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Benington JH, Heller HC. Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol 45: 347-360
... Caffeine can cause sleep disturbances as well within the sleep-wake cycle. If caffeine is consumed into mid-afternoon, it continues to act as an antifatigue agent as well as a diuretic throughout the late 29 evening. It can affect anywhere from 1-3 hrs consumed before bedtime to up to 12 hrs earlier, depending on the individual. ...
... It can affect anywhere from 1-3 hrs consumed before bedtime to up to 12 hrs earlier, depending on the individual. In those individuals vulnerable to stress, disturbed sleep is even more 29,30 probable. Some studies have also reported that students with University which is 2500. ...
Context: University students who deprive themselves of enough nocturnal sleep due to academic activities are at risk of the deleterious effects of sleep deprivation that usually follow. To reverse these effects, they tend to consume substances such as caffeine to counteract fatigue and possibly give them the feeling of alertness they need to perform their daily activities given that there is a popular concern that the academic demands of University training can cause significant stress and the need to gain insight into the effects of caffeine on students.Objective: This study set out to assess the self-reported effects of the consumption of caffeine-containing products on nocturnal sleep and daytime functioning among students of Novena University, Ogume Delta State, Nigeria.Materials and Methods: The study adopted a descriptive cross-sectional design conducted among 400 students comprising 217 males and 183 females selected through random sampling. Data were collected using a 27-item questionnaire containing four sections; socio-demographic characteristics, caffeine consumption pattern, sleeping habits, and daytime functioning. The data was analysed using SPSS version 23 and presented in descriptive and inferential statistics at P <0.05 level of significance.Results: More than one-third of the respondents (68.50%) affirmed consuming caffeine-containing products such as caffeinated drinks and beverages. Only 21.50% affirmed practicing sleep deprivation and 40.10% agreed that their consumption of caffeine-containing products increases during times of academic stress. There was a significant relationship between the hours of sleep of the respondents and their consumption of caffeine. More than half of the respondents (71.90%) affirmed experiencing daytime sleepiness while about 40% affirmed experiencing caffeine-induced daytime dysfunction.Conclusion: There was a significant relationship between the level of caffeine consumption and students’ sleep quality. Caffeine-induced sleep deprivation and caffeine-induced daytime dysfunction are widespread among undergraduate students in the study population.
... Theories also suppose that sleep is essential for memory consolidation, as declarative and non-declarative memories are enhanced after periods of sleep during which synaptic connections strengthen following potentiation during wakefulness, the so-called "synaptic homeostasis hypothesis" (Tononi and Cirelli, 2014). Further, as wakefulness is an energetic challenge to the brain, sleep may act to conserve and replenish energy stores for the brain and allow for repair and restoration processes (Benington and Heller, 1995). It is more than likely, however, that sleep serves many essential functions. ...
... Glucose, the main source of physiological energy, is stored as glycogen exclusively in astrocytes in the brain (Obel et al., 2012). Glycogen stores which are depleted during wakefulness are hypothesized to replenish within astrocytes during sleep (Bellesi et al., 2018;Benington and Heller, 1995;Karnovsky et al., 1983;Scharf et al., 2008). Further, glycogen depletion during sustained wakefulness has been linked to a buildup of sleep pressure itself (Bellesi et al., 2018), pointing to a mechanism through which astrocytes may induce homeostatic sleep drive, process S. ...
Sleep is a vital and evolutionarily conserved process, critical to daily functioning and homeostatic balance. Losing sleep is inherently stressful and leads to numerous detrimental physiological outcomes. Despite sleep disturbances affecting everyone, women and female rodents are often excluded or underrepresented in clinical and pre-clinical studies. Advancing our understanding of the role of biological sex in the responses to sleep loss stands to greatly improve our ability to understand and treat health consequences of insufficient sleep. As such, this review discusses sex differences in response to sleep deprivation, with a focus on the sympathetic nervous system stress response and activation of the hypothalamic-pituitary-adrenal (HPA) axis. We review sex differences in several stress-related consequences of sleep loss, including inflammation, learning and memory deficits, and mood related changes. Focusing on women's health, we discuss the effects of sleep deprivation during the peripartum period. In closing, we present neurobiological mechanisms, including the contribution of sex hormones, orexins, circadian timing systems, and astrocytic neuromodulation, that may underlie potential sex differences in sleep deprivation responses.
... However, some human studies did not find a correlation between sleep and blood glucose [9,47], implying that there are other metabolic markers correlated to sleep. Glycogen has been considered an important regulator of sleep homeostasis [48]. We also showed that body glycogen mirrored sleep phenotypes caused by dietary macronutrient balance. ...
... This indicated the meditative role of glycogen in sleep in dietary balance. However, no evidence yet for a mechanism linking glycogen to sleep modulation [42,[48][49][50]. Glycogen is firstly broken into glucose, indicating glycogen may play its role in sleep through glucose. ...
Dietary protein (P) and carbohydrate (C) have a major impact on sweet taste sensation. However, it remains unclear whether the balance of P and C influences sweet taste sensitivity. Here, we use the nutritional geometry framework (NGF) to address the interaction of protein and carbohydrates and on sweet taste using Drosophila as a model. Our results reveal that high-protein, low-carbohydrate (HPLC) diets sensitize to sweet taste and low-protein, high-carbohydrate (LPHC) diets desensitize sweet taste in both male and female flies. We further investigate the underlying mechanisms of these two diets' effect on sweet taste using RNA sequencing. When compared to the LPHC diet, the mRNA expression of genes involved in the metabolism of glycine, serine, and threonine is significantly upregulated in the HPLC diet, suggesting these amino acids may mediate sweet taste perception. We further find that sweet sensitization occurs in flies fed with the LPHC diet supplemented with serine and threonine. Our study demonstrates that sucrose taste sensitivity is affected by the balance of dietary protein and carbohydrates possibly through changes in serine and threonine.
... However, some human studies did not find a correlation between sleep and blood glucose [9,47], implying that there are other metabolic markers correlated to sleep. Glycogen has been considered an important regulator of sleep homeostasis [48]. We also showed that body glycogen mirrored sleep phenotypes caused by dietary macronutrient balance. ...
... This indicated the meditative role of glycogen in sleep in dietary balance. However, no evidence yet for a mechanism linking glycogen to sleep modulation [42,[48][49][50]. Glycogen is firstly broken into glucose, indicating glycogen may play its role in sleep through glucose. ...
Aims:
Sleep is a fundamental physiological function and is essential for all animals. Sleep is affected by diet compositions including protein (P) and carbohydrates (C), but there has not been a systematic investigation on the effect of dietary macronutrient balance on sleep.
Main methods:
We used the nutritional geometry framework (NGF) to explore the interactive effects on sleep of protein (P) and carbohydrates (C) in the model organism Drosophila. Both female and male flies were fed various diets containing seven ratios of protein-to-carbohydrates at different energetic levels for 5 days and sleep was monitored by the Drosophila Activity Monitor (DAM) system.
Key findings:
Our results showed that the combination of low protein and high carbohydrates (LPHC) prolonged sleep time and sleep quality, with fewer sleep episodes and longer sleep duration. We further found that the effects of macronutrients on sleep mirrored levels of hemolymph glucose and whole-body glycogen. Moreover, transcriptomic analyses revealed that a high-protein, low-carbohydrate (HPLC) diet significantly elevated the gene expression of metabolic pathways when compared to the LPHC diet, with the glycine, serine, and threonine metabolism pathway being most strongly elevated. Further studies confirmed that the contents of glycine, serine, and threonine affected sleep.
Significance:
Our results demonstrate that sleep is affected by the dietary balance of protein and carbohydrates possibly mediated by the change in glucose, glycogen, glycine, serine, and threonine.
... Our findings are consistent with 'energy-charge'-based theories that link changes in astroglial energy substrates with sleep drive [40,41]. As proposed by Benington and Heller [42], waking activation of astroglial NA receptors triggers glycogenolysis and glucose release, which supports neuronal metabolic activity. The progressive depletion of this astroglial energy store during wakefulness increases NREM SWA via the release of neuronal adenosine [42]. ...
... As proposed by Benington and Heller [42], waking activation of astroglial NA receptors triggers glycogenolysis and glucose release, which supports neuronal metabolic activity. The progressive depletion of this astroglial energy store during wakefulness increases NREM SWA via the release of neuronal adenosine [42]. The NA receptor subtype mediating glycogenolysis was not specified, but this likely involves the β2-AR [25,43]. ...
Astrocytes influence sleep expression and regulation, but the cellular signaling pathways involved in these processes are poorly defined. We proposed that astrocytes detect and integrate a neuronal signal that accumulates during wakefulness, thereby leading to increased sleep drive. Noradrenaline (NA) satisfies several criteria for a waking signal integrated by astrocytes. We therefore investigated the role of NA signaling in astrocytes in mammalian sleep. We conditionally knocked out (cKO) β2-adrenergic receptors (β2-AR) selectively in astrocytes in mice and recorded electroencephalographic and electromyographic activity under baseline conditions and in response to sleep deprivation (SDep). cKO of astroglial β2-ARs increased active phase siesta duration under baseline conditions and reduced homeostatic compensatory changes in sleep consolidation and non-rapid eye movement slow-wave activity (SWA) after SDep. Overall, astroglial NA β2-ARs influence mammalian sleep homeostasis in a manner consistent with our proposed model of neuronal–astroglial interactions.
... The state of sleep is a tightly controlled process in part by circadian regulation and homeostatic pressures [1][2][3]. Among several proposed purposes of sleep, such as facilitating the clearance of toxins and memory formation, it is thought to play a role in overall metabolic restoration [4][5][6]. Disrupted sleep has not only been identified as a risk factor for pathophysiolgies, such as neurodegenerative disorders, but has also been associated with altered metabolism in both humans and model organisms [7,8]. Given the potential role sleep plays in metabolic restoration and the role circadian processes play in its regulation, it reasons that metabolic rhythmicity may facilitate separation of incompatible processes. ...
Sleep is an almost universally required state in biology. Disrupted sleep has been associated with adverse health risks including metabolic perturbations. Sleep is in part regulated via circadian mechanisms, however, metabolic dysfunction at different times of day arising from sleep disruption is unclear. We used targeted liquid chromatography-mass spectrometry to probe metabolic alterations using high-resolution temporal sampling of two Drosophila short sleep mutants, fumin and sleepless, across a circadian day. Discriminant analyses revealed overall distinct metabolic profiles for mutants when compared to a wild type dataset. Altered levels of metabolites involved in nicotinate/nicotinamide, alanine, aspartate, and glutamate, glyoxylate and dicarboxylate metabolism, and the TCA cycle were observed in mutants suggesting increased energetic demands. Furthermore, rhythmicity analyses revealed fewer 24 hr rhythmic metabolites in both mutants. Interestingly, mutants displayed two major peaks in phases while wild type displayed phases that were less concerted. In contrast to 24 hr rhythmic metabolites, an increase in the number of 12 hr rhythmic metabolites was observed in fumin while sleepless displayed a decrease. These results support that decreased sleep alters the overall metabolic profile with short sleep mutants displaying altered metabolite levels associated with a number of pathways in addition to altered neurotransmitter levels.
... SWS plays an important role in memory and cognitive function, and reduction in fatigue [9]. In other words, SWS plays an important role in homeostasis, cerebral restoration, and recovery [30,31]. In patients with severe apnea, the amount of SWS is reduced, as shown in our results (Table 2). ...
Background and Objective Prior research suggests that slow wave sleep (SWS) is disrupted in people with obstructive sleep apnea (OSA). However, it was not clear whether the reduction in SWS is related to abnormal breathing or the extent of OSA as determined by the minimum oxygen saturation. Further, there is limited research on the relationship between oxygen saturation and SWS. The present study examined the relationship between SWS and minimum oxygen saturation levels in patients with OSA.Methods The sample consisted of 589 patients with OSA (mean age: 48.54 years) who completed full-night polysomnography.Results Results showed that there was a significant difference in SWS scores across three apnea-hypopnea index (AHI) groups (AHI score 5–15 for mild apnea, 16–30 for moderate apnea, and >30 for severe apnea). Lower SWS scores were observed in the severe apnea group. Additionally, results indicated that as oxygen saturation decreased, the SWS scores decreased.Conclusions Results from this study indicate that oxygen saturation significantly predicts SWS amounts. These findings suggest that interventions for low oxygen saturation could enhance the amounts of SWS. The clinical ramifications of these findings are worthy of consideration.
... To avoid any complications, optimal sleep has been recommended for its valuable physiological processes, which include restorative and regulatory properties [35,36]. ...
The immune system is a very complex network of cells, tissues and organs that work together to defend the body against pathogens. Its two main components are: the innate immune system and the adaptive immune system. However, when this system is compromised, the body's ability to defend itself is impaired, which can increase the risk of developing at least one of the more than 80 autoimmune diseases that affect a significant proportion of the world's population. These illnesses can cause a range of symptoms, including pain, fatigue, rashes, nausea, headaches and dizziness. They can also affect different parts of the body, such as the skin, muscles, joints, tendons, blood and blood vessels, and even other organs. Also, it is not uncommon to suffer from more than one type of autoimmune disease, as they share similarities in their basic immunological mechanisms. In this review, we aim to provide a more comprehensive understanding of the impact and severity of immune dysfunction. We will also describe the advantages and disadvantages of factors considered to promote immune function and summarize current knowledge about the mechanisms of certain autoimmune diseases. We hope to shed light on this complex subject and provide valuable insights into potential treatments and preventive measures for these diseases.
... Sleep is a widespread-possibly universal-feature of animal life (Keene and Duboue 2018), but its definitive purposes continue to elude us. There is increasing acknowledgement, however, that the functions of sleep relate primarily to the brain (Hobson 2005), perhaps encompassing the replenishment of cerebral energy stores depleted during waking (Benington and Heller 1995) and memory consolidation (Rasch and Born 2013). The timing, duration and intensity of sleep are regulated per the "two-process" model, in which an animal's circadian rhythm dictates the time(s) of day when it will tend to sleep, while homeostatic sleep pressure accumulates during waking to drive changes in the depth and duration of sleep (Borbély and Achermann 1999). ...
Sleep pressure builds during wakefulness, but the mechanisms underlying this homeostatic process are poorly understood. One zebrafish model suggests that sleep pressure increases as a function of global neuronal activity, such as during sleep deprivation or acute exposure to drugs that induce widespread brain activation. Given that the arousal-promoting noradrenergic system is important for maintaining heightened neuronal activity during wakefulness, we hypothesised that genetic and pharmacological reduction of noradrenergic tone during drug-induced neuronal activation would dampen subsequent rebound sleep in zebrafish larvae. During stimulant drug treatment, dampening noradrenergic tone with the α2-adrenoceptor agonist clonidine unexpectedly enhanced subsequent rebound sleep, whereas enhancing noradrenergic signalling with a cocktail of α1- and β-adrenoceptor agonists did not enhance rebound sleep. Similarly, CRISPR/Cas9-mediated elimination of the dopamine β-hydroxylase (dbh) gene, which encodes an enzyme required for noradrenalin synthesis, enhanced baseline sleep in larvae but did not prevent additional rebound sleep following acute induction of neuronal activity. Across all drug conditions, c-fos expression immediately after drug exposure correlated strongly with the amount of induced rebound sleep, but was inversely related to the strength of noradrenergic modulatory tone. These results are consistent with a model in which increases in neuronal activity, as reflected by brain-wide levels of c-fos induction, drive a sleep pressure signal that promotes rebound sleep independently of noradrenergic tone.
... The importance of sleep is highlighted by the fact that sleep deprivation leads to an increased demand for sleep, as reflected in EEG recordings which show a compensatory increase in the power of delta oscillations during the NREM sleep stage. While the precise role of sleep remains elusive, there are many hypotheses that include the restoration of the organism's energy and the promotion of memory consolidation, which is necessary for acquiring knowledge during wakefulness [7,8]. Additionally, during sleep, the brain is able Figure 1. ...
Sleep is an essential innate but complex behaviour which is ubiquitous in the animal kingdom. Our knowledge of the distinct neural circuit mechanisms that regulate sleep and wake states in the brain are, however, still limited. It is therefore important to understand how these circuits operate during health and disease. This review will highlight the function of mGlu5 receptors within the thalamocortical circuitry in physiological and pathological sleep states. We will also evaluate the potential of targeting mGlu5 receptors as a therapeutic strategy for sleep disorders that often co-occur with epileptic seizures.
... F.eks. Benington & Hellers restorationsteori [4], der argumenterer for, at søvn spiller en saerlig rolle i forhold til genopfyldning af hjernens glykogendepoter -dens vigtigste energikilde. En anden fremtraedende teori i denne gruppe omhandler det glymfatiske system, hvor Maiken Nedergaard og kolleger har vist, hvordan dyb søvn faciliterer fjernelsen af metaboliske affaldsstoffer via øget gennemstrømning af cerebrospinalvaeske ved de perivaskulaere regioner [5]. ...
Sleep is important for brain health, having both a restorative function and playing an important role in cognitive functions, e.g., attention, memory, learning, and planning. This review finds that sleep disturbances are prevalent and associated with poorer cognitive functioning in neurodegenerative disorders such as Parkinson's disease and in people with non-neurodegenerative diseases such as cancer and mood disorders. Screening for and treating sleep disturbances are potential supplementary approaches to preventing and treating cognitive impairment.
... Exactly how circadian and homeostatic processes interact to organize sleep behavior remains unclear and are likely not operating independently (Deboer et al., 2003(Deboer et al., , 2007Easton et al., 2004;Laposky et al., 2005;Wright et al., 2012;Deboer, 2018). Further, the likely involvement of other processes such as energy metabolism (Benington and Heller, 1995;Scharf et al., 2008;Franken and Dijk, 2009;Dash et al., 2013;Bellesi et al., 2018;Malik et al., 2020), lipid signaling and storage (Thimgan et al., 2010(Thimgan et al., , 2015Yurgel et al., 2018;Ioannou et al., 2019a;Li Y. et al., 2023), astrocyte-neurometabolic coupling through glymphatics (Jessen et al., 2015;Haydon, 2017;Lundgaard et al., 2017), autophagy (Xie et al., 2020;Bedont et al., 2021;Damulewicz et al., 2022b;Guo et al., 2022), and the astrocyte-neuron lactate shuttle (ANLS) (Scharf et al., 2008;Petit et al., 2013) reflect a complex and multivariable network ripe for exploration. ...
Sleep and circadian rhythms are observed broadly throughout animal phyla and influence neural plasticity and cognitive function. However, the few phylogenetically conserved cellular and molecular pathways that are implicated in these processes are largely focused on neuronal cells. Research on these topics has traditionally segregated sleep homeostatic behavior from circadian rest-activity rhythms. Here we posit an alternative perspective, whereby mechanisms underlying the integration of sleep and circadian rhythms that affect behavioral state, plasticity, and cognition reside within glial cells. The brain-type fatty acid binding protein, FABP7, is part of a larger family of lipid chaperone proteins that regulate the subcellular trafficking of fatty acids for a wide range of cellular functions, including gene expression, growth, survival, inflammation, and metabolism. FABP7 is enriched in glial cells of the central nervous system and has been shown to be a clock-controlled gene implicated in sleep/wake regulation and cognitive processing. FABP7 is known to affect gene transcription, cellular outgrowth, and its subcellular localization in the fine perisynaptic astrocytic processes (PAPs) varies based on time-of-day. Future studies determining the effects of FABP7 on behavioral state- and circadian-dependent plasticity and cognitive processes, in addition to functional consequences on cellular and molecular mechanisms related to neural-glial interactions, lipid storage, and blood brain barrier integrity will be important for our knowledge of basic sleep function. Given the comorbidity of sleep disturbance with neurological disorders, these studies will also be important for our understanding of the etiology and pathophysiology of how these diseases affect or are affected by sleep.
... The quantity and quality of sleep are key indicators of human health [1]. Sleep is known to restore energy [2], bolster the immune system [3], ward off infection [4], and impact cognition and behavior [5]. Chronic disruptions in sleep patterns have been linked to cardiovascular disease [6], diabetes [7,8], Alzheimer's disease [9][10][11], depression [12], migraine [13], and many other serious conditions. ...
Sleep is an important indicator of a person's health, and its accurate and cost-effective quantification is of great value in healthcare. The gold standard for sleep assessment and the clinical diagnosis of sleep disorders is polysomnography (PSG). However, PSG requires an overnight clinic visit and trained technicians to score the obtained multimodality data. Wrist-worn consumer devices, such as smartwatches, are a promising alternative to PSG because of their small form factor, continuous monitoring capability, and popularity. Unlike PSG, however, wearables-derived data are noisier and far less information-rich because of the fewer number of modalities and less accurate measurements due to their small form factor. Given these challenges, most consumer devices perform two-stage (i.e., sleep-wake) classification, which is inadequate for deep insights into a person's sleep health. The challenging multi-class (three, four, or five-class) staging of sleep using data from wrist-worn wearables remains unresolved. The difference in the data quality between consumer-grade wearables and lab-grade clinical equipment is the motivation behind this study. In this paper, we present an artificial intelligence (AI) technique termed sequence-to-sequence LSTM for automated mobile sleep staging (SLAMSS), which can perform three-class (wake, NREM, REM) and four-class (wake, light, deep, REM) sleep classification from activity (i.e., wrist-accelerometry-derived locomotion) and two coarse heart rate measures-both of which can be reliably obtained from a consumer-grade wrist-wearable device. Our method relies on raw time-series datasets and obviates the need for manual feature selection. We validated our model using actigraphy and coarse heart rate data from two independent study populations: the Multi-Ethnic Study of Atherosclerosis (MESA; N = 808) cohort and the Osteoporotic Fractures in Men (MrOS; N = 817) cohort. SLAMSS achieves an overall accuracy of 79%, weighted F1 score of 0.80, 77% sensitivity, and 89% specificity for three-class sleep staging and an overall accuracy of 70-72%, weighted F1 score of 0.72-0.73, 64-66% sensitivity, and 89-90% specificity for four-class sleep staging in the MESA cohort. It yielded an overall accuracy of 77%, weighted F1 score of 0.77, 74% sensitivity, and 88% specificity for three-class sleep staging and an overall accuracy of 68-69%, weighted F1 score of 0.68-0.69, 60-63% sensitivity, and 88-89% specificity for four-class sleep staging in the MrOS cohort. These results were achieved with feature-poor inputs with a low temporal resolution. In addition, we extended our three-class staging model to an unrelated Apple Watch dataset. Importantly, SLAMSS predicts the duration of each sleep stage with high accuracy. This is especially significant for four-class sleep staging, where deep sleep is severely underrepresented. We show that, by appropriately choosing the loss function to address the inherent class imbalance, our method can accurately estimate deep sleep time (SLAMSS/MESA: 0.61±0.69 hours, PSG/MESA ground truth: 0.60±0.60 hours; SLAMSS/MrOS: 0.53±0.66 hours, PSG/MrOS ground truth: 0.55±0.57 hours;). Deep sleep quality and quantity are vital metrics and early indicators for a number of diseases. Our method, which enables accurate deep sleep estimation from wearables-derived data, is therefore promising for a variety of clinical applications requiring long-term deep sleep monitoring.
... 21 In non-REM sleep, hippocampal activity did not change compared with wakefulness, which suggested the homeostatic or restorative role of neuronal glycogen in non-REM. 22 And, in non-REM sleep, a profound activation of the limbic core (hippocampus and amygdala) could be related to rich contents of dreams and memory formation. 23,24 Our study found that the left hippocampal perfusion was decreased in insomnia or sleep deprivation which not only led to the deactivation of the hippocampal in non-REM and REM sleep and damaged memory formation and neuronal glycogen restoration. ...
Objectives
Insomnia was associated with cerebral structural changes and Alzheimer’s disease. However, associations among cerebral perfusion, insomnia with cerebral small vessel disease (CSVD), and cognitive performance were little investigated.
Methods
This cross-sectional study included 89 patients with CSVDs and white matter hyperintensities (WMHs). They were dichotomized into the normal sleep and poor sleep group, according to Pittsburgh sleep quality index (PSQI). Baseline characteristics, cognitive performance, and cerebral blood flow (CBF) were measured and compared between the two groups. The association or correlation between cerebral perfusion, cognition, and insomnia was analyzed using binary logistic regression.
Results
Our study found that declined MoCA score ( P = .0317) was more prevalent in those with poor sleep. There was a statistical difference in the recall ( P = .0342) of MMSE, the delayed recall ( P = .0289) of MoCA between the two groups. Logistic regression analysis showed educational background ( P < .001) and insomnia severity index (ISI) score ( P = .039) were independently correlated with MoCA scores. Arterial spin labeling demonstrated that left hippocampal gray matter perfusion was significantly reduced ( P = .0384) in the group with poor sleep. And, negative correlation was found between left hippocampal perfusion and PSQI scores.
Conclusions
In the patients with CSVDs, insomnia severity was associated with cognitive decline. Left hippocampal gray matter perfusion was correlated with PSQI scores in CSVDs.
... Sleep is a widespread -possibly universal -feature of animal life (Keene and Duboue, 2018), but its definitive purposes continue to elude us. There is increasing acknowledgement, however, that the functions of sleep relate primarily to the brain (Hobson, 2005), perhaps encompassing the replenishment of cerebral energy stores depleted during waking (Benington and Heller, 1995) and memory consolidation (Rasch and Born, 2013). The timing, duration and intensity of sleep are regulated per the "two-process" model, in which an animal's circadian rhythm dictates the time(s) of day when it will tend to sleep, while homeostatic sleep pressure accumulates during waking to drive changes in the depth and duration of sleep (Borbély and Achermann, 1999). ...
Sleep pressure builds during wakefulness, but the mechanisms underlying this homeostatic process are poorly understood. One zebrafish model suggests that sleep pressure increases as a function of global neuronal activity, such as during sleep deprivation or acute exposure to drugs that induce widespread brain activation. Given that the arousal-promoting noradrenergic system is important for maintaining heightened neuronal activity during wakefulness, we hypothesised that genetic and pharmacological reduction of noradrenergic tone during drug-induced neuronal activation would dampen subsequent rebound sleep in zebrafish larvae. Unexpectedly, dampening noradrenergic tone with the α2-adrenoceptor agonist clonidine during acute caffeine or pentylenetetrazol treatment enhanced subsequent rebound sleep, while stimulating noradrenergic signalling during caffeine exposure with a cocktail of α1- and β-adrenoceptor agonists did not enhance sleep. Similarly, CRISPR/Cas9-mediated elimination of the dopamine β-hydroxylase ( dbh ) gene, which encodes an enzyme required for noradrenalin synthesis, enhanced baseline sleep in larvae but did not prevent additional rebound sleep following acute induction of neuronal activity. Across all drug conditions, c-fos expression immediately after drug exposure varied inversely with noradrenergic tone and correlated strongly with the amount of induced rebound sleep. These results are consistent with a model in which increases in neuronal activity, as reflected by brain-wide levels of c-fos induction, drive a sleep pressure signal that promotes rebound sleep independently of noradrenergic tone.
... There were several gene changes only observed in the adult brain (Fig. 7), including the downregulation of genes involved in glycolysis/ gluconeogenesis, pentose phosphate pathways, or lipid metabolism. This is consistent with the idea that different energy substrates are used by the awake and sleeping brain (Benington and Heller, 1995;Karnovsky, 1982;Karnovsky et al., 1983;Wisor et al., 2013). Indeed, processes related to elongation of fatty acids are significantly upregulated, more specifically Acetyl-CoA thioesterases (ACOT, Fig. 7) and Hydroxyacyl-CoA dehydrogenase B (Hadhb, Fig. 7). ...
Sleep deprivation (SD) results in profound cellular and molecular changes in the adult mammalian brain. Some of these changes may result in, or aggravate, brain disease. However, little is known about how SD impacts gene expression in developing animals. We examined the transcriptional response in the prefrontal cortex (PFC) to SD across postnatal development in male mice. We used RNA sequencing to identify functional gene categories that were specifically impacted by SD. We find that SD has dramatically different effects on PFC genes depending on developmental age. Gene expression differences after SD fall into 3 categories: present at all ages (conserved), present when mature sleep homeostasis is first emerging, and those unique to certain ages. Developmentally conserved gene expression was limited to a few functional categories, including Wnt-signaling which suggests that this pathway is a core mechanism regulated by sleep. In younger ages, genes primarily related to growth and development are affected while changes in genes related to metabolism are specific to the effect of SD in adults.
... As an endogenous purine nucleoside, adenosine is a sleep-promoting substance. As shown in previous studies, adenosine or adenosine A1 receptor agonists administered intraventricularly or systemically in animals can significantly reduce wakefulness and increase sleep [6][7][8][9]. Conversely, caffeine and theophylline are both adenosine A1 and A2A receptor antagonists and can reduce sleep [10,11]. Sleep time can be prolonged in rodents by inhibiting the activity of adenosine hydrolases such as adenosine kinase (ADK) and adenosine deaminase (ADA), reducing the breakdown of adenosine [12,13]. ...
Sleep disturbances are the most prevalent non-motor symptoms in the preclinical stage of Parkinson’s disease (PD). Adenosine, glial-derived neurotrophic factor (GDNF), and associated neurotransmitters are crucial in the control of sleep arousal. This study aimed to detect the serum levels of adenosine, GDNF, and associated neurotransmitters and explored their correlations with PD with sleep disorders. Demographic characteristics and clinical information of PD patients and healthy participants were assessed. Serum concentrations of adenosine, GDNF, and related neurotransmitters were detected by ELISA and LC-MS. The correlation between serum levels of adenosine, GDNF, and associated neurotransmitters and sleep disorders was explored using logistic regression. PD patients with sleep disorders had higher scores of HAMA, HAMD, ESS, UPDRS-III, and H-Y stage. Lower levels of adenosine, GDNF, and γ-GABA were observed in PD patients who had sleep problems. Logistic regression analysis showed adenosine and GDNF were protective factors for preventing sleep disorders. Adenosine combined with GDNF had a higher diagnostic efficiency in predicting PD with sleep disorders by ROC analysis. This study revealed low adenosine and GDNF levels may be risk factors for sleep disorders in PD. The decrease of serum adenosine and GDNF levels may contribute to the diagnosis of PD with sleep disturbances.
... Human sleep as a reversible physiological state is essential for health and performance in everyday life [7]. Its functions are not fully understood, despite extensive studies on its influence on energy homeostasis, immune function, cognitive performance and behavior, and the influence on various clinical pictures [8][9][10][11]. Sleep can be measured in multiple dimensions such as quantity, continuity, timing and quality [12][13][14][15]. Sensors have been used to study sleep for decades since the early 1950s. ...
Two commercial multisport activity trackers (Garmin Forerunner 945 and Polar Ignite) and the accelerometer ActiGraph GT9X were evaluated in measuring vital data, sleep stages and sleep/wake patterns against polysomnography (PSG). Forty-nine adult patients with suspected sleep disorders (30 males/19 females) completed a one-night PSG sleep examination followed by a multiple sleep latency test (MSLT). Sleep parameters, time in bed (TIB), total sleep time (TST), wake after sleep onset (WASO), sleep onset latency (SOL), awake time (WASO + SOL), sleep stages (light, deep, REM sleep) and the number of sleep cycles were compared. Both commercial trackers showed high accuracy in measuring vital data (HR, HRV, SpO2, respiratory rate), r > 0.92. For TIB and TST, all three trackers showed medium to high correlation, r > 0.42. Garmin had significant overestimation of TST, with MAE of 84.63 min and MAPE of 25.32%. Polar also had an overestimation of TST, with MAE of 45.08 min and MAPE of 13.80%. ActiGraph GT9X results were inconspicuous. The trackers significantly underestimated awake times (WASO + SOL) with weak correlation, r = 0.11–0.57. The highest MAE was 50.35 min and the highest MAPE was 83.02% for WASO for Garmin and ActiGraph GT9X; Polar had the highest MAE of 21.17 min and the highest MAPE of 141.61% for SOL. Garmin showed significant deviations for sleep stages (p < 0.045), while Polar only showed significant deviations for sleep cycle (p = 0.000), r < 0.50. Garmin and Polar overestimated light sleep and underestimated deep sleep, Garmin significantly, with MAE up to 64.94 min and MAPE up to 116.50%. Both commercial trackers Garmin and Polar did not detect any daytime sleep at all during the MSLT test. The use of the multisport activity trackers for sleep analysis can only be recommended for general daily use and for research purposes. If precise data on sleep stages and parameters are required, their use is limited. The accuracy of the vital data measurement was adequate. Further studies are needed to evaluate their use for medical purposes, inside and outside of the sleep laboratory. The accelerometer ActiGraph GT9X showed overall suitable accuracy in detecting sleep/wake patterns.
... Conversely, sleep restriction inhibits this process and thus decreases ATP levels in certain areas of the brain containing sleep-regulating neurons [34] that have been found to be damaged in other neuropsychiatric disorders caused by prolonged thiamine deficiency in alcoholics. Furthermore, the known hypnogenic properties of adenosine [35], the degradation product and ingredient of ATP, have been suggested to be a mediator between lowered ATP levels and sleep induction [36], which further supports our explanation that low thiamine intake may lead to prolonged sleep. ...
Objectives:
Thiamine is thought to modify sleeping patterns, while alcohol use diminishes internal thiamine levels. We investigated the association between thiamine intake and sleep duration and explored possible heterogeneity in the effect according to alcohol use.
Methods:
In total, 15 384 participants aged 19-64 were obtained from the Korea National Health and Nutrition Examination Survey 2012-2016. Nutrient intake, including thiamine, was measured using a food frequency questionnaire. Sleep duration was measured by a self-reported questionnaire. The highest thiamine intake quartile was set as the reference group. Participants were divided into 3 groups, with 7-8 hours of daily sleep as a reference group and those who slept more or less than that as "oversleeping" and "insufficient sleeping," respectively. Multivariate logistic regression was used, adjusting for socioeconomic, medical, and nutritional factors. Additionally, participants were stratified according to high-risk alcohol use defined by the World Health Organization standards on alcohol use.
Results:
Low thiamine intake was associated with oversleeping (Q3: odds ratio [OR], 1.06; 95% confidence interval [CI], 0.86 to 1.32; Q2: OR, 1.24; 95% CI, 0.99 to 1.55; Q1: OR, 1.49; 95% CI, 1.16 to 1.91) and showed a significant trend for higher ORs at lower intake levels (p-trend<0.001). The effect was stronger in the high-risk alcohol use group (Q1: OR, 1.78; 95% CI, 1.28 to 2.49).
Conclusions:
Low thiamine intake was associated with oversleeping, and alcohol use intensified that association. These results were found in a context where overt clinical symptoms due to thiamine deficiency are considered rare. More awareness of the potential relationship of thiamine intake with oversleeping and its related risks should be considered.
... Extracellular levels of adenosine are subsequently dissipated during sleep, particularly during slow wave sleep (7)(8)(9). Although this build-up of sleepiness is best alleviated by sleep, millions of people worldwide do not get enough sleep and instead attempt to manage their sleepiness through the use of caffeine, which is an adenosine receptor antagonist. ...
Sleep is one of the key underpinnings of human health, yet sleep disturbances and impaired sleep are rampant in modern life. Healthy sleep is a whole-body process impacted by circadian rhythm, daily activities, and emotional well-being, among others. When properly aligned, these work in concert to produce restorative and refreshing sleep. When not in balance, however, sleep disorders result. Yet too often, the approach to treatment of sleep disorders is compartmentalized, failing to recognize all of the complex interactions that are involved. This text offers a comprehensive approach to sleep and sleep disorders by delineating the many factors that interplay into healthy sleep. Health care providers can learn how to better manage their patients with sleep disorders by integrating complementary and conventional approaches. Using an evidence-based approach throughout, this book describes the basics of normal sleep then delves into the foundations of integrative sleep medicine, including the circadian rhythm, mind/body-sleep connection, light, dreaming, the gastrointestinal system, and botanicals/supplements. Specific sleep issues and disorders are then addressed from an integrative perspective, including insomnia, obstructive sleep apnea, sleep related movement disorders, and parasomnias.
... Sleep is a plausible candidate to explain variability in women's outcomes, including QoL, after receiving treatment for cancer. Sleep is hypothesised to serve a restorative and recuperative function [5]. Insufficient and disturbed sleep post-cancer treatment could impede recovery, disrupt rehabilitation efforts and compound other psychological, cognitive and health problems, ultimately affecting QoL. ...
Purpose
Sleep disturbance after cancer treatment could compromise recovery. This paper examined the associations between post-treatment sleep problems and health-related quality of life (HRQoL), and the effectiveness of an e-enabled lifestyle intervention on sleep outcomes.
Methods
The Women’s Wellness after Cancer Program (WWACP) was examined in a single blinded, multi-centre randomised controlled trial. Data were collected from 351 women (Mage = 53.2, SD = 8.8; intervention n = 175, control group n = 176) who had completed surgery, chemotherapy and/or radiotherapy for breast, gynaecological or blood cancers within the previous 24 months. Participants completed the Pittsburgh Sleep Quality Index (PSQI) at baseline (prior to intervention randomisation), and at 12 and 24 weeks later. Sociodemographic information, menopausal symptoms (Greene Climacteric Scale) and HRQoL (36-Item Short Form Health Survey; SF-36) were also collected. Linear panel regression was used to examine the association between sleep variables and SF36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. A difference-in-difference regression model approach was used to examine the intervention effect on the sleep outcomes.
Results
After adjustment for potential confounders, the sleep variables (except sleep duration) significantly predicted physical, but not mental, HRQoL. There was no statistically significant effect of the intervention on sleep outcomes at 12 or 24 weeks.
Conclusion
Women who have completed treatment for cancer experience sleep problems that are associated with decreased physical HRQoL. Improving sleep through targeted interventions should improve their physical HRQoL. Improved targeting of the sleep components of the WWACP should be explored.
... A fourth explanation for the lack of a clear wake-duration dependent sleep response in our starlings is that sleep is not homeostatically regulated in this species. This explanation may not seem very likely because it is at odds with some of the most influential theories on sleep homeostasis and sleep function that proposes that sleep is a recovery process from prior wakefulness, for example, to replenish brain energy stores that were depleted in the course of wakefulness [54], or to downscale synapses that were potentiated during waking neuronal activity [55]. However, the view that sleep is homeostatically regulated in relation to the duration of prior wakefulness is largely based on studies in only a handful of mammalian species and no single theory is undisputed or unequivocally proven. ...
... Certain physiological mechanisms have been proposed to support the relation between sleep and behavior. First, sleep is associated to brain functioning and in particular to cerebral glycogen metabolism which, in turn, influences the behavior [40,41]. Second, a melatonin mediated hormonal pathway of the relation between sleep and behavior has been proposed but is currently under discussion [42][43][44]. ...
Study Objectives
The objective of the study was to investigate the association of sleep quality, media use and book reading on internalizing, externalizing and prosocial behavior in early childhood.
Methods
In this cross-sectional study we investigated a data set consisting of three consecutive yearly waves of the prospective Ulm SPATZ Health Study, conducted in southern Germany with 565, 496 and 421 children of 4 to 6 years of age, respectively.
Standardized effects of the overall score and subscales of the Children's Sleep Habits Questionnaire, parent-reported child media use and book reading as well as their interaction term on the total score of the Strengths and Difficulties Questionnaire along with its externalizing, internalizing and prosocial subscales were estimated by multivariate adjusted random intercept mixed models.
Results
Overall sleep quality was associated more with internalizing than externalizing behavior; parasomnias associated with both behaviors. Night waking and sleep anxiety associated only with internalizing behavior. High levels of media use were associated with less internalizing behavior. More book reading resulted in less externalizing and internalizing behavior but more prosocial behavior. Finally, book reading and media use do not interact to determine child’s behavior.
Conclusions
The current work supports a strategy of monitoring sleep quality, reducing media use and promoting book reading in order to avoid behavioral problems in early childhood.
... During NREM sleep, body metabolism slows, body temperature decreases, and oxygen consumption diminishes, so that energy is conserved (Shapiro and Flanigan, 1993). Brain glycogen storage is restored during NREM sleep (Benington and Heller, 1995) and anabolic processes accelerate (Shapiro and Flanigan, 1993). NREM sleep may also play a central role in neurogenesis; REM sleep occurs proportionally and absolutely more during early development, and secures neuronal development (Siegel, 2005). ...
Simple Summary
The welfare of farm animals is important to the animal, farmers and consumers. Sleep is sensitive to disturbances and may be a useful tool in assessing welfare at night. The objective of this study was to look at the effects of 24 h disturbances (feed removal, increased room temperature, footpad pain) on sleep behaviour in laying hens. Sleep during lights-off comprised both slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Averaged over all nights, behaviour during lights-off consisted of 60% SWS and 12% REM sleep, with the remaining 28% attributed to being awake. During lights-off, feed removal and footpad pain had little to no effect on behaviours, while increased room temperature nearly eliminated REM sleep and reduced SWS. During lights-on, footpad pain increased the amount of time hens spent resting and in SWS, with no effects seen for feed removal or increased temperature. Global warming and subsequent increased poultry shed temperatures are likely to result in reduced sleep and welfare in on-farm laying hens, while lack of feed and footpad pain may disrupt sleep less.
Abstract
Ensuring the welfare of commercially kept animals is a legal and ethical responsibility. Sleep behaviour can be sensitive to environmental perturbations and may be useful in assessing welfare state. The objective of this study was to use behavioural and electrophysiological (EEG) measures to observe the effects of 24 h stressors followed by periods of no stressors on laying hen sleep behaviour, and to investigate the use of sleep behaviour as a means of welfare assessment in commercial poultry. Ten laying hens surgically implanted with EEG devices to record their brain activity over four batches were used. Hens were subjected to undisturbed, disturbed and recovery periods for 24 h. Disturbed periods consisted of either feed deprivation, increased ambient temperature (28 °C) or simulated footpad pain via injection of Freund’s adjuvant into the footpad. Sleep state was scored using behaviour data from infrared cameras and EEG data. Over all periods, hens engaged in both SWS (average 60%) and REM sleep (average 12%) during the lights-off period. Feed deprivation and footpad pain had little to no effect on sleep states, while increased ambient temperature significantly reduced REM sleep (to near elimination, p < 0.001) and SWS (p = 0.017). During the lights-on period, footpad pain increased the proportion of time spent resting (p = 0.008) and in SWS (p < 0.001), with feed deprivation or increased ambient temperature (p > 0.05) having no effect. Increasing ambient temperatures are likely to affect sleep and welfare in commercially-kept laying hens in the face of global climate change.
Caffeine has significant effects on neurovascular activity and behavior throughout the sleep-wake cycle. We used a minimally invasive microchip/video system to continuously record effects of caffeine in the drinking water of freely behaving mice. Chronic caffeine shifted both rest and active phases by up to 2 hours relative to the light-dark cycle in a dose-dependent fashion. There was a particular delay in onset of REM sleep as compared with non-REM sleep during the rest phase. Chronic caffeine increased wakefulness during the active phase and consolidated sleep during the rest phase; overall there was no net change in the amount of time spent in the wake, sleep, or REM sleep states during caffeine administration. Despite these effects on wakefulness and sleep, chronic caffeine decreased mean cerebral blood volume (CBV) during the active phase and increased mean CBV during the rest phase. Chronic caffeine also increased heart rate variability in both the sleep and wake states. These results provide new insight into the effects of caffeine on the biology of the sleep-wake cycle. Increased blood flow during sleep caused by chronic caffeine may have implications for its potential neuroprotective effects through vascular mechanisms of brain waste clearance.
Sleep plays an essential role in all studied animals with a nervous system. However, sleep deprivation leads to various pathological changes and neurobehavioral problems. Astrocytes are the most abundant cells in the brain and are involved in various important functions, including neurotransmitter and ion homeostasis, synaptic and neuronal modulation, and blood-brain barrier maintenance; furthermore, they are associated with numerous neurodegenerative diseases, pain, and mood disorders. Moreover, astrocytes are increasingly being recognized as vital contributors to the regulation of sleep-wake cycles, both locally and in specific neural circuits. In this review, we begin by describing the role of astrocytes in regulating sleep and circadian rhythms, focusing on: (i) neuronal activity; (ii) metabolism; (iii) the glymphatic system; (iv) neuroinflammation; and (v) astrocyte-microglia cross-talk. Moreover, we review the role of astrocytes in sleep deprivation comorbidities and sleep deprivation-related brain disorders. Finally, we discuss potential interventions targeting astrocytes to prevent or treat sleep deprivation-related brain disorders. Pursuing these questions would pave the way for a deeper understanding of the cellular and neural mechanisms underlying sleep deprivation-comorbid brain disorders.
The review article enlightens contemporary concept about a role of sleep in cellular energy metabolism, neuroplasticity and glymphatic clearance of waste products. Many researches have demonstrated that prolonged wakefulness is an energetic and a neurophysiologic issue for the brain. The article provides description of biochemical processes that are responsive for energy restoration in sleep, particularly the role of ATP, adenosine and glycogen. Energy metabolism substrates depletion leads to endoplasmic reticulum stress and unfolded protein response. At the same time the conductance of synapses increases that worsens energetic problems. Level of the glymphatic clearance during wakefulness is substantially lower in comparison with sleep, and waste products are not removed fast enough.
The Neuroscience of Sleep and Dreams provides comprehensive coverage of the basic neuroscience of both sleep and dreams for upper-level undergraduate and graduate students. It details new scientific discoveries, places those discoveries within evolutionary context, and links established findings with implications for sleep medicine. This second edition focuses on recent developments in the social nature of sleep and dreams. Coverage includes the neuroscience of all stages of sleep; the lifespan development of these sleep stages; the role of non-REM and REM sleep in health and mental health; comparative sleep; biological rhythms; sleep disorders; sleep memory; dream content; dream phenomenology, and dream functions. Students, scientists, and interested non-specialists will find this book accessible and informative.
Sleep and circadian rhythms are a key part of organismal function. Despite the clear importance of maintaining quality sleep and circadian rhythms, the precise mechanisms responsible for maintaining sleep and circadian function are still actively under investigation. Critically, poor sleep and deterioration of circadian timing are evident across species as organisms age, providing further impetus to understand how sleep and wake behaviors are coordinated, and how these processes are aggravated during the aging process. In the following chapter, we will discuss current models used to study sleep and circadian rhythms, and how these models have given valuable insight into the mechanisms that regulate sleep and circadian timing, with a focus on how these mechanisms are altered with age.
Background:
During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home confinement. Melatonin is a popular anti-inflammatory and antioxidant molecule sold as an over-the-counter dietary supplement.
Objective:
This review discusses the indications for using melatonin in the context of the COVID-19 pandemic, including treatment.
Methods:
A comprehensive search of publications was conducted in electronic databases focusing on the administration of melatonin in COVID-19.
Results:
Stress has a huge negative impact on sleep routines and the quality of life of individuals. Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The administration of melatonin protects against viral and other pathogens and speeds clinical recovery.
Conclusion:
In patients admitted to intensive care units, melatonin decreases the risks of severe complications, such as thrombosis and sepsis, and mortality rates. In addition, it is efficacious in lowering vessel permeability, depression, and sedation, and improving the quality of sleep, which could also help COVID-19 patients achieve better clinical outcomes.
Introduction : En réanimation, le sommeil est déstructuré, fragmenté et non réparateur. Ce mauvais sommeil est associé à une augmentation de la morbi-mortalité et de la durée du sevrage de la ventilation mécanique. Le sevrage ventilatoire est une période critique qui se complique dans 15% des cas. Les échecs de sevrage ventilatoire ont une physiopathologie complexe et le mauvais sommeil pourrait être impliqué en diminuant l’autonomie respiratoire des patients. Objectifs : (1) Evaluer l’impact de la privation de sommeil sur l’endurance musculaire inspiratoire et manuelle ; (2) Explorer les mécanismes physiologiques en cause chez le sujet sain ; (3) Evaluer chez le patient de réanimation la pertinence des mécanismes mis en évidence chez le sujet sain et proposer des mesures protectrices du sommeil en réanimation. Matériel et Méthodes : Chez le sujet sain, ce travail de thèse a comparé l’endurance inspiratoire et manuelle après sommeil normal et après privation aiguë de sommeil, en explorant la commande cérébrale musculaire, le muscle squelettique et les afférences musculaires. Chez le patient de réanimation, la commande cérébrale inspiratoire a été comparée entre les patients réussissant et les patients échouant leur sevrage ventilatoire. Enfin, la capacité d’un algorithme à distinguer les états de veille et de sommeil des patients de réanimation a été évaluée.Résultats : Une privation aiguë de sommeil diminuait l’endurance inspiratoire de 50% et manuelle de 11% chez des hommes sains. Cette perte d’endurance musculaire était associée à une altération de la commande musculaire corticale prémotrice et à une augmentation de la dyspnée et des afférences motrices pour un effort équivalent. Chez les patients de réanimation, une augmentation de 0,425 µV d’amplitude des potentiels prémoteurs inspiratoires prédisait l’échec de sevrage ventilatoire avec une sensibilité de 100% et une spécificité de 87%. L’analyse automatique de polysomnographies de réanimation par un algorithme de détection automatique du sommeil était bien corrélée à la lecture humaine. Conclusions : Lors d’un exercice, la privation aiguë de sommeil entraine une augmentation des afférences musculaires, inhibant la commande prémotrice corticale et réduisant l’endurance des muscles striés squelettiques. La mesure des potentiels prémoteurs inspiratoires prédit efficacement l’échec de sevrage ventilatoire d’un patient intubé. Ainsi, le mauvais sommeil nuit au sevrage ventilatoire des patients. Mais la détection en direct du sommeil de ces patients ouvre la voie à une protection du sommeil tout au long du nycthémère.
Psychological reattachment means mentally tuning into one's work before starting work in the morning. In this daily diary study, we investigated whether psychological reattachment may be beneficial not only for work engagement but also for proactivity during the day. We moreover considered two competing theoretical propositions regarding the role of psychological reattachment in the effect of sleep quality on work engagement and proactivity. The first proposition assumes a cognitive, self-regulatory perspective in which psychological reattachment serves as a moderator, buffering the detrimental effect of poor sleep quality on work engagement and proactivity. The second proposition assumes an energetic process in which psychological reattachment may benefit from a good night's sleep and thus serve as a mediator for the beneficial effect of sleep quality on work engagement and proactivity. We conducted a daily diary study over ten consecutive workdays. Altogether, we collected data from 171 employees on 1186 days. The results indicated that on days with good sleep quality and higher psychological reattachment, work engagement and proactivity were higher. Day-specific psychological reattachment buffered the negative effects of a poor night's sleep on work engagement, supporting the first of our competing hypotheses. Finally, we present ideas on how to foster psychological reattachment in practice.
Background
Prolonged cellular activity may overload cell function, leading to high rates of protein synthesis and accumulation of misfolded or unassembled proteins, which cause endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) to re-establish normal protein homeostasis. Previous molecular work has demonstrated that sleep deprivation (SD) leads to ER stress in neurons, with a number of ER-specific proteins being upregulated to maintain optimal cellular proteostasis. It is still not clear which cellular processes activated by sleep deprivation lead to ER- stress, but increased cellular metabolism, higher request for protein synthesis, and over production of oxygen radicals have been proposed as potential contributing factors. Here, we investigate the transcriptional and ultrastructural ER and mitochondrial modifications induced by sleep loss.
Results
We used gene expression analysis in mouse forebrains to show that SD was associated with significant transcriptional modifications of genes involved in ER stress but also in ER-mitochondria interaction, calcium homeostasis, and mitochondrial respiratory activity. Using electron microscopy, we also showed that SD was associated with a general increase in the density of ER cisternae in pyramidal neurons of the motor cortex. Moreover, ER cisternae established new contact sites with mitochondria, the so-called mitochondria associated membranes (MAMs), important hubs for molecule shuttling, such as calcium and lipids, and for the modulation of ATP production and redox state. Finally, we demonstrated that Drosophila male mutant flies (elav > linker), in which the number of MAMs had been genetically increased, showed a reduction in the amount and consolidation of sleep without alterations in the homeostatic sleep response to SD.
Conclusions
We provide evidence that sleep loss induces ER stress characterized by increased crosstalk between ER and mitochondria. MAMs formation associated with SD could represent a key phenomenon for the modulation of multiple cellular processes that ensure appropriate responses to increased cell metabolism. In addition, MAMs establishment may play a role in the regulation of sleep under baseline conditions.
The first comprehensive book on the subject, The Genetic Basis of Sleep and Sleep Disorders covers detailed reviews of the general principles of genetics and genetic techniques in the study of sleep and sleep disorders. The book contains sections on the genetics of circadian rhythms, of normal sleep and wake states and of sleep homeostasis. There are also sections discussing the role of genetics in the understanding of insomnias, hypersomnias including narcolepsy, parasomnias and sleep-related movement disorders. The final chapter highlights the use of gene therapy in sleep disorders. Written by genetic experts and sleep specialists from around the world, the book is up to date and geared specifically to the needs of both researchers and clinicians with an interest in sleep medicine. This book will be an invaluable resource for sleep specialists, neurologists, geneticists, psychiatrists and psychologists.
This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with sleep disorders. There are detailed reviews of new neuroimaging techniques – including CT, MRI, advanced MR techniques, SPECT and PET – as well as image analysis methods, their roles and pitfalls. Neuroimaging of normal sleep and wake states is covered plus the role of neuroimaging in conjunction with tests of memory and how sleep influences memory consolidation. Each chapter carefully presents and analyzes the key findings in patients with sleep disorders indicating the clinical and imaging features of the various sleep disorders from clinical presentation to neuroimaging, aiding in establishing an accurate diagnosis. Written by neuroimaging experts from around the world, Neuroimaging of Sleep and Sleep Disorders is an invaluable resource for both researchers and clinicians including sleep specialists, neurologists, radiologists, psychiatrists, psychologists.
Wide-ranging and inclusive, this text provides an invaluable review of an expansive selection of topics in human evolution, variation and adaptability for professionals and students in biological anthropology, evolutionary biology, medical sciences and psychology. The chapters are organized around four broad themes, with sections devoted to phenotypic and genetic variation within and between human populations, reproductive physiology and behavior, growth and development, and human health from evolutionary and ecological perspectives. An introductory section provides readers with the historical, theoretical and methodological foundations needed to understand the more complex ideas presented later. Two hundred discussion questions provide starting points for class debate and assignments to test student understanding.
Wide-ranging and inclusive, this text provides an invaluable review of an expansive selection of topics in human evolution, variation and adaptability for professionals and students in biological anthropology, evolutionary biology, medical sciences and psychology. The chapters are organized around four broad themes, with sections devoted to phenotypic and genetic variation within and between human populations, reproductive physiology and behavior, growth and development, and human health from evolutionary and ecological perspectives. An introductory section provides readers with the historical, theoretical and methodological foundations needed to understand the more complex ideas presented later. Two hundred discussion questions provide starting points for class debate and assignments to test student understanding.
Wide-ranging and inclusive, this text provides an invaluable review of an expansive selection of topics in human evolution, variation and adaptability for professionals and students in biological anthropology, evolutionary biology, medical sciences and psychology. The chapters are organized around four broad themes, with sections devoted to phenotypic and genetic variation within and between human populations, reproductive physiology and behavior, growth and development, and human health from evolutionary and ecological perspectives. An introductory section provides readers with the historical, theoretical and methodological foundations needed to understand the more complex ideas presented later. Two hundred discussion questions provide starting points for class debate and assignments to test student understanding.
This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with sleep disorders. There are detailed reviews of new neuroimaging techniques – including CT, MRI, advanced MR techniques, SPECT and PET – as well as image analysis methods, their roles and pitfalls. Neuroimaging of normal sleep and wake states is covered plus the role of neuroimaging in conjunction with tests of memory and how sleep influences memory consolidation. Each chapter carefully presents and analyzes the key findings in patients with sleep disorders indicating the clinical and imaging features of the various sleep disorders from clinical presentation to neuroimaging, aiding in establishing an accurate diagnosis. Written by neuroimaging experts from around the world, Neuroimaging of Sleep and Sleep Disorders is an invaluable resource for both researchers and clinicians including sleep specialists, neurologists, radiologists, psychiatrists, psychologists.
This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with sleep disorders. There are detailed reviews of new neuroimaging techniques – including CT, MRI, advanced MR techniques, SPECT and PET – as well as image analysis methods, their roles and pitfalls. Neuroimaging of normal sleep and wake states is covered plus the role of neuroimaging in conjunction with tests of memory and how sleep influences memory consolidation. Each chapter carefully presents and analyzes the key findings in patients with sleep disorders indicating the clinical and imaging features of the various sleep disorders from clinical presentation to neuroimaging, aiding in establishing an accurate diagnosis. Written by neuroimaging experts from around the world, Neuroimaging of Sleep and Sleep Disorders is an invaluable resource for both researchers and clinicians including sleep specialists, neurologists, radiologists, psychiatrists, psychologists.
This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with sleep disorders. There are detailed reviews of new neuroimaging techniques – including CT, MRI, advanced MR techniques, SPECT and PET – as well as image analysis methods, their roles and pitfalls. Neuroimaging of normal sleep and wake states is covered plus the role of neuroimaging in conjunction with tests of memory and how sleep influences memory consolidation. Each chapter carefully presents and analyzes the key findings in patients with sleep disorders indicating the clinical and imaging features of the various sleep disorders from clinical presentation to neuroimaging, aiding in establishing an accurate diagnosis. Written by neuroimaging experts from around the world, Neuroimaging of Sleep and Sleep Disorders is an invaluable resource for both researchers and clinicians including sleep specialists, neurologists, radiologists, psychiatrists, psychologists.
This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with sleep disorders. There are detailed reviews of new neuroimaging techniques – including CT, MRI, advanced MR techniques, SPECT and PET – as well as image analysis methods, their roles and pitfalls. Neuroimaging of normal sleep and wake states is covered plus the role of neuroimaging in conjunction with tests of memory and how sleep influences memory consolidation. Each chapter carefully presents and analyzes the key findings in patients with sleep disorders indicating the clinical and imaging features of the various sleep disorders from clinical presentation to neuroimaging, aiding in establishing an accurate diagnosis. Written by neuroimaging experts from around the world, Neuroimaging of Sleep and Sleep Disorders is an invaluable resource for both researchers and clinicians including sleep specialists, neurologists, radiologists, psychiatrists, psychologists.
Adenosine is an organic compound present in all the cells throughout the body and is released by all cells, including cells from the central nervous system. This neuromodulator and homeostatic modulator play a vital role in several neurological disorders, including but not limited to stroke, restless legs syndrome, Huntington’s disease, Alzheimer’s disease, etc., via the stimulation of their receptors. Alterations and manipulations of these receptors have led to a broader understanding of Adenosine’s role in these disorders and may also open up venues for managing them in a more efficacious manner. This chapter aims to explain the metabolism of this neuromodulator, summarizes briefly the types of receptors associated with Adenosine—A1, A2A, A2B, and A3 receptors, explains the role of Adenosine and its receptors in several neurological disorders, and gives a more wholesome picture of the effect Adenosine has on the body. A brief overview of adrenergic agonists along with caffeine, the most widely used psychostimulant in the western world, has been described with their roles in neurological disorders.
Every day, we sleep for a third of the day. Sleep is important for cognition, brain waste clearance, metabolism, and immune responses. The molecular mechanisms governing sleep are largely unknown. Here, we used a combination of single-cell RNA sequencing and cell-type-specific proteomics to interrogate the molecular underpinnings of sleep. Different cell types in three important brain regions for sleep (brainstem, cortex, and hypothalamus) exhibited diverse transcriptional responses to sleep need. Sleep restriction modulates astrocyte-neuron crosstalk and sleep need enhances expression of specific sets of transcription factors in different brain regions. In cortex, we also interrogated the proteome of two major cell types: astrocytes and neurons. Sleep deprivation differentially alters the expression of proteins in astrocytes and neurons. Similarly, phosphoproteomics revealed large shifts in cell-type-specific protein phosphorylation. Our results indicate that sleep need regulates transcriptional, translational, and post-translational responses in a cell-specific manner. Joint scRNA-seq and proteomic analysis of the hypothalamus, cortex, and brainstem in mice provides insight into the cellular and molecular underpinnings of sleep homeostasis.
Our modern society suffers from both pervasive sleep loss and substance abuse—what may be the indications for sleep on substance use disorders (SUDs), and could sleep contribute to the individual variations in SUDs? Decades of research in sleep as well as in motivated behaviors have laid the foundation for us to begin to answer these questions. This review is intended to critically summarize the circuit, cellular, and molecular mechanisms by which sleep influences reward function, and to reveal critical challenges for future studies. The review also suggests that improving sleep quality may serve as complementary therapeutics for treating SUDs, and that formulating sleep metrics may be useful for predicting individual susceptibility to SUDs and other reward-associated psychiatric diseases.
Although ATP and/or adenosine derived from astrocytes are known to regulate sleep, the precise mechanisms underlying the somnogenic effects of ATP and adenosine remain unclear. We selectively expressed channelrhodopsin-2 (ChR2), a light-sensitive ion channel, in astrocytes within the ventrolateral preoptic nucleus (VLPO), which is an essential brain nucleus involved in sleep promotion. We then examined the effects of photostimulation of astrocytic ChR2 on neuronal excitability using whole-cell patch-clamp recordings in two functionally distinct types of VLPO neurons: sleep-promoting GABAergic projection neurons and non-sleep-promoting local GABAergic neurons. Optogenetic stimulation of VLPO astrocytes demonstrated opposite outcomes in the two types of VLPO neurons. It led to the inhibition of non-sleep-promoting neurons and excitation of sleep-promoting neurons. These responses were attenuated by blocking of either adenosine A1 receptors or tissue-nonspecific alkaline phosphatase (TNAP). In contrast, exogenous adenosine decreased the excitability of both VLPO neuron populations. Moreover, TNAP was expressed in galanin-negative VLPO neurons, but not in galanin-positive sleep-promoting projection neurons. Taken together, these results suggest that astrocyte-derived ATP is converted into adenosine by TNAP in non-sleep-promoting neurons. In turn, adenosine decreases the excitability of local GABAergic neurons, thereby increasing the excitability of sleep-promoting GABAergic projection neurons. We propose a novel mechanism involving astrocyte-neuron interactions in sleep regulation, wherein endogenous adenosine derived from astrocytes excites sleep-promoting VLPO neurons, and thus decreases neuronal excitability in arousal-related areas of the brain.
Sleep is a nearly ubiquitous phenomenon across the phylogenetic tree, highlighting its essential role in ensuring fitness across evolutionary time. Consequently, chronic disruption of the duration, timing, or structure of sleep can cause widespread problems in multiple physiological systems, including those that regulate energy balance, immune function, and cognitive capacity, among others. Many, if not all these systems, become altered throughout the course of cancer initiation, growth, metastatic spread, treatment, and recurrence. Recent work has demonstrated how changes in sleep influence the development of chronic diseases, including cancer, in both humans and animal models. A common finding is that for some cancers (e.g., breast), chronic disruption of sleep/wake states prior to disease onset is associated with an increased risk for cancer development. Additionally, sleep disruption after cancer initiation is often associated with worse outcomes. Recently, evidence suggesting that cancer itself can affect neuronal circuits controlling sleep and wakefulness has accumulated. Patients with cancer often report difficulty falling asleep, difficulty staying asleep, and severe fatigue, during and even years after treatment. In addition to the psychological stress associated with cancer, cancer itself may alter sleep homeostasis through changes to host physiology and via currently undefined mechanisms. Moreover, cancer treatments (e.g., chemotherapy, radiation, hormonal, and surgical) may further worsen sleep problems through complex biological processes yet to be fully understood. This results in a “chicken or the egg” phenomenon, where it is unclear whether sleep disruption promotes cancer or cancer reciprocally disrupts sleep. This review will discuss existing evidence for both hypotheses and present a framework through which the interactions between sleep and cancer can be dissociated and causally investigated.
The endogenous opioid peptide, beta-endorphin, induces nonconvulsive limbic epileptiform activity when administered intraventricularly to rats. Epileptiform activity is elicited by beta-endorphin in doses that are devoid of analgesic or behavioral signs. Equimolar intraventricular doses of morphine or of the enkephalin analog [DAIa2,Met5]enkephalin-NH2 fail to elicit this limbic epileptiform activity. These observations, together with the recent immunohistochemical localization of beta-endorphin to midline limbic structures, suggest that beta-endorphin may have an important role in the regulation of limbic excitability.
Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations
Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2, D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu1-opioid receptors in the regulation of respiratory timing and EEG activity.
The effects of adenosine and its related nucleotides on cardiovascular function were initially reported by Drury and Szent-Györgyi (1929), who noted in studies performed in a variety of mammalian species, that these compounds were potent bradycardic and blood pressure lowering agents with marked vasoconstrictor effects in the kidney.
The questions of why sleep is required by higher animals, and of what instigates sleep, are hardly novel. Though the answers must ultimately be couched largely in chemical terms, biochemical studies of sleep are not very numerous. Recently, however, the tempo of research has quickened and two reviews have appeared within the past three years that offer a glimpse both of the more historical aspects of the field and of recent progress (Guiditta, 1977; Karnovsky and Reich, 1977). Though these reviews were written completely independently of each other, by authors with entirely different fundamental interests, they cover virtually the same ground, and even offer several identical examples from the literature. This one might take as an indication of how small is the number of biochemical laboratories that are engaged in research on sleep.
Glycogen metabolism in mammalian skeletal muscle is controlled by a regulatory network in which six protein kinases, four protein phosphatases and several thermostable regulatory proteins determine the activation state of glycogen phosphorylase and glycogen synthase, the rate-limiting enzymes of this process. Thirteen phosphorylation sites are involved, twelve of which have been isolated and sequenced and shown to be phosphorylated in vivo. The effects of adrenalin and insulin on the state of phosphorylation of each site have been determined. The neural control of glycogen metabolism is mediated by calcium ions and involves phosphorylase kinase, and a specific calmodulin-dependent glycogen synthase kinase. The beta-adrenergic control of the system is mediated by cyclic AMP, and involves the phosphorylation of phosphorylase kinase, glycogen synthase and inhibitor 1 by cyclic-AMP-dependent protein kinase. Inhibitor 1 is a specific inhibitor of protein phosphatase 1, the major phosphatase involved in the control of glycogen metabolism. The stimulation of glycogen synthesis by insulin results from the dephosphorylation of glycogen synthase at sites (3a + 3b + 3c), which are introduced by the enzyme glycogen synthase kinase 3. The structure, regulation and substrate specificities of the protein phosphatases involved in glycogen metabolism are reviewed. Protein phosphatase 1 can exist in an inactive form termed the Mg-ATP-dependent protein phosphatase, which consists of a complex between the catalytic subunit and a thermostable protein termed inhibitor 2. Activation of this complex is catalysed by glycogen synthase kinase 3. It involves the phosphorylation of inhibitor 2 and its dissociation from the catalytic subunit. Protein phosphatase 2A can be resolved into three forms by ion exchange chromatography. These species contain the same catalytic subunit and other subunits that may have a regulatory function. Protein phosphatase 2B is a Ca2+-dependent enzyme composed of two subunits, A and B. Its activity is increased tenfold by calmodulin, which interacts with the A-subunit. The B-subunit is a Ca2+-binding protein that is homologous with calmodulin. Its N-terminus contains the unusual myristyl blocking group, only found previously in the catalytic subunit of cyclic-AMP-dependent protein kinase. Protein phosphatase 2C is a Mg2+-dependent enzyme that accounts for a very small proportion of the glycogen synthase phosphatase activity in skeletal muscle. It is likely to be involved in the regulation of other metabolic processes in vivo such as cholesterol synthesis. Recent evidence suggests that many of the proteins involved in the control of glycogen metabolism have much wider roles, and that they participate in the neural and hormonal regulation of a variety of intracellular processes.
Adenosine can modulate a bewildering array of physiological processes including vascular tone, hormone action, neural function, platelet aggregation and lymphocyte differentiation. To explain this diversity, it has been proposed that adenosine is a hormone or a hormone second messenger. However, its unique mechanism of formation suggests instead that adenosine is a new type of cellular regulator for which the term ‘retaliatory metabolite’ is proposed.
A monograph communicating the current realities and future possibilities of unifying basic studies on anatomy and cellular physiology with investigations of the behavioral and physiological events of waking and sleep. Steriade established the Laboratory of Neurophysiology at Laval U., Quebec; McCarl
Adenosine (A1) receptor binding sites have been localized in rat brain by an in vitro light microscopic autoradiographic method. The binding of [3H]N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nucleus, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. These localizations suggest possible central nervous system sites of action of adenosine.
Abstract— Prolonged (6 hr) anaesthesia with phenobarbital in mice or rats results in a doubling or tripling of brain glycogen. Increases were also observed if high levels of plasma glucose were maintained for 6 hr. In alloxan diabetes brain glycogen was not elevated in spite of the high plasma glucose concentrations. However, administration of insulin to such diabetic animals, together with enough glucose to maintain high plasma levels, resulted in at least a doubling of brain glycogen in 6 hr. Phenobarbital can still increase brain glycogen in diabetic animals.
In all of the conditions associated with increased glycogen deposition, increases were found in the ratio of brain glucose to plasma glucose. Cerebral glucose-6-P levels were also increased whereas there were no substantial changes in levels of UDP-glucose or glucose-1,6-diphosphate.
Reliable ultrastructural techniques are applied for cytochemical identification of glycogen and localization of glucose‐6‐phosphatase (G6Pase) activity within neurons and glia of the adult mammalian CNS. Modulations in the cerebral localizations of glycogen and G6Pase activity are identified during various experimental conditions (i.e., salt‐stress, fasting, and trauma). The cytochemical reaction for demonstration of G6Pase activity implies that the enzyme acts as a phosphohydrolase to convert glucose‐6‐phosphate to glucose. The degradation of glycogen in vivo is one source of glucose‐6‐phosphate as a substrate for G6Pase. Glycogen is preserved by perfusion‐fixation of the brain with 2% glutaraldehyde‐2% formaldehyde. Chopper sections of this material are postfixed in buffered 1% osmium tetroxide‐1.5% potassium ferrocyanide, which serves as a contrast stain for glycogen, or in buffered 1% osmium tetroxide. Plastic‐embedded ultrathin sections of CNS tissue postfixed in 1% osmium tetroxide are stained for glycogen with periodic acid–thiocarbohydrazide‐silver protein. Intracellular glycogen appears as electron‐dense isodiametric particles and, under normal and experimental conditions, is most abundant within astrocytes. Neuronal glycogen is sparse to negligible normally but appears increased within specific neuronal populations during stressful states.
Optimal preservation of G6Pase activity in the brain is obtained by brief perfusion‐fixation with 2% glutaraldehyde. Tissue sections are incubated in a modified Leskes medium containing glucose‐6‐phosphate or mannose‐6‐phosphate as substrate and lead nitrate. Utilizing the Gomori lead capture technique, G6Pase reaction product is localized within the lumen of the endoplasmic reticulum (ER) and related organelles (i.e., nuclear envelope, Golgi complex) of perikarya, dendrites, and glia. The ER in axons and axon terminals fails to express G6Pase activity under normal conditions but does so in some neurons exhibiting a degenerating appearance. A transient, cytochemical decrease in G6Pase activity may occur within some perikarya during stressed conditions.
The results indicate that within neurons and glia of the adult CNS cytochemical stains are well suited for ultrastructural identification of glycogen and localization of G6Pase activity. Modulations in glycogen particle concentration and in localization of G6Pase activity in the neuron can occur in response to conditions that influence the energy metabolism of the cell. These modulations may reflect differences in the regional utilization of glucose as an energy‐producing substrate and as a derivative of glycogenolysis within the CNS.
Six healthy female volunteers (22–24 years), physically untrained (unfit), sat in baths of warm or cool water for 90 min, between 14.30 h and 17.30 h, on separate occasions. In the former condition (HOT), rectal temperature (Tr) rose by an average of 1.8°C, and in the latter (COOL), a thermoneutral condition, there was a nil Tr change. All-night sleep EEGs were monitored after both occasions and on baseline nights. Following COOL, there was no significant change in any sleep parameter. After HOT there were significant increases in: sleepiness at bed-time, slow wave sleep, and stage 4 sleep. REM sleep was reduced, particularly in the first REM sleep period.RésuméSix femmes volontaires, en bonne santé (22 à 24 ans), non entraînées physiquement, furent assises dans un bain d'eau chaude ou froide pour 90 min, entre 14 h 30 et 17 h 30, en 2 sessions distinctes. Dans la première situation (CHAUDE), la température rectale (Tr) s'élevait en moyenne de 1,8°C, alors que dans la seconde (FROIDE), une situation thermiquement neutre, il n'y avait pas de modification de la Tr. Les EEG de sommeil de la nuit complète furent suivis après les deux types de sessions ainsi que pendant des nuits témoins. Après une session FROIDE, il n'y avait pas de modification des paramètres du sommeil. Une augmentation significative était observée après une session CHAUDE: de l'endormissement à l'heure du coucher, du sommeil à ondes lentes et du stade 4 du sommeil. Le sommeil paradoxal était réduit, particulièrement dans sa première période d'apparition.
Current evidence supports a hypothesis that slow-wave sleep (SWS) in mammals and birds is controlled by thermoregulatory mechanisms, and provides brain and body cooling as a primary homeostatic feedback process. Recent work has identified a medial preoptic area anterior hypothalamic and basal forebrain neuronal network which integrates thermoregulatory and hypnogenic controls. This network induces EEG and behavioral deactivation, in part, through suppression of the reticular activating system. Studies have shown that SWS, like other heat loss processes, is facilitated when brain temperature exceeds a threshold level. This threshold is hypothesized to be determined by responses of POAH thermosensitive neurons and to be regulated by both circadian and homeostatic processes. Many known chemomodulators of SWS appear to act on this hypnogenic thermoregulatory system. At a functional level, SWS-induced brain and body cooling would provide several adaptations including lower energy utilization, reduced cerebral metabolism, protection of the brain against the sustained high temperatures of wakefulness, facilitation of immune defense processes and regulation of the timing of behavioral activity relative to the circadian light-dark cycle. This concept provides a comprehensive model for analysis of sleep homeostasis.
Electrographic and behavioral observations were made on five rodent species under controlled conditions. These were:Mus musculus, Rattus norvegicus, Mesocricetus auratus, Citellus tridecemlineatus and Chinchilla laniger. Normative values for sleep characteristics of the five species were derived from 48 hr recording periods. Analysis of sleep pattern characteristics showed: (1) well defined stages of slow wave sleep and paradoxical sleep in all animals; (2) sleep occupied from 52–60 per cent of each day for the different species; (3) different species differed in percentage of paradoxical sleep ranging from 10 per cent for the mouse to 24 per cent for hamsters and ground squirrels; (4) hibernators slept in significantly longer periods, had higher percentages of paradoxical sleep and slightly higher percentages of total sleep time. Hibernators also seemed to sleep more deeply than non-hibernators.
Continuous EEG recordings were performed in lean (240–250 g) rats, in large size (300–380 g) rats and in Ventromedial Hypothalamic (VMH) lesioned obese (450–470 g) rats, during 4 days of food deprivation and 3 days following food restitution. Though the daily amounts of both Slow Wave Sleep (SWS) and Paradoxical Sleep (PS) were dramatically decreased in lean rats (particularly during the dark phase of the day) by the food deprivation, they remained unchanged in large size rats and also in VMH obese rats. In the latter, there was even a tendency to an increase of SWS during the first two days of starvation. Food restitution brought about a significant rebound in SWS and PS (largely based upon an increase during the dark phase of the diurnal cycle) in lean rats, but had no effect on the sleep parameters of large size and VMH obese rats. Replacement by glucose infusions (100% of the normal daily caloric intake) via a cardiac catheter of oral nutrients in food deprived rats also resulted in a similar increase of sleep duration. These findings suggest that sleep is dependent on the degree of availability of metabolizable substances at the cellular level. In addition, possible causative relations between sleep and feeding are discussed.
The triazolobenzodiazepine triazolam, applied iontophoretically onto rat cerebral cortical neurons, potentiated the magnitude and duration of adenosine-elicited depressions of spontaneous activity. Triazolam did not enhance the depressions evoked by adenosine 5′-N-ethylcarboxamide, an uptake resistant analof of adenosine, suggesting that potentiation of adenosine resulted from an inhibition of adenosine uptake. With larger application currents, triazolam depressed the firing of cortical neurons. This action was blocked by the adenosine antagonist caffeine (20 mg/kg, i.v.) implying that the depression resulted from an accumulation of endogenously released adenosine.
Afternoon body heating has been reported to increase amounts of slow wave sleep (SWS) during the subsequent night in humans. This delayed effect of body heating on SWS has not been previously studied in laboratory animals. We examined the effect of whole body heating during the last 4 h of the light period on sleep and brain temperature (Tbr) during the subsequent twelve hour period in rats. Whole body heating was accomplished by elevating ambient temperature, typically to 33–35°C, which increasedTbr to40±0.5°C. This condition was compared to a sleep-matched control condition, a sleep-deprived control condition and to a baseline condition. Following heating, non-rapid eye movement sleep 2 (NREMS2 or deep NREMS) was significantly increased during the first 2 h of the recovery period compared with baseline and sleep-matched control conditions and during the first hour compared with the totally sleep-deprived condition. NREMS1 was not significantly changed by heating. Rapid eye movement sleep was not different following heating compared to the sleep-matched and sleep-deprived control conditions but was significantly increased during the first hour of the recovery period followiing heating compared to baseline.Tbr was significantly lower for the first 5 h and the 7th h following heating compared to all three other conditions. Possible relationships between the regulation of sleep and temperature are discussed.
The hypothesis that local activation of brain regions during wakefulness affects the EEG recorded from these regions during sleep was tested by applying vibratory stimuli to one hand prior to sleep. Eight subjects slept in the laboratory for five consecutive nights. During a 6-h period prior to night 3, either the left or the right hand was vibrated intermittently (20 min on-8 min off), while prior to night 5 the same treatment was applied to the contralateral hand. The sleep EEG was recorded from frontal, central, parietal and occipital derivations and subjected to spectral analysis. The interhemispheric asymmetry index (IAI) was calculated for spectral power in nonREM sleep in the frequency range 0.25-25.0 Hz for 0.5-Hz or 1-Hz bins. In the first hour of sleep following right-hand stimulation, the IAI of the central derivation was increased relative to baseline, which corresponds to a shift of power towards the left hemisphere. This effect was most prominent in the delta range, was limited to the first hour of sleep and was restricted to the central derivation situated over the somatosensory cortex. No significant changes were observed following left-hand stimulation. Although the effect was small, it is consistent with the hypothesis that the activation of specific neuronal populations during wakefulness may have repercussions on their electrical activity pattern during subsequent sleep.
A new theory of sleep function is presented within the context of the neuronal group selection hypothesis, which emphasizes that neuronal groups compete for neurons via use-dependent synaptic formation and atrophy. It is hypothesized that sleep serves to stabilize these competitive processes by providing a pattern of stimulation that serves to maintain a synaptic infrastructure upon which wakefulness-driven synaptic changes are superimposed. Sleep is 'quantal' in nature in that sleep is a statistical property of a population of neuronal groups in different states. The theory unifies past theories of sleep function yet simultaneously provides a fundamental new paradigm for sleep research.
Microinjections of Leu-enkephalin were made in dorsal hippocampus, caudate nucleus, amygdala, nucleus accumbens and parietal cortex in rats. The effects of enkephalin on the local electrical activity recorded from the area of the microinjection are described. Depression effects (attenuation of amplitudes and slowing) were recorded in caudate nucleus, nucleus accumbens, amygdala and parietal cortex, but not in hippocampus. Activation and epileptiform effects (spikes, seizures) were recorded from all structures studied.
1. Adenosine was determined in rapidly frozen rat and guinea-pig brain and in guinea-pig cerebral tissues after incubation in vitro. Adenosine concentrations were approx. 2nmol/g wet wt. in frozen tissue, diminished at room temperature, and returned to 2nmol/g on incubation in oxygenated glucose/salines. 2. Superfusion with noradrenaline then increased the tissue's adenosine concentration 2.5-fold, and hypoxia caused an 8-fold increase. 3. Electrical stimulation alone or in the presence of noradrenaline or histamine increased the tissue's adenosine and cyclic AMP, but adenosine concentrations reached their peak later and were maintained for longer than those of cyclic AMP. 4. Superfusion with l-glutamate with and without electrical excitation raised adenosine concentrations to 15-34nmol/g. The increases in cyclic AMP on electrical stimulation, superfusion with glutamate or a combination of these treatments were diminished by addition of adenosine deaminase or theophylline. 5. It is concluded that adenosine can be produced endogenously in cerebral systems, in sufficient concentrations to accelerate an adenosine-activated adenylate cyclase, and by this route can contribute to the cerebral actions of electrical stimulation and of the neurohumoral agents. In certain instances cyclic AMP as substrate contributes to an increase in adenosine.
The atypical excitation by opiates and opioid peptides of hippocampal pyramidal cells can be antagonized by iontophoresis
of naloxone, the gamma-aminobutyric acid antagonists bicuculline, or magnesium ion. The recurrent inhibition of these cells
evoked by transcallosal stimulation of the contralateral hippocampus is blocked by enkephalin but only shortened by acetylcholine.
The results suggest that the opioids excite pyramidal neurons indirectly by inhibition of neighboring inhibitory interneurons
(probably containing gamma-aminobutyric acid). This mechanism may be pertinent to the electrographic signs of addictive drugs.
Effects of two nights of sleep loss were assessed in six young adult (18--21 yr.) volunteers (2 women, 4 men). Performance on the Wilkinson Addition Test fell significantly below baseline values during the sleep-loss procedure and recovered after one or two full nights of sleep. Performance on a Serial Alternation Task also declined during sleep loss. Mood and sleepiness, assessed by subjective self-rating scales, showed a significantly less positive mood and a greater degree of sleepiness during sleep loss, with a recovery to baseline levels after one full night of sleep. Sleep tendency, measured at 2-hr. intervals during all waking periods, was assessed using an objective measure of latency to sleep onset, the Sleep Latency Test. The scores fell to about 1 min. at 0600 on the first night of sleep loss and remained at similarly low values throughout the sleep loss period. After one night of recovery sleep the scores remained significantly below baseline levels, which were not achieved until after the second recovery night. The multiple sleep latency test appears to be a valuable operationally defined tool for measuring daytime sleepiness.
This study tested the hypothesis that regulation of a polyphasic sleep-wake cycle in the cat is directed in large part by structures in the basal forebrain region. Cats were prepared surgically for chronic sleep recording and were trained to produce an operant EEG response for food in order to assess behavioral periodicity. Electrographic data were analyzed for sleep-wake patterns, mean periodicity of the REM and operant performance (basic rest-activity) cycle and polyphasic sleep-wake cycle. Bilateral lesions placed in the basal forebrain markedly suppressed expression of sleep for more than three weeks. These lesions significantly shortened the mean periodicity of the polyphasic sleep-wake cycle, but not that of the basic rest-activity cycle. These data support the hypothesis that basal forebrain structures are involved in the genesis and control of slow-wave sleep and the polyphasic sleep-wake cycle.
Brain glycogen is localized almost exclusively to glia, where it undergoes continuous utilization and resynthesis. We have shown that glycogen utilization increases during tactile stimulation of the rat face and vibrissae. Conversely, decreased neuronal activity during hibernation and anesthesia is accompanied by a marked increase in brain glycogen content. These observations support a link between neuronal activity and glial glycogen metabolism. The energetics of glycogen metabolism suggest that glial glycogen is mobilized to meet increased metabolic demands of glia rather than to serve as a substrate for neuronal activity. An advantage to the use of glycogen may be the potentially faster generation of ATP from glycogen than from glucose. Alternatively, glycogen could be utilized if glucose supply is transiently insufficient during the onset of increased metabolic activity. Brain glycogen may have a dynamic role as a buffer between the abrupt increases in focal metabolic demands that occur during normal brain activity and the compensatory changes in focal cerebral blood flow or oxidative metabolism.
The energy metabolism of the brain is one of the most active of all the organs in the body. Oxygen is utilized in the brain almost entirely for the oxidation of carbohydrates. The brain not just consumes oxygen at a rapid rate, but it is dependent on continued uninterrupted oxidative metabolism for maintenance of its functional and structural integrity. Not all of the oxygen consumption of brain is used for energy. The brain contains a variety of oxidases and hydroxylases that function in the synthesis and metabolism of a number of neurotransmitters, neuromodulators, etc. All of these enzymes are present in the brain, and the reactions catalyzed by them utilize oxygen. When the total turnover of the neurotransmitters and the sum total of the maximal velocities of all the oxidases involved in their synthesis and degradation are considered, it is clear that the oxygen consumed in the turnover of the neurotransmitters can account for only a very small, possibly immeasurable, fraction of the total oxygen consumption of the brain.