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The Spring transition to Daylight Saving Time (DST) has been associated with several health and road safety issues. Previous literature has focused primarily on the analysis of historical crash and hospitalization data, without investigating specific crash contributing factors, such as driving fatigue. The present study aims to uncover the effects of DST-related circadian desynchrony and sleep deprivation on driving fatigue, by means of a driving simulator experiment. Eighteen participants (all males, age range 21-30 years, mean = 24.2, SD = 2.9) completed two 50-minute trials (at one week distance, same time and same day of the week) on a monotonous highway environment, the second one taking place in the week after the Spring transition to DST. Driving fatigue was evaluated by analysing several different variables (including driving-based, physiological and subjective indices) and by comparison with a historical cohort of pertinent, matched controls who had also undergone two trials, but in the absence of any time change in between. Results showed a considerable rise in fatigue levels throughout the driving task in both trials, but with significantly poorer performance in the post-DST trial, documented by a worsening in vehicle lateral control and an increase in eyelid closure. However, participants seemed unable to perceive this decrease in their alertness, which most likely prevented them from implementing fatigue-coping strategies. These findings indicate that DST has a detrimental effect on driving fatigue in young male drivers in the week after the Spring transition, and provide valuable insights into the complex relationship between DST and road safety.
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Transcatheter aortic valve replacement possesses a high validity for patients with aortic stenosis who are considered high risk for aortic valve replacement surgery, nowadays it is also considered for patients with intermediate risk or even lower risk in certain situations. The incidence of new conduction abnormalities remains to be a tough problem, in particular, left bundle branch block. New-onset left bundle branch block is a major concern despite improvements in valve technology, and it may affect postoperative prognosis. Understanding the anatomical relationship between the conduction system and the aortic root, clarify factors related to the procedure, devices, and patients, might help to reduce the conduction abnormalities. Physiological pacing has emerged as a reasonable pacing strategy for patients with cardiac insufficiency post-valve replacement, especially combined with left bundle branch block. The purpose of this review is to summarize the current opinion on the incidence of new-onset left bundle branch block associated with transcatheter aortic valve replacement, to offer insights into its anatomical and procedural causes, clinical consequences, and more importantly, the prospect of applying physiological pacing as a therapeutic method for these patients.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Arritmias Cardíacas/etiologia , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/epidemiologia , Bloqueio de Ramo/terapia , Eletrocardiografia/efeitos adversos , Humanos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
The two-process model serves as a major conceptual framework in sleep science. Although dating back more than four decades, it has not lost its relevance for research today. Retracing its origins, I describe how animal experiments aimed at exploring the oscillators driving the circadian sleep-wake rhythm led to the recognition of gradients of sleep states within the daily sleep period. Advances in signal analysis revealed that the level of slow-wave activity in non-rapid eye movement sleep electroencephalogram is high at the beginning of the 12-light period and then declines. After sleep deprivation, the level of slow-wave activity is enhanced. By scheduling recovery sleep to the animal's activity period, the conflict between the sleep-wake-dependent and the circadian influence resulted in a two-stage recovery pattern. These experiments provided the basis for the first version of the two-process model. Sleep deprivation experiments in humans showed that the decline of slow-wave activity during sleep is exponential. The two-process model posits that a sleep-wake-dependent homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C). At present, homeostatic and circadian facets of sleep regulation are being investigated at the synaptic level as well as in the transcriptome and proteome domains. The notion of sleep has been extended from a global phenomenon to local representations, while the master circadian pacemaker has been supplemented by multiple peripheral oscillators. The original interpretation that the emergence of sleep may be viewed as an escape from the rigid control imposed by the circadian pacemaker is still upheld.
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Privação do Sono , Sono , Animais , Ritmo Circadiano/fisiologia , Eletroencefalografia , Homeostase/fisiologia , Humanos , Sono/fisiologia , Vigília/fisiologiaRESUMO
Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.
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Privação do Sono/fisiopatologia , Sono/fisiologia , Vigília/fisiologia , Adulto , Nível de Alerta , Atenção , Ritmo Circadiano/fisiologia , Cognição , Feminino , Voluntários Saudáveis , Humanos , Masculino , Polissonografia , Desempenho Psicomotor , Tempo de Reação , Autorrelato , Transtornos do Sono-Vigília/fisiopatologia , Fatores de TempoRESUMO
OBJECTIVE: The aim of the article is to establish the interrelation of human biological rhythms and circadian hormones producement as well as to determine their impact on the medicine usage. PATIENTS AND METHODS: Materials and methods: The review and latest data analysis of scientific and medical literature were performed. CONCLUSION: Conclusions: Proceeding from the literature sources there is a firm interrelation between human biological rhythms and circadian hormones producement. Following chronotherapy principles will allow to increase effectiveness of diseases treatment, including dental ones. It will also allow to reduce dosage of prescribed medicines as well as their side effects. Prospects for a further research are to identify a clear relationship between circadian biorhythms in patients with chronic generalized periodontitis in order to increase the effectiveness of therapeutic measures.
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Ritmo Circadiano , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cronoterapia , Hormônios , HumanosRESUMO
The circadian system regulates physiology and behavior. Acute challenges to the system, such as those experienced when traveling across time zones, will eventually result in re-synchronization to local environmental time cues, but this re-synchronization is oftentimes accompanied by adverse short-term consequences. When such challenges are experienced chronically, adaptation may not be achieved, as for example in the case of rotating night shift workers. The transient and chronic disturbance of the circadian system is most frequently referred to as "circadian disruption", but many other terms have been proposed and used to refer to similar situations. It is now beyond doubt that the circadian system contributes to health and disease, emphasizing the need for clear terminology when describing challenges to the circadian system and their consequences. The goal of this review is to provide an overview of the terms used to describe disruption of the circadian system, discuss proposed quantifications of disruption in experimental and observational settings with a focus on human research, and highlight limitations and challenges of currently available tools. For circadian research to advance as a translational science, clear, operationalizable, and scalable quantifications of circadian disruption are key, as they will enable improved assessment and reproducibility of results, ideally ranging from mechanistic settings, including animal research, to large-scale randomized clinical trials.
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Ritmo Circadiano , Animais , Humanos , Reprodutibilidade dos TestesRESUMO
STUDY QUESTION: Is circadian desynchrony a risk factor of male reproductive damage in semen parameters and/or reproductive hormones? SUMMARY ANSWER: Circadian desynchrony correlates with decrease of sperm count, which was improved when circadian desynchrony was attenuated. WHAT IS KNOWN ALREADY: Circadian desynchrony caused by work (shift work) and non-work-related reasons is prevalent worldwide and has been found to be associated with decreased female fertility, but whether it harms male reproductive health is unclear. STUDY DESIGN, SIZE, DURATION: A hybrid research was conducted. (i) A cross-sectional study of 1346 Chinese men in 2007 was used to analyze the association between semen/hormone biomarkers and work-related circadian desynchrony, which was divided into rotating shift work and permanent shift work against non-shift work. (ii) A cohort of 796 Chinese undergraduates from 2013 to 2014 was used to analyzed the association between semen/hormone biomarkers and non-work-related circadian desynchrony (between school days and days off). (iii) The biomarker identified simultaneously in both populations was further validated in male C57BL/6J mice housed under conditions simulating circadian desynchrony. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 17 semen/hormone biomarkers were compared among rotating shift workers and permanent shift workers against non-shift workers in the 1346 reproductive-age Chinese men. A total of 14 semen/hormone biomarker was analyzed in the undergraduate cohort for correlation with non-work-related circadian desynchrony (measured by Munich Chronotype Questionnaire) in 2013 and 2014 and compared between the 2 years. Photoperiod-shifting method was used to establish the mouse model, in which the biomarker was examined and molecular mechanism was explored by apoptosis analysis, DNA content analysis, transcriptome sequencing, real-time PCR and western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: Among the semen/hormone biomarkers, sperm count was found to be lower in rotating shift workers, who had a higher risk of low sperm count defined by Chinese Ministry of Health (total sperm/ejaculate < 120 × 106) than non-shift workers (odds ratio = 1.26, 95% CI 1.05-1.52). This biomarker was replicated in the undergraduate cohort, where each hour of circadian desynchrony was associated with 1.16 (95% CI 1.02-1.31) fold odds of low sperm count, and sperm count increased during 2014 in men who reduced circadian desynchrony after 2013. A decrease of sperm count with circadian desynchrony and its recovery after removal of circadian desynchrony was also observed in the mouse model. During asynchrony, increased apoptosis was found in seminiferous tubules and the marker genes of post-spermatocyte stage cells were down-regulated. The most enriched functional pathway was homologous recombination, which happened during meiosis. LIMITATIONS, REASONS FOR CAUTION: The study of human beings was observational while the animal study has potential difference in circadian desynchrony exposure and species susceptibility. Further researches are needed to clarify the causal relationship in men. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide novel insight to the effect of circadian desynchrony on male reproductive health and a potential strategy for prevention of reproductive damage. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key R&D Program of China [2017YFC1002001] and National Natural Science Foundation of China [81871208]. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NA.
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Análise do Sêmen , Espermatozoides , Animais , China/epidemiologia , Estudos Transversais , Feminino , Genitália Masculina , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Espermatozoides , Motilidade dos EspermatozoidesRESUMO
Disturbing the circadian regulation of physiology by disruption of the rhythmic environment is associated with adverse health outcomes but the underlying mechanisms are unknown. Here, the response of central and peripheral circadian clocks to an advance or delay of the light-dark cycle was determined in mice. This identified transient damping of peripheral clocks as a consequence of an advanced light-dark cycle. Similar depression of peripheral rhythm amplitude was observed in mice exposed to repeated phase shifts. To assess the metabolic consequences of such peripheral amplitude depression in isolation, temporally chimeric mice lacking a functional central clock (Vgat-Cre+ Bmal1fl/fl ) were housed in the absence of environmental rhythmicity. In vivo PER2::LUC bioluminescence imaging of anesthetized and freely moving mice revealed that this resulted in a state of peripheral amplitude depression, similar in severity to that observed transiently following an advance of the light-dark cycle. Surprisingly, our mice did not show alterations in body mass or glucose tolerance in males or females on regular or high-fat diets. Overall, our results identify transient damping of peripheral rhythm amplitude as a consequence of exposure to an advanced light-dark cycle but chronic damping of peripheral clocks in isolation is insufficient to induce adverse metabolic outcomes in mice.
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Comportamento Animal , Relógios Biológicos , Ritmo Circadiano , Intolerância à Glucose , Obesidade , Animais , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Intolerância à Glucose/fisiopatologia , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologiaRESUMO
Circadian disruption has been linked to markers for poor health outcomes in humans and animal models. What is it about circadian disruption that is problematic? One hypothesis is that phase resetting of the circadian system, which occurs in response to changes in environmental timing cues, leads to internal desynchrony within the organism. Internal desynchrony is understood as acute changes in phase relationships between biological rhythms from different cell groups, tissues, or organs within the body. Do we have strong evidence for internal desynchrony associated with or caused by circadian clock resetting? Here we review the literature, highlighting several key studies from measures of gene expression in laboratory rodents. We conclude that current evidence offers strong support for the premise that some protocols for light-induced resetting are associated with internal desynchrony. It is important to continue research to test whether internal desynchrony is necessary and/or sufficient for negative health impact of circadian disruption.
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Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Periodicidade , Fotoperíodo , Animais , Relógios Circadianos/genética , Relógios Circadianos/efeitos da radiação , Ritmo Circadiano/genética , Ritmo Circadiano/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Luz , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiopatologia , Núcleo Supraquiasmático/efeitos da radiaçãoRESUMO
Circadian rhythms, or biological oscillations of approximately 24 hours, impact almost all aspects of our lives by regulating the sleep-wake cycle, hormone release, body temperature fluctuation, and timing of food consumption. The molecular machinery governing these rhythms is similar across organisms ranging from unicellular fungi to insects, rodents, and humans. Circadian entrainment, or temporal synchrony with one's environment, is essential for survival. In mammals, the central circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and mediates entrainment to environmental conditions. While the light:dark cycle is the primary environmental cue, arousal-inducing, non-photic signals such as food consumption, exercise, and social interaction are also potent synchronizers. Many of these stimuli enhance dopaminergic signaling suggesting that a cohesive circadian physiology depends on the relationship between circadian clocks and the neuronal circuits responsible for detecting salient events. Here, we review the inner workings of mammalian circadian entrainment, and describe the health consequences of circadian rhythm disruptions with an emphasis on dopamine signaling.
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Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Dopamina/fisiologia , Neurônios Dopaminérgicos/fisiologia , Transdução de Sinais/fisiologia , Núcleo Supraquiasmático/fisiopatologia , Animais , Dopamina/metabolismo , Humanos , Fotoperíodo , Núcleo Supraquiasmático/metabolismoRESUMO
Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light (rLL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 (Per1 and Per2), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under rLL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under rLL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals.SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by synchronizing peripheral clocks throughout the brain and body. Without the SCN, these peripheral clocks rapidly become desynchronized. Here, we provide a unique demonstration that, under lighting conditions in which the central clock in the SCN is dampened, peripheral oscillators in the hippocampus and olfactory bulb become desynchronized, along with the behavioral processes mediated by these clocks. Multiple clocks that adopt different phase relationships may enable processes occurring in different brain regions to be optimized to specific phases of the 24 h day. Moreover, such a dispersed network of dissociable circadian clocks may provide greater flexibility when faced with conflicting environmental signals (e.g., seasonal changes in photoperiod).
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Ritmo Circadiano/fisiologia , Percepção de Forma/fisiologia , Memória/fisiologia , Mascaramento Perceptivo/fisiologia , Reconhecimento Psicológico/fisiologia , Olfato/fisiologia , Navegação Espacial/fisiologia , Animais , Sincronização Cortical/fisiologia , Masculino , Rememoração Mental/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos , Análise e Desempenho de TarefasRESUMO
The detrimental health effects of excessive alcohol consumption are well documented. Alcohol-induced liver disease (ALD) is the leading cause of death from chronic alcohol use. As with many diseases, the etiology of ALD is influenced by how the liver responds to other secondary insults. The molecular circadian clock is an intrinsic cellular timing system that helps organisms adapt and synchronize metabolism to changes in their environment. The clock also influences how tissues respond to toxic, environmental, and metabolic stressors, like alcohol. Consistent with the essential role for clocks in maintaining health, genetic and environmental disruption of the circadian clock contributes to disease. While a large amount of rich literature is available showing that alcohol disrupts circadian-driven behaviors and that circadian clock disruption increases alcohol drinking and preference, very little is known about the role circadian clocks play in alcohol-induced tissue injuries. In this review, recent studies examining the effect alcohol has on the circadian clock in peripheral tissues (liver and intestine) and the impact circadian clock disruption has on development of ALD are presented. This review also highlights some of the rhythmic metabolic processes in the liver that are disrupted by alcohol and potential mechanisms through which alcohol disrupts the liver clock. Improved understanding of the mechanistic links between the circadian clock and alcohol will hopefully lead to the development of new therapeutic approaches for treating ALD and other alcohol-related organ pathologies.
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Relógios Circadianos/fisiologia , Hepatopatias Alcoólicas/metabolismo , Fígado/metabolismo , Ritmo Circadiano/fisiologia , HumanosRESUMO
Sleep timing shifts later during adolescence (second decade). This trend reverses at ~20 years and continues to shift earlier into adulthood. The current analysis examined the hypothesis that a longer free-running circadian period during late adolescence (14-17 years) compared with adulthood (30-45 years) accounts for sleep timing differences. Sex and ancestry were also examined because previous reports find that women and those with African-American ancestry have shorter free-running periods. Circadian period was measured using an ultradian dark-light protocol (2 hr dark/sleep, 2 hr dim room light [~20 lux]/wake) over 3.4 days. Dim light melatonin onsets were measured before and after the ultradian protocol, from which the circadian period was derived. In contrast to our hypothesis, we found that free-running circadian period was similar in adolescents and adults. African-American adults had shorter free-running circadian periods compared with adults of other ancestries. This ancestry difference was not seen in the adolescent group. Finally, we observed a non-significant trend for shorter free-running circadian periods in females compared with males. These data suggest that age-related changes in circadian period after late adolescence do not account for sleep timing differences. These data provide further support for ancestry-related differences in period, particularly in adults. Whether the large difference in circadian period between African-American and other ancestries emerges later in development should be explored.
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Ritmo Circadiano/fisiologia , Sono/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Olfactory sensitivity has traditionally been viewed as a trait that varies according to individual differences but is not expected to change with one's momentary state. Recent research has begun to challenge this position and time of day has been shown to alter detection levels. Links between obesity and the timing of food intake further raise the issue of whether odor detection may vary as a function of circadian processes. To investigate this question, 37 (21 male) adolescents (M age = 13.7 years) took part in a 28-h forced desynchrony (FD) protocol with 17.5 h awake and 10.5 h of sleep, for 7 FD cycles. Odor threshold was measured using Sniffin' Sticks 6 times for each FD cycle (total threshold tests = 42). Circadian phase was determined by intrinsic period derived from dim light melatonin onsets. Odor threshold showed a significant effect of circadian phase, with lowest threshold occurring on average slightly after the onset of melatonin production, or about 1.5â (approximately 21:08 h). Considerable individual variability was observed, however, peak olfactory acuity never occurred between 80.5â and 197.5â (~02:22-10:10 h). These data are the first to show that odor threshold is differentially and consistently influenced by circadian timing, and is not a stable trait. Potential biological relevance for connections between circadian phase and olfactory sensitivity are discussed.
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Ritmo Circadiano/fisiologia , Odorantes , Percepção Olfatória/fisiologia , Limiar Sensorial/fisiologia , Adolescente , Criança , Ingestão de Alimentos , Feminino , Humanos , Masculino , Sono/fisiologia , Vigília/fisiologiaRESUMO
In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle.
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Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Homeostase/fisiologia , Modelos Biológicos , Sono/fisiologia , Animais , Metabolismo Energético , Humanos , Privação do Sono/fisiopatologia , Higiene do Sono/fisiologia , Medicina do Sono/métodos , Núcleo Supraquiasmático/fisiologiaRESUMO
BACKGROUND: Circadian rhythms are essential for adapting to the environment. Chronic alcohol consumption often leads to sleep and circadian disruptions, which may impair the life quality of individuals with alcohol use disorders and contribute to the morbidity associated with alcoholism. METHODS: We used a pair-feeding liquid diet alcohol exposure protocol (6 weeks duration) in PER1::LUC transgenic rats to examine the effects of chronic alcohol exposure on: (i) diurnal rhythms of core body temperature and locomotor activity, (ii) plasma corticosterone (CORT) concentrations, and (iii) rhythms of ex vivo Period1 (Per1) expression in the suprachiasmatic nucleus (SCN), pituitary, and adrenal glands. We followed multiple circadian outputs not only to examine individual components, but also to assess the relative phase relationships among rhythms. RESULTS: We found that chronic alcohol consumption: (i) reduced 24-hour body temperature and locomotor activity counts in the dark period, (ii) advanced the acrophase of diurnal rhythms of body temperature and locomotor activity, (iii) abolished the phase difference between temperature and activity rhythms, (iv) blunted and advanced the diurnal CORT rhythm, and (v) advanced Per1 expression in the adrenal and pituitary glands but not in the SCN. We found that chronic alcohol altered the phase relationships among diurnal rhythms and between the central (SCN) and peripheral (adrenal and pituitary) molecular clocks. CONCLUSIONS: Our findings suggest that desynchrony among internal rhythms is an important and overlooked aspect of alcohol-induced circadian disruptions. The misalignment of phases among rhythms may compromise normal physiological functions and put individuals with chronic alcohol use at greater risk for developing other physical and mental health issues. How this desynchrony occurs and the extent to which it participates in alcohol-related pathologies requires further investigation.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Ritmo Circadiano/efeitos dos fármacos , Glândulas Suprarrenais/química , Animais , Temperatura Corporal/efeitos dos fármacos , Corticosterona/sangue , Masculino , Atividade Motora/efeitos dos fármacos , Proteínas Circadianas Period/análise , Hipófise/química , Ratos , Ratos Transgênicos , Ratos Wistar , Núcleo Supraquiasmático/químicaRESUMO
Extending a normal 24 hours day by four hours is unexpectedly highly disruptive to daily rhythms in gene expression in the blood. Using a paradigm in which human subjects were exposed to a 28 hours day, Archer and colleagues show how this sleep-altering forced desynchrony protocol caused complex disruption to daily rhythms in distinct groups of genes. Such perturbations in the temporal organisation of the blood transcriptome arise quickly, and point to the fragile nature of coordinated genomic activity. Chronic disruption of the daily and circadian rhythms in sleep compromise health and well-being and this study reveals potential new molecular targets to combat the disruptive effects of shift work and jetlag.
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Ritmo Circadiano , Sono , Transcriptoma , Feminino , Humanos , MasculinoRESUMO
The circadian clock disorders in humans remain poorly understood. However, their impact on the development and progression of major human conditions, from cancer to insomnia, metabolic or mental illness becomes increasingly apparent. Addressing human circadian disorders in animal models is, in part, complicated by inverse temporal relationship between the core clock and specific physiological or behavioral processes in diurnal and nocturnal animals. Major advantages of a macaque model for translational circadian research, as a diurnal vertebrate phylogenetically close to humans, are further emphasized by the discovery of the first familial circadian disorder in non-human primates among the rhesus monkeys originating from Cayo Santiago. The remarkable similarity of their pathological phenotypes to human Delayed Sleep Phase Disorder (DSPD), high penetrance of the disorder within one branch of the colony and the large number of animals available provide outstanding opportunities for studying the mechanisms of circadian disorders, their impact on other pathological conditions, and for the development of novel and effective treatment strategies.
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Transtornos Cronobiológicos/etiologia , Relógios Circadianos , Macaca mulatta/fisiologia , Sono , Animais , Humanos , Modelos Animais , Porto RicoRESUMO
Slow waves (SWs, 0.5-4Hz) in field potentials during sleep reflect synchronized alternations between bursts of action potentials and periods of membrane hyperpolarization of cortical neurons. SWs decline during sleep and this is thought to be related to a reduction of synaptic strength in cortical networks and to be central to sleep's role in maintaining brain function. A central assumption in current concepts of sleep function is that SWs during sleep, and associated recovery processes, are independent of circadian rhythmicity. We tested this hypothesis by quantifying all SWs from 12 EEG derivations in 34 participants in whom 231 sleep periods were scheduled across the circadian cycle in a 10-day forced-desynchrony protocol which allowed estimation of the separate circadian and sleep-dependent modulation of SWs. Circadian rhythmicity significantly modulated the incidence, amplitude, frequency and the slope of the SWs such that the peaks of the circadian rhythms in these slow-wave parameters were located during the biological day. Topographical analyses demonstrated that the sleep-dependent modulation of SW characteristics was most prominent in frontal brain areas whereas the circadian effect was similar to or greater than the sleep-dependent modulation over the central and posterior brain regions. The data demonstrate that circadian rhythmicity directly modulates characteristics of SWs thought to be related to synaptic plasticity and that this modulation depends on topography. These findings have implications for the understanding of local sleep regulation and conditions such as ageing, depression, and neurodegeneration which are associated with changes in SWs, neural plasticity and circadian rhythmicity.
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Ondas Encefálicas , Córtex Cerebral/fisiologia , Ritmo Circadiano , Sono/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Fases do Sono/fisiologia , Adulto JovemRESUMO
The environmental light-dark (LD) cycle entrains the central circadian clock located in the suprachiasmatic nucleus (SCN) of mammals. The present study examined the effects of disrupted LD cycles on peripheral clocks in mice housed under a normal 12 h light-12 h dark cycle (LD 12:12) or an ultradian LD 3:3 cycle. Drinking behavior seemed to be free-running with a long period (26.03 h) under ultradian LD 3:3 cycles, in addition to light-induced direct suppression (masking effect). Core body temperature completely lost robust circadian rhythm and acquired a 6-h rhythm with a low amplitude under LD 3:3. Robust circadian expression of Per1, Per2, Clock and Bmal1 mRNAs was similarly flattened to intermediate levels in the liver, heart and white adipose tissue under LD 3:3. Robust circadian expression of Rev-erbα mRNA was completely damped in these tissues. Circadian expression of Dbp, a clock-controlled gene, was also disrupted in these tissues from mice housed under LD 3:3. The aberrant LD cycle seemed to induce the loss of circadian gene expression at the level of transcription, because rhythmic pre-mRNA expression of these genes was also abolished under LD 3:3. In addition to the direct effect of the aberrant LD cycle, abolished systemic time cues such as those of plasma corticosterone and body temperature might be involved in the disrupted expression of these circadian genes under LD 3:3. Our findings suggest that disrupted environmental LD cycles abolish the normal oscillation of peripheral clocks and induce internal desynchrony in mammals.