Methods to estimate body temperature and energy expenditure dynamics in fed and fasted laboratory mice: effects of sleep deprivation and light exposure.

Monitoring body temperature and energy expenditure in freely-moving laboratory mice remains a powerful methodology used widely across a variety of disciplines-including circadian biology, sleep research, metabolic phenotyping, and the study of body temperature regulation. Some of the most pronounced changes in body temperature are observed when small heterothermic species reduce their body temperature during daily torpor. Daily torpor is an energy saving strategy characterized by dramatic reductions in body temperature employed by mice and other species when challenged to meet energetic demands. Typical measurements used to describe daily torpor are the measurement of core body temperature and energy expenditure. These approaches can have drawbacks and developing alternatives for these techniques provides options that can be beneficial both from an animal-welfare and study-complexity perspective. First, this paper presents and assesses a method to estimate core body temperature based on measurements of subcutaneous body temperature, and second, a separate approach to better estimate energy expenditure during daily torpor based on core body temperature. Third, the effects of light exposure during the habitual dark phase and sleep deprivation during the light period on body temperature dynamics were tested preliminary in fed and fasted mice. Together, the here-published approaches and datasets can be used in the future to assess body temperature and metabolism in freely-moving laboratory mice.

Medication Errors in Surgery: A Classification Taxonomy and a Pilot Study in Postcall Residents.

INTRODUCTION: The post-call state in postgraduate medical trainees is associated with impaired decision-making and increased medical errors. An association between post-call state and medication prescription errors for surgery residents is yet to be established. Our objective was to determine whether post-call state is associated with increased proportion of medication prescription errors committed by surgery residents in an academic hospital without a computerized physician order entry (CPOE) system. METHODS: This prospective observational study was conducted at a tertiary academic hospital between June 28 and August 31, 2017. It compared the proportion of medication prescription errors committed by surgery residents in their post-call (PC) and no-call (NC) states. A novel taxonomy was developed to classify medication prescription errors. RESULTS: Sixteen of twenty-one eligible residents (76%) participated in this study. Self-reported hours of sleep per night was significantly higher in the NC group compared to the PC group (6(4-8) vs 2(0-4) hours, P < 0.01). PC residents committed a significantly higher proportion of medication prescription errors versus NC residents (9.2% vs 3.2%; p=0.04). Decision-making and prescription-writing errors comprised 33% and 67% of errors, respectively. CONCLUSIONS: The post-call state in surgery residents is associated with a significantly higher proportion of medication prescription errors in a hospital without a CPOE system. Decision-making and prescription-writing errors could potentially be addressed by additional educational interventions.

Assessment of fitness to perform using a validated self-test in obstetric and gynecological night shifts in the Netherlands.

BACKGROUND: The field of obstetrics and gynecology requires complex decision-making and skills because of unexpected high-risk situations. These skills are influenced by alertness, reaction time, and concentration. Night shifts result in sleep deprivation, which might impair these functions, although it is still unclear to what extent. OBJECTIVE: This study aimed to investigate whether a night shift routinely impairs the obstetrics and gynecology consultants' and residents' fitness to perform and whether this reaches a critical limit compared with relevant frames of reference. STUDY DESIGN: Residents (n=33) and consultants (n=46) in obstetrics and gynecology conducted multiple measurements (n=415) at precall, postcall, and noncall moments with the fitness to perform self-test. The self-test consists of an adaptive pursuit tracking task that is able to objectively measure alertness, reaction time, concentration, and hand-eye coordination and Visual Analog Scale tests to subjectively score alertness. The test is validated with a sociolegal reference of a 0.06% ethanol blood concentration (the peak level after 2 units of alcohol, the legal driving limit). This equals -1.37% on the objective score and -8.17 points on subjective alertness. Linear mixed models were used to analyze the difference within subjects over a night shift, integrating repeated measures over time. RESULTS: The overnight objective difference between postcall and precall measurements was -0.62 (P<.05) for residents and 0.28 (P=NS) for consultants, both not exceeding the sociolegal reference as a group. Objective impairment exceeded the reference for 31% of the residents and 28% of the consultants. Subjective alertness decreased in residents (-18.26; P<.001) and consultants (-10.85; P<.001), both exceeding the reference. No residents had to continue work postcall versus 7.8% of the consultants. None of the consultants that had to continue work were in an objective critically impaired state. CONCLUSION: This study provides insight and awareness of individual performance after night shifts with clear frames of reference. The performance of residents is negatively and significantly affected by night shifts; therefore, a scheduled day off after a night shift is justified. Consultants showed no overall impairment; however, a quarter did exceed the alcohol limit reference after their night shift. If not logistically feasible to schedule a protected day off after a night shift, our group recommends safe shift scheduling, including options to transfer care after a demanding night shift to prevent working in a compromised state.

Home-EEG assessment of possible compensatory mechanisms for sleep disruption in highly irregular shift workers - The ANCHOR study.

STUDY OBJECTIVES: While poor sleep quality has been related to increased risk of Alzheimer's disease, long-time shift workers (maritime pilots) did not manifest evidence of early Alzheimer's disease in a recent study. We explored two hypotheses of possible compensatory mechanisms for sleep disruption: Increased efficiency in generating deep sleep during workweeks (model 1) and rebound sleep during rest weeks (model 2). METHODS: We used data from ten male maritime pilots (mean age: 51.6±2.4 years) with a history of approximately 18 years of irregular shift work. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). A single lead EEG-device was used to investigate sleep in the home/work environment, quantifying total sleep time (TST), deep sleep time (DST), and deep sleep time percentage (DST%). Using multilevel models, we studied the sleep architecture of maritime pilots over time, at the transition of a workweek to a rest week. RESULTS: Maritime pilots reported worse sleep quality in workweeks compared to rest weeks (PSQI = 8.2±2.2 vs. 3.9±2.0; p<0.001). Model 1 showed a trend towards an increase in DST% of 0.6% per day during the workweek (p = 0.08). Model 2 did not display an increase in DST% in the rest week (p = 0.87). CONCLUSIONS: Our findings indicated that increased efficiency in generating deep sleep during workweeks is a more likely compensatory mechanism for sleep disruption in the maritime pilot cohort than rebound sleep during rest weeks. Compensatory mechanisms for poor sleep quality might mitigate sleep disruption-related risk of developing Alzheimer's disease. These results should be used as a starting point for future studies including larger, more diverse populations of shift workers.

Posturographic Balance's Validity in Mental and Physical Fatigue Assessment Among Cadet Pilots.

BACKGROUND: Postural control is adversely affected by mental and physical fatigue, but its validity in fatigue assessment has not been investigated systemically among pilots. We explored the correlations of posturographic balance with physiological and psychological signals among cadet pilots.METHODS: In experiment 1, 37 cadet pilots performed a posturographic balance test, heart rate variability (HRV), and profile of mood states (POMS) during 40 h of sleep deprivation. For experiment 2, physiological signals of 60 subjects, including breathing rate (BR), systolic blood pressure (SBP), and heart rate (HR) were measured under the effects of physical fatigue. Then correlations with a mental and physical fatigue index based on effective posturographic parameters with those subjective and objective methods were analyzed by linear regression.RESULTS: The mental fatigue index correlated linearly with the depression score of the POMS (r = 0.212), standard deviation of normal to normal beats (r = 0.286), and square root of the mean differences of successive beat intervals (r = 0.207). Meanwhile, linear correlations with frequency-domain parameters of HRV such as total power, low frequency power, and high frequency power were also statistically significant. With the increase in the physical fatigue index, physiological signals such as SBP (r = 0.300), HR (r = 0.349), and BR (r = 0.266) increased linearly.CONCLUSIONS: Impairment of postural stability can reflect the aggravation of mental and physical fatigue among cadet pilots, which provides a potential method for assessing fatigue level before flight tasks and preventing errors by pilots.Cheng S, Sun J, Ma J, Dang W, Tang M, Hui D, Zhang L, Hu W. Posturographic balance's validity in mental and physical fatigue assessment among cadet pilots. Aerosp Med Hum Perform. 2018; 89(11):961-966.

Limited Efficacy of Caffeine and Recovery Costs During and Following 5 Days of Chronic Sleep Restriction.

Objectives: To investigate the effects of caffeine on psychomotor vigilance and sleepiness during sleep restriction and following subsequent recovery sleep. Methods: Participants were N = 48 healthy good sleepers. All participants underwent five nights of sleep satiation (time-in-bed [TIB]: 10 hours), followed by five nights of sleep restriction (TIB: 5 hours), and three nights of recovery sleep (TIB: 8 hours) in a sleep laboratory. Caffeine (200 mg) or placebo was administered in the form of chewing gum at 08:00 am and 12:00 pm each day during the sleep restriction phase. Participants completed hourly 10-minute psychomotor vigilance tests and a modified Maintenance of Wakefulness Test approximately every 4 hours during the sleep restriction and recovery phases. Results: Caffeine maintained objective alertness compared to placebo across the first 3 days of sleep restriction, but this effect was no longer evident by the fourth day. A similar pattern of results was found for Maintenance of Wakefulness Test sleep latencies, such that those in the caffeine group (compared to placebo) did not show maintenance of wakefulness relative to baseline after the second night of restriction. Compared to placebo, participants in the caffeine condition displayed slower return to baseline in alertness and wakefulness across the recovery sleep period. Finally, the caffeine group showed greater N3 sleep duration during recovery. Conclusions: Caffeine appears to have limited efficacy for maintaining alertness and wakefulness across 5 days of sleep restriction. Perhaps more importantly, there may be recovery costs associated with caffeine use following conditions of prolonged sleep loss.

Partial Sleep Deprivation Reduces the Efficacy of Orexin-A to Stimulate Physical Activity and Energy Expenditure.

OBJECTIVE: Sufficient sleep is required for weight maintenance. Sleep deprivation due to noise exposure stimulates weight gain by increasing hyperphagia and reducing energy expenditure (EE). Yet the mechanistic basis underlying the weight gain response is unclear. Orexin-A promotes arousal and negative energy balance, and orexin terminals project to the ventrolateral preoptic area (VLPO), which is involved in sleep-to-wake transitions. To determine whether sleep deprivation reduces orexin function in VLPO and to test the hypothesis that sleep deprivation would attenuate the orexin-A-stimulated increase in arousal, physical activity (PA), and EE. METHODS: Electroencephalogram, electromyogram, distance traveled, and EE were determined in male Sprague-Dawley rats following orexin-A injections into VLPO both before and after acute (12-h) and chronic (8 h/d, 9 d) sleep deprivation by noise exposure. RESULTS: Orexin-A in the VLPO significantly increased arousal, PA, total EE, and PA-related EE and reduced sleep and respiratory quotient before sleep deprivation. In contrast to after acute sleep deprivation in which orexin-A failed to stimulate EE during PA only, orexin-A failed to significantly increase arousal, PA, fat oxidation, total EE, and PA-related EE after chronic sleep deprivation. CONCLUSIONS: Sleep deprivation may reduce sensitivity to endogenous stimuli that enhance EE due to PA and thus stimulate weight gain.

Prediagnosis Sleep Duration, Napping, and Mortality Among Colorectal Cancer Survivors in a Large US Cohort.

Study Objectives: Prediagnosis lifestyle factors can influence colorectal cancer (CRC) survival. Sleep deficiency is linked to metabolic dysfunction and chronic inflammation, which may contribute to higher mortality from cardiometabolic conditions and promote tumor progression. We hypothesized that prediagnosis sleep deficiency would be associated with poor CRC survival. No previous study has examined either nighttime sleep or daytime napping in relation to survival among men and women diagnosed with CRC. Methods: We examined self-reported sleep duration and napping prior to diagnosis in relation to mortality among 4869 CRC survivors in the NIH-AARP Diet and Health Study. Vital status was ascertained by linkage to the Social Security Administration Death Master File and the National Death Index. We examined the associations of sleep and napping with mortality using traditional Cox regression (total mortality) and Compositing Risk Regression (cardiovascular disease [CVD] and CRC mortality). Models were adjusted for confounders (demographics, cancer stage, grade and treatment, smoking, physical activity, and sedentary behavior) as well as possible mediators (body mass index and health status) in separate models. Results: Compared to participants reporting 7-8 hours of sleep per day, those who reported <5 hr had a 36% higher all-cause mortality risk (Hazard Ratio (95% Confidence Interval), 1.36 (1.08-1.72)). Short sleep (<5 hr) was also associated with a 54% increase in CRC mortality (Substitution Hazard Ratio (95% Confidence Interval), 1.54 (1.11-2.14)) after adjusting for confounders and accounting for competing causes of death. Compared to no napping, napping 1 hr or more per day was associated with significantly higher total and CVD mortality but not CRC mortality. Conclusion: Prediagnosis short sleep and long napping were associated with higher mortality among CRC survivors.

Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents.

OBJECTIVE: Chronic partial sleep deprivation (SD) by environmental noise exposure increases weight gain and feeding in rodents, which contrasts weight loss after acute SD by physical methods. This study tested whether acute environmental noise exposure reduced sleep and its effect on weight gain, food intake, physical activity, and energy expenditure (EE). It was hypothesized that acute exposure would (1) increase weight gain and feeding and (2) reduce sleep, physical activity, and EE (total and individual components); and (3) behavioral changes would persist throughout recovery from SD. METHODS: Three-month old male Sprague-Dawley rats slept ad libitum, were noise exposed (12-h light cycle), and allowed to recover (36 h). Weight gain, food intake, sleep/wake, physical activity, and EE were measured. RESULTS: Acute environmental noise exposure had no effect on feeding, increased weight gain (P < 0.01), and reduced sleep (P < 0.02), physical activity (P < 0.03), total EE (P < 0.05), and several components (P < 0.05). Reductions in EE and physical activity persisted during recovery. CONCLUSIONS: Reductions in EE during sleep, rest, and physical activity reduce total EE and contribute to weight gain during acute SD and recovery from SD. These data emphasize the importance of increasing physical activity after SD to prevent obesity.

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

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

Operational assessment of the 5-h on/10-h off watchstanding schedule on a US Navy ship: sleep patterns, mood and psychomotor vigilance performance of crewmembers in the nuclear reactor department.

We assessed sleep patterns, psychomotor vigilance performance, work demands and mood of 77 crewmembers of USS NIMITZ (CVN-68) on the rotating 5-h on/10-h off (5/10) watchstanding schedule. Within the 3-day cycle of the 5/10, sleep occurred at distinctly different times each day. On two of these days, sailors typically received only brief, 4-h sleep episodes followed by periods of sustained wakefulness (approximately 22 and 20 h). Crewmembers received approximately seven hours of sleep daily, but reported excessive fatigue and dissatisfaction with their schedule. Crewmembers' mood worsened significantly over the course of the underway phase. Psychomotor vigilance performance (reaction times, lapses) was significantly degraded compared to performance when working circadian-aligned schedules. Overall, standing watch on the 5/10 schedule, combined with other work duties, resulted in poor sleep hygiene. Crewmembers on the 5/10 experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep. Practitioner summary: We assessed crewmembers' sleep patterns, psychomotor vigilance performance and work demands when working a rotating 5-h on/10-h off (5/10) watchstanding schedule. The 5/10, combined with other work duties, resulted in poor sleep hygiene. Crewmembers experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep.

A 6-month assessment of sleep during naval deployment: a case study of a commanding officer.

BACKGROUND: Sleep deprivation is known to be a common problem in the U.S. Navy and has been documented using wrist-worn actigraphy in various operational studies that typically span 2 to 4 wk in duration. However, sleep patterns over an extended period of time have not been objectively measured. CASE REPORT: This 6-mo study used actigraphy and the Fatigue Avoidance Scheduling Tool (FAST) to quantify the sleep patterns of a 39-yr-old Commanding Officer (CO) of an Arleigh Burke class destroyer while the ship was forward-deployed. On average, the CO received 5.2 h of sleep daily and averaged 6 h time in bed each day. The participant received more than 8 h of sleep for only 2% (N = 3) of the study days; for 17% (N = 27) of the days, he received less than 4 h of daily sleep. For 15% of waking time, the CO had a predicted effectiveness of less than 70% on the FAST scale, equating to a blood alcohol equivalent of 0.08%-or legally drunk. The CO's predicted effectiveness was below 65% approximately 10% of waking time. DISCUSSION: Results from this study are aligned with earlier research showing that crewmembers on U.S. Navy ships suffer from chronic sleep restriction. During a typical deployment, personnel accrue a considerable sleep debt even during normal operations. Should critical events with additional sleep restriction occur, the ship has limited reserve capacity, potentially placing her crew and their mission in grave jeopardy.

Stress assessment based on EEG univariate features and functional connectivity measures.

The biological response to stress originates in the brain but involves different biochemical and physiological effects. Many common clinical methods to assess stress are based on the presence of specific hormones and on features extracted from different signals, including electrocardiogram, blood pressure, skin temperature, or galvanic skin response. The aim of this paper was to assess stress using EEG-based variables obtained from univariate analysis and functional connectivity evaluation. Two different stressors, the Stroop test and sleep deprivation, were applied to 30 volunteers to find common EEG patterns related to stress effects. Results showed a decrease of the high alpha power (11 to 12 Hz), an increase in the high beta band (23 to 36 Hz, considered a busy brain indicator), and a decrease in the approximate entropy. Moreover, connectivity showed that the high beta coherence and the interhemispheric nonlinear couplings, measured by the cross mutual information function, increased significantly for both stressors, suggesting that useful stress indexes may be obtained from EEG-based features.

Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area.

STUDY OBJECTIVES: The ventrolateral preoptic area (VLPO) and the orexin/hypocretin neuronal system are key regulators of sleep onset, transitions between vigilance states, and energy homeostasis. Reciprocal projections exist between the VLPO and orexin/hypocretin neurons. Although the importance of the VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are involved in energy balance. The purpose of these studies was to determine if the VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO modulates behaviors (sleep and wakefulness, feeding, spontaneous physical activity [SPA]) to increase energy expenditure. DESIGN AND MEASUREMENTS: Sleep, wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae targeting the VLPO. We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively. RESULTS: Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep with no effect on food intake. Pretreatment with DORA blocked the increase in wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R antagonist reduced SPA stimulated by orexin-A. CONCLUSIONS: These data show the ventrolateral preoptic area is a site of action for orexin-A, which may promote negative energy balance by modulating sleep/wakefulness and stimulating spontaneous physical activity and energy expenditure.

Gender differences in sleep deprivation effects on risk and inequality aversion: evidence from an economic experiment.

Excessive working hours--even at night--are becoming increasingly common in our modern 24/7 society. The prefrontal cortex (PFC) is particularly vulnerable to the effects of sleep loss and, consequently, the specific behaviors subserved by the functional integrity of the PFC, such as risk-taking and pro-social behavior, may be affected significantly. This paper seeks to assess the effects of one night of sleep deprivation on subjects' risk and social preferences, which are probably the most explored behavioral domains in the tradition of Experimental Economics. This novel cross-over study employs thirty-two university students (gender-balanced) participating to 2 counterbalanced laboratory sessions in which they perform standard risk and social preference elicitation protocols. One session was after one night of undisturbed sleep at home, and the other was after one night of sleep deprivation in the laboratory. Sleep deprivation causes increased sleepiness and decreased alertness in all subjects. After sleep loss males make riskier decisions compared to the rested condition, while females do the opposite. Females likewise show decreased inequity aversion after sleep deprivation. As for the relationship between cognitive ability and economic decisions, sleep deprived individuals with higher cognitive reflection show lower risk aversion and more altruistic behavior. These results show that one night of sleep deprivation alters economic behavior in a gender-sensitive way. Females' reaction to sleep deprivation, characterized by reduced risky choices and increased egoism compared to males, may be related to intrinsic psychological gender differences, such as in the way men and women weigh up probabilities in their decision-making, and/or to the different neurofunctional substrate of their decision-making.

The assessment of somatosensory cortex plasticity during sleep deprivation by paired associative stimulation.

Many animal studies suggest that during sleep deprivation (SD) synaptic strength should progressively increase, leading to the saturation of the ability to induce long-term potentiation (LTP). Nevertheless, direct evidences about the effects of sustained wakefulness on cortical plasticity in humans are still lacking. The aim of the present study was to assess changes in the ability to induce LTP-like mechanism in humans during a period of SD by means of a paired associative stimulation (PAS) protocol, which combines median nerve stimulation with transcranial magnetic stimulation (TMS) applied over the contralateral somatosensory cortex. During a 41-h SD protocol, 16 healthy subjects, defined as responders to the PAS protocol after a pre-selection session, were involved in 4 experimental sessions (11.00 a.m. and 11.00 p.m. of first and second day) with: a) pre-PAS somatosensory evoked potentials (SEPs) recordings; b) PAS protocol; c) post-PAS SEPs recordings. The effect of PAS on SEPs early components (N20-P25 complex) was assessed. During the first experimental session (without SD) no significant PAS effects on SEPs components amplitude have been found, and large intra- and inter-individual variability have been observed. A lack of significant changes has been observed also in the subsequent sessions. Our results index a low intra- and inter-individual reliability of the PAS protocol, suggesting particular caution when longitudinally evaluating the effect of this technique on cortical plasticity.

Sleep deprivation alters thyroid hormone economy in rats.

NEW FINDINGS: What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all sleep-deprived and sleep-restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid-stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20-30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation-induced hypothalamic-pituitary-thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.

Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains.

BACKGROUND: Shortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet. RESULTS: Chronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis. Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5-9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD. CONCLUSION: In conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern.