The brain functional connectome is robustly altered by lack of sleep.

PubMed

Kaufmann, Tobias; Elvsåshagen, Torbjørn; Alnæs, Dag; Zak, Nathalia; Pedersen, Per Ø; Norbom, Linn B; Quraishi, Sophia H; Tagliazucchi, Enzo; Laufs, Helmut; Bjørnerud, Atle; Malt, Ulrik F; Andreassen, Ole A; Roussos, Evangelos; Duff, Eugene P; Smith, Stephen M; Groote, Inge R; Westlye, Lars T

2016-02-15

Sleep is a universal phenomenon necessary for maintaining homeostasis and function across a range of organs. Lack of sleep has severe health-related consequences affecting whole-body functioning, yet no other organ is as severely affected as the brain. The neurophysiological mechanisms underlying these deficits are poorly understood. Here, we characterize the dynamic changes in brain connectivity profiles inflicted by sleep deprivation and how they deviate from regular daily variability. To this end, we obtained functional magnetic resonance imaging data from 60 young, adult male participants, scanned in the morning and evening of the same day and again the following morning. 41 participants underwent total sleep deprivation before the third scan, whereas the remainder had another night of regular sleep. Sleep deprivation strongly altered the connectivity of several resting-state networks, including dorsal attention, default mode, and hippocampal networks. Multivariate classification based on connectivity profiles predicted deprivation state with high accuracy, corroborating the robustness of the findings on an individual level. Finally, correlation analysis suggested that morning-to-evening connectivity changes were reverted by sleep (control group)-a pattern which did not occur after deprivation. We conclude that both, a day of waking and a night of sleep deprivation dynamically alter the brain functional connectome. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship among nocturnal sleep deficit, excess weight and metabolic alterations in adolescents.

PubMed

Ruiz, Nelina; Rangel, Airam; Rodríguez, Carla; Rodríguez, Lisette; Rodríguez, Valeria

2014-12-01

Sleep modulates neuroendocrine function and metabolism; therefore, changes in sleep duration may lead to developing obesity during adolescence. To assess the possible association among nocturnal sleep duration, the presence of overweight and metabolic alterations in a group of adolescents. Cross-sectional, analytical study conducted at a school in Valencia, Venezuela, during the 2012-2013 school year. Participants were 12 to 17 year-old adolescents. A survey on nocturnal sleep duration was administered; weight, height and waist circumference were recorded; and glycemia, lipid profile and insulinemia levels were measured. Body mass index and the homeostasis model assessment of insulin resistance (HOMA-IR) index were calculated. Ninety adolescents were included. Compared to the group with normal weight, adolescents with excessive weight had, in average, fewer sleep hours Sundays through Thursdays (p < 0.05) and a higher rate of sleep deficit and sleep debt (p < 0.05). Low HDL cholesterol and insulin resistance was significantly associated with sleep debt (p < 0.05). Among adolescents with sleep debt, the risk of having excess weight was 2.70 times higher (95% CI= 1.09-6.72; p= 0.032) regardless of age, gender, sexual maturity, sleep deficit Sundays through Thursdays, and history of cardiovascular disease and diabetes in first-degree relatives. Nocturnal sleep deficit and sleep debt were significantly associated with excess weight and metabolic alterations related to a high cardiometabolic risk.

Telemetric Study of Sleep Architecture and Sleep Homeostasis in the Day-Active Tree Shrew Tupaia belangeri

PubMed Central

Coolen, Alex; Hoffmann, Kerstin; Barf, R. Paulien; Fuchs, Eberhard; Meerlo, Peter

2012-01-01

Study Objectives: In this study the authors characterized sleep architecture and sleep homeostasis in the tree shrew, Tupaia belangeri, a small, omnivorous, day-active mammal that is closely related to primates. Design: Adult tree shrews were individually housed under a 12-hr light/12-hr dark cycle in large cages containing tree branches and a nest box. The animals were equipped with radio transmitters to allow continuous recording of electroencephalogram (EEG), electromyogram (EMG), and body temperature without restricting their movements. Recordings were performed under baseline conditions and after sleep deprivation (SD) for 6 hr or 12 hr during the dark phase. Measurements and Results: Under baseline conditions, the tree shrews spent a total of 62.4 ± 1.4% of the 24-hr cycle asleep, with 91.2 ± 0.7% of sleep during the dark phase and 33.7 ± 2.8% sleep during the light phase. During the dark phase, all sleep occurred in the nest box; 79.6% of it was non-rapid eye movement (NREM) sleep and 20.4% was rapid eye movement (REM) sleep. In contrast, during the light phase, sleep occurred almost exclusively on the top branches of the cage and only consisted of NREM sleep. SD was followed by an immediate increase in NREM sleep time and an increase in NREM sleep EEG slow-wave activity (SWA), indicating increased sleep intensity. The cumulative increase in NREM sleep time and intensity almost made up for the NREM sleep that had been lost during 6-hr SD, but did not fully make up for the NREM sleep lost during 12-hr SD. Also, only a small fraction of the REM sleep that was lost was recovered, which mainly occurred on the second recovery night. Conclusions: The day-active tree shrew shares most of the characteristics of sleep structure and sleep homeostasis that have been reported for other mammalian species, with some peculiarities. Because the tree shrew is an established laboratory animal in neurobiological research, it may be a valuable model species for studies of

Synaptic plasticity in sleep: learning, homeostasis, and disease

PubMed Central

Wang, Gordon; Grone, Brian; Colas, Damien; Appelbaum, Lior; Mourrain, Philippe

2012-01-01

Sleep is a fundamental and evolutionarily conserved aspect of animal life. Recent studies have shed light on the role of sleep in synaptic plasticity. Demonstrations of memory replay and synapse homeostasis suggest that one essential role of sleep is in the consolidation and optimization of synaptic circuits to retain salient memory traces despite the noise of daily experience. Here, we review this recent evidence, and suggest that sleep creates a heightened state of plasticity, which may be essential for this optimization. Furthermore, we discuss how sleep deficits seen in diseases such as Alzheimer’s disease and autism spectrum disorders might not just reflect underlying circuit malfunction, but could also play a direct role in the progression of those disorders. PMID:21840068

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

PubMed

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 < 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.

Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

PubMed

Lesku, John A; Vyssotski, Alexei L; Martinez-Gonzalez, Dolores; Wilzeck, Christiane; Rattenborg, Niels C

2011-08-22

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

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

PubMed

Thimgan, Matthew S; Suzuki, Yasuko; Seugnet, Laurent; Gottschalk, Laura; Shaw, Paul J

2010-08-31

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.

Role of orexin in respiratory and sleep homeostasis during upper airway obstruction in rats.

PubMed

Tarasiuk, Ariel; Levi, Avishag; Berdugo-Boura, Nilly; Yahalom, Ari; Segev, Yael

2014-05-01

Chronic upper airway obstruction (UAO) elicits a cascade of complex endocrine derangements that affect growth, sleep, and energy metabolism. We hypothesized that elevated hypothalamic orexin has a role in maintaining ventilation during UAO, while at the same time altering sleep-wake activity and energy metabolism. Here, we sought to explore the UAO-induced changes in hypothalamic orexin and their role in sleep-wake balance, respiratory activity, and energy metabolism. The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed; UAO and sham-operated control animals were monitored for 7 weeks. We measured food intake, body weight, temperature, locomotion, and sleep-wake activity. Magnetic resonance imaging was used to quantify subcutaneous and visceral fat tissue volumes. In week 7, the rats were sacrificed and levels of hypothalamic orexin, serum leptin, and corticosterone were determined. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and respiration was also explored. UAO increased hypothalamic orexin mRNA and protein content by 64% and 65%, respectively. UAO led to 30% chronic sleep loss, excessive active phase sleepiness, decreased body temperature, increased food intake, reduction of abdominal and subcutaneous fat tissue volume, and growth retardation. Administration of almorexant normalized sleep but induced severe breathing difficulties in UAO rats, while it had no effect on sleep or on breathing of control animals. In upper airway obstruction animals, enhanced orexin secretion, while crucially important for respiratory homeostasis maintenance, is also responsible for chronic partial sleep loss, as well as considerable impairment of energy metabolism and growth.

Functional data analysis of sleeping energy expenditure

USDA-ARS?s Scientific Manuscript database

Adequate sleep is crucial during childhood for metabolic health, and physical and cognitive development. Inadequate sleep can disrupt metabolic homeostasis and alter sleeping energy expenditure (SEE). Functional data analysis methods were applied to SEE data to elucidate the population structure of ...

Chronic high-caloric diet modifies sleep homeostasis in mice.

PubMed

Panagiotou, Maria; Meijer, Johanna H; Deboer, Tom

2018-05-08

Obesity prevalence and sleep habit changes are commonplace nowadays, due to modern lifestyle. A bidirectional relationship likely exists between sleep quality and metabolic disruptions, that could impact quality of life. In our study, we investigated the effects of a chronic high-caloric diet on sleep architecture and sleep regulation in mice. We studied the effect of three months high-caloric diet (HCD, 45% fat) on sleep and the sleep electroencephalogram (EEG) in C57BL/6J mice during 24-h baseline (BL) recordings, and after 6-h sleep deprivation (SD). We examined the effect of HCD on sleep homeostasis, by performing parameter estimation analysis and simulations of the sleep homeostatic Process S, a measure of sleep pressure, which is reflected in the non-rapid-eye-movement (NREM) sleep slow-wave-activity (SWA, EEG power density between 0.5-4.0 Hz). Compared to controls (n=11, 30.7±0.8g), mice fed with HCD (n=9, 47.6±0.8g) showed an increased likelihood of consecutive NREM-REM sleep cycles, increased REM sleep and decreased NREM sleep EEG SWA. After SD these effects were more pronounced. The simulation resulted in a close fit between the time course of SWA and Process S in both groups. HCD fed mice had a slower time constant (Ti = 15.98 h) for the increase in homeostatic sleep pressure compared to controls (5.95 h) indicating a reduced effect of waking on the increase in sleep pressure. Our results suggest that chronic HCD consumption impacts sleep regulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

PubMed

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.

Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy

PubMed Central

Liu, Yaping; Zhang, Jihui; Lam, Venny; Ho, Crover Kwok Wah; Zhou, Junying; Li, Shirley Xin; Lam, Siu Ping; Yu, Mandy Wai Man; Tang, Xiangdong; Wing, Yun-Kwok

2015-01-01

Objectives: To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. Methods: To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. Results: The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7–149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. Conclusions: Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis. Citation: Liu Y, Zhang J, Lam V, Ho CK, Zhou J, Li SX, Lam SP, Yu MW, Tang X, Wing YK. Altered sleep stage transitions of REM sleep: a novel and stable biomarker of narcolepsy. J Clin Sleep Med 2015

Sleep and the Price of Plasticity: From Synaptic and Cellular Homeostasis to Memory Consolidation and Integration

PubMed Central

Tononi, Giulio; Cirelli, Chiara

2014-01-01

Summary Sleep is universal, tightly regulated, and its loss impairs cognition. But why does the brain need to disconnect from the environment for hours every day? The synaptic homeostasis hypothesis (SHY) proposes that sleep is the price the brain pays for plasticity. During a waking episode, learning statistical regularities about the current environment requires strengthening connections throughout the brain. This increases cellular needs for energy and supplies, decreases signal-to-noise ratios, and saturates learning. During sleep, spontaneous activity renormalizes net synaptic strength and restores cellular homeostasis. Activity-dependent down-selection of synapses can also explain the benefits of sleep on memory acquisition, consolidation, and integration. This happens through the off-line, comprehensive sampling of statistical regularities incorporated in neuronal circuits over a lifetime. This review considers the rationale and evidence for SHY and points to open issues related to sleep and plasticity. PMID:24411729

Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration.

PubMed

Tononi, Giulio; Cirelli, Chiara

2014-01-08

Sleep is universal, tightly regulated, and its loss impairs cognition. But why does the brain need to disconnect from the environment for hours every day? The synaptic homeostasis hypothesis (SHY) proposes that sleep is the price the brain pays for plasticity. During a waking episode, learning statistical regularities about the current environment requires strengthening connections throughout the brain. This increases cellular needs for energy and supplies, decreases signal-to-noise ratios, and saturates learning. During sleep, spontaneous activity renormalizes net synaptic strength and restores cellular homeostasis. Activity-dependent down-selection of synapses can also explain the benefits of sleep on memory acquisition, consolidation, and integration. This happens through the offline, comprehensive sampling of statistical regularities incorporated in neuronal circuits over a lifetime. This Perspective considers the rationale and evidence for SHY and points to open issues related to sleep and plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy.

PubMed

Liu, Yaping; Zhang, Jihui; Lam, Venny; Ho, Crover Kwok Wah; Zhou, Junying; Li, Shirley Xin; Lam, Siu Ping; Yu, Mandy Wai Man; Tang, Xiangdong; Wing, Yun-Kwok

2015-08-15

To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7-149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis. © 2015 American Academy of Sleep Medicine.

Obstructive sleep apnea alters sleep stage transition dynamics.

PubMed

Bianchi, Matt T; Cash, Sydney S; Mietus, Joseph; Peng, Chung-Kang; Thomas, Robert

2010-06-28

Enhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity. We analyzed hypnograms from Sleep Heart Health Study (SHHS) participants using the following stage designations: wake after sleep onset (WASO), non-rapid eye movement (NREM) sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA), medical co-morbidities, or sleepiness (n = 374) with mild (n = 496) or severe OSA (n = 338). WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the "decay" rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution. OSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application.

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

PubMed

Murillo-Rodríguez, Eric; Di Marzo, Vincenzo; Machado, Sergio; Rocha, Nuno B; Veras, André B; Neto, Geraldo A M; Budde, Henning; Arias-Carrión, Oscar; Arankowsky-Sandoval, Gloria

2017-01-01

The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB 1 and CB 2 ), 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

Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences

PubMed Central

Mullette-Gillman, O'Dhaniel A.; Kurnianingsih, Yoanna A.; Liu, Jean C. J.

2015-01-01

Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences. PMID:26500479

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

PubMed Central

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

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

PubMed

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.

Sleep homeostasis in the female rat during the estrous cycle.

PubMed

Schwierin, B; Borbély, A A; Tobler, I

1998-11-16

To investigate whether sleep homeostasis in the female rat is modulated by the estrous cycle, the vigilance states, EEG power spectra and cortical temperature (TCRT) were assessed on the basis of 4-day continuous recordings. A regulatory response was elicited by 6-h sleep deprivation (SD) during the proestrous (PRO) and the estrous (EST) day and compared to the baseline recordings. The vigilance states varied across the estrous cycle. In the PRO dark period the amount of sleep was reduced. The decrease in rapid-eye-movement (REM) sleep was already evident towards the end of the preceding light period, and an increased fragmentation of sleep was present throughout PRO. Compared to the other days of the estrous cycle, slow-wave activity (SWA; EEG power density 0.75-4.75 Hz) in nonREM (NREM) sleep was lower in PRO at the end of the light period and in the beginning of the dark period. High-frequency activity (HFA; EEG power density 10.25-25.0 Hz) was increased in the dark period of PRO. The SD performed during the first 6 h of the light period of PRO and EST enhanced SWA in NREM sleep and reduced sleep fragmentation during the subsequent 6 h. The extent and time course of the response to SD did not differ between the two phases of the estrous cycle. It is concluded that despite the marked baseline variations of the vigilance states and the EEG, homeostatic regulation is little affected by the estrous cycle. Copyright 1998 Elsevier Science B.V.

Cold Exposure and Sleep in the Rat: REM Sleep Homeostasis and Body Size

PubMed Central

Amici, Roberto; Cerri, Matteo; Ocampo-Garcés, Adrian; Baracchi, Francesca; Dentico, Daniela; Jones, Christine Ann; Luppi, Marco; Perez, Emanuele; Parmeggiani, Pier Luigi; Zamboni, Giovanni

2008-01-01

Study Objectives: Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24°C. Design: EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10°C to −10°C and for 4 days during recovery. Setting: Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. Subjects: 24 male albino rats. Interventions: Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature. Measurements and Results: REMS occurrence decreased proportionally with cold exposure, but a fast compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond a “fast rebound” threshold corresponding to 22% of the daily REMS need. A slow REMS rebound apparently allowed the animals to fully restore the previous REMS loss during the following 3 days of recovery. Conclusion: Comparing the present data on rats with data from earlier studies on cats and humans, it appears that small mammals have less tolerance for REMS loss than large ones. In small mammals, this low tolerance may be responsible on a short-term basis for the shorter wake-sleep cycle, and on long-term basis, for the higher percentage of REMS that is quickly recovered following REMS deprivation. Citation: Amici R; Cerri M; Ocampo-Garcés A; Baracchi F; Dentico D; Jones CA; Luppi M; Perez E; Parmeggiani PL; Zamboni G. Cold exposure and sleep in the rat: REM sleep homeostasis and body size. SLEEP 2008;31(5):708–715. PMID:18517040

Sleep alterations and iron deficiency anemia in infancy

PubMed Central

Peirano, Patricio D.; Algarín, Cecilia R.; Chamorro, Rodrigo A.; Reyes, Sussanne C.; Durán, Samuel A.; Garrido, Marcelo I.; Lozoff, Betsy

2013-01-01

Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. An estimated 20-25% of the world’s infants have IDA, with at least as many having iron deficiency without anemia. Infants are at particular risk due to rapid growth and limited dietary sources of iron. We found that infants with IDA showed different motor activity patterning in all sleep-waking states and several differences in sleep states organization. Sleep alterations were still apparent years after correction of anemia with iron treatment in the absence of subsequent IDA. We suggest that altered sleep patterns may represent an underlying mechanism that interferes with optimal brain functioning during sleep and wakefulness in former IDA children. PMID:20620103

Thiol/disulfide homeostasis in pregnant women with obstructive sleep apnea syndrome.

PubMed

Üstündağ, Yasemin; Demirci, Hakan; Balık, Rifat; Erel, Ozcan; Özaydın, Fahri; Kücük, Bilgen; Ertaş, Dilber; Ustunyurt, Emin

2017-11-27

Repetitive episodes of hypoxia and reoxygenation during sleep in patients with obstructive sleep apnea syndrome (OSAS) resemble an ischemia-reperfusion injury. We aimed to test the hypothesis that oxidative stress occurs in pregnant women with OSAS. We also aimed to compare thiol/disulfide homeostasis with ischemia-modified albumin (IMA) and total antioxidant capacity (TAC) as markers of ischemia-reperfusion injury in pregnant women with and without OSAS and healthy control. This study included 29 pregnant women with OSAS, 30 women without OSAS in the third trimester applying for periodic examinations, and 30 healthy women. Serum IMA and TAC (using the ferric reducing power of plasma method) were measured. Serum thiol/disulfide homeostasis was determined by a novel automated method. The mean age of the pregnant women with OSAS was 31.0 ± 4.7 years with a mean gestational age of 36.5 ± 3.0 weeks. The mean age of pregnant women without OSAS was 29.8 ± 4.9 years with a mean gestational age of 36.9 ± 2.7 weeks. The mean age of the nonpregnant control group was 29.7 ± 6.4 years. Both native thiol (291 ± 29 μmol/L versus 314 ± 30 μmol/L; p = .018) and total thiol (325 ± 32 versus 350 ± 32, p = .025) levels were lower in pregnant women with OSAS compared to pregnant women without OSAS, respectively (p < .01). This is the first study demonstrating the thiol/disulfide homeostasis in pregnant women with OSAS. Native thiol and total thiol levels were lower in pregnant women with OSAS compared to those without OSAS. However, dynamic thiol/disulfide homeostasis parameters cannot provide valuable information to discriminate OSAS in pregnant women.

Separating the Contribution of Glucocorticoids and Wakefulness to the Molecular and Electrophysiological Correlates of Sleep Homeostasis

PubMed Central

Mongrain, Valérie; Hernandez, Susana A.; Pradervand, Sylvain; Dorsaz, Stéphane; Curie, Thomas; Hagiwara, Grace; Gip, Phung; Heller, H. Craig; Franken, Paul

2010-01-01

Study Objectives: The sleep-deprivation–induced changes in delta power, an electroencephalographical correlate of sleep need, and brain transcriptome profiles have importantly contributed to current hypotheses on sleep function. Because sleep deprivation also induces stress, we here determined the contribution of the corticosterone component of the stress response to the electrophysiological and molecular markers of sleep need in mice. Design: N/A Settings: Mouse sleep facility. Participants: C57BL/6J, AKR/J, DBA/2J mice. Interventions: Sleep deprivation, adrenalectomy (ADX). Measurements and Results: Sleep deprivation elevated corticosterone levels in 3 inbred strains, but this increase was larger in DBA/2J mice; i.e., the strain for which the rebound in delta power after sleep deprivation failed to reach significance. Elimination of the sleep-deprivation–associated corticosterone surge through ADX in DBA/2J mice did not, however, rescue the delta power rebound but did greatly reduce the number of transcripts affected by sleep deprivation. Genes no longer affected by sleep deprivation cover pathways previously implicated in sleep homeostasis, such as lipid, cholesterol (e.g., Ldlr, Hmgcs1, Dhcr7, −24, Fkbp5), energy and carbohydrate metabolism (e.g., Eno3, G6pc3, Mpdu1, Ugdh, Man1b1), protein biosynthesis (e.g., Sgk1, Alad, Fads3, Eif2c2, −3, Mat2a), and some circadian genes (Per1, −3), whereas others, such as Homer1a, remained unchanged. Moreover, several microRNAs were affected both by sleep deprivation and ADX. Conclusions: Our findings indicate that corticosterone contributes to the sleep-deprivation–induced changes in brain transcriptome that have been attributed to wakefulness per se. The study identified 78 transcripts that respond to sleep loss independent of corticosterone and time of day, among which genes involved in neuroprotection prominently feature, pointing to a molecular pathway directly relevant for sleep function. Citation: Mongrain

Cul3 and the BTB Adaptor Insomniac Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila

PubMed Central

Pfeiffenberger, Cory; Allada, Ravi

2012-01-01

Sleep is homeostatically regulated, such that sleep drive reflects the duration of prior wakefulness. However, despite the discovery of genes important for sleep, a coherent molecular model for sleep homeostasis has yet to emerge. To better understand the function and regulation of sleep, we employed a reverse-genetics approach in Drosophila. An insertion in the BTB domain protein CG32810/insomniac (inc) exhibited one of the strongest baseline sleep phenotypes thus far observed, a ∼10 h sleep reduction. Importantly, this is coupled to a reduced homeostatic response to sleep deprivation, consistent with a disrupted sleep homeostat. Knockdown of the INC-interacting protein, the E3 ubiquitin ligase Cul3, results in reduced sleep duration, consolidation, and homeostasis, suggesting an important role for protein turnover in mediating INC effects. Interestingly, inc and Cul3 expression in post-mitotic neurons during development contributes to their adult sleep functions. Similar to flies with increased dopaminergic signaling, loss of inc and Cul3 result in hyper-arousability to a mechanical stimulus in adult flies. Furthermore, the inc sleep duration phenotype can be rescued by pharmacological inhibition of tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis. Taken together, these results establish inc and Cul3 as important new players in setting the sleep homeostat and a dopaminergic arousal pathway in Drosophila. PMID:23055946

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

PubMed

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.

Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization

PubMed Central

Sutton, Blair C.; Opp, Mark R.

2014-01-01

Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on

Altered Sleep Spindles in Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

PubMed

Yoshiike, Takuya; Nishida, Masaki; Yagishita, Kazuyoshi; Nariai, Tadashi; Ishii, Kenji; Nishikawa, Toru

2016-06-15

Delayed encephalopathy (DE) affects not only the cerebral white matter and globus pallidus but also the cortex and thalamus. However, it remains unknown whether these brain lesions alter sleep along with clinical manifestations of DE. A 46-year-old man with DE underwent repetitive hyperbaric oxygen therapy. The patient was evaluated by not only neuropsychological and neuroimaging testing but polysomnography over the clinical course. Neurological symptoms improved markedly; however, profound frontal cognitive deficits continued. The polysomnography revealed prolonged absence and delayed recovery of sleep spindles across recordings. Alterations in spindle oscillations in DE could provide further insight into sleep regulatory networks. © 2016 American Academy of Sleep Medicine.

Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex.

PubMed

Dash, Michael B; Tononi, Giulio; Cirelli, Chiara

2012-07-01

It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

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

PubMed Central

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. PMID:28769767

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

PubMed

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.

A non-circadian role for clock-genes in sleep homeostasis: a strain comparison.

PubMed

Franken, Paul; Thomason, Ryan; Heller, H Craig; O'Hara, Bruce F

2007-10-18

We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound. In all three strains per expression was increased when animals were kept awake but the rate of increase during the SD as well as the relative increase in per after 6 h SD were highest in the strain for which the sleep rebound was smallest; i.e., DBA/2J (D2). Moreover, whereas in the other two strains per1 and per2 reverted to control levels with recovery sleep, per2 expression specifically, remained elevated in D2 mice. dbp expression increased during the light period both during baseline and during SD although levels were reduced during the latter condition compared to baseline. In contrast to per2, dbp expression reverted to control levels with recovery sleep in D2 only, whereas in the two other strains expression remained decreased. These findings support and extend our previous findings that clock genes in the forebrain are implicated in the homeostatic regulation of sleep and suggest that sustained, high levels of per2 expression may negatively impact recovery sleep.

The effects of partial sleep restriction and altered sleep timing on olfactory performance.

PubMed

McNeil, J; Forest, G; Hintze, L J; Brunet, J-F; Doucet, É

2017-12-01

Olfaction can increase the drive to eat and may partially explain the consistent increases in energy intake (EI) following sleep restriction. We investigated the effects of 50% sleep restriction with altered sleep timing on olfactory performance. We also evaluated whether changes (Δ) in olfactory performance were associated with Δ24 h EI. Twelve men and six women (age: 23±4 years; BMI: 23±3 kg/m 2 ) completed three randomized cross-over conditions: habitual sleep duration, 50% sleep restriction with advanced wake-time, and 50% sleep restriction with delayed bedtime. Sleep was measured in-laboratory (polysomnography). Olfactory performance ('sniffin sticks') and 24 h EI (food menu) were evaluated the next day. A trend for a significant condition*sex interaction was noted for threshold-discrimination-identification (TDI) scores (P=0.09); TDI scores were lowest in women and highest in men, following sleep restriction with advanced wake-time. Δolfactory performance were not associated with Δ24 h EI. The impact of sleep restriction on olfactory performance may differ between sexes. Changes in olfactory performance were not associated with changes in 24 h EI. Studies investigating prolonged effects of sleep loss on the relationship between olfactory performance with EI are needed.

Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased

TRICLOSAN AND ENDOCRINE DISRUPTION: EVIDENCE FOR ALTERATIONS IN THYROID HORMONE HOMEOSTASIS.

EPA Science Inventory

Impact Statement: Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is a chlorinated phenolic antibacterial compound found as an active ingredient in many personal care and household products. Recent studies suggest that triclosan may alter thyroid hormone (TH) homeostasis via ...

Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of mice without altering its duration.

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

Musculoskeletal pain in humans is often associated with poor sleep quality. We used a model in which mechanical hypersensitivity was induced by injection of acidified saline into muscle to study the impact of musculoskeletal sensitization on sleep of mice. A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. We instrumented mice with telemeters to record the electroencephalogram (EEG) and body temperature. We used an established model of musculoskeletal sensitization in which mechanical hypersensitivity was induced using two unilateral injections of acidified saline (pH 4.0). The injections were given into the gastrocnemius muscle and spaced five days apart. EEG and body temperature recordings started prior to injections (baseline) and continued for three weeks after musculoskeletal sensitization was induced by the second injection. Mechanical hypersensitivity was assessed using von Frey filaments at baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second injection. Mice injected with acidified saline developed bilateral mechanical hypersensitivity at the hind paws as measured by von Frey testing and as compared to control mice and baseline data. Sleep during the light period was fragmented in experimental mice injected with acidified saline, and EEG spectra altered. Musculoskeletal sensitization did not alter the duration of time spent in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep. Musculoskeletal sensitization in this model results in a distinct sleep phenotype in which sleep is fragmented during the light period, but the overall duration of sleep is not changed. This study suggests the consequences of musculoskeletal pain include sleep disruption, an observation that has been made in the clinical literature but has yet to be studied using preclinical models.

Diet/Energy Balance Affect Sleep and Wakefulness Independent of Body Weight.

PubMed

Perron, Isaac J; Pack, Allan I; Veasey, Sigrid

2015-12-01

Excessive daytime sleepiness commonly affects obese people, even in those without sleep apnea, yet its causes remain uncertain. We sought to determine whether acute dietary changes could induce or rescue wake impairments independent of body weight. We implemented a novel feeding paradigm that generates two groups of mice with equal body weight but opposing energetic balance. Two subsets of mice consuming either regular chow (RC) or high-fat diet (HFD) for 8 w were switched to the opposite diet for 1 w. Sleep recordings were conducted at Week 0 (baseline), Week 8 (pre-diet switch), and Week 9 (post-diet switch) for all groups. Sleep homeostasis was measured at Week 8 and Week 9. Young adult, male C57BL/6J mice. Differences in total wake, nonrapid eye movement (NREM), and rapid eye movement (REM) time were quantified, in addition to changes in bout fragmentation/consolidation. At Week 9, the two diet switch groups had similar body weight. However, animals switched to HFD (and thus gaining weight) had decreased wake time, increased NREM sleep time, and worsened sleep/wake fragmentation compared to mice switched to RC (which were in weight loss). These effects were driven by significant sleep/wake changes induced by acute dietary manipulations (Week 8 → Week 9). Sleep homeostasis, as measured by delta power increase following sleep deprivation, was unaffected by our feeding paradigm. Acute dietary manipulations are sufficient to alter sleep and wakefulness independent of body weight and without effects on sleep homeostasis. © 2015 Associated Professional Sleep Societies, LLC.

Obesity in mares promotes uterine inflammation and alters embryo lipid fingerprints and homeostasis.

PubMed

Sessions-Bresnahan, Dawn R; Heuberger, Adam L; Carnevale, Elaine M

2018-05-07

Maternal body composition can be an important determinant for development of obesity and metabolic syndrome in adult offspring. Obesity-related outcomes in offspring may include epigenetic alterations; however, mechanisms of fetal programming remain to be fully elucidated. This study was conducted to determine the impact of maternal obesity in the absence of a high fat diet on equine endometrium and preimplantation embryos. Embryos were collected from normal and obese mares at 8 and 16 d and a uterine biopsy at 16 d (0 d = ovulation). With the exception of 8 d embryos, each sample was divided into two pieces. One piece was analyzed for gene expression markers related to carbohydrate metabolism, lipid homeostasis, inflammation, endoplasmic reticulum stress, oxidative stress, mitochondrial stress, and components of the insulin-like growth factor (IGF) system. The second piece was analyzed for lipid content using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Obese mares had elevated concentrations of insulin, leptin and total cholesterol, and they tended to have increased triglycerides and decreased insulin sensitivity. Embryos from obese mares had altered transcript abundance in genes for inflammation and lipid homeostasis, as well as, endoplasmic reticulum, oxidative and mitochondrial stress and altered lipid fingerprints. Endometrium from obese mares had increased expression of inflammatory cytokines, lipid homeostasis regulation, mitochondrial stress, and the IGF2 system. This study demonstrates increased adiposity in mares alters the uterine environment, transcript abundance of genes for cellular functions, and lipid profiles of embryos. These alterations could affect prenatal programming, with potential long-term effects in offspring.

Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice

PubMed Central

Ryu, K.-Y.; Fujiki, N.; Kazantzis, M.; Garza, J. C.; Bouley, D. M.; Stahl, A.; Lu, X.-Y.; Nishino, S.; Kopito, R. R.

2010-01-01

Aims Ubiquitin performs essential roles in a myriad of signalling pathways required for cellular function and survival. Recently, we reported that disruption of the stress-inducible ubiquitin-encoding gene Ubb reduces ubiquitin content in the hypothalamus and leads to adult-onset obesity coupled with a loss of arcuate nucleus neurones and disrupted energy homeostasis in mice. Neuropeptides expressed in the hypothalamus control both metabolic and sleep behaviours. In order to demonstrate that the loss of Ubb results in broad hypothalamic abnormalities, we attempted to determine whether metabolic and sleep behaviours were altered in Ubb knockout mice. Methods Metabolic rate and energy expenditure were measured in a metabolic chamber, and sleep stage was monitored via electroencephalographic/electromyographic recording. The presence of neurodegeneration and increased reactive gliosis in the hypothalamus were also evaluated. Results We found that Ubb disruption leads to early-onset reduced activity and metabolic rate. Additionally, we have demonstrated that sleep behaviour is altered and sleep homeostasis is disrupted in Ubb knockout mice. These early metabolic and sleep abnormalities are accompanied by persistent reactive gliosis and the loss of arcuate nucleus neurones, but are independent of neurodegeneration in the lateral hypothalamus. Conclusions Ubb knockout mice exhibit phenotypes consistent with hypothalamic dysfunction. Our data also indicate that Ubb is essential for the maintenance of the ubiquitin levels required for proper regulation of metabolic and sleep behaviours in mice. PMID:20002312

MicroRNAs Regulate Sleep and Sleep Homeostasis in Drosophila.

PubMed

Goodwin, Patricia R; Meng, Alice; Moore, Jessie; Hobin, Michael; Fulga, Tudor A; Van Vactor, David; Griffith, Leslie C

2018-06-26

To discover microRNAs that regulate sleep, we performed a genetic screen using a library of miRNA sponge-expressing flies. We identified 25 miRNAs that regulate baseline sleep; 17 were sleep-promoting and 8 promoted wake. We identified one miRNA that is required for recovery sleep after deprivation and 8 miRNAs that limit the extent of recovery sleep. 65% of the hits belong to human-conserved families. Interestingly, the majority (75%), but not all, of the baseline sleep-regulating miRNAs are required in neurons. Sponges that target miRNAs in the same family, including the miR-92a/92b/310 family and the miR-263a/263b family, have similar effects. Finally, mutation of one of the screen's strongest hits, let-7, using CRISPR/Cas-9, phenocopies sponge-mediated let-7 inhibition. Cell-type-specific and temporally restricted let-7 sponge expression experiments suggest that let-7 is required in the mushroom body both during development and in adulthood. This screen sets the stage for understanding the role of miRNAs in sleep. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Neuronal machinery of sleep homeostasis in Drosophila.

PubMed

Donlea, Jeffrey M; Pimentel, Diogo; Miesenböck, Gero

2014-02-19

Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila's sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein

PubMed Central

McDowell, Kimberly A.; Shin, David; Roos, Kenneth P.; Chesselet, Marie-Françoise

2018-01-01

Background: Sleep disruptions occur early and frequently in Parkinson’s disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models. Objective: The objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model. Methods: At 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype. Results: Thy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness. Conclusions: Alpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD. PMID:24867919

Diet/Energy Balance Affect Sleep and Wakefulness Independent of Body Weight

PubMed Central

Perron, Isaac J.; Pack, Allan I.; Veasey, Sigrid

2015-01-01

Study Objectives: Excessive daytime sleepiness commonly affects obese people, even in those without sleep apnea, yet its causes remain uncertain. We sought to determine whether acute dietary changes could induce or rescue wake impairments independent of body weight. Design: We implemented a novel feeding paradigm that generates two groups of mice with equal body weight but opposing energetic balance. Two subsets of mice consuming either regular chow (RC) or high-fat diet (HFD) for 8 w were switched to the opposite diet for 1 w. Sleep recordings were conducted at Week 0 (baseline), Week 8 (pre-diet switch), and Week 9 (post-diet switch) for all groups. Sleep homeostasis was measured at Week 8 and Week 9. Participants: Young adult, male C57BL/6J mice. Measurements and Results: Differences in total wake, nonrapid eye movement (NREM), and rapid eye movement (REM) time were quantified, in addition to changes in bout fragmentation/consolidation. At Week 9, the two diet switch groups had similar body weight. However, animals switched to HFD (and thus gaining weight) had decreased wake time, increased NREM sleep time, and worsened sleep/wake fragmentation compared to mice switched to RC (which were in weight loss). These effects were driven by significant sleep/wake changes induced by acute dietary manipulations (Week 8 → Week 9). Sleep homeostasis, as measured by delta power increase following sleep deprivation, was unaffected by our feeding paradigm. Conclusions: Acute dietary manipulations are sufficient to alter sleep and wakefulness independent of body weight and without effects on sleep homeostasis. Citation: Perron IJ, Pack AI, Veasey S. Diet/energy balance affect sleep and wakefulness independent of body weight. SLEEP 2015;38(12):1893–1903. PMID:26158893

Stilbene Glucoside, a Putative Sleep Promoting Constituent from Polygonum multiflorum Affects Sleep Homeostasis by Affecting the Activities of Lactate Dehydrogenase and Salivary Alpha Amylase.

PubMed

Wei, Qian; Ta, Guang; He, Wenjing; Wang, Wei; Wu, Qiucheng

2017-01-01

Chinese herbal medicine (CHM) has been used for treating insomnia for centuries. The most used CHM for insomnia was Polygonum multiflorum. However, the molecular mechanism for CHM preventing insomnia is unknown. Stilbene glucoside (THSG), an important active component of P. multiflorum, may play an important role for treating insomnia. To test the hypothesis, Kunming mice were treated with different dosages of THSG. To examine the sleep duration, a computer-controlled sleep-wake detection system was implemented. Electroencephalogram (EEG) and electromyogram (EMG) electrodes were implanted to determine sleep-wake state. RT-PCR and Western blot was used to measure the levels of lactate dehydrogenase (LDH) and saliva alpha amylase. Spearman's rank correlation coefficient was used to identify the strength of correlation between the variables. The results showed that THSG significantly prolonged the sleep time of the mice (p<0.01). THSG changed sleep profile by reducing wake and rapid eye movement (REM) period, and increasing non-REM period. RT-PCR and Western blot analysis showed that THSG could down-regulate the levels of LDH and saliva alpha amylase (p<0.05). The level of lactate and glucose was positively related with the activity of LDH and saliva alpha amylase (p<0.05), respectively. On the other hand, the activities of LDH and amylase were negatively associated with sleep duration (p<0.05). The levels of lactate and glucose affect sleep homeostasis. Thus, THSG may prevent insomnia by regulating sleep duration via LDH and salivary alpha amylase.

Electrocardiogram-Based Sleep Spectrogram Measures of Sleep Stability and Glucose Disposal in Sleep Disordered Breathing

PubMed Central

Pogach, Melanie S.; Punjabi, Naresh M.; Thomas, Neil; Thomas, Robert J.

2012-01-01

Study Objectives: Sleep disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Experimental sleep fragmentation has been shown to impair insulin sensitivity. Conventional electroencephalogram (EEG)-based sleep-quality measures have been inconsistently associated with indices of glucose metabolism. This analysis explored associations between glucose metabolism and an EEG-independent measure of sleep quality, the sleep spectrogram, which maps coupled oscillations of heart-rate variability and electrocardiogram (ECG)-derived respiration. The method allows improved characterization of the quality of stage 2 non-rapid eye movement (NREM) sleep. Design: Cross-sectional study. Setting: N/A. Participants: Nondiabetic subjects with and without SDB (n = 118) underwent the frequently sampled intravenous glucose tolerance test (FSIVGTT) and a full-montage polysomnogram. The sleep spectrogram was generated from ECG collected during polysomnography. Interventions: N/A. Measurements and Results: Standard polysomnographic stages (stages 1, 2, 3+4, and rapid eye movement [REM]) were not associated with the disposition index (DI) derived from the FSIVGTT. In contrast, spectrographic high-frequency coupling (a marker of stable or “effective” sleep) duration was associated with increased, and very-low-frequency coupling (a marker of wake/REM/transitions) associated with reduced DI. This relationship was noted after adjusting for age, sex, body mass index, slow wave sleep, total sleep time, stage 1, the arousal index, and the apnea-hypopnea index. Conclusions: ECG-derived sleep-spectrogram measures of sleep quality are associated with alterations in glucose-insulin homeostasis. This alternate mode of estimating sleep quality could improve our understanding of sleep and sleep-breathing effects on glucose metabolism. Citation: Pogach MS; Punjabi NM; Thomas N; Thomas RJ. Electrocardiogram-based sleep

Inflammatory Milieu and Cardiovascular Homeostasis in Children With Obstructive Sleep Apnea.

PubMed

Smith, David F; Hossain, Md M; Hura, Arjan; Huang, Guixia; McConnell, Keith; Ishman, Stacey L; Amin, Raouf S

2017-04-01

Biomarkers of atherosclerosis (pro-inflammatory cytokines and acute phase reactants) are elevated in children with obstructive sleep apnea (OSA). However, their association with cardiovascular endpoints in children are not understood. We hypothesized that biomarkers of atherosclerosis in children with OSA correlate with pulse transit time (PTT), a surrogate measure of vascular stiffness, with some positively influencing and others negatively influencing PTT. Children with OSA and matched controls were recruited to the study. Pro-inflammatory cytokines and acute phase reactants were measured at 6:00 pm and 6:00 am. Polysomnography with beat-to-beat blood pressure was performed. PTT during wakefulness and stage 2 sleep was calculated. Diurnal variation of biomarkers and their associations with PTT was estimated. Factor analysis was used to determine the effect of groups of cytokines on PTT. One hundred fifty-five children participated in the study; 90 were healthy controls and 65 had OSA. Children with OSA exhibited a different diurnal variation of biomarkers than healthy controls, with pro-inflammatory cytokines peaking in the morning and acute phase reactants peaking in the afternoon. Structural equation modeling demonstrated that interleukins 6 and 8, tumor necrosis factor-α, and sCD40L had a shortening effect, while serum amyloid A, C-reactive protein, and adiponectin had a prolonging effect on PTT. As a result, there was no difference in PTT between the two groups. The differential relationships of acute phase reactants and pro-inflammatory cytokines with PTT suggest that in children with OSA, these mediators may have opposing actions to maintain cardiovascular homeostasis. © 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.

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

PubMed

Simpson, Norah S; Scott-Sutherland, Jennifer; Gautam, Shiva; Sethna, Navil; Haack, Monika

2017-09-01

Chronic pain conditions are highly co-morbid with insufficient sleep. While the mechanistic relationships between the two are not understood, chronic insufficient sleep may be one pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of three weeks of restricted sleep with limited recovery (five nights of 4-hour sleep/night followed by two nights of 8-hour sleep/night) was compared to three weeks of 8-hour sleep/night (control protocol). Seventeen healthy adults participated, with fourteen completing both three-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared to the control protocol, participants in the sleep-restriction/recovery protocol experienced mild increases in spontaneous pain (p<0.05). Heat-pain thresholds decreased following the first week of sleep restriction (p<0.05), but normalized with longer exposure to sleep restriction. In contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both p<0.05), although only in the last two weeks of the sleep restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity.

PubMed

Gazea, Mary; Patchev, Alexandre V; Anderzhanova, Elmira; Leidmaa, Este; Pissioti, Anna; Flachskamm, Cornelia; Almeida, Osborne F X; Kimura, Mayumi

2018-01-10

Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep. SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY 3-36 can reverse this neurochemical imbalance and

Chronobiology, endocrinology, and energy- and food-reward homeostasis.

PubMed

Gonnissen, H K J; Hulshof, T; Westerterp-Plantenga, M S

2013-05-01

Energy- and food-reward homeostasis is the essential component for maintaining energy balance and its disruption may lead to metabolic disorders, including obesity and diabetes. Circadian alignment, quality sleep and sleep architecture in relation to energy- and food-reward homeostasis are crucial. A reduced sleep duration, quality sleep and rapid-eye movement sleep affect substrate oxidation, leptin and ghrelin concentrations, sleeping metabolic rate, appetite, food reward, hypothalamic-pituitary-adrenal (HPA)-axis activity, and gut-peptide concentrations, enhancing a positive energy balance. Circadian misalignment affects sleep architecture and the glucose-insulin metabolism, substrate oxidation, homeostasis model assessment of insulin resistance (HOMA-IR) index, leptin concentrations and HPA-axis activity. Mood disorders such as depression occur; reduced dopaminergic neuronal signaling shows decreased food reward. A good sleep hygiene, together with circadian alignment of food intake, a regular meal frequency, and attention for protein intake or diets, contributes in curing sleep abnormalities and overweight/obesity features by preventing overeating; normalizing substrate oxidation, stress, insulin and glucose metabolism including HOMA-IR index, and leptin, GLP-1 concentrations, lipid metabolism, appetite, energy expenditure and substrate oxidation; and normalizing food reward. Synchrony between circadian and metabolic processes including meal patterns plays an important role in the regulation of energy balance and body-weight control. Additive effects of circadian alignment including meal patterns, sleep restoration, and protein diets in the treatment of overweight and obesity are suggested. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

PubMed Central

Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

2013-01-01

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

Sleep inertia, sleep homeostatic, and circadian influences on higher-order cognitive functions

PubMed Central

Ronda, Joseph M.; Czeisler, Charles A.; Wright, Kenneth P.

2016-01-01

Summary Sleep inertia, sleep homeostatic, and circadian processes modulate cognition, including reaction time, memory, mood, and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-daylong study that included two 14-daylong 28h forced desynchrony protocols, to examine separate and interacting influences of sleep inertia, sleep homeostasis, and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved over the first ~2-4h of wakefulness (sleep inertia); worsened thereafter until scheduled bedtime (sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~9AM and ~9PM respectively, in individuals with a habitual waketime of 7AM). The relative influences of sleep inertia, sleep homeostasis, and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation, and/or upon awakening from sleep. PMID:25773686

Subchronic arsenic exposure through drinking water alters vascular redox homeostasis and affects physical health in rats.

PubMed

Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kutty, Harikumar Sankaran; Kandasamy, Kannan; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

2014-12-01

We evaluated whether arsenic can alter vascular redox homeostasis and modulate antioxidant status, taking rat thoracic aorta as a model vascular tissue. In addition, we evaluated whether the altered vascular biochemical homeostasis could be associated with alterations in the physical indicators of toxicity development. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. Body weight, food intake, and water consumption were recorded weekly. On the 91st day, rats were sacrificed; vital organs and thoracic aorta were collected. Lipid peroxidation, reactive oxygen species generation, and antioxidants were assessed in the thoracic aorta. Arsenic increased aortic lipid peroxidation and hydrogen peroxide generation while decreased reduced glutathione content in a dose-dependent manner. The activities of the enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were decreased. Further, arsenic at 100 ppm decreased feed intake, water consumption, and body weight from the 11th week onward. At this concentration, arsenic increased the relative weights of the liver and kidney. The results suggest that arsenic causes dose-dependent oxidative stress, reduction in antioxidative defense systems, and body weight loss with alteration in hepato-renal organosomatic indices. Overall, subchronic arsenic exposure through drinking water causes alteration in vascular redox homeostasis and at high concentration affects physical health.

Sleep Architecture and NREM Alterations in Children and Adolescents with Asperger Syndrome

PubMed Central

Bruni, Oliviero; Ferri, Raffaele; Vittori, Elena; Novelli, Luana; Vignati, Manuela; Porfirio, Maria C.; Aricò, Debora; Bernabei, Paola; Curatolo, Paolo

2007-01-01

Study Objectives: To analyze sleep in children with Asperger syndrome (AS) by means of standard sleep questionnaires, to evaluate sleep architecture and NREM sleep alterations by means of cyclic alternating pattern (CAP) and to correlate objective sleep parameters with cognitive behavioral measures. Design: Cross-sectional study involving validated sleep questionnaires, neuropsychological scales, and PSG recording. Setting: Sleep medicine center. Participants: Eight children with AS, 10 children with autism, and 12 healthy control children. Interventions: N/A Measurements and Results: Children with AS had a higher prevalence of problems of initiating sleep and daytime sleepiness. Sleep architecture parameters showed minor differences between the 3 groups. CAP parameters showed an increased percentage of A1 and a decreased percentage of A2 subtypes in subjects with AS vs. controls. All A subtype indexes (number per hour of NREM sleep) were decreased, mostly in sleep stage 2 but not in SWS. With respect to children with autism, subjects with AS showed increased CAP rate in SWS and A1 percentage. In subjects with AS, verbal IQ had a significant positive correlation with total CAP rate and CAP rate in SWS and with global and SWS A1 index. The percentage of A2 negatively correlated with full scale IQ, verbal and performance IQ. CBCL total score correlated positively with CAP rate and A1 index while externalizing score correlated negatively with A3%. Conclusions: This study shows peculiar CAP modifications in children with AS and represents an attempt to correlate the quantification of sleep EEG oscillations with the degree of mental ability/disability. Citation: Bruni O; Ferri R; Vittori E; Novelli L; Vignati M; Porfirio MC; Aricò D; Bernabei P; Curatolo P. Sleep architecture and NREM alterations in children and adolescents with asperger syndrome. SLEEP 2007;30(11):1577-1585. PMID:18041490

Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.

PubMed

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.

Cortical region-specific sleep homeostasis in mice: effects of time of day and waking experience.

PubMed

Guillaumin, Mathilde C C; McKillop, Laura E; Cui, Nanyi; Fisher, Simon P; Foster, Russell G; de Vos, Maarten; Peirson, Stuart N; Achermann, Peter; Vyazovskiy, Vladyslav V

2018-04-25

Sleep-wake history, wake behaviours, lighting conditions and circadian time influence sleep, but neither their relative contribution, nor the underlying mechanisms are fully understood. The dynamics of EEG slow-wave activity (SWA) during sleep can be described using the two-process model, whereby the parameters of homeostatic Process S are estimated using empirical EEG SWA (0.5-4 Hz) in non-rapid eye movement sleep (NREM), and the 24-h distribution of vigilance states. We hypothesised that the influence of extrinsic factors on sleep homeostasis, such as the time of day or wake behaviour, would manifest in systematic deviations between empirical SWA and model predictions. To test this hypothesis, we performed parameter estimation and tested model predictions using NREM SWA derived from continuous EEG recordings from the frontal and occipital cortex in mice. The animals showed prolonged wake periods, followed by consolidated sleep, both during the dark and light phases, and wakefulness primarily consisted of voluntary wheel running, learning a new motor skill or novel object exploration. Simulated SWA matched empirical levels well across conditions, and neither waking experience nor time of day had a significant influence on the fit between data and simulation. However, we consistently observed that Process S declined during sleep significantly faster in the frontal than in the occipital area of the neocortex. The striking resilience of the model to specific wake behaviours, lighting conditions and time of day suggests that intrinsic factors underpinning the dynamics of Process S are robust to extrinsic influences, despite their major role in shaping the overall amount and distribution of vigilance states across 24 h.

Sleep inertia, sleep homeostatic and circadian influences on higher-order cognitive functions.

PubMed

Burke, Tina M; Scheer, Frank A J L; Ronda, Joseph M; Czeisler, Charles A; Wright, Kenneth P

2015-08-01

Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. © 2015 European Sleep Research Society.

Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice.

PubMed

Singh, Anant; Kumar, Anil

2008-04-01

Sleep deprivation is considered as a risk factor for various diseases. Sleep deprivation leads to behavioral, hormonal, neurochemical and biochemical alterations in the animals. The present study was designed to explore the possible involvement of GABAergic mechanism in protective effect of alprazolam against 72h sleep deprivation-induced behavior alterations and oxidative damage in mice. In the present study, sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep-deprived mice brain. Treatment with alprazolam (0.25 and 0.5 mg/kg, ip) significantly improved behavioral alterations. Biochemically, alprazolam treatment significantly restored depleted reduced glutathione, catalase activity, reversed raised lipid peroxidation and nitrite level. Combination of flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) with lower dose of alprazolam (0.25mg/kg) significantly antagonized protective effect of alprazolam. However, combination of muscimol (0.05 mg/kg) with alprazolam (0.25 mg/kg, ip) potentiated protective effect of alprazolam. On the basis of these results, it might be suggested that alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.

Obesity and Altered Sleep: A Pathway to Metabolic Derangements in Children?

PubMed Central

Hakim, Fahed; Kheirandish-Gozal, Leila; Gozal, David

2015-01-01

Obstructive sleep apnea (OSA) is a frequent disorder in children and is primarily associated with adenotonsillar hypertrophy., The prominent increases in childhood overweight and obesity rates in the world even among youngest of children have translated into parallel increases in the prevalence of OSA, and such trends will undoubtedly be associated with deleterious global health outcomes and life expectancy. Even an obesity phenotype in childhood OSA, more close to the adult type, has been recently proposed. Reciprocal interactions between sleep in general, OSA, obesity, and disruptions of metabolic homeostasis have emerged in recent years. These associations have suggested the a priori involvement of complex sets of metabolic and inflammatory pathways all of which may underlie increased risk for increased orexigenic behaviors and dysfunctional satiety, hyperlipidemia, and insulin resistance that ultimately favor the emergence of metabolic syndrome. Here, we will review some of the critical evidence supporting the proposed associations between sleep disruption and the metabolism-obesity complex. In addition, we will describe the more recent evidence linking the potential interactive roles of OSA and obesity on metabolic phenotype. PMID:26072337

Update on energy homeostasis and insufficient sleep.

PubMed

Penev, Plamen D

2012-06-01

Driven by the demands and opportunities of modern life, many people habitually sleep less than 6 h a night. In the sleep clinic, chronic sleep restriction is recognized by the diagnosis of insufficient sleep syndrome (ICSD-9, 307.49-4), which is receiving increased scrutiny as a potential risk to metabolic health. Its relevance for the practicing endocrinologist is highlighted by a stream of epidemiological data that show an association of insufficient sleep with increased incidence of obesity and related morbidities. A central theme of this update is the notion that sleep loss incurs additional metabolic cost, which triggers a set of neuroendocrine, metabolic, and behavioral adaptations aimed at increasing food intake and conserving energy. Although this coordinated response may have evolved to offset the metabolic demands of extended wakefulness in natural habitats with limited food availability, it can be maladaptive in the context of a modern environment that allows many to overeat while maintaining a sedentary lifestyle without sufficient sleep. Importantly, such sleep loss-related metabolic adaptation may undermine the success of behavioral interventions based on reduced caloric intake and increased physical activity to lower metabolic risk in obesity-prone individuals. This emerging perspective is based on data from recently published human interventional studies and requires further experimental support. Nevertheless, it now seems prudent to recommend that overweight and obese individuals attempting to reduce their caloric intake and maintain increased physical activity should obtain adequate sleep and, if needed, seek effective treatment for any coexisting sleep disorders.

Sleep Homeostasis and Synaptic Plasticity

DTIC Science & Technology

2017-06-01

accrued through learning. But how is wake experience translated into sleep drive? Where in the brain does this occur? Is there a discrete sleep drive...neuronal activity in discrete parts of the brain. At the same time, neuronal biochemistry is very similar – flies and man respond in a similar manner to...null phenotypes by expressing rescue construct in discrete regions Task 1C: Verify rescue brain areas by RNAi knockdown (in wildtype) of gene in areas

Shiftwork-Mediated Disruptions of Circadian Rhythms and Sleep Homeostasis Cause Serious Health Problems

PubMed Central

Duan, Pengfei

2018-01-01

Shiftwork became common during the last few decades with the growing demands of human life. Despite the social inactivity and irregularity in habits, working in continuous irregular shifts causes serious health issues including sleep disorders, psychiatric disorders, cancer, and metabolic disorders. These health problems arise due to the disruption in circadian clock system, which is associated with alterations in genetic expressions. Alteration in clock controlling genes further affects genes linked with disorders including major depression disorder, bipolar disorder, phase delay and phase advance sleep syndromes, breast cancer, and colon cancer. A diverse research work is needed focusing on broad spectrum changes caused by jet lag in brain and neuronal system. This review is an attempt to motivate the researchers to conduct advanced studies in this area to identify the risk factors and mechanisms. Its goal is extended to make the shift workers aware about the risks associated with shiftwork. PMID:29607311

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery.

PubMed

Pellegrino, R; Sunaga, D Y; Guindalini, C; Martins, R C S; Mazzotti, D R; Wei, Z; Daye, Z J; Andersen, M L; Tufik, S

2012-11-01

Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

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

NASA Technical Reports Server (NTRS)

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

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

PubMed

McNeil, Jessica; Doucet, Éric; Brunet, Jean-François; Hintze, Luzia Jaeger; Chaumont, Isabelle; Langlois, Émilie; Maitland, Riley; Riopel, Alexandre; Forest, Geneviève

2016-10-01

Experimental evidence suggests that sleep restriction increases energy intake (EI) and may alter energy expenditure (EE). However, it is unknown whether the timing of a sleep restriction period impacts EI and EE the following day. Hence, we examined the effects of sleep restriction with an advanced wake-time or delayed bedtime on next day EI and EE. Twelve men and 6 women (age: 23±4years, body fat: 18.8±10.1%) participated in 3 randomized crossover sessions: control (habitual bed- and wake-times), 50% sleep restriction with an advanced wake-time and 50% sleep restriction with a delayed bedtime. Outcome variables included sleep architecture (polysomnography), EI (food menu), total EE and activity times (accelerometry). Carbohydrate intake was greater on day 2 in the delayed bedtime vs. control session (1386±513 vs. 1579±571kcal; P=0.03). Relative moderate-intensity physical activity (PA) time was greater in the delayed bedtime session vs. control and advanced wake-time sessions on day 1 (26.6±19.9 vs. 16.1±10.6 and 17.5±11.8%; P=0.01), whereas vigorous-intensity PA time was greater following advanced wake-time vs. delayed bedtime on day 1 (2.7±3.0 vs. 1.3±2.4%; P=0.004). Greater stage 1 sleep (β=110kcal, 95% CI for β=42 to 177kcal; P=0.004), and a trend for lower REM sleep (β=-20kcal, 95% CI for β=-41 to 2kcal; P=0.07), durations were associated with greater EI between sleep restriction sessions. These findings suggest that the timing of a sleep restriction period impacts energy balance parameters. Additional studies are needed to corroborate these findings, given the increasing prevalence of shift workers and incidences of sleep disorders and voluntary sleep restriction. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased Automaticity and Altered Temporal Preparation Following Sleep Deprivation

PubMed Central

Kong, Danyang; Asplund, Christopher L.; Ling, Aiqing; Chee, Michael W.L.

2015-01-01

participants also rely more on automatic processes. Citation: Kong D, Asplund CL, Ling A, Chee MWL. Increased automaticity and altered temporal preparation following sleep deprivation. SLEEP 2015;38(8):1219–1227. PMID:25845689

Altered transition metal homeostasis in Niemann-Pick disease, Type C1

PubMed Central

Hung, Ya Hui; Faux, Noel G.; Killilea, David W.; Yanjanin, Nicole; Firnkes, Sally; Volitakis, Irene; Ganio, George; Walterfang, Mark; Hastings, Caroline; Porter, Forbes D.; Ory, Daniel S.; Bush, Ashley I.

2014-01-01

The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1−/− mouse model, and cell culture studies also suggest failure of metal homeostasis in NP-C1. To investigate these findings, we performed a comprehensive transition metal analysis of cerebrospinal fluid (CSF), plasma and tissue samples from human NP-C1 patients and an Npc1−/− mouse model. NPC1 deficiency in the Npc1−/− mouse model resulted in a perturbation of transition metal homeostasis in the plasma and key organs (brain, liver, spleen, heart, lungs, and kidneys). Analysis of human patient CSF, plasma and post-mortem brain tissues also indicated disrupted metal homeostasis. There was a disparity in the direction of metal changes between the human and the Npc1−/− mouse samples, which may reflect species-specific metal metabolism. Nevertheless, common to both species is brain zinc accumulation. Furthermore, treatment with the glucosylceramide synthase inhibitor miglustat, the only drug shown in a controlled clinical trial to have some efficacy for NP-C1, did not correct the alterations in CSF and plasma transition metal and ceruloplasmin (CP) metabolism in NP-C1 patients. These findings highlight the importance of NPC1 function in metal homeostasis, and indicate that metal-targeting therapy may be of value as a treatment for NP-C. PMID:24343124

Altered Sleep and Affect in the Neurotensin Receptor 1 Knockout Mouse

PubMed Central

Fitzpatrick, Karrie; Winrow, Christopher J.; Gotter, Anthony L.; Millstein, Joshua; Arbuzova, Janna; Brunner, Joseph; Kasarskis, Andrew; Vitaterna, Martha H.; Renger, John J.; Turek, Fred W.

2012-01-01

Study Objective: Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model. Design: Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse. Measurements and Results: NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors. Conclusions: Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders. Citation: Fitzpatrick K; Winrow CJ; Gotter AL; Millstein J; Arbuzova J; Brunner J; Kasarskis A; Vitaterna MH; Renger JJ; Turek FW. Altered sleep and affect in the neurotensin receptor 1 knockout mouse. SLEEP 2012;35(7):949-956. PMID:22754041

Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

EPA Science Inventory

Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

PubMed

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.

Chronic Exposure to Type-I IFN under Lymphopenic Conditions Alters CD4 T Cell Homeostasis

PubMed Central

Le Saout, Cecile; Hasley, Rebecca B.; Imamichi, Hiromi; Tcheung, Lueng; Hu, Zonghui; Luckey, Megan A.; Park, Jung-Hyun; Durum, Scott K.; Smith, Mindy; Rupert, Adam W.; Sneller, Michael C.; Lane, H. Clifford; Catalfamo, Marta

2014-01-01

HIV infection and the associated chronic immune activation alter T cell homeostasis leading to CD4 T cell depletion and CD8 T cell expansion. The mechanisms behind these outcomes are not totally defined and only partially explained by the direct cytopathic effect of the virus. In this manuscript, we addressed the impact of lymphopenia and chronic exposure to IFN-α on T cell homeostasis. In a lymphopenic murine model, this interaction led to decreased CD4 counts and CD8 T cell expansion in association with an increase in the Signal Transducer and Activator of Transcription 1 (STAT1) levels resulting in enhanced CD4 T cell responsiveness to IFN-α. Thus, in the setting of HIV infection, chronic stimulation of this pathway could be detrimental for CD4 T cell homeostasis. PMID:24603698

A dopamine receptor d2-type agonist attenuates the ability of stress to alter sleep in mice.

PubMed

Jefferson, F; Ehlen, J C; Williams, N S; Montemarano, J J; Paul, K N

2014-11-01

Although sleep disruptions that accompany stress reduce quality of life and deteriorate health, the mechanisms through which stress alters sleep remain obscure. Psychological stress can alter sleep in a variety of ways, but it has been shown to be particularly influential on rapid eye movement (REM) sleep. Prolactin (PRL), a sexually dimorphic, stress-sensitive hormone whose basal levels are higher in females, has somnogenic effects on REM sleep. In the current study, we examined the relationship between PRL secretion and REM sleep after restraint stress to determine whether: 1) the ability of stress to increase REM sleep is PRL-dependent, and 2) fluctuating PRL levels underlie sex differences in sleep responses to stress. Because dopamine D2 receptors in the pituitary gland are the primary regulator of PRL secretion, D2 receptor agonist, 1-[(6-allylergolin-8β-yl)-carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea (cabergoline), was used to attenuate PRL levels in mice before 1 hour of restraint stress. Mice were implanted with electroencephalographic/electromyographic recording electrodes and received an ip injection of either 0.3-mg/kg cabergoline or vehicle before a control procedure of 1 hour of sleep deprivation by gentle handling during the light phase. Six days after the control procedure, mice received cabergoline or vehicle 15 minutes before 1 hour of restraint stress. Cabergoline blocked the ability of restraint stress to increase REM sleep amount in males but did not alter REM sleep amount after stress in females even though it reduced basal REM sleep amount in female controls. These data provide evidence that the ability for restraint stress to increase REM sleep is dependent on PRL and that sex differences in REM sleep amount may be driven by PRL.

Sleep, Memory & Brain Rhythms.

PubMed

Watson, Brendon O; Buzsáki, György

2015-01-01

Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called "sharp-wave ripple" seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep-REM and non-REM, the latter of which has an abundance of ripple electrical activity-might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function.

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis.

PubMed

Murillo-Rodríguez, Eric; Machado, Sergio; Rocha, Nuno Barbosa; Budde, Henning; Yuan, Ti-Fei; Arias-Carrión, Oscar

2016-12-17

The endocannabinoid system comprises receptors (CB 1 and CB 2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB 1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB 1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.

PubMed

Vanderheyden, William M; George, Sophie A; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R

2015-08-01

Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10 Hz) and sigma (10-15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure.

Exploratory behavior, cortical BDNF expression, and sleep homeostasis.

PubMed

Huber, Reto; Tononi, Giulio; Cirelli, Chiara

2007-02-01

Slow-wave activity (SWA; 0.5-4.0 Hz) during non-rapid eye movement (NREM) sleep is a reliable indicator of sleep need, as it increases with the duration of prior wakefulness and decreases during sleep. However, which biologic process occurring during wakefulness is responsible for the increase of sleep SWA remains unknown. The aim of the study was to determine whether neuronal plasticity underlies the link between waking activities and the SWA response. We manipulated, in rats, the amount of exploratory activity while maintaining the total duration of waking constant. We then measured the extent to which exploration increases cortical expression of plasticity-related genes (BDNF, Arc, Homer, NGFI-A), and the SWA response once the animals were allowed to sleep. Basic neurophysiology and molecular laboratory. Male Wistar Kyoto rats (250-300 g; 2-3 month old). None. We found that, within the same animal, the amount of exploratory behavior during wakefulness could predict the extent to which BDNF was induced, as well as the extent of the homeostatic SWA response during subsequent sleep. This study suggests a direct link between the synaptic plasticity triggered by waking activities and the homeostatic sleep response and identifies BDNF as a major mediator of this link at the molecular level.

Sleep, Memory & Brain Rhythms

PubMed Central

Watson, Brendon O.; Buzsáki, György

2015-01-01

Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called “sharp-wave ripple” seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep–REM and non-REM, the latter of which has an abundance of ripple electrical activity–might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function. PMID:26097242

Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes.

PubMed

Lungato, L; Marques, M S; Pereira, V G; Hix, S; Gazarini, M L; Tufik, S; D'Almeida, V

2013-03-01

Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep-deprived mice did show higher MnSOD gene expression than the control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses. © 2013 The Authors. Scandinavian Journal of Immunology © 2013 Blackwell Publishing Ltd.

Melanin-Concentrating Hormone: A New Sleep Factor?

PubMed Central

Torterolo, Pablo; Lagos, Patricia; Monti, Jaime M.

2011-01-01

Neurons containing the neuropeptide melanin-concentrating hormone (MCH) 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 a high density of MCHergic fibers and receptors. (2) MCHergic neurons are active during sleep, especially during rapid eye movement (REM) sleep. (3) MCH knockout mice have less REM sleep, notably under conditions of negative energy balance. Animals with genetically inactivated MCHR1 also exhibit altered vigilance state architecture and sleep homeostasis. (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. PMID:21516258

The role of sleep in regulating structural plasticity and synaptic strength: Implications for memory and cognitive function.

PubMed

Raven, Frank; Van der Zee, Eddy A; Meerlo, Peter; Havekes, Robbert

2018-06-01

Dendritic spines are the major sites of synaptic transmission in the central nervous system. Alterations in the strength of synaptic connections directly affect the neuronal communication, which is crucial for brain function as well as the processing and storage of information. Sleep and sleep loss bidirectionally alter structural plasticity, by affecting spine numbers and morphology, which ultimately can affect the functional output of the brain in terms of alertness, cognition, and mood. Experimental data from studies in rodents suggest that sleep deprivation may impact structural plasticity in different ways. One of the current views, referred to as the synaptic homeostasis hypothesis, suggests that wake promotes synaptic potentiation whereas sleep facilitates synaptic downscaling. On the other hand, several studies have now shown that sleep deprivation can reduce spine density and attenuate synaptic efficacy in the hippocampus. These data are the basis for the view that sleep promotes hippocampal structural plasticity critical for memory formation. Altogether, the impact of sleep and sleep loss may vary between regions of the brain. A better understanding of the role that sleep plays in regulating structural plasticity may ultimately lead to novel therapeutic approaches for brain disorders that are accompanied by sleep disturbances and sleep loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

Update of sleep alterations in depression

PubMed Central

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

Altered serum copper homeostasis suggests higher oxidative stress and lower antioxidant capability in patients with chronic hepatitis B.

PubMed

Huang, Yansong; Zhang, Yuan; Lin, Zhexuan; Han, Ming; Cheng, Hongqiu

2018-06-01

Copper homeostasis can be altered by inflammation. This study aimed to investigate the alteration of serum copper homeostasis and to explore its clinical significance in patients with chronic hepatitis B (CHB).Thirty-two patients with CHB and 10 aged- and sex-matched healthy controls were recruited. Analyses included serum levels of total copper (TCu), copper ions (Cu), small molecule copper (SMC), ceruloplasmin (CP), Cu/Zn superoxide dismutase 1 (SOD1), urinary copper, and the activities of serum CP and SOD1.The serum TCu and urinary copper levels in patients with CHB were significantly higher than the controls (P = .04 and .003), while the serum Cu was lower than the controls (P = .0002). CP and SOD1 activities in the serum were significantly lower in patients with CHB compared to controls (P = .005) despite higher serum concentrations. In addition, serum alanine aminotransferase inversely correlated with serum CP activity (P = .0318, r = -0.4065).Serum copper homeostasis was altered in this cohort of patients with CHB. The results suggest increased oxidative stress and impaired antioxidant capability in patients with CHB, in addition to necroinflammation. These results may provide novel insights into the diagnosis and treatment of patients with CHB.

The Bidirectional Relationship between Sleep and Immunity against Infections

PubMed Central

Ibarra-Coronado, Elizabeth G.; Pantaleón-Martínez, Ana Ma.; Velazquéz-Moctezuma, Javier; Prospéro-García, Oscar; Méndez-Díaz, Mónica; Pérez-Tapia, Mayra; Pavón, Lenin; Morales-Montor, Jorge

2015-01-01

Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed. PMID:26417606

The Bidirectional Relationship between Sleep and Immunity against Infections.

PubMed

Ibarra-Coronado, Elizabeth G; Pantaleón-Martínez, Ana Ma; Velazquéz-Moctezuma, Javier; Prospéro-García, Oscar; Méndez-Díaz, Mónica; Pérez-Tapia, Mayra; Pavón, Lenin; Morales-Montor, Jorge

2015-01-01

Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.

Sleep Alterations Following Exposure to Stress Predict Fear-Associated Memory Impairments in a Rodent Model of PTSD

PubMed Central

Vanderheyden, William M.; George, Sophie A.; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R.

2015-01-01

Sleep abnormalities such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of post-traumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating these sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stress exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops in rats. SPS resulted in acutely increased REM sleep, transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. We also report reductions in theta (4–10 Hz) and sigma (10–15 Hz) band power during transition to REM sleep which also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure. PMID:26019008

Disturbed Dreaming and the Instability of Sleep: Altered Nonrapid Eye Movement Sleep Microstructure in Individuals with Frequent Nightmares as Revealed by the Cyclic Alternating Pattern

PubMed Central

Simor, Péter; Bódizs, Róbert; Horváth, Klára; Ferri, Raffaele

2013-01-01

Study Objectives: Nightmares are disturbing mental experiences during sleep that usually result in abrupt awakenings. Frequent nightmares are associated with poor subjective sleep quality, and recent polysomnographic data suggest that nightmare sufferers exhibit impaired sleep continuity during nonrapid eye movement (NREM) sleep. Because disrupted sleep might be related to abnormal arousal processes, the goal of this study was to examine polysomnographic arousal-related activities in a group of nightmare sufferers and a healthy control group. Design: Sleep microstructure analysis was carried out by scoring the cyclic alternating pattern (CAP) in NREM sleep and the arousal index in rapid eye movement (REM) sleep on the second night of the polysomnographic examination. Setting: Hospital-based sleep research laboratory. Participants: There were 17 in the nightmare (NMs) group and 23 in the healthy control (CTLs) group. Interventions: N/A. Measurements and Results: The NMs group exhibited reduced amounts of CAP A1 subtype and increased CAP A2 and A3 subtypes, as well as longer duration of CAP A phases in comparison with CTLs. Moreover, these differences remained significant after controlling for the confounding factors of anxious and depressive symptoms. The absolute number and frequency of REM arousals did not differ significantly between the two groups. Conclusions: The results of our study indicate that NREM sleep microstructure is altered during nonsymptomatic nights of nightmares. Disrupted sleep in the NMs group seems to be related to abnormal arousal processes, specifically an imbalance in sleep-promoting and arousing mechanisms during sleep. Citation: Simor P; Bódizs R; Horváth K; Ferri R. Disturbed dreaming and the instability of sleep: altered nonrapid eye movement sleep microstructure in individuals with frequent nightmares as revealed by the cyclic alternating pattern. SLEEP 2013;36(3):413-419. PMID:23449753

Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep.

PubMed

Bagshaw, Andrew P; Rollings, David T; Khalsa, Sakh; Cavanna, Andrea E

2014-01-01

The link between epilepsy and sleep is well established on many levels. The focus of the current review is on recent neuroimaging investigations into the alterations of consciousness that are observed during absence seizures and the descent into sleep. Functional neuroimaging provides simultaneous cortical and subcortical recording of activity throughout the brain, allowing a detailed definition and characterization of large-scale brain networks and the interactions between them. This has led to the identification of a set of regions which collectively form the consciousness system, which includes contributions from the default mode network (DMN), ascending arousal systems, and the thalamus. Electrophysiological and neuroimaging investigations have also clearly demonstrated the importance of thalamocortical and corticothalamic networks in the evolution of sleep and absence epilepsy, two phenomena in which the subject experiences an alteration to the conscious state and a disconnection from external input. However, the precise relationship between the consciousness system, thalamocortical networks, and consciousness itself remains to be clarified. One of the fundamental challenges is to understand how distributed brain networks coordinate their activity in order to maintain and implement complex behaviors such as consciousness and how modifications to this network activity lead to alterations in consciousness. By taking into account not only the level of activation of individual brain regions but also their connectivity within specific networks and the activity and connectivity of other relevant networks, a more specific quantification of brain states can be achieved. This, in turn, may provide a more fundamental understanding of the alterations to consciousness experienced in sleep and epilepsy. © 2013.

Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/β-Catenin Dependent Mechanism

PubMed Central

Wannenes, Francesca; Papa, Vincenza; Greco, Emanuela A.; Fornari, Rachele; Marocco, Chiara; Di Luigi, Luigi; Donini, Lorenzo M.; Lenzi, Andrea

2014-01-01

Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by obesity and sarcopenia (OS), and (4) affected by obesity, sarcopenia, and low BMD (OOS) as compared to subjects with normal body weight and normal BMD (CTL). Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/β-catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered β-catenin cellular compartmentalization and GSK3β phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis. PMID:24963291

Mechanisms altering airway smooth muscle cell Ca+ homeostasis in two asthma models.

PubMed

Kellner, Julia; Tantzscher, Juliane; Oelmez, Hamza; Edelmann, Martin; Fischer, Rainald; Huber, Rudolf Maria; Bergner, Albrecht

2008-01-01

Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist-induced Ca(2+) increase in ASMC have been reported in asthma. The aim of this study was to investigate mechanisms underlying these changes. Murine tracheal smooth muscle cells (MTSMC) from T-bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine-induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Acetylcholine-induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild-type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine-induced Ca(2+) transients could be reversed by blocking inositol-3-phosphate receptors. We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright 2008 S. Karger AG, Basel.

Sleep and meal-time misalignment alters functional connectivity: a pilot resting-state study.

PubMed

Yoncheva, Y N; Castellanos, F X; Pizinger, T; Kovtun, K; St-Onge, M-P

2016-11-01

Delayed sleep and meal times promote metabolic dysregulation and obesity. Altered coordination of sleeping and eating times may impact food-reward valuation and interoception in the brain, yet the independent and collective contributions of sleep and meal times are unknown. This randomized, in-patient crossover study experimentally manipulates sleep and meal times while preserving sleep duration (7.05±0.44 h for 5 nights). Resting-state functional magnetic resonance imaging scans (2 × 5-minute runs) were obtained for four participants (three males; 25.3±4.6 years), each completing all study phases (normal sleep/normal meal; late sleep/normal meal; normal sleep/late meal; and late sleep/late meal). Normal mealtimes were 1, 5, 11 and 12.5 h after awakening; late mealtimes were 4.5, 8.5, 14.5 and 16 h after awakening. Seed-based resting-state functional connectivity (RSFC) was computed for a priori regions-of-interest (seeds) and contrasted across conditions. Statistically significant (P<0.05, whole-brain corrected) regionally specific effects were found for multiple seeds. The strongest effects were linked to the amygdala: increased RSFC for late versus normal mealtimes (equivalent to skipping breakfast). A main effect of sleep and interaction with meal time were also observed. Preliminary findings support the feasibility of examining the effects of sleep and meal-time misalignment, independent of sleep duration, on RSFC in regions relevant to food reward and interoception.

ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS

EPA Science Inventory

ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS

Stoker, Tammy E.1; Laws, Susan C.1; Ferrell, Janet M.1; Cooper, Ralph L.1.

Endocrinology Branch, RTD, NHEERL, ORD, U.S. EPA, RTP, NC, 27711.

The...

Homeostatic response to sleep/rest deprivation by constant water flow in larval zebrafish in both dark and light conditions.

PubMed

Aho, Vilma; Vainikka, Maija; Puttonen, Henri A J; Ikonen, Heidi M K; Salminen, Tiia; Panula, Pertti; Porkka-Heiskanen, Tarja; Wigren, Henna-Kaisa

2017-06-01

Sleep-or sleep-like states-have been reported in adult and larval zebrafish using behavioural criteria. These reversible quiescent periods, displaying circadian rhythmicity, have been used in pharmacological, genetic and neuroanatomical studies of sleep-wake regulation. However, one of the important criteria for sleep, namely sleep homeostasis, has not been demonstrated unequivocally. To study rest homeostasis in zebrafish larvae, we rest-deprived 1-week-old larvae with a novel, ecologically relevant method: flow of water. Stereotyped startle responses to sensory stimuli were recorded after the rest deprivation to study arousal threshold using a high-speed camera, providing an appropriate time resolution to detect species-specific behavioural responses occurring in a millisecond time-scale. Rest-deprived larvae exhibited fewer startle responses than control larvae during the remaining dark phase and the beginning of the light phase, which can be interpreted as a sign of rest homeostasis-often used as equivalent of sleep homeostasis. To address sleep homeostasis further, we probed the adenosinergic system, which in mammals regulates sleep homeostasis. The adenosine A1 receptor agonist, cyclohexyladenosine, administered during the light period, decreased startle responses and increased immobility bouts, while the adenosine antagonist, caffeine, administered during the dark period, decreased immobility bouts. These results suggest that the regulation of sleep homeostasis in zebrafish larvae consists of the same elements as that of other species. © 2017 European Sleep Research Society.

A new strategy to analyze possible association structures between dynamic nocturnal hormone activities and sleep alterations in humans.

PubMed

Kalus, Stefanie; Kneib, Thomas; Steiger, Axel; Holsboer, Florian; Yassouridis, Alexander

2009-04-01

The human sleep process shows dynamic alterations during the night. Methods are needed to examine whether and to what extent such alterations are affected by internal, possibly time-dependent, factors, such as endocrine activity. In an observational study, we examined simultaneously sleep EEG and nocturnal levels of renin, growth hormone (GH), and cortisol (between 2300 and 0700) in 47 healthy volunteers comprising 24 women (41.67 +/- 2.93 yr of age) and 23 men (37.26 +/- 2.85 yr of age). Hormone concentrations were measured every 20 min. Conventional sleep stage scoring at 30-s intervals was applied. Semiparametric multinomial logit models are used to study and quantify possible time-dependent hormone effects on sleep stage transition courses. Results show that increased cortisol levels decrease the probability of transition from rapid-eye-movement (REM) sleep to wakefulness (WAKE) and increase the probability of transition from REM to non-REM (NREM) sleep, irrespective of the time in the night. Via the model selection criterion Akaike's information criterion, it was found that all considered hormone effects on transition probabilities with the initial state WAKE change with time. Similarly, transition from slow-wave sleep (SWS) to light sleep (LS) is affected by a "hormone-time" interaction for cortisol and renin, but not GH. For example, there is a considerable increase in the probability of SWS-LS transition toward the end of the night, when cortisol concentrations are very high. In summary, alterations in human sleep possess dynamic forms and are partially influenced by the endocrine activity of certain hormones. Statistical methods, such as semiparametric multinomial and time-dependent logit regression, can offer ambitious ways to investigate and estimate the association intensities between the nonstationary sleep changes and the time-dependent endocrine activities.

Glycogen metabolism and the homeostatic regulation of sleep.

PubMed

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

2015-02-01

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 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.

Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome.

PubMed

Lassi, Glenda; Priano, Lorenzo; Maggi, Silvia; Garcia-Garcia, Celina; Balzani, Edoardo; El-Assawy, Nadia; Pagani, Marco; Tinarelli, Federico; Giardino, Daniela; Mauro, Alessandro; Peters, Jo; Gozzi, Alessandro; Grugni, Graziano; Tucci, Valter

2016-03-01

Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome. We studied sleep in mutant mice that carry a deletion of Snord116 at the orthologous locus (mouse chromosome 7) of the human PWS critical region (PWScr). In particular, we assessed EEG and temperature profiles, across 24-h, in PWScr (m+/p-) heterozygous mutants compared to wild-type littermates. High-resolution magnetic resonance imaging (MRI) was performed to explore morphoanatomical differences according to the genotype. Moreover, we complemented the mouse work by presenting two patients with a diagnosis of PWS and characterized by atypical small deletions of SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects. By studying the mouse mutant line PWScr(m+/p-), we observed specific rapid eye movement (REM) sleep alterations including abnormal electroencephalograph (EEG) theta waves. Remarkably, we observed identical sleep/EEG defects in the two PWS cases. We report brain morphological abnormalities that are associated with the EEG alterations. In particular, mouse mutants have a bilateral reduction of the gray matter volume in the ventral hippocampus and in the septum areas, which are pivotal structures for maintaining theta rhythms throughout the brain. In PWScr(m+/p-) mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients. Our study indicates that paternally expressed Snord116 is involved in the 24-h regulation of

The temporal structure of behaviour and sleep homeostasis.

PubMed

Vyazovskiy, Vladyslav V; Tobler, Irene

2012-01-01

The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states--NREM and REM sleep, which occur, in rodents, on a time scale of ~5-10 minutes. Neither the mechanisms underlying the time constants of these two processes--the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism.

[Natural factors influencing sleep].

PubMed

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.

Effects of Optogenetic inhibition of BLA on Sleep Brief Optogenetic Inhibition of the Basolateral Amygdala in Mice Alters Effects of Stressful Experiences on Rapid Eye Movement Sleep.

PubMed

Machida, Mayumi; Wellman, Laurie L; Fitzpatrick Bs, Mairen E; Hallum Bs, Olga; Sutton Bs, Amy M; Lonart, György; Sanford, Larry D

2017-04-01

Stressful events can directly produce significant alterations in subsequent sleep, in particular rapid eye movement sleep (REM); however, the neural mechanisms underlying the process are not fully known. Here, we investigated the role of the basolateral nuclei of the amygdala (BLA) in regulating the effects of stressful experience on sleep. We used optogenetics to briefly inhibit glutamatergic cells in BLA during the presentation of inescapable footshock (IS) and assessed effects on sleep, the acute stress response, and fear memory. c-Fos expression was also assessed in the amygdala and the medial prefrontal cortex (mPFC), both regions involved in coping with stress, and in brain stem regions implicated in the regulation of REM. Compared to control mice, peri-shock inhibition of BLA attenuated an immediate reduction in REM after IS and produced a significant overall increase in REM. Moreover, upon exposure to the shock context alone, mice receiving peri-shock inhibition of BLA during training showed increased REM without altered freezing (an index of fear memory) or stress-induced hyperthermia (an index of acute stress response). Inhibition of BLA during REM under freely sleeping conditions enhanced REM only when body temperature was high, suggesting the effect was influenced by stress. Peri-shock inhibition of BLA also led to elevated c-Fos expression in the central nucleus of the amygdala and mPFC and differentially altered c-Fos activity in the selected brain stem regions. Glutamatergic cells in BLA can modulate the effects of stress on REM and can mediate effects of fear memory on sleep that can be independent of behavioral fear. © 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.

Functional Anatomy of Non-REM Sleep

PubMed Central

de Andrés, Isabel; Garzón, Miguel; Reinoso-Suárez, Fernando

2011-01-01

The state of non-REM sleep (NREM), or slow wave sleep, is associated with a synchronized EEG pattern in which sleep spindles and/or K complexes and high-voltage slow wave activity (SWA) can be recorded over the entire cortical surface. In humans, NREM is subdivided into stages 2 and 3–4 (presently named N3) depending on the proportions of each of these polygraphic events. NREM is necessary for normal physical and intellectual performance and behavior. An overview of the brain structures involved in NREM generation shows that the thalamus and the cerebral cortex are absolutely necessary for the most significant bioelectric and behavioral events of NREM to be expressed; other structures like the basal forebrain, anterior hypothalamus, cerebellum, caudal brain stem, spinal cord and peripheral nerves contribute to NREM regulation and modulation. In NREM stage 2, sustained hyperpolarized membrane potential levels resulting from interaction between thalamic reticular and projection neurons gives rise to spindle oscillations in the membrane potential; the initiation and termination of individual spindle sequences depends on corticothalamic activities. Cortical and thalamic mechanisms are also involved in the generation of EEG delta SWA that appears in deep stage 3–4 (N3) NREM; the cortex has classically been considered to be the structure that generates this activity, but delta oscillations can also be generated in thalamocortical neurons. NREM is probably necessary to normalize synapses to a sustainable basal condition that can ensure cellular homeostasis. Sleep homeostasis depends not only on the duration of prior wakefulness but also on its intensity, and sleep need increases when wakefulness is associated with learning. NREM seems to ensure cell homeostasis by reducing the number of synaptic connections to a basic level; based on simple energy demands, cerebral energy economizing during NREM sleep is one of the prevalent hypotheses to explain NREM homeostasis

Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kransler, Kevin M.; Tonucci, David A.; McGarrigle, Barbara P.

2007-10-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 {mu}g/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure tomore » TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis.« less

Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila.

PubMed

Thimgan, Matthew S; Seugnet, Laurent; Turk, John; Shaw, Paul J

2015-05-01

Flies mutant for the canonical clock protein cycle (cyc(01)) exhibit a sleep rebound that is ∼10 times larger than wild-type flies and die after only 10 h of sleep deprivation. Surprisingly, when starved, cyc(01) mutants can remain awake for 28 h without demonstrating negative outcomes. Thus, we hypothesized that identifying transcripts that are differentially regulated between waking induced by sleep deprivation and waking induced by starvation would identify genes that underlie the deleterious effects of sleep deprivation and/or protect flies from the negative consequences of waking. We used partial complementary DNA microarrays to identify transcripts that are differentially expressed between cyc(01) mutants that had been sleep deprived or starved for 7 h. We then used genetics to determine whether disrupting genes involved in lipid metabolism would exhibit alterations in their response to sleep deprivation. Laboratory. Drosophila melanogaster. Sleep deprivation and starvation. We identified 84 genes with transcript levels that were differentially modulated by 7 h of sleep deprivation and starvation in cyc(01) mutants and were confirmed in independent samples using quantitative polymerase chain reaction. Several of these genes were predicted to be lipid metabolism genes, including bubblegum, cueball, and CG4500, which based on our data we have renamed heimdall (hll). Using lipidomics we confirmed that knockdown of hll using RNA interference significantly decreased lipid stores. Importantly, genetically modifying bubblegum, cueball, or hll resulted in sleep rebound alterations following sleep deprivation compared to genetic background controls. We have identified a set of genes that may confer resilience/vulnerability to sleep deprivation and demonstrate that genes involved in lipid metabolism modulate sleep homeostasis. © 2015 Associated Professional Sleep Societies, LLC.

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

PubMed

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, p<0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p<0.05). Moreover, plasma 2AG was elevated 15min post-exercise (+44%, p<0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-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.

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases

USGS Publications Warehouse

Bailey, J. D.; Berardinelli, J.G.; Rocke, T.E.; Bessen, R.A.

2008-01-01

Prion diseases are fatal neurodegenerative diseases that can induce endocrinopathies. The basis of altered endocrine function in prion diseases is not well understood, and the purpose of this study was to investigate the spatiotemporal relationship between energy homeostasis and prion infection in hamsters inoculated with either the 139H strain of scrapie agent, which induces preclinical weight gain, or the HY strain of transmissible mink encephalopathy (TME), which induces clinical weight loss. Temporal changes in body weight, feed, and water intake were measured as well as both non-fasted and fasted concentrations of serum glucose, insulin, glucagon, ??-ketones, and leptin. In 139H scrapie-infected hamsters, polydipsia, hyperphagia, non-fasted hyperinsulinemia with hyperglycemia, and fasted hyperleptinemia were found at preclinical stages and are consistent with an anabolic syndrome that has similarities to type II diabetes mellitus and/or metabolic syndrome X. In HY TME-infected hamsters, hypodipsia, hypersecretion of glucagon (in both non-fasted and fasted states), increased fasted ??-ketones, fasted hypoglycemia, and suppressed non-fasted leptin concentrations were found while feed intake was normal. These findings suggest a severe catabolic syndrome in HY TME infection mediated by chronic increases in glucagon secretion. In both models, alterations of pancreatic endocrine function were not associated with PrPSc deposition in the pancreas. The results indicate that prominent endocrinopathy underlies alterations in body weight, pancreatic endocrine function, and intake of food. The prion-induced alterations of energy homeostasis in 139H scrapie- or HY TME-infected hamsters could occur within areas of the hypothalamus that control food satiety and/or within autonomic centers that provide neural outflow to the pancreas. ?? 2008 Society for Endocrinology.

Alterations of zinc homeostasis in response to Cryptococcus neoformans in a murine macrophage cell line.

PubMed

Dos Santos, Francine Melise; Piffer, Alícia Corbellini; Schneider, Rafael de Oliveira; Ribeiro, Nicole Sartori; Garcia, Ane Wichine Acosta; Schrank, Augusto; Kmetzsch, Lívia; Vainstein, Marilene Henning; Staats, Charley Christian

2017-05-01

To evaluate alterations of zinc homeostasis in macrophages exposed to Cryptococcus neoformans. Materials & methods: Using a fluorescent zinc probe-based flow cytometry and atomic absorption spectrometry, zinc levels were evaluated in J774.A1 cell lines exposed to C. neoformans H99 cells. The transcription profile of macrophage zinc related homeostasis genes - metallothioneins and zinc transporters (ZnTs) of the SLC30 and SLC39 (Zrt-Irt-protein) families - was analyzed by quantitative PCR. Macrophage intracellular labile zinc levels decreased following exposure to C. neoformans. A significant decrease in transcription levels was detected in specific ZnTs from both the Zrt-Irt-protein and ZnT families, especially 24 h after infection. These findings suggest that macrophages may exhibit zinc depletion in response to C. neoformans infection.

Short-term sleep deprivation with exposure to nocturnal light alters mitochondrial bioenergetics in Drosophila.

PubMed

Rodrigues, Nathane Rosa; Macedo, Giulianna Echeverria; Martins, Illana Kemmerich; Gomes, Karen Kich; de Carvalho, Nélson Rodrigues; Posser, Thaís; Franco, Jeferson Luis

2018-05-20

Many studies have shown the effects of sleep deprivation in several aspects of health and disease. However, little is known about how mitochondrial bioenergetics function is affected under this condition. To clarify this, we developed a simple model of short-term sleep deprivation, in which fruit-flies were submitted to a nocturnal light condition and then mitochondrial parameters were assessed by high resolution respirometry (HRR). Exposure of flies to constant light was able to alter sleep patterns, causing locomotor deficits, increasing ROS production and lipid peroxidation, affecting mitochondrial activity, antioxidant defense enzymes and caspase activity. HRR analysis showed that sleep deprivation affected mitochondrial bioenergetics capacity, decreasing respiration at oxidative phosphorylation (OXPHOS) and electron transport system (ETS). In addition, the expression of genes involved in the response to oxidative stress and apoptosis were increased. Thus, our results suggest a connection between sleep deprivation and oxidative stress, pointing to mitochondria as a possible target of this relationship. Copyright © 2018 Elsevier Inc. All rights reserved.

Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays

PubMed Central

Venâncio, Daniel P.; Andersen, Monica L.; Vilamaior, Patricia S. L.; Santos, Fernanda C.; Zager, Adriano; Tufik, Sérgio; Taboga, Sebastião R.; De Mello, Marco T.

2012-01-01

We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR. PMID:22927719

Metabolic Consequences of Sleep-Disordered Breathing

PubMed Central

Jun, Jonathan; Polotsky, Vsevolod Y.

2017-01-01

There is increasing evidence of a causal relationship between sleep-disordered breathing and metabolic dysfunction. Metabolic syndrome (MetS), a cluster of risk factors that promote atherosclerotic cardiovascular disease, comprises central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension, manifestations of altered total body energy regulation. Excess caloric intake is indisputably the key driver of MetS, but other environmental and genetic factors likely play a role; in particular, obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), may induce or exacerbate various aspects of MetS. Clinical studies show that OSA can affect glucose metabolism, cholesterol, inflammatory markers, and nonalcoholic fatty liver disease. Animal models of OSA enable scientists to circumvent confounders such as obesity in clinical studies. In the most widely used model, which involves exposing rodents to IH during their sleep phase, the IH alters circadian glucose homeostasis, impairs muscle carbohydrate uptake, induces hyperlipidemia, and upregulates cholesterol synthesis enzymes. Complicating factors such as obesity or a high-fat diet lead to progressive insulin resistance and liver inflammation, respectively. Mechanisms for these effects are not yet fully understood, but are likely related to energy-conserving adaptations to hypoxia, which is a strong catabolic stressor. Finally, IH may contribute to the morbidity of MetS by inducing inflammation and oxidative stress. Identification of OSA as a potential causative factor in MetS would have immense clinical impact and could improve the management and understanding of both disorders. PMID:19506316

An Adenosine-Mediated Glial-Neuronal Circuit for Homeostatic Sleep.

PubMed

Bjorness, Theresa E; Dale, Nicholas; Mettlach, Gabriel; Sonneborn, Alex; Sahin, Bogachan; Fienberg, Allen A; Yanagisawa, Masashi; Bibb, James A; Greene, Robert W

2016-03-30

Sleep homeostasis reflects a centrally mediated drive for sleep, which increases during waking and resolves during subsequent sleep. Here we demonstrate that mice deficient for glial adenosine kinase (AdK), the primary metabolizing enzyme for adenosine (Ado), exhibit enhanced expression of this homeostatic drive by three independent measures: (1) increased rebound of slow-wave activity; (2) increased consolidation of slow-wave sleep; and (3) increased time constant of slow-wave activity decay during an average slow-wave sleep episode, proposed and validated here as a new index for homeostatic sleep drive. Conversely, mice deficient for the neuronal adenosine A1 receptor exhibit significantly decreased sleep drive as judged by these same indices. Neuronal knock-out of AdK did not influence homeostatic sleep need. Together, these findings implicate a glial-neuronal circuit mediated by intercellular Ado, controlling expression of homeostatic sleep drive. Because AdK is tightly regulated by glial metabolic state, our findings suggest a functional link between cellular metabolism and sleep homeostasis. The work presented here provides evidence for an adenosine-mediated regulation of sleep in response to waking (i.e., homeostatic sleep need), requiring activation of neuronal adenosine A1 receptors and controlled by glial adenosine kinase. Adenosine kinase acts as a highly sensitive and important metabolic sensor of the glial ATP/ADP and AMP ratio directly controlling intracellular adenosine concentration. Glial equilibrative adenosine transporters reflect the intracellular concentration to the extracellular milieu to activate neuronal adenosine receptors. Thus, adenosine mediates a glial-neuronal circuit linking glial metabolic state to neural-expressed sleep homeostasis. This indicates a metabolically related function(s) for this glial-neuronal circuit in the buildup and resolution of our need to sleep and suggests potential therapeutic targets more directly related to

Cognitive Workload and Sleep Restriction Interact to Influence Sleep Homeostatic Responses

PubMed Central

Goel, Namni; Abe, Takashi; Braun, Marcia E.; Dinges, David F.

2014-01-01

responses by increasing subjective fatigue and sleepiness, and producing a global sleep homeostatic response by reducing wake after sleep onset. When combined with sleep restriction, high workload increased local (occipital) sleep homeostasis, suggesting a use-dependent sleep response to visual work. We conclude that sleep restriction and cognitive workload interact to influence sleep homeostasis. Citation: Goel N, Abe T, Braun ME, Dinges DF. Cognitive workload and sleep restriction interact to influence sleep homeostatic responses. SLEEP 2014;37(11):1745-1756. PMID:25364070

Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

PubMed

Mody, Nimesh

2017-11-01

Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

Increased Disease Activity is Associated with Altered Sleep Architecture in an Experimental Model of Systemic Lupus Erythematosus

PubMed Central

Palma, Beatriz Duarte; Tufik, Sergio

2010-01-01

Study Objectives: The aim of this study was to evaluate sleep patterns during the course of the disease in (NZB/NZW)F1 mice, an experimental model of systemic lupus erythematosus (SLE). Design: Female mice were implanted with electrodes for chronic recording of sleep-wake cycles during the entire experimental phase (9, 19, and 29 weeks of age). The disease course was also assessed. At each time-point, blood samples were collected from the orbital plexus to evaluate serum antinuclear antibodies (ANA), which are important serologic parameters of disease evolution. Pain perception was also evaluated. Measurements and Results: During the dark phase, (NZB/NZW)F1 mice aged 19 weeks spent more time in sleep, and, as a consequence, the total waking time was lower when compared with earlier periods. An augmented number of sleep-stage transitions and microarousals were observed at the 29th week of life in both light and dark phases. At this same time-point, the mice showed lower pain thresholds than they had at 9 weeks of life. The disease status was confirmed; the entire group of mice at 29 weeks of life showed positive ANA with high titer levels. Conclusions: The sleep-recording data showed that, during the progress and severe phases of the disease (19 and 29 wks of age, respectively), sleep architecture is altered. According to these results, increased sleep fragmentation, disease activity, and pain sensitivity are features observed in these mice, similar to symptoms of SLE. Citation: Palma BD; Tufik S. Increased disease activity is associated with altered sleep architecture in an experimental model of systemic lupus erythematosus. SLEEP 2010;33(9):1244-1248. PMID:20857872

Sleep-dependent memory consolidation in patients with sleep disorders.

PubMed

Cipolli, Carlo; Mazzetti, Michela; Plazzi, Giuseppe

2013-04-01

Sleep can improve the off-line memory consolidation of new items of declarative and non-declarative information in healthy subjects, whereas acute sleep loss, as well as sleep restriction and fragmentation, impair consolidation. This suggests that, by modifying the amount and/or architecture of sleep, chronic sleep disorders may also lead to a lower gain in off-line consolidation, which in turn may be responsible for the varying levels of impaired performance at memory tasks usually observed in sleep-disordered patients. The experimental studies conducted to date have shown specific impairments of sleep-dependent consolidation overall for verbal and visual declarative information in patients with primary insomnia, for verbal declarative information in patients with obstructive sleep apnoeas, and for visual procedural skills in patients with narcolepsy-cataplexy. These findings corroborate the hypothesis that impaired consolidation is a consequence of the chronically altered organization of sleep. Moreover, they raise several novel questions as to: a) the reversibility of consolidation impairment in the case of effective treatment, b) the possible negative influence of altered prior sleep also on the encoding of new information, and c) the relationships between altered sleep and memory impairment in patients with other (medical, psychiatric or neurological) diseases associated with quantitative and/or qualitative changes of sleep architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Recurrent Circuitry for Balancing Sleep Need and Sleep.

PubMed

Donlea, Jeffrey M; Pimentel, Diogo; Talbot, Clifford B; Kempf, Anissa; Omoto, Jaison J; Hartenstein, Volker; Miesenböck, Gero

2018-01-17

Sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila are integral to sleep homeostasis, but how these cells impose sleep on the organism is unknown. We report that dFB neurons communicate via inhibitory transmitters, including allatostatin-A (AstA), with interneurons connecting the superior arch with the ellipsoid body of the central complex. These "helicon cells" express the galanin receptor homolog AstA-R1, respond to visual input, gate locomotion, and are inhibited by AstA, suggesting that dFB neurons promote rest by suppressing visually guided movement. Sleep changes caused by enhanced or diminished allatostatinergic transmission from dFB neurons and by inhibition or optogenetic stimulation of helicon cells support this notion. Helicon cells provide excitation to R2 neurons of the ellipsoid body, whose activity-dependent plasticity signals rising sleep pressure to the dFB. By virtue of this autoregulatory loop, dFB-mediated inhibition interrupts processes that incur a sleep debt, allowing restorative sleep to rebalance the books. VIDEO ABSTRACT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sleep, Circadian Rhythms, and Performance During Space Shuttle Missions

NASA Technical Reports Server (NTRS)

Neri, David F.; Czeisler, Charles A.; Dijk, Derk-Jan; Wyatt, James K.; Ronda, Joseph M.; Hughes, Rod J.

2003-01-01

Sleep and circadian rhythms may be disturbed during spaceflight, and these disturbances can affect crewmembers' performance during waking hours. The mechanisms underlying sleep and circadian rhythm disturbances in space are not well understood, and effective countermeasures are not yet available. We investigated sleep, circadian rhythms, cognitive performance, and light-dark cycles in five astronauts prior to, during, and after the 16-day STS-90 mission and the IO-day STS-95 mission. The efficacy of low-dose, alternative-night, oral melatonin administration as a countermeasure for sleep disturbances was evaluated. During these missions, scheduled rest activity cycles were 20-35 minutes shorter than 24 hours. Light levels on the middeck and in the Spacelab were very low; whereas on the flight deck (which has several windows), they were highly variable. Circadian rhythm abnormalities were observed. During the second half of the missions, the rhythm of urinary cortisol appeared to be delayed relative to the sleep-wake schedule. Performance during wakefulness was impaired. Astronauts slept only about 6.5 hours per day, and subjective sleep quality was lower in space. No beneficial effects of melatonin (0.3 mg administered prior to sleep episodes on alternate nights) were observed. A surprising finding was a marked increase in rapid eye movement (REM) sleep upon return to Earth. We conclude that these Space Shuttle missions were associated with circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and alterations in REM sleep homeostasis. Shorter than 24-hour rest-activity schedules and exposure to light-dark cycles inadequate for optimal circadian synchronization may have contributed to these disturbances.

Corticotropin Releasing Factor (CRF) Modulates Fear-Induced Alterations in Sleep in Mice

PubMed Central

Yang, Linghui; Tang, Xiangdong; Wellman, Laurie L.; Liu, Xianling; Sanford, Larry D.

2009-01-01

Contextual fear significantly reduces rapid eye movement sleep (REM) during post-exposure sleep in mice and rats. Corticotropin releasing factor (CRF) plays a major role in CNS responses to stressors. We examined the influence of CRF and astressin (AST), a non-specific CRF antagonist, on sleep after contextual fear in BALB/c mice. Male mice were implanted with transmitters for recording sleep via telemetry and with a guide cannula aimed into the lateral ventricle. Recordings for vehicle and handling control were obtained after ICV microinjection of saline (SAL) followed by exposure to a novel chamber. Afterwards, the mice were subjected to shock training (20 trials, 0.5 mA, 0.5 s duration) for 2 sessions. After training, separate groups of mice received ICV microinjections of SAL (0.2 microl, n=9), CRF (0.4 microg, n=8), or AST (1.0 microg, n=8) prior to exposure to the shock context alone. Sleep was then recorded for 20 hours (8-hour light and 12-hour dark period). Compared to handling control, contextual fear significantly decreased REM during the 8-h light period in mice receiving SAL and in mice receiving CRF, but not in the mice receiving AST. Mice receiving CRF exhibited reductions in REM during the 12-h dark period after contextual fear, whereas mice receiving SAL or AST did not. CRF also reduced non-REM (NREM) delta (slow wave) amplitude in the EEG. Only mice receiving SAL prior to contextual fear exhibited significant reductions in NREM and total sleep. These findings demonstrate a role for the central CRF system in regulating alterations in sleep induced by contextual fear. PMID:19376095

Sleep alterations in mammals: did aquatic conditions inhibit rapid eye movement sleep?

PubMed

Madan, Vibha; Jha, Sushil K

2012-12-01

Sleep has been studied widely in mammals and to some extent in other vertebrates. Higher vertebrates such as birds and mammals have evolved an inimitable rapid eye movement (REM) sleep state. During REM sleep, postural muscles become atonic and the temperature regulating machinery remains suspended. Although REM sleep is present in almost all the terrestrial mammals, the aquatic mammals have either radically reduced or completely eliminated REM sleep. Further, we found a significant negative correlation between REM sleep and the adaptation of the organism to live on land or in water. The amount of REM sleep is highest in terrestrial mammals, significantly reduced in semi-aquatic mammals and completely absent or negligible in aquatic mammals. The aquatic mammals are obligate swimmers and have to surface at regular intervals for air. Also, these animals live in thermally challenging environments, where the conductive heat loss is approximately ~90 times greater than air. Therefore, they have to be moving most of the time. As an adaptation, they have evolved unihemispheric sleep, during which they can rove as well as rest. A condition that immobilizes muscle activity and suspends the thermoregulatory machinery, as happens during REM sleep, is not suitable for these animals. It is possible that, in accord with Darwin's theory, aquatic mammals might have abolished REM sleep with time. In this review, we discuss the possibility of the intrinsic role of aquatic conditions in the elimination of REM sleep in the aquatic mammals.

[How does sleeping restore our brain?].

PubMed

Wigren, Henna-Kaisa; Stenberg, Tarja

2015-01-01

The central function of sleep is to keep our brain functional, but what is the restoration that sleep provides? Sleep after learning improves learning outcomes. According to the theory of synaptic homeostasis the total strength of synapses, having increased during the day, is restored during sleep, making room for the next day's experiences. According to the theory of active synaptic consolidation, repetition during sleep strengthens the synapses, and these strengthened synapses form a permanent engram. According to a recent study, removal of waste products from the brain may also be one of the functions of sleep.

Chronic Sleep Restriction during Pregnancy - Repercussion on Cardiovascular and Renal Functioning of Male Offspring

PubMed Central

Lima, Ingrid L. B.; Rodrigues, Aline F. A. C.; Bergamaschi, Cássia T.; Campos, Ruy R.; Hirata, Aparecida E.; Tufik, Sergio; Xylaras, Beatriz D. P.; Visniauskas, Bruna; Chagas, Jair R.; Gomes, Guiomar N.

2014-01-01

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi – tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127±2.6 (19); OCSR: 144±2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: −2.6±0.15 (9); OCRS: −1.6±0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4±15 (18); OSR: 60.2±3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4±0.2 (10); OCSR: 7.4±0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring. PMID:25405471

Chronic sleep restriction during pregnancy--repercussion on cardiovascular and renal functioning of male offspring.

PubMed

Lima, Ingrid L B; Rodrigues, Aline F A C; Bergamaschi, Cássia T; Campos, Ruy R; Hirata, Aparecida E; Tufik, Sergio; Xylaras, Beatriz D P; Visniauskas, Bruna; Chagas, Jair R; Gomes, Guiomar N

2014-01-01

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi - tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127 ± 2.6 (19); OCSR: 144 ± 2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: -2.6 ± 0.15 (9); OCRS: -1.6 ± 0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4 ± 15 (18); OSR: 60.2 ± 3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4 ± 0.2 (10); OCSR: 7.4 ± 0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring.

Aging Does Not Alter Tendon Mechanical Properties During Homeostasis, but does Impair Flexor Tendon Healing

PubMed Central

Ackerman, Jessica E.; Bah, Ibrahima; Jonason, Jennifer H.; Buckley, Mark R.; Loiselle, Alayna E.

2017-01-01

Aging is an important factor in disrupted homeostasis of many tissues. While an increased incidence of tendinopathy and tendon rupture are observed with aging, it is unclear whether this is due to progressive changes in tendon cell function and mechanics over time, or an impaired repair reaction from aged tendons in response to insult or injury. In the present study we examined changes in the mechanical properties of Flexor Digitorum Longus (FDL), Flexor Carpi Ulnaris (FCU), and tail fascicles in both male and female C57Bl/6 mice between 3-27 months of age to better understand the effects of sex and age on tendon homeostasis. No change in max load at failure was observed in any group over the course of aging, although there were significant decreases in toe and linear stiffness in female mice from 3-months to 15, and to 22-27-months. No changes in cell proliferation were observed with aging, although an observable decrease in cellularity occurred in 31-month old tendons. Given that aging did not dramatically alter tendon mechanical homeostasis we hypothesized that a disruption in tendon homeostasis, via acute injury would result in an impaired healing response. Significant decreases in max load, stiffness, and yield load were observed in repairs of 22-month old mice, relative to 4-month old mice. No changes in cell proliferation were observed between young and aged, however a dramatic loss of bridging collagen extracellular matrix was observed in aged repairs suggest that matrix production, but not cell proliferation leads to impaired tendon healing with aging. PMID:28419543

Caffeine Consuming Children and Adolescents Show Altered Sleep Behavior and Deep Sleep

PubMed Central

Aepli, Andrina; Kurth, Salome; Tesler, Noemi; Jenni, Oskar G.; Huber, Reto

2015-01-01

Caffeine is the most commonly ingested psychoactive drug worldwide with increasing consumption rates among young individuals. While caffeine leads to decreased sleep quality in adults, studies investigating how caffeine consumption affects children’s and adolescents’ sleep remain scarce. We explored the effects of regular caffeine consumption on sleep behavior and the sleep electroencephalogram (EEG) in children and adolescents (10–16 years). While later habitual bedtimes (Caffeine 23:14 ± 11.4, Controls 22:17 ± 15.4) and less time in bed were found in caffeine consumers compared to the control group (Caffeine 08:10 ± 13.3, Controls 09:03 ± 16.1), morning tiredness was unaffected. Furthermore, caffeine consumers exhibited reduced sleep EEG slow-wave activity (SWA, 1–4.5 Hz) at the beginning of the night compared to controls (20% ± 9% average reduction across all electrodes and subjects). Comparable reductions were found for alpha activity (8.25–9.75 Hz). These effects, however, disappeared in the morning hours. Our findings suggest that caffeine consumption in adolescents may lead to later bedtimes and reduced SWA, a well-established marker of sleep depth. Because deep sleep is involved in recovery processes during sleep, further research is needed to understand whether a caffeine-induced loss of sleep depth interacts with neuronal network refinement processes that occur during the sensitive period of adolescent development. PMID:26501326

Sleep apnoea.

PubMed

Jun, Jonathan C; Chopra, Swati; Schwartz, Alan R

2016-03-01

Sleep apnoea is a disorder characterised by repetitive pauses in breathing during sleep caused by airway occlusion (obstructive sleep apnoea) or altered control of breathing (central sleep apnoea). In this Clinical Year in Review, we summarise high-impact research from the past year pertaining to management, diagnosis and cardio-metabolic consequences of sleep apnoea. Copyright ©ERS 2016.

Percentage of REM Sleep is Associated with Overnight Change in Leptin

PubMed Central

Olson, Christy A.; Hamilton, Nancy A.; Somers, Virend K.

2016-01-01

Sleep contributes importantly to energy homeostasis, and may impact hormones regulating appetite, such as leptin, an adipocyte derived hormone. There is increasing evidence that sleep duration, and reduced REM sleep, are linked to obesity. Leptin has central neural effects beyond modulation of appetite alone. As sleep is not a unifrom process, interactions between leptin and sleep stages including REM sleep may play a role in the relationship between sleep and obesity. This study examined the relationship between serum leptin and REM sleep in a sample of healthy adults. Participants were 58 healthy adults who underwent polysomnography. Leptin was measured before and after sleep. We hypothesized that lower percentage of REM sleep would be related to lower leptin levels during sleep. The relationship between percentage of REM sleep and leptin was analyzed using hierarchical linear regression. Increased percentage of REM sleep was related to a greater reduction in leptin during sleep even when controlling for age, gender, percent body fat and total sleep time. A greater percentage of REM sleep was accompanied by more marked reductions in leptin. Studies examining the effects of selective REM sleep deprivation on leptin levels, and hence on energy homeostasis in humans, are needed. PMID:26919408

Alteration of ROS Homeostasis and Decreased Lifespan in S. cerevisiae Elicited by Deletion of the Mitochondrial Translocator FLX1

PubMed Central

Giancaspero, Teresa Anna; Dipalo, Emilia; Miccolis, Angelica; Boles, Eckhard; Caselle, Michele; Barile, Maria

2014-01-01

This paper deals with the control exerted by the mitochondrial translocator FLX1, which catalyzes the movement of the redox cofactor FAD across the mitochondrial membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient and small-colony phenotype accompanied by a significant ATP shortage and ROS unbalance in glycerol-grown cells. Moreover, the flx1Δ strain showed H2O2 hypersensitivity and decreased lifespan. The impaired biochemical phenotype found in the flx1Δ strain might be justified by an altered expression of the flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics and cell regulation. A search for possible cis-acting consensus motifs in the regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that might respond to induced metabolic changes by altering the expression of Flx1p. Among these motifs, two are present in the regulatory region of genes encoding proteins involved in flavin homeostasis. This is the first evidence that the mitochondrial flavin cofactor status is involved in controlling the lifespan of yeasts, maybe by changing the cellular succinate level. This is not the only case in which the homeostasis of redox cofactors underlies complex phenotypical behaviours, as lifespan in yeasts. PMID:24895546

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

PubMed

Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

2016-09-01

Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Artificial Outdoor Nighttime Lights Associate with Altered Sleep Behavior in the American General Population

PubMed Central

Ohayon, Maurice M.; Milesi, Cristina

2016-01-01

Study Objectives: Our study aims to explore the associations between outdoor nighttime lights (ONL) and sleep patterns in the human population. Methods: Cross-sectional telephone study of a representative sample of the general US population age 18 y or older. 19,136 noninstitutionalized individuals (participation rate: 83.2%) were interviewed by telephone. The Sleep-EVAL expert system administered questions on life and sleeping habits; health; sleep, mental and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; International Classification of Sleep Disorders, Second Edition; International Classification of Diseases, 10th Edition). Individuals were geolocated by longitude and latitude. Outdoor nighttime light measurements were obtained from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS), with nighttime passes taking place between 19:30 and 22:30 local time. Light data were correlated precisely to the geolocation of each participant of the general population sample. Results: Living in areas with greater ONL was associated with delayed bedtime (P < 0.0001) and wake up time (P < 0.0001), shorter sleep duration (P < 0.01), and increased daytime sleepiness (P < 0.0001). Living in areas with greater ONL also increased the dissatisfaction with sleep quantity and quality (P < 0.0001) and the likelihood of having a diagnostic profile congruent with a circadian rhythm disorder (P < 0.0001). Conclusions: Although they improve the overall safety of people and traffic, nighttime lights in our streets and cities are clearly linked with modifications in human sleep behaviors and also impinge on the daytime functioning of individuals living in areas with greater ONL. Citation: Ohayon MM, Milesi C. Artificial outdoor nighttime lights associate with altered sleep behavior in the american general population. SLEEP 2016;39(6):1311–1320. PMID:27091523

Neuronal redox imbalance results in altered energy homeostasis and early postnatal lethality.

PubMed

Maity-Kumar, Gandhari; Thal, Dietmar R; Baumann, Bernd; Scharffetter-Kochanek, Karin; Wirth, Thomas

2015-07-01

Redox imbalance is believed to contribute to the development and progression of several neurodegenerative disorders. Our aim was to develop an animal model that exhibits neuron-specific oxidative stress in the CNS to study the consequences and eventually find clues regarding the pathomechanisms of oxidative insults in neuronal homeostasis. We therefore generated a novel neuron-specific superoxide dismutase 2 (SOD2)-deficient mouse by deleting exon 3 of the SOD2 gene using CamKIIα promoter-driven Cre expression. These neuron-specific SOD2 knockout (SOD2(nko)) mice, although born at normal frequencies, died at the age of 4 weeks with critical growth retardation, severe energy failure, and several neurologic phenotypes. In addition, SOD2(nko) mice exhibited severe neuronal alterations such as reactive astrogliosis, neuronal cell cycle inhibition, and induction of apoptosis. JNK activation and stabilization of p53, as a result of reactive oxygen species accumulation, are most likely the inducers of neuronal apoptosis in SOD2(nko) mice. It is remarkable that hypothalamic regulation of glucose metabolism was affected, which in turn induced necrotic brain lesions in SOD2(nko) mice. Taken together, our findings suggest that exclusive deficiency of SOD2 in neurons results in an impaired central regulation of energy homeostasis that leads to persistent hypoglycemia, hypoglycemia-related neuropathology, and an early lethality of the mutant mice. © FASEB.

Identification of Genes Associated with Resilience/Vulnerability to Sleep Deprivation and Starvation in Drosophila

PubMed Central

Thimgan, Matthew S.; Seugnet, Laurent; Turk, John; Shaw, Paul J.

2015-01-01

Background and Study Objectives: Flies mutant for the canonical clock protein cycle (cyc01) exhibit a sleep rebound that is ∼10 times larger than wild-type flies and die after only 10 h of sleep deprivation. Surprisingly, when starved, cyc01 mutants can remain awake for 28 h without demonstrating negative outcomes. Thus, we hypothesized that identifying transcripts that are differentially regulated between waking induced by sleep deprivation and waking induced by starvation would identify genes that underlie the deleterious effects of sleep deprivation and/or protect flies from the negative consequences of waking. Design: We used partial complementary DNA microarrays to identify transcripts that are differentially expressed between cyc01 mutants that had been sleep deprived or starved for 7 h. We then used genetics to determine whether disrupting genes involved in lipid metabolism would exhibit alterations in their response to sleep deprivation. Setting: Laboratory. Patients or Participants: Drosophila melanogaster. Interventions: Sleep deprivation and starvation. Measurements and Results: We identified 84 genes with transcript levels that were differentially modulated by 7 h of sleep deprivation and starvation in cyc01 mutants and were confirmed in independent samples using quantitative polymerase chain reaction. Several of these genes were predicted to be lipid metabolism genes, including bubblegum, cueball, and CG4500, which based on our data we have renamed heimdall (hll). Using lipidomics we confirmed that knockdown of hll using RNA interference significantly decreased lipid stores. Importantly, genetically modifying bubblegum, cueball, or hll resulted in sleep rebound alterations following sleep deprivation compared to genetic background controls. Conclusions: We have identified a set of genes that may confer resilience/vulnerability to sleep deprivation and demonstrate that genes involved in lipid metabolism modulate sleep homeostasis. Citation: Thimgan MS

The effects of partial sleep restriction and altered sleep timing on appetite and food reward.

PubMed

McNeil, Jessica; Forest, Geneviève; Hintze, Luzia Jaeger; Brunet, Jean-François; Finlayson, Graham; Blundell, John E; Doucet, Éric

2017-02-01

We examined the effects of partial sleep restriction (PSR) with an advanced wake-time or delayed bedtime on measures of appetite, food reward and subsequent energy intake (EI). Twelve men and 6 women (age: 23 ± 4 years, body fat: 18.8 ± 10.1%) participated in 3 randomized crossover sessions: control (habitual bed- and wake-time), 50% PSR with an advanced wake-time and 50% PSR with a delayed bedtime. Outcome variables included sleep architecture (polysomnography), ad libitum EI (validated food menu), appetite sensations (visual analogue scales), satiety quotient (SQ; mm/100 kcal) and food reward (Leeds Food Preference Questionnaire and the relative-reinforcing value (RRV) of preferred food task). Increased fasting and post-standard breakfast appetite ratings were noted following PSR with an advanced wake-time compared to the control and PSR with a delayed bedtime sessions (Fasting hunger ratings: 77 ± 16 vs. 65 ± 18 and 64 ± 16; P = 0.01; Post-meal hunger AUC: 5982 ± 1781 vs. 4508 ± 2136 and 5198 ± 2201; P = 0.03). Increased explicit wanting and liking for high- relative to low-fat foods were also noted during the advanced wake-time vs. control session (Explicit wanting: -3.5 ± 12.5 vs. -9.3 ± 8.9, P = 0.01; Explicit liking: -1.6 ± 8.5 vs. -7.8 ± 9.6, P = 0.002). No differences in the RRV of preferred food, SQ and ad libitum lunch intake were noted between sessions. These findings suggest that appetite sensations and food reward are increased following PSR with an advanced wake-time, rather than delayed bedtime, vs. However, this did not translate into increased EI during a test meal. Given the increasing prevalence of shift workers and incidences of sleep disorders, additional studies are needed to evaluate the prolonged effects of voluntary sleep restriction with altered sleep timing on appetite and EI measurements. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

Chi, Michael W.; Griffith, Leslie C.; Vecsey, Christopher G.

2014-01-01

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. PMID:25116571

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

PubMed

Chi, Michael W; Griffith, Leslie C; Vecsey, Christopher G

2014-08-11

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.

Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

PubMed

Dworak, Markus; Kim, Tae; Mccarley, Robert W; Basheer, Radhika

2017-06-01

Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders. © 2017 European Sleep Research Society.

Methylmercury alters glutathione homeostasis by inhibiting glutaredoxin 1 and enhancing glutathione biosynthesis in cultured human astrocytoma cells.

PubMed

Robitaille, Stephan; Mailloux, Ryan J; Chan, Hing Man

2016-08-10

Methylmercury (MeHg) is a neurotoxin that binds strongly to thiol residues on protein and low molecular weight molecules like reduced glutathione (GSH). The mechanism of its effects on GSH homeostasis particularly at environmentally relevant low doses is not fully known. We hypothesized that exposure to MeHg would lead to a depletion of reduced glutathione (GSH) and an accumulation of glutathione disulfide (GSSG) leading to alterations in S-glutathionylation of proteins. Our results showed exposure to low concentrations of MeHg (1μM) did not significantly alter GSH levels but increased GSSG levels by ∼12-fold. This effect was associated with a significant increase in total cellular glutathione content and a decrease in GSH/GSSG. Immunoblot analyses revealed that proteins involved in glutathione synthesis were upregulated accounting for the increase in cellular glutathione. This was associated an increase in cellular Nrf2 protein levels which is required to induce the expression of antioxidant genes in response to cellular stress. Intriguingly, we noted that a key enzyme involved in reversing protein S-glutathionylation and maintaining glutathione homeostasis, glutaredoxin-1 (Grx1), was inhibited by ∼50%. MeHg treatment also increased the S-glutathionylation of a high molecular weight protein. This observation is consistent with the inhibition of Grx1 and elevated H2O2 production however; contrary to our original hypothesis we found few S-glutathionylated proteins in the astrocytoma cells. Collectively, MeHg affects multiple arms of glutathione homeostasis ranging from pool management to protein S-glutathionylation and Grx1 activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Why does serotonergic activity drastically decrease during REM sleep?

PubMed

Sato, Kohji

2013-10-01

Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation. Copyright © 2013. Published by Elsevier Ltd.

Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice

PubMed Central

Fisher, Simon P.; Cui, Nanyi; Peirson, Stuart N.; Foster, Russell G.

2018-01-01

Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture. SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we

Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice.

PubMed

Sabir, Meriem; Gaudreault, Pierre-Olivier; Freyburger, Marlène; Massart, Renaud; Blanchet-Cohen, Alexis; Jaber, Manar; Gosselin, Nadia; Mongrain, Valérie

2015-07-01

Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly associated with vigilance and sleep complaints. Because sleep is required for learning, plasticity and recovery, we here evaluated the bidirectional relationship between mTBI and sleep with two specific objectives: (1) Test that mTBI rapidly impairs sleep-wake architecture and the dynamics of the electrophysiological marker of sleep homeostasis (i.e., non-rapid eye movement sleep delta (1-4Hz) activity); (2) evaluate the impact of sleep loss following mTBI on the expression of plasticity markers that have been linked to sleep homeostasis and on genome-wide gene expression. A closed-head injury model was used to perform a 48h electrocorticographic (ECoG) recording in mice submitted to mTBI or Sham surgery. mTBI was found to immediately decrease the capacity to sustain long bouts of wakefulness as well as the amplitude of the time course of ECoG delta activity during wakefulness. Significant changes in ECoG spectral activity during wakefulness, non-rapid eye movement and rapid eye movement sleep were observed mainly on the second recorded day. A second experiment was performed to measure gene expression in the cerebral cortex and hippocampus after a mTBI followed either by two consecutive days of 6h sleep deprivation (SD) or of undisturbed behavior (quantitative PCR and next-generation sequencing). mTBI modified the expression of genes involved in immunity, inflammation and glial function (e.g., chemokines, glial markers) and SD changed that of genes linked to circadian rhythms, synaptic activity/neuronal plasticity, neuroprotection and cell death and survival. SD appeared to affect gene expression in the cerebral cortex more importantly after mTBI than Sham surgery including that of the astrocytic marker Gfap, which was proposed as a marker of clinical outcome after TBI. Interestingly, SD impacted the hippocampal expression of the plasticity elements Arc and EfnA3 only after mTBI. Overall, our

Functional data analysis of sleeping energy expenditure.

PubMed

Lee, Jong Soo; Zakeri, Issa F; Butte, Nancy F

2017-01-01

Adequate sleep is crucial during childhood for metabolic health, and physical and cognitive development. Inadequate sleep can disrupt metabolic homeostasis and alter sleeping energy expenditure (SEE). Functional data analysis methods were applied to SEE data to elucidate the population structure of SEE and to discriminate SEE between obese and non-obese children. Minute-by-minute SEE in 109 children, ages 5-18, was measured in room respiration calorimeters. A smoothing spline method was applied to the calorimetric data to extract the true smoothing function for each subject. Functional principal component analysis was used to capture the important modes of variation of the functional data and to identify differences in SEE patterns. Combinations of functional principal component analysis and classifier algorithm were used to classify SEE. Smoothing effectively removed instrumentation noise inherent in the room calorimeter data, providing more accurate data for analysis of the dynamics of SEE. SEE exhibited declining but subtly undulating patterns throughout the night. Mean SEE was markedly higher in obese than non-obese children, as expected due to their greater body mass. SEE was higher among the obese than non-obese children (p<0.01); however, the weight-adjusted mean SEE was not statistically different (p>0.1, after post hoc testing). Functional principal component scores for the first two components explained 77.8% of the variance in SEE and also differed between groups (p = 0.037). Logistic regression, support vector machine or random forest classification methods were able to distinguish weight-adjusted SEE between obese and non-obese participants with good classification rates (62-64%). Our results implicate other factors, yet to be uncovered, that affect the weight-adjusted SEE of obese and non-obese children. Functional data analysis revealed differences in the structure of SEE between obese and non-obese children that may contribute to disruption of

Copper and ectopic expression of the Arabidopsis transport protein COPT1 alter iron homeostasis in rice (Oryza sativa L.).

PubMed

Andrés-Bordería, Amparo; Andrés, Fernando; Garcia-Molina, Antoni; Perea-García, Ana; Domingo, Concha; Puig, Sergi; Peñarrubia, Lola

2017-09-01

Copper deficiency and excess differentially affect iron homeostasis in rice and overexpression of the Arabidopsis high-affinity copper transporter COPT1 slightly increases endogenous iron concentration in rice grains. Higher plants have developed sophisticated mechanisms to efficiently acquire and use micronutrients such as copper and iron. However, the molecular mechanisms underlying the interaction between both metals remain poorly understood. In the present work, we study the effects produced on iron homeostasis by a wide range of copper concentrations in the growth media and by altered copper transport in Oryza sativa plants. Gene expression profiles in rice seedlings grown under copper excess show an altered expression of genes involved in iron homeostasis compared to standard control conditions. Thus, ferritin OsFER2 and ferredoxin OsFd1 mRNAs are down-regulated whereas the transcriptional iron regulator OsIRO2 and the nicotianamine synthase OsNAS2 mRNAs rise under copper excess. As expected, the expression of OsCOPT1, which encodes a high-affinity copper transport protein, as well as other copper-deficiency markers are down-regulated by copper. Furthermore, we show that Arabidopsis COPT1 overexpression (C1 OE ) in rice causes root shortening in high copper conditions and under iron deficiency. C1 OE rice plants modify the expression of the putative iron-sensing factors OsHRZ1 and OsHRZ2 and enhance the expression of OsIRO2 under copper excess, which suggests a role of copper transport in iron signaling. Importantly, the C1 OE rice plants grown on soil contain higher endogenous iron concentration than wild-type plants in both brown and white grains. Collectively, these results highlight the effects of rice copper status on iron homeostasis, which should be considered to obtain crops with optimized nutrient concentrations in edible parts.

Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.

PubMed

McKillop, Laura E; Fisher, Simon P; Cui, Nanyi; Peirson, Stuart N; Foster, Russell G; Wafford, Keith A; Vyazovskiy, Vladyslav V

2018-04-18

Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture. SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we

Sleep and Human Aging

PubMed Central

Mander, Bryce A.; Winer, Joseph R.; Walker, Matthew P.

2017-01-01

Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? PMID:28384471

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

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

PubMed

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.

Sleep Deprivation and the Epigenome.

PubMed

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.

Role of sleep quality in the metabolic syndrome

PubMed Central

Koren, Dorit; Dumin, Magdalena; Gozal, David

2016-01-01

Emerging evidence has assigned an important role to sleep as a modulator of metabolic homeostasis. The impact of variations in sleep duration, sleep-disordered breathing, and chronotype to cardiometabolic function encompasses a wide array of perturbations spanning from obesity, insulin resistance, type 2 diabetes, the metabolic syndrome, and cardiovascular disease risk and mortality in both adults and children. Here, we critically and extensively review the published literature on such important issues and provide a comprehensive overview of the most salient pathophysiologic pathways underlying the links between sleep, sleep disorders, and cardiometabolic functioning. PMID:27601926

Sleep and Human Aging.

PubMed

Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

2017-04-05

Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? Copyright © 2017. Published by Elsevier Inc.

Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

PubMed

Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

2015-09-01

Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration

PubMed Central

Walrand, Stephane; Short, Kevin R.; Heemstra, Lydia A.; Novak, Colleen M.; Levine, James A.; Coenen-Schimke, Jill M.; Nair, K. Sreekumaran

2014-01-01

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.—Walrand, S., Short, K. R., Heemstra, L. A., Novak, C. M., Levine, J. A., Coenen-Schimke, J. M., Nair, K. S. Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration. PMID:24344330

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

PubMed Central

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

2017-01-01

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. PMID:28193862

Tuberal hypothalamic neurons secreting the satiety molecule Nesfatin-1 are critically involved in paradoxical (REM) sleep homeostasis.

PubMed

Jego, Sonia; Salvert, Denise; Renouard, Leslie; Mori, Masatomo; Goutagny, Romain; Luppi, Pierre-Hervé; Fort, Patrice

2012-01-01

The recently discovered Nesfatin-1 plays a role in appetite regulation as a satiety factor through hypothalamic leptin-independent mechanisms. Nesfatin-1 is co-expressed with Melanin-Concentrating Hormone (MCH) in neurons from the tuberal hypothalamic area (THA) which are recruited during sleep states, especially paradoxical sleep (PS). To help decipher the contribution of this contingent of THA neurons to sleep regulatory mechanisms, we thus investigated in rats whether the co-factor Nesfatin-1 is also endowed with sleep-modulating properties. Here, we found that the disruption of the brain Nesfatin-1 signaling achieved by icv administration of Nesfatin-1 antiserum or antisense against the nucleobindin2 (NUCB2) prohormone suppressed PS with little, if any alteration of slow wave sleep (SWS). Further, the infusion of Nesfatin-1 antiserum after a selective PS deprivation, designed for elevating PS needs, severely prevented the ensuing expected PS recovery. Strengthening these pharmacological data, we finally demonstrated by using c-Fos as an index of neuronal activation that the recruitment of Nesfatin-1-immunoreactive neurons within THA is positively correlated to PS but not to SWS amounts experienced by rats prior to sacrifice. In conclusion, this work supports a functional contribution of the Nesfatin-1 signaling, operated by THA neurons, to PS regulatory mechanisms. We propose that these neurons, likely releasing MCH as a synergistic factor, constitute an appropriate lever by which the hypothalamus may integrate endogenous signals to adapt the ultradian rhythm and maintenance of PS in a manner dictated by homeostatic needs. This could be done through the inhibition of downstream targets comprised primarily of the local hypothalamic wake-active orexin- and histamine-containing neurons.

Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing.

PubMed

Basner, Mathias; Dinges, David F; Mollicone, Daniel; Ecker, Adrian; Jones, Christopher W; Hyder, Eric C; Di Antonio, Adrian; Savelev, Igor; Kan, Kevin; Goel, Namni; Morukov, Boris V; Sutton, Jeffrey P

2013-02-12

The success of interplanetary human spaceflight will depend on many factors, including the behavioral activity levels, sleep, and circadian timing of crews exposed to prolonged microgravity and confinement. To address the effects of the latter, we used a high-fidelity ground simulation of a Mars mission to objectively track sleep-wake dynamics in a multinational crew of six during 520 d of confined isolation. Measurements included continuous recordings of wrist actigraphy and light exposure (4.396 million min) and weekly computer-based neurobehavioral assessments (n = 888) to identify changes in the crew's activity levels, sleep quantity and quality, sleep-wake periodicity, vigilance performance, and workload throughout the record-long 17 mo of mission confinement. Actigraphy revealed that crew sedentariness increased across the mission as evident in decreased waking movement (i.e., hypokinesis) and increased sleep and rest times. Light exposure decreased during the mission. The majority of crewmembers also experienced one or more disturbances of sleep quality, vigilance deficits, or altered sleep-wake periodicity and timing, suggesting inadequate circadian entrainment. The results point to the need to identify markers of differential vulnerability to hypokinesis and sleep-wake changes during the prolonged isolation of exploration spaceflight and the need to ensure maintenance of circadian entrainment, sleep quantity and quality, and optimal activity levels during exploration missions. Therefore, successful adaptation to such missions will require crew to transit in spacecraft and live in surface habitats that instantiate aspects of Earth's geophysical signals (appropriately timed light exposure, food intake, exercise) required for temporal organization and maintenance of human behavior.

Partial sleep deprivation does not alter processes involved in semantic word priming: event-related potential evidence.

PubMed

Tavakoli, Paniz; Muller-Gass, Alexandra; Campbell, Kenneth

2015-03-01

Sleep deprivation has generally been observed to have a detrimental effect on tasks that require sustained attention for successful performance. It might however be possible to counter these effects by altering cognitive strategies. A recent semantic word priming study indicated that subjects used an effortful predictive-expectancy search of semantic memory following normal sleep, but changed to an automatic, effortless strategy following total sleep deprivation. Partial sleep deprivation occurs much more frequently than total sleep deprivation. The present study therefore employed a similar priming task following either 4h of sleep or following normal sleep. The purpose of the study was to determine whether partial sleep deprivation would also lead to a shift in cognitive strategy to compensate for an inability to sustain attention and effortful processing necessary for using the predicative expectancy strategy. Sixteen subjects were presented with word pairs, a prime and a target that were either strongly semantically associated (cat...dog), weakly associated (cow...barn) or not associated (apple...road). The subject's task was to determine if the target word was semantically associated to the prime. A strong priming effect was observed in both conditions. RTs were slower, accuracy lower, and N400 larger to unassociated targets, independent of the amount of sleep. The overall N400 did not differ as a function of sleep. The scalp distribution of the N400 was also similar following both normal sleep and sleep loss. There was thus little evidence of a difference in the processing of the target stimulus as a function of the amount sleep. Similarly, ERPs in the period between the onset of the prime and the subsequent target also did not differ between the normal sleep and sleep loss conditions. In contrast to total sleep deprivation, subjects therefore appeared to use a common predictive expectancy strategy in both conditions. This strategy does however require an

Developmental care does not alter sleep and development of premature infants.

PubMed

Ariagno, R L; Thoman, E B; Boeddiker, M A; Kugener, B; Constantinou, J C; Mirmiran, M; Baldwin, R B

1997-12-01

The Neonatal Individualized Developmental Care Program (NIDCAP) for very low birth weight (VLBW) preterm infants has been suggested by Als et al to improve several medical outcome variables such as time on ventilator, time to nipple feed, the duration of hospital stay, better behavioral performance on Assessment of Preterm Infants' Behavior (APIB), and improved neurodevelopmental outcomes. We have tested the hypothesis of whether the infants who had received NIDCAP would show advanced sleep-wake pattern, behavioral, and neurodevelopmental outcome. Thirty-five VLBW infants were randomly assigned to receive NIDCAP or routine infant care. The goals for NIDCAP intervention were to enhance comfort and stability and to reduce stress and agitation for the preterm infants by: a) altering the environment by decreasing excess light and noise in the neonatal intensive care unit (NICU) and by using covers over the incubators and cribs; b) use of positioning aids such as boundary supports, nests, and buntings to promote a balance of flexion and extension postures; c) modification of direct hands-on caregiving to maximize preparation of infants for, tolerance of, and facilitation of recovery from interventions; d) promotion of self-regulatory behaviors such as holding on, grasping, and sucking; e) attention to the readiness for and the ability to take oral feedings; and f) involving parents in the care of their infants as much as possible. The infants' sleep was recorded at 36 weeks postconceptional age (PCA) and at 3 months corrected age (CA) using the Motility Monitoring System (MMS), an automated, nonintrusive procedure for determining sleep state from movement and respiration patterns. Behavioral and developmental outcome was assessed by the Neurobehavioral Assessment of the Preterm Infant (NAPI) at 36 weeks PCA, the APIB at 42 weeks PCA, and by the Bayley Scales of Infant Development (BSID) at 4, 12, and 24 months CA. Sleep developmental measures at 3 months CA showed a

Osmotic Homeostasis

PubMed Central

Zeidel, Mark L.

2015-01-01

Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal “osmoreceptors” that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance. PMID:25078421

Mice Lacking the Circadian Modulators SHARP1 and SHARP2 Display Altered Sleep and Mixed State Endophenotypes of Psychiatric Disorders

PubMed Central

Shahmoradi, Ali; Reinecke, Lisa; Kroos, Christina; Wichert, Sven P.; Oster, Henrik; Wehr, Michael C.; Taneja, Reshma; Hirrlinger, Johannes; Rossner, Moritz J.

2014-01-01

Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2. PMID:25340473

Environmental disruption of the circadian clock leads to altered sleep and immune responses in mouse.

PubMed

Phillips, Derrick J; Savenkova, Marina I; Karatsoreos, Ilia N

2015-07-01

In mammals, one of the most salient outputs of the circadian (daily) clock is the timing of the sleep-wake cycle. Modern industrialized society has led to a fundamental breakdown in the relationship between our endogenous timekeeping systems and the solar day, disrupting normal circadian rhythms. We have argued that disrupted circadian rhythms could lead to changes in allostatic load, and the capacity of organisms to respond to other environmental challenges. In this set of studies, we apply a model of circadian disruption characterized in our lab in which mice are housed in a 20h long day, with 10h of light and 10h of darkness. We explored the effects of this environmental disruption on sleep patterns, to establish if this model results in marked sleep deprivation. Given the interaction between circadian, sleep, and immune systems, we further probed if our model of circadian disruption also alters the innate immune response to peripheral bacterial endotoxin challenge. Our results demonstrate that this model of circadian disruption does not lead to marked sleep deprivation, but instead affects the timing and quality of sleep. We also show that while circadian disruption does not lead to basal changes in the immune markers we explored, the immune response is affected, both in the brain and the periphery. Together, our findings further strengthen the important role of the circadian timing system in sleep regulation and immune responses, and provide evidence that disrupting the circadian clock increases vulnerability to further environmental stressors, including immunological challenges. Copyright © 2014 Elsevier Inc. All rights reserved.

Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder.

PubMed

Geddes, Maiya R; Tie, Yanmei; Gabrieli, John D E; McGinnis, Scott M; Golby, Alexandra J; Whitfield-Gabrieli, Susan

2016-01-01

Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Alterations in homeostasis after open surgery. A prospective randomized study

PubMed Central

DEDEJ, T.; LAMAJ, E.; MARKU, N.; OSTRENI, V.; BILALI, S.

2013-01-01

Summary Introduction Alterations in homeostasis, and a subsequent increased risk for postoperative thromboembolic complications, are observed as a result of open surgery. Additionally, the stress response to surgical trauma precipitates a transient hypercoagulable state as well as inflammation. This study was conducted to evaluate the patterns in postoperative alterations of blood coagulation, and to detect their correlations with inflammatory markers. Patients and methods The study included 50 patients with comparable demographic data, who were randomly assigned to undergo abdominal surgery. No previous coagulation disorders were noted. Blood samples were collected preoperatively and 72 h postoperatively. The following parameters were measured: prothrombin time (PT) and activated partial thromboplastin time (APTT); fibrinogen (FIB), D-dimer (D-D), and C-reactive protein (CRP) levels; and platelet (PLT) count. Prophylactic doses of low molecular weight heparin were administered to all patients. Results The PT mean value significantly changed from 90.38% before surgery to 81.25% after surgery. No statistical difference was observed between APTT values before and after surgery. FIB levels significantly increased from 381.50 mg/dL preoperatively to 462.57 mg/dL postoperatively. Mean D-D levels also significantly increased from 235.54 μg/L preoperatively to 803.59 μg/L postoperatively. PLT count significantly declined after surgery. Mean CRP levels significantly increased from 12.33 mg/L preoperatively to 44.28 mg/L postoperatively. A strong correlation was observed between D-D and C-RP levels after surgery. Conclusion These results indicate that, despite administering an-tithromboembolic prophylaxis, a hypercoagulable state was observed following surgery. This state was enhanced by inflammation. PMID:24091175

Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

PubMed Central

Lee, Junga; Scheri, Richard C.; Zhang, Yuan; Curtis, Lawrence R.

2008-01-01

Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [14C]CD or [14C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor α (ERα) in a concentration-dependent manner (0–50 μM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice. PMID:18789348

Electroencephalographic studies of sleep

NASA Technical Reports Server (NTRS)

Webb, W. B.; Agnew, H. W., Jr.

1975-01-01

Various experimental studies on sleep are described. The following areas are discussed: (1) effect of altered day length on sleep, (2) effect of a partial loss of sleep on subsequent nocturnal sleep; (3) effect of rigid control over sleep-wake-up times; (4) sleep and wakefulness in a time-free environment; (5) distribution of spindles during a full night of sleep; and (6) effect on sleep and performance of swiftly changing shifts of work.

The 5α-reductase inhibitor finasteride is not associated with alterations in sleep spindles in men referred for polysomnography

PubMed Central

Goldstein, Michael R.; Cook, Jesse D.; Plante, David T.

2015-01-01

Objective Endogenous neurosteroids that potentiate the GABAA receptor are thought to enhance the generation of sleep spindles. This study tested the hypothesis that the 5α-reductase inhibitor finasteride, an agent associated with reductions in neurosteroids, would be associated with reduced sleep spindles in men referred for polysomnography. Methods Spectral analysis and spindle waveform detection were performed on electroencephalographic (EEG) sleep data in the 11–16Hz sigma band, as well as several subranges, from 27 men taking finasteride and 27 matched comparison patients (ages 18 to 81 years). Results No significant differences between groups were observed for spectral power or sleep spindle morphology measures, including spindle density, amplitude, duration, and integrated spindle activity. Conclusions Contrary to our hypothesis, these findings demonstrate that finasteride is not associated with alterations in sleep spindle range activity or spindle morphology parameters. PMID:26494125

Operation of a homeostatic sleep switch.

PubMed

Pimentel, Diogo; Donlea, Jeffrey M; Talbot, Clifford B; Song, Seoho M; Thurston, Alexander J F; Miesenböck, Gero

2016-08-18

Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep. In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex. Artificial activation of these cells induces sleep, whereas reductions in excitability cause insomnia. dFB neurons in sleep-deprived flies tend to be electrically active, with high input resistances and long membrane time constants, while neurons in rested flies tend to be electrically silent. Correlative evidence thus supports the simple view that homeostatic sleep control works by switching sleep-promoting neurons between active and quiescent states. Here we demonstrate state switching by dFB neurons, identify dopamine as a neuromodulator that operates the switch, and delineate the switching mechanism. Arousing dopamine caused transient hyperpolarization of dFB neurons within tens of milliseconds and lasting excitability suppression within minutes. Both effects were transduced by Dop1R2 receptors and mediated by potassium conductances. The switch to electrical silence involved the downregulation of voltage-gated A-type currents carried by Shaker and Shab, and the upregulation of voltage-independent leak currents through a two-pore-domain potassium channel that we term Sandman. Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in response to dopamine. dFB-restricted interference with the expression of Shaker or Sandman decreased or increased sleep, respectively, by slowing the repetitive discharge of dFB neurons in the ON state or blocking their entry into the OFF state. Biophysical changes in a small population of neurons are thus linked to the

Cold exposure and sleep in the rat: REM sleep homeostasis and body size.

PubMed

Amici, Roberto; Cerri, Matteo; Ocampo-Garcés, Adrian; Baracchi, Francesca; Dentico, Daniela; Jones, Christine Ann; Luppi, Marco; Perez, Emanuele; Parmeggiani, Pier Luigi; Zamboni, Giovanni

2008-05-01

Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24 degrees C. EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10 degrees C to -10 degrees C and for 4 days during recovery. Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. 24 male albino rats. Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature. REMS occurrence decreased proportionally with cold exposure, but a fast compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond a "fast rebound" threshold corresponding to 22% of the daily REMS need. A slow REMS rebound apparently allowed the animals to fully restore the previous REMS loss during the following 3 days of recovery. Comparing the present data on rats with data from earlier studies on cats and humans, it appears that small mammals have less tolerance for REMS loss than large ones. In small mammals, this low tolerance may be responsible on a short-term basis for the shorter wake-sleep cycle, and on long-term basis, for the higher percentage of REMS that is quickly recovered following REMS deprivation.

Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

PubMed Central

Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

2012-01-01

Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

PubMed Central

Trksak, George H.; Bracken, Bethany K.; Jensen, J. Eric; Plante, David T.; Penetar, David M.; Tartarini, Wendy L.; Maywalt, Melissa A.; Dorsey, Cynthia M.; Renshaw, Perry F.; Lukas, Scott E.

2013-01-01

In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse. PMID:24250276

Neurocognitive Consequences of Sleep Deprivation

PubMed Central

Goel, Namni; Rao, Hengyi; Durmer, Jeffrey S.; Dinges, David F.

2012-01-01

Sleep deprivation is associated with considerable social, financial, and health-related costs, in large measure because it produces impaired cognitive performance due to increasing sleep propensity and instability of waking neurobehavioral functions. Cognitive functions particularly affected by sleep loss include psychomotor and cognitive speed, vigilant and executive attention, working memory, and higher cognitive abilities. Chronic sleep-restriction experiments—which model the kind of sleep loss experienced by many individuals with sleep fragmentation and premature sleep curtailment due to disorders and lifestyle—demonstrate that cognitive deficits accumulate to severe levels over time without full awareness by the affected individual. Functional neuroimaging has revealed that frequent and progressively longer cognitive lapses, which are a hallmark of sleep deprivation, involve distributed changes in brain regions including frontal and parietal control areas, secondary sensory processing areas, and thalamic areas. There are robust differences among individuals in the degree of their cognitive vulnerability to sleep loss that may involve differences in prefrontal and parietal cortices, and that may have a basis in genes regulating sleep homeostasis and circadian rhythms. Thus, cognitive deficits believed to be a function of the severity of clinical sleep disturbance may be a product of genetic alleles associated with differential cognitive vulnerability to sleep loss. PMID:19742409

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects.

PubMed

Santangeli, Olena; Lehtikuja, Henna; Palomäki, Eeva; Wigren, Henna-Kaisa; Paunio, Tiina; Porkka-Heiskanen, Tarja

2016-12-01

Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood. Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and BDNF gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood. Spontaneous sleep, sleep homeostasis, and BF extracellular adenosine levels were assessed in adulthood. CF rats demonstrated increased number of REM sleep onsets in light and dark periods of the day. Total REM and NREM sleep duration was also increased during the light period. While sleep homeostasis was not severely affected, basal level of adenosine in the BF of both male and female CF rats was lower than in controls. CF did not lead to considerable changes in behavior. Even when the consequences of adverse early-life events are not observed in tests for anxiety and depression, they leave a molecular mark in the brain, which can act as a vulnerability factor for psychopathologies in later life. Sleep is a sensitive indicator for even mild early-life stress. © 2016 Associated Professional Sleep Societies, LLC.

Sleep Variability in Adolescence is Associated with Altered Brain Development

PubMed Central

Telzer, Eva H.; Goldenberg, Diane; Fuligni, Andrew J.; Lieberman, Matthew D.; Galvan, Adriana

2015-01-01

Despite the known importance of sleep for brain development, and the sharp increase in poor sleep during adolescence, we know relatively little about how sleep impacts the developing brain. We present the first longitudinal study to examine how sleep during adolescence is associated with white matter integrity. We find that greater variability in sleep duration one year prior to a DTI scan is associated with lower white matter integrity above and beyond the effects of sleep duration, and variability in bedtime, whereas sleep variability a few months prior to the scan is not associated with white matter integrity. Thus, variability in sleep duration during adolescence may have long-term impairments on the developing brain. White matter integrity should be increasing during adolescence, and so sleep variability is directly at odds with normative developmental trends. PMID:26093368

Slow eye movements distribution during nocturnal sleep.

PubMed

Pizza, Fabio; Fabbri, Margherita; Magosso, Elisa; Ursino, Mauro; Provini, Federica; Ferri, Raffaele; Montagna, Pasquale

2011-08-01

To assess the distribution across nocturnal sleep of slow eye movements (SEMs). We evaluated SEMs distribution in the different sleep stages, and across sleep cycles in nocturnal recordings of 10 healthy women. Sleep was scored according to standard criteria, and the percentage of time occupied by the SEMs was automatically detected. SEMs were differently represented during sleep stages with the following order: wakefulness after sleep onset (WASO): 61%, NREM sleep stage 1: 54%, REM sleep: 43%, NREM sleep stage 2: 21%, NREM sleep stage 3: 7%, and NREM sleep stage 4: 3% (p<0.0001). There was no difference between phasic and tonic REM sleep. SEMs progressively decreased across the NREM sleep cycles (38%, 15%, 13% during NREM sleep stage 2 in the first three sleep cycles, p=0.006), whereas no significant difference was found for REM, NREM sleep stage 1, slow-wave sleep and WASO. Our findings confirm that SEMs are a phenomenon typical of the sleep onset period, but are also found in REM sleep. The nocturnal evolution of SEMs during NREM sleep stage 2 parallels the homeostatic process underlying slow-wave sleep. SEMs are a marker of sleepiness and, potentially, of sleep homeostasis. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Alterations of orexinergic and melanin-concentrating hormone neurons in experimental sleeping sickness.

PubMed

Palomba, M; Seke-Etet, P F; Laperchia, C; Tiberio, L; Xu, Y-Z; Colavito, V; Grassi-Zucconi, G; Bentivoglio, M

2015-04-02

neurons in the pathogenesis of sleep/wake alterations in the disease and to their vulnerability to inflammatory signaling. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism.

PubMed

Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

2015-01-01

Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

PubMed Central

Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

2015-01-01

Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

Sleep variability in adolescence is associated with altered brain development.

PubMed

Telzer, Eva H; Goldenberg, Diane; Fuligni, Andrew J; Lieberman, Matthew D; Gálvan, Adriana

2015-08-01

Despite the known importance of sleep for brain development, and the sharp increase in poor sleep during adolescence, we know relatively little about how sleep impacts the developing brain. We present the first longitudinal study to examine how sleep during adolescence is associated with white matter integrity. We find that greater variability in sleep duration one year prior to a DTI scan is associated with lower white matter integrity above and beyond the effects of sleep duration, and variability in bedtime, whereas sleep variability a few months prior to the scan is not associated with white matter integrity. Thus, variability in sleep duration during adolescence may have long-term impairments on the developing brain. White matter integrity should be increasing during adolescence, and so sleep variability is directly at odds with normative developmental trends. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sleep, sleep-disordered breathing and metabolic consequences.

PubMed

Lévy, P; Bonsignore, M R; Eckel, J

2009-07-01

Sleep profoundly affects metabolic pathways. In healthy subjects, experimental sleep restriction caused insulin resistance (IR) and increased evening cortisol and sympathetic activation. Increased obesity in subjects reporting short sleep duration leads to speculation that, during recent decades, decreased sleeping time in the general population may have contributed to the increasing prevalence of obesity. Causal inference is difficult due to lack of control for confounders and inconsistent evidence of temporal sequence. In the general population, obstructive sleep apnoea (OSA) is associated with glucose intolerance. OSA severity is also associated with the degree of IR. However, OSA at baseline does not seem to significantly predict the development of diabetes. Prevalence of the metabolic syndrome is higher in patients with OSA than in obese subjects without OSA. Treatment with continuous positive airway pressure seems to improve glucose metabolism both in diabetic and nondiabetic OSA but mainly in nonobese subjects. The relative role of obesity and OSA in the pathogenesis of metabolic alterations is still unclear and is intensively studied in clinical and experimental models. In the intermittent hypoxia model in rodents, strong interactions are likely to occur between haemodynamic alterations, systemic inflammation and metabolic changes, modulated by genetic background. Molecular and cellular mechanisms are currently being investigated.

[Sleep disorders in Parkinson's disease: insomnia and sleep fragmentation, daytime hypersomnia, alterations to the circadian rhythm and sleep apnea syndrome].

PubMed

Mondragón-Rezola, E; Arratíbel-Echarren, I; Ruiz-Martínez, J; Martí-Massó, J F

2010-02-08

Sleep disorders in Parkinson's disease are present in 60-98% of patients and reduce their quality of life. To review the pathophysiology, diagnostic approach and management of the different sleep disorders. We describe the pathophysiology associated with neurodegeneration, due to symptoms (motor and nonmotor) and drug therapies. This article reviews insomnia, excessive daytime sleepiness, circadian sleep disorders and sleep apnea. Subjective or objective sleepiness assessment should routinely be performed by physicians looking after Parkinson's disease patients. Management is difficult and should be targeted to the specific sleep disorder and its likely cause.

Altered sleep patterns in patients with non-functional GHRH receptor.

PubMed

Oliveira, Francielle T; Salvatori, Roberto; Marcondes, José; Macena, Larissa B; Oliveira-Santos, Alecia A; Faro, Augusto C N; Campos, Viviane C; Oliveira, Carla R P; Costa, Ursula M M; Aguiar-Oliveira, Manuel H

2017-07-01

GH-releasing hormone (GHRH) exerts hypnotic actions increasing the non-rapid eye movement (NREM) sleep. Conversely, GH stimulates the REM sleep. GH deficiency (GHD) often leads to sleep problems, daytime fatigue and reduced quality of life (QoL). GHD may be due to lack of hypothalamic GHRH or destruction of somatotroph cells. We have described a cohort with isolated GHD (IGHD) due to GHRH resistance caused by a homozygous null mutation (c.57 + 1G > A) in the GHRH receptor gene. They have normal QoL and no obvious complaints of chronic tiredness. The aim of this study was to determine the sleep quality in these subjects. A cross-sectional study was carried out in 21 adult IGHD subjects, and 21 age- and gender-matched controls. Objective sleep assessment included polygraphic records of the awake, stages NREM [N1 (drowsiness), N2 and N3 (already sleeping)] and REM (R). Subjective evaluation included the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and the Epworth Sleepiness Scale. IGHD subjects showed a reduction in sleep efficiency ( P  = 0.007), total sleep time ( P  = 0.028), duration of N2 and R in minutes ( P  = 0.026 and P =  0.046 respectively), but had increased duration and percentage of N1 stage ( P  = 0.029 and P =  0.022 respectively), wake ( P  = 0.007) and wake-time after sleep onset ( P  = 0.017). There was no difference in N3 or in sleep quality questionnaire scores. Patients with IGHD due to GHRH resistance exhibit objective reduction in the sleep quality, with changes in NREM and REM sleep, with no detectable subjective consequences. GHRH resistance seems to have a preponderant role over GHD in the sleep quality of these subjects. © 2017 European Society of Endocrinology.

Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

PubMed Central

Rau, Thomas F.; Lu, Qing; Sharma, Shruti; Sun, Xutong; Leary, Gregory; Beckman, Matthew L.; Hou, Yali; Wainwright, Mark S.; Kavanaugh, Michael; Poulsen, David J.; Black, Stephen M.

2012-01-01

Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD. PMID:22984394

Sleep structure: a new diagnostic tool for stage determination in sleeping sickness.

PubMed

Buguet, Alain; Bisser, Sylvie; Josenando, Théophile; Chapotot, Florian; Cespuglio, Raymond

2005-01-01

Human African trypanosomiasis (HAT), due to the transmission of Trypanosoma brucei (T. b.) gambiense and T. b. rhodesiense by tsetse flies, is re-emerging in inter-tropical Africa. It evolves from the hemolymphatic Stage I to the meningo-encephalitic Stage II. The latter is generally treated with melarsoprol, an arseniate provoking often a deadly encephalopathy. A precise determination of the HAT evolution stage is therefore crucial. Stage II patients show: (i) a deregulation of the 24-h distribution of the sleep-wake alternation; (ii) an alteration of the sleep structure, with frequent sleep onset rapid eye movement (REM) periods (SOREMPs). Gambian HAT was diagnosed in eight patients (four, Stage II; three, Stage I; one, "intermediate" case) at the trypanosomiasis clinic at Viana (Angola). Continuous 48-h polysomnography was recorded on Oxford Medilog 9000-II portable systems before and after treatment with melarsoprol (Stage II) or pentamidine (Stage I and "intermediate" stage). Sleep traces were visually analyzed in 20-s epochs using the PRANA software. Stage II patients showed the complete sleep-wake syndrome, partly reversed by melarsoprol 1 month later. Two Stage I patients did not experience any of these alterations. However, the "intermediate" and one Stage I patients exhibited sleep disruptions and/or SOREMPs, persistent after pentamidine treatment. Polysomnography may represent a diagnostic tool to distinguish the two stages of HAT. Especially, SOREMPs appear shortly after the central nervous system invasion by trypanosomes. The reversibility of the sleep-wake cycle and sleep structure alterations after appropriate treatment constitutes the basis of an evaluation of the healing process.

Sleep deprivation: a mind-body approach.

PubMed

Aguirre, Claudia C

2016-11-01

The purpose of this review is to summarize recent advances in our understanding of the impact sleep disturbances have on our health, with particular focus on the brain. The present review considers the influence of sleep disturbance on the neurovascular unit; the role of sleep disturbance in neurodegenerative diseases; and relevant strategies of neuro-immuno-endocrine interactions that likely contribute to the restorative power of sleep. Given the latest discoveries about the brain's waste clearance system and its relationship to neurodegenerative diseases like Alzheimer's disease, this review gives a brief overview on the molecular mechanisms behind sleep loss-related impairments. Recent evidence indicates that sleep plays a vital role in neuro-immuno-endocrine homeostasis. Sleep loss has been linked to elevated risks for cognitive and mood disorders, underscored by impaired synaptic transmission. The glymphatic system has been shown to be modulated by sleep and implicated in neurodegenerative disorders. Interactions between sleep quality, the immune system, and neurodegenerative disease are complex and a challenge to distil. These interactions are frequently bidirectional, because of sleep's characterization as an early symptom and as a potential factor contributing to the development and progression of mood and cognitive disorders. VIDEO ABSTRACT.

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

PubMed

Lv, Jun; Liu, Dongdong; Ma, Jing; Wang, Xiaoying; Zhang, Jue

2015-01-01

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.

Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models*

PubMed Central

Mochel, Fanny; Durant, Brandon; Meng, Xingli; O'Callaghan, James; Yu, Hua; Brouillet, Emmanuel; Wheeler, Vanessa C.; Humbert, Sandrine; Schiffmann, Raphael; Durr, Alexandra

2012-01-01

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in HdhQ111/+ mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. PMID:22123819

Alcohol and the sleeping brain.

PubMed

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.

The Role of Sleep in Emotional Brain Function

PubMed Central

Goldstein, Andrea N.; Walker, Matthew P.

2014-01-01

Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

PubMed

Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; Dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Antunes, Hanna Karen Moreira

2016-01-01

Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

Altered lipid homeostasis in Drosophila InsP3 receptor mutants leads to obesity and hyperphagia.

PubMed

Subramanian, Manivannan; Metya, Suman Kumar; Sadaf, Sufia; Kumar, Satish; Schwudke, Dominik; Hasan, Gaiti

2013-05-01

Obesity is a complex metabolic disorder that often manifests with a strong genetic component in humans. However, the genetic basis for obesity and the accompanying metabolic syndrome is poorly defined. At a metabolic level, obesity arises from an imbalance between the nutritional intake and energy utilization of an organism. Mechanisms that sense the metabolic state of the individual and convey this information to satiety centers help achieve this balance. Mutations in genes that alter or modify such signaling mechanisms are likely to lead to either obese individuals, who in mammals are at high risk for diabetes and cardiovascular disease, or excessively thin individuals with accompanying health problems. Here we show that Drosophila mutants for an intracellular calcium signaling channel, the inositol 1,4,5-trisphosphate receptor (InsP3R) store excess triglycerides in their fat bodies and become unnaturally obese on a normal diet. Although excess insulin signaling can rescue obesity in InsP3R mutants to some extent, we show that it is not the only cause of the defect. Through mass spectrometric analysis of lipids we find that homeostasis of storage and membrane lipids are altered in InsP3R mutants. Possibly as a compensatory mechanism, InsP3R mutant adults also feed excessively. Thus, reduced InsP3R function alters lipid metabolism and causes hyperphagia in adults. Together, the metabolic and behavioral changes lead to obesity. Our results implicate altered InsP3 signaling as a previously unknown causative factor for metabolic syndrome in humans. Importantly, our studies also suggest preventive dietary interventions.

Effect of long-term sleep restriction and subsequent recovery sleep on the diurnal rhythms of white blood cell subpopulations.

PubMed

Lasselin, Julie; Rehman, Javaid-Ur; Åkerstedt, Torbjorn; Lekander, Mats; Axelsson, John

2015-07-01

While acute modifications of sleep duration induces a wide array of immune function alterations, less is known of how longer periods with insufficient sleep affect immune functions and how they return to normal once recovery sleep is obtained. The purpose of the present study was to investigate the effects of five days of restricted sleep and a subsequent 7-day period of sleep recovery on white blood cell (WBC) subpopulation count and diurnal rhythms. Nine healthy males participated in a sleep protocol consisting of two baseline days (8h of sleep/night), five nights with restricted sleep (4h of sleep/night) and seven days of recovery sleep (8h of sleep/night). During nine of these days, blood was drawn hourly during night-time end every third hour during daytime, and differential WBC count was analyzed. Gradual increase across the days of sleep restriction was observed for total WBC (p<.001), monocytes (p<.001), neutrophils (p<.001) and lymphocytes (p<.05). Subsequent recovery sleep resulted in a gradual decrease in monocytes (p<.001) and lymphocytes (p=.001), but not in neutrophils that remained elevated over baseline level at the end of the 7-day recovery period. These effects were associated with altered diurnal rhythms of total WBC and neutrophils, restricted sleep being associated with higher levels during the night and at awakening, resulting in a flattening of the rhythm. The diurnal alterations were reversed when recovery sleep was allowed, although the amplitude of total WBC, neutrophils and monocytes was increased at the end of the recovery period in comparison to baseline. Altogether, these data show that long-term sleep restriction leads to a gradual increase of circulating WBC subpopulations and alterations of the respective diurnal rhythms. Although some of the effects caused by five days of restricted sleep were restored within the first days of recovery, some parameters were not back to baseline even after a period of seven recovery days. Copyright

Sleep and metabolic function.

PubMed

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.

Altered Nocturnal Cardiovascular Control in Children With Sleep-Disordered Breathing.

PubMed

El-Hamad, Fatima; Immanuel, Sarah; Liu, Xiao; Pamula, Yvonne; Kontos, Anna; Martin, James; Kennedy, Declan; Kohler, Mark; Porta, Alberto; Baumert, Mathias

2017-10-01

To assess cardiovascular control during sleep in children with sleep-disordered breathing (SDB) and the effect of adenotonsillectomy in comparison to healthy nonsnoring children. Cardiorespiratory signals obtained from overnight polysomnographic recordings of 28 children with SDB and 34 healthy nonsnoring children were analyzed. We employed an autoregressive closed-loop model with heart period (RR) and pulse transit time (PTT) as outputs and respiration as an external input to obtain estimates of respiratory gain and baroreflex gain. Mean and variability of PTT were increased in children with SDB across all stages of sleep. Low frequency power of RR and PTT were attenuated during non-rapid eye movement (REM) sleep. Baroreflex sensitivity was reduced in children with SDB in stage 2 sleep, while respiratory gain was increased in slow wave sleep. After adenotonsillectomy, these indices normalized in the SDB group attaining values comparable to those of healthy children. In children with mild-to-moderate SDB, vasomotor activity is increased and baroreflex sensitivity decreased during quiet, event-free non-REM sleep. Adenotonsillectomy appears to reverse this effect. © 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.

Increased Automaticity and Altered Temporal Preparation Following Sleep Deprivation.

PubMed

Kong, Danyang; Asplund, Christopher L; Ling, Aiqing; Chee, Michael W L

2015-08-01

Temporal expectation enables us to focus limited processing resources, thereby optimizing perceptual and motor processing for critical upcoming events. We investigated the effects of total sleep deprivation (TSD) on temporal expectation by evaluating the foreperiod and sequential effects during a psychomotor vigilance task (PVT). We also examined how these two measures were modulated by vulnerability to TSD. Three 10-min visual PVT sessions using uniformly distributed foreperiods were conducted in the wake-maintenance zone the evening before sleep deprivation (ESD) and three more in the morning following approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were determined by a tertile split of participants based on the change in the number of behavioral lapses recorded during ESD and TSD. A subset of participants performed six additional 10-min modified auditory PVTs with exponentially distributed foreperiods during rested wakefulness (RW) and TSD to test the effect of temporal distribution on foreperiod and sequential effects. Sleep laboratory. There were 172 young healthy participants (90 males) with regular sleep patterns. Nineteen of these participants performed the modified auditory PVT. Despite behavioral lapses and slower response times, sleep deprived participants could still perceive the conditional probability of temporal events and modify their level of preparation accordingly. Both foreperiod and sequential effects were magnified following sleep deprivation in vulnerable individuals. Only the foreperiod effect increased in nonvulnerable individuals. The preservation of foreperiod and sequential effects suggests that implicit time perception and temporal preparedness are intact during total sleep deprivation. Individuals appear to reallocate their depleted preparatory resources to more probable event timings in ongoing trials, whereas vulnerable participants also rely more on automatic processes. © 2015 Associated Professional Sleep

Physiology and pathophysiology of potassium homeostasis.

PubMed

Palmer, Biff F; Clegg, Deborah J

2016-12-01

Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

Information processing during NREM sleep and sleep quality in insomnia.

PubMed

Ceklic, Tijana; Bastien, Célyne H

2015-12-01

Insomnia sufferers (INS) are cortically hyperaroused during sleep, which seems to translate into altered information processing during nighttime. While information processing, as measured by event-related potentials (ERPs), during wake appears to be associated with sleep quality of the preceding night, the existence of such an association during nighttime has never been investigated. This study aims to investigate nighttime information processing among good sleepers (GS) and INS while considering concomitant sleep quality. Following a multistep clinical evaluation, INS and GS participants underwent 4 consecutive nights of PSG recordings in the sleep laboratory. Thirty nine GS (mean age 34.56±9.02) and twenty nine INS (mean age 43.03±9.12) were included in the study. ERPs (N1, P2, N350) were recorded all night on Night 4 (oddball paradigm) during NREM sleep. Regardless of sleep quality, INS presented a larger N350 amplitude during SWS (p=0.042) while GS showed a larger N350 amplitude during late-night stage 2 sleep (p=0.004). Regardless of diagnosis, those who slept objectively well showed a smaller N350 amplitude (p=0.020) while those who slept subjectively well showed a smaller P2 (p<0.001) and N350 amplitude (p=0.006). Also, those who reported an objectively bad night as good showed smaller P2 (p< 0.001) and N350 (p=0.010) amplitudes. Information processing seems to be associated with concomitant subjective and objective sleep quality for both GS and INS. However, INS show an alteration in information processing during sleep, especially for inhibition processes, regardless of their sleep quality. Copyright © 2015 Elsevier B.V. All rights reserved.

Sleep deprivation alters functioning within the neural network underlying the covert orienting of attention.

PubMed

Mander, Bryce A; Reid, Kathryn J; Davuluri, Vijay K; Small, Dana M; Parrish, Todd B; Mesulam, M-Marsel; Zee, Phyllis C; Gitelman, Darren R

2008-06-27

One function of spatial attention is to enable goal-directed interactions with the environment through the allocation of neural resources to motivationally relevant parts of space. Studies have shown that responses are enhanced when spatial attention is predictively biased towards locations where significant events are expected to occur. Previous studies suggest that the ability to bias attention predictively is related to posterior cingulate cortex (PCC) activation [Small, D.M., et al., 2003. The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention. Neuroimage 18, 633-41]. Sleep deprivation (SD) impairs selective attention and reduces PCC activity [Thomas, M., et al., 2000. Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity. J. Sleep Res. 9, 335-352]. Based on these findings, we hypothesized that SD would affect PCC function and alter the ability to predictively allocate spatial attention. Seven healthy, young adults underwent functional magnetic resonance imaging (fMRI) following normal rest and 34-36 h of SD while performing a task in which attention was shifted in response to peripheral targets preceded by spatially informative (valid), misleading (invalid), or uninformative (neutral) cues. When rested, but not when sleep-deprived, subjects responded more quickly to targets that followed valid cues than those after neutral or invalid cues. Brain activity during validly cued trials with a reaction time benefit was compared to activity in trials with no benefit. PCC activation was greater during trials with a reaction time benefit following normal rest. In contrast, following SD, reaction time benefits were associated with activation in the left intraparietal sulcus, a region associated with receptivity to stimuli at unexpected locations. These changes may render sleep-deprived individuals less able

Neuroimmunology of disordered sleep in depression and alcoholism.

PubMed

Irwin, M

2001-11-01

The specific functions of sleep are not known, although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed and alcoholic subjects correlates with declines in natural and cellular immunity and is associated with alterations in the complex cytokine network. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the physiological significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep.

Slow wave sleep in the chronically fatigued: Power spectra distribution patterns in chronic fatigue syndrome and primary insomnia.

PubMed

Neu, Daniel; Mairesse, Olivier; Verbanck, Paul; Le Bon, Olivier

2015-10-01

To investigate slow wave sleep (SWS) spectral power proportions in distinct clinical conditions sharing non-restorative sleep and fatigue complaints without excessive daytime sleepiness (EDS), namely the chronic fatigue syndrome (CFS) and primary insomnia (PI). Impaired sleep homeostasis has been suspected in both CFS and PI. We compared perceived sleep quality, fatigue and sleepiness symptom-intensities, polysomnography (PSG) and SWS spectral power distributions of drug-free CFS and PI patients without comorbid sleep or mental disorders, with a good sleeper control group. Higher fatigue without EDS and impaired perceived sleep quality were confirmed in both patient groups. PSG mainly differed in sleep fragmentation and SWS durations. Spectral analysis revealed a similar decrease in central ultra slow power (0.3-0.79Hz) proportion during SWS for both CFS and PI and an increase in frontal power proportions of faster frequencies during SWS in PI only. The latter was correlated to affective symptoms whereas lower central ultra slow power proportions were related to fatigue severity and sleep quality impairment. In combination with normal (PI) or even increased SWS durations (CFS), we found consistent evidence for lower proportions of slow oscillations during SWS in PI and CFS. Observing normal or increased SWS durations but lower proportions of ultra slow power, our findings suggest a possible quantitative compensation of altered homeostatic regulation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Altered sleep and affect in the neurotensin receptor 1 knockout mouse.

PubMed

Fitzpatrick, Karrie; Winrow, Christopher J; Gotter, Anthony L; Millstein, Joshua; Arbuzova, Janna; Brunner, Joseph; Kasarskis, Andrew; Vitaterna, Martha H; Renger, John J; Turek, Fred W

2012-07-01

Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model. Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse. NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors. Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders.

SLEEP AND MENTAL DISORDERS: A META-ANALYSIS OF POLYSOMNOGRAPHIC RESEARCH

PubMed Central

Baglioni, Chiara; Nanovska, Svetoslava; Regen, Wolfram; Spiegelhalder, Kai; Feige, Bernd; Nissen, Christoph; Reynolds, Charles F.; Riemann, Dieter

2016-01-01

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, ADHD, and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the “Comprehensive Meta-Analysis” and “R” softwares. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges’g). Sources of variability, i.e., sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in one condition; however, no two conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in one single variable. PMID:27416139

Developmental changes in sleep biology and potential effects on adolescent behavior and caffeine use

PubMed Central

Carskadon, Mary A; Tarokh, Leila

2014-01-01

Adolescent development includes changes in the biological regulatory processes for the timing of sleep. Circadian rhythm changes and changes to the sleep-pressure system (sleep homeostasis) during adolescence both favor later timing of sleep. These changes, combined with prevailing social pressures, are responsible for most teens sleeping too late and too little; those who sleep least report consuming more caffeine. Although direct research findings are scarce, the likelihood of use and abuse of caffeine-laden products grows across the adolescent years due, in part, to excessive sleepiness. PMID:25293544

Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders.

PubMed

Charrier, Annaëlle; Olliac, Bertrand; Roubertoux, Pierre; Tordjman, Sylvie

2017-04-29

In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause-effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep-wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

Neuroimmunologic aspects of sleep and sleep loss

NASA Technical Reports Server (NTRS)

Rogers, N. L.; Szuba, M. P.; Staab, J. P.; Evans, D. L.; Dinges, D. F.

2001-01-01

The complex and intimate interactions between the sleep and immune systems have been the focus of study for several years. Immune factors, particularly the interleukins, regulate sleep and in turn are altered by sleep and sleep deprivation. The sleep-wake cycle likewise regulates normal functioning of the immune system. Although a large number of studies have focused on the relationship between the immune system and sleep, relatively few studies have examined the effects of sleep deprivation on immune parameters. Studies of sleep deprivation's effects are important for several reasons. First, in the 21st century, various societal pressures require humans to work longer and sleep less. Sleep deprivation is becoming an occupational hazard in many industries. Second, to garner a greater understanding of the regulatory effects of sleep on the immune system, one must understand the consequences of sleep deprivation on the immune system. Significant detrimental effects on immune functioning can be seen after a few days of total sleep deprivation or even several days of partial sleep deprivation. Interestingly, not all of the changes in immune physiology that occur as a result of sleep deprivation appear to be negative. Numerous medical disorders involving the immune system are associated with changes in the sleep-wake physiology--either being caused by sleep dysfunction or being exacerbated by sleep disruption. These disorders include infectious diseases, fibromyalgia, cancers, and major depressive disorder. In this article, we will describe the relationships between sleep physiology and the immune system, in states of health and disease. Interspersed will be proposals for future research that may illuminate the clinical relevance of the relationships between sleeping, sleep loss and immune function in humans. Copyright 2001 by W.B. Saunders Company.

[Midface alterations in childhood as pathogenesis of obstructive sleep apnea syndrome].

PubMed

Rangel Chávez, José de Jesús; Espinosa Martínez, Cynthia; Medina Serpa, Aldo Uzziel

The onset of nasal breathing sets a genetically determined impulse to aerate the face cavities or paranasal sinuses, which in turn initiate its growth creating the useful trafficable space for air during the development of the midface. Considering the evidence that the upper airway obstruction has a primary role in the pathogenesis of respiratory sleep disorders, any condition that causes a permanent difficulty to the nasal airflow during breathing will cause hypo-development of the required amplitude in this airway, reducing the growth stimulation of the sinus cavities and altering the development of the midface as a whole. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.

PubMed

Garza-Lombó, Carla; Posadas, Yanahi; Quintanar, Liliana; Gonsebatt, María E; Franco, Rodrigo

2018-06-20

Essential metals such as copper, iron, manganese, and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our life span, humans are also exposed to xenobiotic metals from natural and anthropogenic sources, including aluminum, arsenic, cadmium, lead, and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals are linked to several neurological disorders, including neurodegeneration and neurodevelopmental alterations. Recent Advances: The redox activity of essential metals is key for neuronal homeostasis and brain function. Alterations in redox homeostasis and signaling are central to the pathological consequences of dysfunctional metal ion homeostasis and increased exposure to xenobiotic metals. Both redox-active and redox-inactive metals trigger oxidative stress and damage in the central nervous system, and the exact mechanisms involved are starting to become delineated. In this review, we aim to appraise the role of essential metals in determining the redox balance in the brain and the mechanisms by which alterations in the homeostasis of essential metals and exposure to xenobiotic metals disturb the cellular redox balance and signaling. We focus on recent literature regarding their transport, metabolism, and mechanisms of toxicity in neural systems. Delineating the specific mechanisms by which metals alter redox homeostasis is key to understand the pathological processes that convey chronic neuronal dysfunction in neurodegenerative and neurodevelopmental disorders. Antioxid. Redox Signal. 28, 1669-1703.

Delayed Sleep Phase Disorder In Temporal Isolation

PubMed Central

Campbell, Scott S.; Murphy, Patricia J.

2007-01-01

Study Objectives: This study sought to characterize sleep and the circadian rhythm of body core temperature of an individual with delayed sleep phase disorder (DSPD) in the absence of temporal cues and social entrainment and to compare those measures to age-matched normal control subjects studied under identical conditions. Design: Polysomnography and body temperature were recorded continuously for 4 days in entrained conditions, followed immediately by 17 days in a “free-running” environment. Setting: Temporal isolation facility in the Laboratory of Human Chronobiology, Weill Cornell Medical College. Participants: One individual who met criteria for delayed sleep phase disorder according to the International Classification of Sleep Disorders Diagnostic and Coding Manual (ICSD-2) and 3 age-matched control subjects. Interventions: None. Measurements and Results: The DSPD subject had a spontaneous period length (tau) of 25.38 hours compared to an average tau of 24.44 hours for the healthy controls. The DSPD subject also showed an altered phase relationship between sleep/wake and body temperature rhythms, as well as longer sleep latency, poorer sleep efficiency, and altered distribution of slow wave sleep (SWS) within sleep episodes, compared to control subjects. Conclusions: Delayed sleep phase disorder may be the reflection of an abnormal circadian timing system characterized not only by a long tau, but also by an altered internal phase relationship between the sleep/wake system and the circadian rhythm of body temperature. The latter results in significantly disturbed sleep, even when DSPD patients are permitted to sleep and wake at their preferred times. Citation: Campbell SS; Murphy PJ. Delayed sleep phase disorder in temporal isolation. SLEEP 2007;30(9):1225-1228. PMID:17910395

Effects of partial sleep deprivation on slow waves during non-rapid eye movement sleep: A high density EEG investigation.

PubMed

Plante, David T; Goldstein, Michael R; Cook, Jesse D; Smith, Richard; Riedner, Brady A; Rumble, Meredith E; Jelenchick, Lauren; Roth, Andrea; Tononi, Giulio; Benca, Ruth M; Peterson, Michael J

2016-02-01

Changes in slow waves during non-rapid eye movement (NREM) sleep in response to acute total sleep deprivation are well-established measures of sleep homeostasis. This investigation utilized high-density electroencephalography (hdEEG) to examine topographic changes in slow waves during repeated partial sleep deprivation. Twenty-four participants underwent a 6-day sleep restriction protocol. Spectral and period-amplitude analyses of sleep hdEEG data were used to examine changes in slow wave energy, count, amplitude, and slope relative to baseline. Changes in slow wave energy were dependent on the quantity of NREM sleep utilized for analysis, with widespread increases during sleep restriction and recovery when comparing data from the first portion of the sleep period, but restricted to recovery sleep if the entire sleep episode was considered. Period-amplitude analysis was less dependent on the quantity of NREM sleep utilized, and demonstrated topographic changes in the count, amplitude, and distribution of slow waves, with frontal increases in slow wave amplitude, numbers of high-amplitude waves, and amplitude/slopes of low amplitude waves resulting from partial sleep deprivation. Topographic changes in slow waves occur across the course of partial sleep restriction and recovery. These results demonstrate a homeostatic response to partial sleep loss in humans. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Adenosine deaminase polymorphism affects sleep EEG spectral power in a large epidemiological sample.

PubMed

Mazzotti, Diego Robles; Guindalini, Camila; de Souza, Altay Alves Lino; Sato, João Ricardo; Santos-Silva, Rogério; Bittencourt, Lia Rita Azeredo; Tufik, Sergio

2012-01-01

Slow wave oscillations in the electroencephalogram (EEG) during sleep may reflect both sleep need and intensity, which are implied in homeostatic regulation. Adenosine is strongly implicated in sleep homeostasis, and a single nucleotide polymorphism in the adenosine deaminase gene (ADA G22A) has been associated with deeper and more efficient sleep. The present study verified the association between the ADA G22A polymorphism and changes in sleep EEG spectral power (from C3-A2, C4-A1, O1-A2, and O2-A1 derivations) in the Epidemiologic Sleep Study (EPISONO) sample from São Paulo, Brazil. Eight-hundred individuals were subjected to full-night polysomnography and ADA G22A genotyping. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the signals from each EEG electrode. The genotype groups were compared in the whole sample and in a subsample of 120 individuals matched according to ADA genotype for age, gender, body mass index, caffeine intake status, presence of sleep disturbance, and sleep-disturbing medication. When compared with homozygous GG genotype carriers, A allele carriers showed higher delta spectral power in Stage 1 and Stages 3+4 of sleep, and increased theta spectral power in Stages 1, 2 and REM sleep. These changes were seen both in the whole sample and in the matched subset. The higher EEG spectral power indicates that the sleep of individuals carrying the A allele may be more intense. Therefore, this polymorphism may be an important source of variation in sleep homeostasis in humans, through modulation of specific components of the sleep EEG.

Sleep and mental disorders: A meta-analysis of polysomnographic research.

PubMed

Baglioni, Chiara; Nanovska, Svetoslava; Regen, Wolfram; Spiegelhalder, Kai; Feige, Bernd; Nissen, Christoph; Reynolds, Charles F; Riemann, Dieter

2016-09-01

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, attention-deficit-hyperactivity disorder (ADHD), and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the "Comprehensive Meta-Analysis" and "R" software. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges' g). Sources of variability, that is, sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in 1 condition; however, no 2 conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in 1 single variable. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Sleep Disturbances as a Risk Factor for Stroke

PubMed Central

Koo, Dae Lim; Nam, Hyunwoo; Thomas, Robert J.; Yun, Chang-Ho

2018-01-01

Sleep, a vital process of human being, is carefully orchestrated by the brain and consists of cyclic transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Autonomic tranquility during NREM sleep is characterized by vagal dominance and stable breathing, providing an opportunity for the cardiovascular-neural axis to restore homeostasis, in response to use, distress or fatigue inflicted during wakefulness. Abrupt irregular swings in sympathovagal balance during REM sleep act as phasic loads on the resting cardiovascular system. Any causes of sleep curtailment or fragmentation such as sleep restriction, sleep apnea, insomnia, periodic limb movements during sleep, and shift work, not only impair cardiovascular restoration but also impose a stress on the cardiovascular system. Sleep disturbances have been reported to play a role in the development of stroke and other cardiovascular disorders. This review aims to provide updated information on the role of abnormal sleep in the development of stroke, to discuss the implications of recent research findings, and to help both stroke clinicians and researchers understand the importance of identification and management of sleep pathology for stroke prevention and care. PMID:29402071

Sleep in childhood and adolescence: age-specific sleep characteristics, common sleep disturbances and associated difficulties.

PubMed

Barclay, Nicola L; Gregory, Alice M

2014-01-01

Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities. Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes-and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co-occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia and emotional/behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice.

PubMed

Loh, K; Merry, T L; Galic, S; Wu, B J; Watt, M J; Zhang, S; Zhang, Z-Y; Neel, B G; Tiganis, T

2012-02-01

Insulin activates insulin receptor protein tyrosine kinase and downstream phosphatidylinositol-3-kinase (PI3K)/Akt signalling in muscle to promote glucose uptake. The insulin receptor can serve as a substrate for the protein tyrosine phosphatase (PTP) 1B and T cell protein tyrosine phosphatase (TCPTP), which share a striking 74% sequence identity in their catalytic domains. PTP1B is a validated therapeutic target for the alleviation of insulin resistance in type 2 diabetes. PTP1B dephosphorylates the insulin receptor in liver and muscle to regulate glucose homeostasis, whereas TCPTP regulates insulin receptor signalling and gluconeogenesis in the liver. In this study we assessed for the first time the role of TCPTP in the regulation of insulin receptor signalling in muscle. We generated muscle-specific TCPTP-deficient (Mck-Cre;Ptpn2(lox/lox)) mice (Mck, also known as Ckm) and assessed the impact on glucose homeostasis and muscle insulin receptor signalling in chow-fed versus high-fat-fed mice. Blood glucose and insulin levels, insulin and glucose tolerance, and insulin-induced muscle insulin receptor activation and downstream PI3K/Akt signalling remained unaltered in chow-fed Mck-Cre;Ptpn2(lox/lox) versus Ptpn2(lox/lox) mice. In addition, body weight, adiposity, energy expenditure, insulin sensitivity and glucose homeostasis were not altered in high-fat-fed Mck-Cre;Ptpn2(lox/lox) versus Ptpn2(lox/lox) mice. These results indicate that TCPTP deficiency in muscle has no effect on insulin signalling and glucose homeostasis, and does not prevent high-fat diet-induced insulin resistance. Thus, despite their high degree of sequence identity, PTP1B and TCPTP contribute differentially to insulin receptor regulation in muscle. Our results are consistent with the notion that these two highly related PTPs make distinct contributions to insulin receptor regulation in different tissues.

Altered slow wave activity in major depressive disorder with hypersomnia: a high density EEG pilot study

PubMed Central

Plante, David T.; Landsness, Eric C.; Peterson, Michael J.; Goldstein, Michael R.; Wanger, Tim; Guokas, Jeff J.; Tononi, Giulio; Benca, Ruth M.

2012-01-01

Hypersomnolence in major depressive disorder (MDD) plays an important role in the natural history of the disorder, but the basis of hypersomnia in MDD is poorly understood. Slow wave activity (SWA) has been associated with sleep homeostasis, as well as sleep restoration and maintenance, and may be altered in MDD. Therefore, we conducted a post-hoc study that utilized high density electroencephalography (hdEEG) to test the hypothesis that MDD subjects with hypersomnia (HYS+) would have decreased SWA relative to age and sex-matched MDD subjects without hypersomnia (HYS−) and healthy controls (n=7 for each group). After correcting for multiple comparisons using statistical non-parametric mapping, HYS+ subjects demonstrated significantly reduced parieto-occipital all-night SWA relative to HYS− subjects. Our results suggest hypersomnolence may be associated with topographic reductions in SWA in MDD. Further research using adequately powered prospective design is indicated to confirm these findings. PMID:22512951

Sleep-Dependent Synaptic Down-Selection (I): Modeling the Benefits of Sleep on Memory Consolidation and Integration

PubMed Central

Nere, Andrew; Hashmi, Atif; Cirelli, Chiara; Tononi, Giulio

2013-01-01

Sleep can favor the consolidation of both procedural and declarative memories, promote gist extraction, help the integration of new with old memories, and desaturate the ability to learn. It is often assumed that such beneficial effects are due to the reactivation of neural circuits in sleep to further strengthen the synapses modified during wake or transfer memories to different parts of the brain. A different possibility is that sleep may benefit memory not by further strengthening synapses, but rather by renormalizing synaptic strength to restore cellular homeostasis after net synaptic potentiation in wake. In this way, the sleep-dependent reactivation of neural circuits could result in the competitive down-selection of synapses that are activated infrequently and fit less well with the overall organization of memories. By using computer simulations, we show here that synaptic down-selection is in principle sufficient to explain the beneficial effects of sleep on the consolidation of procedural and declarative memories, on gist extraction, and on the integration of new with old memories, thereby addressing the plasticity-stability dilemma. PMID:24137153

Train hard, sleep well? Perceived training load, sleep quantity and sleep stage distribution in elite level athletes.

PubMed

Knufinke, Melanie; Nieuwenhuys, Arne; Geurts, Sabine A E; Møst, Els I S; Maase, Kamiel; Moen, Maarten H; Coenen, Anton M L; Kompier, Michiel A J

2018-04-01

Sleep is essential for recovery and performance in elite athletes. While it is generally assumed that exercise benefits sleep, high training load may jeopardize sleep and hence limit adequate recovery. To examine this, the current study assessed objective sleep quantity and sleep stage distributions in elite athletes and calculated their association with perceived training load. Mixed-methods. Perceived training load, actigraphy and one-channel EEG recordings were collected among 98 elite athletes during 7 consecutive days of regular training. Actigraphy revealed total sleep durations of 7:50±1:08h, sleep onset latencies of 13±15min, wake after sleep onset of 33±17min and sleep efficiencies of 88±5%. Distribution of sleep stages indicated 51±9% light sleep, 21±8% deep sleep, and 27±7% REM sleep. On average, perceived training load was 5.40±2.50 (scale 1-10), showing large daily variability. Mixed-effects models revealed no alteration in sleep quantity or sleep stage distributions as a function of day-to-day variation in preceding training load (all p's>.05). Results indicate healthy sleep durations, but elevated wake after sleep onset, suggesting a potential need for sleep optimization. Large proportions of deep sleep potentially reflect an elevated recovery need. With sleep quantity and sleep stage distributions remaining irresponsive to variations in perceived training load, it is questionable whether athletes' current sleep provides sufficient recovery after strenuous exercise. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Development of Circadian Sleep Regulation in the Rat: A Longitudinal Study Under Constant Conditions.

PubMed

Frank, Marcos G; Ruby, Norman F; Heller, Horace Craig; Franken, Paul

2017-03-01

To better understand the development of sleep, we characterized the development of circadian rhythms in sleep and wakefulness in the artificially-reared, isolated rat pup using an experimental design that minimized the effects of maternal separation. Neonatal rats were reared in constant conditions (dim red light) while electroencephalographic and electromyographic signals were continuously recorded for up to 3 weeks. This time period spanned the preweaned and weaned ages. The distribution of sleep-wake states was analyzed to estimate the emergence of circadian rhythms. Overt ~24-hour rhythms in time spent awake and asleep appear by postnatal day (P)17. A marked bi-modal sleep-wake pattern was also observed, evidenced by the appearance of a pronounced ~12-hour component in the periodogram over the subsequent 3 days (P17-P21). This suggested the presence of two ~24-hour components consistent with the dual-oscillator concept. During this 3-day time window, waking bouts became longer resulting in a repartition of the duration of intervals without non-rapid-eye movement (NREM) sleep into short (<30 minutes) and longer inter-NREM sleep episodes. These longer waking bouts did not immediately result in an increase in NREM sleep delta (0.5-4.0 Hz) power, which is an index of sleep homeostasis in adult mammals. The sleep homeostatic response did not fully mature until P25. These results demonstrate that the maturation of circadian organization of sleep-wake behavior precedes the expression of mature sleep homeostasis. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Sleep quality, sleep duration and physical activity in obese adolescents: effects of exercise training.

PubMed

Mendelson, M; Borowik, A; Michallet, A-S; Perrin, C; Monneret, D; Faure, P; Levy, P; Pépin, J-L; Wuyam, B; Flore, P

2016-02-01

Decreased sleep duration and altered sleep quality are risk factors for obesity in youth. Structured exercise training has been shown to increase sleep duration and improve sleep quality. This study aimed at evaluating the impact of exercise training for improving sleep duration, sleep quality and physical activity in obese adolescents (OB). Twenty OB (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 healthy-weight adolescents (HW) completed an overnight polysomnography and wore an accelerometer (SenseWear Bodymedia) for 7 days. OB participated in a 12-week supervised exercise-training programme consisting of 180 min of exercise weekly. Exercise training was a combination of aerobic exercise and resistance training. Sleep duration was greater in HW compared with OB (P < 0.05). OB presented higher apnoea-hypopnoea index than HW (P < 0.05). Physical activity (average daily metabolic equivalent of tasks [METs]) by accelerometer was lower in OB (P < 0.05). After exercise training, obese adolescents increased their sleep duration (+64.4 min; effect size: 0.88; P = 0.025) and sleep efficiency (+7.6%; effect size: 0.76; P = 0.028). Physical activity levels were increased in OB as evidenced by increased steps per day and average daily METs (P < 0.05). Improved sleep duration was associated with improved average daily METs (r = 0.48, P = 0.04). The present study confirms altered sleep duration and quality in OB. Exercise training improves sleep duration, sleep quality and physical activity. © 2015 World Obesity.

Sleep, Health and Wellness at Work: A Scoping Review

PubMed Central

Garbarino, Sergio

2017-01-01

Many occupational factors may interfere with sleep. Sleep disturbances can, in turn, endanger the health and safety of workers. This rapid review of the literature identifies the main factors that alter the quantity and quality of sleep, indicates the effects these alterations have on the wellbeing of workers and suggests some health promotion measures. PMID:29113118

Can sleep deprivation studies explain why human adults sleep?

PubMed

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.

Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex.

PubMed

Gerstner, Jason R; Koberstein, John N; Watson, Adam J; Zapero, Nikolai; Risso, Davide; Speed, Terence P; Frank, Marcos G; Peixoto, Lucia

2016-10-25

Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep). In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV). RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1-3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h) do so on average with a time constant that is similar to the time constant for the discharge of sleep need. We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally distinct classes of genes.

Integration of human sleep-wake regulation and circadian rhythmicity

NASA Technical Reports Server (NTRS)

Dijk, Derk-Jan; Lockley, Steven W.

2002-01-01

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

Pharmacological modulation of mitochondrial calcium homeostasis.

PubMed

Arduino, Daniela M; Perocchi, Fabiana

2018-01-10

Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Obesity alters the ovarian glucidic homeostasis disrupting the reproductive outcome of female rats.

PubMed

Bazzano, María Victoria; Paz, Dante Agustín; Elia, Evelin Mariel

2017-04-01

Obesity constitutes a health problem of increasing worldwide prevalence related to many reproductive problems such as infertility, ovulation dysfunction, preterm delivery, fetal growth disorders, etc. The mechanisms linking obesity to these pathologies are not fully understood. Cafeteria diet (CAF) is the animal model used for the study of obesity that more closely reflects western diet habits. Previously we described that CAF induces obesity associated to hyperglycemia, reduced ovarian reserve, presence of follicular cysts and ovulatory impairments. The aim of the present study was to contribute in the understanding of the physiological mechanisms altered as consequence of obesity. For that purpose, female Wistar rats were fed ad libitum with a standard diet (control group) or CAF (Obese group). We found that CAF fed-rats developed obesity, glucose intolerance and insulin resistance. Ovaries from obese rats showed decreased glucose uptake and became insulin resistant, showing decreased ovarian expression of glucotransporter type 4 and insulin receptor gene expression respect to controls. These animals showed an increased follicular nitric oxyde synthase expression that may be responsible for the ovulatory disruptions and for inflammation, a common feature in obesity. Obese rats resulted subfertile and their pups were macrosomic. We conclude that obesity alters the systemic and the ovarian glucidic homeostasis impairing the reproductive outcome. Since macrosomia is a risk factor for metabolic and obstetric disorders in adult life, we suggest that obesity is impacting not only on health and reproduction but it is also impacting on health and reproduction of the offspring. Published by Elsevier Inc.

Altered Sleep Patterns and Physiologic Characteristics in Spontaneous Dwarf Rats

PubMed Central

Andersen, Monica L; Lee, Kil S; Guindalini, Camila; Leite, Waldemarks A; Bignotto, Magda; Tufik, Sergio

2009-01-01

Spontaneous dwarf rats are a useful experimental model for studying various biologic events associated with pituitary dwarfism. Dwarf rats occurred serendipitously in our colony of Wistar rats during experimental breeding. This study aimed to describe the sleep pattern and physiologic characteristics of these rats compared with normal-sized adult rats. Because growth hormone can attenuate the upregulation of ceruloplasmin expression caused by acute inflammation, we also assessed the basal levels of serum ceruloplasmin in these animals. At 90 d of age, body weight and length were significantly lower in dwarf rats relative to normal rats. Dwarves had lower concentrations of serum testosterone and growth hormone, but progesterone was unchanged. Corticosterone levels did not differ between groups. During the light period, the percentage of sleep time recorded and duration of slow-wave sleep did not differ between groups. However, compared with controls, dwarf rats had marked fragmentation of sleep and less paradoxical sleep. During the dark phase, sleep patterns in dwarf rats were within the normal range. Immunoblotting data showed that the levels of ceruloplasmin in serum were lower in dwarf rats. Our findings provide insight into pathologic processes related to growth hormone deficiency. PMID:19712574

Cellular stress induces a protective sleep-like state in C. elegans.

PubMed

Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

2014-10-20

Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex.

PubMed

Mongrain, Valérie; La Spada, Francesco; Curie, Thomas; Franken, Paul

2011-01-01

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), -6, -12, and -18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and -6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven.

Strokes and their relationship with sleep and sleep disorders.

PubMed

Ferre, A; Ribó, M; Rodríguez-Luna, D; Romero, O; Sampol, G; Molina, C A; Álvarez-Sabin, J

2013-03-01

In the current population, strokes are one of the most important causes of morbidity and mortality, to which new risk factors are increasingly being attributed. Of late, there is increased interest in the relationship between sleep disorders and strokes as regards risk and prognosis. This article presents the changes in sleep architecture and brain activity in stroke patients, as well as the interaction between stroke and sleep disorders, including those which may also influence the outcome and recovery from strokes. The different treatments discussed in the literature are also reviewed, as correct treatment of such sleep disorders may not only improve quality of life and reduce after-effects, but can also increase life expectancy. Sleep disorders are becoming increasingly associated with stroke. In addition to being a risk factor, they can also interfere in the outcome and recovery of stroke patients. This article aims to present an exhaustive and current review on strokes and their relationship with sleep alterations and sleep disorders. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Sleep spindle density in narcolepsy.

PubMed

Christensen, Julie Anja Engelhard; Nikolic, Miki; Hvidtfelt, Mathias; Kornum, Birgitte Rahbek; Jennum, Poul

2017-06-01

Patients with narcolepsy type 1 (NT1) show alterations in sleep stage transitions, rapid-eye-movement (REM) and non-REM sleep due to the loss of hypocretinergic signaling. However, the sleep microstructure has not yet been evaluated in these patients. We aimed to evaluate whether the sleep spindle (SS) density is altered in patients with NT1 compared to controls and patients with narcolepsy type 2 (NT2). All-night polysomnographic recordings from 28 NT1 patients, 19 NT2 patients, 20 controls (C) with narcolepsy-like symptoms, but with normal cerebrospinal fluid hypocretin levels and multiple sleep latency tests, and 18 healthy controls (HC) were included. Unspecified, slow, and fast SS were automatically detected, and SS densities were defined as number per minute and were computed across sleep stages and sleep cycles. The between-cycle trends of SS densities in N2 and NREM sleep were evaluated within and between groups. Between-group comparisons in sleep stages revealed no significant differences in any type of SS. Within-group analyses of the SS trends revealed significant decreasing trends for NT1, HC, and C between first and last sleep cycle. Between-group analyses of SS trends between first and last sleep cycle revealed that NT2 differ from NT1 patients in the unspecified SS density in NREM sleep, and from HC in the slow SS density in N2 sleep. SS activity is preserved in NT1, suggesting that the ascending neurons to thalamic activation of SS are not significantly affected by the hypocretinergic system. NT2 patients show an abnormal pattern of SS distribution. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome.

PubMed

Möller-Levet, Carla S; Archer, Simon N; Bucca, Giselda; Laing, Emma E; Slak, Ana; Kabiljo, Renata; Lo, June C Y; Santhi, Nayantara; von Schantz, Malcolm; Smith, Colin P; Dijk, Derk-Jan

2013-03-19

Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

How (and why) the immune system makes us sleep.

PubMed

Imeri, Luca; Opp, Mark R

2009-03-01

Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.

Brain Energetics During the Sleep-Wake Cycle

PubMed Central

DiNuzzo, Mauro; Nedergaard, Maiken

2017-01-01

Brain activity during wakefulness is associated with high metabolic rates that are believed to support information processing and memory encoding. In spite of loss of consciousness, sleep still carries a substantial energy cost. Experimental evidence supports a cerebral metabolic shift taking place during sleep that suppresses aerobic glycolysis, a hallmark of environment-oriented waking behavior and synaptic plasticity. Recent studies reveal that glial astrocytes respond to the reduction of wake-promoting neuromodulators by regulating volume, composition and glymphatic drainage of interstitial fluid. These events are accompanied by changes in neuronal discharge patterns, astrocyte-neuron interactions, synaptic transactions and underlying metabolic features. Internally-generated neuronal activity and network homeostasis are proposed to account for the high sleep-related energy demand. PMID:29024871

Acute stress alters autonomic modulation during sleep in women approaching menopause.

PubMed

de Zambotti, Massimiliano; Sugarbaker, David; Trinder, John; Colrain, Ian M; Baker, Fiona C

2016-04-01

Hot flashes, hormones, and psychosocial factors contribute to insomnia risk in the context of the menopausal transition. Stress is a well-recognized factor implicated in the pathophysiology of insomnia; however the impact of stress on sleep and sleep-related processes in perimenopausal women remains largely unknown. We investigated the effect of an acute experimental stress (impending Trier Social Stress Task in the morning) on pre-sleep measures of cortisol and autonomic arousal in perimenopausal women with and without insomnia that developed in the context of the menopausal transition. In addition, we assessed the macro- and micro-structure of sleep and autonomic functioning during sleep. Following adaptation to the laboratory, twenty two women with (age: 50.4 ± 3.2 years) and eighteen women without (age: 48.5 ± 2.3 years) insomnia had two randomized in-lab overnight recordings: baseline and stress nights. Anticipation of the task resulted in higher pre-sleep salivary cortisol levels and perceived tension, faster heart rate and lower vagal activity, based on heart rate variability measures, in both groups of women. The effect of the stress manipulation on the autonomic nervous system extended into the first 4 h of the night in both groups. However, vagal tone recovered 4-6 h into the stress night in controls but not in the insomnia group. Sleep macrostructure was largely unaltered by the stress, apart from a delayed latency to REM sleep in both groups. Quantitative analysis of non-rapid eye movement sleep microstructure revealed greater electroencephalographic (EEG) power in the beta1 range (15-≤23 Hz), reflecting greater EEG arousal during sleep, on the stress night compared to baseline, in the insomnia group. Hot flash frequency remained similar on both nights for both groups. These results show that pre-sleep stress impacts autonomic nervous system functioning before and during sleep in perimenopausal women with and without insomnia. Findings also indicate

Sleep architecture and sleep apnea in patients with Cushing's disease.

PubMed

Shipley, J E; Schteingart, D E; Tandon, R; Starkman, M N

1992-12-01

Patients with Cushing's syndrome (CS) frequently have sleep complaints. We evaluated sleep polysomnographically in 22 patients, including 17 with pituitary-ACTH-dependent Cushing's disease (CD) and five with CS from an adrenal tumor. Data were compared to healthy controls of comparable age. Seven patients (32%) demonstrated at least mild sleep apnea (> or = 9.4 events/hour), and four of 22 (18%) had > or = 17.5 events/hour. The apneic CD and CS patients had a trend for a greater complaint of excessive daytime sleepiness. Both apneic and nonapneic groups had considerable snoring and obesity. The electroencephalographic (EEG) sleep of nonapneic patients was compared to that of normal subjects. Nonapneic CD patients differed strikingly from healthy volunteers in sleep continuity and architecture, demonstrating lighter, fragmented sleep. Rapid eye movement (REM) sleep in CD patients bore many similarities to the sleep of patients with major depression, with REM latency being significantly shortened and REM density significantly increased. Continued examination of EEG sleep in CD patients may shed light on similarities in pathophysiology between CD and major depression, disorders which are characterized by both a dysfunction of the hypothalamic-pituitary-adrenal axis and alterations in mood.

Arterial alterations in severely obese children with obstructive sleep apnoea.

PubMed

Dubern, Beatrice; Aggoun, Yacine; Boulé, Michèle; Fauroux, Brigitte; Bonnet, Damien; Tounian, Patrick

2010-05-03

Obstructive sleep apnoea (OSA) in obese adults is associated with cardiovascular disease independently of obesity. Vascular alterations exist in children with obesity and may constitute the first stage in the development of adulthood cardiovascular disease. To investigate the relationship between OSA and early arterial alterations in obese children. Cross-sectional study of a prospective cohort. A total of 51 children with severe obesity managed at a teaching hospital outpatient clinic. Polysomnography was performed. We measured the intima-media thickness and incremental elastic modulus (Einc) to assess the mechanical characteristics of the common carotid artery. Arterial endothelial function was evaluated by measuring flow-mediated dilation and glyceryl trinitrate-mediated dilation (GTNMD) of the brachial artery. A total of 24 (47%) children had a desaturation index (DI) >10/h and 7 (14%) had a respiratory event index >10/h. DI >10/h was associated with significantly higher values of Einc (4.0 + or - 0.5 vs. 2.4 + or - 0.4 mm Hg(-1) x 10(3), p=0.003) and GTNMD (18.0 + or - 1.1 vs. 14.1 + or - 1.0 %, p=0.02) after adjustment for age, sex, body mass index, fasting insulin, and leptin. In the univariate analysis, GTNMD correlated positively with DI (r=0.14, p=0.02) after adjustment for age, sex, fasting insulin and leptin. By multivariate analysis with BMI as an additional independent variable, both GTNMD and Einc correlated significantly with DI (beta=0.4, p=0.02 and beta=0.27, p=0.04, respectively). OSA in children is associated with arterial alterations independently from obesity. The increased vasodilation in response to glyceryl trinitrate reflects pre-existing vasoconstriction probably induced by intermittent hypoxia. OSA should be detected early in children with severe obesity.

Sleep-inducing factors.

PubMed

García-García, Fabio; Acosta-Peña, Eva; Venebra-Muñoz, Arturo; Murillo-Rodríguez, Eric

2009-08-01

Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide.

Sleep and respiration in microgravity

NASA Technical Reports Server (NTRS)

Prisk, G. K.

1998-01-01

Sleep studies conducted during the STS-90 Neurolab mission are explored. The relationship between sleep, melatonin, and circadian phase is reviewed. The study contained both sleep and awake components. The objectives of the sleep component were to test five hypotheses: that circadian rhythms of core body temperature and urinary melatonin are synchronized to required sleep-wake schedules, that spaceflight results in substantial disruption of sleep, that the pattern of chest and abdominal wall motion alters during the different sleep stages in microgravity, that arterial oxygen saturation is reduced during some stages of sleep in microgravity, and that pre-sleep administration of melatonin during microgravity results in improved sleep quality. The awake component tested three hypotheses: that ventilatory response to carbon dioxide is increased during exposure to microgravity and that this exacerbates sleep disruption, that ventilatory response to hypoxia is increased by exposure to microgravity, and that the improved sleep resulting from the pre-sleep administration of melatonin enhances next day cognition when compared to placebo.

Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

PubMed

Janer, Gemma; Navarro, Juan Carlos; Porte, Cinta

2007-09-01

Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARgamma receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

How (and why) the immune system makes us sleep

PubMed Central

Imeri, Luca; Opp, Mark R.

2010-01-01

Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value. PMID:19209176

ALTERATIONS OF FE HOMEOSTASIS IN RAT CARDIOVASCULAR DISEASE MODELS AND ITS CONTRIBUTION TO CARDIOPULMONARY TOXICITY

EPA Science Inventory

Introduction: Fe homeostasis can be disrupted in human cardiovascular diseases (CVD). We addressed how dysregulation of Fe homeostasis affected the pulmonary inflammation/oxidative stress response and disease progression after exposure to Libby amphibole (LA), an asbestifonn mine...

Circadian Rhythms, Sleep Deprivation, and Human Performance

PubMed Central

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

Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miletich, R.S.

The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period,more » phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.« less

The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility.

PubMed

Escalante, Nichole K; Lemire, Paul; Cruz Tleugabulova, Mayra; Prescott, David; Mortha, Arthur; Streutker, Catherine J; Girardin, Stephen E; Philpott, Dana J; Mallevaey, Thierry

2016-12-12

The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1 -/- mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research. © 2016 Escalante et al.

Neutral buoyancy and sleep-deprived serum factors alter expression of cytokines regulating osteogenesis

NASA Astrophysics Data System (ADS)

Gorczynski, Reginald M.; Gorczynski, Christopher P.; Gorczynski, Laura Y.; Hu, Jiang; Lu, Jin; Manuel, Justin; Lee, Lydia

2005-05-01

We examined expression of genes associated with cytokine production, and genes implicated in regulating bone metabolism, in bone stromal and osteoblast cells incubated under standard ground conditions and under conditions of neutral buoyancy, and in the presence/absence of serum from normal or sleep-deprived mice. We observed a clear interaction between these two conditions (exposure to neutral buoyancy and serum stimulation) in promoting enhanced osteoclastogenesis. Both conditions independently altered expression of a number of cytokines implicated in the regulation of bone metabolism. However, using stromal cells from IL-1 and TNF α cytokine r KO mice, we concluded that the increased bone loss under microgravity conditions was not primarily cytokine mediated.

Prion protein modulates glucose homeostasis by altering intracellular iron.

PubMed

Ashok, Ajay; Singh, Neena

2018-04-26

The prion protein (PrP C ), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP -/- ) were significantly lower than wild type (PrP +/+ ) controls. Silencing of PrP C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP C -dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP +/+ but not PrP -/- mice, indicating PrP C -mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP +/+ relative to PrP -/- mice, suggesting that PrP C -mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer's disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.

Predictability of Sleep in Patients with Insomnia

PubMed Central

Vallières, Annie; Ivers, Hans; Beaulieu-Bonneau, Simon; Morin, Charles M.

2011-01-01

Study Objectives: To evaluate whether the night-to-night variability in insomnia follows specific predictable patterns and to characterize sleep patterns using objective sleep and clinical variables. Design: Prospective observational study. Setting: University-affiliated sleep disorders center. Participants: 146 participants suffering from chronic and primary insomnia. Measurements and Results: Daily sleep diaries were completed for an average of 48 days and self-reported questionnaires once. Three nights were spent in the sleep laboratory for polysomnographic (PSG) assessment. Sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time were derived from sleep diaries and PSG. Time-series diary data were used to compute conditional probabilities of having an insomnia night after 1, 2, or 3 consecutive insomnia night(s). Conditional probabilities were submitted to a k-means cluster analysis. A 3-cluster solution was retained. One cluster included 38 participants exhibiting an unpredictable insomnia pattern. Another included 30 participants with a low and decreasing probability to have an insomnia night. The last cluster included 49 participants exhibiting a high probability to have insomnia every night. Clusters differed on age, insomnia severity, and mental fatigue, and on subjective sleep variables, but not on PSG sleep variables. Conclusion: These findings replicate our previous study and provide additional evidence that unpredictability is a less prevalent feature of insomnia than suggested previously in the literature. The presence of the 3 clusters is discussed in term of sleep perception and sleep homeostasis dysregulation. Citation: Vallières A; Ivers H; Beaulieu-Bonneau S; Morin CM. Predictability of sleep in patients with insomnia. SLEEP 2011;34(5):609-617. PMID:21532954

Sleeping on the rubber-hand illusion: Memory reactivation during sleep facilitates multisensory recalibration.

PubMed

Honma, Motoyasu; Plass, John; Brang, David; Florczak, Susan M; Grabowecky, Marcia; Paller, Ken A

2016-01-01

Plasticity is essential in body perception so that physical changes in the body can be accommodated and assimilated. Multisensory integration of visual, auditory, tactile, and proprioceptive signals contributes both to conscious perception of the body's current state and to associated learning. However, much is unknown about how novel information is assimilated into body perception networks in the brain. Sleep-based consolidation can facilitate various types of learning via the reactivation of networks involved in prior encoding or through synaptic down-scaling. Sleep may likewise contribute to perceptual learning of bodily information by providing an optimal time for multisensory recalibration. Here we used methods for targeted memory reactivation (TMR) during slow-wave sleep to examine the influence of sleep-based reactivation of experimentally induced alterations in body perception. The rubber-hand illusion was induced with concomitant auditory stimulation in 24 healthy participants on 3 consecutive days. While each participant was sleeping in his or her own bed during intervening nights, electrophysiological detection of slow-wave sleep prompted covert stimulation with either the sound heard during illusion induction, a counterbalanced novel sound, or neither. TMR systematically enhanced feelings of bodily ownership after subsequent inductions of the rubber-hand illusion. TMR also enhanced spatial recalibration of perceived hand location in the direction of the rubber hand. This evidence for a sleep-based facilitation of a body-perception illusion demonstrates that the spatial recalibration of multisensory signals can be altered overnight to stabilize new learning of bodily representations. Sleep-based memory processing may thus constitute a fundamental component of body-image plasticity.

Sleep-related intermittent hypoxemia and glucose intolerance: a community-based study.

PubMed

Tanno, Sakurako; Tanigawa, Takeshi; Saito, Isao; Nishida, Wataru; Maruyama, Koutatsu; Eguchi, Eri; Sakurai, Susumu; Osawa, Haruhiko; Punjabi, Naresh M

2014-10-01

Intermittent hypoxemia is a fundamental pathophysiological consequence of sleep-disordered breathing and may alter glucose metabolism. To characterize the association between sleep-related intermittent hypoxemia and glucose metabolism, overnight pulse-oximetry and an oral glucose tolerance test were completed in a cohort of middle-aged and older Japanese adults. The study sample consisted of 1836 community-dwelling Japanese (age, 30-79 years; women, 65.5%; mean body mass index, 23.1 kg/m(2)). The oxygen desaturation index (ODI) was quantified during sleep using a ≥3% oxygen desaturation threshold and categorized as normal (<5.0 events/h), mild (5.0-15.0 events/h), and moderate to severe (≥15.0 events/h). The independent associations between the ODI and the prevalence of impaired fasting glucose, impaired glucose tolerance, diabetes, and two metrics of insulin resistance [homeostasis model assessment index for insulin resistance (HOMA-IR) and Matsuda index] were examined. Compared with subjects with an ODI < 5 events/h, the adjusted odds ratio for prevalent impaired fasting glucose, glucose intolerance, and diabetes for subjects with an ODI ≥15.0 events/h were 1.27 (95% confidence interval, 0.72-2.23), 1.69 (1.03-2.76), and 1.28 (0.59-2.79), respectively. Both HOMA-IR and Matsuda index were significantly associated with the severity of sleep-related intermittent hypoxemia as assessed by the ODI (P for trend = 0.03 and 0.007, respectively). Among middle-aged and older Japanese adults, sleep-related intermittent hypoxemia is associated with glucose intolerance and insulin resistance, and may contribute to the development of type 2 diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

Sleep in elite athletes and nutritional interventions to enhance sleep.

PubMed

Halson, Shona L

2014-05-01

Sleep has numerous important physiological and cognitive functions that may be particularly important to elite athletes. Recent evidence, as well as anecdotal information, suggests that athletes may experience a reduced quality and/or quantity of sleep. Sleep deprivation can have significant effects on athletic performance, especially submaximal, prolonged exercise. Compromised sleep may also influence learning, memory, cognition, pain perception, immunity and inflammation. Furthermore, changes in glucose metabolism and neuroendocrine function as a result of chronic, partial sleep deprivation may result in alterations in carbohydrate metabolism, appetite, food intake and protein synthesis. These factors can ultimately have a negative influence on an athlete's nutritional, metabolic and endocrine status and hence potentially reduce athletic performance. Research has identified a number of neurotransmitters associated with the sleep-wake cycle. These include serotonin, gamma-aminobutyric acid, orexin, melanin-concentrating hormone, cholinergic, galanin, noradrenaline, and histamine. Therefore, nutritional interventions that may act on these neurotransmitters in the brain may also influence sleep. Carbohydrate, tryptophan, valerian, melatonin and other nutritional interventions have been investigated as possible sleep inducers and represent promising potential interventions. In this review, the factors influencing sleep quality and quantity in athletic populations are examined and the potential impact of nutritional interventions is considered. While there is some research investigating the effects of nutritional interventions on sleep, future research may highlight the importance of nutritional and dietary interventions to enhance sleep.

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit.

PubMed

Liu, Sha; Liu, Qili; Tabuchi, Masashi; Wu, Mark N

2016-06-02

Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca(2+) levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep Physiology, Abnormal States, and Therapeutic Interventions

PubMed Central

Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

2012-01-01

Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

PubMed Central

Qinna, Nidal A; Badwan, Adnan A

2015-01-01

Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents

Short-term total sleep deprivation alters delay-conditioned memory in the rat.

PubMed

Tripathi, Shweta; Jha, Sushil K

2016-06-01

Short-term sleep deprivation soon after training may impair memory consolidation. Also, a particular sleep stage or its components increase after learning some tasks, such as negative and positive reinforcement tasks, avoidance tasks, and spatial learning tasks, and so forth. It suggests that discrete memory types may require specific sleep stage or its components for their optimal processing. The classical conditioning paradigms are widely used to study learning and memory but the role of sleep in a complex conditioned learning is unclear. Here, we have investigated the effects of short-term sleep deprivation on the consolidation of delay-conditioned memory and the changes in sleep architecture after conditioning. Rats were trained for the delay-conditioned task (for conditioning, house-light [conditioned stimulus] was paired with fruit juice [unconditioned stimulus]). Animals were divided into 3 groups: (a) sleep deprived (SD); (b) nonsleep deprived (NSD); and (c) stress control (SC) groups. Two-way ANOVA revealed a significant interaction between groups and days (training and testing) during the conditioned stimulus-unconditioned stimulus presentation. Further, Tukey post hoc comparison revealed that the NSD and SC animals exhibited significant increase in performances during testing. The SD animals, however, performed significantly less during testing. Further, we observed that wakefulness and NREM sleep did not change after training and testing. Interestingly, REM sleep increased significantly on both days compared to baseline more specifically during the initial 4-hr time window after conditioning. Our results suggest that the consolidation of delay-conditioned memory is sleep-dependent and requires augmented REM sleep during an explicit time window soon after training. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

PubMed

Llorens, Franc; Thüne, Katrin; Sikorska, Beata; Schmitz, Matthias; Tahir, Waqas; Fernández-Borges, Natalia; Cramm, Maria; Gotzmann, Nadine; Carmona, Margarita; Streichenberger, Nathalie; Michel, Uwe; Zafar, Saima; Schuetz, Anna-Lena; Rajput, Ashish; Andréoletti, Olivier; Bonn, Stefan; Fischer, Andre; Liberski, Pawel P; Torres, Juan Maria; Ferrer, Isidre; Zerr, Inga

2017-04-27

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP Sc ). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca 2+ ) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca 2+ responsive genes in sCJD brain tissue, accompanied by two Ca 2+ -dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrP Sc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca 2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention.

Alterations in Skeletal Muscle Cell Homeostasis in a Mouse Model of Cigarette Smoke Exposure

PubMed Central

Caron, Marc-André; Morissette, Mathieu C.; Thériault, Marie-Eve; Nikota, Jake K.; Stämpfli, Martin R.; Debigaré, Richard

2013-01-01

Background Skeletal muscle dysfunction is common in chronic obstructive pulmonary disease (COPD), a disease mainly caused by chronic cigarette use. An important proportion of patients with COPD have decreased muscle mass, suggesting that chronic cigarette smoke exposure may interfere with skeletal muscle cellular equilibrium. Therefore, the main objective of this study was to investigate the kinetic of the effects that cigarette smoke exposure has on skeletal muscle cell signaling involved in protein homeostasis and to assess the reversibility of these effects. Methods A mouse model of cigarette smoke exposure was used to assess skeletal muscle changes. BALB/c mice were exposed to cigarette smoke or room air for 8 weeks, 24 weeks or 24 weeks followed by 60 days of cessation. The gastrocnemius and soleus muscles were collected and the activation state of key mediators involved in protein synthesis and degradation was assessed. Results Gastrocnemius and soleus were smaller in mice exposed to cigarette smoke for 8 and 24 weeks compared to room air exposed animals. Pro-degradation proteins were induced at the mRNA level after 8 and 24 weeks. Twenty-four weeks of cigarette smoke exposure induced pro-degradation proteins and reduced Akt phosphorylation and glycogen synthase kinase-3β quantity. A 60-day smoking cessation period reversed the cell signaling alterations induced by cigarette smoke exposure. Conclusions Repeated cigarette smoke exposure induces reversible muscle signaling alterations that are dependent on the duration of the cigarette smoke exposure. These results highlights a beneficial aspect associated with smoking cessation. PMID:23799102

Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice.

PubMed

Albu, Stefana; Romanowski, Christoph P N; Letizia Curzi, M; Jakubcakova, Vladimira; Flachskamm, Cornelia; Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Schmidt, Ulrike; Rein, Theo; Holsboer, Florian; Hausch, Felix; Paez-Pereda, Marcelo; Kimura, Mayumi

2014-04-01

FK506-binding protein 51 (FKBP51) is a co-chaperone of the glucocorticoid receptor, functionally linked to its activity via an ultra-short negative feedback loop. Thus, FKBP51 plays an important regulatory role in the hypothalamic-pituitary-adrenocortical (HPA) axis necessary for stress adaptation and recovery. Previous investigations illustrated that HPA functionality is influenced by polymorphisms in the gene encoding FKBP51, which are associated with both increased protein levels and depressive episodes. Because FKBP51 is a key molecule in stress responses, we hypothesized that its deletion impacts sleep. To study FKBP51-involved changes in sleep, polysomnograms of FKBP51 knockout (KO) mice and wild-type (WT) littermates were compared at baseline and in the recovery phase after 6-h sleep deprivation (SD) and 1-h restraint stress (RS). Using another set of animals, the 24-h profiles of hippocampal free corticosterone levels were also determined. The most dominant effect of FKBP51 deletion appeared as increased nocturnal wake, where the bout length was significantly extended while non-rapid eye movement sleep (NREMS) and rapid eye movement sleep were rather suppressed. After both SD and RS, FKBP51KO mice exhibited less recovery or rebound sleep than WTs, although slow-wave activity during NREMS was higher in KOs, particularly after SD. Sleep compositions of KOs were nearly opposite to sleep profiles observed in human depression. This might result from lower levels of free corticosterone in FKBP51KO mice, confirming reduced HPA reactivity. The results indicate that an FKBP51 deletion yields a pro-resilience sleep phenotype. FKBP51 could therefore be a therapeutic target for stress-induced mood and sleep disorders. © 2013 European Sleep Research Society.

A Novel BHLHE41 Variant is Associated with Short Sleep and Resistance to Sleep Deprivation in Humans

PubMed Central

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.

2014-01-01

Study Objectives: 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. Design: Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. Results: 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. Conclusions: 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. Citation: 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. PMID:25083013

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

PubMed

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.

Altering Adolescents' Pre-Bedtime Phone Use to Achieve Better Sleep Health.

PubMed

Bartel, K; Scheeren, R; Gradisar, M

2018-01-09

Mobile phone use is often blamed for adolescent sleeping difficulties in the popular and scientific literature, with correlations observed between adolescents' mobile phone use and their bedtime. We aimed to obtain experimental evidence to support these causal claims. A within-subjects experiment (baseline, intervention) was conducted in adolescents' homes, to determine the effect of restricting adolescents' pre-bed mobile phone use on school night sleep habits. Following a baseline week, adolescents were given individualized phone stop times, 1 hour before bed for one school week. An online sleep diary was used to monitor bedtime, lights out time, sleep latency and total sleep. Sixty three adolescents (age range 14-18, M = 16.3, SD = 0.93yrs; 17%male) provided data. During one week of phone restriction, adolescents stopped using their phones earlier (80 min, p < .001), turned their lights off earlier (17 min, p = .01), and slept longer (21 min, p = .01). Participant recruitment was low (26%), indicating many adolescents lack motivation to negotiate changes to their evening phone use. Overall, there are potential benefits of restricted mobile phone use during the pre-sleep period, yet, future research is needed to identify non-technological interventions to increase adherence to phone restriction (e.g., motivational interviewing) or otherwise decrease pre-sleep arousal (e.g., cognitive strategies).

Experiment M133. Sleep monitoring on Skylab

NASA Technical Reports Server (NTRS)

Frost, J. D., Jr.; Shumate, W. H.; Salamy, J. G.; Booher, C. R.

1977-01-01

Subjective sleep logs during 59-day and 84-day Skylab missions indicate that prolonged space flight, with its accompanying weightless state, is not directly associated with major adverse changes in sleep characteristics. Observed alterations in sleep patterns were not of sufficient magnitude to result in significant degradation of performance capacity.

A role for cryptochromes in sleep regulation.

PubMed

Wisor, Jonathan P; O'Hara, Bruce F; Terao, Akira; Selby, Chris P; Kilduff, Thomas S; Sancar, Aziz; Edgar, Dale M; Franken, Paul

2002-12-20

The cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the generation of circadian rhythms, as mice lacking both of these genes (cry1,2-/-) lack circadian rhythms. We studied sleep in cry1,2-/- mice under baseline conditions as well as under conditions of constant darkness and enforced wakefulness to determine whether cryptochromes influence sleep regulatory processes. Under all three conditions, cry1,2-/- mice exhibit the hallmarks of high non-REM sleep (NREMS) drive (i.e., increases in NREMS time, NREMS consolidation, and EEG delta power during NREMS). This unexpected phenotype was associated with elevated brain mRNA levels of period 1 and 2 (per1,2), and albumin d-binding protein (dbp), which are known to be transcriptionally inhibited by CRY1,2. To further examine the relationship between circadian genes and sleep homeostasis, we examined wild type mice and rats following sleep deprivation and found increased levels of per1,2 mRNA and decreased levels of dbp mRNA specifically in the cerebral cortex; these changes subsided with recovery sleep. The expression of per3, cry1,2, clock, npas2, bmal1, and casein-kinase-1epsilon did not change with sleep deprivation. These results indicate that mice lacking cryptochromes are not simply a genetic model of circadian arrhythmicity in rodents and functionally implicate cryptochromes in the homeostatic regulation of sleep.

In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice.

PubMed

Curie, Thomas; Maret, Stephanie; Emmenegger, Yann; Franken, Paul

2015-09-01

That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice. In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery. Mouse sleep-recording facility. Per2::Luciferase knock-in mice. N/A. Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls. Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health. © 2015 Associated Professional Sleep Societies, LLC.

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

PubMed

Jernigan, Nikki L; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-01-01

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca 2+ homeostasis, Ca 2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.

Sleep and Plasticity in Schizophrenia

PubMed Central

Sprecher, Kate E.; Ferrarelli, Fabio

2016-01-01

Schizophrenia is a devastating mental illness with a worldwide prevalence of approximately 1 %. Although the clinical features of the disorder were described over one hundred years ago, its neurobiology is still largely elusive despite several decades of research. Schizophrenia is associated with marked sleep disturbances and memory impairment. Above and beyond altered sleep architecture, sleep rhythms including slow waves and spindles are disrupted in schizophrenia. In the healthy brain, these rhythms reflect and participate in plastic processes during sleep. This chapter discusses evidence that schizophrenia patients exhibit dysfunction of sleep-mediated plasticity on a behavioral, cellular, and molecular level and offers suggestions on how the study of sleeping brain activity can shed light on the pathophysiological mechanisms of the disorder. PMID:25608723

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

PubMed

Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

2017-01-01

Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity

PubMed Central

Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

2017-01-01

Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

Analysis of the QTL for sleep homeostasis in mice: Homer1a is a likely candidate.

PubMed

Mackiewicz, M; Paigen, B; Naidoo, N; Pack, A I

2008-03-14

Electroencephalographic oscillations in the frequency range of 0.5-4 Hz, characteristic of slow-wave sleep (SWS), are often referred to as the delta oscillation or delta power. Delta power reflects sleep intensity and correlates with the homeostatic response to sleep loss. A published survey of inbred strains of mice demonstrated that the time course of accumulation of delta power varied among inbred strains, and the segregation of the rebound of delta power in BxD recombinant inbred strains identified a genomic region on chromosome 13 referred to as the delta power in SWS (or Dps1). The quantitative trait locus (QTL) contains genes that modify the accumulation of delta power after sleep deprivation. Here, we narrow the QTL using interval-specific haplotype analysis and present a comprehensive annotation of the remaining genes in the Dps1 region with sequence comparisons to identify polymorphisms within the coding and regulatory regions. We established the expression pattern of selected genes located in the Dps1 interval in sleep and wakefulness in B6 and D2 parental strains. Taken together, these steps reduced the number of potential candidate genes that may underlie the accumulation of delta power after sleep deprivation and explain the Dps1 QTL. The strongest candidate gene is Homer1a, which is supported by expression differences between sleep and wakefulness and the SNP polymorphism in the upstream regulatory regions.

Novel word learning in older adults: A role for sleep?

PubMed Central

Kurdziel, Laura B. F.; Mantua, Janna; Spencer, Rebecca M. C.

2016-01-01

Sleep is an offline period during which newly acquired semantic information is transformed into longer-lasting memories. Language acquisition, which requires new word learning and semantic integration, is preferentially benefitted by a period of sleep in children and young adults. Specific features of sleep (e.g., sleep stage characteristics) have been associated with enhanced language acquisition and generalization. However, with increasing age, even in healthy individuals, sleep quality and quantity decrease. Simultaneously, deficits in word retrieval and new word learning emerge. It is unknown whether age-related alterations in language ability are linked with alterations in sleep. The goal of this review is to examine changes in language learning and sleep across the lifespan. We consider how sleep detriments that occur with aging could affect abilities to learn novel words and semantic generalization and propose hypotheses to motivate future research in this area. PMID:27291336

Endocannabinoid Signaling Regulates Sleep Stability

PubMed Central

Pava, Matthew J.; Makriyannis, Alexandros; Lovinger, David M.

2016-01-01

The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM bouts (NREM stability). Similarly, direct activation of type 1 cannabinoid (CB1) receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis. PMID:27031992

Endocannabinoid Signaling Regulates Sleep Stability.

PubMed

Pava, Matthew J; Makriyannis, Alexandros; Lovinger, David M

2016-01-01

The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM bouts (NREM stability). Similarly, direct activation of type 1 cannabinoid (CB1) receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.

SLEEP AND THE FUNCTIONAL CONNECTOME

PubMed Central

Picchioni, Dante; Duyn, Jeff H.; Horovitz, Silvina G.

2013-01-01

Sleep and the functional connectome are research areas with considerable overlap. Neuroimaging studies of sleep based on EEG-PET and EEG-fMRI are revealing the brain networks that support sleep, as well as networks that may support the roles and processes attributed to sleep. For example, phenomena such as arousal and consciousness are substantially modulated during sleep, and one would expect this modulation to be reflected in altered network activity. In addition, recent work suggests that sleep also has a number of adaptive functions that support waking activity. Thus the study of sleep may elucidate the circuits and processes that support waking function and complement information obtained from fMRI during waking conditions. In this review, we will discuss examples of this for memory, arousal, and consciousness after providing a brief background on sleep and on studying it with fMRI. PMID:23707592

Epidemiological analysis of structural alterations of the nasal cavity associated with obstructive sleep apnea syndrome (OSA).

PubMed

Mekhitarian Neto, Levon; Fava, Antonio Sérgio; Lopes, Hugo Canhete; Stamm, Aldo

2005-01-01

The objective of this paper is to demonstrate that structural alterations of the nasal cavity, e.g. septal deviation and conchal hypertrophy have high incidence in patients with sleep apnea and hypopnea syndrome and must be addressed with associated specific procedures of the syndrome. Clinical retrospective. A retrospective study of 200 patients was performed, with 196 male and 4 female, attended at the otorhinolaryngology ambulatory of Hospital Prof. Edmundo Vasconcelos and Unidade Paulista de Otorrinolaringologia, all of them subjected to polysomnography, otorhinolaryngological physical exam, endoscopy exam, and surgical treatment with nasal and pharyngeal procedures. All of them were subjected to pharyngeal procedure: uvulopalatopharyngoplasty or uvulopalatoplasty and nose procedure: 176 septoplasty with partial turbinectomy (88%) and 24 isolated turbinectomy, with satisfactory results. We can see that structural alterations of the nasal cavity have high incidence in patients with OSA.

[Sleep apnea and heart failure: pathophysiology, diagnosis and therapy].

PubMed

Monda, Cinzia; Scala, Oriana; Paolillo, Stefania; Savarese, Gianluigi; Cecere, Milena; D'Amore, Carmen; Parente, Antonio; Musella, Francesca; Mosca, Susanna; Filardi, Pasquale Perrone

2010-11-01

Sleep apnea, defined as a pathologic pause in breathing during sleep >10 s, promotes the progression of chronic heart failure and may be a predictor of poor prognosis. It causes, in fact, several mechanical, hemodynamic, chemical and inflammatory changes that negatively compromise cardiovascular homeostasis of heart failure patients. Sleep apnea is recognized as sleep apnea syndrome when specific symptoms, such as sleepiness and headache during the daytime and snoring, are present and is diagnosed with an overnight test called polysomnography. There are two different forms of sleep apnea, central and obstructive. Breathing is interrupted by the loss of respiratory drive and the lack of respiratory effort in the central form, which affects about 40-60% of heart failure patients. In obstructive sleep apnea, breathing stops when throat muscles relax, despite respiratory effort. This form affects about 3% of the general population, while it is present in at least 30% of heart failure patients. The diagnosis of sleep disorders in heart failure becomes very important to help patients adopting lifestyle changes and starting specific therapies to improve quality of life and retard the progression of chronic heart failure.

Implications of Sleep Restriction and Recovery on Metabolic Outcomes

PubMed Central

Killick, Roo; Banks, Siobhan

2012-01-01

Context: Alongside the growing epidemics of obesity and diabetes mellitus, chronic partial sleep restriction is also increasingly common in modern society, and the metabolic implications of this have not been fully illustrated as yet. Whether recovery sleep is sufficient to offset these detriments is an area of ongoing research. Objective: This review seeks to summarize the relevant epidemiological and experimental data in the areas of altered metabolic consequences of both shortened sleep and subsequent recovery sleep. Data Acquisition: The medical literature from 1970 to March 2012 was reviewed for key articles. Data Synthesis: Epidemiological studies suggest associations between shortened sleep and future obesity and diabetes. Experimental data thus far show a probable link between shortened sleep and altered glucose metabolism as well as appetite dysregulation. Conclusion: Sleep often seems undervalued in modern society, but this may have widespread metabolic consequences as described in this review. Acute sleep loss is often unavoidable, but chronic sleep restriction ideally should not be. Understanding the implications of both sleep restriction and recovery on metabolic outcomes will guide public health policy and allow clinical recommendations to be prescribed. PMID:22996147

Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.

PubMed

Song, Xiaopeng; Roy, Bhaswati; Kang, Daniel W; Aysola, Ravi S; Macey, Paul M; Woo, Mary A; Yan-Go, Frisca L; Harper, Ronald M; Kumar, Rajesh

2018-05-10

Brain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting-state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting-state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores. We acquired resting-state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0-Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender). Obstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para-hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic-striatal-cortical FC in OSA showed relationships with behavioral and neuropsychological variables. The compromised hippocampal-cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate-cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Software thresholds alter the bias of actigraphy for monitoring sleep in team-sport athletes.

PubMed

Fuller, Kate L; Juliff, Laura; Gore, Christopher J; Peiffer, Jeremiah J; Halson, Shona L

2017-08-01

Actical ® actigraphy is commonly used to monitor athlete sleep. The proprietary software, called Actiware ® , processes data with three different sleep-wake thresholds (Low, Medium or High), but there is no standardisation regarding their use. The purpose of this study was to examine validity and bias of the sleep-wake thresholds for processing Actical ® sleep data in team sport athletes. Validation study comparing actigraph against accepted gold standard polysomnography (PSG). Sixty seven nights of sleep were recorded simultaneously with polysomnography and Actical ® devices. Individual night data was compared across five sleep measures for each sleep-wake threshold using Actiware ® software. Accuracy of each sleep-wake threshold compared with PSG was evaluated from mean bias with 95% confidence limits, Pearson moment-product correlation and associated standard error of estimate. The Medium threshold generated the smallest mean bias compared with polysomnography for total sleep time (8.5min), sleep efficiency (1.8%) and wake after sleep onset (-4.1min); whereas the Low threshold had the smallest bias (7.5min) for wake bouts. Bias in sleep onset latency was the same across thresholds (-9.5min). The standard error of the estimate was similar across all thresholds; total sleep time ∼25min, sleep efficiency ∼4.5%, wake after sleep onset ∼21min, and wake bouts ∼8 counts. Sleep parameters measured by the Actical ® device are greatly influenced by the sleep-wake threshold applied. In the present study the Medium threshold produced the smallest bias for most parameters compared with PSG. Given the magnitude of measurement variability, confidence limits should be employed when interpreting changes in sleep parameters. Copyright © 2017 Sports Medicine Australia. All rights reserved.

Sleep Loss Reduces the DNA-Binding of BMAL1, CLOCK, and NPAS2 to Specific Clock Genes in the Mouse Cerebral Cortex

PubMed Central

Curie, Thomas; Franken, Paul

2011-01-01

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), −6, −12, and −18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and −6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven. PMID:22039518

Regional Reductions in Sleep Electroencephalography Power in Obstructive Sleep Apnea: A High-Density EEG Study

PubMed Central

Jones, Stephanie G.; Riedner, Brady A.; Smith, Richard F.; Ferrarelli, Fabio; Tononi, Giulio; Davidson, Richard J.; Benca, Ruth M.

2014-01-01

Study Objectives: Obstructive sleep apnea (OSA) is associated with significant alterations in neuronal integrity resulting from either hypoxemia and/or sleep loss. A large body of imaging research supports reductions in gray matter volume, alterations in white matter integrity and resting state activity, and functional abnormalities in response to cognitive challenge in various brain regions in patients with OSA. In this study, we used high-density electroencephalography (hdEEG), a functional imaging tool that could potentially be used during routine clinical care, to examine the regional distribution of neural activity in a non-clinical sample of untreated men and women with moderate/severe OSA. Design: Sleep was recorded with 256-channel EEG in relatively healthy subjects with apnea-hypopnea index (AHI) > 10, as well as age-, sex-, and body mass index-matched controls selected from a research population initially recruited for a study on sleep and meditation. Setting: Sleep laboratory. Patients or Participants: Nine subjects with AHI > 10 and nine matched controls. Interventions: N/A. Measurements and Results: Topographic analysis of hdEEG data revealed a broadband reduction in EEG power in a circumscribed region overlying the parietal cortex in OSA subjects. This parietal reduction in neural activity was present, to some extent, across all frequency bands in all stages and episodes of nonrapid eye movement sleep. Conclusion: This investigation suggests that regional deficits in electroencephalography (EEG) power generation may be a useful clinical marker for neural disruption in obstructive sleep apnea, and that high-density EEG may have the sensitivity to detect pathological cortical changes early in the disease process. Citation: Jones SG; Riedner BA; Smith RF; Ferrarelli F; Tononi G; Davidson RJ; Benca RM. Regional reductions in sleep electroencephalography power in obstructive sleep apnea: a high-density EEG study. SLEEP 2014;37(2):399-407. PMID:24497668

Metabolic and Glycemic Sequelae of Sleep Disturbances in Children and Adults

PubMed Central

Koren, Dorit; O'Sullivan, Katie L.; Mokhlesi, Babak

2015-01-01

The prevalence of obesity in adults and children has increased greatly in the past three decades, as have metabolic sequelae, such as insulin resistance and type 2 diabetes mellitus (T2DM). Sleep disturbances are increasingly recognized as contributors to this widespread epidemic in adults, and data are emerging in children as well. The categories of sleep disturbances that contribute to obesity and its glycemic co-morbidities include the following: (1) alterations of sleep duration, chronic sleep restriction and excessive sleep; (2) alterations in sleep architecture; (3) sleep fragmentation; (4) circadian rhythm disorders and disruption (i.e., shift work); and (5) obstructive sleep apnea. This article reviews current evidence supporting the contributions that these sleep disorders play in the development of obesity, insulin resistance, and T2DM as well as possibly influences on glycemic control in type 1 diabetes, with a special focus on data in pediatric populations. PMID:25398202

The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

NASA Technical Reports Server (NTRS)

Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

2003-01-01

OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

[The relationship between sleep and obesity: current perspective].

PubMed

Piskáčková, Zlata; Forejt, Martin; Martykánová, Lucie

2012-01-01

Disruption of circadian rhythms negatively affects regulation of metabolism and energy homeostasis. Disrupted metabolism in response to disrupted biological rhythms might lead, together with genetic background, to obesity and to other health complications. Results of epidemiologic surveys are consistent with mechanistic theory showing the interconnection between the biological rhythms, sleep and metabolism. Epidemiologic surveys confirm that sleep duration of less than 6 hours increases significantly the risk of obesity. Systematic reviews of epidemiologic surveys examining association of sleep and obesity refer to large heterogeneity in involved subjects, methodological approaches of measuring obesity and sleep, and confounders. Design of study plays also essential role in interpretation and definition of causal relationship. Reduced sleep duration in relation to obesity is in the literature discussed from different points of view: 1. as a possible primary cause of obesity, 2. as a result of comorbidities resulting from obesity and 3. as an accompanied part of the third factor contributing to obesity (e.g. long working hours, chronic emotional stress, overusing of media). Causal relationship between sleep and obesity is not yet fully elucidated, however the association is supposed to be bidirectional. The article gives an overview of current knowledge concerning the influence of sleep on the development of obesity and points to the critical points of current research.

Is Homeostatic Sleep Regulation Under Low Sleep Pressure Modified by Age?

PubMed Central

Munch, Mirjam; Knoblauch, Vera; Blatter, Katharina; Wirz-Justice, Anna; Cajochen, Christian

2007-01-01

Study Objectives: We have previously shown that healthy older volunteers react with an attenuated frontal predominance of sleep electroencephalogram (EEG) delta activity in response to high sleep pressure. Here, we investigated age-related changes in homeostatic sleep regulation under low sleep pressure conditions, with respect to regional EEG differences and their dynamics. Design: Analysis of the sleep EEG during an 8-hour baseline night, during a 40-hour multiple nap protocol (150 minutes of wakefulness and 75 minutes of sleep) and during the following 8-hour recovery night under constant posture conditions. Setting: Centre for Chronobiology, Psychiatric University Clinics, Basel, Switzerland Participants: Sixteen young (20–31 years) and 15 older (57–74 years) healthy volunteers Interventions: N/A. Measurements and Results: All-night EEG spectra revealed an increase in spindle activity (13–15.25 Hz) for both age groups, but only in the young did we find a significant decrease of delta activity (0.5–1.25 Hz) in response to low sleep pressure conditions, predominantly in occipital brain regions. However, delta activity during the first non-rapid eye movement (NREM) sleep episode was equally reduced in both age groups. This response lasted significantly longer in the young (across the first 2 NREM sleep episodes) than in the older participants (only the first NREM sleep episode). Conclusion: The initial EEG delta response to low sleep pressure was similar in healthy older and young participants. Therefore, age-related sleep deteriorations cannot solely be attributed to alterations in the homeostatic sleep-regulatory system. It is, rather, the interplay of circadian and homeostatic factors of sleep regulation, which is changed with aging. Citation: Munch M; Knoblauch V; Blatter K et al. Is homeostatic sleep regulation under low sleep pressure modified by age? SLEEP 2007;30(6):781-792. PMID:17580600

Obstructive sleep apnoea in obese adolescents and cardiometabolic risk markers.

PubMed

Watson, S E; Li, Z; Tu, W; Jalou, H; Brubaker, J L; Gupta, S; Huber, J N; Carroll, A; Hannon, T S

2014-12-01

In paediatric patients, obstructive sleep apnoea is associated with adiposity, especially visceral adiposity. In adults, obstructive sleep apnoea is also associated with a higher prevalence of cardiovascular disease and type 2 diabetes. There are limited and conflicting paediatric studies examining the association between obstructive sleep apnoea and biomarkers of risk for cardiovascular disease and type 2 diabetes in youth. Obstructive sleep apnoea is linked with greater cardiometabolic risk markers in obese adolescents. Fasting insulin and homeostasis model assessment-insulin resistance may be especially linked with obstructive sleep apnoea among obese male Hispanic adolescents. The relationship between obstructive sleep apnoea and cardiometabolic abnormalities in obese adolescents should be considered when evaluating patients found to have obstructive sleep apnoea. Paediatric studies examining the association between obstructive sleep apnoea (OSA) and insulin sensitivity/cardiometabolic risk are limited and conflicting. This study aims to determine if cardiometabolic risk markers are increased among obese youth with obstructive sleep apnoea as compared with their equally obese peers without OSA. We performed a retrospective analysis of 96 patients (age 14.2 ± 1.4 years) who underwent polysomnography for suspected OSA. Fasting lipids, glucose, insulin and haemoglobin A1 c (HbA1 c) were performed as part of routine clinical evaluation. Patients were categorized into two groups by degree of OSA as measured by the apnoea-hypopnoea index (AHI): none or mild OSA (AHI < 5) and moderate or severe OSA (AHI ≥ 5). Despite the similar degrees of obesity, patients with moderate or severe OSA had higher fasting insulin (P = 0.037) and homeostasis model assessment-insulin resistance (HOMA-IR [P = 0.0497]) as compared with those with mild or no OSA. After controlling for body mass index, there was a positive association between the AHI and log�

Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia.

PubMed

Wang, Tengyu; Eskandari, Davoud; Zou, Ding; Grote, Ludger; Hedner, Jan

2015-07-01

The catalytic function of the enzyme carbonic anhydrase (CA) plays a fundamental role in carbon dioxide (CO2), proton (H(+)), and bicarbonate (HCO3(-)) homeostasis. Hypoxia and tissue acidosis have been proposed to increase physiological CA activity in various compartments of the body. We hypothesized that CA activity in blood is upregulated in patients with obstructive sleep apnea (OSA). Cross-sectional analysis of a sleep clinic cohort. Sleep laboratory at a university hospital. Seventy referred patients with suspected OSA (48 males, age 54 ± 13 y, apnea-hypopnea index (AHI) median [interquartile range] 21 [8-41] n/h). N/A. In-laboratory cardiorespiratory polygraphy was used to assess OSA. CA activity was determined by an in vitro assay that quantifies the pH change reflecting the conversion of CO2 and H2O to HCO3(-) and H(+). CA activity was positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity versus logAHI and CA versus logODI4) were independent of sex, age, body mass index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension status, and use of diuretic medication in two generalized linear models (P = 0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated with CA activity after adjustment of sex, age, body mass index, mean oxygen saturation, and AHI (P = 0.046). Carbonic anhydrase (CA) activity increased with apnea-hypopnea index and related nocturnal hypoxemia measures in patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a component that modulates respiratory control and hemodynamic regulation in patients with OSA. © 2015 Associated Professional Sleep Societies, LLC.

Mitochondrial DNA alteration in obstructive sleep apnea.

PubMed

Lacedonia, Donato; Carpagnano, Giovanna E; Crisetti, Elisabetta; Cotugno, Grazia; Palladino, Grazia P; Patricelli, Giulia; Sabato, Roberto; Foschino Barbaro, Maria P

2015-04-07

Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations. 46 OSAS patients (age 59.27 ± 11.38; BMI 30.84 ± 3.64; AHI 36.63 ± 24.18) were compared with 36 control subjects (age 54.42 ± 6.63; BMI 29.06 ± 4.7; AHI 3.8 ± 1.10). In blood cells Content of MtDNA and nuclear DNA (nDNA) was measured in OSAS patients by Real Time PCR. The ratio between MtDNA/nDNA was then calculated. Presence of oxidative stress was evaluated by levels of Reactive Oxygen Metabolites (ROMs), measured by diacron reactive oxygen metabolite test (d-ROM test). MtDNA/nDNA was higher in patients with OSAS than in the control group (150.94 ± 49.14 vs 128.96 ± 45.8; p = 0.04), the levels of ROMs were also higher in OSAS subjects (329.71 ± 70.17 vs 226 ± 36.76; p = 0.04) and they were positively correlated with MtDNA/nDNA (R = 0.5, p < 0.01). In OSAS patients there is a Mitochondrial DNA damage induced by the increase of oxidative stress. Intermittent hypoxia seems to be the main mechanism which leads to this process.

A mechanism for sickness sleep: lessons from invertebrates.

PubMed

Davis, Kristen C; Raizen, David M

2017-08-15

During health, animal sleep is regulated by an internal clock and by the duration of prior wakefulness. During sickness, sleep is regulated by cytokines released from either peripheral cells or from cells within the nervous system. These cytokines regulate central nervous system neurons to induce sleep. Recent research in the invertebrates Caenorhabditis elegans and Drosophila melanogaster has led to new insights into the mechanism of sleep during sickness. Sickness is triggered by exposure to environments such as infection, heat, or ultraviolet light irradiation, all of which cause cellular stress. Epidermal growth factor is released from stressed cells and signals to activate central neuroendocrine cell(s). These neuron(s) release neuropeptides including those containing an amidated arginine(R)-phenylalanine(F) motif at their C-termini (RFamide peptides). Importantly, mechanisms regulating sickness sleep are partially distinct from those regulating healthy sleep. We will here review key findings that have elucidated the central neuroendocrine mechanism of sleep during sickness. Adaptive mechanisms employed in the control of sickness sleep may play a role in correcting cellular homeostasis after various insults. We speculate that these mechanisms may play a maladaptive role in human pathological conditions such as in the fatigue and anorexia associated with autoimmune diseases, with major depression, and with unexplained chronic fatigue. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Neurobiological linkage between stress and sleep

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Heart rate variability in normal and pathological sleep.

PubMed

Tobaldini, Eleonora; Nobili, Lino; Strada, Silvia; Casali, Karina R; Braghiroli, Alberto; Montano, Nicola

2013-10-16

Sleep is a physiological process involving different biological systems, from molecular to organ level; its integrity is essential for maintaining health and homeostasis in human beings. Although in the past sleep has been considered a state of quiet, experimental and clinical evidences suggest a noteworthy activation of different biological systems during sleep. A key role is played by the autonomic nervous system (ANS), whose modulation regulates cardiovascular functions during sleep onset and different sleep stages. Therefore, an interest on the evaluation of autonomic cardiovascular control in health and disease is growing by means of linear and non-linear heart rate variability (HRV) analyses. The application of classical tools for ANS analysis, such as HRV during physiological sleep, showed that the rapid eye movement (REM) stage is characterized by a likely sympathetic predominance associated with a vagal withdrawal, while the opposite trend is observed during non-REM sleep. More recently, the use of non-linear tools, such as entropy-derived indices, have provided new insight on the cardiac autonomic regulation, revealing for instance changes in the cardiovascular complexity during REM sleep, supporting the hypothesis of a reduced capability of the cardiovascular system to deal with stress challenges. Interestingly, different HRV tools have been applied to characterize autonomic cardiac control in different pathological conditions, from neurological sleep disorders to sleep disordered breathing (SDB). In summary, linear and non-linear analysis of HRV are reliable approaches to assess changes of autonomic cardiac modulation during sleep both in health and diseases. The use of these tools could provide important information of clinical and prognostic relevance.

The unrested resting brain: sleep deprivation alters activity within the default-mode network.

PubMed

Gujar, Ninad; Yoo, Seung-Schik; Hu, Peter; Walker, Matthew P

2010-08-01

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network. Indeed, deactivation within these regions alone discriminated sleep-deprived from sleep-control subjects with a 93% degree of sensitivity and 92% specificity. In addition, the relative balance of deactivation within these default nodes significantly correlated with the amount of prior sleep in the control group (and not extended time awake in the deprivation group). Therefore, the stability and the balance of task-related deactivation in key default-mode regions may be dependent on prior sleep, such that a lack thereof disrupts this signature pattern of brain activity, findings that may offer explanatory insights into conditions associated with sleep loss at both a clinical as well as societal level.

Regional reductions in sleep electroencephalography power in obstructive sleep apnea: a high-density EEG study.

PubMed

Jones, Stephanie G; Riedner, Brady A; Smith, Richard F; Ferrarelli, Fabio; Tononi, Giulio; Davidson, Richard J; Benca, Ruth M

2014-02-01

Obstructive sleep apnea (OSA) is associated with significant alterations in neuronal integrity resulting from either hypoxemia and/or sleep loss. A large body of imaging research supports reductions in gray matter volume, alterations in white matter integrity and resting state activity, and functional abnormalities in response to cognitive challenge in various brain regions in patients with OSA. In this study, we used high-density electroencephalography (hdEEG), a functional imaging tool that could potentially be used during routine clinical care, to examine the regional distribution of neural activity in a non-clinical sample of untreated men and women with moderate/severe OSA. Sleep was recorded with 256-channel EEG in relatively healthy subjects with apnea-hypopnea index (AHI) > 10, as well as age-, sex-, and body mass index-matched controls selected from a research population initially recruited for a study on sleep and meditation. Sleep laboratory. Nine subjects with AHI > 10 and nine matched controls. N/A. Topographic analysis of hdEEG data revealed a broadband reduction in EEG power in a circumscribed region overlying the parietal cortex in OSA subjects. This parietal reduction in neural activity was present, to some extent, across all frequency bands in all stages and episodes of nonrapid eye movement sleep. This investigation suggests that regional deficits in electroencephalography (EEG) power generation may be a useful clinical marker for neural disruption in obstructive sleep apnea, and that high-density EEG may have the sensitivity to detect pathological cortical changes early in the disease process.

Disruption of iron homeostasis in mesothelial cells following talc pleurodesis

EPA Science Inventory

The mechanism for biological effect following particle exposure is incompletely understood. One postulate proposed to explain biological effect after particles is an altered iron homeostasis in the host. The fibro-inflammatory properties of particles are exploited therapeutically...

Effect of oxcarbazepine on sleep architecture.

PubMed

Ayala-Guerrero, Fructuoso; Mexicano, Graciela; González, Valentín; Hernandez, Mario

2009-07-01

The most common side effects following administration of antiepileptic drugs involve alterations in sleep architecture and varying degrees of daytime sleepiness. Oxcarbazepine is a drug that is approved as monotherapy for the treatment of partial seizures and generalized tonic-clonic seizures. However, there is no information about its effects on sleep pattern organization; therefore, the objective of this work was to analyze such effects. Animals (Wistar rats) exhibited three different behavioral and electrophysiological states of vigilance: wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep. Oral treatment with oxcarbazepine (100 mg/kg) produced an increment in total sleep time throughout the recording period. This increment involved both SWS and REM sleep. Mean duration of the REM sleep phase was not affected. In contrast, the frequency of this sleep phase increased significantly across the 10-hour period. REM sleep latency shortened significantly. Results obtained in this work indicate that oxcarbazepine's acute effects point to hypnotic properties.

Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.

PubMed

Dallaspezia, Sara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Benedetti, Francesco

2016-03-01

Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control. Copyright © 2015 Elsevier B.V. All rights reserved.

Redox homeostasis: The Golden Mean of healthy living

PubMed Central

Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

2016-01-01

The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia

PubMed Central

Wang, Tengyu; Eskandari, Davoud; Zou, Ding; Grote, Ludger; Hedner, Jan

2015-01-01

Study Objectives: The catalytic function of the enzyme carbonic anhydrase (CA) plays a fundamental role in carbon dioxide (CO2), proton (H+), and bicarbonate (HCO3-) homeostasis. Hypoxia and tissue acidosis have been proposed to increase physiological CA activity in various compartments of the body. We hypothesized that CA activity in blood is upregulated in patients with obstructive sleep apnea (OSA). Design: Cross-sectional analysis of a sleep clinic cohort. Settings: Sleep laboratory at a university hospital. Participants: Seventy referred patients with suspected OSA (48 males, age 54 ± 13 y, apnea-hypopnea index (AHI) median [interquartile range] 21 [8–41] n/h). Interventions: N/A. Measurements and Results: In-laboratory cardiorespiratory polygraphy was used to assess OSA. CA activity was determined by an in vitro assay that quantifies the pH change reflecting the conversion of CO2 and H2O to HCO3- and H+. CA activity was positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity versus logAHI and CA versus logODI4) were independent of sex, age, body mass index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension status, and use of diuretic medication in two generalized linear models (P = 0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated with CA activity after adjustment of sex, age, body mass index, mean oxygen saturation, and AHI (P = 0.046). Conclusions: Carbonic anhydrase (CA) activity increased with apnea-hypopnea index and related nocturnal hypoxemia measures in patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a component that modulates respiratory control and hemodynamic regulation in patients with OSA. Citation: Wang T, Eskandari D, Zou D, Grote L, Hedner J. Increased carbonic anhydrase activity is associated with sleep apnea severity and related hypoxemia. SLEEP 2015

[Non-epileptic paroxysmal sleep disorders].

PubMed

Malagón-Valdez, Jorge

2013-09-06

Non-epileptic paroxysmal disorders during sleep are a great challenge for the clinician. It is important to know the various clinical manifestations for appropriate differential diagnosis, since alterations in sleep, mostly motor, are part of these disorders. Our paper describes the normal sleep stages and electroencephalographic characteristics and polysomnography basic data. The confusions especially with nocturnal frontal lobe epilepsy are frequent and cause unnecessary drugs administered, the emotional burden of the parents or caretakers, which is the diagnosis of epilepsy. We discuss the possible causes of diagnostic errors.

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

PubMed

Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Interaction of sleep quality and sleep duration on glycemic control in patients with type 2 diabetes mellitus.

PubMed

Tang, Yunzhao; Meng, Lingling; Li, Daiqing; Yang, Min; Zhu, Yanjuan; Li, Chenguang; Jiang, Zhenhuan; Yu, Ping; Li, Zhu; Song, Hongna; Ni, Changlin

2014-01-01

Copious evidence from epidemiological and laboratory studies has revealed that sleep status is associated with glucose intolerance, insulin resistance, thus increasing the risk of developing type 2 diabetes. The aim of this study was to reveal the interaction of sleep quality and sleep quantity on glycemic control in patients with type 2 diabetes mellitus. From May 2013 to May 2014, a total of 551 type 2 diabetes patients in Tianjin Metabolic Diseases Hospital were enrolled. Blood samples were taken to measure glycosylated hemoglobin (HbA1c), and all the patients completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire to evaluate their sleep status. "Good sleep quality" was defined as PQSI <5, "average sleep quality" was defined as PQSI 6-8, and "poor sleep quality" was defined as PQSI >8. Poor glycemic control was defined as HbA1c ≥7%. Sleep quantity was categorized as <6, 6-8, and >8 hours/night. Short sleep time was defined as sleep duration <6 hours/night. In the poor glycemic control group, the rate of patients who had insufficient sleep was much higher than that in the other group (χ(2) = 11.16, P = 0.037). The rate of poor sleep quality in poor glycemic control group was much greater than that in the average control group (χ(2) = 9.79, P = 0.007). After adjusted by gender, age, body mass index, and disease duration, the adjusted PSQI score's OR was 1.048 (95% CI 1.007-1.092, P = 0.023) for HbA1c level. The sleep duration's OR was 0.464 (95% CI 0.236-0.912, P = 0.026) for HbA1c level. One-way analysis of variance showed that the poor sleep quality group had the highest homeostasis model assessment-insulin resistance (P < 0.01). Inadequate sleep, in both quality and quantity, should be regarded as a plausible risk factor for glycemic control in type 2 diabetes. Poor sleep might bring much more serious insulin resistance and could be the reason for bad glycemic control. A good night's sleep should be seen as a critical

Metabolic consequences of sleep and circadian disorders.

PubMed

Depner, Christopher M; Stothard, Ellen R; Wright, Kenneth P

2014-07-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.

Metabolic consequences of sleep and circadian disorders

PubMed Central

Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

2014-01-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice

PubMed Central

Curie, Thomas; Maret, Stephanie; Emmenegger, Yann; Franken, Paul

2015-01-01

Study Objectives: That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice. Design: In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery. Settings: Mouse sleep-recording facility. Participants: Per2::Luciferase knock-in mice. Interventions: N/A. Measurements and Results: Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls. Conclusions: Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health. Citation: Curie T, Maret S, Emmenegger Y, Franken P. In

Sleep Disorders in Children: Collaboration for School-Based Intervention

ERIC Educational Resources Information Center

Everhart, D. Erik

2011-01-01

The effects of sleep disturbance on children are wide ranging and include alterations in behavior, mood, cognition, and academic performance. Screening and intervention for pediatric sleep disorders within the schools are not widely implemented, and the concept of integrating school personnel into the multidisciplinary sleep team has yet to be…

CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

PubMed Central

Young, James L.; Mora, Alfonso; Cerny, Anna; Czech, Michael P.; Woda, Bruce; Kurt-Jones, Evelyn A.; Finberg, Robert W.; Corvera, Silvia

2012-01-01

The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis. PMID:22253759

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

PubMed

Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

2016-10-01

Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

The Impact of Sleep and Circadian Disturbance on Hormones and Metabolism

PubMed Central

Kim, Tae Won; Jeong, Jong-Hyun; Hong, Seung-Chul

2015-01-01

The levels of several hormones fluctuate according to the light and dark cycle and are also affected by sleep, feeding, and general behavior. The regulation and metabolism of several hormones are influenced by interactions between the effects of sleep and the intrinsic circadian system; growth hormone, melatonin, cortisol, leptin, and ghrelin levels are highly correlated with sleep and circadian rhythmicity. There are also endogenous circadian mechanisms that serve to regulate glucose metabolism and similar rhythms pertaining to lipid metabolism, regulated through the actions of various clock genes. Sleep disturbance, which negatively impacts hormonal rhythms and metabolism, is also associated with obesity, insulin insensitivity, diabetes, hormonal imbalance, and appetite dysregulation. Circadian disruption, typically induced by shift work, may negatively impact health due to impaired glucose and lipid homeostasis, reversed melatonin and cortisol rhythms, and loss of clock gene rhythmicity. PMID:25861266

Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

PubMed Central

Lanfranco, Fabio; Motta, Giovanna; Minetto, Marco Alessandro; Baldi, Matteo; Balbo, Marcella; Ghigo, Ezio; Arvat, Emanuela; Maccario, Mauro

2010-01-01

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH) secretion coupled to reduced insulin-like growth factor-I (IGF-I) concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL) rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA) axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH) secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death. PMID:20182553

Two hours of evening reading on a self-luminous tablet vs. reading a physical book does not alter sleep after daytime bright light exposure.

PubMed

Rångtell, Frida H; Ekstrand, Emelie; Rapp, Linnea; Lagermalm, Anna; Liethof, Lisanne; Búcaro, Marcela Olaya; Lingfors, David; Broman, Jan-Erik; Schiöth, Helgi B; Benedict, Christian

2016-07-01

The use of electronic devices emitting blue light during evening hours has been associated with sleep disturbances in humans, possibly due to the blue light-mediated suppression of the sleep-promoting hormone melatonin. However, experimental results have been mixed. The present study therefore sought to investigate if reading on a self-luminous tablet during evening hours would alter sleepiness, melatonin secretion, nocturnal sleep, as well as electroencephalographic power spectral density during early slow-wave sleep. Following a constant bright light exposure over 6.5 hours (~569 lux), 14 participants (six females) read a novel either on a tablet or as physical book for two hours (21:00-23:00). Evening concentrations of saliva melatonin were repeatedly measured. Sleep (23:15-07:15) was recorded by polysomnography. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated; participants who had read the novel on a tablet in the first experimental session continued reading the same novel in the physical book, and vice versa. There were no differences in sleep parameters and pre-sleep saliva melatonin levels between the tablet reading and physical book reading conditions. Bright light exposure during daytime has previously been shown to abolish the inhibitory effects of evening light stimulus on melatonin secretion. Our results could therefore suggest that exposure to bright light during the day - as in the present study - may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light. However, this needs to be validated by future studies with larger sample populations. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Age-Related Reduction of Recovery Sleep and Arousal Threshold in Drosophila.

PubMed

Vienne, Julie; Spann, Ryanne; Guo, Fang; Rosbash, Michael

2016-08-01

Physiological studies show that aging affects both sleep quality and quantity in humans, and sleep complaints increase with age. Along with knowledge about the negative effects of poor sleep on health, understanding the enigmatic relationship between sleep and aging is important. Because human sleep is similar to Drosophila (fruit fly) sleep in many ways, we addressed the effects of aging on sleep in this model organism. Baseline sleep was recorded in five different Drosophila genotypes raised at either 21°C or 25°C. The amount of sleep recovered was then investigated after a nighttime of sleep deprivation (12 h) and after chronic sleep deprivation (3 h every night for multiple nights). Finally, the effects of aging on arousal, namely, sensitivity to neuronal and mechanical stimuli, were studied. We show that fly sleep is affected by age in a manner similar to that of humans and other mammals. Not only do older flies of several genotypes have more fragmented sleep and reduced total sleep time compared to young flies, but older flies also fail to recover as much sleep after sleep deprivation. This suggests either lower sleep homeostasis and/or a failure to properly recover sleep. Older flies also show a decreased arousal threshold, i.e., an increased response to neuronal and mechanical wake-promoting stimuli. The reduced threshold may either reflect or cause the reduced recovery sleep of older flies compared to young flies after sleep deprivation. Further studies are certainly needed, but we suggest that the lower homeostatic sleep drive of older flies causes their decreased arousal threshold. © 2016 Associated Professional Sleep Societies, LLC.

The effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach

PubMed Central

Skeldon, Anne C.; Phillips, Andrew J. K.; Dijk, Derk-Jan

2017-01-01

Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity (‘social jet-lag’). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag. PMID:28345624

The effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach.

PubMed

Skeldon, Anne C; Phillips, Andrew J K; Dijk, Derk-Jan

2017-03-27

Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity ('social jet-lag'). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag.

Pathophysiology of Sleep Apnea

PubMed Central

Veasey, Sigrid C.; Morgan, Barbara J.; O'Donnell, Christopher P.

2010-01-01

Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anatomically compromised, collapsible airway, the sleep-induced loss of compensatory tonic input to the upper airway dilator muscle motor neurons leads to collapse of the pharyngeal airway. In turn, the ability of the sleeping subject to compensate for this airway obstruction will determine the degree of cycling of these events. Several of the classic neurotransmitters and a growing list of neuromodulators have now been identified that contribute to neurochemical regulation of pharyngeal motor neuron activity and airway patency. Limited progress has been made in developing pharmacotherapies with acceptable specificity for the treatment of sleep-induced airway obstruction. We review three types of major long-term sequelae to severe OSA that have been assessed in humans through use of continuous positive airway pressure (CPAP) treatment and in animal models via long-term intermittent hypoxemia (IH): 1) cardiovascular. The evidence is strongest to support daytime systemic hypertension as a consequence of severe OSA, with less conclusive effects on pulmonary hypertension, stroke, coronary artery disease, and cardiac arrhythmias. The underlying mechanisms mediating hypertension include enhanced chemoreceptor sensitivity causing excessive daytime sympathetic vasoconstrictor activity, combined with overproduction of superoxide ion and inflammatory effects on resistance vessels. 2) Insulin sensitivity and homeostasis of glucose regulation are negatively impacted by both intermittent hypoxemia and sleep disruption, but whether these influences of OSA are sufficient, independent of obesity, to contribute significantly to the “metabolic syndrome” remains unsettled. 3) Neurocognitive effects include daytime sleepiness and impaired memory and concentration. These effects reflect

Amylin and Leptin: Co-Regulators of Energy Homeostasis and Neuronal Development.

PubMed

Levin, Barry E; Lutz, Thomas A

2017-02-01

While the regulation of energy homeostasis by amylin is already well-characterized, emerging data suggest that amylin is also crucial for the development of neural pathways in the hypothalamus and caudal hindbrain (area postrema, AP; nucleus tractus solitarius, NTS). Exciting new findings demonstrate crucial amylin-leptin interactions in altering the activity of specific hypothalamic and AP neurons, and a role for amylin as a novel class of 'leptin sensitizers' which enhance leptin signaling in both leptin-sensitive and -resistant individuals, in part by stimulating IL-6 production by hypothalamic microglia. This review summarizes these findings and provides a hypothetical framework for future studies to elucidate the mechanisms by which amylin and leptin act individually and as co-conspirators to alter energy homeostasis and neuronal development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sleep in children with autism spectrum disorder.

PubMed

Kotagal, Suresh; Broomall, Eileen

2012-10-01

Children with autism spectrum disorder demonstrate an increased prevalence of difficulties with sleep initiation and maintenance. The consequences may include alterations in daytime behavior, memory, and learning in patients, and significant stress in caretakers. The dysregulation of melatonin synthesis, sensitization to environmental stimuli, behavioral insomnia syndromes, delayed sleep phase syndrome, rapid eye movement sleep behavior disorder, and comorbid anxiety, depression, and epilepsy comprise common etiologic factors. The clinical assessment of sleep problems in this population and a management algorithm are presented. Copyright © 2012 Elsevier Inc. All rights reserved.

Dim light at night does not disrupt timing or quality of sleep in mice.

PubMed

Borniger, Jeremy C; Weil, Zachary M; Zhang, Ning; Nelson, Randy J

2013-10-01

Artificial nighttime illumination has recently become commonplace throughout the world; however, in common with other animals, humans have not evolved in the ecological context of chronic light at night. With prevailing evidence linking the circadian, endocrine, immune, and metabolic systems, understanding these relationships is important to understanding the etiology and progression of several diseases. To eliminate the covariate of sleep disruption in light at night studies, researchers often use nocturnal animals. However, the assumption that light at night does not affect sleep in nocturnal animals remains unspecified. To test the effects of light at night on sleep, we maintained Swiss-Webster mice in standard light/dark (LD) or dim light at night (DLAN) conditions for 8-10 wks and then measured electroencephalogram (EEG) and electromyogram (EMG) biopotentials via wireless telemetry over the course of two consecutive days to determine differences in sleep timing and homeostasis. Results show no statistical differences in total percent time, number of episodes, maximum or average episode durations in wake, slow-wave sleep (SWS), or rapid eye movement (REM) sleep. No differences were evident in SWS delta power, an index of sleep drive, between groups. Mice kept in DLAN conditions showed a relative increase in REM sleep during the first few hours after the dark/light transition. Both groups displayed normal 24-h circadian rhythms as measured by voluntary running wheel activity. Groups did not differ in body mass, but a marked negative correlation of body mass with percent time spent awake and a positive correlation of body mass with time spent in SWS was evident. Elevated body mass was also associated with shorter maximum wake episode durations, indicating heavier animals had more trouble remaining in the wake vigilance state for extended periods of time. Body mass did not correlate with activity levels, nor did activity levels correlate with time spent in

The PAr index, an indicator reflecting altered vitamin B-6 homeostasis, is associated with long-term risk of stroke in the general population: the Hordaland Health Study (HUSK).

PubMed

Zuo, Hui; Tell, Grethe S; Ueland, Per M; Nygård, Ottar; Vollset, Stein E; Midttun, Øivind; Meyer, Klaus; Ulvik, Arve

2018-01-01

Vitamin B-6 homeostasis is altered during inflammation and immune activation. It is unknown whether altered vitamin B-6 homeostasis is associated with the risk of stroke. We investigated the relation between the ratio plasma 4-pyridoxic acid: (pyridoxal + pyridoxal-5'-phosphate) (PAr) as an indicator of altered vitamin B-6 homeostasis and the risk of stroke in the general population. We conducted a prospective analysis of the community-based Hordaland Health Study (HUSK) in 6891 adults (born during 1925-1927 and 1950-1951) without known stroke at baseline (1998-1999). Participants were followed via linkage to the CVDNOR (Cardiovascular Disease in Norway) project and the Cause of Death Registry. HRs and 95% CIs were calculated using Cox proportional hazards analyses. A total of 390 participants (193 men and 197 women) developed stroke over a median follow-up period of 11 y. Study participants with elevated PAr experienced a higher risk of incident stroke in an essentially linear dose-response fashion. The HR (95% CI) for the highest compared with the lowest quartile of PAr was 1.97 (1.42, 2.73; P-trend <0.001) for total stroke and 2.09 (1.42, 3.09; P-trend <0.001) for ischemic stroke after adjustment for age, sex, body mass index (BMI), smoking, education, physical activity, estimated glomerular filtration rate, hypertension, diabetes, total cholesterol, and statin use. PAr had greater predictive strength than did C-reactive protein, current smoking, diabetes, hypertension, estimated glomerular filtration rate, and physical activity. The associations were similar in subgroups stratified by age group, sex, BMI, current smoking, hypertension, diabetes, and statin use at baseline. Higher plasma PAr was independently associated with increased risk of incident stroke in all participants and across all subgroups stratified by conventional risk predictors. Our novel findings point to and expand the range of inflammation and immune activation processes that may be relevant

[Sleep disturbances in children with autistic spectrum disorders].

PubMed

Kelmanson, I A

2015-01-01

An association between sleep disorders and autistic spectrum disorders in children is considered. Characteristic variants of sleep disorders, including resistance to going to bed, frequent night awakenings, parasomnias, changes in sleep structure, primarily, the decrease in the percentage of rapid eye movement sleep, are presented. Attention is focused on the possibility of the direct relationship between sleep disturbance and the pathogenesis of autistic spectrum disorders. A role of pathological alterations in the production of neuromediators and morphological changes in the brain structures characteristic of autistic spectrum disorders in the genesis of sleep disorders in children is discussed. Possible non-pharmacological and pharmacological approaches are suggested.

Homer1a is a core brain molecular correlate of sleep loss.

PubMed

Maret, Stéphanie; Dorsaz, Stéphane; Gurcel, Laure; Pradervand, Sylvain; Petit, Brice; Pfister, Corinne; Hagenbuchle, Otto; O'Hara, Bruce F; Franken, Paul; Tafti, Mehdi

2007-12-11

Sleep is regulated by a homeostatic process that determines its need and by a circadian process that determines its timing. By using sleep deprivation and transcriptome profiling in inbred mouse strains, we show that genetic background affects susceptibility to sleep loss at the transcriptional level in a tissue-dependent manner. In the brain, Homer1a expression best reflects the response to sleep loss. Time-course gene expression analysis suggests that 2,032 brain transcripts are under circadian control. However, only 391 remain rhythmic when mice are sleep-deprived at four time points around the clock, suggesting that most diurnal changes in gene transcription are, in fact, sleep-wake-dependent. By generating a transgenic mouse line, we show that in Homer1-expressing cells specifically, apart from Homer1a, three other activity-induced genes (Ptgs2, Jph3, and Nptx2) are overexpressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.

Alterations in circulating T-cell lymphocyte populations in children with obstructive sleep apnea.

PubMed

Tan, Hui-Leng; Gozal, David; Wang, Yang; Bandla, Hari P R; Bhattacharjee, Rakesh; Kulkarni, Richa; Kheirandish-Gozal, Leila

2013-06-01

Changes in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA. Cross-sectional. Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA). Consecutively recruited children being evaluated for habitual snoring. N/A. Overnight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 ≤ AHI < 5/hTST), moderate-severe OSA (AHI ≥ 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1:Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1:Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1:Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1:Th2 ratios (P = 0.029; r = -0.29). Pediatric OSA is associated with reduced T reg population and altered Th1:Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes

Altering Misperception of Sleep in Insomnia: Behavioral Experiment Versus Verbal Feedback

ERIC Educational Resources Information Center

Tang, Nicole K. Y.; Harvey, Allison G.

2006-01-01

Forty-eight individuals with insomnia were asked to wear an actigraph and keep a sleep diary for 2 nights. On the following day, half were shown the discrepancy between the data recorded on the actigraph and their sleep diary via a behavioral experiment, whereas the other half were told of the discrepancy verbally. Participants were then asked to…

Relationships between parental sleep quality, fatigue, cognitions about infant sleep, and parental depression pre and post-intervention for infant behavioral sleep problems.

PubMed

Hall, Wendy A; Moynihan, Melissa; Bhagat, Radhika; Wooldridge, Joanne

2017-04-04

Maternal and paternal depression has been associated with infants' behavioral sleep problems. Behavioral sleep interventions, which alter parental cognitions about infant sleep, have improved infant sleep problems. This study reports relationships between parental depression, fatigue, sleep quality, and cognitions about infant sleep pre and post-intervention for a behavioral sleep problem. This secondary analysis of data from Canadian parents (n = 455), with healthy infants aged 6-to-8-months exposed to a behavioral sleep intervention, examined baseline data and follow-up data from 18 or 24 weeks post intervention (group teaching or printed material) exposure. Parents reported on sleep quality, fatigue, depression, and cognitions about infant sleep. Data were analyzed using Pearson's r and stepwise regression analysis. Parents' fatigue, sleep quality, sleep cognitions, and depression scores were correlated at baseline and follow-up. At baseline, sleep quality (b = .52, 95% CI .19-.85), fatigue (b = .48, 95% CI .33-.63), doubt about managing infant sleep (b = .44, 95% CI .19-.69), and anger about infant sleep (b = .69, 95% CI .44-.94) were associated with mothers' depression. At baseline, fathers' depression related to sleep quality (b = .42, 95% CI .01-.83), fatigue (b = .47, 95% CI .32-.63), and doubt about managing infant sleep (b = .50, 95% CI .24-.76). At follow-up, mothers' depression was associated with sleep quality (b = .76, 95% CI .41-1.12), fatigue (b = .25, 95% CI .14-.37), doubt about managing infant sleep (b = .44, 95% CI .16-.73), sleep anger (b = .31, 95% CI .02-.59), and setting sleep limits (b = -.22, 95% CI -.41-[-.03]). At follow-up, fathers' depression related to sleep quality (b = .84, 95% CI .46-1.22), fatigue (b = .31, 95% CI .17-.45), sleep doubt (b = .34, 95% CI .05-.62), and setting sleep limits (b = .25, 95% CI .01-.49). Mothers' and fathers' cognitions about infant

Sleep in the Intensive Care Unit

PubMed Central

Friese, Randall S.; Gehlbach, Brian K.; Schwab, Richard J.; Weinhouse, Gerald L.; Jones, Shirley F.

2015-01-01

Sleep is an important physiologic process, and lack of sleep is associated with a host of adverse outcomes. Basic and clinical research has documented the important role circadian rhythm plays in biologic function. Critical illness is a time of extreme vulnerability for patients, and the important role sleep may play in recovery for intensive care unit (ICU) patients is just beginning to be explored. This concise clinical review focuses on the current state of research examining sleep in critical illness. We discuss sleep and circadian rhythm abnormalities that occur in ICU patients and the challenges to measuring alterations in circadian rhythm in critical illness and review methods to measure sleep in the ICU, including polysomnography, actigraphy, and questionnaires. We discuss data on the impact of potentially modifiable disruptors to patient sleep, such as noise, light, and patient care activities, and report on potential methods to improve sleep in the setting of critical illness. Finally, we review the latest literature on sleep disturbances that persist or develop after critical illness. PMID:25594808

Age-Related Reduction of Recovery Sleep and Arousal Threshold in Drosophila

PubMed Central

Vienne, Julie; Spann, Ryanne; Guo, Fang; Rosbash, Michael

2016-01-01

Study Objectives: Physiological studies show that aging affects both sleep quality and quantity in humans, and sleep complaints increase with age. Along with knowledge about the negative effects of poor sleep on health, understanding the enigmatic relationship between sleep and aging is important. Because human sleep is similar to Drosophila (fruit fly) sleep in many ways, we addressed the effects of aging on sleep in this model organism. Methods: Baseline sleep was recorded in five different Drosophila genotypes raised at either 21°C or 25°C. The amount of sleep recovered was then investigated after a nighttime of sleep deprivation (12 h) and after chronic sleep deprivation (3 h every night for multiple nights). Finally, the effects of aging on arousal, namely, sensitivity to neuronal and mechanical stimuli, were studied. Results: We show that fly sleep is affected by age in a manner similar to that of humans and other mammals. Not only do older flies of several genotypes have more fragmented sleep and reduced total sleep time compared to young flies, but older flies also fail to recover as much sleep after sleep deprivation. This suggests either lower sleep homeostasis and/or a failure to properly recover sleep. Older flies also show a decreased arousal threshold, i.e., an increased response to neuronal and mechanical wake-promoting stimuli. The reduced threshold may either reflect or cause the reduced recovery sleep of older flies compared to young flies after sleep deprivation. Conclusions: Further studies are certainly needed, but we suggest that the lower homeostatic sleep drive of older flies causes their decreased arousal threshold. Citation: Vienne J, Spann R, Guo F, Rosbash M. Age-related reduction of recovery sleep and arousal threshold in Drosophila. SLEEP 2016;39(8):1613–1624. PMID:27306274

Sleep architecture in patients with fibromyalgia.

PubMed

Besteiro González, José Luis; Suárez Fernández, Tomás Vicente; Arboleya Rodríguez, Luis; Muñiz, José; Lemos Giráldez, Serafín; Alvarez Fernández, Angel

2011-08-01

The main objective of this work was to evaluate the characteristics of sleep in patients diagnosed with fibromyalgia syndrome. Sleep architecture in 32 patients with fibromyalgia and 20 healthy controls was evaluated. Following the recommendations of the International Federation of Clinical Neurophysiology, polysomnographies were conducted with fibromyalgia patients and the control subjects. The fibromyalgia patients showed alterations in cyclic organization of sleep and an increased number of periodic leg movements associated with cortical arousals. No significant differences were found in respiratory and oximetry variables or in alpha-delta sleep. The results support that fibromyalgia patients present an increase of superficial sleep at the expense of deep sleep and also an increase of periodic leg movements, which could have a pathogenic effect, facilitating the onset of the illness. Lastly, we discuss the results and propose some future lines of research.

Rice Ovate Family Protein 2 (OFP2) alters hormonal homeostasis and vasculature development.

PubMed

Schmitz, Aaron J; Begcy, Kevin; Sarath, Gautam; Walia, Harkamal

2015-12-01

OFP (Ovate Family Protein) is a transcription factor family found only in plants. In dicots, OFPs control fruit shape and secondary cell wall biosynthesis. OFPs are also thought to function through interactions with KNOX and BELL transcription factors. Here, we have functionally characterized OsOFP2, a member of the OFP subgroup associated with regulating fruit shape. OsOFP2 was found to localize to the nucleus and to the cytosol. A putative nuclear export signal was identified within the OVATE domain and was required for the localization of OsOFP2 to distinct cytosolic spots. Rice plants overexpressing OsOFP2 were reduced in height and exhibited altered leaf morphology, seed shape, and positioning of vascular bundles in stems. Transcriptome analysis indicated disruptions of genes associated with vasculature development, lignin biosynthesis, and hormone homeostasis. Reduced expression of the gibberellin biosynthesis gene GA 20-oxidase 7 coincided with lower gibberellin content in OsOFP2 overexpression lines. Also, we found that OsOFP2 was expressed in plant vasculature and determined that putative vascular development KNOX and BELL proteins interact with OsOFP2. KNOX and BELL genes are known to suppress gibberellin biosynthesis through GA20ox gene regulation and can restrict lignin biosynthesis. We propose that OsOFP2 could modulate KNOX-BELL function to control diverse aspects of development including vasculature development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sleep Enhances a Spatially Mediated Generalization of Learned Values

ERIC Educational Resources Information Center

Javadi, Amir-Homayoun; Tolat, Anisha; Spiers, Hugo J.

2015-01-01

Sleep is thought to play an important role in memory consolidation. Here we tested whether sleep alters the subjective value associated with objects located in spatial clusters that were navigated to in a large-scale virtual town. We found that sleep enhances a generalization of the value of high-value objects to the value of locally clustered…

Sleep patterns and predictors of disturbed sleep in a large population of college students.

PubMed

Lund, Hannah G; Reider, Brian D; Whiting, Annie B; Prichard, J Roxanne

2010-02-01

To characterize sleep patterns and predictors of poor sleep quality in a large population of college students. This study extends the 2006 National Sleep Foundation examination of sleep in early adolescence by examining sleep in older adolescents. One thousand one hundred twenty-five students aged 17 to 24 years from an urban Midwestern university completed a cross-sectional online survey about sleep habits that included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, the Horne-Ostberg Morningness-Eveningness Scale, the Profile of Mood States, the Subjective Units of Distress Scale, and questions about academic performance, physical health, and psychoactive drug use. Students reported disturbed sleep; over 60% were categorized as poor-quality sleepers by the PSQI, bedtimes and risetimes were delayed during weekends, and students reported frequently taking prescription, over the counter, and recreational psychoactive drugs to alter sleep/wakefulness. Students classified as poor-quality sleepers reported significantly more problems with physical and psychological health than did good-quality sleepers. Students overwhelmingly stated that emotional and academic stress negatively impacted sleep. Multiple regression analyses revealed that tension and stress accounted for 24% of the variance in the PSQI score, whereas exercise, alcohol and caffeine consumption, and consistency of sleep schedule were not significant predictors of sleep quality. These results demonstrate that insufficient sleep and irregular sleep-wake patterns, which have been extensively documented in younger adolescents, are also present at alarming levels in the college student population. Given the close relationships between sleep quality and physical and mental health, intervention programs for sleep disturbance in this population should be considered. Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.

Role of Sex and the Environment in Moderating Weight Gain Due to Inadequate Sleep.

PubMed

Coborn, Jamie E; Houser, Monica M; Perez-Leighton, Claudio E; Teske, Jennifer A

2017-12-01

The growing prevalence of obesity, inadequate sleep and sleep disorders together with the negative impact of lack of sleep on overall health highlights the need for therapies targeted towards weight gain due to sleep loss. Sex disparities in obesity and sleep disorders are present; yet, the role of sex is inadequately addressed and thus it is unclear whether sensitivity to sleep disruption differs between men and women. Like sex, environmental factors contribute to the development of obesity and poor sleep. The obesogenic environment is characterized by easy access to palatable foods and a low demand for energy expenditure in daily activities. These and other environmental factors are discussed, as they drive altered sleep or their interaction with food choice and intake can promote obesity. We discuss data that suggest differences in sleep patterns and responses to sleep disruption influence sex disparities in weight gain, and that enviromental disturbances alter sleep and interact with features of the obesogenic environment that together promote obesity.

Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures

PubMed Central

Parsons, Michael J; Lester, Kathryn J; Barclay, Nicola L; Archer, Simon N; Nolan, Patrick M; Eley, Thalia C; Gregory, Alice M

2014-01-01

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness–Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours. PMID:24635757

[Evolutionary aspects of sleep and stress interaction: phylo-, ontogenetic approach].

PubMed

Aristakesian, E A

2009-01-01

This work deals the comparative behavioral, somatosensor and neurophysiological characteristics of these forms of passive defensive behavior included in amphibian's sleep-wakefulness cycle and their developmental dynamics in the ascending vertebrates secale. Sleep formation in early postnatal ontogenesis of mature- and immature-born mammals - from undifferent sleep to the mature sleep divided into two phases as well as stress formation are considered in parallel. Comparative phylo-, and ontogenetic analysis of several aspects of stress-reactions, sleep, and immobility phenomenon of cataleptic type allows concluding that amphibians and reptilians catalepsy can be interpreted as preadaptive from of behavior underlying in the stress of homoeothermic animals. Another word, the cataleptic state can be considered as the homologic state of stress-reaction. Catalepsy is the genetically programmed state of poykilothermic animals characterized by comparatively high alertness of animal, its freezing in immobile but active posture with a possibility of fast exit into waking state and alongside with other somatosensor and neurophysiological characteristics determines the entire subsequent complex of evolutionary morphofunctional, neurophysiological and hormonal changes in nomoyptherms. This in many aspects unspecific behavioral adaptive reaction in poykilotherms is realized on the corresponding hormonal and neurophysiological levels of development and promotes to fast mobilization and stabilization their homeostasis. At the higher evolutionary scale after development of most brain neurotransmitter and hypothalamo-pituitary-adrenal systems the leading role in stress regulation begins to be predominent the hormonal reaction. Only in the alertness phase of stress-reaction the elements of activation of extrapyramidal regulatory system of locomotion are observed. This is manifested by the cateleptic immobility. Thus the stress as the general adaptational syndrome reflects the

Effect of Diabetes Sleep Education for T2DM Who Sleep After Midnight: A Pilot Study from China.

PubMed

Li, Mingzhen; Li, Daiqing; Tang, Yunzhao; Meng, Lingling; Mao, Cuixiu; Sun, Lirong; Chang, Baocheng; Chen, Liming

2018-02-01

Our prior study showed that patients with sleep disorders had poor blood pressure (BP), glycemic control, and more severe complications. Therefore, sleep is very important for diabetic control. Our work was to investigate whether individualized diabetes sleep education significantly improve sleep quality and glycemic control in type 2 diabetic patients who sleep after midnight and potential mechanism by a randomized parallel interventional study. T2D patients were randomly recruited to an intervention or control group. Patients received structured special diabetes sleep education program with 3-month follow-up. Pittsburg Sleep Quality Index (PSQI) was scored for each participant. Demographic data, HbA1c, biochemical, and some hormones were also examined. SPSS 13.0 was used for statistical analysis. One hundred patients were approached, and 45 were enrolled into our trial. Eventually, 31 patients completed the study. Patients in the intervention group greatly improved their sleep hygiene. After intervention, PSQI scores were lowered significantly (-1.48 ± 0.88 vs. -0.51 ± 0.71, P < 0.001), as well as significant reduction of HbA1c (-1.5 ± 0.55 vs. -1.11 ± 0.47, P < 0.05). Fasting plasma glucose was also lowered significantly. Homeostasis model assessment of insulin resistance was reduced significantly (-1.29 ± 0.97 vs. 1.04 ± 0.91, P < 0.01). Serum concentrations for interleukin (IL)-6, cortisol, and ghrelin were decreased significantly. Ghrelin (coefficients -0.65, P < 0.001), cortisol (coefficients -0.38, P < 0.05), and IL-6 (coefficients 0.452, P < 0.05) were correlated with HbA1c improvement. The change of ghrelin was negatively associated with the improvement of HbA1c. Diabetes sleep education could improve sleep quality, better blood glucose and BP, and decrease insulin resistance through healthier sleep hygiene. Lower serum concentration of ghrelin might be partly involved in the reduction of HbA1c.

Redox homeostasis: The Golden Mean of healthy living.

PubMed

Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

2016-08-01

The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

Benefits of oxytocin administration in obstructive sleep apnea.

PubMed

Jain, Vivek; Marbach, Joseph; Kimbro, Shawn; Andrade, David C; Jain, Arad; Capozzi, Eleanor; Mele, Kyle; Del Rio, Rodrigo; Kay, Matthew W; Mendelowitz, David

2017-11-01