WorldWideScience

Sample records for human sleep regulation

  1. Sick and tired: how molecular regulators of human sleep schedules and duration impact immune function.

    Science.gov (United States)

    Kurien, Philip A; Chong, S Y Christin; Ptáček, Louis J; Fu, Ying-Hui

    2013-10-01

    Why do we need to sleep? What regulates when we sleep? And what dictates the number of hours we require? These are often viewed as three separate biological questions. Here, we propose they share molecular etiologies, whereby regulators of sleep schedules and sleep duration also govern the physiological purposes of sleep. To support our hypothesis, we review Mendelian human genetic variants sufficient to advance sleep-wake onset (PER2) and shorten sleep length (DEC2), and evaluate their emerging roles in immune responses that may rely on a sound night of slumber. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Combining Human Epigenetics and Sleep Studies in Caenorhabditis elegans: A Cross-Species Approach for Finding Conserved Genes Regulating Sleep.

    Science.gov (United States)

    Huang, Huiyan; Zhu, Yong; Eliot, Melissa N; Knopik, Valerie S; McGeary, John E; Carskadon, Mary A; Hart, Anne C

    2017-06-01

    We aimed to test a combined approach to identify conserved genes regulating sleep and to explore the association between DNA methylation and sleep length. We identified candidate genes associated with shorter versus longer sleep duration in college students based on DNA methylation using Illumina Infinium HumanMethylation450 BeadChip arrays. Orthologous genes in Caenorhabditis elegans were identified, and we examined whether their loss of function affected C. elegans sleep. For genes whose perturbation affected C. elegans sleep, we subsequently undertook a small pilot study to re-examine DNA methylation in an independent set of human participants with shorter versus longer sleep durations. Eighty-seven out of 485,577 CpG sites had significant differential methylation in young adults with shorter versus longer sleep duration, corresponding to 52 candidate genes. We identified 34 C. elegans orthologs, including NPY/flp-18 and flp-21, which are known to affect sleep. Loss of five additional genes alters developmentally timed C. elegans sleep (B4GALT6/bre-4, DOCK180/ced-5, GNB2L1/rack-1, PTPRN2/ida-1, ZFYVE28/lst-2). For one of these genes, ZFYVE28 (also known as hLst2), the pilot replication study again found decreased DNA methylation associated with shorter sleep duration at the same two CpG sites in the first intron of ZFYVE28. Using an approach that combines human epigenetics and C. elegans sleep studies, we identified five genes that play previously unidentified roles in C. elegans sleep. We suggest sleep duration in humans may be associated with differential DNA methylation at specific sites and that the conserved genes identified here likely play roles in C. elegans sleep and in other species. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  3. Adenosine A1 receptors in human sleep regulation studied by electroencephalography (EEG) and positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Geissler, E.

    2007-01-01

    Sleep is an essential physiological process. However, the functions of sleep and the endogenous mechanisms involved in sleep regulation are only partially understood. Convergent lines of evidence support the hypothesis that the build-up of sleep propensity during wakefulness and its decline during sleep are associated with alterations in brain adenosine levels and adenosine receptor concentrations. The non-selective A 1 and A 2A adenosine receptor antagonist caffeine stimulates alertness and is known to attenuate changes in the waking and sleep electroencephalogram (EEG) typically observed after prolonged waking. Several findings point to an important function of the adenosine A 1 receptor (A 1 AR) in the modulation of vigilance states. The A 1 AR is densely expressed in brain regions involved in sleep regulation, and pharmacological manipulations affecting the A 1 AR were shown to influence sleep propensity and sleep depth. However, an involvement of the A 2A adenosine receptor (A 2A AR) is also assumed. The distinct functions of the A 1 and A 2A receptor subtypes in sleep-wake regulation and in mediating the effects of caffeine have not been identified so far. The selective adenosine A 1 receptor antagonist, 8-cyclopentyl-3-(3- 18 Ffluoropropyl)- 1-propylxanthine ( 18 F-CPFPX), offers the opportunity to get further insights into adenosinergic mechanisms by in vivo imaging of the A 1 AR subtype with positron emission tomography (PET). The aim of this thesis was to elucidate the role of adenosine A 1 receptors in human sleep regulation, combining 18 F-CPFPX PET brain imaging and EEG recordings, the gold standard in sleep research. It was hypothesized that sleep deprivation would induce adenosine accumulation and/or changes in A 1 AR density. Thus, the question was addressed whether these effects of prolonged wakefulness can be visualized by altered 18 F-CPFPX binding. Moreover, it was investigated whether radioligand uptake might be influenced by caffeine, since

  4. Sex differences in the circadian regulation of sleep and waking cognition in humans.

    Science.gov (United States)

    Santhi, Nayantara; Lazar, Alpar S; McCabe, Patrick J; Lo, June C; Groeger, John A; Dijk, Derk-Jan

    2016-05-10

    The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.

  5. Sleep regulation and insomnia

    NARCIS (Netherlands)

    van Someren, E.J.W.; Cluydts, R.; Pfaff, D.W.

    2013-01-01

    For years, the subject of sleep failed to generate much interest from either the field of medicine or that of psychology - a curious fact, as a 60-year-old has spent some 20 years out of those 60 sleeping. In fact, up until the age of approximately three years, a child spends more time asleep than

  6. Sex differences in the circadian regulation of sleep and waking cognition in humans

    Science.gov (United States)

    Santhi, Nayantara; Lazar, Alpar S.; McCabe, Patrick J.; Lo, June C.; Groeger, John A.; Dijk, Derk-Jan

    2016-01-01

    The sleep–wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep–wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging. PMID:27091961

  7. Can sleep deprivation studies explain why human adults sleep?

    Science.gov (United States)

    Brown, Lee K

    2012-11-01

    This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

  8. Circadian Rhythms, Sleep Deprivation, and Human Performance

    Science.gov (United States)

    Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

    2014-01-01

    Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

  9. Human genetics and sleep behavior.

    Science.gov (United States)

    Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

    2017-06-01

    Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Normal sleep and its neurophysiological regulation

    NARCIS (Netherlands)

    Hofman, W.F.; Talamini, L.M.; Watson, R.R.

    2015-01-01

    Normal sleep consists of two states: NREM (light and deep sleep) and REM, alternating in a cyclical pattern. The sleep/wake rhythm is regulated by two processes: the sleep propensity, building up during wake, and the circadian rhythm, imposed by the suprachiasmatic nucleus. The arousal pathways in

  11. Shining evolutionary light on human sleep and sleep disorders.

    Science.gov (United States)

    Nunn, Charles L; Samson, David R; Krystal, Andrew D

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  12. Shining evolutionary light on human sleep and sleep disorders.

    OpenAIRE

    Krystal, Andrew; Nunn, CL; Samson, DR; Krystal, AD

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalia

  13. Adenosine A{sub 1} receptors in human sleep regulation studied by electroencephalography (EEG) and positron emission tomography (PET)[Dissertation 17227

    Energy Technology Data Exchange (ETDEWEB)

    Geissler, E

    2007-07-01

    Sleep is an essential physiological process. However, the functions of sleep and the endogenous mechanisms involved in sleep regulation are only partially understood. Convergent lines of evidence support the hypothesis that the build-up of sleep propensity during wakefulness and its decline during sleep are associated with alterations in brain adenosine levels and adenosine receptor concentrations. The non-selective A{sub 1} and A{sub 2A} adenosine receptor antagonist caffeine stimulates alertness and is known to attenuate changes in the waking and sleep electroencephalogram (EEG) typically observed after prolonged waking. Several findings point to an important function of the adenosine A{sub 1} receptor (A{sub 1}AR) in the modulation of vigilance states. The A{sub 1}AR is densely expressed in brain regions involved in sleep regulation, and pharmacological manipulations affecting the A{sub 1}AR were shown to influence sleep propensity and sleep depth. However, an involvement of the A{sub 2A} adenosine receptor (A{sub 2A}AR) is also assumed. The distinct functions of the A{sub 1} and A{sub 2A} receptor subtypes in sleep-wake regulation and in mediating the effects of caffeine have not been identified so far. The selective adenosine A{sub 1} receptor antagonist, 8-cyclopentyl-3-(3-{sup 18}Ffluoropropyl)- 1-propylxanthine ({sup 18}F-CPFPX), offers the opportunity to get further insights into adenosinergic mechanisms by in vivo imaging of the A{sub 1}AR subtype with positron emission tomography (PET). The aim of this thesis was to elucidate the role of adenosine A{sub 1} receptors in human sleep regulation, combining {sup 18}F-CPFPX PET brain imaging and EEG recordings, the gold standard in sleep research. It was hypothesized that sleep deprivation would induce adenosine accumulation and/or changes in A{sub 1}AR density. Thus, the question was addressed whether these effects of prolonged wakefulness can be visualized by altered {sup 18}F-CPFPX binding. Moreover, it was

  14. The Role of ATP in Sleep Regulation

    Directory of Open Access Journals (Sweden)

    Sachiko eChikahisa

    2011-12-01

    Full Text Available One of the functions of sleep is to maintain energy balance in the brain. There are a variety of hypotheses related to how metabolic pathways interact with sleep/wake regulation. A major finding that demonstrates an interaction between sleep and metabolic homeostasis is the involvement of adenosine in sleep homeostasis. An accumulation of adenosine is supplied from ATP, which can act as an energy currency in the cell. Extracellularly, ATP can act as an activity-dependent signaling molecule, especially in regard to communication between neurons and glia, including astrocytes. Furthermore, the intracellular AMP/ATP ratio controls the activity of AMP-activated protein kinase (AMPK, which is a potent energy regulator and is recently reported to play a role in the regulation of sleep homeostasis. Brain ATP may support multiple functions in the regulation of the sleep/wake cycle and sleep homeostasis.

  15. translin Is Required for Metabolic Regulation of Sleep.

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    Murakami, Kazuma; Yurgel, Maria E; Stahl, Bethany A; Masek, Pavel; Mehta, Aradhana; Heidker, Rebecca; Bollinger, Wesley; Gingras, Robert M; Kim, Young-Joon; Ja, William W; Suter, Beat; DiAngelo, Justin R; Keene, Alex C

    2016-04-04

    Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Fruit Flies Help Human Sleep Research

    Science.gov (United States)

    ... like us, without enough sleep, flies feel the effects of sleep deprivation. Cirelli has shown that they are a good model for researching human sleep. She has found fruit fly genes that seem to have a powerful effect on sleep. In time, her research could lead ...

  17. Regulation of adolescent sleep: implications for behavior.

    Science.gov (United States)

    Carskadon, Mary A; Acebo, Christine; Jenni, Oskar G

    2004-06-01

    Adolescent development is accompanied by profound changes in the timing and amounts of sleep and wakefulness. Many aspects of these changes result from altered psychosocial and life-style circumstances that accompany adolescence. The maturation of biological processes regulating sleep/wake systems, however, may be strongly related to the sleep timing and amount during adolescence-either as "compelling" or "permissive" factors. The two-process model of sleep regulation posits a fundamental sleep-wake homeostatic process (process S) working in concert with the circadian biological timing system (process C) as the primary intrinsic regulatory factors. How do these systems change during adolescence? We present data from adolescent participants examining EEG markers of sleep homeostasis to evaluate whether process S shows maturational changes permissive of altered sleep patterns across puberty. Our data indicate that certain aspects of the homeostatic system are unchanged from late childhood to young adulthood, while other features change in a manner that is permissive of later bedtimes in older adolescents. We also show alterations of the circadian timing system indicating a possible circadian substrate for later adolescent sleep timing. The circadian parameters we have assessed include phase, period, melatonin secretory pattern, light sensitivity, and phase relationships, all of which show evidence of changes during pubertal development with potential to alter sleep patterns substantially. However the changes are mediated-whether through process S, process C, or by a combination-many adolescents have too little sleep at the wrong circadian phase. This pattern is associated with increased risks for excessive sleepiness, difficulty with mood regulation, impaired academic performance, learning difficulties, school tardiness and absenteeism, and accidents and injuries.

  18. ON THE ROLE OF PERIOD-2 IN THE CIRCADIAN AND HOMEOSTATIC REGULATION OF SLEEP

    OpenAIRE

    La Spada, F.

    2013-01-01

    Humans spend one third of their life sleeping, then we could raise the basic question: Why do we sleep? Despite the fact that we still don't fully understand its function, we made much progress in understanding at different levels how sleep is regulated. One model suggests that sleep is regulated by two processes: a homeostatic process that tracks the need for sleep and by a circadian rhythm that determines the preferred time-of-day sleep occurs. At the molecular level circadian rhythms ar...

  19. Medical Imaging for Understanding Sleep Regulation

    Science.gov (United States)

    Wong, Kenneth

    2011-10-01

    Sleep is essential for the health of the nervous system. Lack of sleep has a profound negative effect on cognitive ability and task performance. During sustained military operations, soldiers often suffer from decreased quality and quantity of sleep, increasing their susceptibility to neurological problems and limiting their ability to perform the challenging mental tasks that their missions require. In the civilian sector, inadequate sleep and overt sleep pathology are becoming more common, with many detrimental impacts. There is a strong need for new, in vivo studies of human brains during sleep, particularly the initial descent from wakefulness. Our research team is investigating sleep using a combination of magnetic resonance imaging (MRI), positron emission tomography (PET), and electroencephalography (EEG). High resolution MRI combined with PET enables localization of biochemical processes (e.g., metabolism) to anatomical structures. MRI methods can also be used to examine functional connectivity among brain regions. Neural networks are dynamically reordered during different sleep stages, reflecting the disconnect with the waking world and the essential yet unconscious brain activity that occurs during sleep.[4pt] In collaboration with Linda Larson-Prior, Washington University; Alpay Ozcan, Virginia Tech; Seong Mun, Virginia Tech; and Zang-Hee Cho, Gachon University.

  20. Sleep regulation: physiological models and hypotheses.

    Science.gov (United States)

    Borbély, A A

    1995-06-01

    The elucidation of sleep regulation is not an easy task. On one side, there is a multitude of solid yet disparate data, on the other side, the topic is tempting for engaging in wild speculation, particularly with respect to the functions of sleep. Models may exert a moderating influence by mediating between the two extremes. However, also they navigate between the risk of banality in reformulating the obvious, and the peril of fancy in losing touch with empirical reality.

  1. Trigeminal induced arousals during human sleep.

    Science.gov (United States)

    Heiser, Clemens; Baja, Jan; Lenz, Franziska; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A

    2015-05-01

    Arousals caused by external stimuli during human sleep have been studied for most of the sensorial systems. It could be shown that a pure nasal trigeminal stimulus leads to arousals during sleep. The frequency of arousals increases dependent on the stimulus concentration. The aim of the study was to evaluate the influence of different stimulus durations on arousal frequency during different sleep stages. Ten young healthy volunteers with 20 nights of polysomnography were included in the study. Pure trigeminal stimulation with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages to the volunteers using an olfactometer. The application was performed during different sleep stages (light sleep, deep sleep, REM sleep). The number of arousals increased with rising stimulus duration and stimulus concentration during each sleep stage. Trigeminal stimuli during sleep led to arousals in dose- and time-dependent manner.

  2. The role of sleep in human declarative memory consolidation.

    Science.gov (United States)

    Alger, Sara E; Chambers, Alexis M; Cunningham, Tony; Payne, Jessica D

    2015-01-01

    Through a variety of methods, researchers have begun unraveling the mystery of why humans spend one-third of their lives asleep. Though sleep likely serves multiple functions, it has become clear that the sleeping brain offers an ideal environment for solidifying newly learned information in the brain. Sleep , which comprises a complex collection of brain states, supports the consolidation of many different types of information. It not only promotes learning and memory stabilization, but also memory reorganization that can lead to various forms of insightful behavior. As this chapter will describe, research provides ample support for these crucial cognitive functions of sleep . Focusing on the declarative memory system in humans, we review the literature regarding the benefits of sleep for both neutral and emotionally salient declarative memory. Finally, we discuss the literature regarding the impact of sleep on emotion regulation.

  3. A nap to recap or how reward regulates hippocampal-prefrontal memory networks during daytime sleep in humans.

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    Igloi, Kinga; Gaggioni, Giulia; Sterpenich, Virginie; Schwartz, Sophie

    2015-10-16

    Sleep plays a crucial role in the consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information that will be consolidated during sleep remains largely unknown. Here we show that post-learning sleep favors the selectivity of long-term consolidation: when tested three months after initial encoding, the most important (i.e., rewarded, strongly encoded) memories are better retained, and also remembered with higher subjective confidence. Our brain imaging data reveals that the functional interplay between dopaminergic reward regions, the prefrontal cortex and the hippocampus contributes to the integration of rewarded associative memories. We further show that sleep spindles strengthen memory representations based on reward values, suggesting a privileged replay of information yielding positive outcomes. These findings demonstrate that post-learning sleep determines the neural fate of motivationally-relevant memories and promotes a value-based stratification of long-term memory stores.

  4. The suprachiasmatic nucleus regulates sleep timing and amount in mice

    NARCIS (Netherlands)

    Easton, Amy; Meerlo, Peter; Bergmann, Bernard; Turek, Fred W.

    2004-01-01

    Context: Sleep is regulated by circadian and homeostatic processes. The circadian pacemaker, located in the suprachiasmatic nuclei (SCN), regulates the timing and consolidation of the sleep-wake cycle, while a homeostatic mechanism governs the accumulation of sleep debt and sleep, recovery. Recent

  5. Metabolic signals in sleep regulation: recent insights

    Directory of Open Access Journals (Sweden)

    Shukla C

    2016-01-01

    Full Text Available Charu Shukla, Radhika Basheer Department of Psychiatry, VA Boston Healthcare System, Harvard Medical School, West Roxbury, MA, USA Abstract: Sleep and energy balance are essential for health. The two processes act in concert to regulate central and peripheral homeostasis. During sleep, energy is conserved due to suspended activity, movement, and sensory responses, and is redirected to restore and replenish proteins and their assemblies into cellular structures. During wakefulness, various energy-demanding activities lead to hunger. Thus, hunger promotes arousal, and subsequent feeding, followed by satiety that promotes sleep via changes in neuroendocrine or neuropeptide signals. These signals overlap with circuits of sleep-wakefulness, feeding, and energy expenditure. Here, we will briefly review the literature that describes the interplay between the circadian system, sleep-wake, and feeding-fasting cycles that are needed to maintain energy balance and a healthy metabolic profile. In doing so, we describe the neuroendocrine, hormonal/peptide signals that integrate sleep and feeding behavior with energy metabolism. Keywords: sleep, energy balance, hypothalamus, metabolism, homeostasis

  6. Regulation of sleep by neuropeptide Y-like system in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Chunxia He

    Full Text Available Sleep is important for maintenance of normal physiology in animals. In mammals, neuropeptide Y (NPY, a homolog of Drosophila neuropeptide F (NPF, is involved in sleep regulation, with different effects in human and rat. However, the function of NPF on sleep in Drosophila melanogaster has not yet been described. In this study, we investigated the effects of NPF and its receptor-neuropeptide F receptor (NPFR1 on Drosophila sleep. Male flies over-expressing NPF or NPFR1 exhibited increased sleep during the nighttime. Further analysis demonstrated that sleep episode duration during nighttime was greatly increased and sleep latency was significantly reduced, indicating that NPF and NPFR1 promote sleep quality, and their action on sleep is not because of an impact of the NPF signal system on development. Moreover, the homeostatic regulation of flies after sleep deprivation was disrupted by altered NPF signaling, since sleep deprivation decreased transcription of NPF in control flies, and there were less sleep loss during sleep deprivation and less sleep gain after sleep deprivation in flies overexpressing NPF and NPFR1 than in control flies, suggesting that NPF system auto-regulation plays an important role in sleep homeostasis. However, these effects did not occur in females, suggesting a sex-dependent regulatory function in sleep for NPF and NPFR1. NPF in D1 brain neurons showed male-specific expression, providing the cellular locus for male-specific regulation of sleep by NPF and NPFR1. This study brings a new understanding into sleep studies of a sexually dimorphic regulatory mode in female and male flies.

  7. The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss.

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    Matthew S Thimgan

    2010-08-01

    Full Text Available Extended periods of waking result in physiological impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Sleep homeostasis, as with other behaviors, is influenced by both genes and environment. We report here that during periods of starvation, flies remain spontaneously awake but, in contrast to sleep deprivation, do not accrue any of the negative consequences of prolonged waking. Specifically, the homeostatic response and learning impairments that are a characteristic of sleep loss are not observed following prolonged waking induced by starvation. Recently, two genes, brummer (bmm and Lipid storage droplet 2 (Lsd2, have been shown to modulate the response to starvation. bmm mutants have excess fat and are resistant to starvation, whereas Lsd2 mutants are lean and sensitive to starvation. Thus, we hypothesized that bmm and Lsd2 may play a role in sleep regulation. Indeed, bmm mutant flies display a large homeostatic response following sleep deprivation. In contrast, Lsd2 mutant flies, which phenocopy aspects of starvation as measured by low triglyceride stores, do not exhibit a homeostatic response following sleep loss. Importantly, Lsd2 mutant flies are not learning impaired after sleep deprivation. These results provide the first genetic evidence, to our knowledge, that lipid metabolism plays an important role in regulating the homeostatic response and can protect against neuronal impairments induced by prolonged waking.

  8. Emotion, emotion regulation and sleep: An intimate relationship

    Directory of Open Access Journals (Sweden)

    Marie Vandekerckhove

    2017-12-01

    Full Text Available In recent years, research has witnessed an increasing interest in the bidirectional relationship between emotion and sleep. Sleep seems important for restoring daily functioning, whereas deprivation of sleep makes us more emotionally aroused and sensitive to stressful stimuli and events. Sleep appears to be essential to our ability to cope with emotional stress in everyday life. However, when daily stress is insufficiently regulated, it may result in mental health problems and sleep disturbances too. Not only does emotion impact sleep, but there is also evidence that sleep plays a key role in regulating emotion. Emotional events during waking hours affect sleep, and the quality and amount of sleep influences the way we react to these events impacting our general well-being. Although we know that daytime emotional stress affects sleep by influencing sleep physiology, dream patterns, dream content and the emotion within a dream, its exact role is still unclear. Other effects that have been found are the exaggeration of the startle response, decrease in dream recall and elevation of awakening thresholds from rapid eye movement (REM, REM-sleep, increased or decreased latency to REM-sleep, increase in percentage of REM-density, REM-sleep duration, as well as the occurrence of arousals in sleep as a marker of sleep disruption. Equally, the way an individual copes with emotional stress, or the way in which an individual regulates emotion may modulate the effects of emotional stress on sleep. The research presented here supports the idea that adaptive emotion regulation benefits our follow-up sleep. We thus conclude the current review with a call for future research in order to clarify further the precise relationship between sleep, emotion and emotion regulation, as well as to explain further how sleep dissolves our emotional stress.

  9. Emotion, emotion regulation and sleep: An intimate relationship

    OpenAIRE

    Marie Vandekerckhove; Yu-lin Wang

    2017-01-01

    In recent years, research has witnessed an increasing interest in the bidirectional relationship between emotion and sleep. Sleep seems important for restoring daily functioning, whereas deprivation of sleep makes us more emotionally aroused and sensitive to stressful stimuli and events. Sleep appears to be essential to our ability to cope with emotional stress in everyday life. However, when daily stress is insufficiently regulated, it may result in mental health problems and sleep disturban...

  10. Solving the mystery of human sleep schedules one mutation at a time.

    Science.gov (United States)

    Hallows, William C; Ptáček, Louis J; Fu, Ying-Hui

    2013-01-01

    Sleep behavior remains one of the most enigmatic areas of life. The unanswered questions range from "why do we sleep?" to "how we can improve sleep in today's society?" Identification of mutations responsible for altered circadian regulation of human sleep lead to unique opportunities for probing these territories. In this review, we summarize causative circadian mutations found from familial genetic studies to date. We also describe how these mutations mechanistically affect circadian function and lead to altered sleep behaviors, including shifted or shortening of sleep patterns. In addition, we discuss how the investigation of mutations can not only expand our understanding of the molecular mechanisms regulating the circadian clock and sleep duration, but also bridge the pathways between clock/sleep and other human physiological conditions and ailments such as metabolic regulation and migraine headaches.

  11. Sleep in the human hippocampus: a stereo-EEG study.

    Directory of Open Access Journals (Sweden)

    Fabio Moroni

    Full Text Available BACKGROUND: There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii a flattening of the time course of the very low frequencies (up to 1 Hz across sleep cycles, with relatively high levels of power even during REM sleep; iii a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. CONCLUSIONS/SIGNIFICANCE: Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonance may have a supportive role for the processing/consolidation of memory.

  12. translin is required for metabolic regulation of sleep

    OpenAIRE

    Murakami, Kazuma; Yurgel, Maria E.; Stahl, Bethany A.; Masek, Pavel; Mehta, Aradhana; Heidker, Rebecca; Bollinger, Wesley; Gingras, Robert M.; Kim, Young-Joon; Ja, William W.; Suter, Beat; DiAngelo, Justin R.; Keene, Alex C.

    2016-01-01

    Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the iden...

  13. REM sleep complicates period adding bifurcations from monophasic to polyphasic sleep behavior in a sleep-wake regulatory network model for human sleep

    OpenAIRE

    Kalmbach, K.; Booth, V.; Behn, C. G. Diniz

    2017-01-01

    The structure of human sleep changes across development as it consolidates from the polyphasic sleep of infants to the single nighttime sleep period typical in adults. Across this same developmental period, time scales of the homeostatic sleep drive, the physiological drive to sleep that increases with time spent awake, also change and presumably govern the transition from polyphasic to monophasic sleep behavior. Using a physiologically-based, sleep-wake regulatory network model for human sle...

  14. Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

    Science.gov (United States)

    Kim, Bowon; Kocsis, Bernat; Hwang, Eunjin; Kim, Youngsoo; Strecker, Robert E; McCarley, Robert W; Choi, Jee Hyun

    2017-02-28

    Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation.

  15. Glycogen metabolism and the homeostatic regulation of sleep

    KAUST Repository

    Petit, Jean-Marie

    2014-11-16

    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which is associated to an increased energy demand. Astrocytic glycogen depletion participates to an increase of extracellular adenosine release which influences sleep homeostasis. Here, we will review some evidence obtained by studies addressing the question of a key role played by glycogen metabolism in sleep regulation as proposed by this hypothesis or by an alternative hypothesis named “glycogenetic” hypothesis as well as the importance of the confounding effect of glucocorticoïds. Even though actual collected data argue in favor of a role of sleep in brain energy balance-homeostasis, they do not support a critical and direct involvement of glycogen metabolism on sleep regulation. For instance, glycogen levels during the sleep-wake cycle are driven by different physiological signals and therefore appear more as a marker-integrator of brain energy status than a direct regulator of sleep homeostasis. In support of this we provide evidence that blockade of glycogen mobilization does not induce more sleep episodes during the active period while locomotor activity is reduced. These observations do not invalidate the energy hypothesis of sleep but indicate that underlying cellular mechanisms are more complex than postulated by Benington and Heller.

  16. The inappropriate occurrence of rapid eye movement sleep in narcolepsy is not due to a defect in homeostatic regulation of rapid eye movement sleep.

    Science.gov (United States)

    Roman, Alexis; Meftah, Soraya; Arthaud, Sébastien; Luppi, Pierre-Hervé; Peyron, Christelle

    2018-06-01

    Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. The later three symptoms together with a short rapid eye movement (REM) sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates. We first performed 48 hr of REM sleep deprivation using the classic small-platforms-over-water method. We found that narcoleptic mice are similarly REM sleep deprived to WT mice. Although they had shorter sleep latency, Orex-KO mice recovered similarly to WT during the following 10 hr of recovery. Interestingly, Orex-KO mice also had cataplexy episodes immediately after REM sleep deprivation, anticipating REM sleep rebound, at a time of day when cataplexy does not occur in baseline condition. We then evaluated REM sleep propensity using our new automated method of deprivation that performs a specific and efficient REM sleep deprivation. We showed that REM sleep propensity is similar during light phase in Orex-KO and WT mice. However, during the dark phase, REM sleep propensity was not suppressed in Orex-KO mice when hypocretin/orexin neuropeptides are normally released. Altogether our data suggest that in addition to the well-known wake-promoting role of hypocretin/orexin, these neuropeptides would also suppress REM sleep. Therefore, hypocretin/orexin deficiency would facilitate the occurrence of REM sleep at any time of day in an opportunistic manner as seen in human narcolepsy.

  17. ERK phosphorylation regulates sleep and plasticity in Drosophila.

    Directory of Open Access Journals (Sweden)

    William M Vanderheyden

    Full Text Available Given the relationship between sleep and plasticity, we examined the role of Extracellular signal-regulated kinase (ERK in regulating baseline sleep, and modulating the response to waking experience. Both sleep deprivation and social enrichment increase ERK phosphorylation in wild-type flies. The effects of both sleep deprivation and social enrichment on structural plasticity in the LNvs can be recapitulated by expressing an active version of ERK (UAS-ERK(SEM pan-neuronally in the adult fly using GeneSwitch (Gsw Gsw-elav-GAL4. Conversely, disrupting ERK reduces sleep and prevents both the behavioral and structural plasticity normally induced by social enrichment. Finally, using transgenic flies carrying a cAMP response Element (CRE-luciferase reporter we show that activating ERK enhances CRE-Luc activity while disrupting ERK reduces it. These data suggest that ERK phosphorylation is an important mediator in transducing waking experience into sleep.

  18. Formation and suppression of acoustic memories during human sleep.

    Science.gov (United States)

    Andrillon, Thomas; Pressnitzer, Daniel; Léger, Damien; Kouider, Sid

    2017-08-08

    Sleep and memory are deeply related, but the nature of the neuroplastic processes induced by sleep remains unclear. Here, we report that memory traces can be both formed or suppressed during sleep, depending on sleep phase. We played samples of acoustic noise to sleeping human listeners. Repeated exposure to a novel noise during Rapid Eye Movements (REM) or light non-REM (NREM) sleep leads to improvements in behavioral performance upon awakening. Strikingly, the same exposure during deep NREM sleep leads to impaired performance upon awakening. Electroencephalographic markers of learning extracted during sleep confirm a dissociation between sleep facilitating memory formation (light NREM and REM sleep) and sleep suppressing learning (deep NREM sleep). We can trace these neural changes back to transient sleep events, such as spindles for memory facilitation and slow waves for suppression. Thus, highly selective memory processes are active during human sleep, with intertwined episodes of facilitative and suppressive plasticity.Though memory and sleep are related, it is still unclear whether new memories can be formed during sleep. Here, authors show that people could learn new sounds during REM or light non-REM sleep, but that learning was suppressed when sounds were played during deep NREM sleep.

  19. Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans.

    Science.gov (United States)

    Bachmann, Valérie; Klaus, Federica; Bodenmann, Sereina; Schäfer, Nikolaus; Brugger, Peter; Huber, Susanne; Berger, Wolfgang; Landolt, Hans-Peter

    2012-04-01

    Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.

  20. Retino-hypothalamic regulation of light-induced murine sleep

    Directory of Open Access Journals (Sweden)

    Fanuel eMuindi

    2014-08-01

    Full Text Available The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area and the suprachiasmatic nucleus. We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages.

  1. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  2. Conserved properties of Drosophila Insomniac link sleep regulation and synaptic function.

    Science.gov (United States)

    Li, Qiuling; Kellner, David A; Hatch, Hayden A M; Yumita, Tomohiro; Sanchez, Sandrine; Machold, Robert P; Frank, C Andrew; Stavropoulos, Nicholas

    2017-05-01

    Sleep is an ancient animal behavior that is regulated similarly in species ranging from flies to humans. Various genes that regulate sleep have been identified in invertebrates, but whether the functions of these genes are conserved in mammals remains poorly explored. Drosophila insomniac (inc) mutants exhibit severely shortened and fragmented sleep. Inc protein physically associates with the Cullin-3 (Cul3) ubiquitin ligase, and neuronal depletion of Inc or Cul3 strongly curtails sleep, suggesting that Inc is a Cul3 adaptor that directs the ubiquitination of neuronal substrates that impact sleep. Three proteins similar to Inc exist in vertebrates-KCTD2, KCTD5, and KCTD17-but are uncharacterized within the nervous system and their functional conservation with Inc has not been addressed. Here we show that Inc and its mouse orthologs exhibit striking biochemical and functional interchangeability within Cul3 complexes. Remarkably, KCTD2 and KCTD5 restore sleep to inc mutants, indicating that they can substitute for Inc in vivo and engage its neuronal targets relevant to sleep. Inc and its orthologs localize similarly within fly and mammalian neurons and can traffic to synapses, suggesting that their substrates may include synaptic proteins. Consistent with such a mechanism, inc mutants exhibit defects in synaptic structure and physiology, indicating that Inc is essential for both sleep and synaptic function. Our findings reveal that molecular functions of Inc are conserved through ~600 million years of evolution and support the hypothesis that Inc and its orthologs participate in an evolutionarily conserved ubiquitination pathway that links synaptic function and sleep regulation.

  3. Effects of interface pressure distribution on human sleep quality.

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    Zongyong Chen

    Full Text Available High sleep quality promotes efficient performance in the following day. Sleep quality is influenced by environmental factors, such as temperature, light, sound and smell. Here, we investigated whether differences in the interface pressure distribution on healthy individuals during sleep influenced sleep quality. We defined four types of pressure models by differences in the area distribution and the subjective feelings that occurred when participants slept on the mattresses. One type of model was showed "over-concentrated" distribution of pressure; one was displayed "over-evenly" distributed interface pressure while the other two models were displayed intermediate distribution of pressure. A polysomnography analysis demonstrated an increase in duration and proportion of non-rapid-eye-movement sleep stages 3 and 4, as well as decreased number of micro-arousals, in subjects sleeping on models with pressure intermediately distributed compared to models with over-concentrated or over-even distribution of pressure. Similarly, higher scores of self-reported sleep quality were obtained in subjects sleeping on the two models with intermediate pressure distribution. Thus, pressure distribution, at least to some degree, influences sleep quality and self-reported feelings of sleep-related events, though the underlying mechanisms remain unknown. The regulation of pressure models imposed by external sleep environment may be a new direction for improving sleep quality. Only an appropriate interface pressure distribution is beneficial for improving sleep quality, over-concentrated or -even distribution of pressure do not help for good sleep.

  4. A Multispecies Approach to Co-Sleeping : Integrating Human-Animal Co-Sleeping Practices into Our Understanding of Human Sleep.

    Science.gov (United States)

    Smith, Bradley P; Hazelton, Peta C; Thompson, Kirrilly R; Trigg, Joshua L; Etherton, Hayley C; Blunden, Sarah L

    2017-09-01

    Human sleeping arrangements have evolved over time and differ across cultures. The majority of adults share their bed at one time or another with a partner or child, and many also sleep with pets. In fact, around half of dog and cat owners report sharing a bed or bedroom with their pet(s). However, interspecies co-sleeping has been trivialized in the literature relative to interpersonal or human-human co-sleeping, receiving little attention from an interdisciplinary psychological perspective. In this paper, we provide a historical outline of the "civilizing process" that has led to current sociocultural conceptions of sleep as an individual, private function crucial for the functioning of society and the health of individuals. We identify similar historical processes at work in the formation of contemporary constructions of socially normative sleeping arrangements for humans and animals. Importantly, since previous examinations of co-sleeping practices have anthropocentrically framed this topic, the result is an incomplete understanding of co-sleeping practices. By using dogs as an exemplar of human-animal co-sleeping, and comparing human-canine sleeping with adult-child co-sleeping, we determine that both forms of co-sleeping share common factors for establishment and maintenance, and often result in similar benefits and drawbacks. We propose that human-animal and adult-child co-sleeping should be approached as legitimate and socially relevant forms of co-sleeping, and we recommend that co-sleeping be approached broadly as a social practice involving relations with humans and other animals. Because our proposition is speculative and derived from canine-centric data, we recommend ongoing theoretical refinement grounded in empirical research addressing co-sleeping between humans and multiple animal species.

  5. Human gamma oscillations during slow wave sleep.

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    Mario Valderrama

    Full Text Available Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS. At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz and high (60-120 Hz frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern, confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern. This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.

  6. Neural Markers of Responsiveness to the Environment in Human Sleep

    DEFF Research Database (Denmark)

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai

    2016-01-01

    by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep...... could be related to modulation in sleep depth. InREMsleep, however, this relationship was reversed.Wetherefore propose that, in REM sleep, endogenously generated processes compete with the processing of external input. Sleep can thus be seen as a self-regulated process in which external information can...... be processed in lighter stages but suppressed in deeper stages. Last, our results suggest drastically different gating mechanisms in NREM and REM sleep....

  7. The Effect of Dogs on Human Sleep in the Home Sleep Environment.

    Science.gov (United States)

    Patel, Salma I; Miller, Bernie W; Kosiorek, Heidi E; Parish, James M; Lyng, Philip J; Krahn, Lois E

    2017-09-01

    To objectively assess whether a dog in the bedroom or bed disturbs sleep. From August 1, 2015, through December 31, 2015, we evaluated the sleep of humans and dogs occupying the same bedroom to determine whether this arrangement was conducive to sleep. The study included 40 healthy adults without sleep disorders and their dogs (no dogs dog a validated dog accelerometer for 7 nights. The mean ± SD age of the participants (88% women) was 44±14 years and body mass index was 25±6. The mean ± SD age of the dogs was 5±3 years and weight was 15±13 kg. Mean ± SD actigraphy data showed 475±101 minutes in bed, 404±99 minutes total sleep time, 81%±7% sleep efficiency, and 71±35 minutes wake time after sleep onset. The dogs' accelerometer activity during the corresponding human sleep period was characterized as mean ± SD minutes at rest, active, and at play of 413±102, 62±43, and 2±4. The dogs had mean ± SD 85%±15% sleep efficiency. Human sleep efficiency was lower if the dog was on the bed as opposed to simply in the room (P=.003). Humans with a single dog in their bedroom maintained good sleep efficiency; however, the dog's position on/off the bed made a difference. A dog's presence in the bedroom may not be disruptive to human sleep, as was previously suspected. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  8. Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

    Science.gov (United States)

    Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M; Walker, Matthew P

    2015-07-15

    Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. Copyright © 2015 the authors 0270-6474/15/3510135-11$15.00/0.

  9. Functional neuroimaging insights into the physiology of human sleep.

    Science.gov (United States)

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

    2010-12-01

    Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.

  10. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Directory of Open Access Journals (Sweden)

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

  11. Effect of sleep deprivation on the human metabolome

    NARCIS (Netherlands)

    S.K. Davies (Sarah); J.E. Ang (Joo Ern); V.L. Revell (Victoria); B. Holmes (Ben); A. Mann (Anuska); F.P. Robertson (Francesca); N. Cui (Nanyi); B. Middleton (Benita); K. Ackermann (Katrin); M.H. Kayser (Manfred); A.E. Thumser (Alfred); P. Raynaud (Philippe); D.J. Skene (Debra)

    2014-01-01

    textabstractSleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigatedwith the use of a metabolomics approach. Here we have used

  12. Hippocampal sleep features: relations to human memory function

    Directory of Open Access Journals (Sweden)

    Michele eFerrara

    2012-04-01

    Full Text Available The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific pattern of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, NREM sleep in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep

  13. Hippocampal Sleep Features: Relations to Human Memory Function

    Science.gov (United States)

    Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

    2012-01-01

    The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate

  14. Entrainment of the circadian clock in humans: mechanism and implications for sleep disorders.

    Directory of Open Access Journals (Sweden)

    David Metcalfe

    2007-01-01

    Full Text Available Humans exhibit behaviour and physiology controlled by a circadian clock. The circadian period is genetically determined and administered by a series of interlocked autoregulatory feedback loops largely in the suprachiasmatic nuclei of the hypothalamus. The phase of the clock is, however, synchronised by a number of external environmental cues such as light. A failure or change in any one of the requisite clock components may result in the onset of a long-term sleep disorder. This review discusses the mechanism regulating circadian physiology in humans and explores how disturbances of this mechanism may result in sleep pathologies.

  15. [Natural factors influencing sleep].

    Science.gov (United States)

    Jurkowski, Marek K; Bobek-Billewicz, Barbara

    2007-01-01

    Sleep is a universal phenomenon of human and animal lives, although the importance of sleep for homeo-stasis is still unknown. Sleep disturbances influence many behavioral and physiologic processes, leading to health complications including death. On the other hand, sleep improvement can beneficially influence the course of healing of many disorders and can be a prognostic of health recovery. The factors influencing sleep have different biological and chemical origins. They are classical hormones, hypothalamic releasing and inhibitory hormones, neuropeptides, peptides and others as cytokines, prostaglandins, oleamid, adenosine, nitric oxide. These factors regulate most physiologic processes and are likely elements integrating sleep with physiology and physiology with sleep in health and disorders.

  16. Saudi regulations for the accreditation of sleep medicine physicians and technologists

    Directory of Open Access Journals (Sweden)

    Ahmed S BaHammam

    2013-01-01

    Full Text Available The professional content of sleep medicine has grown significantly over the past few decades, warranting the recognition of sleep medicine as an independent specialty. Because the practice of sleep medicine has expanded in Saudi Arabia over the past few years, a national regulation system to license and ascertain the competence of sleep medicine physicians and technologists has become essential. Recently, the Saudi Commission for Health Specialties formed the National Committee for the Accreditation of Sleep Medicine Practice and developed national accreditation criteria. This paper presents the newly approved Saudi accreditation criteria for sleep medicine physicians and technologists.

  17. Effect of Sleep/Wake Cycle on Autonomic Regulation

    International Nuclear Information System (INIS)

    Jabeen, S.

    2015-01-01

    Objective: To evaluate the association between irregular sleep/wake cycle in shift workers and autonomic regulation. Study Design: Cross-sectional, analytical study. Place and Duration of Study: Dow University Hospital, Karachi, from August to November 2013. Methodology: All health care providers working in rotating shifts making a total (n=104) were included. Instrument was an integrated questionnaire applied to assess autonomic regulation, taken from Kroz et al. on scoring criteria, ranging from 18 - 54, where higher rating signifies strong autonomic regulation, indicating a stable Autonomic Nervous System (ANS) and vice versa. Participants were interviewed and their response was recorded by the investigator. Influence of sleep misalignment was measured quantitatively to extract index of autonomic activity. Results: There was a reduced trend in autonomic strength amongst shift workers. The mean score obtained on the Autonomic Scale was 37.8 ± 5.9. Conclusion: Circadian misalignment has an injurious influence on ANS which might be valuable in controlling autonomic dysfunction that leads to fatal triggers in rotating shift workers. (author)

  18. Role of sleep duration in the regulation of glucose metabolism and appetite

    OpenAIRE

    Morselli, Lisa; Leproult, Rachel; Balbo, Marcella; Spiegel, Karine

    2010-01-01

    Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally-induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regu...

  19. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans.

    Science.gov (United States)

    Pellegrino, Renata; Kavakli, Ibrahim Halil; Goel, Namni; Cardinale, Christopher J; Dinges, David F; Kuna, Samuel T; Maislin, Greg; Van Dongen, Hans P A; Tufik, Sergio; Hogenesch, John B; Hakonarson, Hakon; Pack, Allan I

    2014-08-01

    Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loophelix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis. Pellegrino R, Kavakli IH, Goel N, Cardinale CJ, Dinges DF, Kuna ST, Maislin G, Van Dongen HP, Tufik S, Hogenesch JB, Hakonarson H, Pack AI. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans. SLEEP 2014;37(8):1327-1336.

  20. Homeostatic & Circadian Regulation of Wakefulness During Jet Lag and Sleep. Sleep Deprivation: Effect of Wake-Promoting Countermeasures

    National Research Council Canada - National Science Library

    Dinges, David

    2000-01-01

    .... Major human research projects on the effects of induced jet lag and sleep deprivation and their mitigation by sustained low-dose caffeine and naps were undertaken at the University of Pennsylvania...

  1. Obstructive sleep apnea and energy balance regulation: A systematic review.

    Science.gov (United States)

    Shechter, Ari

    2017-08-01

    Obesity and obstructive sleep apnea (OSA) have a reciprocal relationship. Sleep disruptions characteristic of OSA may promote behavioral, metabolic, and/or hormonal changes favoring weight gain and/or difficulty losing weight. The regulation of energy balance (EB), i.e., the relationship between energy intake (EI) and energy expenditure (EE), is complex and multi-factorial, involving food intake, hormonal regulation of hunger/satiety/appetite, and EE via metabolism and physical activity (PA). The current systematic review describes the literature on how OSA affects EB-related parameters. OSA is associated with a hormonal profile characterized by abnormally high leptin and ghrelin levels, which may encourage excess EI. Data on actual measures of food intake are lacking, and not sufficient to make conclusions. Resting metabolic rate appears elevated in OSA vs. Findings on PA are inconsistent, but may indicate a negative relationship with OSA severity that is modulated by daytime sleepiness and body weight. A speculative explanation for the positive EB in OSA is that the increased EE via metabolism induces an overcompensation in the drive for hunger/food intake, which is larger in magnitude than the rise in EI required to re-establish EB. Understanding how OSA affects EB-related parameters can help improve weight loss efforts in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Infant Sleep Predicts Attention Regulation and Behavior Problems at 3-4 Years of Age.

    Science.gov (United States)

    Sadeh, Avi; De Marcas, Gali; Guri, Yael; Berger, Andrea; Tikotzky, Liat; Bar-Haim, Yair

    2015-01-01

    This longitudinal study assessed the role of early sleep patterns in predicting attention regulation and behavior problems. Sleep of 43 infants was assessed using actigraphy at 12 months of age and then reassessed when the children were 3-4 years old. During this follow-up, their attention regulation and behavior problems were also assessed using a computerized test and parental reports. Lower quality of sleep in infancy significantly predicted compromised attention regulation and behavior problems. These findings underscore the need to identify and treat early sleep problems.

  3. Sabotaging the benefits of our own human capital: Work unit characteristics and sleep.

    Science.gov (United States)

    Barnes, Christopher M; Jiang, Kaifeng; Lepak, David P

    2016-02-01

    The strategic human capital literature indicates the importance of human capital to work unit performance. However, we argue that human capital only aids performance when it is translated into actions beneficial to the unit. We examine a set of common human capital leveraging characteristics (including the use of extended shifts, night shifts, shift flexibility, norms for work as a priority over sleep, and norms for constant connectivity) as factors that enhance the effect of human capital on human capital utilization. We also draw from the 2-process model of sleep regulation to examine how these characteristics undermine employee sleep, and thus weaken the link between human capital and work unit performance efficiency. Overall, we propose that human capital leveraging strategies initially enhance the effect of human capital on work unit performance, but over time weaken the effect of human capital on work unit performance efficiency. Thus, strategies intended to enhance the beneficial effect of human capital on work unit performance can end up doing the opposite. (c) 2016 APA, all rights reserved).

  4. Neurons Containing Orexin or Melanin Concentrating Hormone Reciprocally Regulate Wake and Sleep

    Directory of Open Access Journals (Sweden)

    Roda Rani eKonadhode

    2015-01-01

    Full Text Available There is considerable amount of data on arousal neurons whereas there is a paucity of knowledge regarding neurons that make us fall asleep. Indeed, current network models of sleep-wake regulation list many arousal neuronal populations compared to only one sleep group located in the preoptic area. There are neurons outside the preoptic area that are active during sleep, but they have never been selectively manipulated. Indeed, none of the sleep-active neurons have been selectively stimulated. To close this knowledge gap we used optogenetics to selectively manipulate neurons containing melanin concentrating hormone (MCH. The MCH neurons are located in the posterior hypothalamus intermingled with the orexin arousal neurons. Our data indicated that optogenetic stimulation of MCH neurons in wildtype mice (J Neuroscience, 2013 robustly increased both non-REM and REM sleep. MCH neuron stimulation increased sleep during the animal’s normal active period, which is compelling evidence that stimulation of MCH neurons has a powerful effect in counteracting the strong arousal signal from all of the arousal neurons. The MCH neurons represent the only group of sleep-active neurons that when selectively stimulated induce sleep. From a translational perspective this is potentially useful in sleep disorders, such as insomnia, where sleep needs to be triggered against a strong arousal drive. Our studies indicate that the MCH neurons belong within an overall model of sleep-wake regulation.

  5. Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation.

    Science.gov (United States)

    Curie, Thomas; Mongrain, Valérie; Dorsaz, Stéphane; Mang, Géraldine M; Emmenegger, Yann; Franken, Paul

    2013-03-01

    Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis. EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18. Mouse sleep laboratory. Male mice. Sleep deprivation. The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset. Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need. Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation. SLEEP 2013;36(3):311-323.

  6. Sleep/wake firing patterns of human genioglossus motor units.

    Science.gov (United States)

    Bailey, E Fiona; Fridel, Keith W; Rice, Amber D

    2007-12-01

    Although studies of the principal tongue protrudor muscle genioglossus (GG) suggest that whole muscle GG electromyographic (EMG) activities are preserved in nonrapid eye movement (NREM) sleep, it is unclear what influence sleep exerts on individual GG motor unit (MU) activities. We characterized the firing patterns of human GG MUs in wakefulness and NREM sleep with the aim of determining 1) whether the range of MU discharge patterns evident in wakefulness is preserved in sleep and 2) what effect the removal of the "wakefulness" input has on the magnitude of the respiratory modulation of MU activities. Microelectrodes inserted into the extrinsic tongue protrudor muscle, the genioglossus, were used to follow the discharge of single MUs. We categorized MU activities on the basis of the temporal relationship between the spike train and the respiration cycle and quantified the magnitude of the respiratory modulation of each MU using the eta (eta(2)) index, in wakefulness and sleep. The majority of MUs exhibited subtle increases or decreases in respiratory modulation but were otherwise unaffected by NREM sleep. In contrast, 30% of MUs exhibited marked sleep-associated changes in discharge frequency and respiratory modulation. We suggest that GG MUs should not be considered exclusively tonic or phasic; rather, the discharge pattern appears to be a flexible feature of GG activities in healthy young adults. Whether such flexibility is important in the response to changes in the chemical and/or mechanical environment and whether it is preserved as a function of aging or in individuals with obstructive sleep apnea are critical questions for future research.

  7. Bedtime procrastination: A self-regulation perspective on sleep insufficiency in the general population.

    Science.gov (United States)

    Kroese, Floor M; Evers, Catharine; Adriaanse, Marieke A; de Ridder, Denise T D

    2016-05-01

    Getting insufficient sleep has serious consequences in terms of mental and physical health. The current study is the first to approach insufficient sleep from a self-regulation perspective by investigating the phenomenon of bedtime procrastination: going to bed later than intended, without having external reasons for doing so. Data from a representative sample of Dutch adults (N = 2431) revealed that a large proportion of the general population experiences getting insufficient sleep and regularly goes to bed later than they would like to. Most importantly, a relationship between self-regulation and experienced insufficient sleep was found, which was mediated by bedtime procrastination. © The Author(s) 2014.

  8. Selective neuronal lapses precede human cognitive lapses following sleep deprivation.

    Science.gov (United States)

    Nir, Yuval; Andrillon, Thomas; Marmelshtein, Amit; Suthana, Nanthia; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak

    2017-12-01

    Sleep deprivation is a major source of morbidity with widespread health effects, including increased risk of hypertension, diabetes, obesity, heart attack, and stroke. Moreover, sleep deprivation brings about vehicle accidents and medical errors and is therefore an urgent topic of investigation. During sleep deprivation, homeostatic and circadian processes interact to build up sleep pressure, which results in slow behavioral performance (cognitive lapses) typically attributed to attentional thalamic and frontoparietal circuits, but the underlying mechanisms remain unclear. Recently, through study of electroencephalograms (EEGs) in humans and local field potentials (LFPs) in nonhuman primates and rodents it was found that, during sleep deprivation, regional 'sleep-like' slow and theta (slow/theta) waves co-occur with impaired behavioral performance during wakefulness. Here we used intracranial electrodes to record single-neuron activities and LFPs in human neurosurgical patients performing a face/nonface categorization psychomotor vigilance task (PVT) over multiple experimental sessions, including a session after full-night sleep deprivation. We find that, just before cognitive lapses, the selective spiking responses of individual neurons in the medial temporal lobe (MTL) are attenuated, delayed, and lengthened. These 'neuronal lapses' are evident on a trial-by-trial basis when comparing the slowest behavioral PVT reaction times to the fastest. Furthermore, during cognitive lapses, LFPs exhibit a relative local increase in slow/theta activity that is correlated with degraded single-neuron responses and with baseline theta activity. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already present in the MTL.

  9. Sleep

    Science.gov (United States)

    ... Institute (NHLBI). 1 Mood. Sleep affects your mood. Insufficient sleep can cause irritability that can lead to trouble with relationships, ... basics/understanding_sleep.htm#dynamic_activity Centers for Disease ... insufficient rest or sleep among adults—United States, 2008. MMWR, 58 (42), ...

  10. Plasticity during Sleep Is Linked to Specific Regulation of Cortical Circuit Activity

    Directory of Open Access Journals (Sweden)

    Niels Niethard

    2017-09-01

    Full Text Available Sleep is thought to be involved in the regulation of synaptic plasticity in two ways: by enhancing local plastic processes underlying the consolidation of specific memories and by supporting global synaptic homeostasis. Here, we briefly summarize recent structural and functional studies examining sleep-associated changes in synaptic morphology and neural excitability. These studies point to a global down-scaling of synaptic strength across sleep while a subset of synapses increases in strength. Similarly, neuronal excitability on average decreases across sleep, whereas subsets of neurons increase firing rates across sleep. Whether synapse formation and excitability is down or upregulated across sleep appears to partly depend on the cell’s activity level during wakefulness. Processes of memory-specific upregulation of synapse formation and excitability are observed during slow wave sleep (SWS, whereas global downregulation resulting in elimination of synapses and decreased neural firing is linked to rapid eye movement sleep (REM sleep. Studies of the excitation/inhibition balance in cortical circuits suggest that both processes are connected to a specific inhibitory regulation of cortical principal neurons, characterized by an enhanced perisomatic inhibition via parvalbumin positive (PV+ cells, together with a release from dendritic inhibition by somatostatin positive (SOM+ cells. Such shift towards increased perisomatic inhibition of principal cells appears to be a general motif which underlies the plastic synaptic changes observed during sleep, regardless of whether towards up or downregulation.

  11. EphA4 is Involved in Sleep Regulation but Not in the Electrophysiological Response to Sleep Deprivation.

    Science.gov (United States)

    Freyburger, Marlène; Pierre, Audrey; Paquette, Gabrielle; Bélanger-Nelson, Erika; Bedont, Joseph; Gaudreault, Pierre-Olivier; Drolet, Guy; Laforest, Sylvie; Blackshaw, Seth; Cermakian, Nicolas; Doucet, Guy; Mongrain, Valérie

    2016-03-01

    Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. EphA4 knockout (KO) mice, Clock(Δ19/Δ19) mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SLD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SLD was unchanged in EphA4 KO mice. However, SLD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Our results suggest that EphA4 is involved in circadian sleep regulation. © 2016 Associated Professional Sleep Societies, LLC.

  12. Effects of Extreme Sleep Deprivation on Human Performance

    Energy Technology Data Exchange (ETDEWEB)

    Tuan Tran; Kimberly R. Raddatz; Elizabeth T. Cady; Bradford Amstutz; Pete D. Elgin; Christopher Vowels; Gerald Deehan

    2007-04-01

    Sleep is a fundamental recuperative process for the nervous system. Disruption of this homeostatic drive can lead to severe impairments of the operator’s ability to perceive, recognize, and respond to emergencies and/or unanticipated events, putting the operator at risk. Therefore, establishing a comprehensive understanding of how sleep deprivation influences human performance is essential in order to counter fatigue or to develop mitigation strategies. The goal of the present study was to examine the psychological effects of prolonged sleep deprivation (approx. 75 hrs) over a four-day span on a general aviation pilot flying a fixed-based flight simulator. During the study, a series of tasks were employed every four hours in order to examine the pilot’s perceptual and higher level cognitive abilities. Overall, results suggest that the majority of cognitive and perceptual degradation occurs between 30-40 hours into the flight. Limitations and future research directions are also discussed.

  13. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  14. Sleep-dependent directional coupling between human neocortex and hippocampus.

    Science.gov (United States)

    Wagner, Tobias; Axmacher, Nikolai; Lehnertz, Klaus; Elger, Christian E; Fell, Jürgen

    2010-02-01

    Complex interactions between neocortex and hippocampus are the neural basis of memory formation. Two-step theories of memory formation suggest that initial encoding of novel information depends on the induction of rapid plasticity within the hippocampus, and is followed by a second sleep-dependent step of memory consolidation. These theories predict information flow from the neocortex into the hippocampus during waking state and in the reverse direction during sleep. However, experimental evidence that interactions between hippocampus and neocortex have a predominant direction which reverses during sleep rely on cross-correlation analysis of data from animal experiments and yielded inconsistent results. Here, we investigated directional coupling in intracranial EEG data from human subjects using a phase-modeling approach which is well suited to reveal functional interdependencies in oscillatory data. In general, we observed that the anterior hippocampus predominantly drives nearby and remote brain regions. Surprisingly, however, the influence of neocortical regions on the hippocampus significantly increased during sleep as compared to waking state. These results question the standard model of hippocampal-neocortical interactions and suggest that sleep-dependent consolidation is accomplished by an active retrieval of hippocampal information by the neocortex. Copyright 2009 Elsevier Srl. All rights reserved.

  15. Sleep apnoea and driving risk: the need for regulation

    Directory of Open Access Journals (Sweden)

    Walter T. McNicholas

    2015-12-01

    Full Text Available Obstructive sleep apnoea syndrome (OSAS is a highly prevalent chronic respiratory disorder with prevalence among adult males of ≥10%. The most common daytime symptom associated with OSAS is excessive sleepiness, which in more severe manifestations can result in sleepiness at the wheel while driving and probably contributes to the substantial increase in accident risk among patients with OSAS. Fortunately, current evidence indicates that successful therapy of OSAS, particularly with continuous positive airway pressure, can bring the accident risk down to levels similar to an equivalent general population. The recognition of the increased driving accident risk in OSAS prompted the Transport and Mobility Directorate of the European Commission to establish a working group on this topic in 2012, which ultimately led to a revision of Annex III of the EU Driving Licence Directive, which is subject to mandatory implementation by European Union member states by December 2015. This directive specifies that patients with moderate or severe OSAS associated with significant daytime sleepiness should be prohibited from driving until effective therapy is established. These new regulations are designed to balance the legitimate objective of public safety with not penalising OSAS patients who are complying with effective therapy. Successful implementation of regulations on driving in OSAS patients must also include measures to educate relevant stakeholders including patients, medical personnel, traffic police and employers in the transport industry. The key objective is to encourage patients with possible OSAS to seek diagnosis and treatment and not to inhibit OSAS patients from coming forward.

  16. Sleep apnoea and driving risk: the need for regulation.

    Science.gov (United States)

    McNicholas, Walter T; Rodenstein, Daniel

    2015-12-01

    Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent chronic respiratory disorder with prevalence among adult males of ≥10%. The most common daytime symptom associated with OSAS is excessive sleepiness, which in more severe manifestations can result in sleepiness at the wheel while driving and probably contributes to the substantial increase in accident risk among patients with OSAS. Fortunately, current evidence indicates that successful therapy of OSAS, particularly with continuous positive airway pressure, can bring the accident risk down to levels similar to an equivalent general population. The recognition of the increased driving accident risk in OSAS prompted the Transport and Mobility Directorate of the European Commission to establish a working group on this topic in 2012, which ultimately led to a revision of Annex III of the EU Driving Licence Directive, which is subject to mandatory implementation by European Union member states by December 2015. This directive specifies that patients with moderate or severe OSAS associated with significant daytime sleepiness should be prohibited from driving until effective therapy is established. These new regulations are designed to balance the legitimate objective of public safety with not penalising OSAS patients who are complying with effective therapy. Successful implementation of regulations on driving in OSAS patients must also include measures to educate relevant stakeholders including patients, medical personnel, traffic police and employers in the transport industry. The key objective is to encourage patients with possible OSAS to seek diagnosis and treatment and not to inhibit OSAS patients from coming forward. Copyright ©ERS 2015.

  17. Bedtime procrastination: a self-regulation perspective on sleep insufficiency in the general population

    NARCIS (Netherlands)

    Kroese, Floor|info:eu-repo/dai/nl/313869871; Evers, Catharine|info:eu-repo/dai/nl/280594232; Adriaanse, Marieke|info:eu-repo/dai/nl/304823023; de Ridder, Denise|info:eu-repo/dai/nl/070706174

    2016-01-01

    Getting insufficient sleep has serious consequences in terms of mental and physical health. The current study is the first to approach insufficient sleep from a self-regulation perspective by investigating the phenomenon of bedtime procrastination: going to bed later than intended, without having

  18. Regulation of Neuron-Astrocyte Metabolic Coupling across the Sleep-Wake Cycle

    KAUST Repository

    Petit, Jean-Marie; Magistretti, Pierre J.

    2015-01-01

    The aim of this review is to bring into perspective the role of astrocytes and neurometabolic coupling in the regulation of the sleep/wake cycle. The data reviewed also suggest an important role of the astrocytic network. In addition, the role of astrocytes in NMC mechanisms is consistent with the “local and use dependent” sleep hypothesis.

  19. Early Childhood Profiles of Sleep Problems and Self-Regulation Predict Later School Adjustment

    Science.gov (United States)

    Williams, Kate E.; Nicholson, Jan M.; Walker, Sue; Berthelsen, Donna

    2016-01-01

    Background: Children's sleep problems and self-regulation problems have been independently associated with poorer adjustment to school, but there has been limited exploration of longitudinal early childhood profiles that include both indicators. Aims: This study explores the normative developmental pathway for sleep problems and self-regulation…

  20. Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation

    OpenAIRE

    Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

    2016-01-01

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters ...

  1. The circadian regulation of sleep: impact of a functional ADA-polymorphism and its association to working memory improvements.

    Directory of Open Access Journals (Sweden)

    Carolin F Reichert

    Full Text Available Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers, previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM sleep and slow wave sleep concomitant with reduced power between 8-16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is

  2. Unraveling the Neurobiology of Sleep and Sleep Disorders Using Drosophila.

    Science.gov (United States)

    Chakravarti, L; Moscato, E H; Kayser, M S

    2017-01-01

    Sleep disorders in humans are increasingly appreciated to be not only widespread but also detrimental to multiple facets of physical and mental health. Recent work has begun to shed light on the mechanistic basis of sleep disorders like insomnia, restless legs syndrome, narcolepsy, and a host of others, but a more detailed genetic and molecular understanding of how sleep goes awry is lacking. Over the past 15 years, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation. More recently, powerful genetic approaches in the fly have been applied toward studying primary human sleep disorders and other disease states associated with dysregulated sleep. In this review, we discuss the contribution of Drosophila to the landscape of sleep biology, examining not only fundamental advances in sleep neurobiology but also how flies have begun to inform pathological sleep states in humans. © 2017 Elsevier Inc. All rights reserved.

  3. Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

    NARCIS (Netherlands)

    Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

    2008-01-01

    This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

  4. Remission of encephalopathy with status epilepticus (ESES) during sleep renormalizes regulation of slow wave sleep

    DEFF Research Database (Denmark)

    Bölsterli, Bigna K.; Gardella, Elena; Pavlidis, Elena

    2017-01-01

    Objective: In previous studies, we showed an altered overnight decrease of non–rapid-eye-movement (NREM) sleep slow waves in children with encephalopathy related to status epilepticus during sleep (ESES). Here, we test the hypothesis that these alterations renormalize after remission of ESES...

  5. Glycogen metabolism and the homeostatic regulation of sleep

    KAUST Repository

    Petit, Jean-Marie; Burlet-Godinot, Sophie; Magistretti, Pierre J.; Allaman, Igor

    2014-01-01

    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which

  6. Role of sleep duration in the regulation of glucose metabolism and appetite.

    Science.gov (United States)

    Morselli, Lisa; Leproult, Rachel; Balbo, Marcella; Spiegel, Karine

    2010-10-01

    Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with "diabesity" is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Astrocyte regulation of sleep circuits: experimental and modeling perspectives

    Directory of Open Access Journals (Sweden)

    Tommaso eFellin

    2012-08-01

    Full Text Available Integrated within neural circuits, astrocytes have recently been shown to modulate brain rhythms thought to mediate sleep function. Experimental evidence suggests that local impact of astrocytes on single synapses translates into global modulation of neuronal networks and behavior. We discuss these findings in the context of current conceptual models of sleep generation and function, each of which have historically focused on neural mechanisms. We highlight the implications and the challenges introduced by these results from a conceptual and computational perspective. We further provide modeling directions on how these data might extend our knowledge of astrocytic properties and sleep function. Given our evolving understanding of how local cellular activities during sleep lead to functional outcomes for the brain, further mechanistic and theoretical understanding of astrocytic contribution to these dynamics will undoubtedly be of great basic and translational benefit.

  8. Sleep Disorders

    DEFF Research Database (Denmark)

    Rahbek Kornum, Birgitte; Mignot, Emmanuel

    2014-01-01

    mediates circadian regulation of sleep. Misalignment with the rhythm of the sun results in circadian disorders and jet lag. The molecular basis of homeostatic sleep regulation is mostly unknown. A network of mutually inhibitory brain nuclei regulates sleep states and sleep-wake transitions. Abnormalities...... in these networks create sleep disorders, including rapid eye movement sleep behavior disorder, sleep walking, and narcolepsy. Physiological changes associated with sleep can be imbalanced, resulting in excess movements such as periodic leg movements during sleep or abnormal breathing in obstructive sleep apneas....... As every organ in the body is affected by sleep directly or indirectly, sleep and sleep-associated disorders are frequent and only now starting to be understood....

  9. Homeostatic and Circadian Contribution to EEG and Molecular State Variables of Sleep Regulation

    Science.gov (United States)

    Curie, Thomas; Mongrain, Valérie; Dorsaz, Stéphane; Mang, Géraldine M.; Emmenegger, Yann; Franken, Paul

    2013-01-01

    Study Objectives: Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis. Design: EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18. Setting: Mouse sleep laboratory. Participants: Male mice. Interventions: Sleep deprivation. Results: The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset. Conclusions: Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need. Citation: Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state

  10. Impact of physical fitness and daily energy expenditure on sleep efficiency in young and older humans

    NARCIS (Netherlands)

    Oudegeest-Sander, M.H.; Eijsvogels, T.M.H.; Verheggen, R.J.; Poelkens, F.; Hopman, M.T.E.; Jones, H.; Thijssen, D.H.J.

    2013-01-01

    BACKGROUND: Physical activity is known to influence sleep efficiency. Relatively little is known about the relationship between physical activity and sleep efficiency in young and older humans and the impact of exercise training on sleep efficiency in healthy older individuals. OBJECTIVES: To

  11. Why might poor sleep quality lead to depression? A role for emotion regulation.

    Science.gov (United States)

    O'Leary, Kimberly; Bylsma, Lauren M; Rottenberg, Jonathan

    2017-12-01

    Disordered sleep is strongly linked to future depression, but the reasons for this link are not well understood. This study tested one possibility - that poorer sleep impairs emotion regulation (ER), which over time leads to increased depressive symptoms. Our sample contained individuals with a wide range of depression symptoms (current depression, N = 54, remitted depression, N = 36, and healthy control, N = 53), who were followed clinically over six months and reassessed for changes in depressive symptom levels. As predicted, maladaptive ER mediated both cross-sectional and prospective relationships between poor sleep quality and depression symptoms. In contrast, an alternative mediator, physical activity levels, did not mediate the link between sleep quality and depression symptoms. Maladaptive ER may help explain why sleep difficulties contribute to depression symptoms; implications for interventions are discussed.

  12. Melanopsin Regulates Both Sleep-Promoting and Arousal-Promoting Responses to Light.

    Directory of Open Access Journals (Sweden)

    Violetta Pilorz

    2016-06-01

    Full Text Available Light plays a critical role in the regulation of numerous aspects of physiology and behaviour, including the entrainment of circadian rhythms and the regulation of sleep. These responses involve melanopsin (OPN4-expressing photosensitive retinal ganglion cells (pRGCs in addition to rods and cones. Nocturnal light exposure in rodents has been shown to result in rapid sleep induction, in which melanopsin plays a key role. However, studies have also shown that light exposure can result in elevated corticosterone, a response that is not compatible with sleep. To investigate these contradictory findings and to dissect the relative contribution of pRGCs and rods/cones, we assessed the effects of light of different wavelengths on behaviourally defined sleep. Here, we show that blue light (470 nm causes behavioural arousal, elevating corticosterone and delaying sleep onset. By contrast, green light (530 nm produces rapid sleep induction. Compared to wildtype mice, these responses are altered in melanopsin-deficient mice (Opn4-/-, resulting in enhanced sleep in response to blue light but delayed sleep induction in response to green or white light. We go on to show that blue light evokes higher Fos induction in the SCN compared to the sleep-promoting ventrolateral preoptic area (VLPO, whereas green light produced greater responses in the VLPO. Collectively, our data demonstrates that nocturnal light exposure can have either an arousal- or sleep-promoting effect, and that these responses are melanopsin-mediated via different neural pathways with different spectral sensitivities. These findings raise important questions relating to how artificial light may alter behaviour in both the work and domestic setting.

  13. Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory.

    Science.gov (United States)

    Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu

    2014-10-29

    Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.

  14. Roles of the hypocretin/orexins in the regulation of sleep and wakefulness.

    Science.gov (United States)

    Terao, Akira; Haruyama, Takashi; Kimura, Kazuhiro

    2008-01-01

    Hypocretin/orexin is produced exclusively in the dorsal and lateral hypothalamus but its projection is widespread within the brain and plays important roles. In this paper, we review the independent discoveries of the hypocretin/orexin peptides, the neuroanatomy of this system, and the link to the sleep disorder narcolepsy that has led to the idea that this system plays a crucial role in the regulation of sleep and wakefulness.

  15. Hypocretin (orexin regulation of sleep-to-wake transitions

    Directory of Open Access Journals (Sweden)

    Luis eDe Lecea

    2014-02-01

    Full Text Available The hypocretin (Hcrt, also known as orexin, peptides are essential for arousal stability. Here I discuss background information about the interaction of Hcrt with other neuromodulators, including norepinephrine and acetylcholine probed with optogenetics. I conclude that Hcrt neurons integrate metabolic, circadian and limbic inputs and convey this information to a network of neuromodulators, each of which has a different role on the dynamic of sleep-to-wake transitions. This model may prove useful to predict the effects of orexin receptor antagonists in sleep disorders and other conditions.

  16. Sleep-monitoring, experiment M133. [electronic recording system for automatic analysis of human sleep patterns

    Science.gov (United States)

    Frost, J. D., Jr.; Salamy, J. G.

    1973-01-01

    The Skylab sleep-monitoring experiment simulated the timelines and environment expected during a 56-day Skylab mission. Two crewmembers utilized the data acquisition and analysis hardware, and their sleep characteristics were studied in an online fashion during a number of all night recording sessions. Comparison of the results of online automatic analysis with those of postmission visual data analysis was favorable, confirming the feasibility of obtaining reliable objective information concerning sleep characteristics during the Skylab missions. One crewmember exhibited definite changes in certain sleep characteristics (e.g., increased sleep latency, increased time Awake during first third of night, and decreased total sleep time) during the mission.

  17. The Neuroprotective Aspects of Sleep.

    Science.gov (United States)

    Eugene, Andy R; Masiak, Jolanta

    2015-03-01

    Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of sleep is a serious concern that people need to be aware of. When one sleeps, the brain reorganizes and recharges itself, and removes toxic waste byproducts which have accumulated throughout the day. This evidence demonstrates that sleeping can clear the brain and help maintain its normal functioning. Multiple studies have been done to determine the effects of total sleep deprivation; more recently some have been conducted to show the effects of sleep restriction, which is a much more common occurrence, have the same effects as total sleep deprivation. Each phase of the sleep cycle restores and rejuvenates the brain for optimal function. When sleep is deprived, the active process of the glymphatic system does not have time to perform that function, so toxins can build up, and the effects will become apparent in cognitive abilities, behavior, and judgment. As a background for this paper we have reviewed literature and research of sleep phases, effects of sleep deprivation, and the glymphatic system of the brain and its restorative effect during the sleep cycle.

  18. The possible role of human milk nucleotides as sleep inducers.

    Science.gov (United States)

    Sánchez, Cristina L; Cubero, Javier; Sánchez, Javier; Chanclón, Belén; Rivero, Montserrat; Rodríguez, Ana B; Barriga, Carmen

    2009-02-01

    Breast-milk contains a potent mixture of diverse components, such as the non-protein nitrogen fraction which includes nucleotides, whose variation in levels is evident throughout lactation. In addition, these substances play an important role in sleep homeostasis. In the present study, human milk samples were analyzed using a capillary electrophoresis system. The rhythmicity of each nucleotide was studied by cosinor analysis. It was found that the nucleotides 5'AMP, 5'GMP, 5'CMP, and 5'IMP have significant (P inducing the 'hypnotic' action of breast-milk at night in the infant.

  19. The role of sleep in recovery following ischemic stroke: A review of human and animal data

    Directory of Open Access Journals (Sweden)

    Simone B. Duss

    2017-01-01

    Full Text Available Despite advancements in understanding the pathophysiology of stroke and the state of the art in acute management of afflicted patients as well as in subsequent neurorehabilitation training, stroke remains the most common neurological cause of long-term disability in adulthood. To enhance stroke patients’ independence and well-being it is necessary, therefore, to consider and develop new therapeutic strategies and approaches. We postulate that sleep might play a pivotal role in neurorehabilitation following stroke. Over the last two decades compelling evidence for a major function of sleep in neuroplasticity and neural network reorganization underlying learning and memory has evolved. Training and learning of new motor skills and knowledge can modulate the characteristics of subsequent sleep, which additionally can improve memory performance. While healthy sleep appears to support neuroplasticity resulting in improved learning and memory, disturbed sleep following stroke in animals and humans can impair stroke outcome. In addition, sleep disorders such as sleep disordered breathing, insomnia, and restless legs syndrome are frequent in stroke patients and associated with worse recovery outcomes. Studies investigating the evolution of post-stroke sleep changes suggest that these changes might also reflect neural network reorganization underlying functional recovery. Experimental and clinical studies provide evidence that pharmacological sleep promotion in rodents and treatment of sleep disorders in humans improves functional outcome following stroke. Taken together, there is accumulating evidence that sleep represents a “plasticity state” in the process of recovery following ischemic stroke. However, to test the key role of sleep and sleep disorders for stroke recovery and to better understand the underlying molecular mechanisms, experimental research and large-scale prospective studies in humans are necessary. The effects of hospital

  20. Evidence for cortical structural plasticity in humans after a day of waking and sleep deprivation.

    Science.gov (United States)

    Elvsåshagen, Torbjørn; Zak, Nathalia; Norbom, Linn B; Pedersen, Per Ø; Quraishi, Sophia H; Bjørnerud, Atle; Alnæs, Dag; Doan, Nhat Trung; Malt, Ulrik F; Groote, Inge R; Westlye, Lars T

    2017-08-01

    Sleep is an evolutionarily conserved process required for human health and functioning. Insufficient sleep causes impairments across cognitive domains, and sleep deprivation can have rapid antidepressive effects in mood disorders. However, the neurobiological effects of waking and sleep are not well understood. Recently, animal studies indicated that waking and sleep are associated with substantial cortical structural plasticity. Here, we hypothesized that structural plasticity can be observed after a day of waking and sleep deprivation in the human cerebral cortex. To test this hypothesis, 61 healthy adult males underwent structural magnetic resonance imaging (MRI) at three time points: in the morning after a regular night's sleep, the evening of the same day, and the next morning, either after total sleep deprivation (N=41) or a night of sleep (N=20). We found significantly increased right prefrontal cortical thickness from morning to evening across all participants. In addition, pairwise comparisons in the deprived group between the two morning scans showed significant thinning of mainly bilateral medial parietal cortices after 23h of sleep deprivation, including the precuneus and posterior cingulate cortex. However, there were no significant group (sleep vs. sleep deprived group) by time interactions and we can therefore not rule out that other mechanisms than sleep deprivation per se underlie the bilateral medial parietal cortical thinning observed in the deprived group. Nonetheless, these cortices are thought to subserve wakefulness, are among the brain regions with highest metabolic rate during wake, and are considered some of the most sensitive cortical regions to a variety of insults. Furthermore, greater thinning within the left medial parietal cluster was associated with increased sleepiness after sleep deprivation. Together, these findings add to a growing body of data showing rapid structural plasticity within the human cerebral cortex detectable with

  1. Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle.

    Science.gov (United States)

    Shestopalov, Valery I; Panchin, Yuri; Tarasova, Olga S; Gaynullina, Dina; Kovalzon, Vladimir M

    2017-01-01

    During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1 -/- mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle.

  2. Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

    Directory of Open Access Journals (Sweden)

    Valery I. Shestopalov

    2017-07-01

    Full Text Available During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1 hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1−/− mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle.

  3. Sleep as an Occupational Need.

    Science.gov (United States)

    Tester, Nicole J; Foss, Joanne Jackson

    In the same way the human body requires food, hydration, and oxygen, it also requires sleep. Even among healthy people, the amount and quality of sleep substantially influence health and quality of life because sleep helps regulate physiological functioning. Given the impact of sleep on participation, the American Occupational Therapy Association reclassified sleep from an activity of daily living to an occupational domain. Poor sleep is a frequent medical complaint, especially among populations with neurological impairment. Occupational therapy practitioners should consider routinely screening for factors affecting their clients' sleep. By addressing such factors, as well as related routines and habits, practitioners can enhance the effectiveness of rehabilitation, promote health and well-being, and increase engagement and life quality. Practitioners should acknowledge the importance of sleep in practice, and the study of sleep should be prioritized by researchers in the field to meet client needs and establish evidence for interventions. Copyright © 2018 by the American Occupational Therapy Association, Inc.

  4. Regulation of neuron-astrocyte metabolic coupling across the sleep-wake cycle.

    Science.gov (United States)

    Petit, J-M; Magistretti, P J

    2016-05-26

    Over the last thirty years, a growing number of studies showed that astrocytes play a pivotal role in the energy support to synapses. More precisely, astrocytes adjust energy production to neuronal energy needs through different mechanisms grouped under the term "neurometabolic coupling" (NMC). In this review we describe these mechanisms of coupling and how they involve astrocytes. From a physiological point of view, these mechanisms of coupling are particularly important to ensure normal synaptic functioning when neurons undergo rapid and repetitive changes in the firing rate such as during the sleep/wake transitions. Investigations into brain energy metabolism during the sleep/wake cycle have been mainly focused on glucose (Gluc) consumption and on glycogen metabolism. However, the recent development of substrate-specific biosensors allowed measurements of the variation in extracellular levels of glutamate, Gluc and lactate (Lac) with a time resolution compatible with sleep stage duration. Together with gene expression data these experiments allowed to better define the variations of energy metabolite regulation across the sleep/wake cycle. The aim of this review is to bring into perspective the role of astrocytes and NMC in the regulation of the sleep/wake cycle. The data reviewed also suggest an important role of the astrocytic network. In addition, the role of astrocytes in NMC mechanisms is consistent with the "local and use dependent" sleep hypothesis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Regulation of Neuron-Astrocyte Metabolic Coupling across the Sleep-Wake Cycle

    KAUST Repository

    Petit, Jean-Marie

    2015-12-17

    Over the last thirty years, a growing number of studies showed that astrocytes play a pivotal role in the energy support to synapses. More precisely, astrocytes adjust the energy production to the neuronal energy needs through different mechanisms grouped under the term “neurometabolic coupling” (NMC). In this review we describe these mechanisms of coupling and how they involve astrocytes. From a physiological point of view, these mechanisms of coupling are particularly important to ensure normal synaptic functioning when neurons undergo rapid and repetitive changes in firing rate such as during the sleep/wake transitions. Investigations on brain energy metabolism during the sleep/wake cycle have been mainly focused on glucose consumption and on glycogen metabolism. However, the recent development of substrate-specific biosensors allowed measurements of the variation in extracellular levels of glutamate, glucose and lactate with a time resolution compatible with sleep stage duration. Together with gene expression data these experiments allowed to better define the variations of energy metabolites regulation across the sleep/wake cycle. The aim of this review is to bring into perspective the role of astrocytes and neurometabolic coupling in the regulation of the sleep/wake cycle. The data reviewed also suggest an important role of the astrocytic network. In addition, the role of astrocytes in NMC mechanisms is consistent with the “local and use dependent” sleep hypothesis.

  6. Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation.

    Science.gov (United States)

    Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

    2016-05-01

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information.

  7. A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep

    Directory of Open Access Journals (Sweden)

    Salin Paul

    2003-09-01

    Full Text Available Abstract Background Peptidergic neurons containing the melanin-concentrating hormone (MCH and the hypocretins (or orexins are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation. Results Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats. Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200% and slow wave sleep (up to 70% quantities. Conclusion These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.

  8. Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation

    Science.gov (United States)

    Amador, Ariadna; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

    2016-01-01

    The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. PMID:27603791

  9. Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

    Science.gov (United States)

    Plihal, W; Born, J

    1999-09-09

    Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

  10. Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain

    Directory of Open Access Journals (Sweden)

    Sakh Khalsa

    2017-06-01

    Full Text Available Self-imposed short sleep durations are increasingly commonplace in society, and have considerable health and performance implications for individuals. Reduced sleep duration over multiple nights has similar behavioural effects to those observed following acute total sleep deprivation, suggesting that lack of sleep affects brain function cumulatively. A link between habitual sleep patterns and functional connectivity has previously been observed, and the effect of sleep duration on the brain's intrinsic functional architecture may provide a link between sleep status and cognition. However, it is currently not known whether differences in habitual sleep patterns across individuals are related to changes in the brain's white matter, which underlies structural connectivity. In the present study we use diffusion–weighted imaging and a group comparison application of tract based spatial statistics (TBSS to investigate changes to fractional anisotropy (FA and mean diffusivity (MD in relation to sleep duration and quality, hypothesising that white matter metrics would be positively associated with sleep duration and quality. Diffusion weighted imaging data was acquired from a final cohort of 33 (23–29 years, 10 female, mean 25.4 years participants. Sleep patterns were assessed for a 14 day period using wrist actigraphs and sleep diaries, and subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI. Median splits based on total sleep time and PSQI were used to create groups of shorter/longer and poorer/better sleepers, whose imaging data was compared using TBSS followed by post-hoc correlation analysis in regions identified as significantly different between the groups. There were significant positive correlations between sleep duration and FA in the left orbito-frontal region and the right superior corona radiata, and significant negative correlations between sleep duration and MD in right orbito-frontal white matter and the right

  11. Does selection for short sleep duration explain human vulnerability to Alzheimer's disease?

    Science.gov (United States)

    Nesse, Randolph M; Finch, Caleb E; Nunn, Charles L

    2017-01-16

    Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer 's disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD. © The Author(s) 2017. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

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

    Science.gov (United States)

    Giskeødegård, Guro F; Davies, Sarah K; Revell, Victoria L; Keun, Hector; Skene, Debra J

    2015-10-09

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

  13. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease12

    Science.gov (United States)

    Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

    2016-01-01

    Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. PMID:27422503

  14. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease.

    Science.gov (United States)

    Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

    2016-07-01

    Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. © 2016 American Society for Nutrition.

  15. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  16. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi, F.

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11 C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11 C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11 C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  17. A longitudinal assessment of sleep timing, circadian phase, and phase angle of entrainment across human adolescence.

    Directory of Open Access Journals (Sweden)

    Stephanie J Crowley

    Full Text Available The aim of this descriptive analysis was to examine sleep timing, circadian phase, and phase angle of entrainment across adolescence in a longitudinal study design. Ninety-four adolescents participated; 38 (21 boys were 9-10 years ("younger cohort" and 56 (30 boys were 15-16 years ("older cohort" at the baseline assessment. Participants completed a baseline and then follow-up assessments approximately every six months for 2.5 years. At each assessment, participants wore a wrist actigraph for at least one week at home to measure self-selected sleep timing before salivary dim light melatonin onset (DLMO phase - a marker of the circadian timing system - was measured in the laboratory. Weekday and weekend sleep onset and offset and weekend-weekday differences were derived from actigraphy. Phase angles were the time durations from DLMO to weekday sleep onset and offset times. Each cohort showed later sleep onset (weekend and weekday, later weekend sleep offset, and later DLMO with age. Weekday sleep offset shifted earlier with age in the younger cohort and later in the older cohort after age 17. Weekend-weekday sleep offset differences increased with age in the younger cohort and decreased in the older cohort after age 17. DLMO to sleep offset phase angle narrowed with age in the younger cohort and became broader in the older cohort. The older cohort had a wider sleep onset phase angle compared to the younger cohort; however, an age-related phase angle increase was seen in the younger cohort only. Individual differences were seen in these developmental trajectories. This descriptive study indicated that circadian phase and self-selected sleep delayed across adolescence, though school-day sleep offset advanced until no longer in high school, whereupon offset was later. Phase angle changes are described as an interaction of developmental changes in sleep regulation interacting with psychosocial factors (e.g., bedtime autonomy.

  18. Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.

    Directory of Open Access Journals (Sweden)

    Sabra M Abbott

    Full Text Available Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN, the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

  19. Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.

    Science.gov (United States)

    Abbott, Sabra M; Arnold, Jennifer M; Chang, Qing; Miao, Hai; Ota, Nobutoshi; Cecala, Christine; Gold, Paul E; Sweedler, Jonathan V; Gillette, Martha U

    2013-01-01

    Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN), the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

  20. The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

    Science.gov (United States)

    Ghaly, Maurice; Teplitz, Dale

    2004-10-01

    Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

  1. Short Sleep Makes Declarative Memories Vulnerable to Stress in Humans.

    Science.gov (United States)

    Cedernaes, Jonathan; Rångtell, Frida H; Axelsson, Emil K; Yeganeh, Adine; Vogel, Heike; Broman, Jan-Erik; Dickson, Suzanne L; Schiöth, Helgi B; Benedict, Christian

    2015-12-01

    This study sought to investigate the role of nocturnal sleep duration for the retrieval of oversleep consolidated memories, both prior to and after being cognitively stressed for ∼30 minutes the next morning. Participants learned object locations (declarative memory task comprising 15 card pairs) and a finger tapping sequence (procedural memory task comprising 5 digits) in the evening. After learning, participants either had a sleep opportunity of 8 hours (between ∼23:00 and ∼07:00, full sleep condition) or they could sleep between ∼03:00 and ∼07:00 (short sleep condition). Retrieval of both memory tasks was tested in the morning after each sleep condition, both before (∼08:30) and after being stressed (∼09:50). Sleep laboratory. 15 healthy young men. The analyses demonstrated that oversleep memory changes did not differ between sleep conditions. However, in their short sleep condition, following stress hallmarked by increased subjective stress feelings, the men were unable to maintain their pre-stress performance on the declarative memory task, whereas their performance on the procedural memory task remained unchanged. While men felt comparably subjectively stressed by the stress intervention, overall no differences between pre- and post-stress recalls were observed following a full night of sleep. The findings suggest that 8-h sleep duration, within the range recommended by the US National Sleep Foundation, may not only help consolidate newly learned procedural and declarative memories, but also ensure full access to both during periods of subjective stress. © 2015 Associated Professional Sleep Societies, LLC.

  2. Does selection for short sleep duration explain human vulnerability to Alzheimer’s disease?

    Science.gov (United States)

    Nesse, Randolph M; Finch, Caleb E; Nunn, Charles L

    2017-01-01

    Abstract Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer ’s disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin—a peptide hormone that increases markedly during sleep—is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD. PMID:28096295

  3. Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans.

    Science.gov (United States)

    Cedernaes, Jonathan; Fanelli, Flaminia; Fazzini, Alessia; Pagotto, Uberto; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Schiöth, Helgi B; Benedict, Christian

    2016-12-01

    Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30p.m.-7a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5h after awakening (vs. normal sleep, pexercise (+44%, pexercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (pexercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifcally regulated in cortical astrocytes following sleep deprivation in mice

    KAUST Repository

    Petit, Jean Marie

    2013-10-01

    Study Objectives: There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifcally in astrocytes following sleep deprivation. Astrocytes were purifed by fuorescence-activated cell sorting from transgenic mice expressing the green fuorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. Design: 6-hour instrumental sleep deprivation (TSD). Setting: Animal sleep research laboratory. Participants: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Interventions: Basal sleep recordings and sleep deprivation achieved using a modifed cage where animals were gently forced to move. Measurements and Results: Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, a-2-Na/K pump, Glt1, and Ldha mRNAs were signifcantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not signifcant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. Conclusions: This study shows that TSD induces the expression of genes associated with ANLS specifcally in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

  5. Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice.

    Science.gov (United States)

    Petit, Jean-Marie; Gyger, Joël; Burlet-Godinot, Sophie; Fiumelli, Hubert; Martin, Jean-Luc; Magistretti, Pierre J

    2013-10-01

    There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. 6-hour instrumental sleep deprivation (TSD). Animal sleep research laboratory. Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

  6. Human and rat gut microbiome composition is maintained following sleep restriction.

    Science.gov (United States)

    Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

    2017-02-21

    Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

  7. Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome.

    Science.gov (United States)

    Depner, Christopher M; Melanson, Edward L; McHill, Andrew W; Wright, Kenneth P

    2018-06-05

    Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.

  8. Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

    Science.gov (United States)

    Cui, Su-Ying; Li, Sheng-Jie; Cui, Xiang-Yu; Zhang, Xue-Qiong; Yu, Bin; Sheng, Zhao-Fu; Huang, Yuan-Li; Cao, Qing; Xu, Ya-Ping; Lin, Zhi-Ge; Yang, Guang; Song, Jin-Zhi; Ding, Hui; Wang, Zi-Jun; Zhang, Yong-He

    2016-02-01

    The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation. © 2015 International Society for Neurochemistry.

  9. Spontaneous hemodynamic oscillations during human sleep and sleep stage transitions characterized with near-infrared spectroscopy.

    Directory of Open Access Journals (Sweden)

    Tiina Näsi

    Full Text Available Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS and rapid-eye-movement sleep (REM. In particular, we concentrated on slow oscillations (3-150 mHz in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems.

  10. The mathematical structure of the human sleep-wake cycle

    CERN Document Server

    Strogatz, Steven H

    1986-01-01

    Over the past three years I have grown accustomed to the puzzled look which appears on people's faces when they hear that I am a mathematician who studies sleep. They wonder, but are usually too polite to ask, what does mathematics have to do with sleep? Instead they ask the questions that fascinate us all: Why do we have to sleep? How much sleep do we really need? Why do we dream? These questions usually spark a lively discussion leading to the exchange of anecdotes, last night's dreams, and other personal information. But they are questions about the func­ tion of sleep and, interesting as they are, I shall have little more to say about them here. The questions that have concerned me deal instead with the timing of sleep. For those of us on a regular schedule, questions of timing may seem vacuous. We go to bed at night and get up in the morning, going through a cycle of sleeping and waking every 24 hours. Yet to a large extent, the cycle is imposed by the world around us.

  11. Regulation of zebrafish sleep and arousal states: current and prospective approaches

    Directory of Open Access Journals (Sweden)

    Cindy N Chiu

    2013-04-01

    Full Text Available Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal’s well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish has emerged as a promising model system for sleep and arousal research. Here we review experimental evidence that the zebrafish, a diurnal vertebrate, exhibits fundamental behavioral and neurochemical characteristics of mammalian sleep and arousal. We also propose how specific advantages of the zebrafish can be harnessed to advance the field. These include tractable genetics to identify and manipulate molecular and cellular regulators of behavioral states, optical transparency to facilitate in vivo observation of neural structure and function, and amenability to high-throughput drug screens to discover novel therapies for neurological disorders.

  12. Active reward processing during human sleep: insights from sleep-related eating disorder

    Directory of Open Access Journals (Sweden)

    Lampros ePerogamvros

    2012-11-01

    Full Text Available In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED, a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity on reward-related questionnaires. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

  13. β-Amyloid accumulation in the human brain after one night of sleep deprivation.

    Science.gov (United States)

    Shokri-Kojori, Ehsan; Wang, Gene-Jack; Wiers, Corinde E; Demiral, Sukru B; Guo, Min; Kim, Sung Won; Lindgren, Elsa; Ramirez, Veronica; Zehra, Amna; Freeman, Clara; Miller, Gregg; Manza, Peter; Srivastava, Tansha; De Santi, Susan; Tomasi, Dardo; Benveniste, Helene; Volkow, Nora D

    2018-04-24

    The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18 F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep. Copyright © 2018 the Author(s). Published by PNAS.

  14. Discharge patterns of human genioglossus motor units during arousal from sleep.

    Science.gov (United States)

    Wilkinson, Vanessa; Malhotra, Atul; Nicholas, Christian L; Worsnop, Christopher; Jordan, Amy S; Butler, Jane E; Saboisky, Julian P; Gandevia, Simon C; White, David P; Trinder, John

    2010-03-01

    Single motor unit recordings of the human genioglossus muscle reveal motor units with a variety of discharge patterns. Integrated multiunit electromyographic recordings of genioglossus have demonstrated an abrupt increase in the muscle's activity at arousal from sleep. The aim of the present study was to determine the effect of arousal from sleep on the activity of individual motor units as a function of their particular discharge pattern. Genioglossus activity was measured using intramuscular fine-wire electrodes inserted via a percutaneous approach. Arousals from sleep were identified using the ASDA criterion and the genioglossus electromyogram recordings analyzed for single motor unit activity. Sleep research laboratory. Sleep and respiratory data were collected in 8 healthy subjects (6 men). 138 motor units were identified during prearousalarousal sleep: 25% inspiratory phasic, 33% inspiratory tonic, 4% expiratory phasic, 3% expiratory tonic, and 35% tonic. At arousal from sleep inspiratory phasic units significantly increased the proportion of a breath over which they were active, but did not appreciably increase their rate of firing. 80 new units were identified at arousals, 75% were inspiratory, many of which were active for only 1 or 2 breaths. 22% of units active before arousal, particularly expiratory and tonic units, stopped at the arousal. Increased genioglossus muscle activity at arousal from sleep is primarily due to recruitment of inspiratory phasic motor units. Further, activity within the genioglossus motoneuron pool is reorganized at arousal as, in addition to recruitment, approximately 20% of units active before arousals stopped firing.

  15. Sleep Deprivation in Humans, Immunodepression and Glutamine Supplementation

    National Research Council Canada - National Science Library

    Castell, Linda M; Gough, Elizabeth; Cardenas, Rebecca; Miller, James C

    2005-01-01

    This report results from a contract tasking University of Oxford as follows: The Grantee will investigate the immunological response of subjects to one night of sleep deprivation with respect to the following areas...

  16. Sleep Deprivation in Humans, Immunodepression and Glutamine Supplementation

    National Research Council Canada - National Science Library

    Castell, Linda M; Gough, Elizabeth; Cardenas, Rebecca; Miller, James C

    2005-01-01

    ... (I) Are the cytokines linked with eosinophils neutrophils and lymphocytes cell types which are known to be affected by sleep deprivation changed in terms of intracellular cytokine production? (2...

  17. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

    Directory of Open Access Journals (Sweden)

    Gloria E Hoffman

    Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

  18. The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans.

    Science.gov (United States)

    Iannacone, Michael J; Beets, Isabel; Lopes, Lindsey E; Churgin, Matthew A; Fang-Yen, Christopher; Nelson, Matthew D; Schoofs, Liliane; Raizen, David M

    2017-01-17

    In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans , stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1 , which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo , is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.

  19. Functional structure of spontaneous sleep slow oscillation activity in humans.

    Directory of Open Access Journals (Sweden)

    Danilo Menicucci

    Full Text Available BACKGROUND: During non-rapid eye movement (NREM sleep synchronous neural oscillations between neural silence (down state and neural activity (up state occur. Sleep Slow Oscillations (SSOs events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL FINDINGS: We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. CONCLUSIONS/SIGNIFICANCE: This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.

  20. Memory traces of long-range coordinated oscillations in the sleeping human brain.

    Science.gov (United States)

    Piantoni, Giovanni; Van Der Werf, Ysbrand D; Jensen, Ole; Van Someren, Eus J W

    2015-01-01

    Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. © 2014 Wiley Periodicals, Inc.

  1. Sleep Phase Delay in Cystic Fibrosis: A Potential New Manifestation of Cystic Fibrosis Transmembrane Regulator Dysfunction.

    Science.gov (United States)

    Jensen, Judy L; Jones, Christopher R; Kartsonaki, Christiana; Packer, Kristyn A; Adler, Frederick R; Liou, Theodore G

    2017-08-01

    Cystic fibrosis (CF) transmembrane regulator (CFTR) protein dysfunction causes CF. Improving survival allows detection of increasingly subtle disease manifestations. CFTR dysfunction in the central nervous system (CNS) may disturb circadian rhythm and thus sleep phase. We studied sleep in adults to better understand potential CNS CFTR dysfunction. We recruited participants from April 2012 through April 2015 and administered the Munich Chronotype Questionnaire (MCTQ). We compared free-day sleep measurements between CF and non-CF participants and investigated associations with CF survival predictors. We recruited 23 female and 22 male adults with CF aged 18 to 46 years and 26 female and 22 male volunteers aged 18 to 45 years. Compared with volunteers without CF, patients with CF had delayed sleep onset (0.612 h; P = .015), midsleep (1.11 h; P < .001), and wake (1.15 h; P < .001) times and prolonged sleep latency (7.21 min; P = .05) and duration (0.489 h; P = .05). Every hour delay in sleep onset was associated with shorter sleep duration by 0.29 h in patients with CF and 0.75 h in subjects without CF (P = .007) and longer sleep latency by 7.51 min in patients with CF and 1.6 min in volunteers without CF (P = .035). Among patients with CF, FEV 1 % predicted, prior acute pulmonary exacerbations, and weight were independent of all free-day sleep measurements. CF in adults is associated with marked delays in sleep phase consistent with circadian rhythm phase delays. Independence from disease characteristics predictive of survival suggests that sleep phase delay is a primary manifestation of CFTR dysfunction in the CNS. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  2. Minimal olfactory perception during sleep: why odor alarms will not work for humans.

    Science.gov (United States)

    Carskadon, Mary A; Herz, Rachel S

    2004-05-01

    To examine olfactory arousal threshold during sleep in comparison to an auditory tone. On night 1, participants rated odor intensity when awake and experienced olfactory stimuli during stage 1 sleep. Night 2 involved stage 2, stage 4, and rapid-eye-movement (REM) sleep trials using the "staircase" threshold-detection method. Electroencephalogram, electrooculogram, electromyogram, electrocardiogram, and respiration were recorded along with behavioral response. An 800-Hz tone was given on trials when odors failed to arouse. Participants slept in individual rooms. Stimulus-delivery systems were operated from a separate room, where an experimenter observed physiologic recordings and behavioral responses. Three healthy men and 3 women aged 20 to 25 years (mean, 22 years). Two odorants, peppermint and pyridine, at 4 concentrations were presented through nasal cannulas using an air-dilution olfactometer. Tones were played over a speaker. Behavioral (button press and oral) responses, electroencephalographic activation, and changes in breathing and heart rate were assessed. Participants responded to odors on 92% of stage 1 sleep trials. Peppermint was ineffective in stages 2, 4, and REM sleep. Pyridine produced behavioral threshold on 45% of stage 2 trials, none in stage 4, and one third of REM sleep trials. Tones were effective on at least 75% of trials. Heart rate increased significantly only following behavioral responses to odors or tones across sleep stages. The data indicate that human olfaction is not reliably capable of alerting a sleeper.

  3. Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

    Directory of Open Access Journals (Sweden)

    Yuki Motomura

    2017-06-01

    Full Text Available Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD. Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC, and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life.

  4. The effect of exogenous cortisol during sleep on the behavioral and neural correlates of emotional memory consolidation in humans.

    Science.gov (United States)

    van Marle, Hein J F; Hermans, Erno J; Qin, Shaozheng; Overeem, Sebastiaan; Fernández, Guillén

    2013-09-01

    A host of animal work demonstrates that the retention benefit for emotionally aversive over neutral memories is regulated by glucocorticoid action during memory consolidation. Particularly, glucocorticoids may affect systems-level processes that promote the gradual reorganization of emotional memory traces. These effects remain largely uninvestigated in humans. Therefore, in this functional magnetic resonance imaging study we administered hydrocortisone during a polysomnographically monitored night of sleep directly after healthy volunteers studied negative and neutral pictures in a double-blind, placebo-controlled, between-subjects design. The following evening memory consolidation was probed during a recognition memory test in the MR scanner by assessing the difference in brain activity associated with memory for the consolidated items studied before sleep and new, unconsolidated items studied shortly before test (remote vs. recent memory paradigm). Hydrocortisone administration resulted in elevated cortisol levels throughout the experimental night with no group difference at recent encoding or test. Behaviorally, we showed that cortisol enhanced the difference between emotional and neutral consolidated memory, effectively prioritizing emotional memory consolidation. On a neural level, we found that cortisol reduced amygdala reactivity related to the retrieval of these same consolidated, negative items. These findings show that cortisol administration during first post-encoding sleep had a twofold effect on the first 24h of emotional memory consolidation. While cortisol prioritized recognition memory for emotional items, it reduced reactivation of the neural circuitry underlying emotional responsiveness during retrieval. These findings fit recent theories on emotional depotentiation following consolidation during sleep, although future research should establish the sleep-dependence of this effect. Moreover, our data may shed light on mechanisms underlying

  5. Sleep-Dependent Modulation of Metabolic Rate in Drosophila.

    Science.gov (United States)

    Stahl, Bethany A; Slocumb, Melissa E; Chaitin, Hersh; DiAngelo, Justin R; Keene, Alex C

    2017-08-01

    Dysregulation of sleep is associated with metabolic diseases, and metabolic rate (MR) is acutely regulated by sleep-wake behavior. In humans and rodent models, sleep loss is associated with obesity, reduced metabolic rate, and negative energy balance, yet little is known about the neural mechanisms governing interactions between sleep and metabolism. We have developed a system to simultaneously measure sleep and MR in individual Drosophila, allowing for interrogation of neural systems governing interactions between sleep and metabolic rate. Like mammals, MR in flies is reduced during sleep and increased during sleep deprivation suggesting sleep-dependent regulation of MR is conserved across phyla. The reduction of MR during sleep is not simply a consequence of inactivity because MR is reduced ~30 minutes following the onset of sleep, raising the possibility that CO2 production provides a metric to distinguish different sleep states in the fruit fly. To examine the relationship between sleep and metabolism, we determined basal and sleep-dependent changes in MR is reduced in starved flies, suggesting that starvation inhibits normal sleep-associated effects on metabolic rate. Further, translin mutant flies that fail to suppress sleep during starvation demonstrate a lower basal metabolic rate, but this rate was further reduced in response to starvation, revealing that regulation of starvation-induced changes in MR and sleep duration are genetically distinct. Therefore, this system provides the unique ability to simultaneously measure sleep and oxidative metabolism, providing novel insight into the physiological changes associated with sleep and wakefulness in the fruit fly. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  6. Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

    Science.gov (United States)

    Uschakov, Aaron; Grivel, Jeremy; Cvetkovic-Lopes, Vesna; Bayer, Laurence; Bernheim, Laurent; Jones, Barbara E; Mühlethaler, Michel; Serafin, Mauro

    2011-02-08

    We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α(2)-adrenergic receptor (α(2)-AR) agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC), it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations of clonidine up to a thousand times (100 µM) higher than those effective in SDC (100 nM), were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B) agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2)-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2)-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2)-ARs associated with GIRK channels is normally down-regulated (or desensitized) in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

  7. Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

    Directory of Open Access Journals (Sweden)

    Aaron Uschakov

    Full Text Available We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA of hypocretin/orexin (hcrt/orx neurons was changed to an inhibition following sleep deprivation (SD. Here we describe that in control condition (CC, i.e. following 2 hours of natural sleep in the morning, the α(2-adrenergic receptor (α(2-AR agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC, it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK channels. Since concentrations of clonidine up to a thousand times (100 µM higher than those effective in SDC (100 nM, were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2-ARs associated with GIRK channels is normally down-regulated (or desensitized in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

  8. Sleep, Torpor and Memory Impairment

    Science.gov (United States)

    Palchykova, S.; Tobler, I.

    It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species during recovery after prolonged wakefulness or sleep deprivation (SD). When hamsters are totally or partially sleep deprived immediately after emerging from torpor, an additional increase in SWA can be induced. It has been therefore postulated, that these slow- waves are homeostatically regulated, as predicted by the two-process model of sleep regulation, and that during daily torpor a sleep deficit is accumulated as it is during prolonged waking. The predominance of SWA in the frontal EEG observed both after SD and daily torpor provides further evidence for the similarity of these conditions. It has been shown in several animal and human studies that sleep can enhance memory consolidation, and that SD leads to memory impairment. Preliminary data obtained in the Djungarian hamster showed that both SD and daily torpor result in object recognition deficits. Thus, animals subjected to SD immediately after learning, or if they underwent an episode of daily torpor between learning and retention, displayed impaired recognition memory for complex object scenes. The investigation of daily torpor can reveal mechanisms that could have important implications for hypometabolic state induction in other mammalian species, including humans.

  9. Sleep transitions in hypocretin-deficient narcolepsy.

    Science.gov (United States)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-08-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.

  10. Sleep Transitions in Hypocretin-Deficient Narcolepsy

    DEFF Research Database (Denmark)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-01-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain......'s sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype....

  11. Role of N-Arachidonoyl-Serotonin (AA-5-HT in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

    Directory of Open Access Journals (Sweden)

    Eric Murillo-Rodríguez

    2017-05-01

    Full Text Available The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA and 2-arachidonoylglycerol (2-AG], receptors (CB1 and CB2, enzymes such as [fatty acid amide hydrolase (FAHH and monoacylglycerol lipase (MAGL], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1, N-arachidonoyl-serotonin (AA-5-HT in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p. injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W and increased slow wave sleep (SWS as well as rapid eye movement sleep (REMS. Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA, norepinephrine (NE, epinephrine (EP, serotonin (5-HT whereas the levels of adenosine (AD were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD or modafinil (MOD during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD. The

  12. Serum Amyloid A Production Is Triggered by Sleep Deprivation in Mice and Humans: Is That the Link between Sleep Loss and Associated Comorbidities?

    Science.gov (United States)

    de Oliveira, Edson M.; Visniauskas, Bruna; Tufik, Sergio; Andersen, Monica L.; Chagas, Jair R.; Campa, Ana

    2017-01-01

    Serum amyloid A (SAA) was recently associated with metabolic endotoxemia, obesity and insulin resistance. Concurrently, insufficient sleep adversely affects metabolic health and is an independent predisposing factor for obesity and insulin resistance. In this study we investigated whether sleep loss modulates SAA production. The serum SAA concentration increased in C57BL/6 mice subjected to sleep restriction (SR) for 15 days or to paradoxical sleep deprivation (PSD) for 72 h. Sleep restriction also induced the upregulation of Saa1.1/Saa2.1 mRNA levels in the liver and Saa3 mRNA levels in adipose tissue. SAA levels returned to the basal range after 24 h in paradoxical sleep rebound (PSR). Metabolic endotoxemia was also a finding in SR. Increased plasma levels of SAA were also observed in healthy human volunteers subjected to two nights of total sleep deprivation (Total SD), returning to basal levels after one night of recovery. The observed increase in SAA levels may be part of the initial biochemical alterations caused by sleep deprivation, with potential to drive deleterious conditions such as metabolic endotoxemia and weight gain. PMID:28335560

  13. Analysis of meiosis regulators in human gonads

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John E; Jensen, Martin Blomberg

    2012-01-01

    The mitosis-meiosis switch is a key event in the differentiation of germ cells. In humans, meiosis is initiated in fetal ovaries, whereas in testes meiotic entry is inhibited until puberty. The purpose of this study was to examine the expression pattern of meiosis regulators in human gonads...... with their role in initiation and progression of meiosis. The putative meiosis inhibitors, CYP26B1 and NANOS2, were primarily expressed in Leydig cells and spermatocytes, respectively. In conclusion, the expression pattern of the investigated meiotic regulators is largely conserved in the human gonads compared...... with rodents, but with some minor differences, such as a stable expression of CYP26B1 in human fetal ovaries. The sexually dimorphic expression pattern of DMRT1 indicates a similar role in the mitosis-meiosis switch in human gonads as previously demonstrated in mice. The biological importance of the changes...

  14. Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring.

    Directory of Open Access Journals (Sweden)

    Jun Lv

    Full Text Available Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG and functional magnetic resonance imaging (fMRI time series.In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep.In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.

  15. Filtering the reality: functional dissociation of lateral and medial pain systems during sleep in humans.

    Science.gov (United States)

    Bastuji, Hélène; Mazza, Stéphanie; Perchet, Caroline; Frot, Maud; Mauguière, François; Magnin, Michel; Garcia-Larrea, Luis

    2012-11-01

    Behavioral reactions to sensory stimuli during sleep are scarce despite preservation of sizeable cortical responses. To further understand such dissociation, we recorded intracortical field potentials to painful laser pulses in humans during waking and all-night sleep. Recordings were obtained from the three cortical structures receiving 95% of the spinothalamic cortical input in primates, namely the parietal operculum, posterior insula, and mid-anterior cingulate cortex. The dynamics of responses during sleep differed among cortical sites. In sleep Stage 2, evoked potential amplitudes were similarly attenuated relative to waking in all three cortical regions. During paradoxical, or rapid eye movements (REM), sleep, opercular and insular potentials remained stable in comparison with Stage 2, whereas the responses from mid-anterior cingulate abated drastically, and decreasing below background noise in half of the subjects. Thus, while the lateral operculo-insular system subserving sensory analysis of somatic stimuli remained active during paradoxical-REM sleep, mid-anterior cingulate processes related to orienting and avoidance behavior were suppressed. Dissociation between sensory and orienting-motor networks might explain why nociceptive stimuli can be either neglected or incorporated into dreams without awakening the subject. Copyright © 2011 Wiley Periodicals, Inc.

  16. Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.

    Science.gov (United States)

    McHill, Andrew W; Hull, Joseph T; Wang, Wei; Czeisler, Charles A; Klerman, Elizabeth B

    2018-05-21

    Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.

  17. Nap sleep spindle correlates of intelligence.

    Science.gov (United States)

    Ujma, Péter P; Bódizs, Róbert; Gombos, Ferenc; Stintzing, Johannes; Konrad, Boris N; Genzel, Lisa; Steiger, Axel; Dresler, Martin

    2015-11-26

    Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fluid intelligence scores, however more recently it has been shown that only few sleep spindle measures correlate with intelligence in females, and none in males. Sleep spindle regulation underlies a circadian rhythm, however the association between spindles and intelligence has not been investigated in daytime nap sleep so far. In a sample of 86 healthy male human subjects, we investigated the correlation between fluid intelligence and sleep spindle parameters in an afternoon nap of 100 minutes. Mean sleep spindle length, amplitude and density were computed for each subject and for each derivation for both slow and fast spindles. A positive association was found between intelligence and slow spindle duration, but not any other sleep spindle parameter. As a positive correlation between intelligence and slow sleep spindle duration in full-night polysomnography has only been reported in females but not males, our results suggest that the association between intelligence and sleep spindles is more complex than previously assumed.

  18. Neurobiological linkage between stress and sleep

    Science.gov (United States)

    Sanford, Larry D.; Wellman, Laurie L.

    2012-10-01

    Stress can have a significant negative impact on health and stress-induced alterations in sleep are implicated in both human sleep disorders and in psychiatric disorders in which sleep is affected. We have demonstrated that the amygdala, a region critical for regulating emotion, is a key modulator of sleep. Our current research is focused on understanding how the amygdala and stressful emotion affect sleep and on the role sleep plays in recovery from stress. We have implemented animal models to examine the how stress and stress-related memories impact sleep. Experiencing uncontrollable stress and reminders of uncontrollable stress can produce significant reductions in sleep, in particular rapid eye movement sleep. We are using these models to explore the neurobiology linking stress-related emotion and sleep. This research is relevant for sleep disorders such as insomnia and into mental disorders in which sleep is affected such as post-traumatic stress disorder (PTSD), which is typically characterized by a prominent sleep disturbance in the aftermath of exposure to a psychologically traumatic event.

  19. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations.

    Science.gov (United States)

    Mateika, Jason H; Syed, Ziauddin

    2013-09-15

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.

  20. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans; present knowledge and future investigations

    Science.gov (United States)

    Mateika, Jason H.; Syed, Ziauddin

    2013-01-01

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. PMID:23587570

  1. Individual differences in the effects of mobile phone exposure on human sleep: rethinking the problem.

    Science.gov (United States)

    Loughran, Sarah P; McKenzie, Raymond J; Jackson, Melinda L; Howard, Mark E; Croft, Rodney J

    2012-01-01

    Mobile phone exposure-related effects on the human electroencephalogram (EEG) have been shown during both waking and sleep states, albeit with slight differences in the frequency affected. This discrepancy, combined with studies that failed to find effects, has led many to conclude that no consistent effects exist. We hypothesised that these differences might partly be due to individual variability in response, and that mobile phone emissions may in fact have large but differential effects on human brain activity. Twenty volunteers from our previous study underwent an adaptation night followed by two experimental nights in which they were randomly exposed to two conditions (Active and Sham), followed by a full-night sleep episode. The EEG spectral power was increased in the sleep spindle frequency range in the first 30 min of non-rapid eye movement (non-REM) sleep following Active exposure. This increase was more prominent in the participants that showed an increase in the original study. These results confirm previous findings of mobile phone-like emissions affecting the EEG during non-REM sleep. Importantly, this low-level effect was also shown to be sensitive to individual variability. Furthermore, this indicates that previous negative results are not strong evidence for a lack of an effect and, given the far-reaching implications of mobile phone research, we may need to rethink the interpretation of results and the manner in which research is conducted in this field. Copyright © 2011 Wiley Periodicals, Inc.

  2. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  3. Diagnostic value of sleep stage dissociation as visualized on a 2-dimensional sleep state space in human narcolepsy

    DEFF Research Database (Denmark)

    Olsen, Anders Vinther; Stephansen, Jens; Leary, Eileen B.

    2017-01-01

    Type 1 narcolepsy (NT1) is characterized by symptoms believed to represent Rapid Eye Movement (REM) sleep stage dissociations, occurrences where features of wake and REM sleep are intermingled, resulting in a mixed state. We hypothesized that sleep stage dissociations can be objectively detected...... through the analysis of nocturnal Polysomnography (PSG) data, and that those affecting REM sleep can be used as a diagnostic feature for narcolepsy. A Linear Discriminant Analysis (LDA) model using 38 features extracted from EOG, EMG and EEG was used in control subjects to select features differentiating...... wake, stage N1, N2, N3 and REM sleep. Sleep stage differentiation was next represented in a 2D projection. Features characteristic of sleep stage differences were estimated from the residual sleep stage probability in the 2D space. Using this model we evaluated PSG data from NT1 and non...

  4. Sleep-deprivation effect on human performance: a meta-analysis approach

    Energy Technology Data Exchange (ETDEWEB)

    Candice D. Griffith; Candice D. Griffith; Sankaran Mahadevan

    2006-05-01

    Human fatigue is hard to define since there is no direct measure of fatigue, much like stress. Instead fatigue must be inferred from measures that are affected by fatigue. One such measurable output affected by fatigue is reaction time. In this study the relationship of reaction time to sleep deprivation is studied. These variables were selected because reaction time and hours of sleep deprivation are straightforward characteristics of fatigue to begin the investigation of fatigue effects on performance. Meta-analysis, a widely used procedure in medical and psychological studies, is applied to the variety of fatigue literature collected from various fields in this study. Meta-analysis establishes a procedure for coding and analyzing information from various studies to compute an effect size. In this research the effect size reported is the difference between standardized means, and is found to be -0.6341, implying a strong relationship between sleep deprivation and performance degradation.

  5. High-frequency oscillations in human and monkey neocortex during the wake-sleep cycle.

    Science.gov (United States)

    Le Van Quyen, Michel; Muller, Lyle E; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G; Dehghani, Nima; Destexhe, Alain

    2016-08-16

    Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake-sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS.

  6. High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle

    Science.gov (United States)

    Le Van Quyen, Michel; Muller, Lyle E.; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G.; Dehghani, Nima; Destexhe, Alain

    2016-01-01

    Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake–sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS. PMID:27482084

  7. Human reliability under sleep deprivation: Derivation of performance shaping factor multipliers from empirical data

    International Nuclear Information System (INIS)

    Griffith, Candice D.; Mahadevan, Sankaran

    2015-01-01

    This paper develops a probabilistic approach that could use empirical data to derive values of performance shaping factor (PSF) multipliers for use in quantitative human reliability analysis (HRA). The proposed approach is illustrated with data on sleep deprivation effects on performance. A review of existing HRA methods reveals that sleep deprivation is not explicitly included at present, and expert opinion is frequently used to inform HRA model multipliers. In this paper, quantitative data from empirical studies regarding the effect of continuous hours of wakefulness on performance measures (reaction time, accuracy, and number of lapses) are used to develop a method to derive PSF multiplier values for sleep deprivation, in the context of the SPAR-H model. Data is extracted from the identified studies according to the meta-analysis research synthesis method and used to investigate performance trends and error probabilities. The error probabilities in test and control conditions are compared, and the resulting probability ratios are suggested for use in informing the selection of PSF multipliers in HRA methods. Although illustrated for sleep deprivation, the proposed methodology is general, and can be applied to other performance shaping factors. - Highlights: • Method proposed to derive performance shaping factor multipliers from empirical data. • Studies reporting the effect of sleep deprivation on performance are analyzed. • Test data using psychomotor vigilance tasks are analyzed. • Error probability multipliers computed for reaction time, lapses, and accuracy measures.

  8. Role of norepinephrine in the regulation of rapid eye movement sleep

    Indian Academy of Sciences (India)

    Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified ...

  9. Human exposure, health hazards, and environmental regulations

    International Nuclear Information System (INIS)

    Steinemann, Anne

    2004-01-01

    United States environmental regulations, intended to protect human health, generally fail to address major sources of pollutants that endanger human health. These sources are surprisingly close to us and within our control, such as consumer products and building materials that we use within our homes, workplaces, schools, and other indoor environments. Even though these indoor sources account for nearly 90% of our pollutant exposure, they are virtually unregulated by existing laws. Even pollutant levels found in typical homes, if found outdoors, would often violate federal environmental standards. This article examines the importance of human exposure as a way to understand and reduce effects of pollutants on human health. Results from exposure studies challenge traditional thinking about pollutant hazards, and reveal deficiencies in our patchwork of laws. And results from epidemiological studies, showing increases in exposure-related diseases, underscore the need for new protections. Because we cannot rely solely on regulations to protect us, and because health effects from exposures can develop insidiously, greater efforts are needed to reduce and prevent significant exposures before they occur. Recommendations include the development and use of safer alternatives to common products, public education on ways to reduce exposure, systematic monitoring of human exposure to pollutants, and a precautionary approach in decision-making

  10. Sleep quality, posttraumatic stress, depression, and human errors in train drivers: a population-based nationwide study in South Korea.

    Science.gov (United States)

    Jeon, Hong Jin; Kim, Ji-Hae; Kim, Bin-Na; Park, Seung Jin; Fava, Maurizio; Mischoulon, David; Kang, Eun-Ho; Roh, Sungwon; Lee, Dongsoo

    2014-12-01

    Human error is defined as an unintended error that is attributable to humans rather than machines, and that is important to avoid to prevent accidents. We aimed to investigate the association between sleep quality and human errors among train drivers. Cross-sectional. Population-based. A sample of 5,480 subjects who were actively working as train drivers were recruited in South Korea. The participants were 4,634 drivers who completed all questionnaires (response rate 84.6%). None. The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Impact of Event Scale-Revised (IES-R), the State-Trait Anxiety Inventory (STAI), and the Korean Occupational Stress Scale (KOSS). Of 4,634 train drivers, 349 (7.5%) showed more than one human error per 5 y. Human errors were associated with poor sleep quality, higher PSQI total scores, short sleep duration at night, and longer sleep latency. Among train drivers with poor sleep quality, those who experienced severe posttraumatic stress showed a significantly higher number of human errors than those without. Multiple logistic regression analysis showed that human errors were significantly associated with poor sleep quality and posttraumatic stress, whereas there were no significant associations with depression, trait and state anxiety, and work stress after adjusting for age, sex, education years, marital status, and career duration. Poor sleep quality was found to be associated with more human errors in train drivers, especially in those who experienced severe posttraumatic stress. © 2014 Associated Professional Sleep Societies, LLC.

  11. Characteristics of rapid eye movement sleep behavior disorder in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Frandsen, Rune Asger Vestergaard; Knudsen, Stine

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with Parkinsonian disorders, but is also reported in narcolepsy. Most patients...... of hypocretin deficiency. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Moreover, it is likely that hypocretin deficiency independently predicts periodic limb movements in REM and NREM sleep, probably via involvement...... of the dopaminergic system. This supports the hypothesis that an impaired hypocretin system causes general instability of motor regulation during wakefulness, REM and NREM sleep in human narcolepsy. We propose that hypocretin neurons are centrally involved in motor tone control during wakefulness and sleep in humans...

  12. Naive scoring of human sleep based on a hidden Markov model of the electroencephalogram.

    Science.gov (United States)

    Yaghouby, Farid; Modur, Pradeep; Sunderam, Sridhar

    2014-01-01

    Clinical sleep scoring involves tedious visual review of overnight polysomnograms by a human expert. Many attempts have been made to automate the process by training computer algorithms such as support vector machines and hidden Markov models (HMMs) to replicate human scoring. Such supervised classifiers are typically trained on scored data and then validated on scored out-of-sample data. Here we describe a methodology based on HMMs for scoring an overnight sleep recording without the benefit of a trained initial model. The number of states in the data is not known a priori and is optimized using a Bayes information criterion. When tested on a 22-subject database, this unsupervised classifier agreed well with human scores (mean of Cohen's kappa > 0.7). The HMM also outperformed other unsupervised classifiers (Gaussian mixture models, k-means, and linkage trees), that are capable of naive classification but do not model dynamics, by a significant margin (p < 0.05).

  13. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  14. Effects of train noise and vibration on human heart rate during sleep: an experimental study.

    Science.gov (United States)

    Croy, Ilona; Smith, Michael G; Waye, Kerstin Persson

    2013-05-28

    Transportation of goods on railways is increasing and the majority of the increased numbers of freight trains run during the night. Transportation noise has adverse effects on sleep structure, affects the heart rate (HR) during sleep and may be linked to cardiovascular disease. Freight trains also generate vibration and little is known regarding the impact of vibration on human sleep. A laboratory study was conducted to examine how a realistic nocturnal railway traffic scenario influences HR during sleep. Case-control. Healthy participants. 24 healthy volunteers (11 men, 13 women, 19-28 years) spent six consecutive nights in the sleep laboratory. All participants slept during one habituation night, one control and four experimental nights in which train noise and vibration were reproduced. In the experimental nights, 20 or 36 trains with low-vibration or high-vibration characteristics were presented. Polysomnographical data and ECG were recorded. The train exposure led to a significant change of HR within 1 min of exposure onset (p=0.002), characterised by an initial and a delayed increase of HR. The high-vibration condition provoked an average increase of at least 3 bpm per train in 79% of the participants. Cardiac responses were in general higher in the high-vibration condition than in the low-vibration condition (p=0.006). No significant effect of noise sensitivity and gender was revealed, although there was a tendency for men to exhibit stronger HR acceleration than women. Freight trains provoke HR accelerations during sleep, and the vibration characteristics of the trains are of special importance. In the long term, this may affect cardiovascular functioning of persons living close to railways.

  15. Sleep and Self-Regulation from Birth to 7 Years: A Retrospective Study of Children with and Without Attention-Deficit Hyperactivity Disorder at 8 to 9 Years.

    Science.gov (United States)

    Williams, Kate E; Sciberras, Emma

    2016-06-01

    To examine mean level differences and longitudinal and reciprocal relations among behavioral sleep problems, emotional dysregulation, and attentional regulation across early childhood for children with and without attention-deficit hyperactivity disorder (ADHD) at 8 to 9 years. This study used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC)-Infant Cohort (n = 4,109 analyzed). Children with and without ADHD were identified at age 8 to 9 years via parent report of ADHD diagnosis and the 5-item Inattention-Hyperactivity subscale from the Strengths and Difficulties Questionnaire. Maternal report of child sleep problems and self-regulation was collected at 0 to 1, 2 to 3, 4 to 5, and 6 to 7 years of age. Analysis of variance was used to compare mean level differences in sleep problems and emotional and attentional regulation by ADHD group. Longitudinal structural equation modeling examined the relations among sleep and self-regulation across time in children with and without ADHD. Children with ADHD had persistently elevated levels of sleep problems (from infancy) and emotional and attentional dysregulation compared to controls (from 2 to 3 years of age). Sleep problems, emotional dysregulation, and attentional regulation were stable over time for both groups. Sleep problems were associated with greater emotional dysregulation 2 years later from 2 to 3 years of age for both groups, which in turn was associated with poorer attentional regulation. There was no direct relationship between sleep problems and later attentional regulation. Sleep problems in children with and without ADHD are associated with emotional dysregulation, which in turn contributes to poorer attentional functioning. This study highlights the importance of assessing and managing sleep problems in young children.

  16. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  17. Concentrating carbohydrates before sleep improves feeding regulation and metabolic and inflammatory parameters in mice.

    Science.gov (United States)

    Sofer, Sigal; Eliraz, Abraham; Madar, Zecharia; Froy, Oren

    2015-10-15

    New evidance highlights the importance of food timing. Recently, we showed that a low-calorie diet with carbohydrates eaten mostly at dinner changed diurnal hormone secretion and led to greater weight loss and improved metabolic status in obese people. Herein, we set out to test whether concentrated-carbohydrates diet (CCD), in which carbohydrates are fed only before sleep, leads to an improved metabolic status in mouse hypothalamus and peripheral tissues. Diet-induced obese mice were given concentrated or distributed carbohydrate diet for 6 weeks. Obese mice fed CCD ate 8.3% less, were 9.3% leaner and had 39.7% less fat mass. Leptin, ghrelin and adiponectin displayed altered secretion. In addition, these mice exhibited an improved biochemical and inflammatory status. In the hypothalamus, anorexigenic signals were up-regulated and orexigenic signals were down-regulated. In peripheral tissues, CCD promoted adiponectin signaling, repressed gluconeogenesis, enhanced lipid oxidation and lowered inflammation, thus ameliorating the major risk factors of obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Genetic factors in human sleep disorders with special reference to Norrie disease, Prader-Willi syndrome and Moebius syndrome.

    Science.gov (United States)

    Parkes, J D

    1999-06-01

    Sleep-wake problems are common in specific inborn errors of metabolism and structure of the central nervous system. Psychological factors, behavioural difficulties, metabolic disturbances, and widespread rather than focal damage to the nervous system are present in many of these diseases and all influence the sleep-wake cycle. However, a number of conditions cause relatively focal damage to the neuroanatomical substrate of sleeping and waking. These include fatal familial insomnia, with involvement of the prion protein gene on chromosome 20, Norrie disease, the Prader-Willi syndrome and the Moebius syndrome. The last three important conditions, although rare, are considered in detail in this review. They result in sensory deprivation, hypothalamic and mid-brain damage, and involve the X-chromosome, chromosome 15, and chromosome 13, respectively. These conditions cause a wide variety of sleep disturbance, including parasomnias, daytime sleepiness, and a condition like cataplexy. The place of the relevant gene products in normal sleep regulation needs further exploration.

  19. Sleep Sleeping Patch

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The Sleep Sleeping Patch is a new kind of external patch based on modern sleep medicine research achievements, which uses the internationally advanced transdermal therapeutic system (TTS). The Sleep Sleeping Patch transmits natural sleep inducers such as peppermint and liquorice extracts and melatonin through the skin to induce sleep. Clinical research proves that the Sleep Sleeping Patch can effectively improve insomnia and the quality of sleep. Highly effective: With the modern TTS therapy,

  20. The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions

    Directory of Open Access Journals (Sweden)

    Ayumu eInutsuka

    2013-03-01

    Full Text Available The hypothalamus monitors body homeostasis and regulates various behaviors such as feeding, thermogenesis, and sleeping. Orexins (also known as hypocretins were identified as endogenous ligands for two orphan G-protein-coupled receptors in the lateral hypothalamic area. They were initially recognized as regulators of feeding behavior, but they are mainly regarded as key modulators of the sleep/wakefulness cycle. Orexins activate orexin neurons, monoaminergic and cholinergic neurons in the hypothalamus/brainstem regions, to maintain a long, consolidated awake period. Anatomical studies of neural projections from/to orexin neurons and phenotypic characterization of transgenic mice revealed various roles for orexin neurons in the coordination of emotion, energy homeostasis, reward system, and arousal. For example, orexin neurons are regulated by peripheral metabolic cues, including ghrelin, leptin, and glucose concentration. This suggests that they may provide a link between energy homeostasis and arousal states. A link between the limbic system and orexin neurons might be important for increasing vigilance during emotional stimuli. Orexins are also involved in reward systems and the mechanisms of drug addiction. These findings suggest that orexin neurons sense the outer and inner environment of the body and maintain the proper wakefulness level of animals for survival. This review discusses the mechanism by which orexins maintain sleep/wakefulness states and how this mechanism relates to other systems that regulate emotion, reward, and energy homeostasis.

  1. Functional role of diverse changes in sympathetic nerve activity in regulating arterial pressure during REM sleep.

    Science.gov (United States)

    Yoshimoto, Misa; Yoshida, Ikue; Miki, Kenju

    2011-08-01

    This study aimed to investigate whether REM sleep evoked diverse changes in sympathetic outflows and, if so, to elucidate why REM sleep evokes diverse changes in sympathetic outflows. Male Wistar rats were chronically implanted with electrodes to measure renal (RSNA) and lumbar sympathetic nerve activity (LSNA), electroencephalogram, electromyogram, and electrocardiogram, and catheters to measure systemic arterial and central venous pressure; these parameters were measured simultaneously and continuously during the sleep-awake cycle in the same rat. REM sleep resulted in a step reduction in RNSA by 36.1% ± 2.7% (P sleep. In contrast to REM sleep, RSNA, LSNA, systemic arterial pressure, and heart rate increased in a unidirectional manner associated with increases in physical activity levels in the order from NREM sleep, quiet awake, moving, and grooming state. Thus, the relationship between RSNA vs. LSNA and systemic arterial pressure vs. heart rate observed during REM sleep was dissociated compared with that obtained during the other behavioral states. It is suggested that the diverse changes in sympathetic outflows during REM sleep may be needed to increase systemic arterial pressure by balancing vascular resistance between muscles and vegetative organs without depending on the heart.

  2. 76 FR 7695 - Iranian Human Rights Abuses Sanctions Regulations

    Science.gov (United States)

    2011-02-11

    ... DEPARTMENT OF THE TREASURY Office of Foreign Assets Control 31 CFR Part 562 Iranian Human Rights... Iranian Human Rights Abuses Sanctions Regulations, 31 CFR part 562 (the ``Regulations''), to implement E.O...--IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS Subpart A--Relation of This Part to Other Laws and...

  3. TXNIP regulates peripheral glucose metabolism in humans

    DEFF Research Database (Denmark)

    Parikh, Hemang; Carlsson, Emma; Chutkow, William A

    2007-01-01

    combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated...... expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin......-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM....

  4. CHALLENGES IN MAINTAINING EMOTION REGULATION IN A SLEEP AND ENERGY DEPRIVED STATE INDUCED BY THE 4800KM ULTRA-ENDURANCE BICYCLE RACE; THE RACE ACROSS AMERICA (RAAM

    Directory of Open Access Journals (Sweden)

    Ian M. Lahart

    2013-09-01

    Full Text Available Multiday ultra-endurance races present athletes with a significant number of physiological and psychological challenges. We examined emotions, the perceived functionality (optimal-dysfunctional of emotions, strategies to regulate emotions, sleep quality, and energy intake-expenditure in a four-man team participating in the Race Across AMerica (RAAM; a 4856km continuous cycle race. Cyclists reported experiencing an optimal emotional state for less than 50% of total competition, with emotional states differing significantly between each cyclist over time. Coupled with this emotional disturbance, each cyclist experienced progressively worsening sleep deprivation and daily negative energy balances throughout the RAAM. Cyclists managed less than one hour of continuous sleep per sleep episode, high sleep latency and high percentage moving time. Of note, actual sleep and sleep efficiency were better maintained during longer rest periods, highlighting the importance of a race strategy that seeks to optimise the balance between average cycling velocity and sleep time. Our data suggests that future RAAM cyclists and crew should: 1 identify beliefs on the perceived functionality of emotions in relation to best (functional-optimal and worst (dysfunctional performance as the starting point to intervention work; 2 create a plan for support sufficient sleep and recovery; 3 create nutritional strategies that maintain energy intake and thus reduce energy deficits; and 4 prepare for the deleterious effects of sleep deprivation so that they are able to appropriately respond to unexpected stressors and foster functional working interpersonal relationships

  5. Effect of a single 3-hour exposure to bright light on core body temperature and sleep in humans.

    Science.gov (United States)

    Dijk, D J; Cajochen, C; Borbély, A A

    1991-01-02

    Seven human subjects were exposed to bright light (BL, approx. 2500 lux) and dim light (DL, approx. 6 lux) during 3 h prior to nocturnal sleep, in a cross-over design. At the end of the BL exposure period core body temperature was significantly higher than at the end of the DL exposure period. The difference in core body temperature persisted during the first 4 h of sleep. The latency to sleep onset was increased after BL exposure. Rapid-eye movement sleep (REMS) and slow-wave sleep (SWS; stage 3 + 4 of non-REMS) were not significantly changed. Eight subjects were exposed to BL from 20.30 to 23.30 h while their eyes were covered or uncovered. During BL exposure with uncovered eyes, core body temperature decreased significantly less than during exposure with covered eyes. We conclude that bright light immediately affects core body temperature and that this effect is mediated via the eyes.

  6. Losing the left side of the world: rightward shift in human spatial attention with sleep onset.

    Science.gov (United States)

    Bareham, Corinne A; Manly, Tom; Pustovaya, Olga V; Scott, Sophie K; Bekinschtein, Tristan A

    2014-05-28

    Unilateral brain damage can lead to a striking deficit in awareness of stimuli on one side of space called Spatial Neglect. Patient studies show that neglect of the left is markedly more persistent than of the right and that its severity increases under states of low alertness. There have been suggestions that this alertness-spatial awareness link may be detectable in the general population. Here, healthy human volunteers performed an auditory spatial localisation task whilst transitioning in and out of sleep. We show, using independent electroencephalographic measures, that normal drowsiness is linked with a remarkable unidirectional tendency to mislocate left-sided stimuli to the right. The effect may form a useful healthy model of neglect and help in understanding why leftward inattention is disproportionately persistent after brain injury. The results also cast light on marked changes in conscious experience before full sleep onset.

  7. Coupling of Thalamocortical Sleep Oscillations Are Important for Memory Consolidation in Humans.

    Directory of Open Access Journals (Sweden)

    Mohammad Niknazar

    Full Text Available Sleep, specifically non-rapid eye movement (NREM sleep, is thought to play a critical role in the consolidation of recent memories. Two main oscillatory activities observed during NREM, cortical slow oscillations (SO, 0.5-1.0 Hz and thalamic spindles (12-15 Hz, have been shown to independently correlate with memory improvement. Yet, it is not known how these thalamocortical events interact, or the significance of this interaction, during the consolidation process. Here, we found that systemic administration of the GABAergic drug (zolpidem increased both the phase-amplitude coupling between SO and spindles, and verbal memory improvement in humans. These results suggest that thalamic spindles that occur during transitions to the cortical SO Up state are optimal for memory consolidation. Our study predicts that the timely interactions between cortical and thalamic events during consolidation, contribute to memory improvement and is mediated by the level of inhibitory neurotransmission.

  8. Inhale while Dreaming: Human Exposure to Pollutants while Sleeping

    DEFF Research Database (Denmark)

    Corsi, Richard; Spilak, Michal; Boor, E., Brandon

    2012-01-01

    of indoor pollutants, e.g., flame retardants to isocyanates. As such, there is a need for increased dialogue on this subject, end-point relevant research, and action to reduce exposures to high-risk contaminants for most of humanity. This workshop will involve an opening 5–minute presentation related...... discussion related to practical implications of new findings as well as past studies, geographic variations in emissions from mattresses and beddings, methods for reducing population exposures, and suggestions for future research that has practical endpoints and that can lead to reduced exposures....

  9. Dietary methanol regulates human gene activity.

    Directory of Open Access Journals (Sweden)

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  10. Regulation of bone blood flow in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Boushel, Robert; Hellsten, Ylva

    2018-01-01

    of cyclooxygenase (COX) enzyme, thus prostaglandin (PG) synthesis on femoral bone marrow blood flow by positron emission tomography in healthy young men at rest and during one leg dynamic exercise. In an additional group of healthy men, the role of adenosine (ADO) in the regulation of BBF during exercise......The mechanisms that regulate bone blood flow (BBF) in humans are largely unknown. Animal studies suggest that nitric oxide (NO) could be involved and in the present study we investigated the effects of inhibition of nitric oxide synthase (NOS) alone and in combination with inhibition.......036), but did not affect BBF significantly during exercise (5.5±1.4 ml/100g/min, p=0.25). On the other hand, while combined NOS and COX inhibition did not cause any further reduction of blood flow at rest (0.6±0.2 ml/100g/min), the combined blockade reduced BBF during exercise by ~21%, to 5.0±1.8 ml/100g/min (p...

  11. Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

    Science.gov (United States)

    Dijk, D. J.

    1999-01-01

    In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

  12. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  13. [Effect of 24-hour sleep deprivation on the oculomotor reactions of human operator].

    Science.gov (United States)

    Bukhtiiarov, I V; Chistov, S D

    2011-01-01

    The article presents the results of oculomotor reaction investigations during 24-hour sleep deprivation of 10 normal male subjects aged 25 to 30 yrs. Video nistagmograph VNG System VO-25 was used for binocular registration of eye movements. The proposed video procedures for assessment of the functional ability of human operator are a balancing test, investigation of saccadic and smooth tracking eye movements. The balancing test is designed to determine the nystagmic activity, the saccade test, latency, peak velocity and precision of saccades, and the smooth tracking test, standard errors in tracking velocity and displacement In addition to video oculography, velocity of a simple sensorimotor reaction was measured and the self-rating scale of well-being, alertness and mood (SAN) was employed. The balancing test showed balancing nystagmus; occurrence of this nystagmus grew high with desynchronosis. Saccades registered during sleep deprivation pointed to a considerable decline of velocity, less noticeable extension of latency and degradation of precision. Sleep deprivation reduced values of the mean coefficient of gain and increased the standard error in velocity and displacement of smooth eye tracking.

  14. Role of basal ganglia in sleep-wake regulation: neural circuitry and clinical significance

    Directory of Open Access Journals (Sweden)

    Ramalingam Vetrivelan

    2010-11-01

    Full Text Available Researchers over the last decade have made substantial progress towards understanding the roles of dopamine and the basal ganglia in the control of sleep-wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the basal ganglia (BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson’s disease in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine and modafinil may be linked to the ventral periaquductal grey (vPAG dopaminergic circuitry targeting the extra-BG sleep-wake network.

  15. 78 FR 11981 - Special Regulations; Areas of the National Park System, Sleeping Bear Dunes National Lakeshore...

    Science.gov (United States)

    2013-02-21

    ... Lakeshore (SLBE or Lakeshore) was established in 1970 ``for the benefit, inspiration, education, recreation... home destination. SLBE offers visitors recreational activities such as hiking, backpacking, kayaking...-Benefit and Regulatory Flexibility Analyses Leelanau Scenic Heritage Route Trailway, Sleeping Bear Dunes...

  16. Scale-free fluctuations in behavioral performance: delineating changes in spontaneous behavior of humans with induced sleep deficiency.

    Directory of Open Access Journals (Sweden)

    Jeremi K Ochab

    Full Text Available The timing and dynamics of many diverse behaviors of mammals, e.g., patterns of animal foraging or human communication in social networks exhibit complex self-similar properties reproducible over multiple time scales. In this paper, we analyze spontaneous locomotor activity of healthy individuals recorded in two different conditions: during a week of regular sleep and a week of chronic partial sleep deprivation. After separating activity from rest with a pre-defined activity threshold, we have detected distinct statistical features of duration times of these two states. The cumulative distributions of activity periods follow a stretched exponential shape, and remain similar for both control and sleep deprived individuals. In contrast, rest periods, which follow power-law statistics over two orders of magnitude, have significantly distinct distributions for these two groups and the difference emerges already after the first night of shortened sleep. We have found steeper distributions for sleep deprived individuals, which indicates fewer long rest periods and more turbulent behavior. This separation of power-law exponents is the main result of our investigations, and might constitute an objective measure demonstrating the severity of sleep deprivation and the effects of sleep disorders.

  17. Impact of Impulse Control Disorders on Sleep-Wake Regulation in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Atbin Djamshidian

    2015-01-01

    Full Text Available Sleep disturbances are common in patients with Parkinson’s disease (PD and are even more prevalent in patients with behavioural addictions, such as pathological gambling, compulsive sexual behaviour, compulsive buying, binge eating, punding, and the compulsive use of dopamine replacement therapy. An overview of the relationship between these impulse control disorders and sleep disturbances is given and potential underlying mechanisms and treatment strategies are covered.

  18. Comparison of coherence and phase synchronization of the human sleep electroencephalogram

    Czech Academy of Sciences Publication Activity Database

    Mezeiová, K.; Paluš, Milan

    2012-01-01

    Roč. 123, č. 9 (2012), s. 1821-1830 ISSN 1388-2457 R&D Projects: GA MŠk 7E08027 EU Projects: European Commission(XE) 200728 - BRAINSYNC Grant - others:AV ČR - SAS(CZ-SK) Modern Methods for Analysis of Electrophysiological Signals Institutional research plan: CEZ:AV0Z10300504 Keywords : phase synchronization * complete synchronization * mean phase coherence * permutation surrogate data * coherence * human sleep EEG Subject RIV: FH - Neurology Impact factor: 3.144, year: 2012

  19. The multiple time scales of sleep dynamics as a challenge for modelling the sleeping brain.

    Science.gov (United States)

    Olbrich, Eckehard; Claussen, Jens Christian; Achermann, Peter

    2011-10-13

    A particular property of the sleeping brain is that it exhibits dynamics on very different time scales ranging from the typical sleep oscillations such as sleep spindles and slow waves that can be observed in electroencephalogram (EEG) segments of several seconds duration over the transitions between the different sleep stages on a time scale of minutes to the dynamical processes involved in sleep regulation with typical time constants in the range of hours. There is an increasing body of work on mathematical and computational models addressing these different dynamics, however, usually considering only processes on a single time scale. In this paper, we review and present a new analysis of the dynamics of human sleep EEG at the different time scales and relate the findings to recent modelling efforts pointing out both the achievements and remaining challenges.

  20. Functional consequences of brain glycogen deficiency on the sleep-wake cycle regulation in PTG-KO mice

    KAUST Repository

    Burlet-Godinot, S.

    2017-12-31

    Introduction: In the CNS, glycogen is mainly localized in astrocytes where its levels are linked to neuronal activity. Astrocytic glycogen synthesis is regulated by glycogen synthase (GS) activity that is positively controlled by protein targeting to glycogen (PTG) expression levels. Although the role of glycogen in sleep/wake regulation is still poorly understood, we have previously demonstrated that, following a 6 hour gentle sleep deprivation (GSD), PTG mRNA expression and GS activity increased in the brain in mice while glycogen levels were paradoxically maintained and not affected. In order to gain further insight on the role of PTG in this process, we studied the sleep/wake cycle parameters in PTG knockout (PTG-KO) mice under baseline conditions and after a 6 hour GSD. Glycogen levels as well as mRNAs expression of genes related to energy metabolism were also determined in several brain areas. Materials and methods: Adult male C57BL/6J (WT) and PTG-KO mice were sleep-recorded under baseline conditions (24 h recordings, 12 h light/dark cycle) and following 6 hours GSD from ZT00 to ZT06. Vigilance states were visually scored (4 s temporal window). Spectral analysis of the EEG signal was performed using a discrete Fourier transformation. Glycogen measurements and gene expression analysis were assessed using a biochemical assay and quantitative RT-PCR respectively, on separate cohorts in WT vs PTG-KO mice at the end of the 6 hours GSD or in control animals (CTL) in different brain structures. Results: Quantitative analysis of the sleep/wake cycle under baseline conditions did not reveal major differences between the WT and the PTG-KO mice. However, during the dark period, the PTG-KO mice showed a significant increase in the number of wake and slow wave sleep episodes (respectively +26.5±8% and +26.1±8%; p< 0.05) together with a significant shortening in their duration (-21.6±7.2% and -14.3±2.8%; p< 0.01). No such quantitative changes were observed during

  1. Medico-legal implications of sleep apnoea syndrome: Driving license regulations in Europe

    DEFF Research Database (Denmark)

    Alonderis, A.; Barbee, F.; Bonsignore, M.

    2008-01-01

    Background: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulati......Background: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license...... sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries...... it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea...

  2. Quasi-supervised scoring of human sleep in polysomnograms using augmented input variables.

    Science.gov (United States)

    Yaghouby, Farid; Sunderam, Sridhar

    2015-04-01

    The limitations of manual sleep scoring make computerized methods highly desirable. Scoring errors can arise from human rater uncertainty or inter-rater variability. Sleep scoring algorithms either come as supervised classifiers that need scored samples of each state to be trained, or as unsupervised classifiers that use heuristics or structural clues in unscored data to define states. We propose a quasi-supervised classifier that models observations in an unsupervised manner but mimics a human rater wherever training scores are available. EEG, EMG, and EOG features were extracted in 30s epochs from human-scored polysomnograms recorded from 42 healthy human subjects (18-79 years) and archived in an anonymized, publicly accessible database. Hypnograms were modified so that: 1. Some states are scored but not others; 2. Samples of all states are scored but not for transitional epochs; and 3. Two raters with 67% agreement are simulated. A framework for quasi-supervised classification was devised in which unsupervised statistical models-specifically Gaussian mixtures and hidden Markov models--are estimated from unlabeled training data, but the training samples are augmented with variables whose values depend on available scores. Classifiers were fitted to signal features incorporating partial scores, and used to predict scores for complete recordings. Performance was assessed using Cohen's Κ statistic. The quasi-supervised classifier performed significantly better than an unsupervised model and sometimes as well as a completely supervised model despite receiving only partial scores. The quasi-supervised algorithm addresses the need for classifiers that mimic scoring patterns of human raters while compensating for their limitations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Effects of sleep on memory for conditioned fear and fear extinction

    OpenAIRE

    Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R.

    2015-01-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning and extinction memory in the rodent and human, interactions of sleep with th...

  4. Up-regulation of Na + expression in the area postrema of total sleep deprived rats by TOF-SIMS analysis

    Science.gov (United States)

    Mai, Fu-Der; Chen, Bo-Jung; Ling, Yong-Chien; Wu, Un-In; Huang, Yi-Lun; Chang, Hung-Ming

    2008-12-01

    Area postrema (AP) is a circumventricular organ plays an important role in sodium homeostasis and cardiovascular regulation. Since sleep deficiency will cause cardiovascular dysfunction, the present study aims to determine whether sodium level would significantly alter in AP following total sleep deprivation (TSD). Sodium level was investigated in vivo by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Clinical manifestation of cardiovascular function was demonstrated by mean arterial pressure (MAP) values. Results indicated that in normal rats, TOF-SIMS spectrum revealed a major peak of sodium ion counting as 5.61 × 10 5 at m/ z 23. The sodium ions were homogeneous distributed in AP without specific localization. However, following TSD, the sodium intensity was relatively increased (6.73 × 10 5) and the signal for sodium image was strongly expressed throughout AP with definite spatial distribution. MAP of TSD rats is 138 ± 5 mmHg, which is significantly higher than that of normal ones (121 ± 3 mmHg). Regarding AP is an important area for sodium sensation and development of hypernatremic related sympatho-excitation; up-regulation of sodium expression following TSD suggests that high sodium level might over-activate AP, through complex neuronal networks involving in sympathetic regulation, which could lead to the formation of TSD relevant cardiovascular diseases.

  5. Effects of sleep on memory for conditioned fear and fear extinction

    Science.gov (United States)

    Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R.

    2015-01-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. REM may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep’s effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. PMID:25894546

  6. Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

    Directory of Open Access Journals (Sweden)

    Christelle Anaclet

    2010-01-01

    Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle

  7. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

    Science.gov (United States)

    Holst, Sebastian C; Sousek, Alexandra; Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich; Tafti, Mehdi; Landolt, Hans-Peter

    2017-10-05

    Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.

  8. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation

    Science.gov (United States)

    Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich

    2017-01-01

    Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep. PMID:28980941

  9. Sleep and cognition.

    Science.gov (United States)

    Deak, Maryann C; Stickgold, Robert

    2010-07-01

    Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and (3) some proposed models of how sleep facilitates memory consolidation in sleep. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  10. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    Science.gov (United States)

    Meerlo, P.; Koehl, M.; van der Borght, K.; Turek, F. W.

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems. However, few attempts have been made to examine how sleep loss affects the HPA axis response to subsequent stressors. Furthermore, most studies applied short-lasting total sleep deprivation and not restriction of sleep over a longer period of time, as often occurs in human society. Using the rat as our model species, we investigated: (i) the HPA axis activity during and after sleep deprivation and (ii) the effect of sleep loss on the subsequent HPA response to a novel stressor. In one experiment, rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Control rats were placed in nonrotating wheels. In a second experiment, rats were subjected to an 8-day sleep restriction protocol allowing 4 h of sleep each day. To test the effects of sleep loss on subsequent stress reactivity, rats were subjected to a 30-min restraint stress. Blood samples were taken at several time points and analysed for adrenocorticotropic hormone (ACTH) and corticosterone. The results show that ACTH and corticosterone concentrations were elevated during sleep deprivation but returned to baseline within 4 h of recovery. After 1 day of sleep restriction, the ACTH and corticosterone response to restraint stress did not differ between control and sleep deprived rats. However, after 48 h of total sleep deprivation and after 8 days of restricted sleep, the ACTH response to restraint was significantly reduced whereas the corticosterone response was unaffected. These results show that sleep loss not only is a mild activator of the HPA axis itself, but also affects the subsequent response to stress. Alterations in HPA axis regulation may gradually appear under

  11. Chronic disruptions of circadian sleep regulation induce specific proinflammatory responses in the rat colon

    Czech Academy of Sciences Publication Activity Database

    Polidarová, Lenka; Houdek, Pavel; Sumová, Alena

    2017-01-01

    Roč. 34, č. 9 (2017), s. 1273-1287 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GA14-07711S Institutional support: RVO:67985823 Keywords : aging * colon * constant light * melatonin * proinflammatory cytokine * Rgs16 * sleep disruption Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.562, year: 2016

  12. Genetic Dissociation of Daily Sleep and Sleep Following Thermogenetic Sleep Deprivation in Drosophila.

    Science.gov (United States)

    Dubowy, Christine; Moravcevic, Katarina; Yue, Zhifeng; Wan, Joy Y; Van Dongen, Hans P A; Sehgal, Amita

    2016-05-01

    Sleep rebound-the increase in sleep that follows sleep deprivation-is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to habitual daily sleep remain unclear. To address this, we developed an efficient thermogenetic method of inducing sleep deprivation in Drosophila that produces a substantial rebound, and applied the newly developed method to assess sleep rebound in a screen of 1,741 mutated lines. We used data generated by this screen to identify lines with reduced sleep rebound following thermogenetic sleep deprivation, and to probe the relationship between habitual sleep amount and sleep following thermogenetic sleep deprivation in Drosophila. To develop a thermogenetic method of sleep deprivation suitable for screening, we thermogenetically stimulated different populations of wake-promoting neurons labeled by Gal4 drivers. Sleep rebound following thermogenetically-induced wakefulness varies across the different sets of wake-promoting neurons that were stimulated, from very little to quite substantial. Thermogenetic activation of neurons marked by the c584-Gal4 driver produces both strong sleep loss and a substantial rebound that is more consistent within genotypes than rebound following mechanical or caffeine-induced sleep deprivation. We therefore used this driver to induce sleep deprivation in a screen of 1,741 mutagenized lines generated by the Drosophila Gene Disruption Project. Flies were subjected to 9 h of sleep deprivation during the dark period and released from sleep deprivation 3 h before lights-on. Recovery was measured over the 15 h following sleep deprivation. Following identification of lines with reduced sleep rebound, we characterized baseline sleep and sleep depth before and after sleep deprivation for these hits. We identified two lines that consistently exhibit a blunted increase in the duration and depth of sleep after

  13. Human and rat gut microbiome composition is maintained following sleep restriction

    NARCIS (Netherlands)

    Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

    Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome

  14. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans.

    Science.gov (United States)

    Carroll, Judith E; Cole, Steven W; Seeman, Teresa E; Breen, Elizabeth C; Witarama, Tuff; Arevalo, Jesusa M G; Ma, Jeffrey; Irwin, Michael R

    2016-01-01

    Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (psleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in modafinil-induced arousal.

    Directory of Open Access Journals (Sweden)

    Mei-Hong Qiu

    Full Text Available BACKGROUND: We have previously shown that modafinil promotes wakefulness via dopamine receptor D(1 and D(2 receptors; however, the locus where dopamine acts has not been identified. We proposed that the nucleus accumbens (NAc that receives the ventral tegmental area dopamine inputs play an important role not only in reward and addiction but also in sleep-wake cycle and in mediating modafinil-induced arousal. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we further explored the role of NAc in sleep-wake cycle and sleep homeostasis by ablating the NAc core and shell, respectively, and examined arousal response following modafinil administration. We found that discrete NAc core and shell lesions produced 26.5% and 17.4% increase in total wakefulness per day, respectively, with sleep fragmentation and a reduced sleep rebound after a 6-hr sleep deprivation compared to control. Finally, NAc core but not shell lesions eliminated arousal effects of modafinil. CONCLUSIONS/SIGNIFICANCE: These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil.

  16. Human Dignity and the Ethics and Regulation of Technology

    NARCIS (Netherlands)

    Duwell, M.

    2017-01-01

    This chapter investigates how human dignity might be understood as a normative concept for the regulation of technologies. First, various distinctions that are relevant for the way human dignity can be understood are discussed. It is argued that it is particularly important that we should see human

  17. Large Scale Triboelectric Nanogenerator and Self-Powered Flexible Sensor for Human Sleep Monitoring

    Directory of Open Access Journals (Sweden)

    Xiaoheng Ding

    2018-05-01

    Full Text Available The triboelectric nanogenerator (TENG and its application as a sensor is a popular research subject. There is demand for self-powered, flexible sensors with high sensitivity and high power-output for the next generation of consumer electronics. In this study, a 300 mm × 300 mm carbon nanotube (CNT-doped porous PDMS film was successfully fabricated wherein the CNT influenced the micropore structure. A self-powered TENG tactile sensor was established according to triboelectric theory. The CNT-doped porous TENG showed a voltage output seven times higher than undoped porous TENG and 16 times higher than TENG with pure PDMS, respectively. The TENG successfully acquired human motion signals, breath signals, and heartbeat signals during a sleep monitoring experiment. The results presented here may provide an effective approach for fabricating large-scale and low-cost flexible TENG sensors.

  18. Spatial predictions of Rhodesian Human African Trypanosomiasis (sleeping sickness prevalence in Kaberamaido and Dokolo, two newly affected districts of Uganda.

    Directory of Open Access Journals (Sweden)

    Nicola A Batchelor

    2009-12-01

    Full Text Available The continued northwards spread of Rhodesian sleeping sickness or Human African Trypanosomiasis (HAT within Uganda is raising concerns of overlap with the Gambian form of the disease. Disease convergence would result in compromised diagnosis and treatment for HAT. Spatial determinants for HAT are poorly understood across small areas. This study examines the relationships between Rhodesian HAT and several environmental, climatic and social factors in two newly affected districts, Kaberamaido and Dokolo. A one-step logistic regression analysis of HAT prevalence and a two-step logistic regression method permitted separate analysis of both HAT occurrence and HAT prevalence. Both the occurrence and prevalence of HAT were negatively correlated with distance to the closest livestock market in all models. The significance of distance to the closest livestock market strongly indicates that HAT may have been introduced to this previously unaffected area via the movement of infected, untreated livestock from endemic areas. This illustrates the importance of the animal reservoir in disease transmission, and highlights the need for trypanosomiasis control in livestock and the stringent implementation of regulations requiring the treatment of cattle prior to sale at livestock markets to prevent any further spread of Rhodesian HAT within Uganda.

  19. Molecular regulation of human hematopoietic stem cells

    NARCIS (Netherlands)

    van Galen, P.L.J.

    2014-01-01

    Peter van Galen focuses on understanding the determinants that maintain the stem cell state. Using human hematopoietic stem cells (HSCs) as a model, processes that govern self-renewal and tissue regeneration were investigated. Specifically, a role for microRNAs in balancing the human HSC

  20. Comparison of rhythmic masticatory muscle activity during non-rapid eye movement sleep in guinea pigs and humans.

    Science.gov (United States)

    Kato, Takafumi; Toyota, Risa; Haraki, Shingo; Yano, Hiroyuki; Higashiyama, Makoto; Ueno, Yoshio; Yano, Hiroshi; Sato, Fumihiko; Yatani, Hirofumi; Yoshida, Atsushi

    2017-09-27

    Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R-waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time-course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P motor activation in comparison to human subjects. © 2017 European Sleep Research Society.

  1. Functions and Mechanisms of Sleep

    Directory of Open Access Journals (Sweden)

    Mark R. Zielinski

    2016-04-01

    Full Text Available Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep.

  2. Transcranial electrical currents to probe EEG brain rhythms and memory consolidation during sleep in humans.

    Directory of Open Access Journals (Sweden)

    Lisa Marshall

    Full Text Available Previously the application of a weak electric anodal current oscillating with a frequency of the sleep slow oscillation (∼0.75 Hz during non-rapid eye movement sleep (NonREM sleep boosted endogenous slow oscillation activity and enhanced sleep-associated memory consolidation. The slow oscillations occurring during NonREM sleep and theta oscillations present during REM sleep have been considered of critical relevance for memory formation. Here transcranial direct current stimulation (tDCS oscillating at 5 Hz, i.e., within the theta frequency range (theta-tDCS is applied during NonREM and REM sleep. Theta-tDCS during NonREM sleep produced a global decrease in slow oscillatory activity conjoint with a local reduction of frontal slow EEG spindle power (8-12 Hz and a decrement in consolidation of declarative memory, underlining the relevance of these cortical oscillations for sleep-dependent memory consolidation. In contrast, during REM sleep theta-tDCS appears to increase global gamma (25-45 Hz activity, indicating a clear brain state-dependency of theta-tDCS. More generally, results demonstrate the suitability of oscillating-tDCS as a tool to analyze functions of endogenous EEG rhythms and underlying endogenous electric fields as well as the interactions between EEG rhythms of different frequencies.

  3. Characterization of gene expression regulated by human OTK18 ...

    Indian Academy of Sciences (India)

    ing regulated by interactions with the Tat protein (Carlson et al. 2004a). In contrast, OTK18 is ubiquitously expressed in all normal human tissues, and OTK18 expression in HIV-1 ..... and Social Sciences and the UNK Biology Department.

  4. Sympathetic regulation of cerebral blood flow in humans : a review

    NARCIS (Netherlands)

    ter Laan, M.; van Dijk, J. M. C.; Elting, J. W. J.; Staal, M. J.; Absalom, A. R.

    Cerebral blood flow (CBF) is regulated by vasomotor, chemical, metabolic, and neurogenic mechanisms. Even though the innervation of cerebral arteries is quite extensively described and reviewed in the literature, its role in regulation of CBF in humans remains controversial. We believe that

  5. Influence of serial electrical stimulations of perifornical and posterior hypothalamic orexin-containing neurons on regulation of sleep homeostasis and sleep-wakefulness cycle recovery from experimental comatose state and anesthesia-induced deep sleep.

    Science.gov (United States)

    Chijavadze, E; Chkhartishvili, E; Babilodze, M; Maglakelidze, N; Nachkebia, N

    2013-11-01

    The work was aimed for the ascertainment of following question - whether Orexin-containing neurons of dorsal and lateral hypothalamic, and brain Orexinergic system in general, are those cellular targets which can speed up recovery of disturbed sleep homeostasis and accelerate restoration of sleep-wakefulness cycle phases during some pathological conditions - experimental comatose state and/or deep anesthesia-induced sleep. Study was carried out on white rats. Modeling of experimental comatose state was made by midbrain cytotoxic lesions at intra-collicular level.Animals were under artificial respiration and special care. Different doses of Sodium Ethaminal were used for deep anesthesia. 30 min after comatose state and/or deep anesthesia induced sleep serial electrical stimulations of posterior and/or perifornical hypothalamus were started. Stimulation period lasted for 1 hour with the 5 min intervals between subsequent stimulations applied by turn to the left and right side hypothalamic parts.EEG registration of cortical and hippocampal electrical activity was started immediately after experimental comatose state and deep anesthesia induced sleep and continued continuously during 72 hour. According to obtained new evidences, serial electrical stimulations of posterior and perifornical hypothalamic Orexin-containing neurons significantly accelerate recovery of sleep homeostasis, disturbed because of comatose state and/or deep anesthesia induced sleep. Speed up recovery of sleep homeostasis was manifested in acceleration of coming out from comatose state and deep anesthesia induced sleep and significant early restoration of sleep-wakefulness cycle behavioral states.

  6. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    International Nuclear Information System (INIS)

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr.; Gillin, J.C.

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep

  7. Novel transcriptional networks regulated by CLOCK in human neurons.

    Science.gov (United States)

    Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve

    2017-11-01

    The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Test of the Starling resistor model in the human upper airway during sleep.

    Science.gov (United States)

    Wellman, Andrew; Genta, Pedro R; Owens, Robert L; Edwards, Bradley A; Sands, Scott A; Loring, Stephen H; White, David P; Jackson, Andrew C; Pedersen, Ole F; Butler, James P

    2014-12-15

    The human pharyngeal airway during sleep is conventionally modeled as a Starling resistor. However, inspiratory flow often decreases with increasing effort (negative effort dependence, NED) rather than remaining fixed as predicted by the Starling resistor model. In this study, we tested a major prediction of the Starling resistor model--that the resistance of the airway upstream from the site of collapse remains fixed during flow limitation. During flow limitation in 24 patients with sleep apnea, resistance at several points along the pharyngeal airway was measured using a pressure catheter with multiple sensors. Resistance between the nose and the site of collapse (the upstream segment) was measured before and after the onset of flow limitation to determine whether the upstream dimensions remained fixed (as predicted by the Starling resistor model) or narrowed (a violation of the Starling resistor model). The upstream resistance from early to mid inspiration increased considerably during flow limitation (by 35 ± 41 cmH2O · liter(-1) · s(-1), P < 0.001). However, there was a wide range of variability between patients, and the increase in upstream resistance was strongly correlated with the amount of NED (r = 0.75, P < 0.001). Therefore, patients with little NED exhibited little upstream narrowing (consistent with the Starling model), and patients with large NED exhibited large upstream narrowing (inconsistent with the Starling model). These findings support the idea that there is not a single model of pharyngeal collapse, but rather that different mechanisms may dominate in different patients. These differences could potentially be exploited for treatment selection. Copyright © 2014 the American Physiological Society.

  9. cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness.

    Directory of Open Access Journals (Sweden)

    Sonja Langmesser

    Full Text Available Many effects of nitric oxide (NO are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3',5'-monophosphate (cGMP. cGMP activates cGMP-dependent protein kinases (PRKGs, which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1 in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS duration and in non-REM sleep (NREMS consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG power in the delta frequency range (1-4 Hz under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep.

  10. Exposure to dim artificial light at night increases REM sleep and awakenings in humans.

    Science.gov (United States)

    Cho, Chul-Hyun; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Kang, Seung-Gul; Bok, Ki-Nam; Jung, Ki-Young; Kim, Leen; Lee, Eun-Il

    2016-01-01

    Exposure to artificial light at night (ALAN) has become increasing common, especially in developed countries. We investigated the effect of dALAN exposure during sleep in healthy young male subjects. A total of 30 healthy young male volunteers from 21 to 29 years old were recruited for the study. They were randomly divided into two groups depending on light intensity (Group A: 5 lux and Group B: 10 lux). After a quality control process, 23 healthy subjects were included in the study (Group A: 11 subjects, Group B: 12 subjects). Subjects underwent an NPSG session with no light (Night 1) followed by an NPSG session randomly assigned to two different dim light conditions (5 or 10 lux, dom λ: 501.4 nm) for a whole night (Night 2). We found significant sleep structural differences between Nights 1 and 2, but no difference between Groups A and B. Exposure to dALAN during sleep was significantly associated with increased wake time after sleep onset (WASO; F = 7.273, p = 0.014), increased Stage N1 (F = 4.524, p = 0.045), decreased Stage N2 (F = 9.49, p = 0.006), increased Stage R (F = 6.698, p = 0.017) and non-significantly decreased REM density (F = 4.102, p = 0.056). We found that dALAN during sleep affects sleep structure. Exposure to dALAN during sleep increases the frequency of arousals, amount of shallow sleep and amount of REM sleep. This suggests adverse effects of dALAN during sleep on sleep quality and suggests the need to avoid exposure to dALAN during sleep.

  11. Neuronal and molecular mechanisms of sleep homeostasis.

    Science.gov (United States)

    Donlea, Jeffrey M

    2017-12-01

    Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep. This review describes circuits in two neuropil structures, the central complex and mushroom bodies, that influence sleep homeostasis and neuromodulatory systems that influence the accrual of homeostatic sleep need. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The Zfhx3-Mediated Axis Regulates Sleep and Interval Timing in Mice

    Directory of Open Access Journals (Sweden)

    Edoardo Balzani

    2016-07-01

    Full Text Available An AT motif-dependent axis, modulated by the transcription factor Zfhx3, influences the circadian clock in mice. In particular, gain of function of Zfhx3 significantly shortens circadian rhythms and alters the transcriptional activity of an important class of neuropeptides that controls intercellular signaling in the suprachiasmatic nucleus (SCN of the hypothalamus. The ZFHX3/AT axis revealed an important, largely cell-nonautonomous control of the circadian clock. Here, by studying the recently identified circadian mouse mutant Zfhx3Sci/+, we identify significant effects on sleep homeostasis, a phenomenon that is outside the canonical circadian clock system and that is modulated by the activity of those neuropeptides at a circuit level. We show that the Zfhx3Sci/+ mutation accelerates the circadian clock at both the hourly scale (i.e., advancing circadian rhythms and the seconds-to-minutes scale (i.e., anticipating behavioral responses in mice. The in vivo results are accompanied by a significant presence of sleep targets among protein-protein interactions of the Zfhx3Sci/+-dependent network.

  13. Brain and muscle oxygenation monitoring using near-infrared spectroscopy (NIRS) during all-night sleep

    Science.gov (United States)

    Zhang, Zhongxing; Khatami, Ramin

    2013-03-01

    The hemodynamic changes during natural human sleep are still not well understood. NIRS is ideally suited for monitoring the hemodynamic changes during sleep due to the properties of local measurement, totally safe application and good tolerance to motion. Several studies have been conducted using NIRS in both normal subjects and patients with various sleep disorders during sleep to characterize the hemodynamic changing patterns during different sleep stages and during different symptoms such as obstructive apneas. Here we assessed brain and muscle oxygenation changes in 7 healthy adults during all-night sleep with combined polysomnography measurement to test the notion if hemodynamic changes in sleep are indeed brain specific. We found that muscle and brain showed similar hemodynamic changes during sleep initiation. A decrease in HbO2 and tissue oxygenation index (TOI) while an increase in HHb was observed immediately after sleep onset, and an opposite trend was found after transition with progression to deeper slow-wave sleep (SWS) stage. Spontaneous low frequency oscillations (LFO) and very low frequency oscillations (VLFO) were smaller (Levene's test, psleep (LS) and rapid-eye-movement (REM) sleep in both brain and muscle. Spectral analysis of the NIRS signals measured from brain and muscle also showed reductions in VLFO and LFO powers during SWS with respect to LS and REM sleep. These results indicate a systemic attenuation rather than local cerebral reduction of spontaneous hemodynamic activity in SWS. A systemic physiological mechanism may exist to regulate the hemodynamic changes in brain and muscle during sleep.

  14. Episodic memory and appetite regulation in humans.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Brunstrom

    Full Text Available Psychological and neurobiological evidence implicates hippocampal-dependent memory processes in the control of hunger and food intake. In humans, these have been revealed in the hyperphagia that is associated with amnesia. However, it remains unclear whether 'memory for recent eating' plays a significant role in neurologically intact humans. In this study we isolated the extent to which memory for a recently consumed meal influences hunger and fullness over a three-hour period. Before lunch, half of our volunteers were shown 300 ml of soup and half were shown 500 ml. Orthogonal to this, half consumed 300 ml and half consumed 500 ml. This process yielded four separate groups (25 volunteers in each. Independent manipulation of the 'actual' and 'perceived' soup portion was achieved using a computer-controlled peristaltic pump. This was designed to either refill or draw soup from a soup bowl in a covert manner. Immediately after lunch, self-reported hunger was influenced by the actual and not the perceived amount of soup consumed. However, two and three hours after meal termination this pattern was reversed - hunger was predicted by the perceived amount and not the actual amount. Participants who thought they had consumed the larger 500-ml portion reported significantly less hunger. This was also associated with an increase in the 'expected satiation' of the soup 24-hours later. For the first time, this manipulation exposes the independent and important contribution of memory processes to satiety. Opportunities exist to capitalise on this finding to reduce energy intake in humans.

  15. Some remarks on the effects of drugs, lack of sleep and loud noise on human performance.

    NARCIS (Netherlands)

    Sanders, A.F. & A.A. Bunt.

    1971-01-01

    Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that

  16. Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle.

    Science.gov (United States)

    Clasadonte, Jerome; Scemes, Eliana; Wang, Zhongya; Boison, Detlev; Haydon, Philip G

    2017-09-13

    Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Human regional cerebral blood flow during rapid-eye-movement sleep

    DEFF Research Database (Denmark)

    Madsen, P L; Holm, S; Vorstrup, S

    1991-01-01

    Owing to the coupling between CBF and neuronal activity, regional CBF is a reflection of neural activity in different brain regions. In this study we measured regional CBF during polysomnographically well-defined rapid-eye-movement (REM) sleep by the use of single photon emission computerized...... tomography and the new tracer 99mTc-dl-hexamethylpropyleneamine. Eleven healthy volunteers aged between 22 and 27 years were studied. CBF was measured on separate nights during REM sleep and during EEG-verified wakefulness. On awakening from REM sleep, all subjects reported visual dreams. During REM sleep...... dream experiences. On the other hand, the reduced involvement of the inferior frontal cortex observed during REM sleep might explain the poor temporal organization and bizarreness often experienced in dreams....

  18. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt

    NARCIS (Netherlands)

    Weljie, Aalim M; Meerlo, Peter; Goel, Namni; Sengupta, Arjun; Kayser, Matthew S; Abel, Ted; Birnbaum, Morris J; Dinges, David F; Sehgal, Amita

    2015-01-01

    Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the

  19. Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans.

    Science.gov (United States)

    Bonafide, Christopher P; Aucutt-Walter, Natalie; Divittore, Nicole; King, Tonya; Bixler, Edward O; Cronin, Arthur J

    2008-04-01

    Postoperative patients are sleep deprived. Opioids, commonly administered for postoperative pain control, are often mistakenly considered inducers of naturally occurring sleep. This study describes the effect of the opioid remifentanil on nocturnal sleep in healthy volunteers. In addition, this study tests the hypothesis that opioid-induced sleep disturbance is caused by a circadian pacemaker disturbance, reflected by suppressed nocturnal plasma concentration of melatonin. Polysomnography was performed in 10 volunteers from 11:00 pm to 7:00 am for four nights at 6-day intervals. On two nights, remifentanil (0.01-0.04 microg x kg x min) was infused from 10:30 pm to 7:00 am, and either a placebo capsule or 3.0 mg melatonin was administered at 10:30 pm. On two additional nights, saline was infused, and the placebo or melatonin capsules were administered at 10:30 pm. Blood was drawn at 12:00 am, 3:00 am, and 6:00 am to measure the plasma concentration of melatonin and cortisol. A repeated-measures analysis of variance model was used to determine the effect of remifentanil on sleep stages, the effect of remifentanil on the plasma concentration of melatonin, and the effect of exogenous melatonin on remifentanil-induced sleep disturbance. Remifentanil inhibited rapid eye movement sleep (14.1 +/- 7.2% to 3.9 +/- 6.9%). The amount of slow wave sleep decreased from 6.8 +/- 7.6% to 3.2 +/- 6.1%, but this decrease was not statistically significant. Remifentanil did not decrease melatonin concentration. Melatonin administration did not prevent remifentanil-induced sleep disturbance. An overnight constant infusion of remifentanil inhibits rapid eye movement sleep without suppressing the nocturnal melatonin surge.

  20. Discharge patterns of human tensor palatini motor units during sleep onset.

    Science.gov (United States)

    Nicholas, Christian L; Jordan, Amy S; Heckel, Leila; Worsnop, Christopher; Bei, Bei; Saboisky, Julian P; Eckert, Danny J; White, David P; Malhotra, Atul; Trinder, John

    2012-05-01

    Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. Sleep laboratory. Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. Sleep onset. Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP.

  1. Neuroscience-driven discovery and development of sleep therapeutics

    NARCIS (Netherlands)

    Dresler, M.; Spoormaker, V.I.; Beitinger, P.; Czisch, M.; Kimura, M.; Steiger, A.; Holsboer, F.

    2014-01-01

    Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite the fact that disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological,

  2. Regulation of human cytokines by Cordyceps militaris.

    Science.gov (United States)

    Sun, Yong; Shao, Yani; Zhang, Zhiguo; Wang, Lianfen; Mariga, Alfred M; Pang, Guangchang; Geng, Chaoyu; Ho, Chi-Tang; Hu, Qiuhui; Zhao, Liyan

    2014-12-01

    Cordyceps (Cordyceps militaris) exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits). In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses) on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70), interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines. Copyright © 2014. Published by Elsevier B.V.

  3. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  4. Acute Effect of Alcohol Intake on Cardiovascular Autonomic Regulation During the First Hours of Sleep in a Large Real-World Sample of Finnish Employees: Observational Study.

    Science.gov (United States)

    Pietilä, Julia; Helander, Elina; Korhonen, Ilkka; Myllymäki, Tero; Kujala, Urho M; Lindholm, Harri

    2018-03-16

    Sleep is fundamental for good health, and poor sleep has been associated with negative health outcomes. Alcohol consumption is a universal health behavior associated with poor sleep. In controlled laboratory studies, alcohol intake has been shown to alter physiology and disturb sleep homeostasis and architecture. The association between acute alcohol intake and physiological changes has not yet been studied in noncontrolled real-world settings. The aim of this study was to assess the effects of alcohol intake on the autonomic nervous system (ANS) during sleep in a large noncontrolled sample of Finnish employees. From a larger cohort, this study included 4098 subjects (55.81%, 2287/4098 females; mean age 45.1 years) who had continuous beat-to-beat R-R interval recordings of good quality for at least 1 day with and for at least 1 day without alcohol intake. The participants underwent continuous beat-to-beat R-R interval recording during their normal everyday life and self-reported their alcohol intake as doses for each day. Heart rate (HR), HR variability (HRV), and HRV-derived indices of physiological state from the first 3 hours of sleep were used as outcomes. Within-subject analyses were conducted in a repeated measures manner by studying the differences in the outcomes between each participant's days with and without alcohol intake. For repeated measures two-way analysis of variance, the participants were divided into three groups: low (≤0.25 g/kg), moderate (>0.25-0.75 g/kg), and high (>0.75 g/kg) intake of pure alcohol. Moreover, linear models studied the differences in outcomes with respect to the amount of alcohol intake and the participant's background parameters (age; gender; body mass index, BMI; physical activity, PA; and baseline sleep HR). Alcohol intake was dose-dependently associated with increased sympathetic regulation, decreased parasympathetic regulation, and insufficient recovery. In addition to moderate and high alcohol doses, the

  5. The Functions of Sleep

    Directory of Open Access Journals (Sweden)

    Samson Z Assefa

    2015-08-01

    Full Text Available Sleep is a ubiquitous component of animal life including birds and mammals. The exact function of sleep has been one of the mysteries of biology. A considerable number of theories have been put forward to explain the reason(s for the necessity of sleep. To date, while a great deal is known about what happens when animals sleep, there is no definitive comprehensive explanation as to the reason that sleep is an inevitable part of animal functioning. It is well known that sleep is a homeostatically regulated body process, and that prolonged sleep deprivation is fatal in animals. In this paper, we present some of the theories as to the functions of sleep and provide a review of some hypotheses as to the overall physiologic function of sleep. To better understand the purpose for sleeping, we review the effects of sleep deprivation on physical, neurocognitive and psychic function. A better understanding of the purpose for sleeping will be a great advance in our understanding of the nature of the animal kingdom, including our own.

  6. Decorin gene expression and its regulation in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Velez-DelValle, Cristina; Marsch-Moreno, Meytha; Castro-Munozledo, Federico [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico); Kuri-Harcuch, Walid, E-mail: walidkuri@gmail.com [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico)

    2011-07-22

    Highlights: {yields} We showed that cultured human diploid epidermal keratinocytes express and synthesize decorin. {yields} Decorin is found intracytoplasmic in suprabasal cells of cultures and in human epidermis. {yields} Decorin mRNA expression in cHEK is regulated by pro-inflammatory and proliferative cytokines. {yields} Decorin immunostaining of psoriatic lesions showed a lower intensity and altered intracytoplasmic arrangements. -- Abstract: In various cell types, including cancer cells, decorin is involved in regulation of cell attachment, migration and proliferation. In skin, decorin is seen in dermis, but not in keratinocytes. We show that decorin gene (DCN) is expressed in the cultured keratinocytes, and the protein is found in the cytoplasm of differentiating keratinocytes and in suprabasal layers of human epidermis. RT-PCR experiments showed that DCN expression is regulated by pro-inflammatory and proliferative cytokines. Our data suggest that decorin should play a significant role in keratinocyte terminal differentiation, cutaneous homeostasis and dermatological diseases.

  7. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  8. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt.

    Science.gov (United States)

    Weljie, Aalim M; Meerlo, Peter; Goel, Namni; Sengupta, Arjun; Kayser, Matthew S; Abel, Ted; Birnbaum, Morris J; Dinges, David F; Sehgal, Amita

    2015-02-24

    Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets (n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction (P discovery rate neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.

  9. Cortical deactivation induced by visual stimulation in human slow-wave sleep

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Law, Ian; Lund, Torben E

    2002-01-01

    . It is unresolved whether this negative BOLD response pattern is of developmental neurobiological origin particular to a given age or to a general effect of sleep or sedative drugs. To further elucidate this issue, we used fMRI and positron emission tomography (PET) to study the brain activation pattern during......It has previously been demonstrated that sleeping and sedated young children respond with a paradoxical decrease in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the rostro-medial occipital visual cortex during visual stimulation...... visual stimulation in spontaneously sleeping adult volunteers. In five sleeping volunteers fMRI studies confirmed a robust signal decrease during stimulation in the rostro-medial occipital cortex. A similar relative decrease at the same location was found during visual stimulation...

  10. Sleep Disorders

    Science.gov (United States)

    ... the day, even if you have had enough sleep? You might have a sleep disorder. The most common kinds are Insomnia - a hard time falling or staying asleep Sleep apnea - breathing interruptions during sleep Restless legs syndrome - ...

  11. Sleep Problems

    Science.gov (United States)

    ... For Consumers Consumer Information by Audience For Women Sleep Problems Share Tweet Linkedin Pin it More sharing ... 101 KB) En Español Medicines to Help You Sleep Tips for Better Sleep Basic Facts about Sleep ...

  12. Sympathetic and Catecholaminergic Alterations in Sleep Apnea with Particular Emphasis on Children.

    Directory of Open Access Journals (Sweden)

    Fahed eHakim

    2012-01-01

    Full Text Available Sleep is involved in the regulation of major organ functions in the human body, and disruption of sleep potentially can elicit organ dysfunction. Obstructive sleep apnea (OSA is the most prevalent sleep disorder of breathing in adults and children, and its manifestations reflect the interactions between intermittent hypoxia (IH, intermittent hypercapnia, increased intra-thoracic pressure swings, and sleep fragmentation, as elicited by the episodic changes in upper airway resistance during sleep. The sympathetic nervous system is an important modulator of the cardiovascular, immune, endocrine and metabolic systems, and alterations in autonomic activity may lead to metabolic imbalance and organ dysfunction. Here we review how OSA and its constitutive components can lead to perturbation of the autonomic nervous system in general, and to altered regulation of catecholamines, both of which then playing an important role in some of the mechanisms underlying OSA-induced morbidities.

  13. Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations

    Directory of Open Access Journals (Sweden)

    Gabriela Hurtado-Alvarado

    2013-01-01

    Full Text Available A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis. Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002–2013 on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.

  14. Avalanche analysis from multi-electrode ensemble recordings in cat, monkey and human cerebral cortex during wakefulness and sleep.

    Directory of Open Access Journals (Sweden)

    Nima eDehghani

    2012-08-01

    Full Text Available Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep and REM sleep, using high-density electrode arrays in cat motor cortex (96 electrodes, monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes in epileptic patients. In neuronal avalanches defined from units (up to 160 single units, the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs and in particular LFP negative peaks (nLFPs among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and pre-motor cortices. In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man.

  15. Sleep and Athletic Performance.

    Science.gov (United States)

    Watson, Andrew M

    Sleep is an essential component of health and well-being, with significant impacts on physical development, emotional regulation, cognitive performance, and quality of life. Along with being an integral part of the recovery and adaptive process between bouts of exercise, accumulating evidence suggests that increased sleep duration and improved sleep quality in athletes are associated with improved performance and competitive success. In addition, better sleep may reduce the risk of both injury and illness in athletes, not only optimizing health but also potentially enhancing performance through increased participation in training. Despite this, most studies have found that athletes fail to obtain the recommended amount of sleep, threatening both performance and health. Athletes face a number of obstacles that can reduce the likelihood of obtaining proper sleep, such as training and competition schedules, travel, stress, academic demands, and overtraining. In addition, athletes have been found to demonstrate poor self-assessment of their sleep duration and quality. In light of this, athletes may require more careful monitoring and intervention to identify individuals at risk and promote proper sleep to improve both performance and overall health. This review attempts to highlight the recent literature regarding sleep issues in athletes, the effects of sleep on athletic performance, and interventions to enhance proper sleep in athletes.

  16. Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster but Not in Amnesiac Mutant Flies

    Directory of Open Access Journals (Sweden)

    Michael W. Chi

    2014-08-01

    Full Text Available Sleep has many important biological functions, but how sleep is regulated remains poorly understood. In humans, social isolation and other stressors early in life can disrupt adult sleep. In fruit flies housed at different population densities during early adulthood, social enrichment was shown to increase subsequent sleep, but it is unknown if population density during early development can also influence adult sleep. To answer this question, we maintained Drosophila larvae at a range of population densities throughout larval development, kept them isolated during early adulthood, and then tested their sleep patterns. Our findings reveal that flies that had been isolated as larvae had more fragmented sleep than those that had been raised at higher population densities. This effect was more prominent in females than in males. Larval population density did not affect sleep in female flies that were mutant for amnesiac, which has been shown to be required for normal memory consolidation, adult sleep regulation, and brain development. In contrast, larval population density effects on sleep persisted in female flies lacking the olfactory receptor or83b, suggesting that olfactory signals are not required for the effects of larval population density on adult sleep. These findings show that population density during early development can alter sleep behavior in adulthood, suggesting that genetic and/or structural changes are induced by this developmental manipulation that persist through metamorphosis.

  17. Effects of sleep on memory for conditioned fear and fear extinction.

    Science.gov (United States)

    Pace-Schott, Edward F; Germain, Anne; Milad, Mohammed R

    2015-07-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning, and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. Rapid eye movement (REM) may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction, and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep's effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  18. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...... hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation...

  19. Mathematical Models of the Use of Caffeine as a Counter Measure to the Deterioration of Neurobehaviorial Functioning During Sleep Deprivation

    National Research Council Canada - National Science Library

    Jewett, Megan

    2000-01-01

    The specific aims are to refine mathematical models that predict homeostatic and circadian regulation of human alertness and short-term memory during sleep deprivation, and to validate these models...

  20. Regional cerebral blood flow and oxygen consumption during normal human sleep

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Ken [Toho Univ., Tokyo (Japan). School of Medicine

    1989-09-01

    Regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rCEF) and regional cerebral metabolic rate for oxygen (rCMRO{sub 2}) were measured using the continuous inhalation technique for {sup 15}O with positron emission tomography (PET) during both wakefulness and sleep. Ten paid volunteers, with a mean age of 21.6 yrs., were deprived of sleep for a period of approximately 20 hours, and the experiments were performed mostly in the morning. {sup 15}O activity of both whole blood and the plasma, pixel count of PET, total arterial blood oxygen content were used for analysis of rCBF, rOEF and rCMRO{sub 2}. PET scannings were carried out mostly during the very light non-rapid eye movement (NREM) sleep, i.e. stage 1 and/or 2, and wakefulness. About 10 minutes after the start of continuous inhalation of {sup 15}O gas, the {sup 15}O activity of the brain was found to be in a steady-state condition. During this steady-state condition, PET scannings were performed for about 10 minutes. Regions of interest, square in shape and having an area of 2.8 cm{sup 3}, were set in each cortex on PET images of a horizontal cross-section of the brain, set at 45 mm above the orbitomeatal line. The rCBF and rCMRO{sub 2} were analysed in 5 of 10 male subjects during both wakefulness and NREM sleep, and only 3 were done during three sleep stages, including REM sleep. Levels of rCBF and rCMRO{sub 2} were found to be decreased in NREM sleep, and the decreasing rates were calculated at 10.2% and 7.6% from the level of wakefulness, respectively. There was no significant difference in the mean value of rOEF between wakefulness and NREM sleep. There were no significant regional differences found in the rate of decrease among the frontal, temporal and occipital cortices. It was considered that the decrease of rCBF and rCMRO{sub 2} during NREM sleep suggested a decrease of the activity levels in the cerebral functions. (author).

  1. Regional cerebral blood flow and oxygen consumption during normal human sleep

    International Nuclear Information System (INIS)

    Takahashi, Ken

    1989-01-01

    Regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rCEF) and regional cerebral metabolic rate for oxygen (rCMRO 2 ) were measured using the continuous inhalation technique for 15 O with positron emission tomography (PET) during both wakefulness and sleep. Ten paid volunteers, with a mean age of 21.6 yrs., were deprived of sleep for a period of approximately 20 hours, and the experiments were performed mostly in the morning. 15 O activity of both whole blood and the plasma, pixel count of PET, total arterial blood oxygen content were used for analysis of rCBF, rOEF and rCMRO 2 . PET scannings were carried out mostly during the very light non-rapid eye movement (NREM) sleep, i.e. stage 1 and/or 2, and wakefulness. About 10 minutes after the start of continuous inhalation of 15 O gas, the 15 O activity of the brain was found to be in a steady-state condition. During this steady-state condition, PET scannings were performed for about 10 minutes. Regions of interest, square in shape and having an area of 2.8 cm 3 , were set in each cortex on PET images of a horizontal cross-section of the brain, set at 45 mm above the orbitomeatal line. The rCBF and rCMRO 2 were analysed in 5 of 10 male subjects during both wakefulness and NREM sleep, and only 3 were done during three sleep stages, including REM sleep. Levels of rCBF and rCMRO 2 were found to be decreased in NREM sleep, and the decreasing rates were calculated at 10.2% and 7.6% from the level of wakefulness, respectively. There was no significant difference in the mean value of rOEF between wakefulness and NREM sleep. There were no significant regional differences found in the rate of decrease among the frontal, temporal and occipital cortices. It was considered that the decrease of rCBF and rCMRO 2 during NREM sleep suggested a decrease of the activity levels in the cerebral functions. (author)

  2. Physicians' attentional performance following a 24-hour observation period: do we need to regulate sleep prior to work?

    Science.gov (United States)

    Smyth, P; Maximova, K; Jirsch, J D

    2017-08-01

    The tradition of physicians working while sleep deprived is increasingly criticised. Medical regulatory bodies have restricted resident physician duty-hours, not addressing the greater population of physicians. We aimed to assess factors such as sleep duration prior to a 24-hour observation period on physicians' attention. We studied 70 physicians (mean age 38 years old (SD 10.8 years)): 36 residents and 34 faculty from call rosters at the University of Alberta. Among 70 physicians, 52 (74%) performed overnight call; 18 did not perform overnight call and were recruited to control for the learning effect of repetitive neuropsychological testing. Attentional Network Test (ANT) measured physicians' attention at the beginning and end of the 24-hour observation period. Participants self-reported ideal sleep needs, sleep duration in the 24 hours prior to (ie, baseline) and during the 24-hour observation period (ie, follow-up). Median regression models examined effects on ANT parameters. Sleep deprivation at follow-up was associated with reduced attentional accuracy following the 24-hour observation period, but only for physicians more sleep deprived at baseline. Other components of attention were not associated with sleep deprivation after adjusting for repetitive testing. Age, years since medical school and caffeine use did not impact changes in ANT parameters. Our study suggests that baseline sleep before 24 hours of observation impacts the accuracy of physicians' attentional testing at 24 hours. Further study is required to determine if optimising physician sleep prior to overnight call shifts is a sustainable strategy to mitigate the effects of sleep deprivation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Stress, arousal, and sleep

    NARCIS (Netherlands)

    Sanford, Larry D.; Suchecki, Deborah; Meerlo, Peter; Meerlo, Peter; Benca, Ruth M.; Abel, Ted

    2015-01-01

    Stress is considered to be an important cause of disrupted sleep and insomnia. However, controlled and experimental studies in rodents indicate that effects of stress on sleep-wake regulation are complex and may strongly depend on the nature of the stressor. While most stressors are associated with

  4. Interactions between sleep disorders and oral diseases.

    Science.gov (United States)

    Huynh, N T; Emami, E; Helman, J I; Chervin, R D

    2014-04-01

    Dental sleep medicine is a rapidly growing field that is in close and direct interaction with sleep medicine and comprises many aspects of human health. As a result, dentists who encounter sleep health and sleep disorders may work with clinicians from many other disciplines and specialties. The main sleep and oral health issues that are covered in this review are obstructive sleep apnea, chronic mouth breathing, sleep-related gastroesophageal reflux, and sleep bruxism. In addition, edentulism and its impact on sleep disorders are discussed. Improving sleep quality and sleep characteristics, oral health, and oral function involves both pathophysiology and disease management. The multiple interactions between oral health and sleep underscore the need for an interdisciplinary clinical team to manage oral health-related sleep disorders that are commonly seen in dental practice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Influencing circadian and sleep-wake regulation for prevention and intervention in mood and anxiety disorders

    DEFF Research Database (Denmark)

    Frank, Ellen; Benabou, Marion; Bentzley, Brandon

    2014-01-01

    for the inability to study living brain tissue through the study of homeostatic mechanisms in fibroblasts, pluripotent human cells, and mitochondria and determine how homeostasis is disturbed at the level of these peripheral tissues through exogenous stress. We also emphasize the remarkable opportunities...

  6. Regulation of human renin expression in chorion cell primary cultures

    International Nuclear Information System (INIS)

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

    1990-01-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

  7. [Sleep disorders in epilepsy].

    Science.gov (United States)

    Kotova, O V; Akarachkova, E S

    2014-01-01

    The review of the literature on sleep disorders in epilepsy over the last two decades is presented. Paroxysmal phenomena of epileptic origin, nonepileptic paroxysms, antiepileptic drugs, polypragmasia and comorbid depression may affect sleep in epilepsy.Shortening of sleep time may cause seizures, hallucinations and depression because sleep plays an important role in the regulation of excitatory and inhibitory processes in the brain both in healthy people and in patients with epilepsy. According to the literature data, drugs (short treatment courses of hypnotics) or nonpharmacological methods should be used for treatment insomnia inpatients with epilepsy.

  8. Linear and non-linear interdependence of EEG and HRV frequency bands in human sleep.

    Science.gov (United States)

    Chaparro-Vargas, Ramiro; Dissanayaka, P Chamila; Patti, Chanakya Reddy; Schilling, Claudia; Schredl, Michael; Cvetkovic, Dean

    2014-01-01

    The characterisation of functional interdependencies of the autonomic nervous system (ANS) stands an evergrowing interest to unveil electroencephalographic (EEG) and Heart Rate Variability (HRV) interactions. This paper presents a biosignal processing approach as a supportive computational resource in the estimation of sleep dynamics. The application of linear, non-linear methods and statistical tests upon 10 overnight polysomnographic (PSG) recordings, allowed the computation of wavelet coherence and phase locking values, in order to identify discerning features amongst the clinical healthy subjects. Our findings showed that neuronal oscillations θ, α and σ interact with cardiac power bands at mid-to-high rank of coherence and phase locking, particularly during NREM sleep stages.

  9. Cortical deactivation induced by visual stimulation in human slow-wave sleep

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Law, Ian; Lund, Torben E

    2002-01-01

    It has previously been demonstrated that sleeping and sedated young children respond with a paradoxical decrease in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the rostro-medial occipital visual cortex during visual stimulation. It is unreso...... that this decrease was secondary to a relative rCBF decrease. Possible mechanisms for the paradoxical response pattern during sleep include an active inhibition of the visual cortex or a disruption of an energy-consuming process...

  10. The Effects of Sleep Deprivation on Pain

    OpenAIRE

    Kundermann, Bernd; Krieg, Jürgen-Christian; Schreiber, Wolfgang; Lautenbacher, Stefan

    2004-01-01

    Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can c...

  11. Alcohol and the sleeping brain.

    Science.gov (United States)

    Colrain, Ian M; Nicholas, Christian L; Baker, Fiona C

    2014-01-01

    Alcohol acts as a sedative that interacts with several neurotransmitter systems important in the regulation of sleep. Acute administration of large amounts of alcohol prior to sleep leads to decreased sleep-onset latency and changes in sleep architecture early in the night, when blood alcohol levels are high, with subsequent disrupted, poor-quality sleep later in the night. Alcohol abuse and dependence are associated with chronic sleep disturbance, lower slow-wave sleep, and more rapid-eye-movement sleep than normal, that last long into periods of abstinence and may play a role in relapse. This chapter outlines the evidence for acute and chronic alcohol effects on sleep architecture and sleep electroencephalogram, evidence for tolerance with repeated administration, and possible underlying neurochemical mechanisms for alcohol's effects on sleep. Also discussed are sex differences as well as effects of alcohol on sleep homeostasis and circadian regulation. Evidence for the role of sleep disruption as a risk factor for developing alcohol dependence is discussed in the context of research conducted in adolescents. The utility of sleep-evoked potentials in the assessment of the effects of alcoholism on sleep and the brain and in abstinence-mediated recovery is also outlined. The chapter concludes with a series of questions that need to be answered to determine the role of sleep and sleep disturbance in the development and maintenance of problem drinking and the potential beneficial effects of the treatment of sleep disorders for maintenance of abstinence in alcoholism. © 2014 Elsevier B.V. All rights reserved.

  12. Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats.

    Science.gov (United States)

    Hu, Zhenzhen; Lee, Chung-Il; Shah, Vikash Kumar; Oh, Eun-Hye; Han, Jin-Yi; Bae, Jae-Ryong; Lee, Kinam; Chong, Myong-Soo; Hong, Jin Tae; Oh, Ki-Wan

    2013-01-01

    Cordycepin (3'-deoxyadenosine) is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs), like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs). Sleep was recorded using electroencephalogram (EEG) for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM) sleep. Interestingly, cordycepin increased θ (theta) waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B) were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

  13. Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats

    Directory of Open Access Journals (Sweden)

    Zhenzhen Hu

    2013-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs, like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs. Sleep was recorded using electroencephalogram (EEG for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM sleep. Interestingly, cordycepin increased θ (theta waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

  14. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Science.gov (United States)

    Trivedi, Malav S; Holger, Dana; Bui, Anh Tuyet; Craddock, Travis J A; Tartar, Jaime L

    2017-01-01

    Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD) in young adult humans can influence systemic (plasma-derived) redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09) underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's sleep deprivation (maintaining wakefulness) uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  15. Cognitive Emotional Regulation Model in Human-Robot Interaction

    OpenAIRE

    Liu, Xin; Xie, Lun; Liu, Anqi; Li, Dan

    2015-01-01

    This paper integrated Gross cognitive process into the HMM (hidden Markov model) emotional regulation method and implemented human-robot emotional interaction with facial expressions and behaviors. Here, energy was the psychological driving force of emotional transition in the cognitive emotional model. The input facial expression was translated into external energy by expression-emotion mapping. Robot’s next emotional state was determined by the cognitive energy (the stimulus after cognition...

  16. Legal regulation of the protection of animals in human care

    OpenAIRE

    Kubánková, Lenka

    2014-01-01

    This diploma thesis summarizes regulation of animal in human care protection. It describes international conventions and also European Union and Czech laws. It includes definition of animal and categorizations of animals. The status of animal in Czech civil law is content of this thesis too. On international level are the most important conventions of Council of Europe. The part of this work concerning European Union includes conceptual tools, primary law and secondary law. The main law in Cz...

  17. Overnight changes in the slope of sleep slow waves during infancy.

    Science.gov (United States)

    Fattinger, Sara; Jenni, Oskar G; Schmitt, Bernhard; Achermann, Peter; Huber, Reto

    2014-02-01

    Slow wave activity (SWA, 0.5-4.5 Hz) is a well-established marker for sleep pressure in adults. Recent studies have shown that increasing sleep pressure is reflected by an increased synchronized firing pattern of cortical neurons, which can be measured by the slope of sleep slow waves. Thus we aimed at investigating whether the slope of sleep slow waves might provide an alternative marker to study the homeostatic regulation of sleep during early human development. All-night sleep electroencephalography (EEG) was recorded longitudinally at 2, 4, 6, and 9 months after birth. Home recording. 11 healthy full-term infants (5 male, 6 female). None. The slope of sleep slow waves increased with age. At all ages the slope decreased from the first to the last hour of non rapid-eye-movement (NREM) sleep, even when controlling for amplitude differences (P why the steepest slope was found in the occipital derivation. Our results provide evidence that the homeostatic regulation of sleep develops early in human infants.

  18. Sleep and Chronic Disease

    Science.gov (United States)

    ... regulates appetite and the expenditure of energy. 3 Depression The relationship between sleep and depression is complex. ... Promotion , Division of Population Health Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  19. Effects of ambient temperature on sleep and cardiovascular regulation in mice: the role of hypocretin/orexin neurons.

    Directory of Open Access Journals (Sweden)

    Viviana Lo Martire

    Full Text Available The central neural pathways underlying the physiological coordination between thermoregulation and the controls of the wake-sleep behavior and cardiovascular function remain insufficiently understood. Growing evidence supports the involvement of hypocretin (orexin peptides in behavioral, cardiovascular, and thermoregulatory functions. We investigated whether the effects of ambient temperature on wake-sleep behavior and cardiovascular control depend on the hypothalamic neurons that release hypocretin peptides. Orexin-ataxin3 transgenic mice with genetic ablation of hypocretin neurons (n = 11 and wild-type controls (n = 12 were instrumented with electrodes for sleep scoring and a telemetric blood pressure transducer. Simultaneous sleep and blood pressure recordings were performed on freely-behaving mice at ambient temperatures ranging between mild cold (20°C and the thermoneutral zone (30°C. In both mouse groups, the time spent awake and blood pressure were higher at 20°C than at 30°C. The cold-related increase in blood pressure was significantly smaller in rapid-eye-movement sleep (REMS than either in non-rapid-eye-movement sleep (NREMS or wakefulness. Blood pressure was higher in wakefulness than either in NREMS or REMS at both ambient temperatures. This effect was significantly blunted in orexin-ataxin3 mice irrespective of ambient temperature and particularly during REMS. These data demonstrate that hypocretin neurons are not a necessary part of the central pathways that coordinate thermoregulation with wake-sleep behavior and cardiovascular control. Data also support the hypothesis that hypocretin neurons modulate changes in blood pressure between wakefulness and the sleep states. These concepts may have clinical implications in patients with narcolepsy with cataplexy, who lack hypocretin neurons.

  20. Effects of ambient temperature on sleep and cardiovascular regulation in mice: the role of hypocretin/orexin neurons.

    Science.gov (United States)

    Lo Martire, Viviana; Silvani, Alessandro; Bastianini, Stefano; Berteotti, Chiara; Zoccoli, Giovanna

    2012-01-01

    The central neural pathways underlying the physiological coordination between thermoregulation and the controls of the wake-sleep behavior and cardiovascular function remain insufficiently understood. Growing evidence supports the involvement of hypocretin (orexin) peptides in behavioral, cardiovascular, and thermoregulatory functions. We investigated whether the effects of ambient temperature on wake-sleep behavior and cardiovascular control depend on the hypothalamic neurons that release hypocretin peptides. Orexin-ataxin3 transgenic mice with genetic ablation of hypocretin neurons (n = 11) and wild-type controls (n = 12) were instrumented with electrodes for sleep scoring and a telemetric blood pressure transducer. Simultaneous sleep and blood pressure recordings were performed on freely-behaving mice at ambient temperatures ranging between mild cold (20°C) and the thermoneutral zone (30°C). In both mouse groups, the time spent awake and blood pressure were higher at 20°C than at 30°C. The cold-related increase in blood pressure was significantly smaller in rapid-eye-movement sleep (REMS) than either in non-rapid-eye-movement sleep (NREMS) or wakefulness. Blood pressure was higher in wakefulness than either in NREMS or REMS at both ambient temperatures. This effect was significantly blunted in orexin-ataxin3 mice irrespective of ambient temperature and particularly during REMS. These data demonstrate that hypocretin neurons are not a necessary part of the central pathways that coordinate thermoregulation with wake-sleep behavior and cardiovascular control. Data also support the hypothesis that hypocretin neurons modulate changes in blood pressure between wakefulness and the sleep states. These concepts may have clinical implications in patients with narcolepsy with cataplexy, who lack hypocretin neurons.

  1. Effects of chronic sleep deprivation on the extracellular signal-regulated kinase pathway in the temporomandibular joint of rats.

    Directory of Open Access Journals (Sweden)

    Chuan Ma

    Full Text Available OBJECTIVES: To examine the possible involvement and regulatory mechanisms of extracellular signal-regulated kinase (ERK pathway in the temporomandibular joint (TMJ of rats subjected to chronic sleep deprivation (CSD. METHODS: Rats were subjected to CSD using the modified multiple platform method (MMPM. The serum levels of corticosterone (CORT and adrenocorticotropic hormone (ACTH were tested and histomorphology and ultrastructure of the TMJ were observed. The ERK and phospho-ERK (p-ERK expression levels were detected by Western blot analysis, and the MMP-1, MMP-3, and MMP-13 expression levels were detected by real-time quantitative polymerase chain reaction (PCR and Western blotting. RESULTS: The elevated serum CORT and ACTH levels confirmed that the rats were under CSD stress. Hematoxylin and eosin (HE staining and scanning electron microscopy (SEM showed pathological alterations in the TMJ following CSD; furthermore, the p-ERK was activated and the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13 were upregulated after CSD. In the rats administered with the selective ERK inhibitor U0126, decreased tissue destruction was observed. Phospho-ERK activation was visibly blocked and the MMP-1, MMP-3, and MMP-13 mRNA and protein levels were lower than the corresponding levels in the CSD without U0126 group. CONCLUSION: These findings indicate that CSD activates the ERK pathway and upregulates the MMP-1, MMP-3, and MMP-13 mRNA and protein levels in the TMJ of rats. Thus, CSD induces ERK pathway activation and causes pathological alterations in the TMJ. ERK may be associated with TMJ destruction by promoting the expression of MMPs.

  2. Cutaneous warming promotes sleep onset

    NARCIS (Netherlands)

    Raymann, Roy J. E. M.; Swaab, Dick F.; van Someren, Eus J. W.

    2005-01-01

    Sleep occurs in close relation to changes in body temperature. Both the monophasic sleep period in humans and the polyphasic sleep periods in rodents tend to be initiated when core body temperature is declining. This decline is mainly due to an increase in skin blood flow and consequently skin

  3. Cutaneous warming promotes sleep onset.

    NARCIS (Netherlands)

    Raymann, R.J.E.M.; Swaab, D.F.; Someren, E.J.W. van

    2005-01-01

    Sleep occurs in close relation to changes in body temperature. Both the monophasic sleep period in humans and the polyphasic sleep periods in rodents tend to be initiated when core body temperature is declining. This decline is mainly due to an increase in skin blood flow and consequently skin

  4. Self-regulated dynamical criticality in human ECoG

    Directory of Open Access Journals (Sweden)

    Guillermo eSolovey

    2012-07-01

    Full Text Available Mounting experimental and theoretical results indicate that neural systems are poised near a critical state. In human subjects, however, most evidence comes from functional MRI studies, an indirect measurement of neuronal activity with poor temporal resolution. Electrocorticography (ECoG provides a unique window into human brain activity: each electrode records, with high temporal resolution, the activity resulting from the sum of the local field potentials of sim 10^5 neurons. We show that the human brain ECoG recordings display features of self-regulated dynamical criticality: dynamical modes of activation drift around the critical stability threshold, moving in and out of the unstable region and equilibrating the global dynamical state at a very fast time scale. Moreover, the analysis also reveals differences between the resting state and a motor task, associated with increased stability of a fraction of the dynamical modes.

  5. Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS).

    Science.gov (United States)

    Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

    2016-09-01

    Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

  6. Sleep Quiz

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Sleep Quiz Past Issues / Summer 2007 Table of Contents ... on. Photo: iStock Take the National Center on Sleep Disorders Research Sleep Quiz TRUE OR FALSE ? _____1. ...

  7. Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

    Science.gov (United States)

    Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

    2010-01-01

    Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

  8. Sleep and metabolic function.

    Science.gov (United States)

    Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.

  9. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  10. Sleep loss and structural plasticity.

    Science.gov (United States)

    Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

    2017-06-01

    Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Intermittent hypoxia initiated plasticity in humans: A multipronged therapeutic approach to treat sleep apnea and overlapping co-morbidities.

    Science.gov (United States)

    Mateika, Jason H; Komnenov, Dragana

    2017-01-01

    Over the past three decades exposure to intermittent hypoxia (IH) has generally been considered a stimulus associated with a number of detrimental outcomes. However, there is sufficient evidence to link IH to many beneficial outcomes but they have largely been ignored, particularly in the field of sleep medicine in the United States. Recent reviews have postulated that this apparent contradiction is related to the severity and duration of exposure to IH; mild forms of IH initiate beneficial outcomes while severe forms of IH are coupled to detrimental consequences. In the present review we explore the role that IH has in initiating respiratory plasticity and the potential this form of plasticity has to mitigate obstructive sleep apnea (OSA) in humans. In taking this approach, we address the possibility that IH could serve as an adjunct therapy coupled with continuous positive airway pressure (CPAP) to treat OSA. Our working hypothesis is that exposure to mild IH leads to respiratory plasticity that manifests in increased stability of the upper airway, which could ultimately reduce the CPAP required to treat OSA. In turn, this reduction could increase CPAP compliance and extend the length of treatment each night, which might improve the magnitude of outcome measures. Improved treatment compliance coupled with the direct effect that IH has on numerous overlapping conditions (i.e. asthma, chronic obstructive pulmonary disease, spinal cord injury) may well lead to substantial improvements that exceed outcomes following treatment with CPAP alone. Overall, this review will consider evidence from the published literature which suggests that IH could serve as an effective multipronged therapeutic approach to treat sleep apnea and its overlapping co-morbidities. Published by Elsevier Inc.

  12. The Degree of Radiation-Induced DNA Strand Breaks Is Altered by Acute Sleep Deprivation and Psychological Stress and Is Associated with Cognitive Performance in Humans.

    Science.gov (United States)

    Moreno-Villanueva, Maria; von Scheven, Gudrun; Feiveson, Alan; Bürkle, Alexander; Wu, Honglu; Goel, Namni

    2018-03-27

    Sleep deprivation is associated with impaired immune responses, cancer, and morbidity and mortality, and can degrade cognitive performance, although individual differences exist in such responses. Sleep deprivation induces DNA strand breaks and DNA base oxidation in animals, and psychological stress is associated with increased DNA damage in humans. It remains unknown whether sleep deprivation or psychological stress in humans affects DNA damage response from environmental stressors, and whether these responses predict cognitive performance during sleep deprivation. Sixteen healthy adults (ages 29-52;mean age±SD, 36.4±7.1 years;7 women) participated in a 5-day experiment involving two 8 hour time-in-bed [TIB] baseline nights, followed by 39 hours total sleep deprivation (TSD), and two 8-10 hour TIB recovery nights. A modified Trier Social Stress Test was conducted on the day after TSD. Psychomotor Vigilance Tests measured behavioral attention. DNA damage was assessed in blood cells collected at 5 time points, and blood cells were irradiated ex-vivo. TSD, alone or in combination with psychological stress, did not induce significant increases in DNA damage. By contrast, radiation-induced DNA damage decreased significantly in response to TSD, but increased back to baseline when combined with psychological stress. Cognitively-vulnerable individuals had more radiation-induced DNA strand breaks before TSD, indicating their greater sensitivity to DNA damage from environmental stressors. Our results provide novel insights into the molecular consequences of sleep deprivation, psychological stress, and performance vulnerability. They are important for situations involving sleep loss, radiation exposure and cognitive deficits, including cancer therapy, environmental toxicology, and space medicine.

  13. Jaw-opening reflex and corticobulbar motor excitability changes during quiet sleep in non-human primates

    DEFF Research Database (Denmark)

    Yao, Dongyuan; Lavigne, Gilles J.; Lee, Jye-Chang

    2013-01-01

    Study Objective: To test the hypothesis that the reflex and corticobulbar motor excitability of jaw muscles is reduced during sleep. Design: Polysomnographic recordings in the electrophysiological study. Setting: University sleep research laboratories. Participants and Interventions: The reflex a...

  14. Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

    Science.gov (United States)

    Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

    2015-04-01

    Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. © 2014 John Wiley & Sons Ltd.

  15. Discrimination of Fearful and Angry Emotional Voices in Sleeping Human Neonates: a Study of the Mismatch Brain Responses

    Directory of Open Access Journals (Sweden)

    Dandan eZhang

    2014-12-01

    Full Text Available Appropriate processing of human voices with different threat-related emotions is of evolutionarily adaptive value for the survival of individuals. Nevertheless, it is still not clear whether the sensitivity to threat-related information is present at birth. Using an oddball paradigm, the current study investigated the neural correlates underlying automatic processing of emotional voices of fear and anger in sleeping neonates. Event-related potential data showed that the frontocentral scalp distribution of the neonatal brain could discriminate fearful voices from angry voices; the mismatch response (MMR was larger in response to the deviant stimuli of anger, compared with the standard stimuli of fear. Furthermore, this fear-anger MMR discrimination was observed only when neonates were in active sleep state. Although the neonates’ sensitivity to threat-related voices is not likely associated with a conceptual understanding of fearful and angry emotions, this special discrimination in early life may provide a foundation for later emotion and social cognition development.

  16. Functional neuroimaging of sleep disorders

    International Nuclear Information System (INIS)

    Qiu Chun; Zhao Jun; Guan Yihui

    2013-01-01

    Sleep disorders may affect the health and normal life of human badly. However, the pathophysiology underlying adult sleep disorders is still unclear. Functional neuroimaging can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. This paper reviews functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). Metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging) are mainly reviewed, as well as neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy). Meanwhile, here are some brief introduction of different kinds of sleep disorders. (authors)

  17. Structural insights into central hypertension regulation by human aminopeptidase A.

    Science.gov (United States)

    Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

    2013-08-30

    Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.

  18. Structural Insights into Central Hypertension Regulation by Human Aminopeptidase A*

    Science.gov (United States)

    Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

    2013-01-01

    Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3′ subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors. PMID:23888046

  19. Functional consequences of brain glycogen deficiency on the sleep-wake cycle regulation in PTG-KO mice

    KAUST Repository

    Burlet-Godinot, S.; Allaman, I.; Grenningloh, G.; Roach, P.J.; Depaoli-Roach, A.A.; Magistretti, Pierre J.; Petit, J.-M.

    2017-01-01

    in the brain in mice while glycogen levels were paradoxically maintained and not affected. In order to gain further insight on the role of PTG in this process, we studied the sleep/wake cycle parameters in PTG knockout (PTG-KO) mice under baseline conditions

  20. The Effects of Sleep Deprivation on Pain

    Directory of Open Access Journals (Sweden)

    Bernd Kundermann

    2004-01-01

    Full Text Available Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can counteract analgesic effects of pharmacological treatments involving opioidergic and serotoninergic mechanisms of action. The heterogeneity of the human data and the exclusive interest in rapid eye movement sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity. The significance of opioidergic and serotoninergic processes as mediating mechanisms of the hyperalgesic changes produced by sleep deprivation are discussed.

  1. Obstructive Sleep Apnea, Oxidative Stress, and Cardiovascular Disease: Evidence from Human Studies

    Directory of Open Access Journals (Sweden)

    Hans-Joachim Eisele

    2015-01-01

    Full Text Available Obstructive sleep apnea (OSA is a frequent disease mainly affecting obese people and caused by repetitive collapse of the upper airways during sleep. The increased morbidity and mortality of OSA are mainly thought to be the consequence of its adverse effects on cardiovascular (CV health. In this context, oxidative stress induced by nocturnal intermittent hypoxia has been identified to play a major role. This is suggested by biomarker studies in OSA patients showing excessively generated reactive oxygen species from leukocytes, reduced plasma levels of nitrite and nitrate, increased lipid peroxidation, and reduced antioxidant capacity. Biopsy studies complement these findings by demonstrating reduced endothelial nitric oxide synthase expression and increased nitrotyrosine immunofluorescence in the vasculature of these patients. Furthermore, oxidative stress in OSA correlates with surrogate markers of CV disease such as endothelial function, intima-media thickness, and high blood pressure. Continuous positive airway pressure therapy reverses oxidative stress in OSA. The same may be true for antioxidants; however, more studies are needed to clarify this issue.

  2. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Wildschiødtz, Gordon

    1991-01-01

    on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography...... associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep.......It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions...

  3. Regulating hematology/oncology research involving human participants.

    Science.gov (United States)

    Kapp, Marshall B

    2002-12-01

    The conduct of hematology/oncology research, particularly clinical trials involving human participants, is an extensively regulated enterprise. Professionals in the specialty of hematology/oncology have important stakes in the success of biomedical research endeavors. Knowledge about and compliance strategies regarding the pertinent regulatory parameters are essential for avoiding negative legal repercussions for involved professionals. At the same time, there is a need to be aware of and actively resist the danger that strong [legal] protectionism might inadvertently result in undermining physician investigators' sense of personal moral responsibility in the conduct of human experiments. For all the limitations of that virtue in the protection of human subjects, it is surely not one that we would want medical scientists to be without [47]. Members of the potential participant pool, financial sponsors, and the general public must be convinced that everyone involved in the research enterprise is committed to operating within acceptable legal and ethical boundaries if the atmosphere of confidence and trust that is indispensable to the continued process and progress of investigation aimed at extending and improving quality of life for all of us in the future is to continue and flourish [48].

  4. Piezo1 regulates mechanotransductive release of ATP from human RBCs.

    Science.gov (United States)

    Cinar, Eyup; Zhou, Sitong; DeCourcey, James; Wang, Yixuan; Waugh, Richard E; Wan, Jiandi

    2015-09-22

    Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca(2+) influx decrease significantly. Remarkably, a critical extracellular Ca(2+) concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease.

  5. Sleep deprivation impairs spatial retrieval but not spatial learning in the non-human primate grey mouse lemur.

    Directory of Open Access Journals (Sweden)

    Anisur Rahman

    Full Text Available A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus, which is an interesting model of aging and Alzheimer's disease (AD. Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.

  6. Time delay between cardiac and brain activity during sleep transitions

    NARCIS (Netherlands)

    Long, X.; Arends, J.B.A.M.; Aarts, R.M.; Haakma, R.; Fonseca, P.; Rolink, J.

    2015-01-01

    Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by

  7. A model of BIS/BAS sensitivity, emotion regulation difficulties, and depression, anxiety, and stress symptoms in relation to sleep quality.

    Science.gov (United States)

    Markarian, Shaunt A; Pickett, Scott M; Deveson, Danielle F; Kanona, Brenda B

    2013-11-30

    Recent research has indicated that interactions between behavioral inhibition system (BIS)/behavioral activation system (BAS) sensitivity and emotion regulation (ER) difficulties increases risk for psychopathology. Considering sleep quality (SQ) has been linked to emotion regulation difficulties (ERD) and psychopathology, further investigation of a possible mechanism is needed. The current study examined associations between BIS/BAS sensitivity, ERD, and SQ to depression, anxiety, and stress symptoms in an undergraduate sample (n=459). Positive relationships between BIS sensitivity and both ERD and stress symptoms, and negative relationships between BAS-reward sensitivity and both ERD and depression symptoms were observed. Furthermore, ERD were positively related to depression, anxiety, and stress symptoms. Succeeding analyses revealed differential relationships between ERD and depression, anxiety, and stress symptoms among good quality and poor quality sleepers. The findings are discussed within the context of personality dimensions and self-regulatory mechanisms, along with implications for the treatment of depression, anxiety and sleep difficulties. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. YY1 positively regulates human UBIAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Nobuaki, E-mail: nfunahashi@ri.ncgm.go.jp [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Hirota, Yoshihisa [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka (Japan); Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Suhara, Yoshitomo [Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama (Japan); Okano, Toshio [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan)

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1

  9. YY1 positively regulates human UBIAD1 expression

    International Nuclear Information System (INIS)

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-01-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K 1 ) and a series of bacterial menaquionones (MK-n; vitamin K 2 ). Menadione (vitamin K 3 ) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter

  10. The Function of Sleep

    Directory of Open Access Journals (Sweden)

    Daniel A. Barone

    2015-06-01

    Full Text Available The importance of sleep can be ascertained by noting the effects of its loss, which tends to be chronic and partial, on cognition, mood, alertness, and overall health. Many theories have been put forth to explain the function of sleep in humans, including proposals based on energy conservation, ecological adaptations, neurocognitive function, neural plasticity, nervous system and physical health, and performance. Most account for only a portion of sleep behavior and few are based on strong experimental support. In this review, we present theories proposing why sleep is necessary and supporting data demonstrating the effects of inadequate sleep, with the intention of gleaning further information as to its necessity, which remains one of the most perplexing mysteries in biology.

  11. Update of sleep alterations in depression

    Directory of Open Access Journals (Sweden)

    Andrés Barrera Medina

    2014-09-01

    Full Text Available Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy.

  12. Update of sleep alterations in depression

    Science.gov (United States)

    Medina, Andrés Barrera; Lechuga, DeboraYoaly Arana; Escandón, Oscar Sánchez; Moctezuma, Javier Velázquez

    2014-01-01

    Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy. PMID:26483922

  13. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Directory of Open Access Journals (Sweden)

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  14. Regulation of potassium transport in human lens epithelial cells.

    Science.gov (United States)

    Lauf, Peter K; Warwar, Ronald; Brown, Thomas L; Adragna, Norma C

    2006-01-01

    The major K influx pathways and their response to thiol modification by N-ethylmaleimide (NEM) and protein kinase and phosphatase inhibitors were characterized in human lens epithelial B3 (HLE-B3) cells with Rb as K congener. Ouabain (0.1 mM) and bumetanide (5 microM) discriminated between the Na/K pump ( approximately 35% of total Rb influx) and Na-K-2Cl cotransport (NKCC) ( approximately 50%). Cl-replacement with nitrate or sulfamate revealed 100 microM, activated the Na/K pump and abolished NKCC but did not affect KCC. The data suggest at least partial inverse regulation of KCC and NKCC in HLE-B3 cells by signaling cascades involving serine, threonine and tyrosine phosphorylation/dephosphorylation equilibria.

  15. EML proteins in microtubule regulation and human disease.

    Science.gov (United States)

    Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

    2016-10-15

    The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  16. Investigating microenvironmental regulation of human chordoma cell behaviour.

    Directory of Open Access Journals (Sweden)

    Priya Patel

    Full Text Available The tumour microenvironment is complex and composed of many different constituents, including matricellular proteins such as connective tissue growth factor (CCN2, and is characterized by gradients in oxygen levels. In various cancers, hypoxia and CCN2 promote stem and progenitor cell properties, and regulate the proliferation, migration and phenotype of cancer cells. Our study was aimed at investigating the effects of hypoxia and CCN2 on chordoma cells, using the human U-CH1 cell line. We demonstrate that under basal conditions, U-CH1 cells express multiple CCN family members including CCN1, CCN2, CCN3 and CCN5. Culture of U-CH1 cells in either hypoxia or in the presence of recombinant CCN2 peptide promoted progenitor cell-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia induced the most robust increase in progenitor-like characteristics in U-CH1 cells, including increased expression of the notochord-associated markers T, CD24, FOXA1, ACAN and CA12, increased cell growth and tumour-sphere formation, and a decrease in the percentage of vacuolated cells present in the heterogeneous population. Interestingly, the effects of recombinant CCN2 peptide on U-CH1 cells were more pronounced under normoxia than hypoxia, promoting increased expression of CCN1, CCN2, CCN3 and CCN5, the notochord-associated markers SOX5, SOX6, T, CD24, and FOXA1 as well as increased tumour-sphere formation. Overall, this study highlights the importance of multiple factors within the tumour microenvironment and how hypoxia and CCN2 may regulate human chordoma cell behaviour.

  17. The human oxytocin gene promoter is regulated by estrogens.

    Science.gov (United States)

    Richard, S; Zingg, H H

    1990-04-15

    Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be

  18. Chronobiological methods of human body self-regulation reserve evaluation

    Directory of Open Access Journals (Sweden)

    Sergey N. Zaguskin

    2013-05-01

    Full Text Available Aims Chronodiagnostical methods for evaluating reserve and unfavourable responses of human cardiac function and under prolonged stress load. Materials and methods 24-h ECG R–R interval recording of Holter-monitoring ECG recording and 1-h IPI and RespI recordings of healthy young and elderly subjects, post- MI patients, subjects suffered from chronic cerebral ischemia leading to a cognitive decline, healthy subjects following post-stress load, as well as R– R intervals recordings of the AHA ECG database of heart failure and AF. Chronodiagnostics, using non-linear symbolic dynamics method and redundancy quotient of ECG PI, RespI and R– R intervals; differential temperature survey to evaluate cellular immunity; biocontrolled laser therapy. Results Self-regulation reserve reduction of oxygen transfer body systems and increase in unfavourable response probability under stress load are accompanied by the amplitude and fluctuation increase of redundancy quotient in the ECG IPI, RespI and R–R intervals, as well as increase of hierarchical desynchronosis with dominating sympathicotonia and vagotonia, decrease in cellular immunity, reduction in rate spectrum of the ECG IPI and R–R intervals. Conclusion Symbolic dynamics method provides distinction between age-related and abnormal changes in hierarchy of cardiac rhythms. The amplitude and fluctuation increase of redundancy quotient indicates the increase of control intensity with oxygen transfer body systems and predicts the reduction of self-regulation reserve in cardiac rhythms and unfavourable response probability.

  19. Nonrandom variability in respiratory cycle parameters of humans during stage 2 sleep.

    Science.gov (United States)

    Modarreszadeh, M; Bruce, E N; Gothe, B

    1990-08-01

    We analyzed breath-to-breath inspiratory time (TI), expiratory time (TE), inspiratory volume (VI), and minute ventilation (Vm) from 11 normal subjects during stage 2 sleep. The analysis consisted of 1) fitting first- and second-order autoregressive models (AR1 and AR2) and 2) obtaining the power spectra of the data by fast-Fourier transform. For the AR2 model, the only coefficients that were statistically different from zero were the average alpha 1 (a1) for TI, VI, and Vm (a1 = 0.19, 0.29, and 0.15, respectively). However, the power spectra of all parameters often exhibited peaks at low frequency (less than 0.2 cycles/breath) and/or at high frequency (greater than 0.2 cycles/breath), indicative of periodic oscillations. After accounting for the corrupting effects of added oscillations on the a1 estimates, we conclude that 1) breath-to-breath fluctuations of VI, and to a lesser extent TI and Vm, exhibit a first-order autoregressive structure such that fluctuations of each breath are positively correlated with those of immediately preceding breaths and 2) the correlated components of variability in TE are mostly due to discrete high- and/or low-frequency oscillations with no underlying autoregressive structure. We propose that the autoregressive structure of VI, TI, and Vm during spontaneous breathing in stage 2 sleep may reflect either a central neural mechanism or the effects of noise in respiratory chemical feedback loops; the presence of low-frequency oscillations, seen more often in Vm, suggests possible instability in the chemical feedback loops. Mechanisms of high-frequency periodicities, seen more often in TE, are unknown.

  20. Sleep and Obesity

    Directory of Open Access Journals (Sweden)

    Chenzhao Ding

    2018-03-01

    Full Text Available Rising global prevalence and incidence of obesity lead to increased cardiovascular-renal complications and cancers. Epidemiological studies reported a worldwide trend towards suboptimal sleep duration and poor sleep quality in parallel with this obesity epidemic. From rodents and human models, it is highly plausible that abnormalities in sleep, both quantity and quality, impact negatively on energy metabolism. While excess dietary intake and physical inactivity are the known drivers of the obesity epidemic, promotion of healthy sleep habits has emerged as a new target to combat obesity. In this light, present review focuses on the existing literature examining the relationship between sleep physiology and energy homeostasis. Notably, sleep dysregulation perturbs the metabolic milieu via alterations in hormones such as leptin and ghrelin, eating behavior, neuroendocrine and autonomic nervous systems. In addition, shift work and trans-meridian air travel may exert a negative influence on the hypothalamic-pituitary-adrenal axis and trigger circadian misalignment, leading to impaired glucose tolerance and increased fat accumulation. Amassing evidence has also suggested that uncoupling of the circadian clock can increase the risk of adverse metabolic health. Given the importance of sleep in maintaining energy homeostasis and that it is potentially modifiable, promoting good sleep hygiene may create new avenues for obesity prevention and treatment.

  1. Sleep-Active Neurons: Conserved Motors of Sleep

    Science.gov (United States)

    Bringmann, Henrik

    2018-01-01

    Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The “motor” of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the “drivers” of the sleep motor: arousal inhibits “sleep-active” neurons whereas various sleep-promoting “tiredness” pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems. PMID:29618588

  2. Sleep deprivation impairs object recognition in mice

    NARCIS (Netherlands)

    Palchykova, S; Winsky-Sommerer, R; Meerlo, P; Durr, R; Tobler, Irene

    2006-01-01

    Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in in object

  3. Developmental regulation of human truncated nerve growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. (Abbott Laboratories, Abbott Park, IL (USA))

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  4. Developmental regulation of human truncated nerve growth factor receptor

    International Nuclear Information System (INIS)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R.

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system

  5. Self-organized dynamical complexity in human wakefulness and sleep: Different critical brain-activity feedback for conscious and unconscious states

    Science.gov (United States)

    Allegrini, Paolo; Paradisi, Paolo; Menicucci, Danilo; Laurino, Marco; Piarulli, Andrea; Gemignani, Angelo

    2015-09-01

    Criticality reportedly describes brain dynamics. The main critical feature is the presence of scale-free neural avalanches, whose auto-organization is determined by a critical branching ratio of neural-excitation spreading. Other features, directly associated to second-order phase transitions, are: (i) scale-free-network topology of functional connectivity, stemming from suprathreshold pairwise correlations, superimposable, in waking brain activity, with that of ferromagnets at Curie temperature; (ii) temporal long-range memory associated to renewal intermittency driven by abrupt fluctuations in the order parameters, detectable in human brain via spatially distributed phase or amplitude changes in EEG activity. Herein we study intermittent events, extracted from 29 night EEG recordings, including presleep wakefulness and all phases of sleep, where different levels of mentation and consciousness are present. We show that while critical avalanching is unchanged, at least qualitatively, intermittency and functional connectivity, present during conscious phases (wakefulness and REM sleep), break down during both shallow and deep non-REM sleep. We provide a theory for fragmentation-induced intermittency breakdown and suggest that the main difference between conscious and unconscious states resides in the backwards causation, namely on the constraints that the emerging properties at large scale induce to the lower scales. In particular, while in conscious states this backwards causation induces a critical slowing down, preserving spatiotemporal correlations, in dreamless sleep we see a self-organized maintenance of moduli working in parallel. Critical avalanches are still present, and establish transient auto-organization, whose enhanced fluctuations are able to trigger sleep-protecting mechanisms that reinstate parallel activity. The plausible role of critical avalanches in dreamless sleep is to provide a rapid recovery of consciousness, if stimuli are highly arousing.

  6. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors during the day, and especially ... team at an AASM accredited sleep center . Quick Sleep Tips Follow these tips to establish healthy sleep ...

  7. Obstructive Sleep Apnea

    Medline Plus

    Full Text Available ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ...

  8. Obstructive Sleep Apnea

    Science.gov (United States)

    ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ...

  9. Regulation of MYCN expression in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Jacobs, Joannes FM; Bokhoven, Hans van; Leeuwen, Frank N van; Hulsbergen-van de Kaa, Christina A; Vries, I Jolanda M de; Adema, Gosse J; Hoogerbrugge, Peter M; Brouwer, Arjan PM de

    2009-01-01

    Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (ΔMYCN) that was recently identified in fetal tissues. Both MYCNOS and ΔMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level. Expression of MYCN, MYCNOS and ΔMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay (QPCR). In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR (gQPCR). Both ΔMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:ΔMYCN expression was identical in all tested NBs. This indicates that ΔMYCN and MYCN are co-regulated, which suggests that ΔMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage (p = 0.007). In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level. The MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by ΔMYCN

  10. Sleep Apnea

    Science.gov (United States)

    Sleep apnea is a common disorder that causes your breathing to stop or get very shallow. Breathing ... an hour. The most common type is obstructive sleep apnea. It causes your airway to collapse or ...

  11. 29 CFR 553.222 - Sleep time.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Sleep time. 553.222 Section 553.222 Labor Regulations... Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.222 Sleep time... enforcement personnel in accordance with section 7(a)(1) of the Act, the public agency may exclude sleep time...

  12. Entropy Information of Cardiorespiratory Dynamics in Neonates during Sleep

    Directory of Open Access Journals (Sweden)

    Maristella Lucchini

    2017-05-01

    Full Text Available Sleep is a central activity in human adults and characterizes most of the newborn infant life. During sleep, autonomic control acts to modulate heart rate variability (HRV and respiration. Mechanisms underlying cardiorespiratory interactions in different sleep states have been studied but are not yet fully understood. Signal processing approaches have focused on cardiorespiratory analysis to elucidate this co-regulation. This manuscript proposes to analyze heart rate (HR, respiratory variability and their interrelationship in newborn infants to characterize cardiorespiratory interactions in different sleep states (active vs. quiet. We are searching for indices that could detect regulation alteration or malfunction, potentially leading to infant distress. We have analyzed inter-beat (RR interval series and respiration in a population of 151 newborns, and followed up with 33 at 1 month of age. RR interval series were obtained by recognizing peaks of the QRS complex in the electrocardiogram (ECG, corresponding to the ventricles depolarization. Univariate time domain, frequency domain and entropy measures were applied. In addition, Transfer Entropy was considered as a bivariate approach able to quantify the bidirectional information flow from one signal (respiration to another (RR series. Results confirm the validity of the proposed approach. Overall, HRV is higher in active sleep, while high frequency (HF power characterizes more quiet sleep. Entropy analysis provides higher indices for SampEn and Quadratic Sample entropy (QSE in quiet sleep. Transfer Entropy values were higher in quiet sleep and point to a major influence of respiration on the RR series. At 1 month of age, time domain parameters show an increase in HR and a decrease in variability. No entropy differences were found across ages. The parameters employed in this study help to quantify the potential for infants to adapt their cardiorespiratory responses as they mature. Thus, they

  13. Entropy Information of Cardiorespiratory Dynamics in Neonates during Sleep.

    Science.gov (United States)

    Lucchini, Maristella; Pini, Nicolò; Fifer, William P; Burtchen, Nina; Signorini, Maria G

    2017-05-01

    Sleep is a central activity in human adults and characterizes most of the newborn infant life. During sleep, autonomic control acts to modulate heart rate variability (HRV) and respiration. Mechanisms underlying cardiorespiratory interactions in different sleep states have been studied but are not yet fully understood. Signal processing approaches have focused on cardiorespiratory analysis to elucidate this co-regulation. This manuscript proposes to analyze heart rate (HR), respiratory variability and their interrelationship in newborn infants to characterize cardiorespiratory interactions in different sleep states (active vs. quiet). We are searching for indices that could detect regulation alteration or malfunction, potentially leading to infant distress. We have analyzed inter-beat (RR) interval series and respiration in a population of 151 newborns, and followed up with 33 at 1 month of age. RR interval series were obtained by recognizing peaks of the QRS complex in the electrocardiogram (ECG), corresponding to the ventricles depolarization. Univariate time domain, frequency domain and entropy measures were applied. In addition, Transfer Entropy was considered as a bivariate approach able to quantify the bidirectional information flow from one signal (respiration) to another (RR series). Results confirm the validity of the proposed approach. Overall, HRV is higher in active sleep, while high frequency (HF) power characterizes more quiet sleep. Entropy analysis provides higher indices for SampEn and Quadratic Sample entropy (QSE) in quiet sleep. Transfer Entropy values were higher in quiet sleep and point to a major influence of respiration on the RR series. At 1 month of age, time domain parameters show an increase in HR and a decrease in variability. No entropy differences were found across ages. The parameters employed in this study help to quantify the potential for infants to adapt their cardiorespiratory responses as they mature. Thus, they could be useful

  14. Leptin regulates dopamine responses to sustained stress in humans.

    Science.gov (United States)

    Burghardt, Paul R; Love, Tiffany M; Stohler, Christian S; Hodgkinson, Colin; Shen, Pei-Hong; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar

    2012-10-31

    Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.

  15. APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

    Science.gov (United States)

    Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

    2015-05-05

    Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Arvicanthis ansorgei, a Novel Model for the Study of Sleep and Waking in Diurnal Rodents

    Science.gov (United States)

    Hubbard, Jeffrey; Ruppert, Elisabeth; Calvel, Laurent; Robin-Choteau, Ludivine; Gropp, Claire-Marie; Allemann, Caroline; Reibel, Sophie; Sage-Ciocca, Dominique; Bourgin, Patrice

    2015-01-01

    Study Objectives: Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms. Design: Video-electroencephalogram (EEG), electromyogram (EMG), and electrooculogram (EOG) recordings. Setting: Rodent sleep laboratory. Participants: Fourteen male Arvicanthis ansorgei, aged 3 mo. Interventions: 12 h light (L):12 h dark (D) baseline condition, 24-h constant darkness, 6-h sleep deprivation. Measurements and Results: Wake and rapid eye movement (REM) sleep showed similar electrophysiological characteristics as nocturnal rodents. On average, animals spent 12.9 h ± 0.4 awake per 24-h cycle, of which 6.88 h ± 0.3 was during the light period. NREM sleep accounted for 9.63 h ± 0.4, which of 5.13 h ± 0.2 during dark period, and REM sleep for 89.9 min ± 6.7, which of 52.8 min ± 4.4 during dark period. The time-course of sleep and waking across the 12 h light:12 h dark was overall inverted to that observed in rats or mice, though with larger amounts of crepuscular activity at light and dark transitions. A dominant crepuscular regulation of sleep and waking persisted under constant darkness, showing the lack of a strong circadian drive in the absence of clock reinforcement by external cues, such as a running wheel. Conservation of the homeostatic regulation was confirmed with the observation of higher delta power following sustained waking periods and a 6-h sleep deprivation, with subsequent decrease during recovery sleep. Conclusions: Arvicanthis ansorgei is a valid diurnal rodent model for studying the regulatory mechanisms of sleep and so represents a valuable tool for further understanding the nocturnality/diurnality switch. Citation: Hubbard J, Ruppert E, Calvel L, Robin-Choteau L, Gropp CM

  17. Computer Simulation of Noise Effects of the Neighborhood of Stimulus Threshold for a Mathematical Model of Homeostatic Regulation of Sleep-Wake Cycles

    Directory of Open Access Journals (Sweden)

    Wuyin Jin

    2017-01-01

    Full Text Available The noise effects on a homeostatic regulation of sleep-wake cycles’ neuronal mathematical model determined by the hypocretin/orexin and the local glutamate interneurons spatiotemporal behaviors are studied within the neighborhood of stimulus threshold in this work; the neuronal noise added to the stimulus, the conductance, and the activation variable of the modulation function are investigated, respectively, based on a circadian input skewed in sine function. The computer simulation results suggested that the increased amplitude of external current input will lead to the fact that awakening time is advanced but the sleepy time remains the same; for the bigger conductance and modulation noise, the regulatory mechanism of the model sometimes will be collapsed and the coupled two neurons of the model show very irregular activities; the falling asleep or wake transform appears at nondeterminate time.

  18. Repeated sleep restriction in rats leads to homeostatic and allostatic responses during recovery sleep.

    Science.gov (United States)

    Kim, Youngsoo; Laposky, Aaron D; Bergmann, Bernard M; Turek, Fred W

    2007-06-19

    Recent studies indicate that chronic sleep restriction can have negative consequences for brain function and peripheral physiology and can contribute to the allostatic load throughout the body. Interestingly, few studies have examined how the sleep-wake system itself responds to repeated sleep restriction. In this study, rats were subjected to a sleep-restriction protocol consisting of 20 h of sleep deprivation (SD) followed by a 4-h sleep opportunity each day for 5 consecutive days. In response to the first 20-h SD block on day 1, animals responded during the 4-h sleep opportunity with enhanced sleep intensity [i.e., nonrapid eye movement (NREM) delta power] and increased rapid eye movement sleep time compared with baseline. This sleep pattern is indicative of a homeostatic response to acute sleep loss. Remarkably, after the 20-h SD blocks on days 2-5, animals failed to exhibit a compensatory NREM delta power response during the 4-h sleep opportunities and failed to increase NREM and rapid eye movement sleep times, despite accumulating a sleep debt each consecutive day. After losing approximately 35 h of sleep over 5 days of sleep restriction, animals regained virtually none of their lost sleep, even during a full 3-day recovery period. These data demonstrate that the compensatory/homeostatic sleep response to acute SD does not generalize to conditions of chronic partial sleep loss. We propose that the change in sleep-wake regulation in the context of repeated sleep restriction reflects an allostatic process, and that the allostatic load produced by SD has direct effects on the sleep-wake regulatory system.

  19. Characterization of scale-free properties of human electrocorticography in awake and slow wave sleep states

    Directory of Open Access Journals (Sweden)

    John M Zempel

    2012-06-01

    Full Text Available Like many complex dynamic systems, the brain exhibits scale-free dynamics that follow power law scaling. Broadband power spectral density (PSD of brain electrical activity exhibits state-dependent power law scaling with a log frequency exponent that varies across frequency ranges. Widely divergent naturally occurring neural states, awake and slow wave sleep (SWS periods, were used evaluate the nature of changes in scale-free indices. We demonstrate two analytic approaches to characterizing electrocorticographic (ECoG data obtained during Awake and SWS states. A data driven approach was used, characterizing all available frequency ranges. Using an Equal Error State Discriminator (EESD, a single frequency range did not best characterize state across data from all six subjects, though the ability to distinguish awake and SWS states in individual subjects was excellent. Multisegment piecewise linear fits were used to characterize scale-free slopes across the entire frequency range (0.2-200 Hz. These scale-free slopes differed between Awake and SWS states across subjects, particularly at frequencies below 10 Hz and showed little difference at frequencies above 70 Hz. A Multivariate Maximum Likelihood Analysis (MMLA method using the multisegment slope indices successfully categorized ECoG data in most subjects, though individual variation was seen. The ECoG spectrum is not well characterized by a single linear fit across a defined set of frequencies, but is best described by a set of discrete linear fits across the full range of available frequencies. With increasing computational tractability, the use of scale-free slope values to characterize EEG data will have practical value in clinical and research EEG studies.

  20. A new theoretical approach to the functional meaning of sleep and dreaming in humans based on the maintenance of 'predictive psychic homeostasis'.

    Science.gov (United States)

    Agnati, Luigi F; Barlow, Peter W; Baluška, František; Tonin, Paolo; Guescini, Michele; Leo, Giuseppina; Fuxe, Kjell

    2011-11-01

    Different theories have been put forward during the last decade to explain the functional meaning of sleep and dreaming in humans. In the present paper, a new theory is presented which, while taking advantage of these earlier theories, introduces the following new and original aspects:   • Circadian rhythms relevant to various organs of the body affect the reciprocal interactions which operate to maintain constancy of the internal milieu and thereby also affect the sleep/wakefulness cycle. Particular attention is given to the constancy of natraemia and osmolarity and to the permissive role that the evolution of renal function has had for the evolution of the central nervous system and its integrative actions. • The resetting of neuro-endocrine controls at the onset of wakefulness leads to the acquisition of new information and its integration within previously stored memories. This point is dealt with in relation to Moore-Ede's proposal for the existence of a 'predictive homeostasis'. • The concept of 'psychic homeostasis' is introduced and is considered as one of the most important states since it is aimed at the well-being, or eudemonia, of the human psyche. Sleep and dreaming in humans are discussed as important functions for the maintenance of a newly proposed composite state: that of 'predictive psychic homeostasis'. On the basis of these assumptions, and in accordance with the available neurobiological data, the present paper puts forward the novel hypothesis that sleep and dreaming play important functions in humans by compensating for psychic allostatic overloads. Hence, both consolatory dreams and disturbing nightmares can be part of the vis medicatrix naturae, the natural healing power, in this case, the state of eudemonia.

  1. Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifcally regulated in cortical astrocytes following sleep deprivation in mice

    KAUST Repository

    Petit, Jean Marie; Gyger, Joë l; Burlet-Godinot, Sophie; Fiumelli, Hubert; Martin, Jean Luc; Magistretti, Pierre J.

    2013-01-01

    deprivation (TSD). Setting: Animal sleep research laboratory. Participants: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Interventions: Basal sleep recordings and sleep deprivation achieved using a

  2. Cellular and Chemical Neuroscience of Mammalian Sleep

    OpenAIRE

    Datta, Subimal

    2010-01-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

  3. Sleep and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Dongwoo Kang

    2015-06-01

    Full Text Available Sleep architecture and sleep patterns normally change with aging. In preclinical Alzheimer’s disease (AD, the accumulation of amyloid plaques begins 10 to 20 years before any cognitive symptoms progress. Soluble amyloid-β (Aβ is secreted during physiological synaptic activity. Since synaptic activity is correlated with sleep and awake state, a degree of Aβ fluctuates in a diurnal sleep pattern. In animal and human studies, a degree of sleep quality showed a significant correlation with brain levels of Aβ and a risk of AD. Conversely, Aβ aggregation would debilitate neuronal function in brain regions critical to sleep and wake promotion. This bidirectional relationship can be explained as positive feedback loop and associated factors that influence this relationship. In AD, the degree of sleep disturbances is much more severe compared with in the normal elderly. Further, Sundowning syndrome and a reduction of melatonin level cause a stressful neuropsychiatric symptoms and a disruption of physiological sleep rhythm, respectively. In AD patients, a correlation between sleep architectural modifications and learning performances has been reported. Moreover, executive function and emotional reactivity might be attenuated by sleep disturbances, too. However, sleep disturbance does not impact cognitive functions of all patients with AD. This could support an individual and potentially genetically determined susceptibility. Sleep disturbances have an important effect on patients and caregivers. It has a critical value to confirm and treat individuals with sleep disorders and to explore whether good quality of sleep in humans can decrease the progression of preclinical to symptomatic AD.

  4. Sleep Deprivation Promotes Habitual Control over Goal-Directed Control: Behavioral and Neuroimaging Evidence.

    Science.gov (United States)

    Chen, Jie; Liang, Jie; Lin, Xiao; Zhang, Yang; Zhang, Yan; Lu, Lin; Shi, Jie

    2017-12-06

    Sleep is one of the most fundamental processes of life, playing an important role in the regulation of brain function. The long-term lack of sleep can cause memory impairments, declines in learning ability, and executive dysfunction. In the present study, we evaluated the effects of sleep deprivation on instrumental learning behavior, particularly goal-directed and habitual actions in humans, and investigated the underlying neural mechanisms. Healthy college students of either gender were enrolled and randomly divided into sleep deprivation group and sleep control group. fMRI data were collected. We found that one night of sleep deprivation led to greater responsiveness to stimuli that were associated with devalued outcomes in the slips-of-action test, indicating a deficit in the formation of goal-directed control and an overreliance on habits. Furthermore, sleep deprivation had no effect on the expression of acquired goal-directed action. The level of goal-directed action after sleep deprivation was positively correlated with baseline working memory capacity. The neuroimaging data indicated that goal-directed learning mainly recruited the ventromedial PFC (vmPFC), the activation of which was less pronounced during goal-directed learning after sleep deprivation. Activation of the vmPFC during goal-directed learning during training was positively correlated with the level of goal-directed action performance. The present study suggests that people rely predominantly on habits at the expense of goal-directed control after sleep deprivation, and this process involves the vmPFC. These results contribute to a better understanding of the effects of sleep loss on decision-making. SIGNIFICANCE STATEMENT Understanding the cognitive consequences of sleep deprivation has become extremely important over the past half century, given the continued decline in sleep duration in industrialized societies. Our results provide novel evidence that goal-directed action may be

  5. Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans.

    Science.gov (United States)

    Singh, Nisha; Sharpley, Ann L; Emir, Uzay E; Masaki, Charles; Herzallah, Mohammad M; Gluck, Mark A; Sharp, Trevor; Harmer, Catherine J; Vasudevan, Sridhar R; Cowen, Philip J; Churchill, Grant C

    2016-06-01

    Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function. We now report that in a double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm, and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder that can be tested in future clinical trials.

  6. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  7. Obstructive sleep apnea.

    Science.gov (United States)

    White, David P; Younes, Magdy K

    2012-10-01

    Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive collapse of the pharyngeal airway during sleep. Control of pharyngeal patency is a complex process relating primarily to basic anatomy and the activity of many pharyngeal dilator muscles. The control of these muscles is regulated by a number of processes including respiratory drive, negative pressure reflexes, and state (sleep) effects. In general, patients with OSA have an anatomically small airway the patency of which is maintained during wakefulness by reflex-driven augmented dilator muscle activation. At sleep onset, muscle activity falls, thereby compromising the upper airway. However, recent data suggest that the mechanism of OSA differs substantially among patients, with variable contributions from several physiologic characteristics including, among others: level of upper airway dilator muscle activation required to open the airway, increase in chemical drive required to recruit the pharyngeal muscles, chemical control loop gain, and arousal threshold. Thus, the cause of sleep apnea likely varies substantially between patients. Other physiologic mechanisms likely contributing to OSA pathogenesis include falling lung volume during sleep, shifts in blood volume from peripheral tissues to the neck, and airway edema. Apnea severity may progress over time, likely due to weight gain, muscle/nerve injury, aging effects on airway anatomy/collapsibility, and changes in ventilatory control stability. © 2012 American Physiological Society

  8. Sleep, Neuronal Plasticity and Brain Function

    NARCIS (Netherlands)

    Meerlo, Peter; Benca, Ruth M.; Abel, Ted

    2015-01-01

    Sleep is truly one of the biggest mysteries in behavioral neuroscience. Humans spend a substantial portion of their lives asleep, as do all other mammalian and bird species that have been studied to date, yet the functions of sleep remain elusive and continue to be a topic of debate among sleep

  9. Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

    Science.gov (United States)

    Zielinski, Mark R; Dunbrasky, Danielle L; Taishi, Ping; Souza, Gianne; Krueger, James M

    2013-08-01

    Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.

  10. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain.

    Science.gov (United States)

    Kim, Youngsoo; Elmenhorst, David; Weisshaupt, Angela; Wedekind, Franziska; Kroll, Tina; McCarley, Robert W; Strecker, Robert E; Bauer, Andreas

    2015-10-01

    Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in β-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. © 2015 European Sleep Research Society.

  11. Signaling pathways in PACAP regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Falktoft, B.; Georg, B.; Fahrenkrug, J.

    2009-01-01

    Ganglia expressing the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) innervate vasoactive intestinal peptide (VIP) containing neurons suggesting a role of PACAP in regulating VIP expression. Human NB-1 neuroblastoma cells were applied to study PACAP regulated VIP gene...... in PACAP regulation of the FOS and VIP gene expressions suggest for the first time a role of FOS in PACAP-induced VIP gene expression in human NB-1 neuroblastoma cells. (C) 2009 Elsevier Ltd. All rights reserved Udgivelsesdato: 2009/10...

  12. Regulation of human protein S gene (PROS1) transcription

    NARCIS (Netherlands)

    Wolf, Cornelia de

    2006-01-01

    This thesis describes the investigation of the transcriptional regulation of the gene for anticoagulant plasma Protein S, PROS1. Protein S is a cofactor for Protein C in the Protein C anticoagulant pathway. The coagulation cascade is negatively regulated by this pathway through inactivation of

  13. 78 FR 2229 - Health and Human Services Acquisition Regulation

    Science.gov (United States)

    2013-01-10

    ... information (regardless of the form or method of the recording) of a scientific or technical nature (including... (HHSAR)--to add two clauses, ``Patent Rights-- Exceptional Circumstances'' and ``Rights in Data....227-11 and 352.227-14'' by any of the following methods: Regulations.gov : http://www.regulations.gov...

  14. Topical review: sleep bruxism and the role of peripheral sensory influences.

    Science.gov (United States)

    Kato, Takafumi; Thie, Norman M; Huynh, Nelly; Miyawaki, Shouichi; Lavigne, Gilles J

    2003-01-01

    Sleep bruxism (SB) is an unusual orofacial movement described as a parafunction in dentistry and as a parasomnia in sleep medicine. Since several peripheral influences could be involved in sleep-wake regulation and the genesis of rhythmic jaw movements, the authors have reviewed the relevant literature to facilitate understanding of mechanisms possibly involved in SB genesis. Various animal and human studies indicate that during either wakefulness or anesthesia, orofacial sensory inputs (e.g., from periodontium, mucosa, and muscle) could influence jaw muscle activity. However, the role of these sensory inputs in jaw motor activity during sleep is unclear. Interestingly, during sleep, the jaw is usually open due to motor suppression; tooth contact most likely occurs in association with sleep arousal. Recent physiologic evidence supports an association between sleep arousal and SB; a sequential change from autonomic (cardiac) and brain cortical activities precede SB-related jaw motor activity. This suggests that the central and/or autonomic nervous systems, rather than peripheral sensory factors, have a dominant role in SB genesis. However, some peripheral sensory factors may exert an influence on SB through their interaction with sleep-wake mechanisms. The intent of this review is to integrate various physiologic concepts in order to better understand the mechanisms underlying the genesis of SB.

  15. Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

    Science.gov (United States)

    Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

    2009-01-01

    Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

  16. Analysis of the effects of non-supine sleeping positions on the stress, strain, deformation and intraocular pressure of the human eye

    Science.gov (United States)

    Volpe, Peter A.

    This thesis presents analytical models, finite element models and experimental data to investigate the response of the human eye to loads that can be experienced when in a non-supine sleeping position. The hypothesis being investigated is that non-supine sleeping positions can lead to stress, strain and deformation of the eye as well as changes in intraocular pressure (IOP) that may exacerbate vision loss in individuals who have glaucoma. To investigate the quasi-static changes in stress and internal pressure, a Fluid-Structure Interaction simulation was performed on an axisymmetrical model of an eye. Common Aerospace Engineering methods for analyzing pressure vessels and hyperelastic structural walls are applied to developing a suitable model. The quasi-static pressure increase was used in an iterative code to analyze changes in IOP over time.

  17. Voluntary Sleep Loss in Rats

    Science.gov (United States)

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  18. Sleep and Sleep-wake Rhythm in Older Adults with Intellectual Disabilities

    NARCIS (Netherlands)

    E. van de Wouw-Van Dijk (Ellen)

    2013-01-01

    textabstractEveryone who has experienced poor sleep knows how it affects daytime functioning and wellbeing. A good night’s rest and a stable sleep-wake rhythm are therefore very important. The sleep-wake rhythm is regulated by several brain structures. People with an intellectual disability (ID) all

  19. Effects of (± 3,4-Methylenedioxymethamphetamine (MDMA on Sleep and Circadian Rhythms

    Directory of Open Access Journals (Sweden)

    Una D. McCann

    2007-01-01

    Full Text Available Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA, may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in normal sleep regulation. In particular, MDMA has been found to damage brain serotonin (5-HT neurons in a variety of animal species, including nonhuman primates, with growing evidence that humans are also susceptible to MDMA-induced brain 5-HT neurotoxicity. 5-HT is an important modulator of sleep and circadian rhythms and, therefore, individuals who sustain MDMA-induced 5-HT neurotoxicity may be at risk for developing chronic abnormalities in sleep and circadian patterns. In turn, such abnormalities could play a significant role in other alterations reported in abstinent in MDMA users (e.g., memory disturbance. This paper will review preclinical and clinical studies that have explored the effects of prior MDMA exposure on sleep, circadian activity, and the circadian pacemaker, and will highlight current gaps in knowledge and suggest areas for future research.

  20. Sleep disorders - overview

    Science.gov (United States)

    Insomnia; Narcolepsy; Hypersomina; Daytime sleepiness; Sleep rhythm; Sleep disruptive behaviors; Jet lag ... excessive daytime sleepiness) Problems sticking to a regular sleep schedule (sleep rhythm problem) Unusual behaviors during sleep ( ...

  1. Central sleep apnea

    Science.gov (United States)

    Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... Central sleep apnea results when the brain temporarily stops sending signals to the muscles that control breathing. The condition ...

  2. Sleep Apnea (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Obstructive Sleep Apnea KidsHealth / For Parents / Obstructive Sleep Apnea What's ... How Is Sleep Apnea Treated? Print What Is Sleep Apnea? Brief pauses in breathing during sleep are ...

  3. Negative emotionality moderates associations among attachment, toddler sleep, and later problem behaviors.

    Science.gov (United States)

    Troxel, Wendy M; Trentacosta, Christopher J; Forbes, Erika E; Campbell, Susan B

    2013-02-01

    Secure parent-child relationships are implicated in children's self-regulation, including the ability to self-soothe at bedtime. Sleep, in turn, may serve as a pathway linking attachment security with subsequent emotional and behavioral problems in children. We used path analysis to examine the direct relationship between attachment security and maternal reports of sleep problems during toddlerhood and the degree to which sleep serves as a pathway linking attachment with subsequent teacher-reported emotional and behavioral problems. We also examined infant negative emotionality as a vulnerability factor that may potentiate attachment-sleep-adjustment outcomes. Data were drawn from 776 mother-infant dyads participating in the National Institute of Child and Human Development Study of Early Child Care. After statistically adjusting for mother and child characteristics, including child sleep and emotional and behavioral problems at 24 months, we found no evidence for a statistically significant direct path between attachment security and sleep problems at 36 months; however, there was a direct relationship between sleep problems at 36 months and internalizing problems at 54 months. Path models that examined the moderating influence of infant negative emotionality demonstrated significant direct relationships between attachment security and toddler sleep problems and between sleep problems and subsequent emotional and behavioral problems, but only among children characterized by high negative emotionality at 6 months. In addition, among this subset, there was a significant indirect path between attachment and internalizing problems through sleep problems. These longitudinal findings implicate sleep as one critical pathway linking attachment security with adjustment difficulties, particularly among temperamentally vulnerable children. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  4. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Directory of Open Access Journals (Sweden)

    Malav S Trivedi

    Full Text Available Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD in young adult humans can influence systemic (plasma-derived redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09 underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's < 0.01. Parallel to the well-recognized fact that sleep deprivation (maintaining wakefulness uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  5. The relationship of sleep with temperature and metabolic rate in a hibernating primate.

    Directory of Open Access Journals (Sweden)

    Andrew D Krystal

    Full Text Available STUDY OBJECTIVES: It has long been suspected that sleep is important for regulating body temperature and metabolic-rate. Hibernation, a state of acute hypothermia and reduced metabolic-rate, offers a promising system for investigating those relationships. Prior studies in hibernating ground squirrels report that, although sleep occurs during hibernation, it manifests only as non-REM sleep, and only at relatively high temperatures. In our study, we report data on sleep during hibernation in a lemuriform primate, Cheirogaleus medius. As the only primate known to experience prolonged periods of hibernation and as an inhabitant of more temperate climates than ground squirrels, this animal serves as an alternative model for exploring sleep temperature/metabolism relationships that may be uniquely relevant to understanding human physiology. MEASUREMENTS AND RESULTS: We find that during hibernation, non-REM sleep is absent in Cheirogaleus. Rather, periods of REM sleep occur during periods of relatively high ambient temperature, a pattern opposite of that observed in ground squirrels. Like ground squirrels, however, EEG is marked by ultra-low voltage activity at relatively low metabolic-rates. CONCLUSIONS: These findings confirm a sleep-temperature/metabolism link, though they also suggest that the relationship of sleep stage with temperature/metabolism is flexible and may differ across species or mammalian orders. The absence of non-REM sleep suggests that during hibernation in Cheirogaleus, like in the ground squirrel, the otherwise universal non-REM sleep homeostatic response is greatly curtailed or absent. Lastly, ultra-low voltage EEG appears to be a cross-species marker for extremely low metabolic-rate, and, as such, may be an attractive target for research on hibernation induction.

  6. Cold hands, warm feet: sleep deprivation disrupts thermoregulation and its association with vigilance.

    Science.gov (United States)

    Romeijn, Nico; Verweij, Ilse M; Koeleman, Anne; Mooij, Anne; Steimke, Rosa; Virkkala, Jussi; van der Werf, Ysbrand; Van Someren, Eus J W

    2012-12-01

    Vigilance is affected by induced and spontaneous skin temperature fluctuations. Whereas sleep deprivation strongly affects vigilance, no previous study examined in detail its effect on human skin temperature fluctuations and their association with vigilance. In a repeated-measures constant routine design, skin temperatures were assessed continuously from 14 locations while performance was assessed using a reaction time task, including eyes-open video monitoring, performed five times a day for 2 days, after a normal sleep or sleep deprivation night. Participants were seated in a dimly lit, temperature-controlled laboratory. Eight healthy young adults (five males, age 22.0 ± 1.8 yr (mean ± standard deviation)). One night of sleep deprivation. Mixed-effect regression models were used to evaluate the effect of sleep deprivation on skin temperature gradients of the upper (ear-mastoid), middle (hand-arm), and lower (foot-leg) body, and on the association between fluctuations in performance and in temperature gradients. Sleep deprivation induced a marked dissociation of thermoregulatory skin temperature gradients, indicative of attenuated heat loss from the hands co-occurring with enhanced heat loss from the feet. Sleep deprivation moreover attenuated the association between fluctuations in performance and temperature gradients; the association was best preserved for the upper body gradient. Sleep deprivation disrupts coordination of fluctuations in thermoregulatory skin temperature gradients. The dissociation of middle and lower body temperature gradients may therefore be evaluated as a marker for sleep debt, and the upper body gradient as a possible aid in vigilance assessment when sleep debt is unknown. Importantly, our findings suggest that sleep deprivation affects the coordination between skin blood flow fluctuations and the baroreceptor-mediated cardiovascular regulation that prevents venous pooling of blood in the lower limbs when there is the orthostatic

  7. Sleep, immunity and inflammation in gastrointestinal disorders.

    Science.gov (United States)

    Ali, Tauseef; Choe, James; Awab, Ahmed; Wagener, Theodore L; Orr, William C

    2013-12-28

    Sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many research endeavors. An estimated 70 million Americans suffer from some form of sleep disorder. Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability, slower response times and performance detriments. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. Several research studies support the associations among sleep, immune function and inflammation. Here, we review the current research linking sleep, immune function, and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders. Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep. The inflammatory cytokines such as tumor necrosis factor, interleukin-1 (IL-1), and IL-6 have been shown to be a significant contributor of sleep disturbances. On the other hand, sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines. Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease, gastro-esophageal reflux, liver disorders and colorectal cancer. In turn, abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases. Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.

  8. Sleep disordered breathing following spinal cord injury

    DEFF Research Database (Denmark)

    Biering-Sørensen, Fin; Jennum, Poul; Laub, Michael

    2009-01-01

    Individuals with spinal cord injury (SCI) commonly complain about difficulty in sleeping. Although various sleep disordered breathing definitions and indices are used that make comparisons between studies difficult, it seems evident that the frequency of sleep disorders is higher in individuals...... with SCI, especially with regard to obstructive sleep apnea. In addition, there is a correlation between the incidence of sleep disturbances and the spinal cord level injured, age, body mass index, neck circumference, abdominal girth, and use of sedating medications. Regulation of respiration is dependent...... on wakefulness and sleep. Thus, it is important to be aware of basic mechanisms in the regulation and control of sleep and awake states. Supine position decreases the vital capacity in tetraplegic individuals, and diminished responsiveness to Pa(CO)(2) may further decrease ventilatory reserve. There also may...

  9. Cellular and chemical neuroscience of mammalian sleep.

    Science.gov (United States)

    Datta, Subimal

    2010-05-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Manipulating the circadian and sleep cycles to protect against metabolic disease

    Directory of Open Access Journals (Sweden)

    Kazunari eNohara

    2015-03-01

    Full Text Available Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g. obesity involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude enhancing small molecules (CEMs identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep and metabolism will also have far-reaching implications for various chronic human diseases and aging.

  11. Manipulating the circadian and sleep cycles to protect against metabolic disease.

    Science.gov (United States)

    Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng Jake

    2015-01-01

    Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock, and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g., obesity) involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small molecules (CEMs) identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep, and metabolism will also have far-reaching implications for various chronic human diseases and aging.

  12. Impact of Acute Sleep Deprivation on Sarcasm Detection

    OpenAIRE

    Deliens, Ga?tane; Stercq, Fanny; Mary, Alison; Slama, Hichem; Cleeremans, Axel; Peigneux, Philippe; Kissine, Mikhail

    2015-01-01

    There is growing evidence that sleep plays a pivotal role on health, cognition and emotional regulation. However, the interplay between sleep and social cognition remains an uncharted research area. In particular, little is known about the impact of sleep deprivation on sarcasm detection, an ability which, once altered, may hamper everyday social interactions. The aim of this study is to determine whether sleep-deprived participants are as able as sleep-rested participants to adopt another pe...

  13. Top-down control of arousal and sleep: Fundamentals and clinical implications.

    Science.gov (United States)

    Krone, Lukas; Frase, Lukas; Piosczyk, Hannah; Selhausen, Peter; Zittel, Sulamith; Jahn, Friederike; Kuhn, Marion; Feige, Bernd; Mainberger, Florian; Klöppel, Stefan; Riemann, Dieter; Spiegelhalder, Kai; Baglioni, Chiara; Sterr, Annette; Nissen, Christoph

    2017-02-01

    Mammalian sleep emerges from attenuated activity in the ascending reticular arousal system (ARAS), the main arousal network of the brain. This system originates in the brainstem and activates the thalamus and cortex during wakefulness via a well-characterized 'bottom-up' pathway. Recent studies propose that a less investigated cortico-thalamic 'top-down' pathway also regulates sleep. The present work integrates the current evidence on sleep regulation with a focus on the 'top-down' pathway and explores the potential to translate this information into clinically relevant interventions. Specifically, we elaborate the concept that arousal and sleep continuity in humans can be modulated by non-invasive brain stimulation (NIBS) techniques that increase or decrease cortical excitability. Based on preclinical studies, the modulatory effects of the stimulation are thought to extend to subcortical arousal networks. Further exploration of the 'top-down' regulation of sleep and its modulation through non-invasive brain stimulation techniques may contribute to the development of novel treatments for clinical conditions of disrupted arousal and sleep, which are among the major health problems worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Complex sound processing during human REM sleep by recovering information from long-term memory as revealed by the mismatch negativity (MMN).

    Science.gov (United States)

    Atienza, M; Cantero, J L

    2001-05-18

    Perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. Evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. Therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human REM sleep. The MMN, an objective measure of the automatic change detection in auditory cortex, was used to evaluate long-term learning effects on pre-attentive processing during wakefulness and REM sleep. When subjects learned to discriminate two complex auditory patterns in wakefulness, an increase in the MMN was obtained in both wake and REM states. The automatic detection of the infrequent complex auditory pattern may therefore be improved in both brain states by reactivating information from long-term memory. These findings suggest that long-term learning-related neural changes are accessible during REM sleep as well.

  15. Chronic social stress leads to altered sleep homeostasis in mice.

    Science.gov (United States)

    Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

    2017-06-01

    Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The role of sleep and sleep deprivation in consolidating fear memories.

    Science.gov (United States)

    Menz, M M; Rihm, J S; Salari, N; Born, J; Kalisch, R; Pape, H C; Marshall, L; Büchel, C

    2013-07-15

    Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation.

    Science.gov (United States)

    Irwin, Michael R; Olmstead, Richard; Carroll, Judith E

    2016-07-01

    Sleep disturbance is associated with inflammatory disease risk and all-cause mortality. Here, we assess global evidence linking sleep disturbance, sleep duration, and inflammation in adult humans. A systematic search of English language publications was performed, with inclusion of primary research articles that characterized sleep disturbance and/or sleep duration or performed experimental sleep deprivation and assessed inflammation by levels of circulating markers. Effect sizes (ES) and 95% confidence intervals (CI) were extracted and pooled using a random effect model. A total of 72 studies (n > 50,000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Sleep disturbance was associated with higher levels of CRP (ES .12; 95% CI = .05-.19) and IL-6 (ES .20; 95% CI = .08-.31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES .09; 95% CI = .01-.17) but not IL-6 (ES .03; 95% CI: -.09 to .14). The extreme of long sleep duration was associated with higher levels of CRP (ES .17; 95% CI = .01-.34) and IL-6 (ES .11; 95% CI = .02-20). Neither sleep disturbances nor sleep duration was associated with TNFα. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα. Some heterogeneity among studies was found, but there was no evidence of publication bias. Sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Loss of consciousness is related to hyper-correlated gamma-band activity in anesthetized macaques and sleeping humans.

    Science.gov (United States)

    Bola, Michał; Barrett, Adam B; Pigorini, Andrea; Nobili, Lino; Seth, Anil K; Marchewka, Artur

    2018-02-15

    Loss of consciousness can result from a wide range of causes, including natural sleep and pharmacologically induced anesthesia. Important insights might thus come from identifying neuronal mechanisms of loss and re-emergence of consciousness independent of a specific manipulation. Therefore, to seek neuronal signatures of loss of consciousness common to sleep and anesthesia we analyzed spontaneous electrophysiological activity recorded in two experiments. First, electrocorticography (ECoG) acquired from 4 macaque monkeys anesthetized with different anesthetic agents (ketamine, medetomidine, propofol) and, second, stereo-electroencephalography (sEEG) from 10 epilepsy patients in different wake-sleep stages (wakefulness, NREM, REM). Specifically, we investigated co-activation patterns among brain areas, defined as correlations between local amplitudes of gamma-band activity. We found that resting wakefulness was associated with intermediate levels of gamma-band coupling, indicating neither complete dependence, nor full independence among brain regions. In contrast, loss of consciousness during NREM sleep and propofol anesthesia was associated with excessively correlated brain activity, as indicated by a robust increase of number and strength of positive correlations. However, such excessively correlated brain signals were not observed during REM sleep, and were present only to a limited extent during ketamine anesthesia. This might be related to the fact that, despite suppression of behavioral responsiveness, REM sleep and ketamine anesthesia often involve presence of dream-like conscious experiences. We conclude that hyper-correlated gamma-band activity might be a signature of loss of consciousness common across various manipulations and independent of behavioral responsiveness. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Losing Neutrality: The Neural Basis of Impaired Emotional Control without Sleep.

    Science.gov (United States)

    Simon, Eti Ben; Oren, Noga; Sharon, Haggai; Kirschner, Adi; Goldway, Noam; Okon-Singer, Hadas; Tauman, Rivi; Deweese, Menton M; Keil, Andreas; Hendler, Talma

    2015-09-23

    Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive-emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality. Significance statement: Sleep loss is known as a robust modulator of emotional reactivity, leading to increased anxiety and stress elicited by seemingly minor triggers. In this work, we aimed to portray the neural basis of these emotional impairments and their possible association with frontal regulation of emotional processing, also known as cognitive control of emotion. Using specifically suited EEG and f

  20. Transposable element activity, genome regulation and human health.

    Science.gov (United States)

    Wang, Lu; Jordan, I King

    2018-03-02

    A convergence of novel genome analysis technologies is enabling population genomic studies of human transposable elements (TEs). Population surveys of human genome sequences have uncovered thousands of individual TE insertions that segregate as common genetic variants, i.e. TE polymorphisms. These recent TE insertions provide an important source of naturally occurring human genetic variation. Investigators are beginning to leverage population genomic data sets to execute genome-scale association studies for assessing the phenotypic impact of human TE polymorphisms. For example, the expression quantitative trait loci (eQTL) analytical paradigm has recently been used to uncover hundreds of associations between human TE insertion variants and gene expression levels. These include population-specific gene regulatory effects as well as coordinated changes to gene regulatory networks. In addition, analyses of linkage disequilibrium patterns with previously characterized genome-wide association study (GWAS) trait variants have uncovered TE insertion polymorphisms that are likely causal variants for a variety of common complex diseases. Gene regulatory mechanisms that underlie specific disease phenotypes have been proposed for a number of these trait associated TE polymorphisms. These new population genomic approaches hold great promise for understanding how ongoing TE activity contributes to functionally relevant genetic variation within and between human populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Incorporating Human Factors into design change processes - a regulator's perspective

    International Nuclear Information System (INIS)

    Staples, L.; McRobbie, H.

    2003-01-01

    Nuclear power plants in Canada must receive written approval from the Canadian Nuclear Safety Commission (CNSC) when making certain changes that are defined in their licenses. The CNSC expects the design change process to include a method for ensuring that the human-machine interface and workplace design support the safe and reliable performance of required tasks. When reviewing design changes for approval, the CNSC looks for evidence of analysis work, use of appropriate human factors design guide-lines, and verification and validation testing of the design. In addition to reviewing significant design changes, evaluations are conducted to ensure design change processes adequately address human performance. Findings from reviews and evaluations highlight the need to integrate human factors into the design change process, provide human factors training and support to engineering staff, establish processes to ensure coordination between the various groups with a vested interest in human factors, and develop more rigorous methods to validate changes to maintenance, field operations and testing interfaces. (author)

  2. Uncovering the genetic landscape for multiple sleep-wake traits.

    Directory of Open Access Journals (Sweden)

    Christopher J Winrow

    Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

  3. Molecular imaging of in vivo calcium ion expression in area postrema of total sleep deprived rats: Implications for cardiovascular regulation by TOF-SIMS analysis

    Science.gov (United States)

    Mai, Fu-Der; Chen, Li-You; Ling, Yong-Chien; Chen, Bo-Jung; Wu, Un-In; Chang, Hung-Ming

    2010-05-01

    Excessive calcium influx in chemosensitive neurons of area postrema (AP) is detrimental for sympathetic activation and participates in the disruption of cardiovascular activities. Since total sleep deprivation (TSD) is a stressful condition known to harm the cardiovascular function, the present study is aimed to determine whether the in vivo calcium expression in AP would significantly alter following TSD by the use of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and calretinin (a specific calcium sensor protein in AP neurons) immunohistochemistry. The results indicated that in normal rats, the calcium intensity was estimated to be 0.5 × 10 5 at m/ z 40.08. However, following TSD, the intensity for calcium ions was greatly increased to 1.2 × 10 5. Molecular imaging revealed that after TSD, various strongly expressed calcium signals were distributed throughout AP with clear identified profiles instead of randomly scattered within this region in normal rats. Immunohistochemical staining corresponded well with ionic image in which a majority of calcium-enriched gathering co-localized with calretinin positive neurons. The functional significance of TSD-induced calcium augmentation was demonstrated by increased heart rate and mean arterial pressure, clinical markers for cardiovascular dysfunction. Considering AP-mediated sympathetic activation is important for cardiovascular regulation, exaggerated calcium influx in AP would render this neurocircuitry more vulnerable to over-excitation, which might serve as the underlying mechanism for the development of TSD-relevant cardiovascular deficiency.

  4. An experimental study on the effect of noise and sleep loss on human performance using the measure of TCI during NPP maintenance

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Hyun Jun

    2008-02-15

    There are various stressors in NPP maintenance, such as environmental stressors and work-related stressors. These stressors degrade human performance and increase human error. Stress has not been largely considered as a factor of human error in root cause analyses. Recently, however, regulatory bodies and research institutes have worked to manage the physical condition of the operator and improve the environment and methods of NPP maintenance. These efforts have focused on reducing the incidence of human error due to stress. It is necessary to study how much stress affects human performance before these efforts are complete. The objectives of the present study are to formulate a Task Concentration Index (TCI) based on Electrocardiogram (ECG) signals in order to evaluate the degree to which a person concentrates on a task experimentally. With the TCI, the study will also evaluate the effects of noise and sleep loss on human performance during NPP maintenance tasks. Stress influences the efficiency of information processing and data input and output. Stress and human error are tightly linked in a closed-loop combination. The human body responds to stress by activating the nervous system and specific hormones. Therefore, physiological signals are changed by stress. A spectral analysis of Heart Rate Variability (HRV) provides a noninvasive technique for indirectly measuring sympathetic and parasympathetic modulation during specific tasks. The high-frequency component (HF, 0.15∼0.4Hz) reflects momentary respiration and is mediated by the parasympathetic nervous system. The low-frequency component (LF, 0.04∼0.15Hz) has been interpreted mainly as an indicator of sympathetic influences (especially when expressed in normalized units). When the level of stress is high, the Normalized Low Frequency component (NoLF) of HRV signals is generally higher than the normal state. The difference in NoLF readings between a normal state and during a task could be used to evaluate

  5. An experimental study on the effect of noise and sleep loss on human performance using the measure of TCI during NPP maintenance

    International Nuclear Information System (INIS)

    Jo, Hyun Jun

    2008-02-01

    There are various stressors in NPP maintenance, such as environmental stressors and work-related stressors. These stressors degrade human performance and increase human error. Stress has not been largely considered as a factor of human error in root cause analyses. Recently, however, regulatory bodies and research institutes have worked to manage the physical condition of the operator and improve the environment and methods of NPP maintenance. These efforts have focused on reducing the incidence of human error due to stress. It is necessary to study how much stress affects human performance before these efforts are complete. The objectives of the present study are to formulate a Task Concentration Index (TCI) based on Electrocardiogram (ECG) signals in order to evaluate the degree to which a person concentrates on a task experimentally. With the TCI, the study will also evaluate the effects of noise and sleep loss on human performance during NPP maintenance tasks. Stress influences the efficiency of information processing and data input and output. Stress and human error are tightly linked in a closed-loop combination. The human body responds to stress by activating the nervous system and specific hormones. Therefore, physiological signals are changed by stress. A spectral analysis of Heart Rate Variability (HRV) provides a noninvasive technique for indirectly measuring sympathetic and parasympathetic modulation during specific tasks. The high-frequency component (HF, 0.15∼0.4Hz) reflects momentary respiration and is mediated by the parasympathetic nervous system. The low-frequency component (LF, 0.04∼0.15Hz) has been interpreted mainly as an indicator of sympathetic influences (especially when expressed in normalized units). When the level of stress is high, the Normalized Low Frequency component (NoLF) of HRV signals is generally higher than the normal state. The difference in NoLF readings between a normal state and during a task could be used to evaluate

  6. Dissimilarity of slow-wave activity enhancement by torpor and sleep deprivation in a hibernator

    NARCIS (Netherlands)

    Strijkstra, AM; Daan, S

    1998-01-01

    Sleep regulation processes have been hypothesized to be involved in function and timing of arousal episodes in hibernating ground squirrels. We investigated the importance of sleep regulation during arousal episodes by sleep deprivation experiments. After sleep deprivation of 4, 12, and 24 h,

  7. Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

    OpenAIRE

    Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

    2017-01-01

    Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundam...

  8. ER-16 regulation. Requirements for granting the permit exceptional use of medical devices in humans

    International Nuclear Information System (INIS)

    2015-01-01

    The purpose of this regulation is to establish requirements for applying for a permit exceptional use of medical equipment in Human Beings, the procedures for the evaluation process and bestowal. This regulation is aimed at researchers and designers of medical equipment, related to or associated with National Health Service's priority programs of interest to health.

  9. [Relationships between sleep and addiction].

    Science.gov (United States)

    Cañellas, Francesca; de Lecea, Luis

    2012-01-01

    While it is well known that there is an interaction between sleep disorders and substance abuse, it is certainly more complex than was previously thought. There is a positive relationship both between having a substance use disorder and suffering from a sleep disorder, and vice versa. The effects on sleep depend on the substance used, but it has been shown that both during use and in withdrawal periods consumers have various sleep problems, and basically more fragmented sleep. We know that sleep problems must be taken into account to prevent addiction relapses. Recent research shows that the hypocretinergic system defined by neuropeptide hypocretin / orexin (Hcrt / ox), located in the lateral hypothalamus and involved in, among other things, the regulation of the sleep-wake cycle, may play an important role in addictive behaviors. Different studies have demonstrated interactions between the hypocretinergic system, acute response to stress circuits and reward systems. We also know that selective optogenetic activation of the hypocretinergic system increases the probability of transition from sleep to wakefulness, and is sufficient for initiating an addictive compulsive behavior relapse. Hypocretinergic system activation could explain the hyperarousal associated with stress and addiction. Improved knowledge of this interaction would help us to understand better the mechanisms of addiction and find new strategies for the treatment of addictions.

  10. Association of napping and night-time sleep with impaired glucose regulation, insulin resistance and glycated haemoglobin in Chinese middle-aged adults with no diabetes: a cross-sectional study.

    Science.gov (United States)

    Baoying, Huang; Hongjie, Chen; Changsheng, Qiu; Peijian, Wu; Qingfei, Lin; Yinghua, Lin; Huibin, Huang; Jixing, Liang; Liantao, Li; Ling, Chen; Kaka, Tang; Zichun, Chen; Lixiang, Lin; Jieli, Lu; Yufang, Bi; Guang, Ning; Penli, Zhu; Junping, Wen; Gang, Chen

    2014-07-23

    To assess associations between napping and night-time sleep duration with impaired glucose regulation, insulin resistance (IR) and glycated haemoglobin (HbA1c). Cross-sectional study. Fujian Province, China, from June 2011 to January 2012. This study enrolled 9028 participants aged 40-65 years. Data of 7568 participants with no diabetes were included for analysis. Type 2 diabetes was defined applying WHO criteria. Participants' daytime napping and night-time sleep duration data were collected using a standardised self-reported Chinese-language questionnaire about sleep frequency and quality. Anthropometric and laboratory parameters were also measured. IR was defined as a HOMA-IR index value >2.50. ORs and 95% CIs were derived from multivariate logistic regression models. Participants (mean age 51.1±7.0 years) included 3060 males and 4508 females with average night-time sleep of 7.9 h. A higher proportion of males napped than females. After adjustment for potential confounders, ORs for HbA1c >6.0% were 1.28 and 1.26 for those napping ≤1 h and >1 h (p=0.002 and p=0.018), respectively. Statistically significant differences in IR between nappers and non-nappers were only marginal clinically. Odds for HbA1c >6.0% were significantly lower in participants with longer night-time sleep durations than in the reference group (>8 h vs 6-8 h). Odds for IR were significantly lower in participants whose night-time sleep hours deviated from the reference group (8 h vs 6-8 h) Chinese middle-aged adults with no diabetes who napped had higher HbA1c and IR; those with shorter night-time sleep durations had increased HbA1c. Night-time sleep hours that are either 8 tend to be associated with lower odds for IR. Further studies are necessary to determine the underlying clinical significance and mechanisms behind these associations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Medicines for sleep

    Science.gov (United States)

    Benzodiazepines; Sedatives; Hypnotics; Sleeping pills; Insomnia - medicines; Sleep disorder - medicines ... are commonly used to treat allergies. While these sleep aids are not addictive, your body becomes used ...

  12. Regulating corporate social and human rights responsibilities at the UN plane

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2009-01-01

    Globalisation's unprecedented growth and transborder activities of business coupled with increasing awareness of the impact of business on societies and human rights has resulted in demands for the international society to regulate corporate social and human rights responsibilities. This not only...... challenges traditional notions of duty bearers under international law, but also calls for novel approaches for the United Nations (UN) to implement central parts of the Charter's human rights aims and to address corporate behaviour in a state-centred international law-making order that lacks the willingness...... businesses' impact on human rights. The pattern of using these forms suggests an institutionalisation of reflexive regulation as a regulatory process drawing on public-private regulation, and of an emerging UN based 'Global Administrative Law' in order to meet regulatory challenges in living up to the human...

  13. Sleep Deprivation and the Epigenome

    Directory of Open Access Journals (Sweden)

    Marie E. Gaine

    2018-02-01

    Full Text Available Sleep deprivation disrupts the lives of millions of people every day and has a profound impact on the molecular biology of the brain. These effects begin as changes within a neuron, at the DNA and RNA level, and result in alterations in neuronal plasticity and dysregulation of many cognitive functions including learning and memory. The epigenome plays a critical role in regulating gene expression in the context of memory storage. In this review article, we begin by describing the effects of epigenetic alterations on the regulation of gene expression, focusing on the most common epigenetic mechanisms: (i DNA methylation; (ii histone modifications; and (iii non-coding RNAs. We then discuss evidence suggesting that sleep loss impacts the epigenome and that these epigenetic alterations might mediate the changes in cognition seen following disruption of sleep. The link between sleep and the epigenome is only beginning to be elucidated, but clear evidence exists that epigenetic alterations occur following sleep deprivation. In the future, these changes to the epigenome could be utilized as biomarkers of sleep loss or as therapeutic targets for sleep-related disorders.

  14. Sleep Deprivation and the Epigenome.

    Science.gov (United States)

    Gaine, Marie E; Chatterjee, Snehajyoti; Abel, Ted

    2018-01-01

    Sleep deprivation disrupts the lives of millions of people every day and has a profound impact on the molecular biology of the brain. These effects begin as changes within a neuron, at the DNA and RNA level, and result in alterations in neuronal plasticity and dysregulation of many cognitive functions including learning and memory. The epigenome plays a critical role in regulating gene expression in the context of memory storage. In this review article, we begin by describing the effects of epigenetic alterations on the regulation of gene expression, focusing on the most common epigenetic mechanisms: (i) DNA methylation; (ii) histone modifications; and (iii) non-coding RNAs. We then discuss evidence suggesting that sleep loss impacts the epigenome and that these epigenetic alterations might mediate the changes in cognition seen following disruption of sleep. The link between sleep and the epigenome is only beginning to be elucidated, but clear evidence exists that epigenetic alterations occur following sleep deprivation. In the future, these changes to the epigenome could be utilized as biomarkers of sleep loss or as therapeutic targets for sleep-related disorders.

  15. Recent advances in measuring cerebral blood flow and metabolism in human aging, cerebrovascular disease, dementia, sleep and the epilepsies

    International Nuclear Information System (INIS)

    Meyer, J.S.; Baylor Univ., Houston, TX

    1986-01-01

    The 133 Xe inhalation method, positron emission tomography (PET) scanning, X-ray transmission tomography by inhalation of 37.5% stable xenon gas during CT scanning, and nuclear magnetic resonance (NMR) techniques contributions to knowledge of normal aging, cerebrovascular disorders, the dementias, Parkinson's disease, epilepsy, normal and abnormal sleep, migraine and cluster headache are summarized. 62 refs.; 4 figs.; 2 tabs

  16. Laws and regulations associated with ownership of human ...

    African Journals Online (AJOL)

    2015-05-12

    May 12, 2015 ... to persons and which is, as an independent entity, subject to judicial control by a ... exclusive right in human tissue is acquired by any person who obtains .... The effect of such an event could result in the patient experiencing.

  17. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  18. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  19. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    International Nuclear Information System (INIS)

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-01-01

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial β-oxidation. The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that plays an important role in the regulation of β-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPARα and found that PPARα induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPARα regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  20. Androgen-Dependent Regulation of Human MUC1 Mucin Expression

    Directory of Open Access Journals (Sweden)

    Stephen Mitchell

    2002-01-01

    Full Text Available MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor. (20AR activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1protein expression: 1 AR+MUCi + [DAR17+19. (20AR transfectants of DU-145, ZR-75-1, MDA-MB-453, and T47D]; 2 AR-MUCi+ [DZeoi. (20AR- vector control, DU-145, BT20, MDA-MB231, and MCF7]; 3 AIR +MUCi -. (20LNCaP and LNCaP-r. Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 pM to 1 µM. Cell surface MUC1expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide. (204-OH, a nonsteroidal AR antagonist. The functional significance of MUC1expression was investigated with a cell-cell aggregation assay. Only AR+ MUC1 + cell lines showed a significant increase in MUC1expression with AR activation. (20P. (20range =.01 to .0001, reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1was associated with a significant. (20P. (20range =.002 to .001 reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.

  1. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures.

    Science.gov (United States)

    Potter, Gregory D M; Skene, Debra J; Arendt, Josephine; Cade, Janet E; Grant, Peter J; Hardie, Laura J

    2016-12-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

  2. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

    Science.gov (United States)

    Skene, Debra J.; Arendt, Josephine; Cade, Janet E.; Grant, Peter J.; Hardie, Laura J.

    2016-01-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important. PMID:27763782

  3. Sleep and sedation in the pediatric intensive care unit.

    Science.gov (United States)

    Carno, Margaret-Ann; Connolly, Heidi V

    2005-09-01

    Sleep is an important and necessary function of the human body. Somatic growth and cellular repair occur during sleep. Critically ill children have disturbed sleep while in the pediatric intensive care unit related both to the illness itself and to light, noise, and caregiver activities disrupting an environment conducive to sleep. Medications administered in the pediatric intensive care unit can also disrupt sleep. This article reviews what is known about sleep in the pediatric intensive care unit and the effects of common sedation medications on sleep.

  4. Prioritizing Sleep Health: Public Health Policy Recommendations.

    Science.gov (United States)

    Barnes, Christopher M; Drake, Christopher L

    2015-11-01

    The schedules that Americans live by are not consistent with healthy sleep patterns. In addition, poor access to educational and treatment aids for sleep leaves people engaging in behavior that is harmful to sleep and forgoing treatment for sleep disorders. This has created a sleep crisis that is a public health issue with broad implications for cognitive outcomes, mental health, physical health, work performance, and safety. New public policies should be formulated to address these issues. We draw from the scientific literature to recommend the following: establishing national standards for middle and high school start times that are later in the day, stronger regulation of work hours and schedules, eliminating daylight saving time, educating the public regarding the impact of electronic media on sleep, and improving access to ambulatory in-home diagnostic testing for sleep disorders. © The Author(s) 2015.

  5. Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.

    Science.gov (United States)

    Halassa, Michael M; Florian, Cedrick; Fellin, Tommaso; Munoz, James R; Lee, So-Young; Abel, Ted; Haydon, Philip G; Frank, Marcos G

    2009-01-29

    Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep, and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wild-type mice mimicked the transgenic phenotype, we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.

  6. Estimating adolescent sleep need using dose-response modeling.

    Science.gov (United States)

    Short, Michelle A; Weber, Nathan; Reynolds, Chelsea; Coussens, Scott; Carskadon, Mary A

    2018-04-01

    This study will (1) estimate the nightly sleep need of human adolescents, (2) determine the time course and severity of sleep-related deficits when sleep is reduced below this optimal quantity, and (3) determine whether sleep restriction perturbs the circadian system as well as the sleep homeostat. Thirty-four adolescents aged 15 to 17 years spent 10 days and nine nights in the sleep laboratory. Between two baseline nights and two recovery nights with 10 hours' time in bed (TIB) per night, participants experienced either severe sleep restriction (5-hour TIB), moderate sleep restriction (7.5-hour TIB), or no sleep restriction (10-hour TIB) for five nights. A 10-minute psychomotor vigilance task (PVT; lapse = response after 500 ms) and the Karolinska Sleepiness Scale were administered every 3 hours during wake. Salivary dim-light melatonin onset was calculated at baseline and after four nights of each sleep dose to estimate circadian phase. Dose-dependent deficits to sleep duration, circadian phase timing, lapses of attention, and subjective sleepiness occurred. Less TIB resulted in less sleep, more lapses of attention, greater subjective sleepiness, and larger circadian phase delays. Sleep need estimated from 10-hour TIB sleep opportunities was approximately 9 hours, while modeling PVT lapse data suggested that 9.35 hours of sleep is needed to maintain optimal sustained attention performance. Sleep restriction perturbs homeostatic and circadian systems, leading to dose-dependent deficits to sustained attention and sleepiness. Adolescents require more sleep for optimal functioning than typically obtained.

  7. Human genetics as a tool to identify progranulin regulators.

    Science.gov (United States)

    Nicholson, Alexandra M; Finch, NiCole A; Rademakers, Rosa

    2011-11-01

    Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases.

  8. CAROTID BODY CHEMO-REFLEX: A DRIVER OF AUTONOMIC ABNORMALITIES IN SLEEP APNEA

    Science.gov (United States)

    Prabhakar, Nanduri R.

    2016-01-01

    Carotid bodies are the principal peripheral chemoreceptors for detecting changes in arterial blood oxygen levels, and the resulting chemo-reflex is a potent regulator of the sympathetic tone, blood pressure, and breathing. Sleep apnea is a disease of the respiratory system affecting several million adult humans. Apneas occur during sleep often due to obstruction of the upper airway (obstructive sleep apnea, OSA) or due to defective respiratory rhythm generation by the central nervous system (central sleep apnea). Patients with sleep apnea exhibit several co-morbidities; most notable among them being the heightened sympathetic nerve activity, and hypertension. Emerging evidence suggests that intermittent hypoxia (IH) resulting from periodic apnea stimulates the carotid body and the ensuing chemo-reflex mediates the increased sympathetic tone and hypertension in sleep apnea patients. Rodent models of IH, simulating the O2 saturation profiles encountered during sleep apnea have provided important insights into the cellular and molecular mechanisms underlying the heightened carotid body chemo-reflex. This article describes how IH affects the carotid body function, and discusses the cellular, molecular and epigenetic mechanisms underlying the exaggerated chemo-reflex. PMID:27474260

  9. Robust, synergistic regulation of human gene expression using TALE activators.

    Science.gov (United States)

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  10. Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions

    OpenAIRE

    Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

    2015-01-01

    This study examined the shift of the human mesenchymal stem cell (hMSC) cytokine signature induced by oxygen tension. Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These results elucidate important aspects of using MSCs in regenerative medicine, contribute to improving the efficacy of such therapies, and highlight the interest in using c...

  11. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  12. Genetic regulation of pituitary gland development in human and mouse.

    Science.gov (United States)

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

    2009-12-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

  13. let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis

    Directory of Open Access Journals (Sweden)

    M. Patterson

    2014-11-01

    Full Text Available It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.

  14. Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

    Science.gov (United States)

    Zhang, Beilin; Gao, Yanxia; Li, Yang; Yang, Jing; Zhao, Hua

    2016-01-01

    Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis.

  15. Healthy Sleep

    Science.gov (United States)

    ... quality sleep, ask yourself Do you have trouble getting up in the morning? Do you have trouble focusing during the day? Do you doze off during the day? If you answered yes to these three questions, you should work on ...

  16. MHC class II molecules regulate growth in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K

    1994-01-01

    MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

  17. Muscle metaboreflex and autonomic regulation of heart rate in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Adlan, Ahmed M; Shantsila, Alena

    2013-01-01

    ) conditions, but attenuated with β-adrenergic blockade (0.2 ± 1 beats min(-1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg......We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling...... exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β1-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR...

  18. TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep.

    Directory of Open Access Journals (Sweden)

    Reto Huber

    2007-03-01

    Full Text Available Sleep slow wave activity (SWA is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning.To test this hypothesis directly, we used transcranial magnetic stimulation (TMS in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1+/-17.4%, p<0.01, n = 10. Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep.These results provide direct evidence for a link between plastic changes and the local regulation of sleep need.

  19. Dopamine Regulates Approach-Avoidance in Human Sensation-Seeking.

    Science.gov (United States)

    Norbury, Agnes; Kurth-Nelson, Zeb; Winston, Joel S; Roiser, Jonathan P; Husain, Masud

    2015-04-09

    Sensation-seeking is a trait that constitutes an important vulnerability factor for a variety of psychopathologies with high social cost. However, little is understood either about the mechanisms underlying motivation for intense sensory experiences or their neuropharmacological modulation in humans. Here, we first evaluate a novel paradigm to investigate sensation-seeking in humans. This test probes the extent to which participants choose either to avoid or self-administer an intense tactile stimulus (mild electric stimulation) orthogonal to performance on a simple economic decision-making task. Next we investigate in a different set of participants whether this behavior is sensitive to manipulation of dopamine D2 receptors using a within-subjects, placebo-controlled, double-blind design. In both samples, individuals with higher self-reported sensation-seeking chose a greater proportion of mild electric stimulation-associated stimuli, even when this involved sacrifice of monetary gain. Computational modelling analysis determined that people who assigned an additional positive economic value to mild electric stimulation-associated stimuli exhibited speeding of responses when choosing these stimuli. In contrast, those who assigned a negative value exhibited slowed responses. These findings are consistent with involvement of low-level, approach-avoidance processes. Furthermore, the D2 antagonist haloperidol selectively decreased the additional economic value assigned to mild electric stimulation-associated stimuli in individuals who showed approach reactions to these stimuli under normal conditions (behavioral high-sensation seekers). These findings provide the first direct evidence of sensation-seeking behavior being driven by an approach-avoidance-like mechanism, modulated by dopamine, in humans. They provide a framework for investigation of psychopathologies for which extreme sensation-seeking constitutes a vulnerability factor. © The Author 2015. Published by

  20. Pediatric sleep apnea

    Science.gov (United States)

    Sleep apnea - pediatric; Apnea - pediatric sleep apnea syndrome; Sleep-disordered breathing - pediatric ... Untreated pediatric sleep apnea may lead to: High blood pressure Heart or lung problems Slow growth and development

  1. Changing your sleep habits

    Science.gov (United States)

    ... falling asleep; Sleep hygiene References American Academy of Sleep Medicine. Insomnia. Updated March 4, 2015. SleepEducation.org. sleepeducation. ... T, Dement WC, eds. Principles and Practice of Sleep Medicine . 6th ed. Philadelphia, PA: Elsevier; 2017:chap 86. ...

  2. Obstructive Sleep Apnoea

    African Journals Online (AJOL)

    Cheyne-Stokes respiration), obstructive sleep apnoea and mixed or complex sleep apnoea.1. Obstructive sleep apnoea (OSA) is the most common of these three disorders and is defined as airway obstruction during sleep, accompanied by at least ...

  3. Snoring and Sleep Apnea

    Science.gov (United States)

    ... Find an ENT Doctor Near You Snoring and Sleep Apnea Snoring and Sleep Apnea Patient Health Information ... newsroom@entnet.org . Insight into sleeping disorders and sleep apnea Forty-five percent of normal adults snore ...

  4. Prostaglandins - universal biological regulators in the human body (literature review

    Directory of Open Access Journals (Sweden)

    О. V. Tymoshchuk

    2018-02-01

    Full Text Available Recently, researchers of different industries pay great attention to the problem of prostaglandins. Objective: to study and systematize the basic questions of structure, biological action and metabolism of prostaglandins in the human body and using their analogues in pharmacy through the domestic and foreign literature data analysis. Prostaglandins – biologically active substances which are similar in effect to hormones, but are synthesized in cells of different tissues. Prostaglandins as universal cellular mediators are widely distributed in the body, synthesized in small amounts in almost all tissues, have both local and systemic effects. For each prostaglandin there is a target organ. On chemical structure they are small molecules related to eicosanoids - a group of fat-like substances (lipids. Depending on the chemical structure prostaglandins are divided into series (A, B, C, D, E, F, G, H, I and J and three groups (1–3; type F isomers are to be indicated by additional letters α and β. Prostaglandins have an extremely wide range of physiological effects in the body and have three main functions: supporting, molecular, neurotransmitter. Most prostaglandins interact with specific receptors of plasma membranes, but some prostaglandins (group A can act without receptors. There is no stock of prostaglandins in the body, their life cycle is short, and they are quickly produced in response to biological stimulants exposure, have their effect in extremely small quantity and are rapidly inactivated in the bloodstream. Due to the extremely rapid breakdown of prostaglandins in the body they work near their place of secretion. Preparations of prostaglandins and their derivatives are used in experimental and clinical medicine for abortion and induction of labor, treatment of stomach ulcers, asthma, certain heart diseases, congenital heart defects in newborns, glaucoma, atherosclerosis, rheumatic and neurological diseases, kidney diseases, diabetes

  5. Regulation of repp86 stability by human Siah2

    International Nuclear Information System (INIS)

    Szczepanowski, Monika; Adam-Klages, Sabine; Kruse, Marie-Luise; Pollmann, Marc; Klapper, Wolfram; Parwaresch, Reza; Heidebrecht, Hans-Juergen

    2007-01-01

    Human repp86 is a nuclear protein that is expressed in a tightly limited period of time during the cell cycle and plays an essential role in its progression. Manipulation of repp86 expression by reduction of endogenous repp86 or overexpression of exogenous repp86 results in cell cycle arrest. We found that repp86 interacts with human Siah2, which is a known mediator for proteasomal degradation. Siah2 failed to interact with repp86 lacking the first 67 N-terminal amino acids. Overexpression of Siah2 reduced endogenous and exogenous repp86 at the protein level without affecting its mRNA, as shown by cotransfection and RT-PCR experiments. Furthermore, MG-132-a specific inhibitor of the proteasome-blocked the degradation of repp86 in Siah2 overexpressing cells. Moreover, transiently transfected Siah2 abrogated the mitotic arrest in repp86 overexpressing cells. Our data show that Siah2 is an important mediator of repp86 protein degradation

  6. THE NEUROBIOLOGY OF SLEEP AND WAKEFULNESS

    Science.gov (United States)

    Schwartz, Michael D.; Kilduff, Thomas S.

    2015-01-01

    SYNOPSIS Since the discovery of Rapid Eye Movement (REM) sleep in the late 1950s, identification of the neural circuitry underlying wakefulness, sleep onset and the alternation between REM and non-REM (NREM) sleep has been an active area of investigation. Synchronization and desynchronization of cortical activity as detected in the electroencephalogram (EEG) is due to a corticothalamocortical loop, intrinsic cortical oscillators, monoaminergic and cholinergic afferent input to the thalamus, and the basal forebrain cholinergic input directly to the cortex. The monoaminergic and cholinergic systems are largely wake-promoting; the brainstem cholinergic nuclei are also involved in REM sleep regulation. These wake-promoting systems receive excitatory input from the hypothalamic hypocretin/orexin system. Sleep-promoting nuclei are GABAergic in nature and found in the preoptic area, brainstem and lateral hypothalamus. Although the pons is critical for the expression of REM sleep, recent research has suggested that melanin-concentrating hormone/GABAergic cells in the lateral hypothalamus "gate" REM sleep. The temporal distribution of sleep and wakefulness is due to interaction between the circadian system and the sleep homeostatic system. Although the hypothalamic suprachiasmatic nuclei contain the circadian pacemaker, the neural circuitry underlying the sleep homeostat is less clear. Prolonged wakefulness results in the accumulation of extracellular adenosine, possibly from glial sources, which is an important feedback molecule for the sleep homeostatic system. Cortical neuronal nitric oxide (nNOS) neurons may also play a role in propagating slow waves through the cortex in NREM sleep. Several neuropeptides and other neurochemicals likely play important roles in sleep/wake control. Although the control of sleep and wakefulness seemingly involves multiple redundant systems, each of these systems provides a vulnerability that can result in sleep/wake dysfunction that may

  7. Commercial Human Spaceflight: Self-Regulation is the Future

    Science.gov (United States)

    Sgobba, Tommaso

    2013-09-01

    In 2004, the US private spaceflight industry welcomed a law (i.e. the Commercial Space Launch Amendment Act (CSLAA)) postponing until December 23, 2012 or until an accident occurs, the ability by the FAA to issue safety standards and regulations except for aspects of public safety. The Congress later extended the original deadline nearly three years to October 1, 2015.It goes without saying that while government regulations are postponed a commercial spaceflight company has in any case all interest to build a safe vehicles according to the state-of-art. No doubt that their engineers will routinely apply well established technical standards for developing or procuring subsystems and equipment, like pressurized tanks, batteries or pyro valves. They will also at certain points take decisions about redundancy levels when defining, for example, the on-board computers architecture, or the landing system. There will be trade-offs to be made considering cost and mass constraints and acceptable risk thresholds defined. Some key safety decisions will be taken at technical level, other will be necessarily deferred to the company management due to potential impact on the overall project cost and schedule.Therefore the on-going debate is not truly about making or not a commercial space system safe (for those on-board), but about who should bear, at this initial stage of industry development, responsibility to ensure that best practices are known and consistently applied. Responsibility which traditionally belongs to government agencies but that the CSLAA "de facto" delegates to each manufacturer.This paper tries to demonstrate that the traditional model of government establishing detailed safety regulations and certifying compliance is no longer valid for the development of highly advanced systems, and that the current trend is instead for relevant industrial community as a whole to take the lead in developing detailed safety standards and policies and verifying their

  8. Sleep in Othello

    Science.gov (United States)

    Dimsdale, Joel E.

    2009-01-01

    Some of our best descriptions of sleep disorders come from literature. While Shakespeare is well known for his references to insomnia and sleep walking, his works also demonstrate a keen awareness of many other sleep disorders. This paper examines sleep themes in Shakespeare's play Othello. The play indicates Shakespeare's astute eye for sleep deprivation, sexual parasomnias, and effects of stress and drugs on sleep. Citation: Dimsdale JE. Sleep in Othello. J Clin Sleep Med 2009;5(3):280-281. PMID:19960651

  9. Sleep Tips: 7 Steps to Better Sleep

    Science.gov (United States)

    ... turn every night. Consider simple tips for better sleep, from setting a sleep schedule to including physical activity in your daily ... factors that can interfere with a good night's sleep — from work stress and family responsibilities to unexpected ...

  10. Astronauts Need Their Rest Too: Sleep-Wake Actigraphy and Light Exposure During Space Flight

    Science.gov (United States)

    Czeisler, Charles; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

    2002-01-01

    The success and effectiveness of human space flight depends on astronauts' ability to maintain a high level of cognitive performance and vigilance. This alert state ensures the proper operation of sophisticated instrumentation. An important way for humans to remedy fatigue and maintain alertness is to get plenty of rest. Astronauts, however, commonly experience difficulty sleeping while in space. During flight, they may also experience disruption of the body's circadian rhythm - the natural phases the body goes through every day as we oscillate between states of high activity during the waking day and recuperation, rest, and repair during nighttime sleep. Both of these factors are associated with impairment of alertness and performance, which could have important consequences during a mission in space. The human body was designed to sleep at night and be alert and active during the day. We receive these cues from the time of day or amount of light, such as the rising or setting of the sun. However, in the environment of the Space Shuttle or the International Space Station where light levels are highly variable, the characteristics of a 24-hour light/dark cycle are not present to cue the astronauts' bodies about what time of the day it is. Astronauts orbiting Earth see a sunset and sunrise every 90 minutes, sending potentially disruptive signals to the area of the brain that regulates sleep. On STS-107, researchers will measure sleep-wake activity with state-of-the-art technology to quantify how much sleep astronauts obtain in space. Because light is the most powerful time cue to the body's circadian system, individual light exposure patterns of the astronauts will also be monitored to determine if light exposure is associated with sleep disruption. The results of this research could lead to the development of a new treatment for sleep disturbances, enabling crewmembers to avoid the decrements in alertness and performance due to sleep deprivation. What we learn

  11. Sleep and its disorders in translational medicine.

    Science.gov (United States)

    Paterson, Louise M; Nutt, David J; Wilson, Sue J

    2011-09-01

    The study of sleep is a useful approach to studying the brain in psychiatric disorders and in investigating the effects of psychotropic drugs. Sleep physiology lends itself well to pharmacological and physiological manipulation, as it has the advantage of a functional output, the electroencephalograph, which is common to all mammals, and can be measured in freely moving (or naturally sleeping) animals under controlled laboratory conditions or in a naturalistic home environment. The complexity of sleep architecture varies between species but all share features which are comparable. In addition, sleep architecture is sensitive to changes in brain neurotransmitters such as serotonin, so cross-species sleep measurement can be combined with pharmacological manipulation to investigate the receptor mechanisms controlling sleep-wake regulation and sleep architecture in response to known and novel agents. Translational approaches such as these have improved our understanding of sleep circuitry and facilitated the development of new treatments for sleep disorders, particularly insomnia. This review provides examples of how research findings within the sleep field have been translated between animal models, healthy volunteers and patient populations with particular focus on the serotonergic system.

  12. Sleeping to fuel the immune system: mammalian sleep and resistance to parasites

    Directory of Open Access Journals (Sweden)

    Opp Mark R

    2009-01-01

    Full Text Available Abstract Sleep is an enigma. Why animals forgo eating and reproducing, while potentially increasing their risk of predation remains unknown. Although some may question whether all animals sleep, it is clear that all living organisms possess defenses against attack by pathogens. Immune responses of humans and animals are impaired by sleep loss, and responses to immune challenge include altered sleep. Thus, sleep is hypothesized to be a component of the acute phase response to infection and to function in host defense. Examining phylogenetic relationships among sleep parameters, components of the mammalian immune system and resistance to infection may provide insight into the evolution of sleep and lead to a greater appreciation for the role of sleep in host defense.

  13. Sleeping brain, learning brain. The role of sleep for memory systems.

    Science.gov (United States)

    Peigneux, P; Laureys, S; Delbeuck, X; Maquet, P

    2001-12-21

    The hypothesis that sleep participates in the consolidation of recent memory traces has been investigated using four main paradigms: (1) effects of post-training sleep deprivation on memory consolidation, (2) effects of learning on post-training sleep, (3) effects of within sleep stimulation on the sleep pattern and on overnight memories, and (4) re-expression of behavior-specific neural patterns during post-training sleep. These studies convincingly support the idea that sleep is deeply involved in memory functions in humans and animals. However, the available data still remain too scarce to confirm or reject unequivocally the recently upheld hypothesis that consolidations of non-declarative and declarative memories are respectively dependent upon REM and NREM sleep processes.

  14. Cell shape regulates global histone acetylation in human mammaryepithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Le Beyec, Johanne; Xu, Ren; Lee, Sun-Young; Nelson, Celeste M.; Rizki, Aylin; Alcaraz, Jordi; Bissell, Mina J.

    2007-02-28

    Extracellular matrix (ECM) regulates cell morphology and gene expression in vivo; these relationships are maintained in three-dimensional (3D) cultures of mammary epithelial cells. In the presence of laminin-rich ECM (lrECM), mammary epithelial cells round up and undergo global histone deacetylation, a process critical for their functional differentiation. However, it remains unclear whether lrECM-dependent cell rounding and global histone deacetylation are indeed part of a common physical-biochemical pathway. Using 3D cultures as well as nonadhesive and micropatterned substrata, here we showed that the cell 'rounding' caused by lrECM was sufficient to induce deacetylation of histones H3 and H4 in the absence of biochemical cues. Microarray and confocal analysis demonstrated that this deacetylation in 3D culture is associated with a global increase in chromatin condensation and a reduction in gene expression. Whereas cells cultured on plastic substrata formed prominent stress fibers, cells grown in 3D lrECM or on micropatterns lacked these structures. Disruption of the actin cytoskeleton with cytochalasin D phenocopied the lrECM-induced cell rounding and histone deacetylation. These results reveal a novel link between ECM-controlled cell shape and chromatin structure, and suggest that this link is mediated by changes in the actin cytoskeleton.

  15. Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea.

    Science.gov (United States)

    Beaudin, Andrew E; Pun, Matiram; Yang, Christina; Nicholl, David D M; Steinback, Craig D; Slater, Donna M; Wynne-Edwards, Katherine E; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

    2014-05-09

    Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH. Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02). COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA. www.clinicaltrials.gov. Unique identifier: NCT01280006.

  16. Mitochondrial regulation of epigenetics and its role in human diseases

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Tollefsbol, Trygve O; Singh, Keshav K

    2012-01-01

    as the sole pathogenic factor suggesting that additional mechanisms contribute to lack of genotype and clinical phenotype correlationship. An increasing number of studies have identified a possible effect on the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction....... In particular, these studies demonstrate reversible or irreversible changes in genomic DNA methylation profiles of the nuclear genome. Here we review how mitochondria damage checkpoint (mitocheckpoint) induces epigenetic changes in the nucleus. Persistent pathogenic mutations in mtDNA may also lead...... to epigenetic changes causing genomic instability in the nuclear genome. We propose that "mitocheckpoint" mediated epigenetic and genetic changes may play key roles in phenotypic variation related to mitochondrial diseases or host of human diseases in which mitochondrial defect plays a primary role....

  17. Sleep in Othello

    OpenAIRE

    Dimsdale, Joel E.

    2009-01-01

    Some of our best descriptions of sleep disorders come from literature. While Shakespeare is well known for his references to insomnia and sleep walking, his works also demonstrate a keen awareness of many other sleep disorders. This paper examines sleep themes in Shakespeare's play Othello. The play indicates Shakespeare's astute eye for sleep deprivation, sexual parasomnias, and effects of stress and drugs on sleep.

  18. Comparisons of Portable Sleep Monitors of Different Modalities: Potential as Naturalistic Sleep Recorders

    Directory of Open Access Journals (Sweden)

    Masahiro Matsuo

    2016-07-01

    Full Text Available Background: Humans spend more than a fourth of their life sleeping, and sleep quality has been significantly linked to health. However, the objective examination of ambulatory sleep quality remains a challenge, since sleep is a state of unconsciousness, which limits the reliability of self-reports. Therefore, a non-invasive, continuous, and objective method for the recording and analysis of naturalistic sleep is required.Objective: Portable sleep recording devices provide a suitable solution for the ambulatory analysis of sleep quality. In this study, the performance of two activity-based sleep monitors (Actiwatch and MTN-210 and a single-channel EEG-based sleep monitor (SleepScope were compared in order to examine their reliability for the assessment of sleep quality.Methods: Twenty healthy adults were recruited for this study. First, data from daily activity recorded by Actiwatch and MTN-210 were compared to determine whether MTN-210, a more affordable device, could yield data similar to Actiwatch, the de-facto standard. In addition, sleep detection ability was examined using data obtained by polysomnography as reference. One simple analysis included comparing the sleep/wake detection ability of Actiwatch, MTN-210, and SleepScope. Furthermore, the fidelity of sleep stage determination was examined using SleepScope in finer time resolution. Results: The results indicate that MTN-210 demonstrates an activity pattern comparable to that of Actiwatch, although their sensitivity preferences were not identical. Moreover, MTN-210 provides assessment of sleep duration comparable to that of the wrist-worn Actiwatch when MTN-210 was attached to the body. SleepScope featured superior overall sleep detection performance among the three methods tested. Furthermore, SleepScope was able to provide information regarding sleep architecture, although systemic bias was found. Conclusion: The present results suggest that single-channel EEG-based sleep monitors are

  19. FMRFamide signaling promotes stress-induced sleep in Drosophila.

    Science.gov (United States)

    Lenz, Olivia; Xiong, Jianmei; Nelson, Matthew D; Raizen, David M; Williams, Julie A

    2015-07-01

    Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. A review on environmental factors regulating arsenic methylation in humans

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2009-01-01

    Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers

  1. The Correlation between Clinical Variables and Sleep Onset Rapid Eye Movement Period Frequencies in Narcoleptic Patients

    Directory of Open Access Journals (Sweden)

    Jin Hwa Jeong

    2010-11-01

    Full Text Available Background and Objective A diagnosis of narcolepsy is defined by less than 8 minutes of mean sleep latency, and two or more sleep onset rapid eye movement periods on the Multiple Sleep Latency Test. This study examined the relationship between the sleep onset rapid eye movement period frequencies during Multiple Sleep Latency Test and narcoleptic symptom severity. Methods From March 2004 to August 2009, 126 patients suffering from excessive daytime sleepiness who visited the Sleep Disorders Clinic of St. Vincent’s Hospital at the Catholic University of Korea were tested by polysomnography and Multiple Sleep Latency Test. Subjects were divided into three groups according to the number of sleep onset rapid eye movement periods that appeared on the Multiple Sleep Latency Test. Symptom severity instruments included the Epworth Sleepiness Scale and the Stanford Center for Narcolepsy Sleep Inventory, and various sleep parameters. In addition, we performed human leukocyte antigen genotyping for human leukocyte antigen-DQB1*0602 on all patients. Results Among the three groups classified by the number of sleep onset rapid eye movement periods during Multiple Sleep Latency Test, we found no significant differences in demographic features, Epworth Sleepiness Scale, and most polysomnographic findings. However, we observed cataplexy, hypnagogic hallucination, sleep paralysis, and human leukocyte antigen-DQB1*0602 positivity more frequently in groups with higher sleep onset rapid eye movement period frequencies. In addition, the proportions of stage II sleep, REM sleep latency from polysomnography, and mean sleep latency and mean REM sleep latency from the Multiple Sleep Latency Test significantly decreased with increasing sleep onset rapid eye movement period frequency. Conclusions In this study, we demonstrated that sleep onset rapid eye movement period frequency during Multiple Sleep Latency Test correlated with sleep architecture, daytime symptom

  2. Sialylation regulates myofibroblast differentiation of human skin fibroblasts.

    Science.gov (United States)

    Sasaki, Norihiko; Itakura, Yoko; Toyoda, Masashi

    2017-04-18

    differentiation in LP fibroblasts was restored by a sialidase inhibitor. Desialylation of CD44 with increased sialidase during the process to senescence reduced the localization of CD44 in lipid rafts after TGF-β1 stimulation, leading to the inhibition of myofibroblast differentiation. Thus, regulation of sialylation may be an attractive strategy for the prevention and regenerative therapy of age-related skin diseases, cosmetic skin alterations, and chronic wounds caused by delayed healing in elderly people.

  3. Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review

    Science.gov (United States)

    Jennings, Aaron

    2017-01-01

    The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human exposure

  4. Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review.

    Science.gov (United States)

    Li, Zijian; Jennings, Aaron

    2017-07-22

    Abstract : The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human

  5. Leptin Regulates Proliferation and Apoptosis in Human Prostate

    Directory of Open Access Journals (Sweden)

    Eduardo Leze

    2012-01-01

    Full Text Available This paper aimed to evaluate the leptin role on the cellular proliferation and the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic genes in the human prostate tissue. Methods. Fifteen samples of hyperplasic prostate tissue were divided in four symmetric parts maintained in RPMI medium supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with 50 ng/mL leptin (L or not (C. After 3 hours of incubation, gene expression was evaluated by real time RT-PCR. Cellular proliferation was evaluated by immunohistochemistry for PCNA. Results. The leptin treatment led to an increase cellular proliferation (C=21.8±0.5; L=64.8±0.9; P<0.0001 and in the expression of Bax (C=0.4±0.1; L=0.9±0.2; P<0.05 while Bcl-2 (C=19.9±5.6; L=5.6±1.8; P<0.05, Bcl-x (C=0.2±0.06; L=0.07±0.02; P<0.05, and aromatase expressions (C=1.9±0.6; L=0.4±0.1; P<0.04 were significantly reduced. Conclusion. Leptin has an important role in maintaining the physiological growth of the prostate since it stimulates both cellular proliferation and apoptosis, with the decrement in the aromatase gene expression.

  6. Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.

    Science.gov (United States)

    Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

    2015-07-01

    : Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. ©AlphaMed Press.

  7. AMPK regulation of the growth of cultured human keratinocytes

    International Nuclear Information System (INIS)

    Saha, Asish K.; Persons, Kelly; Safer, Joshua D.; Luo Zhijun; Holick, Michael F.; Ruderman, Neil B.

    2006-01-01

    AMP kinase (AMPK) is a fuel sensing enzyme that responds to cellular energy depletion by increasing processes that generate ATP and inhibiting others that require ATP but are not acutely necessary for survival. In the present study, we examined the relationship between AMPK activation and the growth (proliferation) of cultured human keratinocytes and assessed whether the inhibition of keratinocyte growth by vitamin D involves AMPK activation. In addition, we explored whether the inhibition of keratinocyte proliferation as they approach confluence could be AMPK-related. Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). At concentrations of 10 -4 and 10 -3 M, AICAR inhibited keratinocyte growth by 50% and 95%, respectively, based on measurements of thymidine incorporation into DNA. It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK activation had occurred. Incubation with the thiazolidinedione, troglitazone (10 -6 M) caused similar alterations in P-AMPK, P-ACC, and cell growth. In contrast, the well known inhibition of keratinocyte growth by 1,25-dihydroxyvitamin D 3 (10 -7 and 10 -6 M) was not associated with changes in P-AMPK or P-ACC. Like most cells, the growth of keratinocytes diminished as they approached confluence. Thus, it was of note that we found a progressive increase in P-AMPK (1.5- to 2-fold, p 3 is AMPK-independent

  8. Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

    Directory of Open Access Journals (Sweden)

    Bonnie H Y Yeung

    Full Text Available Stanniocalcin-1 (STC1, a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam formation, followed by cell migration. In this study, staurosporine (STS treatment induced human keratinocyte (HaCaT e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK, the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

  9. Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

    Science.gov (United States)

    Yeung, Bonnie H Y; Wong, Chris K C

    2011-01-01

    Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

  10. Pharmacological treatment of sleep disorders and its relationship with neuroplasticity.

    Science.gov (United States)

    Abad, Vivien C; Guilleminault, Christian

    2015-01-01

    Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

  11. The Role of Sleep in Childhood Psychiatric Disorders

    Science.gov (United States)

    Alfano, Candice A.; Gamble, Amanda L.

    2009-01-01

    Although sleep problems often comprise core features of psychiatric disorders, inadequate attention has been paid to the complex, reciprocal relationships involved in the early regulation of sleep, emotion, and behavior. In this paper, we review the pediatric literature examining sleep in children with primary psychiatric disorders as well as…

  12. mTORC1 directly phosphorylates and regulates human MAF1.

    OpenAIRE

    Michels Annemieke A; Robitaille Aaron M; Buczynski-Ruchonnet Diane; Hodroj Wassim; Reina Jaime H; Hall Michael N; Hernandez Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the p...

  13. Substrate Specificity, Membrane Topology, and Activity Regulation of Human Alkaline Ceramidase 2 (ACER2)*

    OpenAIRE

    Sun, Wei; Jin, Junfei; Xu, Ruijuan; Hu, Wei; Szulc, Zdzislaw M.; Bielawski, Jacek; Obeid, Lina M.; Mao, Cungui

    2010-01-01

    Human alkaline ceramidase 2 (ACER2) plays an important role in cellular responses by regulating the hydrolysis of ceramides in cells. Here we report its biochemical characterization, membrane topology, and activity regulation. Recombinant ACER2 was expressed in yeast mutant cells (Δypc1Δydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressiong yeast cells were used to biochemically characterize ACER2. ACER2 catalyzed the hydrolysis of various ceramides and followed...

  14. Hypoxia regulates microRNA expression in the human carotid body

    International Nuclear Information System (INIS)

    Mkrtchian, Souren; Lee, Kian Leong; Kåhlin, Jessica; Ebberyd, Anette; Poellinger, Lorenz; Fagerlund, Malin Jonsson; Eriksson, Lars I.

    2017-01-01

    The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

  15. Hypoxia regulates microRNA expression in the human carotid body

    Energy Technology Data Exchange (ETDEWEB)

    Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Lee, Kian Leong, E-mail: csilkl@nus.edu.sg [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Kåhlin, Jessica [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Ebberyd, Anette [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Poellinger, Lorenz [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Fagerlund, Malin Jonsson; Eriksson, Lars I. [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden)

    2017-03-15

    The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

  16. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    Science.gov (United States)

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  17. Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology.

    Science.gov (United States)

    Bergen, Werner G; Brandebourg, Terry D

    2016-06-01

    For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review. © 2016 by the Society for Experimental Biology and Medicine.

  18. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

    DEFF Research Database (Denmark)

    Eskildsen, Tilde; Taipaleenmäki, Hanna; Stenvang, Jan

    2011-01-01

    Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators......-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore...

  19. EEG-guided transcranial magnetic stimulation reveals rapid shifts in motor cortical excitability during the human sleep slow oscillation

    DEFF Research Database (Denmark)

    Bergmann, Til O; Mölle, Matthias; Schmidt, Marlit A

    2012-01-01

    Evoked cortical responses do not follow a rigid input–output function but are dynamically shaped by intrinsic neural properties at the time of stimulation. Recent research has emphasized the role of oscillatory activity in determining cortical excitability. Here we employed EEG-guided transcranial......, closely resembling a spontaneous SO. However, both MEPs and TEPs were consistently larger when evoked during SO up-states than during down-states, and ampliudes within each SO state depended on the actual EEG potential at the time and site of stimulation. These results provide first-time evidence...... magnetic stimulation (TMS) during non-rapid eye movement sleep to examine whether the spontaneous

  20. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells

    International Nuclear Information System (INIS)

    Anisowicz, A.; Bardwell, L.; Sager, R.

    1987-01-01

    Comparison by subtractive hybridization of mRNAs revealed a moderately abundant message in highly tumorigenic CHEF/16 cells present at very low levels in closely related nontumorigenic CHEF/18 cells. After cloning and sequencing the corresponding cDNA, computer comparison showed closest homology with the human connective tissue-activating peptide III (CTAP III). The human tumor cell cDNA hybridizing with the Chinese hamster clone was isolated, sequenced, and found to have closer similarity to the Chinese hamster gene than to CTAP III. Thus, the cloned cDNAs from Chinese hamster and human cells represent a different gene, named gro. Studies of its transcriptional regulation have shown that expression is tightly regulated by growth status in normal Chinese hamster and human cells and relaxed in the tumorigenic cells so far examined

  1. PKCα expression regulated by Elk-1 and MZF-1 in human HCC cells

    International Nuclear Information System (INIS)

    Hsieh, Y.-H.; Wu, T.-T.; Tsai, J.-H.; Huang, C.-Y.; Hsieh, Y.-S.; Liu, J.-Y.

    2006-01-01

    Our previous study found that PKCα was highly expressed in the poor-differentiated human HCC cells and associated with cell migration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKCα expression enhancement in the poor-differentiated human HCC cells was found neither by DNA amplification nor by increasing mRNA stability using differential PCR and mRNA decay assays. After screening seven transcription factors in the putative cis-acting regulatory elements of human PKCα promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant reduction in the PKCα mRNA level. They also reduced cell proliferation, cell migratory and invasive capabilities, and DNA binding activities in the PKCα promoter region. Over-expression assay confirmed that the PKCα expression may be modulated by these two factors at the transcriptional level. Therefore, these results may provide a novel mechanism for PKCα expression regulation in human HCC cells

  2. Regulating (for the benefit of) future persons: a different perspective on the FDA's jurisdiction to regulate human reproductive cloning.

    Science.gov (United States)

    Javitt, Gail H; Hudson, Kathy

    2003-01-01

    The Food and Drug Administration (FDA) has taken the position that human reproductive cloning falls within its regulatory jurisdiction. This position has been subject to criticism on both procedural and substantive grounds. Some have contended that the FDA has failed to follow administrative law principles in asserting its jurisdiction, while others claim the FDA is ill suited to the task of addressing the ethical and social implications of human cloning. This Article argues, that, notwithstanding these criticisms, the FDA could plausibly assert jurisdiction over human cloning as a form of human gene therapy, an area in which the FDA is already regarded as having primary regulatory authority. Such an assertion would require that the FDA's jurisdiction extend to products affecting future persons, i.e., those not yet born. This Article demonstrates, for the first time, that such jurisdiction was implicit in the enactment of the 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act and that the FDA has historically relied on such authority in promulgating regulations for drugs and devices.

  3. Individual Differences in Diabetes Risk: Role of Sleep Disturbances

    Science.gov (United States)

    2008-08-01

    daily metabolic and hormonal processes and appetite regulation. It is clear that chronic sleep deprivation has deleterious effects on carbohydrate...163−78. 15. Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, et al. A prospective study of self-reported sleep duration and...Normative sleep data, cognitive function and daily living activities in older adults in the community. Sleep 2005 Aug 1;28(8):981−9. 33. Singh M

  4. Essential roles of GABA transporter-1 in controlling rapid eye movement sleep and in increased slow wave activity after sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Xin-Hong Xu

    Full Text Available GABA is the major inhibitory neurotransmitter in the mammalian central nervous system that has been strongly implicated in the regulation of sleep. GABA transporter subtype 1 (GAT1 constructs high affinity reuptake sites for GABA and regulates GABAergic transmission in the brain. However, the role of GAT1 in sleep-wake regulation remains elusive. In the current study, we characterized the spontaneous sleep-wake cycle and responses to sleep deprivation in GAT1 knock-out (KO mice. GAT1 KO mice exhibited dominant theta-activity and a remarkable reduction of EEG power in low frequencies across all vigilance stages. Under baseline conditions, spontaneous rapid eye movement (REM sleep of KO mice was elevated both during the light and dark periods, and non-REM (NREM sleep was reduced during the light period only. KO mice also showed more state transitions from NREM to REM sleep and from REM sleep to wakefulness, as well as more number of REM and NREM sleep bouts than WT mice. During the dark period, KO mice exhibited more REM sleep bouts only. Six hours of sleep deprivation induced rebound increases in NREM and REM sleep in both genotypes. However, slow wave activity, the intensity component of NREM sleep was briefly elevated in WT mice but remained completely unchanged in KO mice, compared with their respective baselines. These results indicate that GAT1 plays a critical role in the regulation of REM sleep and homeostasis of NREM sleep.

  5. Sleep Disturbances in Newborns

    OpenAIRE

    Yasova Barbeau, Daphna; Weiss, Michael D.

    2017-01-01

    The purpose of this review is to serve as an introduction to understanding sleep in the fetus, the preterm neonate and the term neonate. Sleep appears to have numerous important roles, particularly in the consolidation of new information. The sleep cycle changes over time, neonates spend the most time in active sleep and have a progressive shortening of active sleep and lengthening of quiet sleep. Additionally, the sleep cycle is disrupted by many things including disease state and environmen...

  6. Sleep disorders as core symptoms of depression.

    Science.gov (United States)

    Nutt, David; Wilson, Sue; Paterson, Louise

    2008-01-01

    Links between sleep and depression are strong. About three quarters of depressed patients have insomnia symptoms, and hypersomnia is present in about 40% of young depressed adults and 10% of older patients, with a preponderance in females. The symptoms cause huge distress, have a major impact on quality of life, and are a strong risk factor for suicide. As well as the subjective experience of sleep symptoms, there are well-documented changes in objective sleep architecture in depression. Mechanisms of sleep regulation and how they might be disturbed in depression are discussed. The sleep symptoms are often unresolved by treatment, and confer a greater risk of relapse and recurrence. Epidemiological studies have pointed out that insomnia in nondepressed subjects is a risk factor for later development of depression. There is therefore a need for more successful management of sleep disturbance in depression, in order to improve quality of life in these patients and reduce an important factor in depressive relapse and recurrence.

  7. Systematic review of sleep disorders in cancer patients: can the prevalence of sleep disorders be ascertained?

    International Nuclear Information System (INIS)

    Otte, Julie L; Carpenter, Janet S; Manchanda, Shalini; Rand, Kevin L; Skaar, Todd C; Weaver, Michael; Chernyak, Yelena; Zhong, Xin; Igega, Christele; Landis, Carol

    2015-01-01

    Although sleep is vital to all human functioning and poor sleep is a known problem in cancer, it is unclear whether the overall prevalence of the various types of sleep disorders in cancer is known. The purpose of this systematic literature review was to evaluate if the prevalence of sleep disorders could be ascertained from the current body of literature regarding sleep in cancer. This was a critical and systematic review of peer-reviewed, English-language, original articles published from 1980 through 15 October 2013, identified using electronic search engines, a set of key words, and prespecified inclusion and exclusion criteria. Information from 254 full-text, English-language articles was abstracted onto a paper checklist by one reviewer, with a second reviewer randomly verifying 50% (k = 99%). All abstracted data were entered into an electronic database, verified for accuracy, and analyzed using descriptive statistics and frequencies in SPSS (v.20) (North Castle, NY). Studies of sleep and cancer focus on specific types of symptoms of poor sleep, and there are no published prevalence studies that focus on underlying sleep disorders. Challenging the current paradigm of the way sleep is studied in cancer could produce better clinical screening tools for use in oncology clinics leading to better triaging of patients with sleep complaints to sleep specialists, and overall improvement in sleep quality

  8. Ancient and recent positive selection transformed opioid cis-regulation in humans.

    Directory of Open Access Journals (Sweden)

    Matthew V Rockman

    2005-12-01

    Full Text Available Changes in the cis-regulation of neural genes likely contributed to the evolution of our species' unique attributes, but evidence of a role for natural selection has been lacking. We found that positive natural selection altered the cis-regulation of human prodynorphin, the precursor molecule for a suite of endogenous opioids and neuropeptides with critical roles in regulating perception, behavior, and memory. Independent lines of phylogenetic and population genetic evidence support a history of selective sweeps driving the evolution of the human prodynorphin promoter. In experimental assays of chimpanzee-human hybrid promoters, the selected sequence increases transcriptional inducibility. The evidence for a change in the response of the brain's natural opioids to inductive stimuli points to potential human-specific characteristics favored during evolution. In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

  9. Inducible, tunable and multiplex human gene regulation using CRISPR-Cpf1-based transcription factors | Office of Cancer Genomics

    Science.gov (United States)

    Targeted and inducible regulation of mammalian gene expression is a broadly important research capability that may also enable development of novel therapeutics for treating human diseases. Here we demonstrate that a catalytically inactive RNA-guided CRISPR-Cpf1 nuclease fused to transcriptional activation domains can up-regulate endogenous human gene expression. We engineered drug-inducible Cpf1-based activators and show how this system can be used to tune the regulation of endogenous gene transcription in human cells.

  10. Melanin-concentrating hormone (MCH: a new sleep factor?

    Directory of Open Access Journals (Sweden)

    Pablo eTorterolo

    2011-03-01

    Full Text Available Neurons that utilize the neuropeptide melanin-concentrating hormone (MCH as a neuromodulator are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows:1. The areas related to the control of sleep and wakefulness have an important density of MCHergic fibers and receptors.2. MCHergic neurons are active during sleep, especially during REM sleep.3. Genetically-modified animals without MCH have less REM sleep, notably under conditions of negative energy balance. 4. Systemically administered MCHR1 antagonists reduce sleep. 5. Intraventricular microinjection of MCH increases both slow wave sleep (SWS and REM sleep; however, the increment in REM sleep is more pronounced.6. Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus.7. Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency.All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.

  11. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  12. Reading from an iPad or from a book in bed: the impact on human sleep. A randomized controlled crossover trial.

    Science.gov (United States)

    Grønli, Janne; Byrkjedal, Ida Kristiansen; Bjorvatn, Bjørn; Nødtvedt, Øystein; Hamre, Børge; Pallesen, Ståle

    2016-05-01

    To objectively and subjectively compare whether reading a story for 30 min from an iPad or from a book in bed prior to sleep will differentially affect sleep. Sixteen students (12 females, mean age 25.1 ± 2.9 years) underwent ambulatory (sleeping in their own beds at home) polysomnographic (PSG) recordings in a counterbalanced crossover design consisting of three PSG nights (one adaptation night, two test nights) and two different reading materials: read from an iPad or from a book. Illumination was measured during reading and Karolinska Sleepiness Scale was completed prior to turning the light off. Sleep diaries were kept to assess subjective sleep parameters from day to day. Illumination was higher in the iPad condition compared to the book condition (58.3 ± 6.9 vs 26.7 ± 8.0 lux, p book. No parameters of sleep state timing and sleep onset latency differed between the two reading conditions. Although there was no direct effect on time spent in different sleep states and self-reported sleep onset latency, the use of an iPad which emits blue enriched light impinges acutely on sleepiness and EEG characteristics of sleep pressure. Hence, the use of commercially available tablets may have consequences in terms of alertness, circadian physiology, and sleep. Published by Elsevier B.V.

  13. Sleep disorders associated with primary mitochondrial diseases.

    Science.gov (United States)

    Ramezani, Ryan J; Stacpoole, Peter W

    2014-11-15

    Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

  14. Sleep Applications to Assess Sleep Quality.

    Science.gov (United States)

    Fietze, Ingo

    2016-12-01

    This article highlights the potential uses that smartphone applications may have for helping those with sleep problems. Applications in smartphones offer the promised possibility of detection of sleep. From the author's own experience, one can also conclude that sleep applications are approximately as good as polysomnography in detection of sleep time, similar to the conventional wearable actimeters. In the future, sleep applications will help to further enhance awareness of sleep health and to distinguish those who actually poorly and only briefly sleep from those who suffer more likely from paradox insomnia. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Circadian Sleep-Wake Rhythm of Older Adults with Intellectual Disabilities

    Science.gov (United States)

    Maaskant, Marijke; van de Wouw, Ellen; van Wijck, Ruud; Evenhuis, Heleen M.; Echteld, Michael A.

    2013-01-01

    The circadian sleep-wake rhythm changes with aging, resulting in a more fragmented sleep-wake pattern. In individuals with intellectual disabilities (ID), brain structures regulating the sleep-wake rhythm might be affected. The aims of this study were to compare the sleep-wake rhythm of older adults with ID to that of older adults in the general…

  16. Effects of SWS deprivation on subsequent EEG power density and spontaneous sleep duration

    NARCIS (Netherlands)

    Dijk, Derk Jan; Beersma, Domien G.M.

    In order to test predictions of the 2-process model of sleep regulation, the effects of slow wave sleep (SWS) deprivation by acoustic stimulation during the first part of the sleep period on EEG power density and sleep duration were investigated in 2 experiments. In the first experiment, 8 subjects

  17. The feed-back regulation of erythropoietin production in healthy humans

    International Nuclear Information System (INIS)

    Klausen, T.

    1998-01-01

    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  18. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human