, cardio-metabolic risk factors and outcomes, inflammatory disease risk, and all-cause mortality. The affective disorder dysregulation caused by insufficient sleep has become an increasingly serious health problem. However, to date, not much attention has been paid to the mild affective dysregulation caused by insufficient sleep, and there is no clear and standard therapeutic method to treat it. The Xiaoyao Pill is a classic Chinese medicinal formula, with the effect of dispersing stagnated hepatoqi, invigorating the spleen, and nourishing the blood. Therefore, it is most commonly used to treat gynecological diseases in China. In the present study, the effects of the Xiaoyao Pill on affective dysregulation of sleep-deprived mice and its underlying molecular mechanisms were investigated. Forty adult female mice were used in the present study. The sleep deprivation model was established by improving the multi-platform water environment method. After 7 consecutive days of sleep deprivation, the mice were administrated low (LXYP, 0.32mg/kg) and high (HXYP, 0.64 mg/kg) doses of the Xiaoyao Pill for two weeks. Then, the body weight, behavioral deficits, and histopathology were evaluated. Meanwhile, the expression of c-fos protein and the concentrations of monoamine neurotransmitters in the hippocampus and prefrontal cortex were determined after two weeks of treatment. Xiaoyao Pill treatment significantly increased body weight and sucrose consumption and decreased the irritability scores of the sleep-deprived mice. Meanwhile, Xiaoyao Pill treatment prevented brain injury and inhibited the expression of c-fos protein in the hippocampus and prefrontal cortex. In addition, HXYP treatment significantly upregulated the levels of NE in the hippocampus and prefrontal cortex (p < 0.01). LXYP treatment significantly up-regulated the levels of 5-HT in the prefrontal cortex. Meanwhile, both HXYP and LXYP treatment significantly upregulated the levels of DA in the prefrontal cortex (p < 0.05 or p < 0.01) of sleep-deprived mice. The present study demonstrates that Xiaoyao Pill treatment prevented the behavioral deficits of mice induced by sleep deprivation by promoting the recovery of brain tissue injury and up-regulating the levels of NE, 5-HT, and DA in the brain tissue.

Use of Actigraphy for a Rat Behavioural Sleep Study.

Previous studies of animal behavioural sleep is mainly divided into two study types, observation by video recording or counts by sensor, both of which require a complex environment and procedure. An actigraph unit is a commercially available product which can provide non-invasive monitoring human rest/activity cycles. The goal of this study was to evaluate whether actigraphy can be applied for analysing behavioural sleep in rats, since no reports have described utilization of the actigraphy unit for monitoring sleep of small animals. The actigraph unit was held on the chest of eight male rats by a loose elastic belt. The rats spent two days in a normal condition, followed by two days of sleep deprivation. Total counts measured by the actigraph could be clearly divided into two phases, sleep phase and awake phase, when the rats were kept in the normal cage. Next, the rats were moved into the sleep-deviation cage, and the total counts were significantly higher during daytime, indicating the successful induction of sleep deprivation. These results showed that the actigraphy unit monitored rest/activity cycles of rats, which will contribute to making sleep behaviour experiments easier.

Very-Short-Term Sleep Deprivation Slows Early Recovery of Lymphocytes in Septic Patients.

Sleep plays an important role in immune function. However, the effects of very-short-term sleep deprivation on the early recovery of immune function after sepsis remain unclear. This study was conducted in the intensive care unit to investigate the effects of 2 consecutive days of sleep deprivation (SD) on lymphocyte recovery over the following few days in septic patients who were recovering from a critical illness. The patients' self-reports of sleep quality was assessed using the Richards–Campbell Sleep Questionnaire at 0 and 24 h after inclusion. The demographic, clinical, laboratory, treatment, and outcome data were collected and compared between the good sleep group and poor sleep group. We found that 2 consecutive days of SD decreased the absolute lymphocyte count (ALC) and ALC recovery at 3 days after SD. Furthermore, post-septic poor sleep decreased the plasma levels of atrial natriuretic peptide (ANP) immediately after 2 consecutive days of SD. The ANP levels at 24 h after inclusion were positively correlated with ALC recovery, the number of CD3+ T cells, or the number of CD3+ CD4+ cells in the peripheral blood on day 5 after inclusion. Our data suggested that very-short-term poor sleep quality could slow down lymphocyte recovery over the following few days in septic patients who were recovering from a critical illness. Our results underscore the significance of very-short-term SD on serious negative effects on the immune function. Therefore, it is suggested that continuous SD or several short-term SD with short intervals should be avoided in septic patients.

Paradoxical sleep deprivation induces oxidative stress in the submandibular glands of Wistar rats.

Paradoxical sleep deprivation has been associated with impaired salivary secretion in rats. However, the mechanism that underlies this is not known. Therefore, this study assessed salivary and serum oxidative stress levels following paradoxical sleep deprivation in rats. Twenty-one male Wistar rats randomly divided into three groups of seven rats each as; Control (C); partialsleep-deprived (PSD); and total sleep-deprived (TSD) wereused. Malondialdehyde (MDA) concentration, Superoxide dismutase (SOD), and catalase activities were evaluated insaliva, serum, and submandibular glands after seven daysof sleep deprivation. Data were expressed as mean±standard error of the mean and analyzed using one-way ANOVA, Tukey HSD post hoc, and Pearson's correlation tests. Serum MDA levels were significantly higher in both the TSD and PSD groups compared to the control group whereas only the TSD group showed higher submandibular MDA levels compared to the PSD group and the control group. Submandibular SOD activity was significantly lower in both the TSD and PSD groups compared to the control group. Serum catalase activity was significantly lower in the TSD group only compared to the control group. These results have demonstrated for the first time that paradoxical sleep deprivation was associated with changes in the oxidant/antioxidant defense system in the submandibular salivary glands of male Wistar rats which may contribute to impairment in salivary secretion.

Treadmill exercise ameliorates chronic REM sleep deprivation-induced anxiety-like behavior and cognitive impairment in C57BL/6J mice

Various sleep disorders have deleterious effects on mental and cognitive performance. Exercise, as an alternative therapeutic strategy, exerts beneficial impacts on human health. In the present study, we aimed to evaluate the effects of 4 weeks treadmill exercise (4W-TE) on anxiety-like behavior and cognitive performance in mice exposed to 2 months REM sleep deprivation (2M-SD) (20 h per day). Behavioral performance of mice in elevated plus maze test (EPM), open field test (OFT), Y maze test (YM) and Morris water maze test (MWM) was recorded and analyzed 28 h after the last day of sleep deprivation. After behavioral tests, various neurotransmitters including norepinephrine (NE), dopamine (DA), serotonin (5-HT) and γ-aminobutyric acid (GABA) in mouse hippocampus were quantified using high performance liquid chromatography. The hippocampal levels of insulin-like growth factor-1 (IGF-1) and brain derived neurotrophic factor (BDNF) were further detected using ELISA. Behavioral data indicated that 2M-SD exposure induced anxiety-like behaviors and cognitive impairment, as evidenced by the decreased open-arm entries in EPM, reduced central area travels in OFT, declined spontaneous alteration in YM and prolonged escaping latency in MWM. In addition, 2M-SD exposure increased NE and DA, decreased 5-HT and GABA, and reduced IGF-1 and BDNF levels in mouse hippocampus. Interestingly, all these behavioral, neurochemical and neurobiological changes can be ameliorated by 4W-TE training. In summary, these findings confirm the beneficial impacts of exercise on health and provide further experimental evidence for future application of exercise as an alternative therapy against the mental and cognitive problems in patients with sleep disorders.

Effects of butylphthalide on microglia activation in frontal lobe of rats after chronic sleep deprivation

Objective: To evaluate the effects of butylphthalide on microglia activation and inflammatory factors in frontal lobe of rats after chronic sleep deprivation. Methods: Rats were divided into four groups(n＝8): control group, platform group, chronic sleep deprivation group and butylphthalide intervention group. Chronic sleep deprivation was performed in rats of chronic sleep deprivation group and butylphthalide intervention group for 18 h per day using the multiple platforms method, and sleep deprivation lasted for 28 days. At the same time, rats in platform group were put in platform, while rats in control group were in normal sleep. After 28 days of sleep deprivation, rats in butylphthalide intervention group were intraperitoneally injected with butylphthalide 100 mg/kg for 14 days, meanwhile rats in other groups were intraperitoneally injected with saline. Then brains were collected and ionized calcium binding adaptor molecule-1 (Iba-1) positive cells in cortex in frontal lobe were studied and counted. The expressions of inducible nitric oxide synthase (iNOS) and arginase1 (Arg1) in frontal lobe were detected by Western blot, and the mRNA levels of interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α) were determined by real-time PCR. Results: Compared with control or platform group, the Iba-1 positive cells in chronic sleep deprivation group were large with long process, and increased cell counts were also found in the chronic sleep deprivation group (all P＜0. 05). Moreover, the mRNA expression levels of iNOS, IL-1, IL-6, TNF-α were increased, while the expression of Arg1 was decreased in frontal lobe in rats of the chronic sleep deprivation group compared with the control or platform group (all P＜0. 05). The Iba-1 positive cells in butylphthalide intervention group were reduced compared with chronic sleep deprivation group (P＜0. 05). And the mRNA expression levels of iNOS, IL-1, IL-6 and TNF-α were decreased, while the expression of Arg1 did not chang in rats of the butylphthalide intervention group compared with the chronic sleep deprivation group (all P＜0. 05). Conclusion: Butylphthalide might inhibit the activation and decrease the inflammatory factors in frontal lobe of rats after chronic sleep deprivation.

Sleep-deprived cognitive impairment in aging mice is alleviated by rapamycin.

Sleep deprivation-induced cognitive impairment is a major health concern and an age-related risk factor for dementia. There is an urgent need to develop ways of preventing the adverse neurological effects of sleep deprivation, but current preclinical animal models of short-term sleep deprivation are not well described. C57BL6 mice of varying ages were sleep deprived for 4 hours a day for 4 days, and then tested with a Box maze navigation task. Sleep deprived mice at young, middle and older ages showed learning impairment that varied by strain and gender. In general, females were more sensitive to sleep deprivation than males. To determine whether sleep deprivation-induced learning impairment would respond to therapeutic intervention, an independent cohort of mice was treated with rapamycin daily during the 4 days of sleep deprivation. Mice that were sleep deprived and treated with rapamycin showed significant improvement in learning time suggesting that the cognitive impairment might be associated in part with molecular and cellular mechanisms targeted by rapamycin. The observations from this study suggest that aging mice would be productive models to study pathobiology and therapeutic intervention of cognitive impairment triggered by age-related sleeping disorders in people.

A study of skin characteristics with long-term sleep restriction in Korean women in their 40s.

Previous studies have demonstrated increased pore size and darkening skin color with total sleep deprivation. There are many studies of skin characteristics with short-term sleep restriction, but there are few studies on skin characteristics when sleep is restricted more than three consecutive days. This study evaluated skin changes with sleep limited to 4hours per night for six nights. The study included 32 Korean women in their 40s. Skin hydration, desquamation, barrier recovery, texture, gloss, transparency, elasticity, crow's feet, frown lines, and color were measured. Individual sleep time was monitored by smartwatches. Subjects slept 8hours per night for six nights in week one and 4hours per night for six nights in week two. Skin hydration was significantly reduced after 1day of sleep deprivation, and it continued to decrease. Skin gloss, desquamation, transparency, elasticity, and wrinkles were significantly aggravated after 1day of sleep deprivation. Skin texture was significantly aggravated on the fourth day of sleep restriction. Elasticity was most affected by reduced sleep, with a standardized coefficient of -.320, indicating a significant decrease over time as compared to other characteristics. Skin hydration was gradually decreased with sleep restriction. Skin texture did not change after only 1day of sleep restriction. It is a new finding that elasticity decreases more than other skin characteristics with prolonged sleep restriction.

Effects of strategic early-morning caffeine gum administration on association between salivary alpha-amylase and neurobehavioural performance during 50 h of sleep deprivation

Self-assessment is the most common method for monitoring performance and safety in the workplace. However, discrepancies between subjective and objective measures have increased interest in physiological assessment of performance. In a double-blind placebo-controlled study, 23 healthy adults were randomly assigned to either a placebo (n = 11; 5 F, 6 M) or caffeine condition (n = 12; 4 F, 8 M) while undergoing 50 h (i.e. two days) of total sleep deprivation. In previous work, higher salivary alpha-amylase (sAA) levels were associated with improved psychomotor vigilance and simulated driving performance in the placebo condition. In this follow-up article, the effects of strategic caffeine administration on the previously reported diurnal profiles of sAA and performance, and the association between sAA and neurobehavioural performance were investigated. Participants were given a 10 h baseline sleep opportunity (monitored via standard polysomnography techniques) prior to undergoing sleep deprivation (total sleep time: placebo = 8.83 ± 0.48 h; caffeine = 9.01 ± 0.48 h). During sleep deprivation, caffeine gum (200 mg) was administered at 01:00 h, 03:00 h, 05:00 h, and 07:00 h to participants in the caffeine condition (n = 12). This strategic administration of caffeine gum (200 mg) has been shown to be effective at maintaining cognitive performance during extended wakefulness. Saliva samples were collected, and psychomotor vigilance and simulated driving performance assessed at three-hour intervals throughout wakefulness. Caffeine effects on diurnal variability were compared with previously reported findings in the placebo condition (n = 11). The impact of caffeine on the circadian profile of sAA coincided with changes in neurobehavioural performance. Higher sAA levels were associated with improved performance on the psychomotor vigilance test during the first 24 h of wakefulness in the caffeine condition. However, only the association between sAA and response speed (i.e. reciprocal-transform of mean reaction time) was consistent across both days of sleep deprivation. The association between sAA and driving performance was not consistent across both days of sleep deprivation. Results show that the relationship between sAA and reciprocal-transform of mean reaction time on the psychomotor vigilance test persisted in the presence of caffeine, however the association was relatively weaker as compared with the placebo condition.

Impact of Partial Sleep Deprivation on Psychological Functioning: Effects on Mindfulness and Basic Psychological Need Satisfaction

Extending previous research on the psychological costs of sleep deprivation, the present study examined the impact of insufficient sleep on the capacity to be mindful as well as on the satisfaction of individuals’ basic psychological needs, two psychological sources of mental health. The interrelationship between these two psychological resources and fatigue following sleep deprivation was also examined. Participants were 49 adults (77% female; Mage = 32.81 years, SD = 13.09 years) who were randomly assigned to either an experimental (N = 23) or a control (N = 26) group. The study had a 4-day within-person design. In the experimental group, a baseline assessment day was followed by 3 days of partial sleep deprivation (i.e., 5-h sleep per night), whereas participants in the control group slept as usual across the 4-day period. Participants rated their fatigue and psychological functioning each evening and wore an actigraph watch which monitored their sleep. Participants reported increased fatigue after 1 day of sleep deprivation, whereas it took 3 days of sleep deprivation before their mindfulness and need satisfaction deteriorated. Mediational analyses indicated that decreased need satisfaction after 3 days of sleep deprivation was completely accounted for (i.e., explained) by increased fatigue and subsequent decreases in mindfulness. These findings build on previous research by showing that mindfulness and need-based experiences not only precede but also follow from sleep at night.

Prolonged sleep deprivation decreases cell proliferation and immature newborn neurons in both dorsal and ventral hippocampus of male rats

Previous studies have indicated that sleep deprivation negatively affects hippocampal neurogenesis, which may explain the reason for the relation between sleep loss and depression. Increasing evidence indicates that the hippocampus is anatomically and functionally segregated along a dorsolateral (cognitive function)/ventromedial (control for mood and stress response) axis. Thus, the present study was conducted to elucidate regional differences in the adverse effects of sleep deprivation on hippocampal neurogenesis. Male Sprague-Dawley rats were subjected to sleep deprivation using the “platform on the water” method for 24- or 72-h. Quantification of hippocampal cell proliferation and immature newborn neurons was stereologically estimated using immunostaining with Ki-67 and doublecortin (DCX), respectively, by optical fractionator method. A consecutive three days of sleep deprivation significantly reduced the density of Ki-67- and DCX-immunopositive cells both in the dorsal and ventral hippocampal subgranular zone and the decrease in DCX-labeled cells was more pronounced in the ventral hippocampus than in dorsal region. Our results indicate that prolonged sleep deprivation decreases hippocampal cell proliferation and neurogenesis in both the dorsal and ventral dentate gyrus. Future studies will be needed to clarify the impact of sleep deprivation-induced decreases in hippocampal neurogenesis on the development of depression.

Decreased salivary alpha-amylase levels are associated with performance deficits during sleep loss

During sleep deprivation, neurobehavioral functions requiring sustained levels of attention and alertness are significantly impaired. Discrepancies between subjective measures of sleepiness and objective performance during sustained operations have led to interest in physiological monitoring of operator performance. Alertness, vigilance, and arousal are modulated by the wake-promoting actions of the central noradrenergic system. Salivary alpha-amylase (sAA) has been proposed as a sensitive peripheral measure of noradrenergic activity, but limited research has investigated the relationship between sAA and performance. In a laboratory-controlled environment, we investigated the relationship between sAA levels, subjective sleepiness, and performance during two days (50h) of total sleep deprivation. Beginning at 09:00, twelve healthy participants (5 females) aged 22.5±2.5years (mean±SD) provided saliva samples, recorded ratings of subjective sleepiness, completed a brief 3-min psychomotor vigilance task (PVT-B) and performed a 40-min simulated driving task, at regular 3h intervals during wakefulness. Ratings of subjective sleepiness exhibited a constant linear increase (p<0.001) during sleep deprivation. In contrast, sAA levels showed a marked diurnal profile, with levels increasing during the day (p<0.001) and steadily declining in the evening and early-morning (p<0.001). PVT-B (mean reaction time and mean slowest 10% reaction time) and simulated driving performance (speed deviation and lane deviation) also exhibited diurnal profiles across the two days of sleep deprivation. Performance peaked in the afternoon (p<0.001) and then steadily worsened as wakefulness continued into the evening and early-morning (p<0.001). Further analysis revealed that higher sAA levels in the hour preceding each performance assessment were associated with better PVT-B and driving performance (p<0.001). These findings suggest that sAA measures may be suitable indicators of performance deficits during sustained wakefulness and highlight the potential for sAA to be considered for physiological monitoring of performance. In operational environments sAA levels, as part of a panel of physiological measures, may be useful for assessing fitness-for-duty prior to safety being compromised or when performance deficits are unknown.

An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep

Sheep have large brains with human-like anatomy, making them a useful species for studying brain function. Sleep homeostasis has not been studied in sheep. Here, we establish correlates of sleep homeostasis in sheep through a sleep deprivation experiment. We then use these correlates to elucidate the nature of sleep deficits in a naturally occurring ovine model of neuronal ceroid lipofuscinosis (NCL, Batten disease) caused by a mutation in CLN5 In humans, mutations in this gene lead to cortical atrophy and blindness, as well as sleep abnormalities. We recorded electroencephalograms (EEGs) from unaffected and early stage CLN5(-/-) (homozygous, affected) sheep over 3 consecutive days, the second day being the sleep deprivation day. In unaffected sheep, sleep deprivation led to increased EEG delta (0.5-4 Hz) power during non-rapid eye movement (NREM) sleep, increased time spent in the NREM sleep state, and increased NREM sleep bout length. CLN5(-/-) sheep showed comparable increases in time spent in NREM sleep and NREM sleep bout duration, verifying the presence of increased sleep pressure in both groups. Importantly, CLN5(-/-) sheep did not show the increase in NREM sleep delta power seen in unaffected sheep. This divergent delta power response is consistent with the known cortical degeneration in CLN5(-/-) sheep. We conclude that, whereas sleep homeostasis is present in CLN5(-/-) sheep, underlying CLN5(-/-) disease processes prevent its full expression, even at early stages. Such deficits may contribute to early abnormalities seen in sheep and patients and warrant further study. Sleep abnormalities pervade most neurological diseases, including the neuronal ceroid lipofuscinoses (NCLs). Here, we show that, in an ovine model of a variant late-infantile NCL, there is abnormal expression of sleep homeostasis. Whereas some sleep pressure correlates respond to sleep deprivation, the strongest electroencephalogram (EEG) correlate of sleep pressure, non-REM delta power, failed to increase. This highlights the relevance of sleep deficits in this disease, in which the drive for sleep exists but the underlying disease prevents its full expression. Sleep abnormalities could contribute to early disease symptoms such as behavioral disorder and cognitive decline. Our study also shows sleep homeostatic EEG correlates in sheep, opening up new opportunities for studying sleep in a large social mammal with complex human-like brain neuroanatomy.

Effect of acute sleep deprivation on left atrial mechanics assessed by three-dimensional echocardiography.

Although sleep deprivation (SD) affects cardiovascular system in many ways, physio-pathological changes in cardiac chamber volume and function have not been described well. The aim of the present study was to investigate the effect of SD on left atrial (LA) and ventricular function with three-dimensional (3D) echocardiography. Thirty-two healthy individuals (12 females, mean age 33.25 ± 8.18) were evaluated. Echocardiographic examination was performed once after a night of regular sleep and a night of sleep debt. Beside conventional parameters, 3D phasic volumes and function were measured using a commercially available 3D echocardiography system and offline analysis software. Mean sleep duration of the study group was 8.15 ± 2.19 h in the day of regular sleep and 2.56 ± 2.25 h in the day of sleep deprivation. There was a significant prolongation in deceleration time (180.83 ± 15.34 vs. 166.44 ± 26.12; p = 0.044) and increase in E/e' (6.95 ± 1.26 vs. 6.38 ± 0.85; p = 0.005). Among 3D measurements, the difference in left ventricular ejection fraction (EF), LA EF, LA reservoir function and LA active EF were not significant. Mean LA passive EF of the individuals was significantly lower after night shift (24.10 ± 7.66 vs. 31.49 ± 7.75; p = 0.006). Acute SD is associated with a reduction in LA passive emptying function in healthy adults. 3D-derived indices were sufficient to show subclinical diastolic dysfunction according to impairment in passive phase of LA ejection. Prospective large-scale studies are needed to enlighten this issue.