The hypnotic effect of propofol in the medial preoptic area of the rat

Recent introduction of the intravenous anesthetic propofol as an ICU sedative has allowed a deeply sedated state to be maintained for extended periods in the ICU without delays in emergence. Although such sedation has been advocated to promote physiologic sleep, little evidence exists to support such a strategy. To explore propofol's effect on sleep regulation, we administered propofol directly into the medial preoptic area (MPA) of the rat, an anatomic site where administration of other sedatives (triazolam and phenobarbital) also induce sleep. We performed three two-hour sleep studies in the daytime with the lights on following the administration of propofol (8 ng or 40 ng) or vehicle (intralipid). The higher dose of propofol significantly reduced sleep latency and increased nonREM and total sleep times when compared to vehicle. REM sleep times, intermittent waking times and number of transitions were not altered. Mean nonREM sleep bout length was increased significantly at the higher dose. These findings suggest that propofol may enhance sleep by acting at a hypothalamic site.     

Pimozide attentuates d-amphetamine-induced sleep changes in man.

Pretreatment with pimozide (mean dose = 13 mg/day) blocked the effect of d-amphetamine (20 mg base, administered by intravenous bolus infusion at 0815) on all-night EEG sleep patterns in seven hospitalized psychiatric patients. Each patient was studied for five nights (2 nights baseline, 1 night on the day of the infusion, and 2 nights recovery) with and without pretreatment with pimozide. Without treatment with pimozide, d-amphetamine significantly reduced duration of total sleep, REM and nonREM sleep, Stage I, and Stage II. With coadministration of pimozide, d-amphetamine had no effect on sleep. These results suggest that the d-amphetamine induced changes in sleep are mediated by dopaminergic neurons.     

From slow waves to sleep homeostasis: new perspectives

EEG slow waves are the epitome of deep nonREM sleep. The level of slow-wave activity (SWA; defined as spectral power in the 0.5-4.5 Hz band) in the initial part of sleep is determined by prior sleep and waking, and thereby represents a marker of a homeostatic sleep regulating process (Process S). Models based on SWA were successful in simulating sleep architecture in a variety of experimental protocols. SWA is an exceptional sleep variable in that it is little influenced by circadian phase and variations of the photoperiod. There is recent evidence that it is not waking per se but the absence of sleep, which engenders a rise in sleep propensity. Thus animals emerging from the hypometabolic states of hibernation or daily torpor exhibit an increase in SWA akin to sleep deprivation. Recent human studies showed SWA to be a marker of a local, use-dependent facet of sleep. Selective activation of specific cortical areas during waking enhanced SWA over the activated region during sleep. A frontal predominance of power in the 2-Hz band was documented in the initial part of a normal sleep episode. Sleep homeostasis may be a valuable concept for exploring the evolutionary origin of sleep. Thus 'rest homeostasis' has been demonstrated in invertebrate species, and the search for homologies of rest and sleep on a molecular genetic level has begun. Conceptualizing and characterizing sleep as a regulated process may eventually shed light on its function.     

Sleep and EEG spectra in the pigeon (Columba livia) under baseline conditions and after sleep deprivation

Summary Sleep in adult domestic pigeons was studied by continuous 24-h recording of the EEG, EMG and EOG. Vigilance states were scored on the basis of behavioral observations, visual scoring of the polygraph records, and EEG power spectra.The animals showed a clear nocturnal preference for sleep. Throughout the dark period, EEG slow-wave activity was at a uniform level, whereas REM sleep (REMS) showed an increasing trend.EEG power density values differed significantly between the vigilance states. In general the values were highest in nonREM sleep (NREMS), intermediate in waking (W) and lowest in REMS.Twenty-four hour sleep deprivation reduced W and increased REMS, effects that are well documented in mammals. Unlike in mammals, EEG slow-wave activity remained unchanged, whereas EOG activity in W and NREMS was enhanced.Abbreviations EEG electroencephalogram - EMG electromyogram - EOG electrooculogram - SD sleep deprivation - L light - D dark - LD light dark - NREMS non rapid eye movement sleep - REMS REM sleep     

Effects of the Seasons and of Bright Light Administered at Different Times of Day on Sleep EEG and Mood in Patients with Seasonal Affective Disorder

The study examines objective characteristics of sleep in women (n=31) with and without seasonal affective disorder, winter type, before and after a week of light treatment (at either 0800-1000 h, 1600-1800 h or 1800-2000 h). Subsamples of 13 patients and 7 controls were studied additionally in summer, and, among these patients, 9 were also recorded in spring and fall. Ranking the results from the lowest to the largest degree of deviation of sleep structure in patients from the norm yields the sequence: spring -> summer -> winter after light treatment -> fall -> winter before light treatment. In winter before light treatment the total amounts and percentage of slow wave sleep were significantly lower in responders to light (n=13) compared to both nonresponders (n=8) and controls (n=10), while following light treatment the difference disappeared. The reduced amounts of slow wave sleep in the depressive state predicted higher reduction and low posttreatment scores on psychiatric scales. Light treatment and summer season showed similar effects on patients' sleep: they caused an increase of slow wave sleep and a decline of sleep stage 2. Our data do not suggest that time of light treatment is important to achieve an antidepressant effect. Moreover, phase shifting effects of light treatment and of changing season on sleep EEG were not considerable. At the same time, subjective ratings of arousal demonstrated an advance shift of the arousal rhythm after morning and a delay shift after afternoon LT. We did not find significant changes in total amounts and percentage of REM sleep over time. The data suggest that abnormally increased need for REM sleep results in the hypersomnia and may be considered as a trait marker of winter depression. An abnormal architecture of nonREM sleep appears to be a state marker of those patients who benefit from bright light administered during waking hours.     

Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats

Recent work indicates that the orexin/hypocretin-containing neurons of the lateral hypothalamus are involved in control of REM sleep phenomena, but site-specific actions in control of wakefulness have been less studied. Orexin-containing neurons project to both brainstem and forebrain regions that are known to regulate sleep and wakefulness, including the field of cholinergic neurons in the basal forebrain (BF) that is implicated in regulation of wakefulness, and includes, in the rat, the horizontal limb of the diagonal band, the substantia innominata, and the magnocellular preoptic region. The present study used microdialysis perfusion of orexin-A directly in the cholinergic BF region of rat to test the hypothesis that orexin-A enhances W via a local action in the BF. A significant dose-dependent increase in W was produced by the perfusion of three doses of orexin-A in the BF (0.1, 1.0, and 10.0 microM), with 10.0 microM producing more than a 5-fold increase in wakefulness, which occupied 44% of the light (inactive) phase recording period. Orexin-A perfusion also produced a significant dose-dependent decrease in nonREM sleep, and a trend-level decrease in REM sleep. The results clearly demonstrate a potent capacity of orexin-A to induce wakefulness via a local action in the BF, and are consistent with previous work indicating that the BF cholinergic zone neurons have a critical role in the regulation of EEG activation and W. The data suggest further that orexin-A has a significant role in the regulation of arousal/wakefulness, in addition to the previously described role of orexin in the regulation and expression of REM sleep and REM sleep-related phenomena.     

Influence of the Scandinavian dissociated diet regime on the structure of sleep in athletes

Electroencephalographic sleep changes were studied in seven young male cyclists who were given a high carbohydrate diet after a high protein and fat isocaloric diet, during six days. high carbohydrate diet was associated with significantly more slow wave sleep, while significantly more rapid eye movement sleep was found after consuming a high protein fat diet.     

Dietary fatty acids promote sleep through a taste‐independent mechanism

Consumption of foods that are high in fat contribute to obesity and metabolism‐related disorders. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable taste of dietary fatty acids promotes food consumption, activates reward centers in mammals and underlies hedonic feeding. Despite the central role of dietary fats in the regulation of food intake and the etiology of metabolic diseases, little is known about how fat consumption regulates sleep. The fruit fly, Drosophila melanogaster, provides a powerful model system for the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented fatty acids into the diet of Drosophila and measured their effects on sleep and activity. We found that flies fed a diet of hexanoic acid, a medium‐chain fatty acid that is a by‐product of yeast fermentation, slept more than flies starved on an agar diet. To assess whether dietary fatty acids regulate sleep through the taste system, we assessed sleep in flies with a mutation in the hexanoic acid receptor Ionotropic receptor 56D, which is required for fatty acid taste perception. We found that these flies also sleep more than agar‐fed flies when fed a hexanoic acid diet, suggesting the sleep promoting effect of hexanoic acid is not dependent on sensory perception. Taken together, these findings provide a platform to investigate the molecular and neural basis for fatty acid‐dependent modulation of sleep.     

Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats

Objective: We assessed the relationship between a high‐fat (HF) diet and central apnea during rapid eye movement and non‐rapid eye movement sleep stages by recording ventilatory parameters in 28 non‐obese rats in which insulin resistance had been induced by an HF diet. We also studied whether metformin (an anti‐hyperglycemic drug frequently used to treat insulin resistance) could reverse sleep apnea or prevent its occurrence in this experimental paradigm. Research Methods and Procedures: Rats were fed with a standard diet (10 rats), an HF diet (8 rats), or an HF diet concomitantly with metformin treatment (10 rats). Each animal was instrumented for electroencephalographic and electromyographic recording. After 3 weeks, ventilatory parameters during sleep were recorded with a body plethysmograph. All rats were treated with metformin for 1 week, after which time the ventilatory measurements were measured again. Results: Our results showed that the three groups of animals did not differ in terms of body growth over the entire experimental period. The HF diet did not modify sleep structure or minute ventilation in the different sleep stages. A great increase (+266 ± 48%) in central apnea frequency was observed in insulin‐resistant rats. This was explained by an increase in both post‐sigh (+195 ± 35%) and spontaneous apnea (+437 ± 65%) in the different sleep stages. These increases were suppressed by metformin treatment. Discussion: Insulin resistance induced by the HF diet could be the promoter of sleep apnea in non‐obese rats. Metformin is an efficient curative and preventive treatment for sleep apnea, suggesting that insulin resistance modifies the ventilatory drive independently of obesity.     

High calorie diet augments age-associated sleep impairment in Drosophila

The fruit fly, Drosophila melanogaster is an established model used for aging and longevity studies and more recently for sleep studies. Mammals and Drosophila share various physiological, pathological, pharmacological and genetic similarities in these processes. In particular, sleep is essential for survival in both species and both have age-associated sleep quality alterations. Here we report that a high calorie diet, which accelerates the aging process and reduces lifespan across species, also accelerates age-associated sleep changes in Drosophila. These changes are more evident in the dopamine transporter mutant, fumin, that displays a short sleep phenotype due to enhanced dopaminergic signaling. With normal food, fumin mutants sleep for only one third of the time that the control flies do, but still show equivalent longevity. However, when on a mildly high calorie diet, their sleep length shows a marked decrease and they have a reduced longevity. These data indicate that the age-associated change in sleep in Drosophila is a physiologically regulated aging process that is tightly linked to calorie intake and that the dopamine level plays an important role. In addition, this provides another evidence that sleep is essential for the longevity of Drosophila.     

Sensitivity to alcohol in mice with an altered brain fatty acid composition

Ethanol-induced sleep onset times, sleep times and blood alcohol levels upon awakening were measured in mice fed an essential fatty acid deficient, Purina Chow or unsaturated fat diet for nine months. These values in animals fed the essential fatty acid deficient and Purina Chow diets did not differ, but mice fed the unsaturated fat diet had longer sleep times and lower blood alcohol levels upon awakening than mice fed essential fatty acid deficient or Purina Chow diets. Crude brain mitochondrial fractions isolated from mice fed the essential fatty acid deficient diet had decreased levels of docosahexaenoic [22:6(n-3)] and increased levels of eicosatrienoic [20:3(n-9)], docosatrienoic [22:3(n-9)] and docosapentaenoic [22:5(n-6)] acids compared to mice fed the Purina Chow diet. The unsaturated fat diet decreased 22:6(n-3) and increased 22:5(n-6) compared to the Purina Chow dietary regimen. The longer sleep times and lower blood alcohol levels found in mice fed the unsaturated fat diet probably resulted from an artifact due to the obesity of the mice fed this diet and from the hinderance of obesity to the righting reflex (our measure of ethanol potency). We conclude that the alteration of several polyunsaturated fatty acid components in the brain has little or no influence on the sensitivity of the nervous system to alcohol.     

Association of total energy intake,diet quality and sleep disorders in university-term female students

Sleep and Biological Rhythms - The aim of this study is to determine the relationship between diet quality and overall sleep quality, sleep duration, and presence of insomnia in the university-term...     

Dietary Modulation of Drosophila Sleep-Wake Behaviour

Background

A complex relationship exists between diet and sleep but despite its impact on human health, this relationship remains uncharacterized and poorly understood. Drosophila melanogaster is an important model for the study of metabolism and behaviour, however the effect of diet upon Drosophila sleep remains largely unaddressed.

Methodology/Principal Findings

Using automated behavioural monitoring, a capillary feeding assay and pharmacological treatments, we examined the effect of dietary yeast and sucrose upon Drosophila sleep-wake behaviour for three consecutive days. We found that dietary yeast deconsolidated the sleep-wake behaviour of flies by promoting arousal from sleep in males and shortening periods of locomotor activity in females. We also demonstrate that arousal from nocturnal sleep exhibits a significant ultradian rhythmicity with a periodicity of 85 minutes. Increasing the dietary sucrose concentration from 5% to 35% had no effect on total sucrose ingestion per day nor any affect on arousal, however it did lengthen the time that males and females remained active. Higher dietary sucrose led to reduced total sleep by male but not female flies. Locomotor activity was reduced by feeding flies Metformin, a drug that inhibits oxidative phosphorylation, however Metformin did not affect any aspects of sleep.

Conclusions

We conclude that arousal from sleep is under ultradian control and regulated in a sex-dependent manner by dietary yeast and that dietary sucrose regulates the length of time that flies sustain periods of wakefulness. These findings highlight Drosophila as an important model with which to understand how diet impacts upon sleep and wakefulness in mammals and humans.     

Weight gain and the sleeping electroencephalogram: study of 10 patients with anorexia nervosa.

The relation between reduced nutritional intake, with consequent weight loss, and sleep disturbance was studied by comparing certain sleep encephalogram patterns in a group of inpatients with anorexia nervosa before, during, and after a regimen of refeeding with a normal diet to a matched population mean weight. At low body weights patients had less sleep and more restlessness, especially in the last four hours of the night. During refeeding and weight gain slow-wave sleep initially increased and then tended to decrease during the final stage of restoration of weight back to matched population mean levels. With the overall weight gain, however, there was a significant increase in length of sleep and rapid eye movement sleep, the latter increasing especially during the later stages of weight gain. These results reaffirm that insomnia, and especially early morning waking, is associated with low body weight in anorexia nervosa, and their implications are discussed with particular reference to a hypothetical association between various anabolic profiles and the need for differing components of sleep.     

Chronic Powder Diet After Weaning Induces Sleep,Behavioral, Neuroanatomical,and Neurophysiological Changes in Mice

The purpose of this study is to clarify the effects of chronic powder diet feeding on sleep patterns and other physiological/anatomical changes in mice. C57BL/6 male mice were divided into two groups from weaning: a group fed with solid food (SD) and a group fed with powder food (PD), and sleep and physiological and anatomical changes were compared between the groups. PD exhibited less cranial bone structure development and a significant weight gain. Furthermore, these PD mice showed reduced number of neurogenesis in the hippocampus. Sleep analysis showed that PD induced attenuated diurnal sleep/wake rhythm, characterized by increased sleep during active period and decreased sleep during rest period. With food deprivation (FD), PD showed less enhancement of wake/locomotor activity compared to SD, indicating reduced food-seeking behavior during FD. These results suggest that powder feeding in mice results in a cluster of detrimental symptoms caused by abnormal energy metabolism and anatomical/neurological changes.     

Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss

Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-h blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean (s.d.) age 41 (5) years; BMI 27.4 (2.0) kg/m(2)) completed two 14-day treatments with hypocaloric diet and 8.5- or 5.5-h nighttime sleep opportunity in random order 7 (3) months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free fatty acids (FFA), 24-h blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 (0.3) BMI units) during each treatment. Bedtime restriction reduced sleep by 131 (30) min/day. Recurrent sleep curtailment decreased 24-h serum insulin concentrations (i.e., enhanced 24-h insulin economy) without changes in oral glucose tolerance and 24-h glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA, which suppressed normally following glucose ingestion, and lower total and low-density lipoprotein cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-h insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.     

Re-patterning sleep architecture in Drosophila through gustatory perception and nutritional quality

Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary factors and sleep behavior in Drosophila melanogaster. Dietary sugar rapidly altered sleep behavior by modulating the number of sleep episodes during both the light and dark phase of the circadian period, independent of an intact circadian rhythm and without affecting total sleep, latency to sleep, or waking activity. The effect of sugar on sleep episode number was consistent with a change in arousal threshold for waking. Dietary protein had no significant effect on sleep or wakefulness. Gustatory perception of sugar was necessary and sufficient to increase the number of sleep episodes, and this effect was blocked by activation of bitter-sensing neurons. Further addition of sugar to the diet blocked the effects of sweet gustatory perception through a gustatory-independent mechanism. However, gustatory perception was not required for diet-induced fat accumulation, indicating that sleep and energy storage are mechanistically separable. We propose a two-component model where gustatory and metabolic cues interact to regulate sleep architecture in response to the quantity of sugar available from dietary sources. Reduced arousal threshold in response to low dietary availability may have evolved to provide increased responsiveness to cues associated with alternative nutrient-dense feeding sites. These results provide evidence that gustatory perception can alter arousal thresholds for sleep behavior in response to dietary cues and provide a mechanism by which organisms tune their behavior and physiology to environmental cues.     

Plasma renin activity and serum aldosterone during prolonged physical strain. The significance of sleep and energy deprivation

Plasma renin activity (PRA), serum aldosterone and the serum and urinary levels of sodium and potassium have been investigated in 24 young men participating in a 5-day military training course with heavy continuous physical exercise, energy and sleep deprivation. The subjects were divided into three groups. Group 1 did not get any extra sleep or food, group 2 were compensated for the energy deficiency, and group 3 slept 3 h each night. The basic diet given to all the subjects was about 5,000 kJ and 2 g NaCl X 24 h-1 X cadet-1. The high calorie diet contained approximately 25,000-35,000 kJ and 20 g of NaCl X 24 h-1 X cadet-1. The study showed that serum aldosterone and PRA were extremely activated during such prolonged physical strain combined with lack of food and salt, whereas sleep deprivation did not seem to have any large influence. Only small variations were found in the serum levels of sodium and potassium and the urinary level of potassium during the course, whereas a decrease was seen in urinary sodium concentration. The fairly good correlations between the decrease in urinary sodium levels and the increase in PRA (r = 0.7) and further between PRA and serum aldosterone (r = 0.8) during the course indicate that there is a causal connection between the decrease in urinary sodium excretion and the increase in PRA and serum aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phylogenetic analysis of the ecology and evolution of mammalian sleep

The amount of time asleep varies greatly in mammals, from 3 h in the donkey to 20 h in the armadillo. Previous comparative studies have suggested several functional explanations for interspecific variation in both the total time spent asleep and in rapid-eye movement (REM) or "quiet" (non-REM) sleep. In support of specific functional benefits of sleep, these studies reported correlations between time in specific sleep states (NREM or REM) and brain size, metabolic rate, and developmental variables. Here we show that estimates of sleep duration are significantly influenced by the laboratory conditions under which data are collected and that, when analyses are limited to data collected under more standardized procedures, traditional functional explanations for interspecific variation in sleep durations are no longer supported. Specifically, we find that basal metabolic rate correlates negatively rather than positively with sleep quotas, and that neither adult nor neonatal brain mass correlates positively with REM or NREM sleep times. These results contradict hypotheses that invoke energy conservation, cognition, and development as drivers of sleep variation. Instead, the negative correlations of both sleep states with basal metabolic rate and diet are consistent with trade-offs between sleep and foraging time. In terms of predation risk, both REM and NREM sleep quotas are reduced when animals sleep in more exposed sites, whereas species that sleep socially sleep less. Together with the fact that REM and NREM sleep quotas correlate strongly with each other, these results suggest that variation in sleep primarily reflects ecological constraints acting on total sleep time, rather than the independent responses of each sleep state to specific selection pressures. We propose that, within this ecological framework, interspecific variation in sleep duration might be compensated by variation in the physiological intensity of sleep.