Mounir Chennaoui

Effect of acute sleep deprivation on vascular function in healthy subjects

Sleep disorders are associated with inflammation and sympathetic activation, which are suspected to induce endothelial dysfunction, a key factor in the increased risk of cardiovascular disease. Less is known about the early effects of acute sleep deprivation on vascular function. We evaluated microvascular reactivity and biological markers of endothelial activation during continuous 40 h of total sleep deprivation (TSD) in 12 healthy men (29 +/- 3 yr). The days before [day 1 (D1)] and during TSD (D3), at 1200 and 1800, endothelium-dependent and -independent cutaneous vascular conductance was assessed by iontophoresis of acetylcholine and sodium nitroprusside, respectively, coupled to laser-Doppler flowmetry. At 0900, 1200, 1500, and 1800, heart rate (HR) and instantaneous blood pressure (BP) were recorded in the supine position. At D1, D3, and the day after one night of sleep recovery (D4), markers of vascular endothelial cell activation, including soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and interleukin-6 were measured from blood samples at 0800. Compared with D1, plasma levels of E-selectin were raised at D3, whereas intercellular adhesion molecule-1 and interleukin-6 were raised at D4 (P < 0.05). The endothelium-dependent and -independent CVC were significantly decreased after 29 h of TSD (P < 0.05). By contrast, HR, systolic BP, and the normalized low-frequency component of HR variability (0.04-0.15 Hz), a marker of the sympathetic activity, increased significantly within 32 h of TSD (P < 0.05). In conclusion, acute exposure to 40 h of TSD appears to cause vascular dysfunction before the increase in sympathetic activity and systolic BP.

Sleep and exercise: a reciprocal issue?

Sleep and exercise influence each other through complex, bilateral interactions that involve multiple physiological and psychological pathways. Physical activity is usually considered as beneficial in aiding sleep although this link may be subject to multiple moderating factors such as sex, age, fitness level, sleep quality and the characteristics of the exercise (intensity, duration, time of day, environment). It is therefore vital to improve knowledge in fundamental physiology in order to understand the benefits of exercise on the quantity and quality of sleep in healthy subjects and patients. Conversely, sleep disturbances could also impair a persons cognitive performance or their capacity for exercise and increase the risk of exercise-induced injuries either during extreme and/or prolonged exercise or during team sports. This review aims to describe the reciprocal fundamental physiological effects linking sleep and exercise in order to improve the pertinent use of exercise in sleep medicine and prevent sleep disorders in sportsmen.

Site-dependent effects of an acute intensive exercise on extracellular 5-HT and 5-HIAA levels in rat brain

Previous neurochemical studies have reported different pattern of 5-HT release during exercise varying across either exercise conditions or forebrain sites. This in vivo microdialysis study is the first to examine the impact of an acute intensive treadmill running (2 h at 25 m.min(-1), which is close to exhaustion time), on extracellular 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in two different brain areas in rats, the ventral hippocampus and the frontal cortex. Hippocampal and cortical 5-HT levels increased significantly after 90 min of exercise and were maximal in the first 30 min of recovery. Thereafter, cortical 5-HT levels followed a rapid and significant decrease when hippocampal levels are still maximal. During exercise, changes in extracellular 5-HIAA levels paralleled 5-HT changes, but showed no difference between the two brain areas during recovery. Thus, an intensive exercise induces a delayed increase in brain 5-HT release but recovery seems to display site-dependent patterns.

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29±3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P<0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.

Effects of Combined Stress during Intense Training on Cellular Immunity, Hormones and Respiratory Infections

Objectives: This study was designed to determine immune and hormonal changes and their relationship with the incidence of upper respiratory tract infections (URTIs) during an extremely stressful military training (3 weeks of physical conditioning followed by a 5-day combat course with energy restriction, sleep deprivation and psychological stress). Methods: Blood samples were collected from 21 cadets (21 ± 2 years old) before training and after the combat course for analysis of leukocyte and lymphocyte subpopulations, serum cytokines [interleukin-6 (IL-6), IL-1β and IL-10], and hormones [catecholamines, cortisol, leptin, total insulin-like growth factor I (IGF-I), prolactin, dehydroepiandrosterone sulfate (DHEAS) and testosterone]. Symptoms of URTI were recorded from health logs and medical examinations during training. Results: After the combat course, total leukocyte and neutrophil counts were significantly increased while total lymphocytes were unchanged. In lymphocyte subsets, NK cells were reduced (p < 0.01), while CD4+ and CD19+ (B) cells were increased. Levels of IL-6 were increased (p < 0.01), while those of IL-1β and IL-10 were unchanged. Norepinephrine and dopamine levels were increased, while those of cortisol were reduced. Levels of leptin, testosterone, prolactin and total IGF-I were reduced, while those of DHEAS were increased. The incidence of URTI increased during the training (χ2 = 53.48, p < 0.05). After training data analysis showed a significant correlation between URTIs and NK cells (p = 0.0023). Training-induced changes in immune and hormonal parameters were correlated. Conclusions: Blood NK cell levels are related to increased respiratory infections during physical training in a multistressor environment. The training-induced decreases in immunostimulatory hormone levels may have triggered immunosuppression.

Changes in circulating microRNAs levels with exercise modality

Here, we studied muscle-specific and muscle-related miRNAs in plasma of exercising humans. Our aim was to determine whether they are affected by eccentric and/or concentric exercise modes and could be biomarkers of muscle injuries or possible signaling molecules. On two separate days, nine healthy subjects randomly performed two 30-min walking exercises, one downhill (high eccentric component) and one uphill (high concentric component). Perceived exertion and heart rate were higher during the uphill exercise, while subjective pain and ankle plantar flexor strength losses within the first 48-h were higher following the downhill exercise. Both exercises increased serum creatine kinase and myoglobin with no significant differences between conditions. Plasma levels of circulating miRNAs assessed before, immediately after, and at 2-, 6-, 24-, 48-, and 72-h recovery showed that 1) hsa-mir-1, 133a, 133b, and 208b were not affected by concentric exercise but significantly increased during early recovery of eccentric exercise (2 to 6 h); 2) hsa-mir-181b and 214 significantly and transiently increased immediately after the uphill, but not downhill, exercise. The muscle-specific hsa-mir-206 was not reliably quantified and cardiac-specific hsa-mir-208a remained undetectable. In conclusion, changes in circulating miRNAs were dependent on the exercise mode. Circulating muscle-specific miRNAs primarily responded to a downhill exercise (high eccentric component) and could potentially be alternative biomarkers of muscle damage. Two muscle-related miRNAs primarily responded to an uphill exercise (high exercise intensity), suggesting they could be markers or mediators of physiological adaptations.

Insomnia and accidents: cross-sectional study (EQUINOX) on sleep-related home, work and car accidents in 5293 subjects with insomnia from 10 countries.

The link between sleepiness and the risk of motor vehicle accidents is well known, but little is understood regarding the risk of home, work and car accidents of subjects with insomnia. An international cross‐sectional survey was conducted across 10 countries in a population of subjects with sleep disturbances. Primary care physicians administered a questionnaire that included assessment of sociodemographic characteristics, sleep disturbance and accidents (motor vehicle, work and home) related to sleep problems to each subject. Insomnia was defined using the International Classification of Sleep Disorders (ICSD‐10) criteria. A total of 5293 subjects were included in the study, of whom 20.9% reported having had at least one home accident within the past 12 months, 10.1% at least one work accident, 9% reported having fallen asleep while driving at least once and 4.1% reported having had at least one car accident related to their sleepiness. All types of accident were reported more commonly by subjects living in urban compared to other residential areas. Car accidents were reported more commonly by employed subjects, whereas home injuries were reported more frequently by the unemployed. Car accidents were reported more frequently by males than by females, whereas home accidents were reported more commonly by females. Patients with insomnia have high rates of home accidents, car accidents and work accidents related to sleep disturbances independently of any adverse effects of hypnotic treatments. Reduced total sleep time may be one factor explaining the high risk of accidents in individuals who complain of insomnia.

Sleep debt and obesity

Abstract Short sleep duration has been shown to be associated with elevated body mass index (BMI) in many epidemiological studies. Several pathways could link sleep deprivation to weight gain and obesity, including increased food intake, decreased energy expenditure, and changes in levels of appetite-regulating hormones, such as leptin and ghrelin. A relatively new factor that is contributing to sleep deprivation is the use of multimedia (e.g. television viewing, computer, and internet), which may aggravate sedentary behavior and increase caloric intake. In addition, shift-work, long working hours, and increased time commuting to and from work have also been hypothesized to favor weight gain and obesity-related metabolic disorders, because of their strong link to shorter sleep times. This article reviews the epidemiological, biological, and behavioral evidence linking sleep debt and obesity.

Effect of a Probiotics Supplementation on Respiratory Infections and Immune and Hormonal Parameters during Intense Military Training

This study examined the effect of a probiotics supplementation on respiratory tract infection (RTI) and immune and hormonal changes during the French Commando training (3-week training followed by a 5-day combat course). Cadets (21 +/- 0.4 years) received either a probiotics (n = 24) or a placebo (n = 23) supplementation over the training period. We found no difference in the RTI incidence between groups but a significantly greater proportion of rhinopharyngitis in the probiotic group (p < 0.05). Among immune parameters, the major finding was an immunoglobulin A decrease after the combat course only in the placebo group (p < 0.01), but the difference between the two groups was not significant. A greater increase in dehydroepiandrostane sulfate was observed in the probiotics group after the combat course (p < 0.05). This study suggested that the benefits of a probiotics supplementation in a multistressor environment relied mainly on its capacity to prevent the infection to spread throughout the respiratory tract.

Effects of physical training on IL-1β, IL-6 and IL-1ra concentrations in various brain areas of the rat

There is increasing evidence that voluntary physical activity and exercise training have beneficial effects on brain function by facilitating neurovegetative, neuroadaptative and neuroprotective processes. Cytokines are chronically expressed at elevated levels within the CNS in many neurological disorders and may contribute to the histopathological, pathophysiological, and cognitive deficits associated with such disorders. In the present study, we examined the influence of seven weeks of physical training on IL-1b, IL-6 and IL-1ra concentrations in hypothalamus, pituitary, hippocampus, cerebellum and frontal cortex in rats. We determined circulating concentrations of cytokines, corticosterone, prolactin and leptin. Two groups of 10 rats were investigated: one group (trained rats) was progressively trained (5 days/week); the other group (sedentary rats) was used as a sedentary group. The training program induced a decrease of (i) IL-1b concentration in the hippocampus (0.7 +/- 0.16 versus 0.99 +/- 0.14 pg/mg protein; p < 0.05), (ii) IL-6 concentration in the cerebellum (10.7 +/- 1.00 in trained rats versus 14.8 +/- 1.34 pg/mg protein in sedentary rats; p < 0.05), (iii) IL-1ra concentration in the pituitary (245 +/- 14.31 versus 328 +/- 17.73 pg/mg protein; p < 0.01). We also found positive correlations between (i) serum prolactin and the concentration of IL-6 in the cerebellum, (ii) serum leptin and the concentration of IL-1ra in the pituitary. There was no effect of physical training on IL-1b, IL-6, and IL-1ra serum levels. These findings suggest that the decrease in particular pro-inflammatory, central cytokines such as IL-1b and IL-6 induced by the training program may play a role in the positive effects of regular physical activity on the central nervous system.