Modelling maintenance of wakefulness in rats: comparing potential non-invasive sleep-restriction methods and their effects on sleep and attentional performance.

While several methods have been used to restrict the sleep of experimental animals, it is often unclear whether these different forms of sleep restriction have comparable effects on sleep-wake architecture or functional capacity. The present study compared four models of sleep restriction, using enforced wakefulness by rotation of cylindrical home cages over 11 h in male Wistar rats. These included an electroencephalographic-driven 'Biofeedback' method and three non-invasive methods where rotation was triggered according to a 'Constant', 'Decreasing' or random protocol based upon the 'Weibull' distribution fit to an archival Biofeedback dataset. Sleep-wake architecture was determined using polysomnography, and functional capacity was assessed immediately post-restriction with a simple response latency task, as a potential homologue of the human psychomotor vigilance task. All sleep restriction protocols resulted in sleep loss, behavioural task disengagement and rebound sleep, although no model was as effective as real-time electroencephalographic-Biofeedback. Decreasing and Weibull protocols produced greater recovery sleep than the Constant protocol, mirrored by comparably poorer simple response latency task performance. Increases in urinary corticosterone levels following Constant and Decreasing protocols suggested that stress levels may differ between protocols. Overall, these results provide insight into the value of choosing a specific sleep restriction protocol, not only from the perspective of animal welfare and the use of less invasive procedures, but also translational validity. A more considered choice of the physiological and functional effects of sleep-restriction protocols in rodents may improve correspondence with specific types of excessive daytime sleepiness in humans.

Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation.

Understanding how metabolite levels change over the 24 hour day is of crucial importance for clinical and epidemiological studies. Additionally, the association between sleep deprivation and metabolic disorders such as diabetes and obesity requires investigation into the links between sleep and metabolism. Here, we characterise time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles. Healthy male participants (n = 15) completed an in-laboratory study comprising one 24 h sleep/wake cycle prior to 24 h of continual wakefulness under highly controlled environmental conditions. Urine samples were collected over set 2-8 h intervals and analysed by (1)H NMR spectroscopy. Significant changes were observed with respect to both time of day and sleep deprivation. Of 32 identified metabolites, 7 (22%) exhibited cosine rhythmicity over at least one 24 h period; 5 exhibiting a cosine rhythm on both days. Eight metabolites significantly increased during sleep deprivation compared with sleep (taurine, formate, citrate, 3-indoxyl sulfate, carnitine, 3-hydroxyisobutyrate, TMAO and acetate) and 8 significantly decreased (dimethylamine, 4-DTA, creatinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 4-DEA, 4-hydroxyphenylacetate). These data indicate that sampling time, the presence or absence of sleep and the response to sleep deprivation are highly relevant when identifying biomarkers in urinary metabolic profiling studies.

Napping reverses the salivary interleukin-6 and urinary norepinephrine changes induced by sleep restriction.

CONTEXT: Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep. OBJECTIVES: Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown. DESIGN: This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects. SETTING: The study was conducted in a laboratory-based study. PARTICIPANTS: The subjects were 11 healthy young men. INTERVENTION: We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00. MAIN OUTCOME MEASURES: Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods. RESULTS: The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition. CONCLUSIONS: Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.

Effects of food or sleep deprivation during civilian survival training on clinical chemistry variables.

OBJECTIVE: To describe clinical chemistry and weight changes after short-term food or sleep deprivation or multiple deprivations during civilian survival training. METHODS: Data from one baseline-controlled two-period crossover study designed to compare sleep deprivation for up to 50 hours with food deprivation for up to 66 hours (n = 12) and data from regular multiple-deprivations survival training comparing participants (n = 33) with nondeprived instructors (n = 10). RESULTS: Food deprivation was associated with decreased body weight, blood glucose, serum triglycerides, sodium, chloride, and urine pH, and there were increases in blood and urine ketones and serum free fatty acids. Sleep deprivation was associated with a minor decrease in hemoglobin and erythrocyte particle count and volume fraction and an increase in leukocytes. CONCLUSIONS: The clinical chemistry and body weight changes associated with food deprivation were qualitatively similar to those observed in fasting obese patients but developed quicker in the survival training setting. Sleep deprivation had few effects on the clinical chemistry profile except for hematological variables. Physicians evaluating clinical chemistry data from patients subjected to short-term food or sleep deprivation should take the physiological state into account in their assessment.

The effect of sleep restriction and psychological load on the diurnal metabolic changes in tryptamine-related compounds in human urine.

OBJECTIVE: The effect of a severely stressful situation (sleep restriction and psychological load) on the diurnal changes in novel tryptamine-related compounds (hydroxydiacetyltryptamine, sulphatoxymelatonin, and dihydromelatonin) was evaluated in human subjects for 16 days. METHODS: The subjects were allowed to sleep for 5 h on days three through 12 and for 8 h on the other days. On days three through 12, the subjects were asked to perform a psychological task. The first two and the last 4 days were viewed as control days. A performance test was administered to evaluate the extent of the subjects' fatigue. Total urine was sampled by collecting it into bottles three times a day [(1) during the sleeping period, (2) in the morning, and (3) in the afternoon]. Seven tryptamine-related compounds in urine were assayed using HPLC-fluorometry. RESULTS: The urine melatonin level was high at night and low during the day. In contrast, urinary levels of hydroxydiacetyltryptamine and sulphatoxydiacetyltryptamine were low at night and high during the day. Dihydromelatonin was undetectable in urine during the sleeping period. Sleep restriction and psychological load did not affect diurnal changes in urinary melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels. The concentrations of hydroxymelatonin and sulphatoxymelatonin in urine did not show diurnal changes and decreased gradually during the experimental days. A principal component analysis confirmed the diurnal changes and suggested two novel metabolic pathways: (1) N-acetylserotonin to sulphtoxydiacetyltryptamine via hydroxydiacetyltryptamine, and (2) melatonin to dihydromelatonin. CONCLUSION: Severely stressful situations did not affect diurnal changes in melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels in urine.

Excess diuresis and natriuresis during acute sleep deprivation in healthy adults.

The transition from wakefulness to sleep is associated with a pronounced decline in diuresis, a necessary physiological process that allows uninterrupted sleep. The aim of this study was to assess the effect of acute sleep deprivation (SD) on urine output and renal water, sodium, and solute handling in healthy young volunteers. Twenty young adults (10 male) were recruited for two 24-h studies under standardized dietary conditions. During one of the two admissions, subjects were deprived of sleep. Urine output, electrolyte excretions, and osmolar excretions were calculated. Activated renin, angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide were measured in plasma, whereas prostaglandin E(2) and melatonin were measured in urine. SD markedly increased the diuresis and led to excess renal sodium excretion. The effect was more pronounced in men who shared significantly higher diuresis levels during SD compared with women. Renal water handling and arginine vasopressin levels remained unaltered during SD, but the circadian rhythm of the hormones of the renin-angiotensin-aldosterone system was significantly affected. Urinary melatonin and prostaglandin E(2) excretion levels were comparable between SD and baseline night. Hemodynamic changes were characterized by the attenuation of nocturnal blood pressure dipping and an increase in creatinine clearance. Acute deprivation of sleep induces natriuresis and osmotic diuresis, leading to excess nocturnal urine production, especially in men. Hemodynamic changes during SD may, through renal and hormonal processes, be responsible for these observations. Sleep architecture disturbances should be considered in clinical settings with nocturnal polyuria such as enuresis in children and nocturia in adults.

Sleep deprivation impairs 12-hr urine volume excretion in old rats.

Excessive nocturnal urine volumes (UVs) predict almost double the death rate in older adults. Furthermore, sleep-depriving environments may increase nocturnal UVs in old age. Thus, a pilot study was designed to examine the effects of sleep-depriving lighting treatments on the 12-hr UV excretion in young adult rats (6 months, n = 6), middle-aged rats (12 months, n = 12), old rats (16 months, n = 6), and old-old rats (>20 months, n = 5). Each animal was exposed continuously to the treatments beginning with 7 days each of standard laboratory lighting conditions of on 12 hr/off 12 hr, then 7 days continuous dim lighting, and finally 7 days of continuous dim lighting plus sleep deprivation with a noxious noise. Age group and lighting condition treatments influenced 24-hr urine volume excretion (F (2, 29) = 2.41, p = .007, r(2) = .8193). During sleep deprivation, rest-phase 12-hr urine volume excretion increased in both the old and old-old rats (F (2, 5) = 7.79, p < .00001).

Intra-individual variability in sleep duration and fragmentation: associations with stress.

Despite growing evidence that there is substantial nightly, intra-individual variability in sleep duration and fragmentation, few studies have investigated the correlates of such variability. The current study examined whether intra-individual variability in sleep parameters was associated with psychosocial and physiological indices of stress, especially among those high in negative affect. Participants were 184 adults aged 46-78 (53% men and 41% Black) in the Pittsburgh SleepSCORE study. Wrist actigraphy was used to estimate sleep duration and fragmentation for nine nights, and overnight samples of urinary norepinephrine were collected for two nights. Stressful life events, depression, and anxiety were also reported. Intra-individual differences exceeded between-person differences in actigraphy-measured sleep duration and fragmentation. Stressful life events were associated with increased nightly variability in duration and fragmentation (ps<.05). Negative affect moderated associations between norepinephrine and variability in sleep, such that the greatest variability in actigraphy measures was among those with both high norepinephrine levels and high negative affect (ps<.05). These data suggest that both psychosocial and physiological stress are related to increased nightly variability in individuals' sleep duration and fragmentation, particularly among those reporting negative emotions. These results may have implications for both sleep and health research.

[Stress effects of 72-hour sleep deprivation].

Stress effects of 3-d (72-hr) continuous vigilance were studied for renal excretion of 17-oxycorticoids (17-KS), electrolytes (potassium and sodium), and liquid. The investigation involved 12 male subjects aged 23 to 36. Baseline parameters displayed diurnal variations with comparatively high day and comparatively low night values. During the 72-hr vigilance, significant and consistent (statistically fiducial) intensification of 17-KS and potassium excretion occurred in the night-time, i.e., in the period of naturally low values, but only in the first two sleepless nights. As for sodium and liquid excretion, stress-related reduction in these parameters was more consistent and distinct in the day-time, i.e., in the period of naturally high values, rather than in the nighttime. Therefore, the two factors that should be accounted for by investigators of continuous vigilance (and, maybe, other stresses) are the anticipated direction of a stress-reaction and baseline diurnal variation of parameters under study. If stress is expected to increase a parameter, measurements should be done when the parameter is naturally low and, vice versa, if stress is known to reduce a parameter, then measurement should be planned in the period when it is naturally high. If direction of stress-related changes is predictable, investigations can be performed on a twenty-four hour basis.