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Sample records for generating circadian rhythms

  1. Circadian Rhythms

    MedlinePLUS

    ... NIGMS Home > Science Education > Circadian Rhythms Fact Sheet Circadian Rhythms Fact Sheet Tagline (Optional) Middle/Main Content Area En español What are circadian rhythms? Circadian rhythms are physical, mental and behavioral changes ...

  2. Circadian Rhythms

    MedlinePLUS

    ... chronobiology. Are circadian rhythms the same thing as biological clocks? No, but they are related. Our biological clocks drive our circadian rhythms. What are biological clocks? The biological clocks that control circadian rhythms ...

  3. Biological Clocks & Circadian Rhythms

    ERIC Educational Resources Information Center

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  4. Ageing and Circadian rhythms

    PubMed Central

    Giebultowicz, Jadwiga M.; Long, Dani M.

    2015-01-01

    Circadian clocks are cell-autonomous molecular feedback loops that generate daily rhythms in gene expression, cellular functions, physiological processes and behavior. The mechanisms of circadian clocks are well understood in young fruit flies Drosophila melanogaster, but less is known about how circadian system changes during organismal aging. Similar as in humans, rest/activity rhythms tend to weaken with age in fruit flies, suggesting conservation of aging-related changes in the circadian system. It has been shown that aging is associated with reduced expression of core clock genes in peripheral head clocks while similar reduction may not occur in central clock neurons regulating behavioral rhythms. Arrhythmic flies with mutations in core clock genes display accelerated aging and shortened lifespan suggesting that weakened circadian rhythms may contribute to aging phenotypes. To understand whether strong circadian clocks support organism’s healthspan and lifespan, future research needs to focus on age-related changes in clock genes as well as clock-controlled genes in specific organs and tissues. PMID:26000238

  5. Sleep and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.

    1991-01-01

    Three interacting processes are involved in the preservation of circadian rhythms: (1) endogenous rhythm generation mechanisms, (2) entrainment mechanisms to keep these rhythms 'on track', and (3) exogenous masking processes stemming from changes in environment and bahavior. These processes, particularly the latter two, can be dramatically affected in individuals of advanced age and in space travelers, with a consequent disruption in sleep and daytime functioning. This paper presents results of a phase-shift experiment investigating the age-related effects of the exogeneous component of circadian rhythms in various physiological and psychological functions by comparing these functions in middle aged and old subjects. Dramatic differences were found between the two age groups in measures of sleep, mood, activation, and performance efficiency.

  6. Biological Clocks & Circadian Rhythms

    ERIC Educational Resources Information Center

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  7. Circadian Rhythms in Cyanobacteria.

    PubMed

    Cohen, Susan E; Golden, Susan S

    2015-12-01

    Life on earth is subject to daily and predictable fluctuations in light intensity, temperature, and humidity created by rotation of the earth. Circadian rhythms, generated by a circadian clock, control temporal programs of cellular physiology to facilitate adaptation to daily environmental changes. Circadian rhythms are nearly ubiquitous and are found in both prokaryotic and eukaryotic organisms. Here we introduce the molecular mechanism of the circadian clock in the model cyanobacterium Synechococcus elongatus PCC 7942. We review the current understanding of the cyanobacterial clock, emphasizing recent work that has generated a more comprehensive understanding of how the circadian oscillator becomes synchronized with the external environment and how information from the oscillator is transmitted to generate rhythms of biological activity. These results have changed how we think about the clock, shifting away from a linear model to one in which the clock is viewed as an interactive network of multifunctional components that are integrated into the context of the cell in order to pace and reset the oscillator. We conclude with a discussion of how this basic timekeeping mechanism differs in other cyanobacterial species and how information gleaned from work in cyanobacteria can be translated to understanding rhythmic phenomena in other prokaryotic systems. PMID:26335718

  8. Stochastic simulations on a model of circadian rhythm generation.

    PubMed

    Miura, Shigehiro; Shimokawa, Tetsuya; Nomura, Taishin

    2008-01-01

    Biological phenomena are often modeled by differential equations, where states of a model system are described by continuous real values. When we consider concentrations of molecules as dynamical variables for a set of biochemical reactions, we implicitly assume that numbers of the molecules are large enough so that their changes can be regarded as continuous and they are described deterministically. However, for a system with small numbers of molecules, changes in their numbers are apparently discrete and molecular noises become significant. In such cases, models with deterministic differential equations may be inappropriate, and the reactions must be described by stochastic equations. In this study, we focus a clock gene expression for a circadian rhythm generation, which is known as a system involving small numbers of molecules. Thus it is appropriate for the system to be modeled by stochastic equations and analyzed by methodologies of stochastic simulations. The interlocked feedback model proposed by Ueda et al. as a set of deterministic ordinary differential equations provides a basis of our analyses. We apply two stochastic simulation methods, namely Gillespie's direct method and the stochastic differential equation method also by Gillespie, to the interlocked feedback model. To this end, we first reformulated the original differential equations back to elementary chemical reactions. With those reactions, we simulate and analyze the dynamics of the model using two methods in order to compare them with the dynamics obtained from the original deterministic model and to characterize dynamics how they depend on the simulation methodologies. PMID:18585851

  9. [Circadian rhythms and chronic diseases].

    PubMed

    Suter, Paolo M

    2015-11-11

    Everything in nature and life is occurring in a rhythmic manner. The major “Zeitgeber” is the change of light and dark during a 24 h day. This circadian rhythm is besides others reflected in circadian rhythms of behaviors or different biochemical parameters. A disruption of the circadian rhythm has a high pathophysiological potential. In this article a few basic issues about the role of circadian rhythms and the pathophysiological importance of desynchronisation are reviewed. PMID:26558932

  10. The suprachiasmatic nucleus functions beyond circadian rhythm generation

    PubMed Central

    Hu, Kun; Scheer, Frank A.J.L.; Ivanov, Plamen Ch.; Buijs, Ruud M.; Shea, Steven A.

    2009-01-01

    We recently discovered that human activity possesses a complex temporal organization characterized by scale-invariant/self-similar fluctuations from seconds to ~4 hour—statistical properties of fluctuations remain the same at different time scales. Here, we show that scale-invariant activity patterns are essentially identical in humans and rats, and exist for up to ~24 hour: six-times longer than previously documented. Theoretically, such scale-invariant patterns can be produced by a neural network of interacting control nodes—system components with feedback loops—operating at different time scales. However such control nodes have not yet been identified in any neurophysiological model of scale invariance/self-similarity in mammals. Here we demonstrate that the endogenous circadian pacemaker (suprachiasmastic nucleus; SCN), known to modulate locomotor activity with a periodicity of ~24 hour, also acts as a major neural control node responsible for the generation of scale-invariant locomotor patterns over a broad range of time scales from minutes to at least 24 hour (rather than solely at ~24 hour). Remarkably, we found that SCN lesion in rats completely abolished the scale-invariant locomotor pattern between 4 and 24 hour and significantly altered the patterns at time scales <4 hour. Identification of the control nodes of a neural network responsible for scale invariance is the critical first step in understanding the neurophysiological origin of scale invariance/self-similarity. PMID:17920204

  11. [Circadian rhythm sleep disorder].

    PubMed

    Mishima, Kazuo

    2013-12-01

    Primary pathophysiology of circadian rhythm sleep disorders(CRSDs) is a misalignment between the endogenous circadian rhythm phase and the desired or socially required sleep-wake schedule, or dysfunction of the circadian pacemaker and its afferent/efferent pathways. CRSDs consist of delayed sleep phase type, advanced sleep phase type, free-running type, irregular sleep-wake type, shift work type and jet lag type. Chronotherapy using strong zeitgebers (time cues), such as bright light and melatonin/ melatonin type 2 receptor agonist, is effective when administered with proper timing. Bright light is the strongest entraining agent of circadian rhythms. Bright light therapy (appropriately-timed exposure to bright light) for CRSDs is an effective treatment option, and can shift the sleep-wake cycle to earlier or later times, in order to correct for misalignment between the circadian system and the desired sleep-wake schedule. Timed administration of melatonin, either alone or in combination with light therapy has also been shown to be useful in the treatment of CRSDs. PMID:24437262

  12. Circadian Rhythm Sleep Disorders

    PubMed Central

    Kim, Min Ju; Lee, Jung Hie; Duffy, Jeanne F.

    2014-01-01

    Objective To review circadian rhythm sleep disorders, including underlying causes, diagnostic considerations, and typical treatments. Methods Literature review and discussion of specific cases. Results Survey studies 1,2 suggest that up to 3% of the adult population suffers from a circadian rhythm sleep disorder (CRSD). However, these sleep disorders are often confused with insomnia, and an estimated 10% of adult and 16% of adolescent sleep disorders patients may have a CRSD 3-6. While some CRSD (such as jet lag) can be self-limiting, others when untreated can lead to adverse medical, psychological, and social consequences. The International Classification of Sleep Disorders classifies CRSD as dyssomnias, with six subtypes: Advanced Sleep Phase Type, Delayed Sleep Phase Type, Irregular Sleep Wake Type, Free Running Type, Jet Lag Type, and Shift Work Type. The primary clinical characteristic of all CRSD is an inability to fall asleep and wake at the desired time. It is believed that CRSD arise from a problem with the internal biological clock (circadian timing system) and/or misalignment between the circadian timing system and the external 24-hour environment. This misalignment can be the result of biological and/or behavioral factors. CRSD can be confused with other sleep or medical disorders. Conclusions Circadian rhythm sleep disorders are a distinct class of sleep disorders characterized by a mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep. If untreated, CRSD can lead to insomnia and excessive daytime sleepiness, with negative medical, psychological, and social consequences. It is important for physicians to recognize potential circadian rhythm sleep disorders so that appropriate diagnosis, treatment, and referral can be made. PMID:25368503

  13. Genetics of Circadian Rhythms.

    PubMed

    Andreani, Tomas S; Itoh, Taichi Q; Yildirim, Evrim; Hwangbo, Dae-Sung; Allada, Ravi

    2015-12-01

    Nearly all organisms exhibit time-dependent behavior and physiology across a 24-hour day known as circadian rhythms. These outputs are manifestations of endogenous cyclic gene expression patterns driven by the activity of a core transcription/translation feedback loop. Cyclic gene expression determines highly tissue-specific functional activity regulating such processes as metabolic state, endocrine activity, and neural excitability. Entrainment of these cellular clocks is achieved through exogenous daily inputs, such as light and food. Dysregulation of the transcription/translation feedback loop has been shown to result in a wide range of disorders and diseases driving increased interest in circadian therapies. PMID:26568119

  14. Studying circadian rhythms in Drosophila melanogaster

    PubMed Central

    Tataroglu, Ozgur; Emery, Patrick

    2014-01-01

    Circadian rhythms have a profound influence on most bodily functions: from metabolism to complex behaviors. They ensure that all these biological processes are optimized with the time-of-day. They are generated by endogenous molecular oscillators that have a period that closely, but not exactly, matches day length. These molecular clocks are synchronized by environmental cycles such as light intensity and temperature. Drosophila melanogaster has been a model organism of choice to understand genetically, molecularly and at the level of neural circuits how circadian rhythms are generated, how they are synchronized by environmental cues, and how they drive behavioral cycles such as locomotor rhythms. This review will cover a wide range of techniques that have been instrumental to our understanding of Drosophila circadian rhythms, and that are essential for current and future research. PMID:24412370

  15. The Neurobiology of Circadian Rhythms.

    PubMed

    Sollars, Patricia J; Pickard, Gary E

    2015-12-01

    There is a growing recognition that the coordinated timing of behavioral, physiologic, and metabolic circadian rhythms is a requirement for a healthy body and mind. In mammals, the primary circadian oscillator is the hypothalamic suprachiasmatic nucleus (SCN), which is responsible for circadian coordination throughout the organism. Temporal homeostasis is recognized as a complex interplay between rhythmic clock gene expression in brain regions outside the SCN and in peripheral organs. Abnormalities in this intricate circadian orchestration may alter sleep patterns and contribute to the pathophysiology of affective disorders. PMID:26600101

  16. Aging and Circadian Rhythms.

    PubMed

    Duffy, Jeanne F; Zitting, Kirsi-Marja; Chinoy, Evan D

    2015-12-01

    Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. This article reviews key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep. PMID:26568120

  17. Phenotyping Circadian Rhythms in Mice.

    PubMed

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

    Circadian rhythms take place with a periodicity of 24 hr, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the "central pacemaker" of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hr as manifest when an animal is placed into constant dark or "free-running" conditions. Simple measurements of an organism's activity in free-running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their homecage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are presented here including the process of entrainment, determination of tau (period length) in free-running conditions, determination of circadian periodicity in response to light disruption (e.g., jet lag studies), and evaluation of clock plasticity in non-24-hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of environmental surroundings. PMID:26331760

  18. Circadian rhythms, sleep, and metabolism

    PubMed Central

    Huang, Wenyu; Ramsey, Kathryn Moynihan; Marcheva, Biliana; Bass, Joseph

    2011-01-01

    The discovery of the genetic basis for circadian rhythms has expanded our knowledge of the temporal organization of behavior and physiology. The observations that the circadian gene network is present in most living organisms from eubacteria to humans, that most cells and tissues express autonomous clocks, and that disruption of clock genes results in metabolic dysregulation have revealed interactions between metabolism and circadian rhythms at neural, molecular, and cellular levels. A major challenge remains in understanding the interplay between brain and peripheral clocks and in determining how these interactions promote energy homeostasis across the sleep-wake cycle. In this Review, we evaluate how investigation of molecular timing may create new opportunities to understand and develop therapies for obesity and diabetes. PMID:21633182

  19. Phenotyping Circadian Rhythms in Mice

    PubMed Central

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

    Circadian rhythms take place with a periodicity of twenty-four hours, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the “central pacemaker” of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hours as manifest when an animal is placed into constant dark- or “free running”- conditions. Simple measurements of an organism's activity in free running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their home cage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are outlined here including the process of entrainment, determination of tau (period length) in free running conditions, determination of circadian periodicity in response to light disruption (i.e. jet lag studies), and evaluation of clock plasticity in non-twenty-four hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of one's environmental surroundings. PMID:26331760

  20. Characteristics of circadian rhythms in human functions.

    PubMed

    Wever, R A

    1986-01-01

    Circadian rhythms are of endogenous origin, in humans as in all organisms. Under temporal isolation, i.e., after exclusion of all environmental time cues, circadian rhythmicity persists but with a period slightly deviating from 24 hours; in human, freerunning circadian rhythms always show periods close to 25 hours. In a minority of experiments, overt rhythms of different variables do not run in mutual synchrony but internally desynchronized in the steady state. This means that, indeed, most physiological rhythms, and particularly that of body temperature, hold a period close to 25 hours; it is mainly the sleep-wake rhythm (but also the overt rhythms of several more variables) which shows freerunning periods being considerably longer or shorter than 25 hours. This state of the rhythm is not concerned by the presence or absence of naps; rather, this state is characterized by a considerable stretching or compressing of the entire sleep-wake cycle. The period and other parameters of freerunning rhythms can be modified by continuously operating stimuli. Also the tendency toward the spontaneous occurrence of internal desynchronization does not depend only on personality data (e.g., neuroticism, or age) but also on the external conditions. Whereas constant light in the normal range of artificial illumination (intensities between 0 and 1500 lux) does not affect freerunning human circadian rhythms, the period is longer and the tendency toward internal desynchronization is higher under constant bright light (intensity greater than 3000 lux) than under constant light of normal intensity (or total darkness). This result has been confirmed with various physiological functions, e.g. the rhythms of deep body temperature and melatonin excretion. Social contacts (when subjects do not live singly isolated but in groups) or behavioral stress operates in the same direction as bright light. On the other hand, physical workload does not affect freerunning rhythms. Under natural conditions, the endogenously generated rhythms are synchronized to the 24-hour day. Under laboratory conditions (i.e., under temporal isolation), also artificial zeitgebers can be effective but only within limited ranges of periods; the width of such a range of entrainment is an indicator of the strength of the zeitgeber under consideration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3462338

  1. Circadian Rhythm Control: Neurophysiological Investigations

    NASA Technical Reports Server (NTRS)

    Glotzbach, S. F.

    1985-01-01

    The suprachiasmatic nucleus (SCN) was implicated as a primary component in central nervous system mechanisms governing circadian rhythms. Disruption of the normal synchronization of temperature, activity, and other rhythms is detrimental to health. Sleep wake disorders, decreases in vigilance and performance, and certain affective disorders may result from or be exacerbated by such desynchronization. To study the basic neurophysiological mechanisms involved in entrainment of circadian systems by the environment, Parylene-coated, etched microwire electrode bundles were used to record extracellular action potentials from the small somata of the SCN and neighboring hypothalamic nuclei in unanesthetized, behaving animals. Male Wistar rats were anesthetized and chronically prepared with EEG ane EMG electrodes in addition to a moveable microdrive assembly. The majority of cells had firing rates 10 Hz and distinct populations of cells which had either the highest firing rate or lowest firing rate during sleep were seen.

  2. Neurobiology of Circadian Rhythm Regulation.

    PubMed

    Rosenwasser, Alan M; Turek, Fred W

    2015-12-01

    Over the past few decades, multilevel research has elucidated the basic neuroanatomy, neurochemistry, and molecular neurobiology of the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The circadian timing system is composed of a large number of cellular oscillators located in the SCN, in non-SCN brain structures, and throughout the body. Cellular-level oscillations are generated by a molecular feedback loop in which circadian clock genes rhythmically regulate their own transcription, as well as that of hundreds of clock-controlled genes. The maintenance of proper coordination within this network of cellular- and tissue-level clocks is essential for health and well-being. PMID:26568118

  3. Circadian rhythms: glucocorticoids and arthritis.

    PubMed

    Cutolo, Maurizio; Sulli, Alberto; Pizzorni, Carmen; Secchi, Maria Elena; Soldano, Stefano; Seriolo, Bruno; Straub, Rainer H; Otsa, Kati; Maestroni, Georges J

    2006-06-01

    Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time-dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time-dependent inflammatory reaction with effects opposite those of cortisol. Interestingly, cortisol and MLT show an opposite response to the light. The light conditions in the early morning have a strong impact on the morning cortisol peak, whereas MLT is synthesized in a strictly nocturnal pattern. Recently, a diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and MLT. The interferon (IFN)-gamma/interleukin (IL)-10 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma MLT. Accordingly, the intensity of the arthritic pain varies consistently as a function of the hour of the day: pain is greater after waking up in the morning than in the afternoon or evening. The reduced cortisol and adrenal androgen secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with glucocoticoids, should be clearly considered as a "relative adrenal insufficiency" in the presence of a sustained inflammatory process, and allows Th1 type cytokines to be produced in higher amounts during the late night. In conclusion, the right timing (early morning) for the glucocorticoid therapy in arthritis is fundamental and well justified by the circadian rhythms of the inflammatory mechanisms. PMID:16855156

  4. Therapeutics for Circadian Rhythm Sleep Disorders

    PubMed Central

    Dodson, Ehren R.; Zee, Phyllis C

    2010-01-01

    Synopsis The sleep-wake cycle is regulated by the interaction of endogenous circadian and homeostatic processes. The circadian system provides timing information for most physiological rhythms, including the sleep and wake cycle. In addition, the central circadian clock located in the suprachiasmatic nucleus of the hypothalamus has been shown to promote alertness during the day. Circadian rhythm sleep disorders arise when there is a misalignment between the timing of the endogenous circadian rhythms and the external environment or when there is dysfunction of the circadian clock or its entrainment pathways. The primary synchronizing agents of the circadian system are light and melatonin. Light is the strongest entraining agent of circadian rhythms and timed exposure to bright light is often used in the treatment of circadian rhythm sleep disorders. In addition, timed administration of melatonin, either alone or in combination with light therapy has been shown to be useful in the treatment of the following circadian rhythm sleep disorders: delayed sleep phase, advanced sleep phase, free-running, irregular sleep wake, jet lag and shift work. PMID:21243069

  5. Circadian rhythms in myocardial metabolism and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in myocardial function and dysfunction are firmly established in both animal models and humans. For example, the incidence of arrhythmias and sudden cardiac death increases when organisms awaken. Such observations have classically been explained by circadian rhythms in neurohumoral...

  6. Circadian rhythms and treatment implications in depression.

    PubMed

    Monteleone, Palmiero; Martiadis, Vassilis; Maj, Mario

    2011-08-15

    In humans almost all physiological and behavioural functions occur on a rhythmic basis. Therefore the possibility that delays, advances or desynchronizations of circadian rhythms may play a role in the pathophysiology of psychiatric disorders is an interesting field of research. In particular mood disorders such as seasonal affective disorder and major depression have been linked to circadian rhythms alterations. Furthermore, the antidepressant efficacy of both pharmacological and non-pharmacological strategies affecting endogenous circadian rhythms, such as new antidepressant medications, light-therapy and sleep deprivation, is consistent with the idea that circadian alterations may represent a core component of depression, at least in a subgroup of depressed patients. This paper briefly describes the molecular and genetic mechanisms regulating the endogenous clock system, and reviews the literature supporting the relationships between depression, antidepressant treatments and changes in circadian rhythms. PMID:20691746

  7. Circadian Rhythm Sleep-Wake Disorders.

    PubMed

    Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C

    2015-12-01

    The circadian system regulates the timing and expression of nearly all biological processes, most notably, the sleep-wake cycle, and disruption of this system can result in adverse effects on both physical and mental health. The circadian rhythm sleep-wake disorders (CRSWDs) consist of 5 disorders that are due primarily to pathology of the circadian clock or to a misalignment of the timing of the endogenous circadian rhythm with the environment. This article outlines the nature of these disorders, the association of many of these disorders with psychiatric illness, and available treatment options. PMID:26600110

  8. Circadian Rhythms and Obesity in Mammals

    PubMed Central

    Froy, Oren

    2012-01-01

    Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity. PMID:24527263

  9. Circadian rhythms, sleep, and the menstrual cycle.

    PubMed

    Baker, Fiona C; Driver, Helen S

    2007-09-01

    Women with ovulatory menstrual cycles have a circadian rhythm superimposed on the menstrual-associated rhythm; in turn, menstrual events affect the circadian rhythm. In this paper, we review circadian rhythms in temperature, selected hormone profiles, and sleep-wake behavior in healthy women at different phases of the menstrual cycle. The effects on menstrual cycle rhythmicity of disrupted circadian rhythms, for example, with shiftwork and altered circadian rhythms in women with menstrual-related mood disturbances, are discussed. Compared to the follicular phase, in the post-ovulation luteal phase, body temperature is elevated, but the amplitude of the temperature rhythm is reduced. Evidence indicates that the amplitude of other rhythms, such as melatonin and cortisol, may also be blunted in the luteal phase. Subjective sleep quality is lowest around menses, but the timing and composition of sleep remains relatively stable across the menstrual cycle in healthy women, apart from an increase in spindle frequency activity and a minor decrease in rapid eye movement (REM) sleep during the luteal phase. Disruption of circadian rhythms is associated with disturbances in menstrual function. Female shiftworkers compared to non-shiftworkers are more likely to report menstrual irregularity and longer menstrual cycles. There also is accumulating evidence that circadian disruption increases the risk of breast cancer in women, possibly due to altered light exposure and reduced melatonin secretion. Further investigations into the biological consequences of circadian disruption in women will offer insight into some menstrual-associated disorders, including mood changes, as well as reproductive function and possible links with breast cancer. PMID:17383933

  10. CIRCADIAN RHYTHMS FROM MULTIPLE OSCILLATORS: LESSONS FROM DIVERSE ORGANISMS

    PubMed Central

    Bell-Pedersen, Deborah; Cassone, Vincent M.; Earnest, David J.; Golden, Susan S.; Hardin, Paul E.; Thomas, Terry L.; Zoran, Mark J.

    2009-01-01

    The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated tissues can partition clock function to generate and coordinate different rhythms. In both cases, the temporal coordination of a multi-oscillator system is essential for producing robust circadian rhythms of gene expression and biological activity. PMID:15951747

  11. Attenuated Circadian Rhythms in Mice Lacking the Prokineticin 2 Gene

    PubMed Central

    Li, Jia-Da; Hu, Wang-Ping; Boehmer, Lisa; Cheng, Michelle Y.; Lee, Alex G.; Jilek, Alexander; Siegel, Jerome M.; Zhou, Qun-Yong

    2009-01-01

    Circadian clocks drive daily rhythms in virtually all organisms. In mammals, the suprachiasmatic nucleus (SCN) is recognized as the master clock that synchronizes central and peripheral oscillators to evoke circadian rhythms of diverse physiology and behavior. How the timing information is transmitted from the SCN clock to generate overt circadian rhythms is essentially unknown. Prokineticin 2 (PK2), a clock-controlled gene that encodes a secreted protein, has been indicated as a candidate SCN clock output signal that regulates circadian locomotor rhythm. Here we report the generation and analysis of PK2-null mice. The reduction of locomotor rhythms in PK2-null mice was apparent in both hybrid and inbred genetic backgrounds. PK2-null mice also displayed significantly reduced rhythmicity for a variety of other physiological and behavioral parameters, including sleep—wake cycle, body temperature, circulating glucocorticoid and glucose levels, as well as the expression of peripheral clock genes. In addition, PK2-null mice showed accelerated acquisition of food anticipatory activity during a daytime food restriction. We conclude that PK2, acting as a SCN output factor, is important for the maintenance of robust circadian rhythms. PMID:17093083

  12. Circadian Rhythm in Cytokines Administration.

    PubMed

    Trufakin, Valery A; Shurlygina, Anna V

    2016-01-01

    In recent times, a number of diseases involving immune system dysfunction have appeared. This increases the importance of research aimed at finding and developing optimized methods for immune system correction. Numerous studies have found a positive effect in using cytokines to treat a variety of diseases, yet the clinical use of cytokines is limited by their toxicity. Research in the field of chronotherapy, aimed at designing schedules of medicine intake using circadian biorhythms of endogenous production of factors, and receptors' expression to the factors on the target cells, as well as chronopharmacodynamics and chronopharmacokinetics of medicines may contribute to the solution of this problem. Advantages of chronotherapy include a greater effectiveness of treatment, reduced dose of required drugs, and minimized adverse effects. This review presents data on the presence of circadian rhythms of spontaneous and induced cytokine production, as well as the expression of cytokine receptors in the healthy body and in a number of diseases. The article reviews various effects of cytokines, used at different times of the day in humans and experimental animals, as well as possible mechanisms underlying the chronodependent effects of cytokines. The article presents the results of chronotherapeutic modes of administering IL-2, interferons, G-CSF, and GM-CSF in treatment of various types of cancer as well as in experimental models of immune suppression and inflammation, which lead to a greater effectiveness of therapy, the possibility of reducing or increasing the dosage, and reduced drug toxicity. Further research in this field will contribute to the effectiveness and safety of cytokine therapy. PMID:26349494

  13. Sleep and circadian rhythm disruption in neuropsychiatric illness.

    PubMed

    Jagannath, Aarti; Peirson, Stuart N; Foster, Russell G

    2013-10-01

    Sleep and circadian rhythm disruption (SCRD) is a common feature in many neuropsychiatric diseases including schizophrenia, bipolar disorder and depression. Although the precise mechanisms remain unclear, recent evidence suggests that this comorbidity is not simply a product of medication or an absence of social routine, but instead reflects commonly affected underlying pathways and mechanisms. For example, several genes intimately involved in the generation and regulation of circadian rhythms and sleep have been linked to psychiatric illness. Further, several genes linked to mental illness have recently been shown to also play a role in normal sleep and circadian behaviour. Here we describe some of the emerging common mechanisms that link circadian rhythms, sleep and SCRD in severe mental illnesses. A deeper understanding of these links will provide not only a greater understanding of disease mechanisms, but also holds the promise of novel avenues for therapeutic intervention. PMID:23618559

  14. Seasonality in freerunning circadian rhythms in man.

    PubMed

    Wirz-Justice, A; Wever, R A; Aschoff, J

    1984-06-01

    Retrospective analysis of data collected over 15 years in normal subjects isolated from time cures showed seasonal rhythms in the circadian period of the core temperature rhythm, in the amount of sleep (both shorter in spring and longer in autumn), and in the incidence of internal desynchronisation (most often in summer). Women slept longer than men at all times of year. PMID:6472481

  15. Suprachiasmatic stimulation phase shifts rodent circadian rhythms.

    PubMed

    Rusak, B; Groos, G

    1982-03-12

    The integrity of the suprachiasmatic nuclei (SCN) of the hypothalamus is essential to the expression of normal circadian rhythms in rodents. Electrical stimulation of the SCN caused phase shifts and period changes in the freerunning feeding rhythms of rats and activity rhythms of hamsters. The phase response curve for SCN stimulation appears to parallel that for light pulses. These findings strengthen the hypothesis derived from lesion studies that the SCN are the dominant light-entrained oscillators in the rodent circadian system. PMID:7063851

  16. [Circadian rhythm variability in arterial blood pressure].

    PubMed

    Sobrino, Javier; Casañas, Laura; Izquierdo, Clotilde; Clavell, Josefina

    2006-06-01

    Summary Chrono-biology consists of the scientific study of biological rhythms and their underlying mechanisms. This study is based on the certainty that for many physiological variables these exists a reproducible pattern in the time of maximum and minimum values. The study of circadian rhythm variations on biological parameters which affect numerous pathologies permits one to foresee rhythmical cycles and to synchronize pharmacological rules to make it possible to obtain improvements in patients' responses. Knowing the circadian rhythm in hypertensive patients brings data related to the prognosis and is a basic tool to introduce the concept of a chronological administration of medicines in providing antihypertensive treatment; this is chronotherapy. PMID:16875366

  17. Characterisation of circadian rhythms of various duckweeds.

    PubMed

    Muranaka, T; Okada, M; Yomo, J; Kubota, S; Oyama, T

    2015-01-01

    The plant circadian clock controls various physiological phenomena that are important for adaptation to natural day-night cycles. Many components of the circadian clock have been identified in Arabidopsis thaliana, the model plant for molecular genetic studies. Recent studies revealed evolutionary conservation of clock components in green plants. Homologues of clock-related genes have been isolated from Lemna gibba and Lemna aequinoctialis, and it has been demonstrated that these homologues function in the clock system in a manner similar to their functioning in Arabidopsis. While clock components are widely conserved, circadian phenomena display diversity even within the Lemna genus. In order to survey the full extent of diversity in circadian rhythms among duckweed plants, we characterised the circadian rhythms of duckweed by employing a semi-transient bioluminescent reporter system. Using a particle bombardment method, circadian bioluminescent reporters were introduced into nine strains representing five duckweed species: Spirodela polyrhiza, Landoltia punctata, Lemna gibba, L. aequinoctialis and Wolffia columbiana. We then monitored luciferase (luc+) reporter activities driven by AtCCA1, ZmUBQ1 or CaMV35S promoters under entrainment and free-running conditions. Under entrainment, AtCCA1::luc+ showed similar diurnal rhythms in all strains. This suggests that the mechanism of biological timing under day-night cycles is conserved throughout the evolution of duckweeds. Under free-running conditions, we observed circadian rhythms of AtCCA1::luc+, ZmUBQ1::luc+ and CaMV35S::luc+. These circadian rhythms showed diversity in period length and sustainability, suggesting that circadian clock mechanisms are somewhat diversified among duckweeds. PMID:24942699

  18. [Circadian rhythms in man (author's transl)].

    PubMed

    Aschoff, J

    1978-01-01

    The circadian system of man consists of a multiplicity of self-sustaining oscillators which are coupled to each other and which can be entrained by periodic factors in the environment, the zeitebers. From the interaction of these two forces results a high degree of temporal order within the organism. Freerunning circadian rhythms to be observed in isolated subjects living in constant conditions, usually have periods close to 25 h. The circadian system can split into components that freerun with different frequencies (internal desynchronization) and that partially can be entrained by zeitgeber. Analysis of the circadian organization has become of increasing importance for theory and practive in medicine. PMID:582509

  19. Heterogeneity induces rhythms of weakly coupled circadian neurons.

    PubMed

    Gu, Changgui; Liang, Xiaoming; Yang, Huijie; Rohling, Jos H T

    2016-01-01

    The main clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms in mammals. The SCN is composed of approximately twenty thousand heterogeneous self-oscillating neurons, that have intrinsic periods varying from 22 h to 28 h. They are coupled through neurotransmitters and neuropeptides to form a network and output a uniform periodic rhythm. Previous studies found that the heterogeneity of the neurons leads to attenuation of the circadian rhythm with strong cellular coupling. In the present study, we investigate the heterogeneity of the neurons and of the network in the condition of constant darkness. Interestingly, we found that the heterogeneity of weakly coupled neurons enables them to oscillate and strengthen the circadian rhythm. In addition, we found that the period of the SCN network increases with the increase of the degree of heterogeneity. As the network heterogeneity does not change the dynamics of the rhythm, our study shows that the heterogeneity of the neurons is vitally important for rhythm generation in weakly coupled systems, such as the SCN, and it provides a new method to strengthen the circadian rhythm, as well as an alternative explanation for differences in free running periods between species in the absence of the daily cycle. PMID:26898574

  20. Heterogeneity induces rhythms of weakly coupled circadian neurons

    PubMed Central

    Gu, Changgui; Liang, Xiaoming; Yang, Huijie; Rohling, Jos H. T.

    2016-01-01

    The main clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms in mammals. The SCN is composed of approximately twenty thousand heterogeneous self-oscillating neurons, that have intrinsic periods varying from 22 h to 28 h. They are coupled through neurotransmitters and neuropeptides to form a network and output a uniform periodic rhythm. Previous studies found that the heterogeneity of the neurons leads to attenuation of the circadian rhythm with strong cellular coupling. In the present study, we investigate the heterogeneity of the neurons and of the network in the condition of constant darkness. Interestingly, we found that the heterogeneity of weakly coupled neurons enables them to oscillate and strengthen the circadian rhythm. In addition, we found that the period of the SCN network increases with the increase of the degree of heterogeneity. As the network heterogeneity does not change the dynamics of the rhythm, our study shows that the heterogeneity of the neurons is vitally important for rhythm generation in weakly coupled systems, such as the SCN, and it provides a new method to strengthen the circadian rhythm, as well as an alternative explanation for differences in free running periods between species in the absence of the daily cycle. PMID:26898574

  1. Circadian rhythms of women with fibromyalgia

    NASA Technical Reports Server (NTRS)

    Klerman, E. B.; Goldenberg, D. L.; Brown, E. N.; Maliszewski, A. M.; Adler, G. K.

    2001-01-01

    Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

  2. From circadian rhythms to cancer chronotherapeutics.

    PubMed

    Lévi, Francis

    2002-01-01

    Mammalian circadian rhythms result from a complex organization involving molecular clocks within nearly all "normal" cells and a dedicated neuroanatomical system, which coordinates the so-called "peripheral oscillators." The core of the central clock system is constituted by the suprachiasmatic nuclei that are located on the floor of the hypothalamus. Our understanding of the mechanisms of circadian rhythm generation and coordination processes has grown rapidly over the past few years. In parallel, we have learnt how to use the predictable changes in cellular metabolism or proliferation along the 24h time scale in order to improve treatment outcome for a variety of diseases, including cancer. The chronotherapeutics of malignant diseases has emerged as a result of a consistent development ranging from experimental, clinical, and technological prerequisites to multicenter clinical trials of chronomodulated delivery schedules. Indeed large dosing-time dependencies characterize the tolerability of anticancer agents in mice or rats, a better efficacy usually results from treatment administration near the least toxic circadian time in rodent tumor models. Programmable in time multichannel pumps have allowed to test the chronotherapy concepts in cancer patients and to implement chronomodulated delivery schedules in current practice. Clinical phase I and II trials have established the feasibility, the safety, and the activity of the chronotherapy schedules, so that this treatment method has undergone further evaluation in international multicenter phase III trials. Overall, more than 2,000 patients with metastatic disease have been registered in chronotherapy trials. Improved tolerability and/or better antitumor activity have been demonstrated in randomized multicenter studies involving large patient cohorts. The relation between circadian rhythmicity and quality of life and even survival has also been a puzzling finding over the recent years. An essential step toward further developments of circadian-timed therapy has been the recent constitution of a Chronotherapy cooperative group within the European Organization for Research and Treatment of Cancer. This group now involves over 40 institutions in 12 countries. It is conducting currently six trials and preparing four new studies. The 19 contributions in this special issue reflect the current status and perspectives of the several components of cancer chronotherapeutics. PMID:11962669

  3. Circadian Rhythms, Sleep, and Substance Abuse

    PubMed Central

    Hasler, Brant P.; Smith, Leisha J.; Cousins, Jennifer C.; Bootzin, Richard R.

    2011-01-01

    Substance abuse is linked to numerous mental and physical health problems, including disturbed sleep. The association between substance use and sleep appears to be bidirectional, in that substance use may directly cause sleep disturbances, and difficulty sleeping may be a risk factor for relapse to substance use. Growing evidence similarly links substance use to disturbances in circadian rhythms, although many gaps in knowledge persist, particularly regarding whether circadian disturbance leads to substance abuse or dependence. Given the integral role circadian rhythms play in regulating sleep, circadian mechanisms may account in part for sleep-substance abuse interactions. Furthermore, a burgeoning research base supports a role for the circadian system in regulating reward processing, indicating that circadian mechanisms may be directly linked to substance abuse independently of sleep pathways. More work in this area is needed, particularly in elucidating how sleep and circadian disturbance may contribute to initiation of, and/or relapse to, substance use. Sleep and circadian-based interventions could play a critical role in the prevention and treatment of substance use disorders. PMID:21620743

  4. Circadian rhythms of performance: new trends

    NASA Technical Reports Server (NTRS)

    Carrier, J.; Monk, T. H.

    2000-01-01

    This brief review is concerned with how human performance efficiency changes as a function of time of day. It presents an overview of some of the research paradigms and conceptual models that have been used to investigate circadian performance rhythms. The influence of homeostatic and circadian processes on performance regulation is discussed. The review also briefly presents recent mathematical models of alertness that have been used to predict cognitive performance. Related topics such as interindividual differences and the postlunch dip are presented.

  5. Circadian rhythms in Macaca mulatta monkeys during Bion 11 flight

    NASA Technical Reports Server (NTRS)

    Alpatov, A. M.; Hoban-Higgins, T. M.; Klimovitsky, V. Y.; Tumurova, E. G.; Fuller, C. A.

    2000-01-01

    Circadian rhythms of primate brain temperature, head and ankle skin temperature, motor activity, and heart rate were studied during spaceflight and on the ground. In space, the circadian rhythms of all the parameters were synchronized with diurnal Zeitgebers. However, in space the brain temperature rhythm showed a significantly more delayed phase angle, which may be ascribed to an increase of the endogenous circadian period.

  6. Circadian rhythm of human salivary chromogranin A.

    PubMed

    Den, Rei; Toda, Masahiro; Nagasawa, Shingo; Kitamura, Kazuyuki; Morimoto, Kanehisa

    2007-02-01

    We investigated the circadian rhythm of chromogranin A (CgA) concentrations in saliva and blood samples from 40 male college students collected at 7 : 00, 8 : 00, 10 : 30, 12 : 30, 17 : 30, and 22 : 30. CgA concentrations were determined by ELISA. Salivary CgA levels peaked upon awakening, and then quickly decreased to the nadir after 1 hour and maintained a low level throughout the day. On the other hand, plasma CgA did not show any obvious circadian rhythm. These findings suggest that salivary and plasma CgA has different routes of secretion. PMID:17379958

  7. 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

  8. Procedures for numerical analysis of circadian rhythms

    PubMed Central

    REFINETTI, ROBERTO; LISSEN, GERMAINE CORNÉ; HALBERG, FRANZ

    2010-01-01

    This article reviews various procedures used in the analysis of circadian rhythms at the populational, organismal, cellular and molecular levels. The procedures range from visual inspection of time plots and actograms to several mathematical methods of time series analysis. Computational steps are described in some detail, and additional bibliographic resources and computer programs are listed. PMID:23710111

  9. Molecular Regulation of Circadian Rhythms by Polyamines.

    PubMed

    Galluzzi, Lorenzo; Pietrocola, Federico; Kroemer, Guido

    2015-11-01

    In this issue of Cell Metabolism, Zwighaft and colleagues (Zwighaft et al., 2015) describe a novel mechanism through which intracellular polyamines regulate circadian rhythms. These findings are significant, as they add yet another layer of complexity to the interplay between environmental, dietary, and organismal factors in the molecular control of daily behavioral oscillations. PMID:26536485

  10. CSF generation by pineal gland results in a robust melatonin circadian rhythm in the third ventricle as an unique light/dark signal.

    PubMed

    Tan, Dun-Xian; Manchester, Lucien C; Reiter, Russel J

    2016-01-01

    Pineal gland is an important organ for the regulation of the bio-clock in all vertebrate species. Its major secretory product is melatonin which is considered as the chemical expression of darkness due to its circadian peak exclusively at night. Pineal melatonin can be either released into the blood stream or directly enter into the CSF of the third ventricle via the pineal recess. We have hypothesized that rather than the peripheral circulatory melatonin circadian rhythm serving as the light/dark signal, it is the melatonin rhythm in CSF of the third ventricle that serves this purpose. This is due to the fact that melatonin circadian rhythm in the CSF is more robust in terms of its extremely high concentration and its precise on/off peaks. Thus, extrapineal-generated melatonin or diet-derived melatonin which enters blood would not interfere with the bio-clock function of vertebrates. In addition, based on the relationship of the pineal gland to the CSF and the vascular structure of this gland, we also hypothesize that pineal gland is an essential player for CSF production. We feel it participates in both the formation and reabsorption of CSF. The mechanisms associated with these processes are reviewed and discussed in this brief review. PMID:26804589

  11. Circadian rhythms, alcohol and gut interactions.

    PubMed

    Forsyth, Christopher B; Voigt, Robin M; Burgess, Helen J; Swanson, Garth R; Keshavarzian, Ali

    2015-06-01

    The circadian clock establishes rhythms throughout the body with an approximately 24 hour period that affect expression of hundreds of genes. Epidemiological data reveal chronic circadian misalignment, common in our society, significantly increases the risk for a myriad of diseases, including cardiovascular disease, diabetes, cancer, infertility and gastrointestinal disease. Disruption of intestinal barrier function, also known as gut leakiness, is especially important in alcoholic liver disease (ALD). Several studies have shown that alcohol causes ALD in only a 20-30% subset of alcoholics. Thus, a better understanding is needed of why only a subset of alcoholics develops ALD. Compelling evidence shows that increased gut leakiness to microbial products and especially LPS play a critical role in the pathogenesis of ALD. Clock and other circadian clock genes have been shown to regulate lipid transport, motility and other gut functions. We hypothesized that one possible mechanism for alcohol-induced intestinal hyperpermeability is through disruption of central or peripheral (intestinal) circadian regulation. In support of this hypothesis, our recent data shows that disruption of circadian rhythms makes the gut more susceptible to injury. Our in vitro data show that alcohol stimulates increased Clock and Per2 circadian clock proteins and that siRNA knockdown of these proteins prevents alcohol-induced permeability. We also show that intestinal Cyp2e1-mediated oxidative stress is required for alcohol-induced upregulation of Clock and Per2 and intestinal hyperpermeability. Our mouse model of chronic alcohol feeding shows that circadian disruption through genetics (in Clock(?19) mice) or environmental disruption by weekly 12h phase shifting results in gut leakiness alone and exacerbates alcohol-induced gut leakiness and liver pathology. Our data in human alcoholics show they exhibit abnormal melatonin profiles characteristic of circadian disruption. Taken together our data support circadian mechanisms for alcohol-induced gut leakiness that could provide new therapeutic targets for ALD. PMID:25499101

  12. Metabolic circadian rhythms in embryonic turtles.

    PubMed

    Loudon, Fiona Kay; Spencer, Ricky-John; Strassmeyer, Alana; Harland, Karen

    2013-07-01

    Oviparous species are model organisms for investigating embryonic development of endogenous physiological circadian rhythms without the influence of maternal biorhythms. Recent studies have demonstrated that heart rates and metabolic rates of embryonic turtles are not constant or always maximal and can be altered in response to the presence of embryos at a more advanced stage of development within the nest. A first step in understanding the physiological mechanisms underpinning these responses in embryonic ectothermic organisms is to develop metabolic profiles (e.g., heart rate) at different temperatures throughout incubation. Heart beat and rhythmic patterns or changes in development may represent important signals or cues within a nest and may be vital to coordinate synchronous hatching well in advance of the final stages of incubation. We developed baseline embryonic heart-rate profiles of embryos of the short-necked Murray River turtle (Emydura macquarii) to determine the stage of embryogenesis that metabolic circadian rhythms become established, if at all. Eggs were incubated at constant temperatures (26°C and 30°C) and heart rates were monitored at 6-h intervals over 24 h every 7-11 days until hatching. Circadian heart rate rhythms were detected at the mid-gestation period and were maintained until hatching. Heart rates throughout the day varied by up to 20% over 24 h and were not related to time of day. This study demonstrated that endogenous metabolic circadian rhythms in developing embryos in turtle eggs establish earlier in embryogenesis than those documented in other vertebrate taxa during embryogenesis. Early establishment of circadian rhythms in heart rates may be critical for communication among embryos and synchrony in hatching and emergence from the nest. PMID:23652198

  13. Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening.

    PubMed

    Zhang, Xiaoxiao; Beebe, Tyler; Jen, Nelson; Lee, Chia-An; Tai, Yuchong; Hsiai, Tzung K

    2015-09-15

    Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (µECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) (Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young's modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm(-3). These innovations enabled physiological ECG telemetry in the fish's natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for µECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery. PMID:25909335

  14. A circadian rhythm of conidiation in Neurospora crassa (L-12)

    NASA Technical Reports Server (NTRS)

    Miyoshi, Yashuhiro

    1993-01-01

    Two fungi growth chambers containing six growth tubes each are used in this experiment. One chamber is for the space experiment; the other is for the simultaneous ground control experiment. The hyphae of Neurospora crassa band A mutant are inoculated at one end of each tube. Both the chambers are kept at 3 C plus or minus 1.5 C to stop hyphae growth until the Spacelab is activated. After the activation, each chamber is transferred simultaneously to the Spacelab and a phytotron in KSC and kept in continuous light at the same temperature. After about 24 hours of light exposure, each chamber is inserted into a growth chamber bag to keep it in constant darkness. The circadian rhythm of conidiation is initiated by this light to dark transition. After the dark incubation for 5 days at room temperature, both the growth chambers are kept at 3 C plus or minus 1.5 C to stop growth of the hyphae. After the space shuttle lands, both conidiation patterns are compared and analyzed. It has been known that numerous physiological phenomena show circadian rhythms. They are characterized by the fact that the oscillation can persist under constant conditions of light and temperature. Therefore, it has been accepted by most investigators that the generation mechanism of the circadian rhythm is endogeneous. However, one cannot reject the possibility that these rhythms are caused by some geophysical exogeneous factor having a 24-hour period, such as atmospheric pressure, gravity, or electromagnetic radiation. We use Neurospora crassa band A mutual which shows an obvious circadian rhythm in its spore-forming (conidiation) on the ground, and we intend to attempt the conidation of this mutant in the Spacelab where 24-hour periodicity is severely attenuated and to elucidate the effect of the geophysical exogeneous factor in the generation mechanism of the circadian rhythm.

  15. Circadian Rhythms, Sleep, and Disorders of Aging.

    PubMed

    Mattis, Joanna; Sehgal, Amita

    2016-04-01

    Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders. PMID:26947521

  16. Circadian rhythms synchronize mitosis in Neurospora crassa

    PubMed Central

    Hong, Christian I.; Zámborszky, Judit; Baek, Mokryun; Labiscsak, Laszlo; Ju, Kyungsu; Lee, Hyeyeong; Larrondo, Luis F.; Goity, Alejandra; Chong, Hin Siong; Belden, William J.; Csikász-Nagy, Attila

    2014-01-01

    The cell cycle and the circadian clock communicate with each other, resulting in circadian-gated cell division cycles. Alterations in this network may lead to diseases such as cancer. Therefore, it is critical to identify molecular components that connect these two oscillators. However, molecular mechanisms between the clock and the cell cycle remain largely unknown. A model filamentous fungus, Neurospora crassa, is a multinucleate system used to elucidate molecular mechanisms of circadian rhythms, but not used to investigate the molecular coupling between these two oscillators. In this report, we show that a conserved coupling between the circadian clock and the cell cycle exists via serine/threonine protein kinase-29 (STK-29), the Neurospora homolog of mammalian WEE1 kinase. Based on this finding, we established a mathematical model that predicts circadian oscillations of cell cycle components and circadian clock-dependent synchronized nuclear divisions. We experimentally demonstrate that G1 and G2 cyclins, CLN-1 and CLB-1, respectively, oscillate in a circadian manner with bioluminescence reporters. The oscillations of clb-1 and stk-29 gene expression are abolished in a circadian arrhythmic frqko mutant. Additionally, we show the light-induced phase shifts of a core circadian component, frq, as well as the gene expression of the cell cycle components clb-1 and stk-29, which may alter the timing of divisions. We then used a histone hH1-GFP reporter to observe nuclear divisions over time, and show that a large number of nuclear divisions occur in the evening. Our findings demonstrate the circadian clock-dependent molecular dynamics of cell cycle components that result in synchronized nuclear divisions in Neurospora. PMID:24474764

  17. Chronobiology and obesity: Interactions between circadian rhythms and energy regulation.

    PubMed

    Summa, Keith C; Turek, Fred W

    2014-05-01

    Recent advances in the understanding of the molecular, genetic, neural, and physiologic basis for the generation and organization of circadian clocks in mammals have revealed profound bidirectional interactions between the circadian clock system and pathways critical for the regulation of metabolism and energy balance. The discovery that mice harboring a mutation in the core circadian gene circadian locomotor output cycles kaput (Clock) develop obesity and evidence of the metabolic syndrome represented a seminal moment for the field, clearly establishing a link between circadian rhythms, energy balance, and metabolism at the genetic level. Subsequent studies have characterized in great detail the depth and magnitude of the circadian clock's crucial role in regulating body weight and other metabolic processes. Dietary nutrients have been shown to influence circadian rhythms at both molecular and behavioral levels; and many nuclear hormone receptors, which bind nutrients as well as other circulating ligands, have been observed to exhibit robust circadian rhythms of expression in peripheral metabolic tissues. Furthermore, the daily timing of food intake has itself been shown to affect body weight regulation in mammals, likely through, at least in part, regulation of the temporal expression patterns of metabolic genes. Taken together, these and other related findings have transformed our understanding of the important role of time, on a 24-h scale, in the complex physiologic processes of energy balance and coordinated regulation of metabolism. This research has implications for human metabolic disease and may provide unique and novel insights into the development of new therapeutic strategies to control and combat the epidemic of obesity. PMID:24829483

  18. Environmental synchronizers of squirrel monkey circadian rhythms

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Fuller, C. A.; Moore-Ede, M. C.

    1977-01-01

    Various temporal signals in the environment were tested to determine if they could synchronize the circadian timing system of the squirrel monkey (Saimiri sciureus). The influence of cycles of light and dark, eating and fasting, water availability and deprivation, warm and cool temperature, sound and quiet, and social interaction and isolation on the drinking and activity rhythms of unrestrained monkeys was examined. In the absence of other time cues, 24-hr cycles of each of these potential synchronizers were applied for up to 3 wk, and the periods of the monkey's circadian rhythms were examined. Only light-dark cycles and cycles of food availability were shown to be entraining agents, since they were effective in determining the period and phase of the rhythmic variables. In the presence of each of the other environmental cycles, the monkey's circadian rhythms exhibited free-running periods which were significantly different from 24 hr with all possible phase relationships between the rhythms and the environmental cycles being examined.

  19. A novel animal model linking adiposity to altered circadian rhythms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Researchers have provided evidence for a link between obesity and altered circadian rhythms (e.g., shift work, disrupted sleep), but the mechanism for this association is still unknown. Adipocytes possess an intrinsic circadian clock, and circadian rhythms in adipocytokines and adipose tissue metab...

  20. Emergence of coherent oscillations in stochastic models for circadian rhythms

    NASA Astrophysics Data System (ADS)

    Gonze, Didier; Halloy, José; Goldbeter, Albert

    2004-10-01

    Most living organisms have developed the capability of generating autonomously sustained oscillations with a period close to 24 h. The mechanism responsible for these circadian rhythms relies on the negative regulation exerted by a protein on the expression of its own gene. Deterministic models for circadian rhythms account for the occurrence of autonomous oscillations of the limit cycle type, for their entrainment by light-dark cycles, and for their phase shifting by light pulses. Such models, however, do not take into consideration the molecular fluctuations which arise when the number of molecules involved in the regulatory mechanism is low. Here we resort to a stochastic description of a core model for circadian rhythms to study the emergence of coherent oscillations in gene expression in the presence of molecular noise. We show that despite the “bar code” pattern of gene activation, robust circadian oscillations can be observed. Simulations of the deterministic, fully developed version of the circadian model indicate, however, that sustained oscillations only emerge above a critical value of the rate constants characterizing the reversible binding of repressor to the gene, while below this value the system evolves towards an excitable steady state. This explains why, depending on whether or not the critical value of these rate constants is exceeded, stochastic simulations of the model produce coherent oscillations or very noisy oscillations with a highly variable period.

  1. Quantification of human performance circadian rhythms.

    PubMed

    Freivalds, A; Chaffin, D B; Langolf, G D

    1983-09-01

    The quantification of worker performance changes during a shift is critical to establishing worker productivity. This investigation examined the existence of circadian rhythms in response variables that relate most meaningfully to the physiological and neurological state of the body for three subjects maintaining a resting posture for 25 hours on five separate occasions. Significant circadian variation ranging from 3% to 11% of the mean value was detected for elbow flexion strength, physiological tremor, simple reaction time, information processing rate and critical eye-hand tracking capacity. PMID:6637808

  2. Circadian rhythm asynchrony in man during hypokinesis.

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Vernikos-Danellis, J.; Cronin, S. E.; Leach, C. S.; Rambaut, P. C.; Mack, P. B.

    1972-01-01

    Posture and exercise were investigated as synchronizers of certain physiologic rhythms in eight healthy male subjects in a defined environment. Four subjects exercised during bed rest. Body temperature (BT), heart rate, plasma thyroid hormone, and plasma steroid data were obtained from the subjects for a 6-day ambulatory equilibration period before bed rest, 56 days of bed rest, and a 10-day recovery period after bed rest. The results indicate that the mechanism regulating the circadian rhythmicity of the cardiovascular system is rigorously controlled and independent of the endocrine system, while the BT rhythm is more closely aligned to the endocrine system.

  3. Circadian rhythms have broad implications for understanding brain and behavior

    PubMed Central

    Silver, Rae; Kriegsfeld, Lance J.

    2015-01-01

    Circadian rhythms are generated by an endogenously organized timing system that drives daily rhythms in behavior, physiology and metabolism. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock. The SCN is synchronized to environmental changes in the light:dark cycle by direct, monosynaptic innervation via the retino-hypothalamic tract. In turn, the SCN coordinates the rhythmic activities of innumerable subordinate clocks in virtually all bodily tissues and organs. The core molecular clockwork is composed of a transcriptional/post-translational feedback loop in which clock genes and their protein products periodically suppress their own transcription. This primary loop connects to downstream output genes by additional, interlocked transcriptional feedback loops to create tissue-specific ‘circadian transcriptomes’. Signals from peripheral tissues inform the SCN of the internal state of the organism and the brain’s master clock is modified accordingly. A consequence of this hierarchical, multilevel feedback system is that there are ubiquitous effects of circadian timing on genetic and metabolic responses throughout the body. This overview examines landmark studies in the history of the study of circadian timing system, and highlights our current understanding of the operation of circadian clocks with a focus on topics of interest to the neuroscience community. PMID:24799154

  4. Circadian rhythms in neuronal activity propagate through output circuits.

    PubMed

    Cavey, Matthieu; Collins, Ben; Bertet, Claire; Blau, Justin

    2016-04-01

    Twenty-four hour rhythms in behavior are organized by a network of circadian pacemaker neurons. Rhythmic activity in this network is generated by intrinsic rhythms in clock neuron physiology and communication between clock neurons. However, it is poorly understood how the activity of a small number of pacemaker neurons is translated into rhythmic behavior of the whole animal. To understand this, we screened for signals that could identify circadian output circuits in Drosophila melanogaster. We found that leucokinin neuropeptide (LK) and its receptor (LK-R) were required for normal behavioral rhythms. This LK/LK-R circuit connects pacemaker neurons to brain areas that regulate locomotor activity and sleep. Our experiments revealed that pacemaker neurons impose rhythmic activity and excitability on LK- and LK-R-expressing neurons. We also found pacemaker neuron-dependent activity rhythms in a second circadian output pathway controlled by DH44 neuropeptide-expressing neurons. We conclude that rhythmic clock neuron activity propagates to multiple downstream circuits to orchestrate behavioral rhythms. PMID:26928065

  5. Sleep, circadian rhythms, and athletic performance.

    PubMed

    Thun, Eirunn; Bjorvatn, Bjørn; Flo, Elisabeth; Harris, Anette; Pallesen, Ståle

    2015-10-01

    Sleep deprivation and time of day are both known to influence performance. A growing body of research has focused on how sleep and circadian rhythms impact athletic performance. This review provides a systematic overview of this research. We searched three different databases for articles on these issues and inspected relevant reference lists. In all, 113 articles met our inclusion criteria. The most robust result is that athletic performance seems to be best in the evening around the time when the core body temperature typically is at its peak. Sleep deprivation was negatively associated with performance whereas sleep extension seems to improve performance. The effects of desynchronization of circadian rhythms depend on the local time at which performance occurs. The review includes a discussion of differences regarding types of skills involved as well as methodological issues. PMID:25645125

  6. INTRINSIC CIRCADIAN RHYTHMS IN THE CARDIOMYOCYTE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cardiomyocyte possesses a fully functional circadian clock. Circadian clocks are a set of proteins that generate self-sustained transcriptional positive and negative feedback loops with a free-running period of 24 hours. These intracellular molecular mechanisms confer the selective advantage of ...

  7. Temperature compensation and entrainment in circadian rhythms

    NASA Astrophysics Data System (ADS)

    Bodenstein, C.; Heiland, I.; Schuster, S.

    2012-06-01

    To anticipate daily variations in the environment and coordinate biological activities into a daily cycle many organisms possess a circadian clock. In the absence of external time cues the circadian rhythm persists with a period of approximately 24 h. The clock phase can be shifted by single pulses of light, darkness, chemicals, or temperature and this allows entrainment of the clock to exactly 24 h by cycles of these zeitgebers. On the other hand, the period of the circadian rhythm is kept relatively constant within a physiological range of constant temperatures, which means that the oscillator is temperature compensated. The mechanisms behind temperature compensation and temperature entrainment are not fully understood, neither biochemically nor mathematically. Here, we theoretically investigate the interplay of temperature compensation and entrainment in general oscillatory systems. We first give an analytical treatment for small temperature shifts and derive that every temperature-compensated oscillator is entrainable to external small-amplitude temperature cycles. Temperature compensation ensures that this entrainment region is always centered at the endogenous period regardless of possible seasonal temperature differences. Moreover, for small temperature cycles the entrainment region of the oscillator is potentially larger for rectangular pulses. For large temperature shifts we numerically analyze different circadian clock models proposed in the literature with respect to these properties. We observe that for such large temperature shifts sinusoidal or gradual temperature cycles allow a larger entrainment region than rectangular cycles.

  8. Circadian rhythms, sleep, and performance in space

    NASA Technical Reports Server (NTRS)

    Mallis, M. M.; DeRoshia, C. W.

    2005-01-01

    Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed.

  9. N-nitrosomelatonin enhances photic synchronization of mammalian circadian rhythms.

    PubMed

    Baidanoff, Fernando M; Plano, Santiago A; Doctorovich, Fabio; Suárez, Sebastián A; Golombek, Diego A; Chiesa, Juan J

    2014-04-01

    Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide-donor, N-nitrosomelatonin, to enhance the photic synchronization of circadian rhythms in hamsters. The intraperitoneal administration of this drug before a sub-saturating light pulse at circadian time 18 generated a twofold increase of locomotor rhythm phase-advances, having no effect over saturating light pulses. This potentiation was also obtained even when inhibiting suprachiasmatic nitric oxide synthase activity. However, N-nitrosomelatonin had no effect on light-induced phase delays at circadian time 14. The photic-enhancing effects were correlated with an increased suprachiasmatic immunoreactivity of FBJ murine osteosarcoma viral oncogene and period1. Moreover, in vivo nitric oxide release by N-nitrosomelatonin was verified by measuring nitrate and nitrite levels in suprachiasmatic nuclei homogenates. The compound also accelerated resynchronization to an abrupt 6-h advance in the light:dark cycle (but not resynchronization to a 6-h delay). Here, we demonstrate the chronobiotic properties of N-nitrosomelatonin, emphasizing the importance of nitric oxide-mediated transduction for circadian phase advances. PMID:24261470

  10. Circadian rhythms. A protein fold switch joins the circadian oscillator to clock output in cyanobacteria.

    PubMed

    Chang, Yong-Gang; Cohen, Susan E; Phong, Connie; Myers, William K; Kim, Yong-Ick; Tseng, Roger; Lin, Jenny; Zhang, Li; Boyd, Joseph S; Lee, Yvonne; Kang, Shannon; Lee, David; Li, Sheng; Britt, R David; Rust, Michael J; Golden, Susan S; LiWang, Andy

    2015-07-17

    Organisms are adapted to the relentless cycles of day and night, because they evolved timekeeping systems called circadian clocks, which regulate biological activities with ~24-hour rhythms. The clock of cyanobacteria is driven by a three-protein oscillator composed of KaiA, KaiB, and KaiC, which together generate a circadian rhythm of KaiC phosphorylation. We show that KaiB flips between two distinct three-dimensional folds, and its rare transition to an active state provides a time delay that is required to match the timing of the oscillator to that of Earth's rotation. Once KaiB switches folds, it binds phosphorylated KaiC and captures KaiA, which initiates a phase transition of the circadian cycle, and it regulates components of the clock-output pathway, which provides the link that joins the timekeeping and signaling functions of the oscillator. PMID:26113641

  11. Circadian rhythms in healthy aging--effects downstream from the pacemaker

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Kupfer, D. J.

    2000-01-01

    Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

  12. Circadian rhythm disorder in a rare disease: Smith-Magenis syndrome.

    PubMed

    De Leersnyder, Hélène; Claustrat, Bruno; Munnich, Arnold; Verloes, Alain

    2006-06-27

    Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome, caused by interstitial deletion of chromosome 17p11.2. The SMS phenotype include distinctive facial features, developmental delay and neurobehavioral abnormalities. The patients present major sleep disturbances ascribed to a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Treatment with morning beta-blockers and evening melatonin reinstated a normally timed melatonin circadian rhythm, improved daytime behavior and restored normal sleep habits, resulting in a greatly improved quality of life for both SMS patients and their family. SMS is the demonstration of biological basis for sleep disorder in a genetic disease. Considering that clock genes mediate generation of circadian rhythms, we suggest that haploinsufficiency for a circadian system gene mapping to chromosome 17p11.2 may cause the inversion of circadian rhythm in SMS. PMID:16723183

  13. Circadian Activity Rhythms, Time Urgency, and Achievement Concerns.

    ERIC Educational Resources Information Center

    Watts, Barbara L.

    Many physiological and psychological processes fluctuate throughout the day in fairly stable, rhythmic patterns. The relationship between individual differences in circadian activity rhythms and a sense of time urgency were explored as well as a number of achievement-related variables. Undergraduates (N=308), whose circadian activity rhythms were…

  14. A Circadian Rhythm Regulating Hyphal Melanization in Cercospora Kikuchii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms, biochemical or developmental processes with a period length of approximately 24 hours, are thoroughly documented in plants and animals. However, virtually all of what is currently known about circadian rhythms in fungi is derived from the model fungus, Neurospora crassa, including...

  15. [Circadian rhythm disruption and human development].

    PubMed

    Kohyama, Jun

    2013-12-01

    Ontogenetic developments of rest-activity, sleep-wakefulness, temperature and several hormone rhythms in humans were reviewed. The reported effects of environment on these alterations were also summarized. Then, disorders or conditions which often encounter during early stage of life and reveal circadian rhythm disruptions were described. These disorders or conditions included severe brain damage, visual disturbance, developmental disorders(autistic spectrum disorder and attention deficit/hyperactivity disorder), Rett syndrome, Angelman syndrome, Smith-Magenis syndrome, epilepsy, Yonaki, and inadequate sleep hygiene. Finally, it was emphasized that we should pay special attention on the development of youngsters who showed sleep disturbance during early stage of life with special reference to the later occurrence of developmental disorders. PMID:24437259

  16. Circadian temperature rhythms of older people

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Reynolds, C. F. 3rd; Kupfer, D. J.; Houck, P. R.

    1995-01-01

    This collection of studies had the aim of exploring whether older (77+ years) men and women have circadian body temperature rhythms different from those of younger adults. A total of 20 older men and 28 older women were compared with either 22 young men or 14 middle-aged men in four protocols; all but the first protocol using a subset of the sample. The four protocols were: 1) 24 h, and 2) 72 h data collections on a normal laboratory routine (sleeping at night); 3) between 36 h and 153 h of field data collection at home; and 4) 36 h of a constant conditions routine (wakeful bedrest under temporal isolation) in the laboratory. There was some evidence for an age-related phase advance in temperature rhythm, especially for the older men on a normal routine, though this was not present in the constant conditions protocol, where 5 of the older subjects showed major delays in the timing of the body temperature trough (10:00 or later). There was no statistically significant evidence from any of the protocols that older subjects generally had lower temperature rhythm amplitudes than younger adults. Only when older men were compared with younger men in 24-h rhythm amplitude by simple t-test did any comparison involving amplitude achieve statistical significance (p < 0.05).

  17. Characterization of neurospora circadian rhythms in space

    NASA Technical Reports Server (NTRS)

    Ferraro, James S.

    1987-01-01

    To determine whether the circadian rhythm of conidiation in neurospora crassa is endogenously derived or is driven by some geophysical time cue, an experiment was conducted on space shuttle flight STS-9, where inoculated race tubes were exposed to the microgravity environment of space. The results demonstated that the rhythm can persist in space. However, there were several minor alterations noted; an increase in the period of the oscillation and the variability of the growth rate and a diminished rhythm amplitude, which eventually damped out in 25% of the flight tubes. On day seven of the flight, the tubes were exposed to light while their growth fronts were marked. It appears that some aspects of this marking process reinstated a robust rhythm in all the tubes which continued throughout the remainder of the flight. It was hypothesized that the damping found prior to the marking procedure on STS-9 may have been a result of the hypergravity pulse of launch and not due to the microgravity of the orbital lab; furthermore, that the marking procedure, by exposing the samples to light, had reinstated rhythmicity. To test this, an investigation was conducted into the effects of acute and chronic exposure to hypergravity.

  18. Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm Type

    PubMed Central

    Zee, Phyllis C.; Vitiello, Michael V.

    2009-01-01

    Irregular Sleep Wake Rhythm Disorder (ISWRD) is characterized by the relative absence of a circadian pattern in an individual’s sleep-wake cycle. Significant changes in circadian regulation occur with aging and with neurodegenerative diseases, such as Alzheimer’s disease prevalent in older adults, which are likely to contribute to the prevalence of ISWRD seen in these populations, although ISWRD is also seen in traumatic brain injury and mental retardation populations. ISWRD is thought to result from some combination of; degeneration or decreased neuronal activity of suprachiasmatic nucleus (SCN) neurons, decreased responsiveness of the circadian clock to entraining agents such as light and activity, and decreased exposure to bright light and structured social and physical activity during the day. Treatment of ISWRD seeks to consolidate sleep during the night and wakefulness during the day; primarily through restoring or enhancing exposure to the various SCN time cues, or “zeitgebers”. Studies of the effectiveness of pharmacologic treatments for ISWRD have generally yielded negative or inconsistent results. In general multi-modal non-pharmacological approaches involving increased exposure to light, increased physical and social activities and improved sleep hygiene have been the most successful therapeutic approaches. PMID:20160950

  19. Circadian rhythms in rheumatology - a glucocorticoid perspective

    PubMed Central

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in regulating and controlling immune responses. Dysfunction of the HPA axis has been implicated in the pathogenesis of rheumatoid arthritis (RA) and other rheumatic diseases. The impact of glucocorticoid (GC) therapy on HPA axis function also remains a matter of concern, particularly for longer treatment duration. Knowledge of circadian rhythms and the influence of GC in rheumatology is important: on the one hand we aim for optimal treatment of the daily undulating inflammatory symptoms, for example morning stiffness and swelling; on the other, we wish to disturb the HPA axis as little as possible. This review describes circadian rhythms in RA and other chronic inflammatory diseases, dysfunction of the HPA axis in RA and other rheumatic diseases and the recent concept of the hepato-hypothalamic-pituitary-adrenal-renal axis, the problem of adrenal suppression by GC therapy and how it can be avoided, and evidence that chronotherapy with modified release prednisone effective at 02:00 a.m. can inhibit proinflammatory sequelae of nocturnal inflammation better compared with GC administration in the morning but does not increase the risk of HPA axis insufficiency in RA. PMID:25608777

  20. Gut clock: implication of circadian rhythms in the gastrointestinal tract.

    PubMed

    Konturek, P C; Brzozowski, T; Konturek, S J

    2011-04-01

    Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an endocrine encoding of the environmental light-dark cycle, conveying photic information which is used by organisms for both circadian and seasonal organization. Motor and secretory activity, as well as the rhythm of cell proliferation in the GIT and liver, are subject to many circadian rhythms, mediated by autonomic cells and some enterohormones (gastrin, ghrelin and somatostatin). Disruption of circadian physiology, due to sleep disturbance or shift work, may result in various gastrointestinal diseases, such as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or peptic ulcer disease. In addition, circadian disruption accelerates aging, and promotes tumorigenesis in the liver and GIT. Identification of the molecular basis and role of melatonin in the regulation of circadian rhythm allows researchers and clinicians to approach gastrointestinal diseases from a chronobiological perspective. Clinical studies have demonstrated that the administration of melatonin improves symptoms in patients with IBS and GERD. Moreover, our own studies indicate that melatonin significantly protects gastrointestinal mucosa, and has strong protective effects on the liver in patients with non-alcoholic steatohepatitis (NASH). Recently, it has been postulated that disruption of circadian regulation may lead to obesity by shifting food intake schedules. Future research should focus on the role of clock genes in the pathophysiology of the GIT and liver. PMID:21673361

  1. Robustness of circadian rhythms with respect to molecular noise

    NASA Astrophysics Data System (ADS)

    Gonze, Didier; Halloy, José; Goldbeter, Albert

    2002-01-01

    We use a core molecular model capable of generating circadian rhythms to assess the robustness of circadian oscillations with respect to molecular noise. The model is based on the negative feedback exerted by a regulatory protein on the expression of its gene. Such a negative regulatory mechanism underlies circadian oscillations of the PER protein in Drosophila and of the FRQ protein in Neurospora. The model incorporates gene transcription into mRNA, translation of mRNA into protein, reversible phosphorylation leading to degradation of the regulatory protein, transport of the latter into the nucleus, and repression of gene expression by the nuclear form of the protein. To assess the effect of molecular noise, we perform stochastic simulations after decomposing the deterministic model into elementary reaction steps. The oscillations predicted by the stochastic simulations agree with those obtained with the deterministic version of the model. We show that robust circadian oscillations can occur already with a limited number of mRNA and protein molecules, in the range of tens and hundreds, respectively. Entrainment by light/dark cycles and cooperativity in repression enhance the robustness of circadian oscillations with respect to molecular noise.

  2. Circadian rhythms and addiction: Mechanistic insights and future directions

    PubMed Central

    Logan, Ryan W.; Williams, Wilbur P.; McClung, Colleen A.

    2014-01-01

    Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction, and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction. PMID:24731209

  3. Preliminary characterization of persisting circadian rhythms during space flight: Neurospora as a model system

    NASA Technical Reports Server (NTRS)

    Sulzman, F. W.

    1981-01-01

    The effects of the Spacelab environment on the circadian rhythms in microorganisms are investigated. Neurospora is chosen because of its well characterized circadian rhythm of growth. Growth rate, banding patterns, and circadian period and phase information are studied.

  4. Barley Hv CIRCADIAN CLOCK ASSOCIATED 1 and Hv PHOTOPERIOD H1 Are Circadian Regulators That Can Affect Circadian Rhythms in Arabidopsis

    PubMed Central

    Martí, María C.; Laurie, David A.; Greenland, Andy J.; Hall, Anthony; Webb, Alex A. R.

    2015-01-01

    Circadian clocks regulate many aspects of plant physiology and development that contribute to essential agronomic traits. Circadian clocks contain transcriptional feedback loops that are thought to generate circadian timing. There is considerable similarity in the genes that comprise the transcriptional and translational feedback loops of the circadian clock in the plant Kingdom. Functional characterisation of circadian clock genes has been restricted to a few model species. Here we provide a functional characterisation of the Hordeum vulgare (barley) circadian clock genes Hv CIRCADIAN CLOCK ASSOCIATED 1 (HvCCA1) and Hv PHOTOPERIODH1, which are respectively most similar to Arabidopsis thaliana CIRCADIAN CLOCK ASSOCIATED 1 (AtCCA1) and PSEUDO RESPONSE REGULATOR 7 (AtPRR7). This provides insight into the circadian regulation of one of the major crop species of Northern Europe. Through a combination of physiological assays of circadian rhythms in barley and heterologous expression in wild type and mutant strains of A. thaliana we demonstrate that HvCCA1 has a conserved function to AtCCA1. We find that Hv PHOTOPERIOD H1 has AtPRR7-like functionality in A. thaliana and that the effects of the Hv photoperiod h1 mutation on photoperiodism and circadian rhythms are genetically separable. PMID:26076005

  5. Circadian rhythm in Alzheimer disease after trazodone use.

    PubMed

    Grippe, Talyta C; Gonçalves, Bruno S B; Louzada, Luciana L; Quintas, Juliana L; Naves, Janeth O S; Camargos, Einstein F; Nóbrega, Otávio T

    2015-11-01

    A circadian rhythm is a cycle of approximately 24?h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD. PMID:26376345

  6. Activity in the ferret: oestradiol effects and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Stockman, E. R.; Albers, H. E.; Baum, M. J.; Wurtman, R. J. (Principal Investigator)

    1985-01-01

    The present study was conducted to determine whether oestradiol increases activity in the European ferret (Mustela furo), whether this effect is sexually dimorphic, and whether a 24-h rhythm is present in the ferret's daily activity. The activity of male and female adult, postpubertally gonadectomized ferrets was monitored while they were maintained singly on a 13:11 light-dark cycle, before and after implantation with oestradiol-17 beta. Gonadectomized male and female ferrets exhibited equal levels of activity, and neither sex exhibited a significant change in activity following oestradiol implantation. None of the ferrets exhibited a strong circadian rhythm, although weak 24-h rhythms and shorter harmonic rhythms were present. Golden hamsters (Mesocricetus auratus), monitored in an identical manner, exhibited strong circadian rhythms. It was concluded that oestradiol administration may not cause an increase in activity in the ferret, and that this species lacks a strong circadian activity rhythm.

  7. Synergistic interactions between the molecular and neuronal circadian networks drive robust behavioral circadian rhythms in Drosophila melanogaster.

    PubMed

    Weiss, Ron; Bartok, Osnat; Mezan, Shaul; Malka, Yuval; Kadener, Sebastian

    2014-04-01

    Most organisms use 24-hr circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila melanogaster CLOCK (CLK) and CYCLE (CYC) initiates the circadian system by promoting rhythmic transcription of hundreds of genes. However, it is still not clear whether high amplitude transcriptional oscillations are essential for circadian timekeeping. In order to address this issue, we generated flies in which the amplitude of CLK-driven transcription can be reduced partially (approx. 60%) or strongly (90%) without affecting the average levels of CLK-target genes. The impaired transcriptional oscillations lead to low amplitude protein oscillations that were not sufficient to drive outputs of peripheral oscillators. However, circadian rhythms in locomotor activity were resistant to partial reduction in transcriptional and protein oscillations. We found that the resilience of the brain oscillator is depending on the neuronal communication among circadian neurons in the brain. Indeed, the capacity of the brain oscillator to overcome low amplitude transcriptional oscillations depends on the action of the neuropeptide PDF and on the pdf-expressing cells having equal or higher amplitude of molecular rhythms than the rest of the circadian neuronal groups in the fly brain. Therefore, our work reveals the importance of high amplitude transcriptional oscillations for cell-autonomous circadian timekeeping. Moreover, we demonstrate that the circadian neuronal network is an essential buffering system that protects against changes in circadian transcription in the brain. PMID:24698952

  8. Effects of exercise on circadian rhythms and mobility in aging Drosophila melanogaster

    PubMed Central

    Rakshit, Kuntol; Wambua, Rebecca; Giebultowicz, Tomasz M.; Giebultowicz, Jadwiga M.

    2013-01-01

    Daily life functions such as sleep and feeding oscillate with circa 24 h period due to endogenous circadian rhythms generated by circadian clocks. Genetic or environmental disruption of circadian rhythms is associated with various aging-related phenotypes. Circadian rhythms decay during normal aging, and there is a need to explore strategies that could avert age-related changes in the circadian system. Exercise was reported to delay aging in mammals. Here, we investigated whether daily exercise via stimulation of upward climbing movement could improve circadian rest/activity rhythms in aging Drosophila melanogaster. We found that repeated exercise regimen did not strengthen circadian locomotor activity rhythms in aging flies and had no effect on their lifespan. We also tested the effects of exercise on mobility and determined that regular exercise lowered age-specific climbing ability in both wild type and clock mutant flies. Interestingly, the climbing ability was most significantly reduced in flies carrying a null mutation in the core clock gene period, while rescue of this gene significantly improved climbing to wild type levels. Our work highlights the importance of period in sustaining endurance in aging flies exposed to physical challenge. PMID:23916842

  9. Preliminary characterization of persisting circadian rhythms during space flight

    NASA Technical Reports Server (NTRS)

    Sultzman, F. M.

    1984-01-01

    In order to evaluate the function of the circadian timing system in space, the circadian rhythm of conidiation of the fungus Neurospora crassa was monitored in constant darkness on the STS 9 flight of the Space Shuttle Columbia. During the first 7 days of spaceflight many tubes showed a marked reduction in the apparent amplitude of the conidiation rhythm, and some cultures appeared arrhythmic. There was more variability in the growth rate and circadian rhythms of individual cultures in space than is usually seen on earth. The results of this experiment indicate that while the circadian rhythm of Neurospora conidiation can persist outside of the earth's environment, either the timekeeping process or its expression is altered in space.

  10. Circadian rhythms: to sync or not to sync.

    PubMed

    Mazuski, Cristina; Herzog, Erik D

    2015-04-20

    Using real-time imaging of circadian gene expression, a new study reveals how a light pulse briefly desynchronizes clock neurons in the fly brain before they settle into a new, synchronized daily rhythm. PMID:25898105

  11. Preliminary characterization of persisting circadian rhythms during space flight

    NASA Astrophysics Data System (ADS)

    Sulzman, Frank M.

    In order to evaluate the function of the circadian timing system in space, the circadian rhythm of conidiation of the fungus Neurospora crassa was monitored in constant darkness on the STS 9 flight of the Space Shuttle Columbia. During the first 7 days of spaceflight many tubes showed a marked reduction in the apparent amplitude of the conidiation rhythm, and some cultures appeared arrhythmic. There was more variability in the growth rate and circadian rhythms of individual cultures in space than is usually seen on earth. The results of this experiment indicate that while the circadian rhythm of Neurospora conidiation can persist outside of the earth's environment, either the timekeeping process or its expression is altered in space.

  12. Circadian rhythms and period expression in the Hawaiian cricket genus Laupala.

    PubMed

    Fergus, Daniel J; Shaw, Kerry L

    2013-05-01

    Daily activity times and circadian rhythms of crickets have been a subject of behavioral and physiological study for decades. However, recent studies suggest that the underlying molecular mechanism of cricket endogenous clocks differ from the model of circadian rhythm generation in Drosophila. Here we examine the circadian free-running periods of walking and singing in two Hawaiian swordtail cricket species, Laupala cerasina and Laupala paranigra, that differ in the daily timing of mating related activities. Additionally, we examine variation in sequence and daily cycling of the period (per) gene transcript between these species. The species differed significantly in free-running period of singing, but did not differ significantly in the free-running period of locomotion. Like in Drosophila, per transcript abundance showed cycling consistent with a role in circadian rhythm generation. The amino acid differences identified between these species suggest a potential of the per gene in interspecific behavioral variation in Laupala. PMID:23436058

  13. Circadian rhythms and period expression in the Hawaiian cricket genus Laupala

    PubMed Central

    Fergus, Daniel J.; Shaw, Kerry L.

    2013-01-01

    Daily activity times and circadian rhythms of crickets have been a subject of behavioral and physiological study for decades. However, recent studies suggest that the underlying molecular mechanism of cricket endogenous clocks differ from the model of circadian rhythm generation in Drosophila. Here we examine the circadian free-running periods of walking and singing in two Hawaiian swordtail cricket species, Laupala cerasina and Laupala paranigra, that differ in the daily timing of mating related activities. Additionally, we examine variation in sequence and daily cycling of the period (per) gene transcript between these species. The species differed significantly in free-running period of singing, but did not differ significantly in the free-running period of locomotion. Like in Drosophila, per transcript abundance showed cycling consistent with a role in circadian rhythm generation. The amino acid differences identified between these species suggest a potential of the per gene in interspecific behavioral variation in Laupala. PMID:23436058

  14. Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

    NASA Astrophysics Data System (ADS)

    Li, Ying; Liu, Zengrong

    MicroRNAs (miRNAs) interact with 3‧untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

  15. Genetic basis of incidence and period length of circadian rhythm for locomotor activity in populations of a seed beetle.

    PubMed

    Harano, T; Miyatake, T

    2010-09-01

    Circadian rhythms are ubiquitous in a wide variety of organisms, although their genetic variation has been analyzed in only a few species. We found genetic differences in the circadian rhythm of adult locomotor activity among strains of the adzuki bean beetle, Callosobruchus chinensis, which differed in origin and have been maintained in isolation. All beetles in some strains clearly had free-running rhythms in constant darkness whereas most beetles in other strains were arrhythmic. The period of free-running rhythm varied from approximately 19 to 23 h between the strains. F(1) males from reciprocal crosses among strains with different periods of circadian rhythms had circadian periods that were intermediate between their parental strains. Segregation of the circadian rhythm appeared in the F(2) generation. These findings are consistent with the hypothesis that variation in the period length of circadian rhythm is explained by a major autosomal gene with additive effects and no dominance. This hypothesis was supported by the joint scaling test for the free-running period in the F(1) and F(2) generations. We discuss possible causes for genetic variation in circadian rhythm in the C. chinensis strains in terms of random factors and selection. PMID:20145671

  16. [Circadian variations of performances and basic rhythms].

    PubMed

    Querrioux-Coulombier, G; Rossi, J P

    1995-12-01

    Difficulties with chronopsychology studies include a masking effect of variables, the combination of different rhythms and variations of strategies. An experiment is conducted to analyze the role of circadian variations of elementary processes in the variations of performance for a complex task. Twenty-four subjects solved anagrams and tried to find the rule of anagram construction, during two sessions, at 10 am and 5 pm. Responses were classified in three groups: (a) discovery of the anagram construction rule (R2 responses); (b) resolution of anagram without discovery of rule (R1 responses); (c) failure, no resolution of anagram (R0 responses). During the second session, R2 performances were better at 10 am than at 5 pm. In contrast, R1 performances were better at 5 pm than at 10 am. Rule application was faster at 10 am than at 5 pm. Results are discussed in terms of variations of short-term memory capacity (Folkard and Monk, 1980). Using chronopsychology to analyze the role of elementary processes in a complex task is discussed. PMID:11541063

  17. Circadian rhythm of body temperature during prolonged undersea voyages.

    PubMed

    Colquhoun, W P; Paine, M W; Fort, A

    1978-05-01

    Circadian rhythms of oral temperature were assessed in 12 watchkeepers during a prolonged submarine voyage and compared with a "standard" rhythm obtained from nonwatchkeepers ashore. Initially, the parameters of the rhythms were similar to those of the standard; however, among eight ratings working 4-h watches in a rapidly rotating cycle, considerable changes in the rhythms occurred as the voyage progressed, and concurrent alterations in sleep patterning were observed. The most characteristic change in the rhythm was a marked decline in its amplitude. In most subjects, the rhythm also tended to depart from its original circadian pattern; in at least one case, it effectively disintegrated. One subject's rhythm appeared to "free-run" with a period greater than 24 h. A strong circadian rhythm was maintained in only one of these eight subjects. In four officers whose watch times were at fixed hours, adaptation of the rhythm to unusual times of sleep occurred in 2 of 3 cases where the schedule demanded it. The results are discussed in relation to the design of optimal watchkeeping systems for submariners. PMID:655989

  18. Rev-erb-alpha: an integrator of circadian rhythms and metabolism.

    PubMed

    Duez, Hélène; Staels, Bart

    2009-12-01

    The endogenous circadian clock ensures daily rhythms in diverse behavioral and physiological processes, including locomotor activity and sleep/wake cycles, but also food intake patterns. Circadian rhythms are generated by an internal clock system, which synchronizes these daily variations to the day/night alternance. In addition, circadian oscillations may be reset by the time of food availability in peripheral metabolic organs. Circadian rhythms are seen in many metabolic pathways (glucose and lipid metabolism, etc.) and endocrine secretions (insulin, etc.). As a consequence, misalignment of the internal timing system vs. environmental zeitgebers (light, for instance), as experienced during jetlag or shift work, may result in disruption of physiological cycles of fuel utilization or energy storage. A large body of evidence from both human and animal studies now points to a relationship between circadian disorders and altered metabolic response, suggesting that circadian and metabolic regulatory networks are tightly connected. After a review of the current understanding of the molecular circadian core clock, we will discuss the hypothesis that clock genes themselves link the core molecular clock and metabolic regulatory networks. We propose that the nuclear receptor and core clock component Rev-erb-alpha behaves as a gatekeeper to timely coordinate the circadian metabolic response. PMID:19696364

  19. Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

    PubMed Central

    Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

    2013-01-01

    Abstract Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful. Antioxid. Redox Signal. 19, 192–208 PMID:23198849

  20. 'The clocks that time us'--circadian rhythms in neurodegenerative disorders.

    PubMed

    Videnovic, Aleksandar; Lazar, Alpar S; Barker, Roger A; Overeem, Sebastiaan

    2014-12-01

    Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep-wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep-wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep-wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases. PMID:25385339

  1. ‘The clocks that time us’—circadian rhythms in neurodegenerative disorders

    PubMed Central

    Videnovic, Aleksandar; Lazar, Alpar S.; Barker, Roger A.; Overeem, Sebastiaan

    2015-01-01

    Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep–wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep–wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep–wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep–wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases. PMID:25385339

  2. Redox rhythm reinforces the circadian clock to gate immune response

    PubMed Central

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E.; Dong, Xinnian

    2015-01-01

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism’s metabolic activities1–3. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated4–7. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant’s redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid (SA) does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism. PMID:26098366

  3. Redox rhythm reinforces the circadian clock to gate immune response.

    PubMed

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

    2015-07-23

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism. PMID:26098366

  4. Circadian Rhythms of Ethylene Emission in Arabidopsis1[w

    PubMed Central

    Thain, Simon C.; Vandenbussche, Filip; Laarhoven, Lucas J.J.; Dowson-Day, Mandy J.; Wang, Zhi-Yong; Tobin, Elaine M.; Harren, Frans J.M.; Millar, Andrew J.; Van Der Straeten, Dominique

    2004-01-01

    Ethylene controls multiple physiological processes in plants, including cell elongation. Consequently, ethylene synthesis is regulated by internal and external signals. We show that a light-entrained circadian clock regulates ethylene release from unstressed, wild-type Arabidopsis (Arabidopsis thaliana) seedlings, with a peak in the mid-subjective day. The circadian clock drives the expression of multiple ACC SYNTHASE genes, resulting in peak RNA levels at the phase of maximal ethylene synthesis. Ethylene production levels are tightly correlated with ACC SYNTHASE 8 steady-state transcript levels. The expression of this gene is controlled by light, by the circadian clock, and by negative feedback regulation through ethylene signaling. In addition, ethylene production is controlled by the TIMING OF CAB EXPRESSION 1 and CIRCADIAN CLOCK ASSOCIATED 1 genes, which are critical for all circadian rhythms yet tested in Arabidopsis. Mutation of ethylene signaling pathways did not alter the phase or period of circadian rhythms. Mutants with altered ethylene production or signaling also retained normal rhythmicity of leaf movement. We conclude that circadian rhythms of ethylene production are not critical for rhythmic growth. PMID:15516515

  5. Circadian Rhythms in Stomatal Responsiveness to Red and Blue Light.

    PubMed Central

    Gorton, H. L.; Williams, W. E.; Assmann, S. M.

    1993-01-01

    Stomata of many plants have circadian rhythms in responsiveness to environmental cues as well as circadian rhythms in aperture. Stomatal responses to red light and blue light are mediated by photosynthetic photoreceptors; responses to blue light are additionally controlled by a specific blue-light photoreceptor. This paper describes circadian rhythmic aspects of stomatal responsiveness to red and blue light in Vicia faba. Plants were exposed to a repeated light:dark regime of 1.5:2.5 h for a total of 48 h, and because the plants could not entrain to this short light:dark cycle, circadian rhythms were able to "free run" as if in continuous light. The rhythm in the stomatal conductance established during the 1.5-h light periods was caused both by a rhythm in sensitivity to light and by a rhythm in the stomatal conductance established during the preceding 2.5-h dark periods. Both rhythms peaked during the middle of the subjective day. Although the stomatal response to blue light is greater than the response to red light at all times of day, there was no discernible difference in period, phase, or amplitude of the rhythm in sensitivity to the two light qualities. We observed no circadian rhythmicity in net carbon assimilation with the 1.5:2.5 h light regime for either red or blue light. In continuous white light, small rhythmic changes in photosynthetic assimilation were observed, but at relatively high light levels, and these appeared to be attributable largely to changes in internal CO2 availability governed by stomatal conductance. PMID:12231947

  6. Inositols affect the mating circadian rhythm of Drosophila melanogaster

    PubMed Central

    Sakata, Kazuki; Kawasaki, Haruhisa; Suzuki, Takahiro; Ito, Kumpei; Negishi, Osamu; Tsuno, Takuo; Tsuno, Hiromi; Yamazaki, Youta; Ishida, Norio

    2015-01-01

    Accumulating evidence indicates that the molecular circadian clock underlies the mating behavior of Drosophila melanogaster. However, information about which food components affect circadian mating behavior is scant. The ice plant, Mesembryanthemum crystallinum has recently become a popular functional food. Here, we showed that the close-proximity (CP) rhythm of D. melanogaster courtship behavior was damped under low-nutrient conditions, but significantly enhanced by feeding the flies with powdered ice plant. Among various components of ice plants, we found that myo-inositol increased the amplitude and slightly shortened the period of the CP rhythm. Real-time reporter assays showed that myo-inositol and D-pinitol shortened the period of the circadian reporter gene Per2-luc in NIH 3T3 cells. These data suggest that the ice plant is a useful functional food and that the ability of inositols to shorten rhythms is a general phenomenon in insects as well as mammals. PMID:26097456

  7. Circadian rhythms and risk for substance use disorders in adolescence

    PubMed Central

    Hasler, Brant P.; Soehner, Adriane M.; Clark, Duncan B.

    2014-01-01

    Purpose of the review This article explores recent research in adolescent circadian rhythms, neurobiological changes influencing affective regulation and reward responding, and the emergence of substance use and related problems. Recent findings Recent findings have confirmed that adolescents with drug and alcohol problems are also beset by sleep problems, and have advanced our understanding of the relationship between sleep problems and substance involvement in this developmental period. During adolescence, a shift to later preferred sleep times interacts with early school start times to cause sleep loss and circadian misalignment. Sleep loss and circadian misalignment may disrupt reward-related brain function and impair inhibitory control. Deficits or delays in mature reward and inhibitory functions may contribute to adolescent alcohol use and other substance involvement. Summary An integration of the available research literature suggests that changes in sleep and circadian rhythms during adolescence may contribute to accelerated substance use and related problems. PMID:25247459

  8. Sleep, circadian rhythms, and the pathogenesis of Alzheimer Disease

    PubMed Central

    Musiek, Erik S; Xiong, David D; Holtzman, David M

    2015-01-01

    Disturbances in the sleep–wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep–wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep–wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep–wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD. PMID:25766617

  9. 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.

  10. Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

    PubMed Central

    Quera Salva, M.A.; Hartley, S.

    2012-01-01

    Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC). Melatonin (N-acetyl-5-hydroxytryptamine) is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD) and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light) or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse. PMID:23650464

  11. Observer Design for a Core Circadian Rhythm Network

    PubMed Central

    Zhang, Yuhuan

    2014-01-01

    The paper investigates the observer design for a core circadian rhythm network in Drosophila and Neurospora. Based on the constructed highly nonlinear differential equation model and the recently proposed graphical approach, we design a rather simple observer for the circadian rhythm oscillator, which can well track the state of the original system for various input signals. Numerical simulations show the effectiveness of the designed observer. Potential applications of the related investigations include the real-world control and experimental design of the related biological networks. PMID:25121122

  12. Circadian rhythms and clock genes in psychotic disorders.

    PubMed

    Lamont, Elaine Waddington; Coutu, Daniel L; Cermakian, Nicolas; Boivin, Diane B

    2010-01-01

    Numerous lines of evidence suggest that a disordered circadian system contributes to the etiology and symptomatology of major psychiatric disorders. Sleep disturbances, particularly rapid eye movement (REM) sleep, have been observed in bipolar affective disorder (BPD) and schizophrenia. Therapies aimed at altering the timing and duration of sleep and realigning circadian rhythms, including sleep scheduling, wake extension, light therapy and drug therapies that alter sleep and circadian rhythms appear beneficial for affective disorders. Interventional studies aiming to correct sleep and circadian disturbances in schizophrenia are scarce, although exogenous melatonin has been shown to improve both sleep structure and psychotic symptoms. The study of molecular clock mechanisms in psychiatric disorders is also gaining interest. Genetics studies have found associations with CLOCK, PERIOD1, PERIOD3, and TIMELESS in schizophrenia. Most research on BPD has focused on polymorphisms of CLOCK, but the lithium target GSK-3 may also be significant. New research examining the role of circadian rhythms and clock genes in major mental illness is likely to produce rapid advances in circadian-based therapeutics. PMID:20686197

  13. Loss of dopamine disrupts circadian rhythms in a mouse model of Parkinson's disease.

    PubMed

    Fifel, Karim; Cooper, Howard M

    2014-11-01

    Although a wide range of physiological functions regulated by dopamine (DA) display circadian variations, the role of DA in the generation and/or modulation of these rhythms is unknown. In Parkinson's disease (PD) patients, in addition to the classical motor symptoms, disturbances of the pattern of daily rest/wake cycles are common non-motor symptoms. We investigated daily and circadian rhythms of rest/activity behaviors in a transgenic MitoPark mouse model with selective inactivation of mitochondrial transcription factor A (Tfam) resulting in a slow and progressive degeneration of DA neurons in midbrain structures. Correlated with this, MitoPark mice show a gradual reduction in locomotor activity beginning at about 20weeks of age. In a light-dark cycle, MitoPark mice exhibit a daily pattern of rest/activity rhythms that shows an age-dependent decline in both the amplitude and the stability of the rhythm, coupled with an increased fragmentation of day/night activities. When the circadian system is challenged by exposure to constant darkness or constant light conditions, control littermates retain a robust free-running circadian locomotor rhythm, whereas in MitoPark mice, locomotor rhythms are severely disturbed or completely abolished. Re-exposure to a light/dark cycle completely restores daily locomotor rhythms. MitoPark mice and control littermates express similar masking behaviors under a 1h light/1h dark regime, suggesting that the maintenance of a daily pattern of rest/activity in arrhythmic MitoPark mice can be attributed to the acute inhibitory and stimulatory effects of light and darkness. These results imply that, in addition to the classical motor abnormalities observed in PD, the loss of the midbrain DA neurons leads to impairments of the circadian control of rest/activity rhythms. PMID:25171792

  14. Environmental effects on circadian rhythms in photosynthesis and stomatal opening.

    PubMed

    Hennessey, T L; Freeden, A L; Field, C B

    1993-03-01

    Persistent circadian rhythms in photosynthesis and stomatal opening occurred in bean (Phaseolus vulgaris L.) plants transferred from a natural photoperiod to a variety of constant conditions. Photosynthesis, measured as carbon assimilation, and stomatal opening, as conductance to water vapor, oscillated with a freerunning period close to 24 h under constant moderate light, as well as under light-limiting and CO2-limiting conditions. The rhythms damped under constant conditions conducive to high photosynthetic rates, as did rates of carbon assimilation and stomatal conductance, and this damping correlated with the accumulation of carbohydrate. No rhythm in respiration occurred in plants transferred to constant darkness, and the rhythm in stomatal opening damped rapidly in constant darkness. Damping of rhythms also occurred in leaflets exposed to constant light and CO2-free air, demonstrating that active photosynthesis and not simply light was necessary for sustained expression of these rhythms. PMID:24178493

  15. Circadian rhythms of temperature and activity in obese and lean Zucker rats

    NASA Technical Reports Server (NTRS)

    Murakami, D. M.; Horwitz, B. A.; Fuller, C. A.

    1995-01-01

    The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.

  16. Multiparameter data acquisition systems for studies of circadian rhythms

    SciTech Connect

    Groh, K.R.; Ehret, C.F.; Eisler, W.J. Jr.; LeBuis, D.A.

    1985-01-01

    Long-term, simultaneous monitoring of multiple metabolic circadian cycles such as energy metabolism, animal activity, and body temperature together have revealed ultradian fine-structure rhythms which are dependent on circadian phase and the perturbations of environmental influences. Because of the variation between individual animals, these experiments need to have large sample sizes for each experimental condition. To this end we have designed, constructed and used four microcomputer controlled data acquisition systems to collect circadian data from individually housed rats and mice. 11 refs., 6 figs.

  17. An endogenous circadian rhythm of respiratory control in humans

    PubMed Central

    Spengler, Christina M; Czeisler, Charles A; Shea, Steven A

    2000-01-01

    Many physiological and behavioural functions have circadian rhythms – endogenous oscillations with a period of approximately 24 h that can occur even in the absence of sleep. We determined whether there is an endogenous circadian rhythm in breathing, metabolism and ventilatory chemosensitivity in humans. Ten healthy, adult males were studied throughout 4 days in a stable laboratory environment. After two initial baseline days (16 h wakefulness plus 8 h sleep) that served to achieve a steady state, subjects were studied under constant behavioural and environmental conditions throughout 41 h of wakefulness. Ventilation, metabolism and the magnitude of the hypercapnic ventilatory response (HCVR) were measured every 2 h. Individuals’ data were aligned according to circadian phase (core body temperature minimum; CBTmin) and averaged. In the group average data, there was a significant and large amplitude circadian variation in HCVR slope (average of ±0.4 l min?1 mmHg?1; corresponding to ±12.1 % of 24 h mean), and a smaller amplitude rhythm in the HCVR x-axis intercept (average of ±1.1 mmHg; ±2.1 % of 24 h mean). Despite a significant circadian variation in metabolism (±3.2 % of 24 h mean), there were no detectable rhythms in tidal volume, respiratory frequency or ventilation. This small discrepancy between metabolism and ventilation led to a small but significant circadian variation in end-tidal PCO2(PET,CO2; ±0.6 mmHg; ±1.5 % of 24 h mean). The circadian minima of the group-averaged respiratory variables occurred 6-8 h earlier than CBTmin, suggesting that endogenous changes in CBT across the circadian cycle have less of an effect on respiration than equivalent experimentally induced changes in CBT. Throughout these circadian changes, there were no correlations between HCVR parameters (slope or x-axis intercept) and either resting ventilation or resting PET,CO2. This suggests that ventilation and PET,CO2 are little influenced by central chemosensory respiratory control in awake humans even when at rest under constant environmental and behavioural conditions. The characteristic change in PET,CO2 during non-rapid eye movement sleep was shown to be independent of circadian variations in PET,CO2, and probably reflects a change from predominantly behavioural to predominantly chemosensory respiratory control. This study has documented the existence and magnitude of circadian variations in respiration and respiratory control in awake humans for the first time under constant behavioural and environmental conditions. These results provide unique insights into respiratory control in awake humans, and highlight the importance of considering the phase of the circadian cycle in studies of respiratory control. PMID:10922018

  18. Circadian rhythms in anesthesia and critical care medicine: potential importance of circadian disruptions.

    PubMed

    Brainard, Jason; Gobel, Merit; Bartels, Karsten; Scott, Benjamin; Koeppen, Michael; Eckle, Tobias

    2015-03-01

    The rotation of the earth and associated alternating cycles of light and dark--the basis of our circadian rhythms--are fundamental to human biology and culture. However, it was not until 1971 that researchers first began to describe the molecular mechanisms for the circadian system. During the past few years, groundbreaking research has revealed a multitude of circadian genes affecting a variety of clinical diseases, including diabetes, obesity, sepsis, cardiac ischemia, and sudden cardiac death. Anesthesiologists, in the operating room and intensive care units, manage these diseases on a daily basis as they significantly affect patient outcomes. Intriguingly, sedatives, anesthetics, and the intensive care unit environment have all been shown to disrupt the circadian system in patients. In the current review, we will discuss how newly acquired knowledge of circadian rhythms could lead to changes in clinical practice and new therapeutic concepts. PMID:25294583

  19. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

    Harfmann, Brianna D.; Schroder, Elizabeth A.; Esser, Karyn A.

    2015-01-01

    Circadian rhythms are the approximate 24-h biological cycles that function to prepare an organism for daily environmental changes. They are driven by the molecular clock, a transcriptional:translational feedback mechanism that in mammals involves the core clock genes Bmal1, Clock, Per1/2, and Cry1/2. The molecular clock is present in virtually all cells of an organism. The central clock in the suprachiasmatic nucleus (SCN) has been well studied, but the clocks in the peripheral tissues, such as heart and skeletal muscle, have just begun to be investigated. Skeletal muscle is one of the largest organs in the body, comprising approximately 45% of total body mass. More than 2300 genes in skeletal muscle are expressed in a circadian pattern, and these genes participate in a wide range of functions, including myogenesis, transcription, and metabolism. The circadian rhythms of skeletal muscle can be entrained both indirectly through light input to the SCN and directly through time of feeding and activity. It is critical for the skeletal muscle molecular clock not only to be entrained to the environment but also to be in synchrony with rhythms of other tissues. When circadian rhythms are disrupted, the observed effects on skeletal muscle include fiber-type shifts, altered sarcomeric structure, reduced mitochondrial respiration, and impaired muscle function. Furthermore, there are detrimental effects on metabolic health, including impaired glucose tolerance and insulin sensitivity, which skeletal muscle likely contributes to considering it is a key metabolic tissue. These data indicate a critical role for skeletal muscle circadian rhythms for both muscle and systems health. Future research is needed to determine the mechanisms of molecular clock function in skeletal muscle, identify the means by which skeletal muscle entrainment occurs, and provide a stringent comparison of circadian gene expression across the diverse tissue system of skeletal muscle. PMID:25512305

  20. Circadian rhythms in human performance and mood under constant conditions

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Reynolds, C. F. 3rd; Berga, S. L.; Jarrett, D. B.; Begley, A. E.; Kupfer, D. J.

    1997-01-01

    This study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well-being. Seventeen healthy young adults were studied under 36 h of 'unmasking' conditions (constant wakeful bedrest, temporal isolation, homogenized 'meals') during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well-being) were obtained followed by one of two performance batteries. On odd-numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even-numbered hours, performance (% hits, response speed) was measured at a 25-30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). In conclusion: (1) between-task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

  1. PPAR{alpha} is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

    SciTech Connect

    Shirai, Hidenori; Oishi, Katsutaka; Kudo, Takashi; Shibata, Shigenobu; Ishida, Norio . E-mail: n.ishida@aist.go.jp

    2007-06-08

    Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPAR{alpha} ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3 h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erb{alpha} was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPAR{alpha} is involved in circadian clock control independently of the SCN and that PPAR{alpha} could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS.

  2. ANIMAL RESPONSES TO CIRCADIAN RHYTHMS IN FORAGE QUALITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Net photosynthesis and respiration in growing plants cause a circadian rhythm in forage quality. Soluble sugar concentrations increase in plants during the day causing a dilution in ADF and NDF. Herbivores show a strong preference for afternoon (PM) vs morning (AM) harvested forage. Cattle, sheep, g...

  3. My Path from Chemistry to Phytochrome and Circadian Rhythms

    PubMed Central

    Tobin, Elaine M.

    2016-01-01

    I summarize my scientific journey from my first interest in science to my career investigating how plants use the phytochrome photoreceptor to regulate what genes they express. I then describe how this work led to an understanding of how circadian rhythms function in plants and to the discovery of CCA1, a component of the plant central oscillator. PMID:27014288

  4. Neuroimaging, cognition, light and circadian rhythms

    PubMed Central

    Gaggioni, Giulia; Maquet, Pierre; Schmidt, Christina; Dijk, Derk-Jan; Vandewalle, Gilles

    2014-01-01

    In humans, sleep and wakefulness and the associated cognitive processes are regulated through interactions between sleep homeostasis and the circadian system. Chronic disruption of sleep and circadian rhythmicity is common in our society and there is a need for a better understanding of the brain mechanisms regulating sleep, wakefulness and associated cognitive processes. This review summarizes recent investigations which provide first neural correlates of the combined influence of sleep homeostasis and circadian rhythmicity on cognitive brain activity. Markers of interindividual variations in sleep-wake regulation, such as chronotype and polymorphisms in sleep and clock genes, are associated with changes in cognitive brain responses in subcortical and cortical areas in response to manipulations of the sleep-wake cycle. This review also includes recent data showing that cognitive brain activity is regulated by light, which is a powerful modulator of cognition and alertness and also directly impacts sleep and circadian rhythmicity. The effect of light varied with age, psychiatric status, PERIOD3 genotype and changes in sleep homeostasis and circadian phase. These data provide new insights into the contribution of demographic characteristics, the sleep-wake cycle, circadian rhythmicity and light to brain functioning. PMID:25071478

  5. Photoperiodic regulation of the hamster testis: dependence on circadian rhythms.

    PubMed Central

    Eskes, G A; Zucker, I

    1978-01-01

    The testes of hamsters exposed to short days (10 hr of light per day) regress within 13 weeks. Administration of 7.5% deuterium oxide to hamsters lengthens the period of free running circadian activity rhythms by 2.2% and prevents testicular regression during short-day exposure. This consistent with predictions derived from an external coincidence model for photoperiodic time measurement: Deuterium oxide changes phase relationships between the light-dark cycle and the circadian system, the hamster's daily photosensitive phase is stimulated with light during short days, and the testes remain large. Conservation of the period of circadian rhythms within narrow limits has adaptive significance for hamster photoperiodism and for the occurrence and phasing of the annual reproductive cycle. Images PMID:273214

  6. Relationship between Oxidative Stress, Circadian Rhythms, and AMD

    PubMed Central

    Fanjul-Moles, María Luisa; López-Riquelme, Germán Octavio

    2016-01-01

    This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed. PMID:26885250

  7. Circadian rhythms and fractal fluctuations in forearm motion

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Hilton, Michael F.

    2005-03-01

    Recent studies have shown that the circadian pacemaker --- an internal body clock located in the brain which is normally synchronized with the sleep/wake behavioral cycles --- influences key physiologic functions such as the body temperature, hormone secretion and heart rate. Surprisingly, no previous studies have investigated whether the circadian pacemaker impacts human motor activity --- a fundamental physiologic function. We investigate high-frequency actigraph recordings of forearm motion from a group of young and healthy subjects during a forced desynchrony protocol which allows to decouple the sleep/wake cycles from the endogenous circadian cycle while controlling scheduled behaviors. We investigate both static properties (mean value, standard deviation), dynamical characteristics (long-range correlations), and nonlinear features (magnitude and Fourier-phase correlations) in the fluctuations of forearm acceleration across different circadian phases. We demonstrate that while the static properties exhibit significant circadian rhythms with a broad peak in the afternoon, the dynamical and nonlinear characteristics remain invariant with circadian phase. This finding suggests an intrinsic multi-scale dynamic regulation of forearm motion the mechanism of which is not influenced by the circadian pacemaker, thus suggesting that increased cardiac risk in the early morning hours is not related to circadian-mediated influences on motor activity.

  8. Renal electrolyte circadian rhythms - Independence from feeding and activity patterns

    NASA Technical Reports Server (NTRS)

    Moore-Ede, M. C.; Herd, J. A.

    1977-01-01

    Experiments were conducted on six unanesthetized chair-acclimatized adult male squirrel monkeys (Saimiri sciureus) weighing 600-900 g to determine whether internal synchronization is the result of simple passive dependence of renal excretory rhythms on endogenous rhythms of those variable that influence electrolyte excretion such as dietary intake and muscular activity. Independence of the urinary rhythms from diurnal variations in feeding, drinking, and activity was secured by depriving the animals of food, water, and training them to perform a two-hourly schedule of feeding, drinking, and activity throughout day and night. Results indicate that the internal synchronization which is normally observed between the behavioral and urinary rhythms cannot be explained by any direct dependence of renal function on behavioral patterns. The most probable mechanism for circadian internal synchronization is that the various behavioral and renal rhythms are controlled by potentially independent separate oscillators which are normally kept in synchrony with one another.

  9. Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers.

    PubMed

    Yon, Felipe; Joo, Youngsung; Cortés Llorca, Lucas; Rothe, Eva; Baldwin, Ian T; Kim, Sang-Gyu

    2016-02-01

    The rhythmic opening/closing and volatile emissions of flowers are known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach has led to the identification of core circadian clock components in Arabidopsis thaliana, the involvement of these clock components in floral rhythms has remained untested, probably because of the weak diurnal rhythms in A. thaliana flowers. Here, we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents and move vertically through a 140° arc. We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission and pedicel movement, but not flower closing. We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known to be core clock components. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. PMID:26439540

  10. Light and Gravity Effects on Circadian Rhythms of Rhesus Macaques

    NASA Technical Reports Server (NTRS)

    Fuller, Charles

    1997-01-01

    Temporal integration of a biological organism's physiological, behavioral and biochemical systems depends upon its circadian timing system. The endogenous period of this timing system is typically synchronized to the 24- hour day by environmental cues. The daily alternation of light and dark has long been known as one of the most potent environmental synchronizers influencing the circadian timing system. Alterations in the lighting environment (length or intensity of light exposure) can also affect the homeostatic state of the organism. A series of experiments was performed using rhesus monkeys with the objective of defining the fundamental properties of the circadian rhythm of body temperature. Three major experiments were performed in addition to several preliminary studies. These experiments explored 1.) the response of the rhesus body temperature rhythm to varying day length and light intensity; 2.) the response of the body temperature rhythm to light exposure as a function of time of day; and 3.) the characteristics of the metabolic heat production rhythm which is responsible for the daily cycle in body temperature. Results of these three completed experiments will be reported here. In addition, preliminary experiments were also performed in social entrainment of rhesus circadian rhythms and the properties of rhesus body temperature rhythms in constant conditions, where no external time cues were provided. Four adult male rhesus monkeys served as subjects in all experiments. All experiments were performed at the California Regional Primate Research Center. Each animal was implanted with a biotelemetry unit that measured deep body temperature. All surgeries were performed by a board certified veterinary surgeon under sterile conditions. The biotelemetry implants also provided an index of activity level in each animal. For metabolic heat production measurements, oxygen consumption and carbon dioxide production were measured and the caloric equivalent of these was calculated. Specific methodologies are described in detail.

  11. Quantification of Circadian Rhythms in Single Cells

    PubMed Central

    Westermark, Pål O.; Welsh, David K.; Okamura, Hitoshi; Herzel, Hanspeter

    2009-01-01

    Bioluminescence techniques allow accurate monitoring of the circadian clock in single cells. We have analyzed bioluminescence data of Per gene expression in mouse SCN neurons and fibroblasts. From these data, we extracted parameters such as damping rate and noise intensity using two simple mathematical models, one describing a damped oscillator driven by noise, and one describing a self-sustained noisy oscillator. Both models describe the data well and enabled us to quantitatively characterize both wild-type cells and several mutants. It has been suggested that the circadian clock is self-sustained at the single cell level, but we conclude that present data are not sufficient to determine whether the circadian clock of single SCN neurons and fibroblasts is a damped or a self-sustained oscillator. We show how to settle this question, however, by testing the models' predictions of different phases and amplitudes in response to a periodic entrainment signal (zeitgeber). PMID:19956762

  12. Quantification of circadian rhythms in single cells.

    PubMed

    Westermark, PÃ¥l O; Welsh, David K; Okamura, Hitoshi; Herzel, Hanspeter

    2009-11-01

    Bioluminescence techniques allow accurate monitoring of the circadian clock in single cells. We have analyzed bioluminescence data of Per gene expression in mouse SCN neurons and fibroblasts. From these data, we extracted parameters such as damping rate and noise intensity using two simple mathematical models, one describing a damped oscillator driven by noise, and one describing a self-sustained noisy oscillator. Both models describe the data well and enabled us to quantitatively characterize both wild-type cells and several mutants. It has been suggested that the circadian clock is self-sustained at the single cell level, but we conclude that present data are not sufficient to determine whether the circadian clock of single SCN neurons and fibroblasts is a damped or a self-sustained oscillator. We show how to settle this question, however, by testing the models' predictions of different phases and amplitudes in response to a periodic entrainment signal (zeitgeber). PMID:19956762

  13. Microarray Analysis of Natural Socially-Regulated Plasticity in Circadian Rhythms of Honey Bees

    PubMed Central

    Rodriguez-Zas, Sandra L.; Southey, Bruce R.; Shemesh, Yair; Rubin, Elad B.; Cohen, Mira; Robinson, Gene E.; Bloch, Guy

    2012-01-01

    Honey bee workers care for ("nurse") the brood around the clock without circadian rhythmicity, but then they forage outside with strong circadian rhythms and a consolidated nightly rest. This chronobiological plasticity is associated with variation in the expression of the canonical “clock genes” that regulate the circadian clock: nurse bees show no brain rhythms of expression, while foragers do. These results suggest that the circadian system is organized differently in nurses and foragers. Nurses switch to activity with circadian rhythms shortly after removed from the hive suggesting that at least some clock cells in their brain continue to measure time while in the hive. We performed a microarray genome-wide survey to determine general patterns of brain gene expression in nurses and foragers sampled around the clock. We found 160 and 541 transcripts that exhibited significant sinusoidal oscillations in nurses and foragers, respectively, with peaks of expression distributed throughout the day in both task groups. Consistent with earlier studies, transcripts of genes involved in circadian rhythms, including Clockwork Orange that has not been studied before in bees, oscillated in foragers but not in nurses. The oscillating transcripts also were enriched for genes involved in the visual system, “development” and “response to stimuli” (foragers), “muscle contraction” and “microfilament motor gene expression” (nurses), and “generation of precursor metabolites” and “energy” (both). Transcripts of genes encoding P450 enzymes oscillated in both nurses and foragers but with a different phase. This study identified new putative clock-controlled genes in the honey bee and suggests that some brain functions show circadian rhythmicity even in nurse bees that are active around the clock. PMID:22306970

  14. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  15. Circadian rhythms in liver metabolism and disease

    PubMed Central

    Ferrell, Jessica M.; Chiang, John Y.L.

    2015-01-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  16. Circadian biology: rhythms leave their imprint.

    PubMed

    Ray, David W

    2015-03-01

    A recent study has revealed that loss of neuronal expression of the paternally imprinted gene Ube3a in Angelman syndrome results in selective neuronal loss of robust circadian oscillations, with a resulting behavioural phenotype, and adipose tissue accumulation. PMID:25734270

  17. Circadian Rhythms and Mood Disorders: Are the Phenomena and Mechanisms Causally Related?

    PubMed

    Bechtel, William

    2015-01-01

    This paper reviews some of the compelling evidence of disrupted circadian rhythms in individuals with mood disorders (major depressive disorder, seasonal affective disorder, and bipolar disorder) and that treatments such as bright light, designed to alter circadian rhythms, are effective in treating these disorders. Neurotransmitters in brain regions implicated in mood regulation exhibit circadian rhythms. A mouse model originally employed to identify a circadian gene has proven a potent model for mania. While this evidence is suggestive of an etiological role for altered circadian rhythms in mood disorders, it is compatible with other explanations, including that disrupted circadian rhythms and mood disorders are effects of a common cause and that genes and proteins implicated in both simply have pleiotropic effects. In light of this, the paper advances a proposal as to what evidence would be needed to establish a direct causal link between disruption of circadian rhythms and mood disorders. PMID:26379559

  18. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A.

    2015-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1?/? and Clock?19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

  19. Calculating activation energies for temperature compensation in circadian rhythms

    NASA Astrophysics Data System (ADS)

    Bodenstein, C.; Heiland, I.; Schuster, S.

    2011-10-01

    Many biological species possess a circadian clock, which helps them anticipate daily variations in the environment. In the absence of external stimuli, the rhythm persists autonomously with a period of approximately 24 h. However, single pulses of light, nutrients, chemicals or temperature can shift the clock phase. In the case of light- and temperature-cycles, this allows entrainment of the clock to cycles of exactly 24 h. Circadian clocks have the remarkable property of temperature compensation, that is, the period of the circadian rhythm remains relatively constant within a physiological range of temperatures. For several organisms, temperature-regulated processes within the circadian clock have been identified in recent years. However, how these processes contribute to temperature compensation is not fully understood. Here, we theoretically investigate temperature compensation in general oscillatory systems. It is known that every oscillator can be locally temperature compensated around a reference temperature, if reactions are appropriately balanced. A balancing is always possible if the control coefficient with respect to the oscillation period of at least one reaction in the oscillator network is positive. However, for global temperature compensation, the whole physiological temperature range is relevant. Here, we use an approach which leads to an optimization problem subject to the local balancing principle. We use this approach to analyse different circadian clock models proposed in the literature and calculate activation energies that lead to temperature compensation.

  20. Sleep and Circadian Rhythms in Four Orbiting Astronauts

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.; Buysse, Daniel J.; Billy, Bart D.; Kennedy, Kathy S.; Willrich, Linda M.

    1999-01-01

    INTRODUCTION The study of human sleep and circadian rhythms in space has both operational and scientific significance. Operationally, U.S. Spaceflight is moving away from brief missions with durations of less than one week. Most space shuttle missions now last two weeks or more, and future plans involving space stations, lunar bases and interplanetary missions all presume that people will be living away from the gravity and time cues of earth for months at a time. Thus, missions are moving away from situations where astronauts can "tough it out" for comparatively brief durations, to situations where sleep and circadian disruptions are likely to become chronic, and thus resistant to short term pharmacological or behavioral manipulations. As well as the operational significance, there is a strong theoretical imperative for studying the sleep and circadian rhythms of people who are removed from the gravity and time cues of earth. Like other animals, in humans, the Circadian Timekeeping System (CTS) is entrained to the correct period (24h) and temporal orientation by various time cues ("zeitgebers"), the most powerful of which is the alternation of daylight and darkness. In leaving Earth, astronauts are removing themselves from the prime zeitgeber of their circadian system -- the 24h alternation of daylight and darkness.

  1. A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms.

    PubMed

    Park, Noheon; Kim, Hee-Dae; Cheon, Solmi; Row, Hansang; Lee, Jiyeon; Han, Dong-Hee; Cho, Sehyung; Kim, Kyungjin

    2015-01-01

    The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (Bmal1GT?C) allele. The homozygous mutant (Bmal1GT?C/GT?C) mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (Bmal1+/GT?C) mice displayed a gradual loss of rhythms, in contrast to Bmal1+/- mice where rhythms were sustained. Bmal1GT?C/GT?C mice also showed arrhythmic mRNA and protein expression in the SCN and liver. Lack of circadian reporter oscillation was also observed in cultured fibroblast cells, indicating that the arrhythmicity of Bmal1GT?C/GT?C mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in Bmal1+/GT?C and Bmal1GT?C/GT?C mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1GT?C was unable to activate transcription of Per1 promoter and BMAL1-dependent CLOCK degradation. These results indicate that the C-terminal region of Bmal1 has pivotal roles in the regulation of circadian rhythms and the Bmal1GT?C mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1. PMID:26394143

  2. A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms

    PubMed Central

    Cheon, Solmi; Row, Hansang; Lee, Jiyeon; Han, Dong-Hee; Cho, Sehyung; Kim, Kyungjin

    2015-01-01

    The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (Bmal1GT?C) allele. The homozygous mutant (Bmal1GT?C/GT?C) mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (Bmal1+/GT?C) mice displayed a gradual loss of rhythms, in contrast to Bmal1+/- mice where rhythms were sustained. Bmal1GT?C/GT?C mice also showed arrhythmic mRNA and protein expression in the SCN and liver. Lack of circadian reporter oscillation was also observed in cultured fibroblast cells, indicating that the arrhythmicity of Bmal1GT?C/GT?C mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in Bmal1+/GT?C and Bmal1GT?C/GT?C mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1GT?C was unable to activate transcription of Per1 promoter and BMAL1-dependent CLOCK degradation. These results indicate that the C-terminal region of Bmal1 has pivotal roles in the regulation of circadian rhythms and the Bmal1GT?C mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1. PMID:26394143

  3. Metabolic Cycles in Yeast Share Features Conserved among Circadian Rhythms

    PubMed Central

    Causton, Helen C.; Feeney, Kevin A.; Ziegler, Christine A.; O’Neill, John S.

    2015-01-01

    Summary Cell-autonomous circadian rhythms allow organisms to temporally orchestrate their internal state to anticipate and/or resonate with the external environment [1, 2]. Although ?24-hr periodicity is observed across aerobic eukaryotes, the central mechanism has been hard to dissect because few simple models exist, and known clock proteins are not conserved across phylogenetic kingdoms [1, 3, 4]. In contrast, contributions to circadian rhythmicity made by a handful of post-translational mechanisms, such as phosphorylation of clock proteins by casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3), appear conserved among phyla [3, 5]. These kinases have many other essential cellular functions and are better conserved in their contribution to timekeeping than any of the clock proteins they phosphorylate [6]. Rhythmic oscillations in cellular redox state are another universal feature of circadian timekeeping, e.g., over-oxidation cycles of abundant peroxiredoxin proteins [7–9]. Here, we use comparative chronobiology to distinguish fundamental clock mechanisms from species and/or tissue-specific adaptations and thereby identify features shared between circadian rhythms in mammalian cells and non-circadian temperature-compensated respiratory oscillations in budding yeast [10]. We find that both types of oscillations are coupled with the cell division cycle, exhibit period determination by CK1 and GSK3, and have peroxiredoxin over-oxidation cycles. We also explore how peroxiredoxins contribute to YROs. Our data point to common mechanisms underlying both YROs and circadian rhythms and suggest two interpretations: either certain biochemical systems are simply permissive for cellular oscillations (with frequencies from hours to days) or this commonality arose via divergence from an ancestral cellular clock. PMID:25866393

  4. Circadian rhythms and attention deficit hyperactivity disorder: The what, the when and the why.

    PubMed

    Coogan, Andrew N; Baird, Alison L; Popa-Wagner, Aurel; Thome, Johannes

    2016-06-01

    Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterised by impulsivity, inattention and hyperactivity. Aside from these core psychopathologies, sleep disturbances are found to be highly comorbid with ADHD, and indeed dysregulated sleep may contribute to some of the symptoms of the disorder. It is not clear how sleep disturbances come to be so common in ADHD, but one putative mechanism is through the circadian timekeeping system. This system underpins the generation of near 24-hour rhythms in a host of physiological, behavioural and psychological parameters, and is a key determinant of the sleep/wake cycle. In this paper we review the evidence for sleep and circadian rhythm disturbance in ADHD, examine the possible mechanistic links between these factors and the disorder and discuss future directions through which the circadian clock can be targetted for ADHD symptom relief. PMID:26776072

  5. Circadian and ultradian rhythms of clock gene expression in the suprachiasmatic nucleus of freely moving mice

    PubMed Central

    Ono, Daisuke; Honma, Ken-ichi; Honma, Sato

    2015-01-01

    In mammals, the temporal order of physiology and behavior is primarily regulated by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Rhythms are generated in cells by an auto-regulatory transcription/translation feedback loop, composed of several clock genes and their protein products. Taking advantage of bioluminescence reporters, we have succeeded in continuously monitoring the expression of clock gene reporters Per1-luc, PER2::LUC and Bmal1-ELuc in the SCN of freely moving mice for up to 3 weeks in constant darkness. Bioluminescence emitted from the SCN was collected with an implanted plastic optical fiber which was connected to a cooled photomultiplier tube. We found robust circadian rhythms in the clock gene expression, the phase-relation of which were the same as those observed ex vivo. The circadian rhythms were superimposed by episodic bursts which had ultradian periods of approximately 3.0?h. Episodic bursts often accompanied activity bouts, but stoichiometric as well as temporal analyses revealed no causality between them. Clock gene expression in the SCN in vivo is regulated by the circadian pacemaker and ultradian rhythms of unknown origin. PMID:26194231

  6. Circadian and ultradian rhythms of clock gene expression in the suprachiasmatic nucleus of freely moving mice.

    PubMed

    Ono, Daisuke; Honma, Ken-ichi; Honma, Sato

    2015-01-01

    In mammals, the temporal order of physiology and behavior is primarily regulated by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Rhythms are generated in cells by an auto-regulatory transcription/translation feedback loop, composed of several clock genes and their protein products. Taking advantage of bioluminescence reporters, we have succeeded in continuously monitoring the expression of clock gene reporters Per1-luc, PER2::LUC and Bmal1-ELuc in the SCN of freely moving mice for up to 3 weeks in constant darkness. Bioluminescence emitted from the SCN was collected with an implanted plastic optical fiber which was connected to a cooled photomultiplier tube. We found robust circadian rhythms in the clock gene expression, the phase-relation of which were the same as those observed ex vivo. The circadian rhythms were superimposed by episodic bursts which had ultradian periods of approximately 3.0 h. Episodic bursts often accompanied activity bouts, but stoichiometric as well as temporal analyses revealed no causality between them. Clock gene expression in the SCN in vivo is regulated by the circadian pacemaker and ultradian rhythms of unknown origin. PMID:26194231

  7. Age, circadian rhythms, and sleep loss in flight crews

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Nguyen, DE; Rosekind, Mark R.; Connell, Linda J.

    1993-01-01

    Age-related changes in trip-induced sleep loss, personality, and the preduty temperature rhythm were analyzed in crews from various flight operations. Eveningness decreased with age. The minimum of the baseline temperature rhythm occurred earlier with age. The amplitude of the baseline temperature rhythm declined with age. Average daily percentage sleep loss during trips increased with age. Among crewmembers flying longhaul flight operations, subjects aged 50-60 averaged 3.5 times more sleep loss per day than subjects aged 20-30. These studies support previous findings that evening types and subjects with later peaking temperature rhythms adapt better to shift work and time zone changes. Age and circadian type may be important considerations for duty schedules and fatigue countermeasures.

  8. Influence of physical workload on freerunning circadian rhythms of man.

    PubMed

    Wever, R A

    1979-08-01

    While living under constant conditions and complete isolation from environmental time cues for about 4 weeks, 9 male subjects exercised on a bicycle ergometer seven times per 'day' during two weeks and refrained from physical activities during the other 2 weeks. The freerunning circadian rhythms of wakefulness and sleep and of rectal temperature showed, on the average, no difference between the two sections with regard to the autonomous period and the tendency towards internal desynchronization. Even in the one experiment in which the two rhythms became internally desynchronized, the periods of the rhythms remained unchanged during the time the subject worked on the bicycle. Only in one out of the nine subjects, the autonomous period was considerably longer under the influence of work than without it. The hypothesis is advanced that the period of an autonomous rhythm becomes normally independent of physical workload by way of a compensation mechanism. PMID:574252

  9. Circadian rhythms in Neurospora crassa: a mutation affecting temperature compensation.

    PubMed Central

    Mattern, D L; Forman, L R; Brody, S

    1982-01-01

    The circadian rhythm of conidiation (spore formation) in Neurospora crassa is known to be temperature compensated, that is, the period is only slightly affected by the incubation temperature. Thus, the Q10 (the relative rate enhancement corresponding to a 10 degrees C rise in temperature) of the rhythm of the bd csp strain from 14 to 30 degrees C was 1.1, whereas the Q10 of the uncompensated growth rate in the same interval was 2.4. A mutation at the cel locus resulted in loss of the temperature-compensation property in cultures grown below 22 degrees C. The Q10 of the rhythm below 22 degrees C was 2.2, and periods of about 40 hr were observed. In contrast, the Q10 of the rhythm above 22 degrees C was 1.1, with circadian periods of 18-21 hr. Thus, cel displayed a threshold temperature or "break point" for the temperature compensation of its rhythm. Supplementation of cel strains, which require fatty acids, with unsaturated or short-chain fatty acids raised the threshold temperature to 26 degrees C, whereas supplementation with long-chain saturated fatty acids lowered it to 18 degrees C. These data suggest a role for fatty acids, as liquid components or as cellular metabolites, in the mechanism of temperature compensation. PMID:6461008

  10. Functional absence of brain photoreceptors mediating entrainment of circadian rhythms in the adult rat.

    PubMed

    Groos, G A; van der Kooy, D

    1981-01-15

    The photic energy penetrating into the brain was increased in adult rats sustaining craniotomies sealed with transparent plastic. After blinding, these animals failed to entrain their circadian food intake rhythm to light-dark cycles. Short pulses of light did not phase-shift the freerunning rhythm. We conclude that adult rats lack brain photoreceptors mediating entrainment of circadian rhythms. PMID:7202675

  11. Links between Circadian Rhythms and Psychiatric Disease.

    PubMed

    Karatsoreos, Ilia N

    2014-01-01

    Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmental exposure, or developmental insult. Rather, it is a complex interaction between these various influences that likely leads to the development of clinically relevant syndromes. Our lab is exploring the links between environmental exposures and neurobehavioral function by investigating how disruption of the circadian (daily) clock alters the structure and function of neural circuits, with the hypothesis that disrupting this crucial homeostatic system can directly contribute to altered vulnerability of the organism to other factors that interact to produce psychiatric illness. This review explores some historical and more recent findings that link disrupted circadian clocks to neuropsychiatric disorders, particularly depression, mania, and schizophrenia. We take a comparative approach by exploring the effects observed in human populations, as well as some experimental models used in the laboratory to unravel mechanistic and causal relationships between disruption of the circadian clock and behavioral abnormalities. This is a rich area of research that we predict will contribute greatly to our understanding of how genes, environment, and development interact to modulate an individual's vulnerability to psychiatric disorders. PMID:24834040

  12. The pineal and circadian rhythms of temperature selection and locomotion in lizards.

    PubMed

    Innocenti, A; Minutini, L; Foà, A

    1993-05-01

    The existence of a circadian rhythm of behavioral temperature selection has been demonstrated in lizards (Podarcis sicula) held on a thermal gradient in constant darkness. This rhythm becomes temporarily abolished during 1 week following parietalectomy and 2-3 weeks following pinealectomy. Parietalectomy does not affect the locomotor rhythm, while pinealectomy invariably lengthens the freerunning period of this rhythm. These results support the contention of separate control systems for the temperature selection rhythm and the locomotor rhythm. As neither rhythm is definitively abolished by parietalectomy and pinealectomy, other pacemaking components exist elsewhere in the circadian system of Podarcis sicula which can control both rhythms. PMID:8511207

  13. Circadian Rhythms, Metabolism, and Chrononutrition in Rodents and Humans.

    PubMed

    Johnston, Jonathan D; Ordovás, José M; Scheer, Frank A; Turek, Fred W

    2016-03-01

    Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial responses. Recent work has elucidated the metabolic roles of circadian clocks in key metabolic tissues, including liver, pancreas, white adipose, and skeletal muscle. For example, tissue-specific clock disruption in a single peripheral organ can cause obesity or disruption of whole-organism glucose homeostasis. This review explains mechanistic insights gained from transgenic animal studies and how these data are being translated into the study of human genetics and physiology. The principles of chrononutrition have already been demonstrated to improve human weight loss and are likely to benefit the health of individuals with metabolic disease, as well as of the general population. PMID:26980824

  14. Implications of circadian rhythm and stress in addiction vulnerability

    PubMed Central

    Becker-Krail, Darius; McClung, Colleen

    2016-01-01

    In the face of chronic stress, some individuals can maintain normal function while others go on to develop mental illness. Addiction, affecting one in every twelve people in America, is a substance use disorder long associated with stressful life events and disruptions in the sleep/wake cycle. The circadian and stress response systems have evolved to afford adaptability to environmental changes and allow for maintenance of functional stability, or homeostasis. This mini-review will discuss how circadian rhythms and stress individually affect drug response, affect each other, and how their interactions may regulate reward-related behavior. In particular, we will focus on the interactions between the circadian clock and the regulation of glucocorticoids by the hypothalamic-pituitary-adrenal (HPA) axis. Determining how these two systems act on dopaminergic reward circuitry may not only reveal the basis for vulnerability to addiction, but may also illuminate potential therapeutic targets for future investigation. PMID:26913197

  15. Implicit Associations Have a Circadian Rhythm

    PubMed Central

    Zadra, Jonathan R.; Proffitt, Dennis R.

    2014-01-01

    The current study shows that people's ability to inhibit implicit associations that run counter to their explicit views varies in a circadian pattern. The presence of this rhythmic variation suggests the involvement of a biological process in regulating automatic associations—specifically, with the current data, associations that form undesirable social biases. In 1998, Greenwald, McGhee, and Schwartz introduced the Implicit Association Test as a means of measuring individual differences in implicit cognition. The IAT is a powerful tool that has become widely used. Perhaps most visibly, studies employing the IAT demonstrate that people generally hold implicit biases against social groups, which often conflict with their explicitly held views. The IAT engages inhibitory processes similar to those inherent in self-control tasks. Because the latter processes are known to be resource-limited, we considered whether IAT scores might likewise be resource dependent. Analyzing IAT performance from over a million participants across all times of day, we found a clear circadian pattern in scores. This finding suggests that the IAT measures not only the strength of implicit associations, but also the effect of variations in the physiological resources available to inhibit their undesirable influences on explicit behavior. PMID:25365254

  16. Circadian rhythms affect electroretinogram, compound eye color, striking behavior and locomotion of the praying mantis Hierodula patellifera.

    PubMed

    Schirmer, Aaron E; Prete, Frederick R; Mantes, Edgar S; Urdiales, Andrew F; Bogue, Wil

    2014-11-01

    Many behaviors and physiological processes oscillate with circadian rhythms that are synchronized to environmental cues (e.g. light onset), but persist with periods of ~24 h in the absence of such cues. We used a multilevel experimental approach to assess whether circadian rhythms modulate several aspects of the visual physiology and behavior of the praying mantis Hierodula patellifera. We used electroretinograms (ERGs) to assess compound eye sensitivity, colorimetric photographic analyses to assess compound eye color changes (screening pigment migration), behavioral assays of responsiveness to computer-generated prey-like visual stimuli and analyses of locomotor activity patterns on a modified treadmill apparatus. Our results indicate that circadian clocks control and/or modulate each of the target behaviors. Strong rhythms, persisting under constant conditions, with periods of ~24 h were evident in photoreceptor sensitivity to light, appetitive responsiveness to prey-like stimuli and gross locomotor activity. In the first two cases, responsiveness was highest during the subjective night and lowest during the subjective day. Locomotor activity was strongly clustered around the transition time from day to night. In addition, pigment migration and locomotor behavior responded strongly to light:dark cycles and anticipated the light-dark transition, suggesting that the circadian clocks modulating both were entrained to environmental light cues. Together, these data indicate that circadian rhythms operate at the cellular, cellular systems and organismal level in H. patellifera. Our results represent an intriguing first step in uncovering the complexities of circadian rhythms in the Mantodea. PMID:25214491

  17. Circadian rhythm dissociation in an environment with conflicting temporal information

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Fuller, C. A.; Hiles, L. G.; Moore-Ede, M. C.

    1978-01-01

    The relative contributions of light-dark (LD) cycles and eating-fasting (EF) cycles in providing temporal information to the circadian time-keeping system were examined in chair-acclimatized squirrel monkeys (Saimiri sciureus). The circadian rhythms of drinking, colonic temperature, urine volume, and urinary potassium excretion were measured with the LD and EF cycles providing either conflicting phases or periods. In conflicting phase experiments, animals were exposed to 24-hr LD cycles consisting of 12 hr of 600 lx followed by 12 hr of less than 1 lx and concurrent 24-hr EF cycles in which the animals ate for 3 hr and then fasted for 21 hr. One group had food available at the beginning and a second group at the end of the light period. In conflicting period experiments, monkeys were exposed to 23-hr LD cycles and 24-hr EF cycles. Analysis of the rhythms showed that both phase and period information were conveyed to the drinking and urinary rhythms by the EF cycle, and to the temperature rhythm by the LD cycle.

  18. cap alpha. -Methyl-p-tyrosine shifts circadian temperature rhythms

    SciTech Connect

    Cahill, A.L.; Ehret, C.F.

    1982-09-01

    ..cap alpha..-Methyl-p-tyrosine shifts the acrophase (time of highest temperature) of the circadian temperature rhythm of the rat to earlier or later times of day depending on the phase of the cicadian cycle at which the drug is administered. When ..cap alpha..-methyl-p-tyrosine methyl ester HCl is injected intraperitoneally at a dose of 100 mg/kg late in the projected 8-h light phase, the acrophase of the intraperitoneal temperature rhythm is delayed by up to 3 h.However, when the same dose of drug is given 9-10 h into the projected 16-h dark phase of the daily cycle, the acrophase of the temperature rhythm occurs about 2 h earlier than expected. The times of ..cap alpha..-methyl-p-tyrosine administration leading to maximal phase delays or advances are correlated with the times of minimal and maximal turnover of norepinephrine in the hypothalamus. These results suggest that changing rates of norepinephrine turnover in the hypothalamus may regulate the circadian temperature rhythm in rats. The results also emphasize the fact that the effects of drugs may vary as a function of the time of administration. This fact must be taken into account in pharmacologic testing.

  19. Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans.

    PubMed

    Wang, Joshua L; Lim, Andrew S; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Lo, Men-Tzung; Schneider, Julie A; Buchman, Aron S; Bennett, David A; Hu, Kun; Saper, Clifford B

    2015-08-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day-night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age-matched controls is correlated with the number of vasoactive intestinal peptide-expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging- and AD-related circadian disturbances. PMID:25921596

  20. Photic and Pineal Modulation of Food Anticipatory Circadian Activity Rhythms in Rodents

    PubMed Central

    Patton, Danica F.; Parfyonov, Maksim; Gourmelen, Sylviane; Opiol, Hanna; Pavlovski, Ilya; Marchant, Elliott G.; Challet, Etienne; Mistlberger, Ralph E.

    2013-01-01

    Restricted daily feeding schedules entrain circadian oscillators that generate food anticipatory activity (FAA) rhythms in nocturnal rodents. The location of food-entrainable oscillators (FEOs) necessary for FAA remains uncertain. The most common procedure for inducing circadian FAA is to limit food access to a few hours in the middle of the light period, when activity levels are normally low. Although light at night suppresses activity (negative masking) in nocturnal rodents, it does not prevent the expression of daytime FAA. Nonetheless, light could reduce the duration or magnitude of FAA. If so, then neural or genetic ablations designed to identify components of the food-entrainable circadian system could alter the expression of FAA by affecting behavioral responses to light. To assess the plausibility of light as a potential mediating variable in studies of FAA mechanisms, we quantified FAA in rats and mice alternately maintained in a standard full photoperiod (12h of light/day) and in a skeleton photoperiod (two 60 min light pulses simulating dawn and dusk). In both species, FAA was significantly and reversibly enhanced in the skeleton photoperiod compared to the full photoperiod. In a third experiment, FAA was found to be significantly attenuated in rats by pinealectomy, a procedure that has been reported to enhance some effects of light on behavioral circadian rhythms. These results indicate that procedures affecting behavioral responses to light can significantly alter the magnitude of food anticipatory rhythms in rodents. PMID:24324709

  1. Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms.

    PubMed

    Lee, Ivan T; Chang, Alexander S; Manandhar, Manabu; Shan, Yongli; Fan, Junmei; Izumo, Mariko; Ikeda, Yuichi; Motoike, Toshiyuki; Dixon, Shelley; Seinfeld, Jeffrey E; Takahashi, Joseph S; Yanagisawa, Masashi

    2015-03-01

    Circadian behavior in mammals is orchestrated by neurons within the suprachiasmatic nucleus (SCN), yet the neuronal population necessary for the generation of timekeeping remains unknown. We show that a subset of SCN neurons expressing the neuropeptide neuromedin S (NMS) plays an essential role in the generation of daily rhythms in behavior. We demonstrate that lengthening period within Nms neurons is sufficient to lengthen period of the SCN and behavioral circadian rhythms. Conversely, mice without a functional molecular clock within Nms neurons lack synchronous molecular oscillations and coherent behavioral daily rhythms. Interestingly, we found that mice lacking Nms and its closely related paralog, Nmu, do not lose in vivo circadian rhythms. However, blocking vesicular transmission from Nms neurons with intact cell-autonomous clocks disrupts the timing mechanisms of the SCN, revealing that Nms neurons define a subpopulation of pacemakers that control SCN network synchrony and in vivo circadian rhythms through intercellular synaptic transmission. PMID:25741729

  2. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    PubMed

    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA. PMID:23918383

  3. Biomarkers for Circadian Rhythm Disruption Independent of Time of Day

    PubMed Central

    Van Dycke, Kirsten C. G.; Pennings, Jeroen L. A.; van Oostrom, Conny T. M.; van Kerkhof, Linda W. M.; van Steeg, Harry; van der Horst, Gijsbertus T. J.; Rodenburg, Wendy

    2015-01-01

    Frequent shift work causes disruption of the circadian rhythm and might on the long-term result in increased health risk. Current biomarkers evaluating the presence of circadian rhythm disturbance (CRD), including melatonin, cortisol and body temperature, require 24-hr (“around the clock”) measurements, which is tedious. Therefore, these markers are not eligible to be used in large-scale (human) studies. The aim of the present study was to identify universal biomarkers for CRD independent of time of day using a transcriptomics approach. Female FVB mice were exposed to six shifts in a clockwise (CW) and counterclockwise (CCW) CRD protocol and sacrificed at baseline and after 1 shift, 6 shifts, 5 days recovery and 14 days recovery, respectively. At six time-points during the day, livers were collected for mRNA microarray analysis. Using a classification approach, we identified a set of biomarkers able to classify samples into either CRD or non-disrupted based on the hepatic gene expression. Furthermore, we identified differentially expressed genes 14 days after the last shift compared to baseline for both CRD protocols. Non-circadian genes differentially expressed upon both CW and CCW protocol were considered useful, universal markers for CRD. One candidate marker i.e. CD36 was evaluated in serum samples of the CRD animals versus controls. These biomarkers might be useful to measure CRD and can be used later on for monitoring the effectiveness of intervention strategies aiming to prevent or minimize chronic adverse health effects. PMID:25984797

  4. Circadian rhythm studies in neuronal ceroid-lipofuscinosis (NCL).

    PubMed

    Heikkilä, E; Hàtònen, T H; Telakivi, T; Laakso, M L; Heiskala, H; Salmi, T; Alila, A; Santavuori, P

    1995-06-01

    Sleep disorders are common in NCL patients. The patients have problems such as frequent awakenings, difficulties with sleep onset, nightmares, and night terrors. The aim of the study was to examine whether the sleep disturbance in NCL can be explained on the basis of desynchronised circadian rhythms. Therefore we studied diurnal patterns of melatonin, cortisol, body temperature, and motor activity of 14 patients. The group consisted of 8 JNCL patients, 5 INCL children, and one boy with Jansky-Bielschowsky disease of the variant type. There were healthy age- and sex-matched control subjects. The blood samples for serum melatonin and cortisol were collected every 2 hours during 24-hour periods. Body temperature was recorded continuously for a 24-hour period by a polygraph. Diurnal motor activity was measured by wrist actigraphy for 5 days. In most of our patients sleep was fragmented and the sleep phase was irregular. Disturbances in the daily hormonal rhythms occurred only in the minority of the patients and only at an advanced stage of the disease. Although disturbances in the body temperature rhythm were found in about half of the patients, a general failure in the circadian regulatory system does not explain the frequent disturbances of the sleep-wake cycle of the NCL patients. PMID:7668335

  5. Therapeutic applications of circadian rhythms for the cardiovascular system

    PubMed Central

    Tsimakouridze, Elena V.; Alibhai, Faisal J.; Martino, Tami A.

    2015-01-01

    The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach toward cardiovascular (and other) diseases. Here we describe leading-edge therapeutic applications of circadian biology including (1) timing of therapy to maximize efficacy in treating heart disease (chronotherapy); (2) novel biomarkers discovered by testing for genomic, proteomic, metabolomic, or other factors at different times of day and night (chronobiomarkers); and (3) novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs). Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically. PMID:25941487

  6. Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver.

    PubMed

    Ando, Hitoshi; Ushijima, Kentaro; Shimba, Shigeki; Fujimura, Akio

    2016-02-01

    Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production-related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon. PMID:26653333

  7. Comparison of circadian rhythms in male and female humans

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Deroshia, C. W.; Vernikos-Danellis, J.; Rosenblatt, W. S.; Hetherington, N. W.

    1977-01-01

    Heart rate (HR) and rectal temperature (RT) data were obtained from 12 female and 27 male subjects. The subjects were housed in a facility where the environment was controlled. Human male and female RT and HR exhibit a circadian rhythm with an excursion of about 1.2 C and 30 beats/min, respectively. The acrophases, amplitudes, and level crossings are only slightly different between the sexes. The male HR and RT circadian wave forms are more stable than those of the females. However, the actual RT and HR of males were always lower than that of females at all time points around the clock. The HR during sleep in females is 15 per cent below the daily mean heart rate and in males, 22 per cent.

  8. Aging, circadian rhythms and depressive disorders: a review

    PubMed Central

    Campos Costa, Inês; Nogueira Carvalho, Hugo; Fernandes, Lia

    2013-01-01

    Introduction: Aging is typically associated with impairing behavioral patterns that are frequently and inappropriately seen as normal. Circadian rhythm changes and depressive disorders have been increasingly proposed as the two main overlapping and interpenetrating changes that take place in older age. This study aims to review the state of the art on the subject concerning epidemiology, pathophysiological mechanism, clinical findings and relevance, as well as available treatment options. Materials and Methods: A nonsystematic review of all English language PubMed articles published between 1995 and December 2012 using the terms “circadian rhythms”, “mood disorders”, “depression”, “age”, “aging”, “elderly” and “sleep”. Discussion and conclusion: Sleep disorders, mainly insomnia, and depression have been demonstrated to be highly co-prevalent and mutually precipitating conditions in the elderly population. There is extensive research on the pathophysiological mechanisms through which age conditions circadian disruption, being the disruption of the Melatonin system one of the main changes. However, research linking clearly and unequivocally circadian disruption and mood disorders is still lacking. Nonetheless, there are consistently described molecular changes on shared genes and also several proposed pathophysiological models linking depression and sleep disruption, with clinical studies also suggesting a bi-directional relationship between these pathologies. In spite of this suggested relation, clinical evaluation of these conditions in elderly patients consistently reveals itself rather complicated due to the frequently co-existing co-morbidities, some of them having been demonstrated to alter sleep and mood patters. This is the case of strokes, forms of dementia such as Alzheimer and Parkinson, several neurodegenerative disorders, among others. Although there are to the present no specific treatment guidelines, available treatment options generally base themselves on the premise that depression and sleep disturbances share a bidirectional relationship and so, the adoption of measures that address specifically one of the conditions will reciprocally benefit the other. Treatment options range from Cognitive Behavioral Therapy, Chronotherapy, and Light therapy, to drugs such as Melatonin/Melatonin agonists, antidepressants and sedatives. PMID:24319642

  9. Independence of genetic variation between circadian rhythm and development time in the seed beetle, Callosobruchus chinensis.

    PubMed

    Harano, Tomohiro; Miyatake, Takahisa

    2011-03-01

    A positive genetic correlation between periods of circadian rhythm and developmental time supports the hypothesis that circadian clocks are implicated in the timing of development. Empirical evidence for this genetic correlation in insects has been documented in two fly species. In contrast, here we show that there is no evidence of genetic correlation between circadian rhythm and development time in the adzuki bean beetle, Callosobruchus chinensis. This species has variation that is explained by a major gene in the expression and period length of circadian rhythm between strains. In this study, we found genetic variation in development time between the strains. The development time was not covaried with either the incidence or the period length of circadian rhythm among the strains. Crosses between strains suggest that development time is controlled by a polygene. In the F(2) individuals from the crosses, the circadian rhythm is attributable to allelic variation in the major gene. Across the F(2) individuals, development time was not correlated with either the expression or the period length of circadian rhythm. Thus, we found no effects of major genes responsible for variation in the circadian rhythm on development time in C. chinensis. Our findings collectively give no support to the hypothesis that the circadian clock is involved in the regulation of development time in this species. PMID:21211539

  10. Circadian rhythms in myocardial metabolism and contractile function; influence of workload and oleate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple extra-cardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its ...

  11. Effect of hypergravity on the circadian rhythms of white rats.

    NASA Technical Reports Server (NTRS)

    Lafferty, J. F.

    1972-01-01

    The effects of artificial gravity on the circadian rhythm of white rats was observed by comparing feeding activity at 1.0 and 1.75 g. The feeding cycle data were obtained by observing the number of feeding switch responses, as well as the amount of food obtained, as a function of time. One of the three subjects clearly established a free-running cycle with a period of 24.742 hr. During a 40-day exposure to the 1.75 g environment, the subjects maintained the same feeding cycle period which was established at 1.0 g. While the results of this study indicate that the activity rhythms of rats are insensitive to gravity levels between 1.0 and 1.75 g, the effects of gravity levels below 1.0 g are yet to be determined.

  12. Circadian rhythms of chloroplast orientation and photosynthetic capacity in ulva.

    PubMed

    Britz, S J; Briggs, W R

    1976-07-01

    Ulva lactuca L. var. latissima (L.) Decandolle and var. rigida (C. Agardh) Le Jolis and U. mutabilis Foyn have a circadian rhythm of chloroplast orientation which results in large changes in the light-absorption properties of the thallus. During the day, the chloroplasts cover the outer face of the cells and absorbance is high. At night, the chloroplasts are along the side walls and absorbance is low. Enteromorpha linza (L.) J. Agardh, E. intestinalis (L.) Link, E. sp., and Monostroma grevillei (Thuret) Wittrock, members of the Ulvales, were not observed to have this rhythmic movement. Chloroplasts, when in the face position, could not be induced to move to the sides by high intensity light up to 80,000 lux. Unrelated to chloroplast position per se and light-absorption efficiency, there is a rhythm of photosynthetic capacity which peaks just before midday and which continues in constant darkness. PMID:16659613

  13. Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight. Part 1; Circadian Rhythms and Temperature Regulation

    NASA Technical Reports Server (NTRS)

    Fuller, C. A.; Alpatov, A. M.; Hoban-Higgins, T. M.; Klimovitsky, V. Y.

    1994-01-01

    Mammals have developed the ability to adapt to most variations encountered in their everyday environment. For example, homeotherms have developed the ability to maintain the internal cellular environment at a relatively constant temperature. Also, in order to compensate for temporal variations in the terrestrial environment, the circadian timing system has evolved. However, throughout the evolution of life on earth, living organisms have been exposed to the influence of an unvarying level of earth's gravity. As a result changes in gravity produce adaptive responses which are not completely understood. In particular, spaceflight has pronounced effects on various physiological and behavioral systems. Such systems include body temperature regulation and circadian rhythms. This program has examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite, COSMOS 2044, were exposed to 14 days of microgravity while constantly monitoring the circadian patterns temperature regulation, heart rate and activity. This experiment has extended our previous observations from COSMOS 1514, as well as providing insights into the physiological mechanisms that produce these changes.

  14. Circadian Rhythms in Gene Expression: Relationship to Physiology, Disease, Drug Disposition and Drug Action

    PubMed Central

    Sukumaran, Siddharth; Almon, Richard R.; DuBois, Debra C.; Jusko, William J.

    2010-01-01

    Circadian rhythms (24 h cycles) are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body. Components of this core clock mechanism regulate the circadian rhythms in genome-wide mRNA expression, which in turn regulate various biological processes. Disruption of circadian rhythms can be either the cause or the effect of various disorders including metabolic syndrome, inflammatory diseases and cancer. Furthermore, circadian rhythms in gene expression regulate both the action and disposition of various drugs and affect therapeutic efficacy and toxicity based on dosing time. Understanding the regulation of circadian rhythms in gene expression plays an important role in both optimizing the dosing time for existing drugs and in development of new therapeutics targeting the molecular clock. PMID:20542067

  15. Aging human circadian rhythms: conventional wisdom may not always be right

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.

    2005-01-01

    This review discusses the ways in which the circadian rhythms of older people are different from those of younger adults. After a brief discussion of clinical issues, the review describes the conventional wisdom regarding age-related changes in circadian rhythms. These can be summarized as four assertions regarding what happens to people as they get older: 1) the amplitude of their circadian rhythms reduces, 2) the phase of their circadian rhythms becomes earlier, 3) their natural free-running period (tau) shortens, and 4) their ability to tolerate abrupt phase shifts (e.g., from jet travel or night work) worsens. The review then discusses the empirical evidence for and against these assertions and discusses some alternative explanations. The conclusions are that although older people undoubtedly have earlier circadian phases than younger adults, and have more trouble coping with shift work and jet lag, evidence for the assertions about rhythm amplitude and tau are, at best, mixed.

  16. Period doubling observed in the circadian photosynthetic rhythm of the prokaryotic cyanobacterium Cyanothece RF-1

    NASA Astrophysics Data System (ADS)

    Yen, Tsu-Chiang; Cheng, Da-Long

    2005-03-01

    The circadian rhythm is an endogenous biological clock that governs biochemical phenomena or behavior in organisms. The Cyanothece RF-1 is the first prokaryote shown to exhibit circadian nitrogen-fixing rhythm. The observation of the circadian photosynthetic rhythm of this strain was recently reported by the authors. In this work, the dissolved-oxygen variation in the culture of Cyanothece RF-1 was recorded, which would reveal the photosynthetic activity of the strain. For a culture of about 1x10^8 cells/ml in concentration, a period-doubling pattern was clearly displayed in the circadian photosynthetic rhythm signals. The mechanism corresponding to this nonlinear effect will be discussed. These results represent the first observation of the period doubling in the circadian rhythm of a prokaryotic cyanobacterium.

  17. Thoracic surface temperature rhythms as circadian biomarkers for cancer chronotherapy

    PubMed Central

    Roche, Véronique Pasquale; Mohamad-Djafari, Ali; Innominato, Pasquale Fabio; Karaboué, Abdoulaye; Gorbach, Alexander; Lévi, Francis Albert

    2014-01-01

    The disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification resulted in cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Collected at baseline, during and after therapy longitudinal data sets were processed using Fast Fourier Transform Cosinor and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p<0.05) for 49/61 temperature time series (80.3%), and 15/16 rest-activity patterns (93.7%) at baseline. However, individual circadian amplitudes varied from 0.04 °C to 2.86 °C for skin surface temperature (median, 0.72 °C), and from 16.6 to 146.1 acc/min for rest-activity (median, 88.9 acc/min). Thirty-nine pairs of baseline temperature and rest-activity time series (75%) were correlated (r>|0.7|; p<0.05). Individual circadian acrophases at baseline were scattered from 15:18 to 6:05 for skin surface temperature, and from 12:19 to 15:18 for rest-activity, with respective median values of 01:10 (25–75% quartiles, 22:35–3:07) and 14:12 (13:14–14:31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. In contrast, transient or sustained disruption of these biomarkers was found for the five other patients, as indicated by the lack of any statistically significant dominant period in the circadian range. No consistent correlation (r<|0.7|, p ? 0.05) was found between paired rest-activity and temperature time series during fixed chronotherapy delivery. In conclusion, large inter-patient differences in circadian amplitudes and acrophases of skin surface temperature were demonstrated for the first time in cancer patients, despite rather similar rest-activity acrophases. The patient-dependent coupling between both CTS biomarkers, and its possible alteration on a fixed chronotherapy protocol, support the concept of personalized cancer chronotherapy. PMID:24397341

  18. AMPK Regulates Circadian Rhythms in a Tissue- and Isoform-Specific Manner

    PubMed Central

    Um, Jee-Hyun; Pendergast, Julie S.; Springer, Danielle A.; Foretz, Marc; Viollet, Benoit; Brown, Alexandra; Kim, Myung K.; Yamazaki, Shin; Chung, Jay H.

    2011-01-01

    Background AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKIα and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo. Methodology/Principal Finding The catalytic subunit of AMPK has two isoforms: α1 and α2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPKα1−/− and AMPKα2−/− mice. We found that both α1−/− and α2−/− mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but α1−/− mice have a shorter circadian period whereas α2−/− mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in α1−/− mice, but not in α2−/− mice. The circadian pattern of core clock gene expression was severely disrupted in fat in α1−/− mice, but it was severely disrupted in the heart and skeletal muscle of α2−/− mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both α1−/− and α2−/− mice. The circadian rhythm of nicotinamide phosphoryl-transferase (NAMPT) activity, which converts nicotinamide (NAM) to NAD+, is an important regulator of the circadian clock. We found that the NAMPT rhythm was absent in AMPK-deficient tissues and cells. Conclusion/Significance This study demonstrates that the catalytic activity of AMPK regulates circadian rhythm of behavior, energy metabolism and gene expression in isoform- and tissue-specific manners. PMID:21483791

  19. Circadian rhythm disruption in a mouse model of Rett syndrome circadian disruption in RTT.

    PubMed

    Li, Quan; Loh, Dawn H; Kudo, Takashi; Truong, Danny; Derakhshesh, Matthew; Kaswan, Zoë MacDowell; Ghiani, Cristina A; Tsoa, Rosemarie; Cheng, Yin; Sun, Yi E; Colwell, Christopher S

    2015-05-01

    Disturbances in the sleep/wake cycle are prevalent in patients with Rett syndrome (RTT). We sought to determine whether the circadian system is disrupted in a RTT model, Mecp2(-/y) mice. We found that MeCP2 mutants showed decreased strength and precision of daily rhythms of activity coupled with extremely fragmented sleep. The central circadian clock (suprachiasmatic nucleus) exhibited significant reduction in the number of neurons expressing vasoactive intestinal peptide (VIP) as well as compromised spontaneous neural activity. The molecular clockwork was disrupted both centrally in the SCN and in peripheral organs, indicating a general disorganization of the circadian system. Disruption of the molecular clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice were vulnerable to circadian disruption as chronic jet lag accelerated mortality. Our finds suggest an integral role of MeCP2 in the circadian timing system and provides a possible mechanistic explanation for the sleep/wake distrubances observed in RTT patients. The work raises the possibility that RTT patients may benefit from a temporally structured environment. PMID:25779967

  20. Effect of circadian rhythm on CNS oxygen toxicity.

    NASA Technical Reports Server (NTRS)

    Hof, D. G.; Dexter, J. D.; Mengel, C. E.

    1971-01-01

    The circadian rhythm in susceptibility to oxygen toxicity seizures was investigated by using six groups of 20 male Sprague-Dawley rats (101-196 gm.). The animals were given standard chow, exposed to standard diurnal conditions of light (0700-1900 hr) and dark (1900-0700 hr), and fasted for 15-16 hr prior to exposure to hyperbaric oxygen. The animals were placed in a previously oxygen flushed chamber and raised to 60 psi (gauge) oxygen at a rate of 3 psi/min. Time of exposure started with attainment of 60 psi. End point was first convulsion. The animals' weights were equally distributed within the groups, and the groups were defined by hour of exposure. Time of exposure in minutes prior to seizure was significantly longer in those exposed at 0700-0800 hr and 1000-1100 hr than in four other groups. There was no relationship between animals' weights and time of exposure to seizures. All R values were negative, and the highest R value was -035. These data suggest a definite circadian rhythm in susceptibility to oxygen toxicity seizures.

  1. Circadian rhythms in rheumatology--a glucocorticoid perspective.

    PubMed

    Spies, Cornelia M; Straub, Rainer H; Cutolo, Maurizio; Buttgereit, Frank

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in regulating and controlling immune responses. Dysfunction of the HPA axis has been implicated in the pathogenesis of rheumatoid arthritis (RA) and other rheumatic diseases. The impact of glucocorticoid (GC) therapy on HPA axis function also remains a matter of concern, particularly for longer treatment duration. Knowledge of circadian rhythms and the influence of GC in rheumatology is important: on the one hand we aim for optimal treatment of the daily undulating inflammatory symptoms, for example morning stiffness and swelling; on the other, we wish to disturb the HPA axis as little as possible. This review describes circadian rhythms in RA and other chronic inflammatory diseases, dysfunction of the HPA axis in RA and other rheumatic diseases and the recent concept of the hepato-hypothalamic-pituitary-adrenal-renal axis, the problem of adrenal suppression by GC therapy and how it can be avoided, and evidence that chronotherapy with modified release prednisone effective at 02:00 a.m. can inhibit proinflammatory sequelae of nocturnal inflammation better compared with GC administration in the morning but does not increase the risk of HPA axis insufficiency in RA. PMID:25608777

  2. Wavelet-based analysis of circadian behavioral rhythms.

    PubMed

    Leise, Tanya L

    2015-01-01

    The challenging problems presented by noisy biological oscillators have led to the development of a great variety of methods for accurately estimating rhythmic parameters such as period and amplitude. This chapter focuses on wavelet-based methods, which can be quite effective for assessing how rhythms change over time, particularly if time series are at least a week in length. These methods can offer alternative views to complement more traditional methods of evaluating behavioral records. The analytic wavelet transform can estimate the instantaneous period and amplitude, as well as the phase of the rhythm at each time point, while the discrete wavelet transform can extract the circadian component of activity and measure the relative strength of that circadian component compared to those in other frequency bands. Wavelet transforms do not require the removal of noise or trend, and can, in fact, be effective at removing noise and trend from oscillatory time series. The Fourier periodogram and spectrogram are reviewed, followed by descriptions of the analytic and discrete wavelet transforms. Examples illustrate application of each method and their prior use in chronobiology is surveyed. Issues such as edge effects, frequency leakage, and implications of the uncertainty principle are also addressed. PMID:25662453

  3. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    PubMed Central

    Bonmati-Carrion, Maria Angeles; Arguelles-Prieto, Raquel; Martinez-Madrid, Maria Jose; Reiter, Russel; Hardeland, Ruediger; Rol, Maria Angeles; Madrid, Juan Antonio

    2014-01-01

    Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system. PMID:25526564

  4. Internal noise-sustained circadian rhythms in a Drosophila model.

    PubMed

    Li, Qianshu; Lang, Xiufeng

    2008-03-15

    Circadian rhythmic processes, mainly regulated by gene expression at the molecular level, have inherent stochasticity. Their robustness or resistance to internal noise has been extensively investigated by most of the previous studies. This work focuses on the constructive roles of internal noise in a reduced Drosophila model, which incorporates negative and positive feedback loops, each with a time delay. It is shown that internal noise sustains reliable oscillations with periods close to 24 h in a region of parameter space, where the deterministic kinetics would evolve to a stable steady state. The amplitudes of noise-sustained oscillations are significantly affected by the variation of internal noise level, and the best performance of the oscillations could be found at an optimal noise intensity, indicating the occurrence of intrinsic coherence resonance. In the oscillatory region of the deterministic model, the coherence of noisy circadian oscillations is suppressed by internal noise, while the period remains nearly constant over a large range of noise intensity, demonstrating robustness of the Drosophila model for circadian rhythms to intrinsic noise. In addition, the effects of time delay in the positive feedback on the oscillations are also investigated. It is found that the time delay could efficiently tune the performance of the noise-sustained oscillations. These results might aid understanding of the exploitation of intracellular noise in biochemical and genetic regulatory systems. PMID:17993496

  5. Role for LSM genes in the regulation of circadian rhythms.

    PubMed

    Perez-Santángelo, Soledad; Mancini, Estefanía; Francey, Lauren J; Schlaen, Ruben Gustavo; Chernomoretz, Ariel; Hogenesch, John B; Yanovsky, Marcelo J

    2014-10-21

    Growing evidence suggests that core spliceosomal components differentially affect RNA processing of specific genes; however, whether changes in the levels or activities of these factors control specific signaling pathways is largely unknown. Here we show that some SM-like (LSM) genes, which encode core components of the spliceosomal U6 small nuclear ribonucleoprotein complex, regulate circadian rhythms in plants and mammals. We found that the circadian clock regulates the expression of LSM5 in Arabidopsis plants and several LSM genes in mouse suprachiasmatic nucleus. Further, mutations in LSM5 or LSM4 in Arabidopsis, or down-regulation of LSM3, LSM5, or LSM7 expression in human cells, lengthens the circadian period. Although we identified changes in the expression and alternative splicing of some core clock genes in Arabidopsis lsm5 mutants, the precise molecular mechanism causing period lengthening remains to be identified. Genome-wide expression analysis of either a weak lsm5 or a strong lsm4 mutant allele in Arabidopsis revealed larger effects on alternative splicing than on constitutive splicing. Remarkably, large splicing defects were not observed in most of the introns evaluated using RNA-seq in the strong lsm4 mutant allele used in this study. These findings support the idea that some LSM genes play both regulatory and constitutive roles in RNA processing, contributing to the fine-tuning of specific signaling pathways. PMID:25288739

  6. Sleep and circadian rhythm disruption and recognition memory in schizophrenia.

    PubMed

    Tam, Shu K E; Pritchett, David; Brown, Laurence A; Foster, Russell G; Bannerman, David M; Peirson, Stuart N

    2015-01-01

    Schizophrenia patients often show irregularities in sleep and circadian rhythms and deficits in recognition memory. Similar phenotypes are seen in schizophrenia-relevant genetic mouse models, such as synaptosomal associated protein of 25 kDa (Snap-25) point mutant mice, vasoactive intestinal peptide receptor 2 (Vipr2) knockout mice, and neuregulin 1 (Nrg1)-deficient mice. Sleep and circadian abnormalities and impaired recognition memory may be causally related in both schizophrenia patients and schizophrenia-relevant mouse models, since sleep deprivation, abnormal photic input, and the manipulation of core clock genes (cryptochrome 1/2) can all disrupt object recognition memory in rodent models. The recognition deficits observed in patients and mouse models (both schizophrenia-related and -unrelated) are discussed here in terms of the dual-process theory of recognition, which postulates that there are two recognition mechanisms-recollection versus familiarity-that can be selectively impaired by brain lesions, neuropsychiatric conditions, and putatively, sleep and circadian rhythm disruption. However, based on this view, the findings from patient studies and studies using genetic mouse models (Nrg1 deficiency) seem to be inconsistent with each other. Schizophrenia patients are impaired at recollection (and to a lesser extent, familiarity judgments), but Nrg1-deficient mice are impaired at familiarity-based object recognition, raising concerns regarding the validity of using these genetically modified mice to model recognition phenotypes observed in patients. This issue can be resolved in future animal studies by examining performance in different variants of the spontaneous recognition task-the standard, perirhinal cortex-dependent, object recognition task versus the hippocampus-dependent object-place recognition task-in order to see which of the two recognition mechanisms is more disrupted. PMID:25707284

  7. Circadian rhythm phase shifts and endogenous free-running circadian period differ between African-Americans and European-Americans

    PubMed Central

    Eastman, Charmane I.; Suh, Christina; Tomaka, Victoria A.; Crowley, Stephanie J.

    2015-01-01

    Successful adaptation to modern civilization requires the internal circadian clock to make large phase shifts in response to circumstances (e.g., jet travel and shift work) that were not encountered during most of our evolution. We found that the magnitude and direction of the circadian clock's phase shift after the light/dark and sleep/wake/meal schedule was phase-advanced (made earlier) by 9 hours differed in European-Americans compared to African-Americans. European-Americans had larger phase shifts, but were more likely to phase-delay after the 9-hour advance (to phase shift in the wrong direction). The magnitude and direction of the phase shift was related to the free-running circadian period, and European-Americans had a longer circadian period than African-Americans. Circadian period was related to the percent Sub-Saharan African and European ancestry from DNA samples. We speculate that a short circadian period was advantageous during our evolution in Africa and lengthened with northern migrations out of Africa. The differences in circadian rhythms remaining today are relevant for understanding and treating the modern circadian-rhythm-based disorders which are due to a misalignment between the internal circadian rhythms and the times for sleep, work, school and meals. PMID:25670162

  8. Circadian rhythm phase shifts and endogenous free-running circadian period differ between African-Americans and European-Americans.

    PubMed

    Eastman, Charmane I; Suh, Christina; Tomaka, Victoria A; Crowley, Stephanie J

    2015-01-01

    Successful adaptation to modern civilization requires the internal circadian clock to make large phase shifts in response to circumstances (e.g., jet travel and shift work) that were not encountered during most of our evolution. We found that the magnitude and direction of the circadian clock's phase shift after the light/dark and sleep/wake/meal schedule was phase-advanced (made earlier) by 9?hours differed in European-Americans compared to African-Americans. European-Americans had larger phase shifts, but were more likely to phase-delay after the 9-hour advance (to phase shift in the wrong direction). The magnitude and direction of the phase shift was related to the free-running circadian period, and European-Americans had a longer circadian period than African-Americans. Circadian period was related to the percent Sub-Saharan African and European ancestry from DNA samples. We speculate that a short circadian period was advantageous during our evolution in Africa and lengthened with northern migrations out of Africa. The differences in circadian rhythms remaining today are relevant for understanding and treating the modern circadian-rhythm-based disorders which are due to a misalignment between the internal circadian rhythms and the times for sleep, work, school and meals. PMID:25670162

  9. Circadian Sleep-Wake Rhythm of Older Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Maaskant, Marijke; van de Wouw, Ellen; van Wijck, Ruud; Evenhuis, Heleen M.; Echteld, Michael A.

    2013-01-01

    The circadian sleep-wake rhythm changes with aging, resulting in a more fragmented sleep-wake pattern. In individuals with intellectual disabilities (ID), brain structures regulating the sleep-wake rhythm might be affected. The aims of this study were to compare the sleep-wake rhythm of older adults with ID to that of older adults in the general…

  10. Circadian Sleep-Wake Rhythm of Older Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Maaskant, Marijke; van de Wouw, Ellen; van Wijck, Ruud; Evenhuis, Heleen M.; Echteld, Michael A.

    2013-01-01

    The circadian sleep-wake rhythm changes with aging, resulting in a more fragmented sleep-wake pattern. In individuals with intellectual disabilities (ID), brain structures regulating the sleep-wake rhythm might be affected. The aims of this study were to compare the sleep-wake rhythm of older adults with ID to that of older adults in the general…

  11. Circadian susceptibility rhythm of the rat to alloxan.

    PubMed

    Hernandez, R E; Kühl, J F; Halberg, E; Halberg, F; Shiotsuka, R N; Haus, E

    1978-01-01

    The susceptibility of rats to alloxan undergoes a circadin rhythm. The toxicity rhythm, presumably involving injury to liver, kidney and other sites, pancreatic beta-cells in particular, is demonstrated in pooled data from 370 mature inbred Fischer or Minnesota Sprague-Dawley rats of both sexes kept in light from 06(00) to 18(00) alternating with darkness, some with free access to Purina laboratory chow with tap water at all times and some other rats subjected to one of three starvation schedules: 1) a 28-h fast before an intravenous alloxan injection; 2) a 28-h fast, except for a 4-h ad libitum feeding before injection; 3) a 28-h fast, except for a 4-h pre-injection tube-feeding of Nutrament (Mead and Johnson, Evansville, Indiana), 1.5 ml/100 g body weight. Survival time data on an additional 200 inbred Fischer rats reveal, next, that susceptibility to alloxan increases as the starvation span is lengthened from 24 to 84 h. The shortening in survival time indicative of this susceptibility increase is nonlinear; a circadian rhythmic change in susceptibility to alloxan is seen as a statistically significant wave-form indicative of the basic (persisting) rhythm, of applied interest as well to students of experimental diabetes. PMID:747984

  12. Effects of 24-hour shift work with nighttime napping on circadian rhythm characteristics in ambulance personnel.

    PubMed

    Motohashi, Y; Takano, T

    1993-12-01

    Forty-two ambulance personnel engaged in a 24-h shift system participated in a chronobiological field study to study the effects of 24-h shift work on circadian rhythm characteristics. Autorhythmometry of circadian rhythms of oral temperature, right and left grip strengths, and heart rate plus subjective assessment of drowsiness, fatigue, and attention was performed every approximately 4 h except during sleep for 7 days. Cosinor and power spectral analyses were applied to the longitudinal data of each individual. Changes in circadian period different from 24 h of oral temperature, grip strengths, and heart rate plus subjective drowsiness, fatigue, and attention were observed in ambulance personnel. The incidence of circadian periodicity different from 24 h in oral temperature and right and left grip strength was 28.6%, 35.7%, and 47.6%, respectively. The incidence was relatively lower than that of shift workers engaged in a discontinuous 8-h shift system we reported on previously. Working conditions allowing ambulance personnel to nap when not called for emergency (for > 4 h) might contribute to a stabilization of circadian rhythms. Furthermore, long nighttime ambulance service amounting to > 100 min was significantly associated with a high incidence of at least one prominent circadian period among oral temperature and right and left grip strength rhythms different from 24 h. In conclusion, 24-h shift work altered the characteristics of circadian rhythms of ambulance personnel; nighttime naps seemed to have a favorable effect on averting changes in circadian rhythms. PMID:8111871

  13. FTO modulates circadian rhythms and inhibits the CLOCK-BMAL1-induced transcription.

    PubMed

    Wang, Chao-Yung; Shie, Shian-Sen; Hsieh, I-Chang; Tsai, Ming-Lung; Wen, Ming-Shien

    2015-08-28

    Variations in the human fat mass and obesity-associated gene, which encodes FTO, an 2-oxoglutarate-dependent nucleic acid demethylase, are associated with increased risk of obesity. These FTO variations were recently shown to affect IRX3 and the exact function of FTO is still controversial. Obesity is closely linked to circadian rhythm. To understand the role of FTO in circadian rhythm, we analyzed the circadian rhythm of FTO deficient mice. FTO deficient mice had robust circadian locomotor activity rhythms with prolonged periods. The light-induced phase shifts of circadian rhythms were also significantly affected in FTO deficient mice. Tissue explants of FTO deficient mice maintained robust peripheral rhythms with prolonged period. Overexpress of FTO represses the transcriptional activation by CLOCK and BMAL1. Core clock genes expression of mRNA and protein were also altered in FTO deficient mice. Furthermore, FTO co-immunoprecipitated with CRY1/2 in a circadian manner. These results indicate a fundamental link between the circadian rhythm and FTO and extend the function of FTO to the core clockwork machinery. PMID:26188089

  14. [The influence of interfered circadian rhythm on pregnancy and neonatal rats].

    PubMed

    Chen, Wen-Jun; Sheng, Wen-Jie; Guo, Yin-Hua; Tan, Yong

    2015-10-25

    The aim of this study was to observe the influence of interfered circadian rhythm on pregnancy of rats and growth of neonatal rats, and to explore the relationship between the interfered circadian rhythm and the changes of melatonin and progesterone. Continuous light was used to inhibit melatonin secretion and therefore the interfered circadian rhythm animal model was obtained. The influence of interfered circadian rhythm on delivery of pregnant rats was observed. Serum was collected from rats during different stages of pregnancy to measure the concentrations of melatonin and progesterone. In order to observe the embryo resorption rate, half of pregnant rats were randomly selected to undergo a laparotomy, and the remainder was used to observe delivery and assess the growth of neonatal rats after delivery. The results showed that the interfered circadian rhythm induced adverse effects on pregnancy outcomes, including an increase of embryo resorption rate and a decrease in the number of live births; inhibited the secretion of melatonin along with decreased serum progesterone level; prolonged the stage of labor, but not the duration of pregnancy; and disturbed the fetal intrauterine growth and the growth of neonatal rats. The results suggest that interfered circadian rhythm condition made by continuous light could make adverse effects on both pregnant rats and neonatal rats. The results of our study may provide a way to modulate pregnant women's circadian rhythm and a possibility of application of melatonin on pregnant women. PMID:26490070

  15. Persistence of Eclosion Rhythm in Drosophila melanogaster After 600 Generations in an Aperiodic Environment

    NASA Astrophysics Data System (ADS)

    Sheeba, V.; Sharma, V. K.; Chandrashekaran, M. K.; Joshi, A.

    The ubiquity of circadian rhythms suggests that they have an intrinsic adaptive value (Ouyang et al. 1998; Ronneberg and Foster 1997). Some experiments have shown that organisms have enhanced longevity, development time or growth rates when maintained in environments whose periodicity closely matches their endogenous period (Aschoff et al. 1971; Highkin and Hanson 1954; Hillman 1956; Pittendrigh and Minis 1972; Went 1960). So far there has been no experimental evidence to show that circadian rhythms per se (i.e. periodicity itself, as opposed to phasing properties of a rhythm) confer a fitness advantage. We show that the circadian eclosion rhythm persists in a population of the fruitfly Drosophila melanogaster maintained in constant conditions of light, temperature, and humidity for over 600 generations. The results suggest that even in the absence of any environmental cycle there exists some intrinsic fitness value of circadian rhythms.

  16. Transcriptional control of circadian metabolic rhythms in the liver.

    PubMed

    Li, S; Lin, J D

    2015-09-01

    Diurnal metabolic rhythms add an important temporal dimension to metabolic homeostasis in mammals. Although it remains a challenge to untangle the intricate networks of crosstalk among the body clock, nutrient signalling and tissue metabolism, there is little doubt that the rhythmic nature of nutrient and energy metabolism is a central aspect of metabolic physiology. Disruption of the synchrony between clock and metabolism has been causally linked to diverse pathophysiological states. As such, restoring the rhythmicity of body physiology and therapeutic targeting directed at specific time windows during the day may have important implications in human health and medicine. In this review, we summarize recent findings on the integration of hepatic glucose metabolism and the body clock through a regulatory network centred on the PPAR? coactivator 1 (PGC-1) transcriptional coactivators. In addition, we discuss the transcriptional mechanisms underlying circadian control of the autophagy gene programme and autophagy in the liver. PMID:26332966

  17. Attenuated Food Anticipatory Activity and Abnormal Circadian Locomotor Rhythms in Rgs16 Knockdown Mice

    PubMed Central

    Hayasaka, Naoto; Aoki, Kazuyuki; Kinoshita, Saori; Yamaguchi, Shoutaroh; Wakefield, John K.; Tsuji-Kawahara, Sachiyo; Horikawa, Kazumasa; Ikegami, Hiroshi; Wakana, Shigeharu; Murakami, Takamichi; Ramabhadran, Ram; Miyazawa, Masaaki; Shibata, Shigenobu

    2011-01-01

    Regulators of G protein signaling (RGS) are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs) of G protein ?-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN), the master circadian light-entrainable oscillator (LEO) of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA) targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO)-driven elevated food-anticipatory activity (FAA) observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phase-advanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s). PMID:21408016

  18. Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse.

    PubMed

    Tsuchiya, Yoshiki; Minami, Yoichi; Umemura, Yasuhiro; Watanabe, Hitomi; Ono, Daisuke; Nakamura, Wataru; Takahashi, Tomoyuki; Honma, Sato; Kondoh, Gen; Matsuishi, Toyojiro; Yagita, Kazuhiro

    2015-12-01

    Methyl-CpG-binding protein 2 (Mecp2) is an X-linked gene encoding a methylated DNA-binding nuclear protein which regulates transcriptional activity. The mutation of MECP2 in humans is associated with Rett syndrome (RTT), a neurodevelopmental disorder. Patients with RTT frequently show abnormal sleep patterns and sleep-associated problems, in addition to autistic symptoms, raising the possibility of circadian clock dysfunction in RTT. In this study, we investigated circadian clock function in Mecp2-deficient mice. We successfully generated both male and female Mecp2-deficient mice on the wild-type C57BL/6 background and PER2(Luciferase) (PER2(Luc) ) knock-in background using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Generated Mecp2-deficient mice recapitulated reduced activity in mouse models of RTT, and their activity rhythms were diminished in constant dark conditions. Furthermore, real-time bioluminescence imaging showed that the amplitude of PER2(Luc) -driven circadian oscillation was significantly attenuated in Mecp2-deficient SCN neurons. On the other hand, in vitro circadian rhythm development assay using Mecp2-deficient mouse embryonic stem cells (ESCs) did not show amplitude changes of PER2(Luc) bioluminescence rhythms. Together, these results show that Mecp2 deficiency abrogates the circadian pacemaking ability of the SCN, which may be a therapeutic target to treat the sleep problems of patients with RTT. PMID:26456390

  19. Gravity and thermoregulation: metabolic changes and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Robinson, E. L.; Fuller, C. A.

    2000-01-01

    Gravity appears to alter thermoregulation through changes in both the regulated level of body temperature and the rhythmic organization of temperature regulation. Gravity has been hypothesized to have an associated metabolic cost. Increased resting energy expenditure and dietary intake have been observed in animals during centrifuge experiments at hypergravity. Thus far, only animals have shown a corresponding reduction in metabolism in microgravity. Altered heat loss has been proposed as a response to altered gravitational environments, but remains documented only as changes in skin temperature. Changes in circadian timing, including the body temperature rhythm, have been shown in both hypergravity and microgravity, and probably contribute to alterations in sleep and performance. Changes in body temperature regulation may result from circadian disturbance, from the direct or indirect actions of gravity on the regulated temperature, or from changes in thermoregulatory effectors (heat production and heat loss) due to altered gravitational load and convective changes. To date, however, we have little data on the underlying thermoregulatory changes in altered gravity, and thus the precise mechanisms by which gravity alters temperature regulation remain largely unknown.

  20. Circadian rhythms in house sparrows: lighting ad lib.

    PubMed

    Binkley, S; Mosher, K; Reilly, K B

    1983-12-01

    House sparrows, Passer domesticus, have circadian rhythms of locomotor activity that can be entrained by light-dark cycles. Perch-hopping activity was studied in house sparrows that were given control of their own lighting. In one series of experiments, sparrows permitted to select their own lighting most commonly chose circadian freerunning cycles. The period of the selected freerunning cycles was 23.2 hr (0.9 hr shorter than the period length the sparrows exhibited in constant dark). The average self-imposed "photoperiods" in the selected freerunning cycles ranged from 8.2-10.0 hr. In a second series of experiments, sparrows were exposed to LDLD1:6:1:16. This cycle can be interpreted ambiguously as the skeleton of a short photoperiod, LD8:16, or of a long photoperiod, LD18:6. All the birds (13 birds; 23 trials) interpreted the skeleton cycle as a short photoperiod because they entrained to it as they would to LD8:16. PMID:6665073

  1. Circadian Rhythms in Acute Intermittent Porphyria—a Pilot Study

    PubMed Central

    Larion, Sebastian; Caballes, F. Ryan; Hwang, Sun-Il; Lee, Jin-Gyun; Rossman, Whitney Ellefson; Parsons, Judy; Steuerwald, Nury; Li, Ting; Maddukuri, Vinaya; Groseclose, Gale; Finkielstein, Carla V.; Bonkovsky, Herbert L.

    2013-01-01

    Acute intermittent porphyria (AIP) is an inherited disorder of heme synthesis wherein a partial deficiency of porphobilinogen [PBG] deaminase [PBGD], with other factors may give rise to biochemical and clinical manifestations of disease. The biochemical hallmarks of active AIP are relative hepatic heme deficiency and uncontrolled up-regulation of hepatic 5-aminolevulinic acid [ALA] synthase-1 [ALAS1] with overproduction of ALA and PBG. The treatment of choice is intravenous heme, which restores the deficient regulatory heme pool of the liver and represses ALAS1. Recently, heme has been shown to influence circadian rhythms by controlling their negative feedback loops. We evaluated whether subjects with AIP exhibited an altered circadian profile. Over a 21 h period, we measured levels of serum cortisol, melatonin, ALA, PBG, and mRNA levels [in peripheral blood mononuclear cells] of selected clock-controlled genes and genes involved in heme synthesis in 10 Caucasian [European-American] women who were either post-menopausal or had been receiving female hormone therapy, 6 of whom have AIP and 4 do not and are considered controls. Four AIP subjects with biochemical activity exhibited higher levels of PBG and lower levels and dampened oscillation of serum cortisol, and a trend for lower levels of serum melatonin, than controls or AIP subjects without biochemical activity. Levels of clock-controlled gene mRNAs showed significant increases over baseline in all subjects at 5 am and 11 pm, whereas mRNA levels of ALAS1, ALAS2, and PBGD were increased only at 11 pm in subjects with active AIP. This pilot study provides evidence for disturbances of circadian markers in women with active AIP that may trigger or sustain some common clinical features of AIP. PMID:23650938

  2. Circadian rhythms in fatty acid-induced depression of myocardial contractile function: Potential mediation by the circadian clock within the cardiomyocyte

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in susceptibility to cardiovascular (CV) pathologic events (e.g., arrhythmias, myocardial infarction) are well established. These phenomena have been explained largely by diurnal variations in neurohumoral influences, such as sympathetic activity. Circadian clocks are intracellular...

  3. Rhythms in Energy Storage Control the Ability of the Cyanobacterial Circadian Clock to Reset

    PubMed Central

    Pattanayak, Gopal K.; Phong, Connie; Rust, Michael J.

    2015-01-01

    Summary Circadian clocks are oscillatory systems that schedule daily rhythms of organismal behavior. The ability of the clock to reset its phase in response to external signals is critical for proper synchronization with the environment. In the model clock from cyanobacteria, the KaiABC proteins that comprise the core oscillator [1, 2] are directly sensitive to metabolites. Reduced ATP/ADP ratio and the oxidized quinones cause clock phase shifts in vitro [3, 4]. But it is unclear what determine the metabolic response of the cell to darkness and thus the magnitude of clock resetting. We show that the cyanobacterial circadian clock generates a rhythm in metabolism that causes cells to accumulate glycogen in anticipation of nightfall. Mutation of the histidine kinase CikA creates an insensitive clock input phenotype by misregulating clock output genome-wide, leading to over-accumulation of glycogen and subsequently high ATP in the dark. Conversely, we show that disrupting glycogen metabolism results in low ATP in the dark and makes the clock hypersensitive to dark pulses. The observed changes in cellular energy are sufficient to recapitulate phase shifting phenotypes in an in vitro model of the clock. Our results show that clock input phenotypes can arise from metabolic dysregulation and illustrate a framework for circadian biology where clock outputs feed back through metabolism to control input mechanisms. PMID:25127221

  4. Rhythms in energy storage control the ability of the cyanobacterial circadian clock to reset.

    PubMed

    Pattanayak, Gopal K; Phong, Connie; Rust, Michael J

    2014-08-18

    Circadian clocks are oscillatory systems that schedule daily rhythms of organismal behavior. The ability of the clock to reset its phase in response to external signals is critical for proper synchronization with the environment. In the model clock from cyanobacteria, the KaiABC proteins that comprise the core oscillator are directly sensitive to metabolites. Reduced ATP/ADP ratio and oxidized quinones cause clock phase shifts in vitro. However, it is unclear what determines the metabolic response of the cell to darkness and thus the magnitude of clock resetting. We show that the cyanobacterial circadian clock generates a rhythm in metabolism that causes cells to accumulate glycogen in anticipation of nightfall. Mutation of the histidine kinase CikA creates an insensitive clock-input phenotype by misregulating clock output genome wide, leading to overaccumulation of glycogen and subsequently high ATP in the dark. Conversely, we show that disruption of glycogen metabolism results in low ATP in the dark and makes the clock hypersensitive to dark pulses. The observed changes in cellular energy are sufficient to recapitulate phase-shifting phenotypes in an in vitro model of the clock. Our results show that clock-input phenotypes can arise from metabolic dysregulation and illustrate a framework for circadian biology where clock outputs feed back through metabolism to control input mechanisms. PMID:25127221

  5. Electrochemical Detection of Circadian Redox Rhythm in Cyanobacterial Cells via Extracellular Electron Transfer.

    PubMed

    Nishio, Koichi; Pornpitra, Tunanunkul; Izawa, Seiichiro; Nishiwaki-Ohkawa, Taeko; Kato, Souichiro; Hashimoto, Kazuhito; Nakanishi, Shuji

    2015-06-01

    Recent research on cellular circadian rhythms suggests that the coupling of transcription-translation feedback loops and intracellular redox oscillations is essential for robust circadian timekeeping. For clarification of the molecular mechanism underlying the circadian rhythm, methods that allow for the dynamic and simultaneous detection of transcription/translation and redox oscillations in living cells are needed. Herein, we report that the cyanobacterial circadian redox rhythm can be electrochemically detected based on extracellular electron transfer (EET), a process in which intracellular electrons are exchanged with an extracellular electrode. As the EET-based method is non-destructive, concurrent detection with transcription/translation rhythm using bioluminescent reporter strains becomes possible. An EET pathway that electrochemically connected the intracellular region of cyanobacterial cells with an extracellular electrode was constructed via a newly synthesized electron mediator with cell membrane permeability. In the presence of the mediator, the open circuit potential of the culture medium exhibited temperature-compensated rhythm with approximately 24 h periodicity. Importantly, such circadian rhythm of the open circuit potential was not observed in the absence of the electron mediator, indicating that the EET process conveys the dynamic information regarding the intracellular redox state to the extracellular electrode. These findings represent the first direct demonstration of the intracellular circadian redox rhythm of cyanobacterial cells. PMID:25975263

  6. Circadian PER2::LUC rhythms in the olfactory bulb of freely moving mice depend on the suprachiasmatic nucleus but not on behaviour rhythms.

    PubMed

    Ono, Daisuke; Honma, Sato; Honma, Ken-Ichi

    2015-12-01

    The temporal order of physiology and behaviour in mammals is regulated by the coordination of the master circadian clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in various tissues outside the SCN. Because the circadian oscillator(s) in the olfactory bulb (OB) is regarded as SCN independent, we examined the relationship between the SCN master clock and the circadian clock in the OB. We also examined the role of vasoactive intestinal peptide receptor 2 in the circadian organization of the OB. We continuously monitored the circadian rhythms of a clock gene product PER2 in the SCN and OB of freely moving mice by means of a bioluminescence reporter and an optical fibre implanted in the brain. Robust circadian rhythms were detected in the OB and SCN for up to 19 days. Bilateral SCN lesions abolished the circadian behaviour rhythms and disorganized the PER2 rhythms in the OB. The PER2 rhythms in the OB showed more than one oscillatory component of a similar circadian period, suggesting internal desynchronization of constituent oscillators. By contrast, significant circadian PER2 rhythms were detected in the vasoactive intestinal peptide receptor 2-deficient mice, despite the substantial deterioration or abolition of circadian behavioural rhythms. These findings indicate that the circadian clock in the OB of freely moving mice depends on the SCN master clock but not on the circadian behavioural rhythms. The circadian PER2::LUC rhythm in the cultured OB was as robust as that in the cultured SCN but reset by slice preparation, suggesting that culturing of the slice reinforces the circadian rhythm. PMID:26489367

  7. Neurospora circadian rhythms in space - A reexamination of the endogenous-exogenous question

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Ellman, D.; Wassmer, G.; Fuller, C. A.; Moore-Ede, M.

    1984-01-01

    To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of the results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected.

  8. Circadian Rhythms in Neurospora crassa: Effects of Saturated Fatty Acids

    PubMed Central

    Mattern, Daniell; Brody, Stuart

    1979-01-01

    To assess their effects on the conidiation rhythm in Neurospora, 14 saturated fatty acids from 6 to 24 carbons long were used to supplement the bd csp and bd csp cel strains. Both strains express a circadian spore-forming rhythm when grown on solid media; the cel mutation confers a partial fatty acid requirement. Fatty acid supplements from 8 to 13 carbons long lengthened the free-running period of bd csp cel compared with the control value of 21 h; the maximal effect (33 h) was obtained with nonanoic acid (9:0) at a concentration of 5 × 10?4 M. In contrast, the period of bd csp remained unchanged under all experimental conditions. The short-chain fatty acids (<14 carbons) reduced the rate of advance of the growth front in both strains, compared with unsupplemented controls. However, this inhibition did not appear to be responsible for the lengthened periods in bd csp cel. Nor was direct incorporation of the short-chain (period-lengthening) fatty acids into mycelial total lipids responsible, since such incorporation was not observed. In fact, extensive metabolic conversion of these supplements by both strains was indicated by the disappearance of short-chain fatty acids from the agar media coupled with their absence in mycelial lipids, and by the liberation of 14CO2 from cultures supplemented with [1-14C]lauric acid (12:0). PMID:158008

  9. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT in...

  10. Treatment of a Circadian Rhythm Disturbance in a 2-Year-Old Blind Child.

    ERIC Educational Resources Information Center

    Mindell, J. A.; And Others

    1996-01-01

    The use of sleep scheduling and a daytime routine for the treatment of circadian rhythm disorder was found helpful in decreasing a blind 2-year old's nighttime wake periods and daytime sleepiness. (DB)

  11. Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model

    PubMed Central

    Zhao, Ningbo; Tang, Hong; Yang, Kai; Chen, Dan

    2013-01-01

    Background Recent studies show that circadian rhythm changes are closely related to the occurrence and development of various tumors, such as breast, liver, and prostate. However, there are significant differences in circadian rhythm between different tumors. At present, the circadian rhythm characteristics of oral cancer remain unknown. The purpose of this study is to investigate the circadian rhythm characteristics of the in vivo growth of oral squamous cell carcinoma (OSCC). Materials and methods Thirty-two nude mice were placed under 12-hour light/12-hour dark cycles. The human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice. After 3 weeks, eight mice were sacrificed at four time points, including 4 hours after light onset (HALO), 10 HALO, 16 HALO, and 22 HALO, during a period of 24 hours. The volume of excised tumors was measured and the proliferative index (PI) and apoptotic index (AI) of tumor cells were determined by flow cytometry. A cosine analysis method was used to determine whether the tumor volume, PI, and AI obeyed a circadian rhythm. Results There was a significant circadian rhythm in the tumor volume and PI of OSCC cells. For the tumor volume, there were significant differences between the four time points. The peak and trough values of the tumor volume appeared at 3.23 HALO and 15.23 HALO, whereas the peak and trough values of PI appeared at 6.60 HALO and 18.16 HALO, respectively. However, there was no circadian rhythm in the AI of tumor cells, despite significant differences between the four time points. Conclusion This study demonstrates, for the first time, that the tumor volume and PI of in vivo growing OSCC undergo circadian rhythms. These results support the assertion that time factor should be considered in the occurrence, development, treatment, efficacy evaluation and pathophysiology of OSCC. PMID:23378773

  12. Non-Circadian Expression Masking Clock-Driven Weak Transcription Rhythms in U2OS Cells

    PubMed Central

    Hoffmann, Julia; Symul, Laura; Shostak, Anton; Fischer, Tamás; Naef, Felix; Brunner, Michael

    2014-01-01

    U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome. PMID:25007071

  13. Rhythm and blues. Neurochemical, neuropharmacological and neuropsychological implications of a hypothesis of circadian rhythm dysfunction in the affective disorders.

    PubMed

    Healy, D

    1987-01-01

    Current views on the organisation and functions of the circadian rhythm system are outlined. Evidence is presented supportive of the notion that the pathophysiology of the affective disorders involves a disruption of circadian rhythms and that the primary locus of action of agents effective in the affective disorders is on the circadian rhythm system. Potential disruptions of this system are enumerated. Such a hypothesis, it is argued, might potentially unite the disparate neurochemical and neuroendocrinological findings emerging in both depression and mania. There are in addition neuropsychological and nosological implications of such a framework, which may help bridge the divide between molecular and behavioural approaches to research on the affective disorders which are outlined. PMID:3124158

  14. Cell cycle oscillators. Temperature compensation of the circadian rhythm of cell division in Euglena.

    PubMed

    Anderson, R W; Laval-Martin, D L; Edmunds, L N

    1985-03-01

    The effects of different constant temperatures ranging from 16 degrees to 32 degrees C on the free-running, circadian rhythm of cell division were examined in axenic, photoautotrophic batch cultures of the unicellular algal flagellate Euglena gracilis Klebs. A comparative study was undertaken on the wild-type (Z strain) and a diuron-(DCMU)-resistant (ZR) strain. Although the overall growth rate (g) of both strains was rather dependent on temperature, lengthening increasingly at temperatures both higher and lower than the optimum range (about 23 degrees-29 degrees C), the free-running period (tau) of the oscillator hypothesized to underlie the overt rhythmicity in the cell division cycle (CDC) was found to be temperature-compensated over at least a 10 degrees C range. The degree of temperature compensation was most striking in the Z strain (Q10 = 1.05) over the permissive temperature interval of 22 degrees-32 degrees C, where periodic growth could occur. This Z strain had a slightly faster growth rate and displayed a higher degree of synchrony than that observed in the ZR strain, whose circadian clock was not as well compensated (Q10 = 1.23) over the permissive temperature interval of 18 degrees-28 degrees C. These results imply that the CDC is regulated by a circadian oscillator sharing the same features as those generating the many other overt biochemical and physiological circadian periodicities that have been documented for Euglena. PMID:3918876

  15. Temperature regulates circadian rhythms of immune responses in red swamp crayfish Procambarus clarkii.

    PubMed

    Dong, Chaohua; Bai, Suhua; Du, Liqiang

    2015-08-01

    As an ectothermic animal, crayfish immunity and their resistance to pathogen can be significantly affected by environmental factors such as light and temperature. It has been found for a long time that multiple immune parameters of animals and human are circadian-regulated by light-entrained circadian rhythm. Whether temperature also affects the immune rhythm of animals still remains unclear. In the present study, we investigated the effect of temperature cycles on the rhythm of crayfish immunity and their resistance. Survival experiments demonstrated that temperature cycles of 24 °C and 18 °C effectively entrained the circadian rhythm of crayfish resistance to Aeromonas hydrophila in constant dark. After being exposed to temperature cycles, the crayfish injected at different time points exhibited significant difference in resistance to A. hydrophila. Bacterial growth and total hemocyte count (THC) also showed circadian variation in crayfish subjected to temperature cycles, but phenoloxidase (PO) activity didn't show rhythmic change under the same conditions. Quantitative real-time PCR revealed that basal expression of crustin1 and astacidin in crayfish subjected to temperature cycles was circadian-rhythmic, but induced expression by A. hydrophila didn't show the same rhythm. In contrast, crayfish maintained at constant temperature showed completely arrhythmic in bacterial resistance, immune parameters mentioned above and the expression of antimicrobial peptides. The results present here collectively indicated that temperature cycles entrained circadian rhythm of some immune parameters and shaped crayfish resistance to bacteria. PMID:26004319

  16. Maternity-related plasticity in circadian rhythms of bumble-bee queens

    PubMed Central

    Eban-Rothschild, Ada; Belluci, Selma; Bloch, Guy

    2011-01-01

    Unlike most animals studied so far in which the activity with no circadian rhythms is pathological or linked to deteriorating performance, worker bees and ants naturally care for their sibling brood around the clock with no apparent ill effects. Here, we tested whether bumble-bee queens that care alone for their first batch of offspring are also capable of a similar chronobiological plasticity. We monitored locomotor activity of Bombus terrestris queens at various life cycle stages, and queens for which we manipulated the presence of brood or removed the ovaries. We found that gynes typically emerged from the pupae with no circadian rhythms, but after several days showed robust rhythms that were not affected by mating or diapauses. Colony-founding queens with brood showed attenuated circadian rhythms, irrespective of the presence of ovaries. By contrast, queens that lost their brood switched again to activity with strong circadian rhythms. The discovery that circadian rhythms in bumble-bee queens are regulated by the life cycle and the presence of brood suggests that plasticity in the circadian clock of bees is ancient and related to maternal behaviour or physiology, and is not a derived trait that evolved with the evolution of the worker caste. PMID:21508036

  17. Circadian-Rhythm Sleep Disorders in Persons Who Are Totally Blind.

    ERIC Educational Resources Information Center

    Sack, R. L.; Blood, M. L.; Hughes, R. J.; Lewy, A. J.

    1998-01-01

    Discusses the diagnosis and management of "non-24-hour sleep-wake syndrome," a form of cyclic insomnia to which people who are totally blind are prone. Covered are incidence and clinical features, formal diagnostic criteria, the biological basis of circadian sleep disorders, circadian rhythms in blind people, pharmacological entrainment, and the…

  18. Circadian-Rhythm Sleep Disorders in Persons Who Are Totally Blind.

    ERIC Educational Resources Information Center

    Sack, R. L.; Blood, M. L.; Hughes, R. J.; Lewy, A. J.

    1998-01-01

    Discusses the diagnosis and management of "non-24-hour sleep-wake syndrome," a form of cyclic insomnia to which people who are totally blind are prone. Covered are incidence and clinical features, formal diagnostic criteria, the biological basis of circadian sleep disorders, circadian rhythms in blind people, pharmacological entrainment, and the…

  19. Fatigue and Circadian Activity Rhythms in Breast Cancer Patients Before and After Chemotherapy: A Controlled Study

    PubMed Central

    Liu, Lianqi; Rissling, Michelle; Neikrug, Ariel; Fiorentino, Lavinia; Natarajan, Loki; Faierman, Michelle; Sadler, Georgia Robins; Dimsdale, Joel E.; Mills, Paul J.; Parker, Barbara A.; Ancoli-Israel, Sonia

    2013-01-01

    Background Breast cancer (BC) patients often experience cancer-related fatigue (CRF) before, during, and after their chemotherapy. Circadian rhythms are 24-hour cycles of behavior and physiology that are generated by internal pacemakers and entrained by zeitgebers (e.g., light). A few studies have suggested a relationship between fatigue and circadian rhythms in some clinical populations. Methods One hundred and forty-eight women diagnosed with stage I-III breast cancer and scheduled to receive at least four cycles of adjuvant or neoadjuvant chemotherapy, and 61 controls (cancer-free healthy women) participated in this study. Data were collected before (Baseline) and after four cycles of chemotherapy (Cycle-4). Fatigue was assessed with the Short Form of Multidimensional Fatigue Symptom Inventory (MFSI-SF); circadian activity rhythm (CAR) was recorded with wrist actigraphy (six parameters included: amplitude, acrophase, mesor, up-mesor, down-mesor and F-statistic). A mixed model analysis was used to examine changes in fatigue and CAR parameters compared to controls, and to examine the longitudinal relationship between fatigue and CAR parameters in BC patients. Results More severe CRF (total and subscale scores) and disrupted CAR (amplitude, mesor and F-statistic) were observed in BC patients compared to controls at both Baseline and Cycle-4 (all p's<0.05); BC patients also experienced more fatigue and decreased amplitude and mesor, as well as delayed up-mesor time at Cycle-4 compared to Baseline (all p's<0.05). The increased total MFSI-SF scores were significantly associated with decreased amplitude, mesor and F-statistic (all p's<0.006). Conclusion CRF exists and CAR is disrupted even before the start of chemotherapy. The significant relationship between CRF and CAR indicate possible underlying connections. Re-entraining the disturbed CAR using effective interventions such as bright light therapy might also improve CRF. PMID:23412418

  20. Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

    PubMed Central

    2011-01-01

    Background The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc) mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression. Results We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin) is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b) and cryptochrome 3 (cry3), in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh) and serotonin-N-acetyltransferase (aanat2), involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT) siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their WT siblings. Conclusion Our data suggests that circadian rhythms can be initiated and maintained in the absence of SCN and other tissues in the ventral brain. However, the SCN may have a role in regulating the amplitude of rhythms when environmental cues are absent. This provides some of the first evidence that the SCN of teleosts is not essential for establishing circadian rhythms during development. Several SCN-independent circadian rhythms have also been found in mammalian species. Thus, zebrafish may serve as a model system for understanding how vertebrate embryos coordinate rhythms that are controlled by different circadian clocks. PMID:21232144

  1. Robust circadian rhythms in organoid cultures from PERIOD2::LUCIFERASE mouse small intestine

    PubMed Central

    Moore, Sean R.; Pruszka, Jill; Vallance, Jefferson; Aihara, Eitaro; Matsuura, Toru; Montrose, Marshall H.; Shroyer, Noah F.; Hong, Christian I.

    2014-01-01

    Disruption of circadian rhythms is a risk factor for several human gastrointestinal (GI) diseases, ranging from diarrhea to ulcers to cancer. Four-dimensional tissue culture models that faithfully mimic the circadian clock of the GI epithelium would provide an invaluable tool to understand circadian regulation of GI health and disease. We hypothesized that rhythmicity of a key circadian component, PERIOD2 (PER2), would diminish along a continuum from ex vivo intestinal organoids (epithelial ‘miniguts’), nontransformed mouse small intestinal epithelial (MSIE) cells and transformed human colorectal adenocarcinoma (Caco-2) cells. Here, we show that bioluminescent jejunal explants from PERIOD2::LUCIFERASE (PER2::LUC) mice displayed robust circadian rhythms for >72 hours post-excision. Circadian rhythms in primary or passaged PER2::LUC jejunal organoids were similarly robust; they also synchronized upon serum shock and persisted beyond 2 weeks in culture. Remarkably, unshocked organoids autonomously synchronized rhythms within 12 hours of recording. The onset of this autonomous synchronization was slowed by >2 hours in the presence of the glucocorticoid receptor antagonist RU486 (20 ?M). Doubling standard concentrations of the organoid growth factors EGF, Noggin and R-spondin enhanced PER2 oscillations, whereas subtraction of these factors individually at 24 hours following serum shock produced no detectable effects on PER2 oscillations. Growth factor pulses induced modest phase delays in unshocked, but not serum-shocked, organoids. Circadian oscillations of PER2::LUC bioluminescence aligned with Per2 mRNA expression upon analysis using quantitative PCR. Concordant findings of robust circadian rhythms in bioluminescent jejunal explants and organoids provide further evidence for a peripheral clock that is intrinsic to the intestinal epithelium. The rhythmic and organotypic features of organoids should offer unprecedented advantages as a resource for elucidating the role of circadian rhythms in GI stem cell dynamics, epithelial homeostasis and disease. PMID:24997189

  2. Circadian rhythm-related genes: implication in autoimmunity and type 1 diabetes.

    PubMed

    Lebailly, B; Boitard, C; Rogner, U C

    2015-09-01

    Recent gene association and functional studies have proven the implication of several circadian rhythm-related genes in diabetes. Diabetes has been related to variation in central circadian regulation and peripheral oscillation. Different transcriptional regulators have been identified. Circadian genes are clearly implicated in metabolic pathways, pancreatic function and in type 2 diabetes. Much less evidence has been shown for the link between circadian regulation and type 1 diabetes. The hypothesis that circadian genes are involved in type 1 diabetes is reinforced by findings that the immune system undergoes circadian variation and that several autoimmune diseases are associated with circadian genes. Recent findings in the non-obese diabetic mouse model pinpoint to specific mechanisms controlling type 1 diabetes by the clock-related gene Arntl2 in the immune system. PMID:26332978

  3. Circadian locomotor rhythms in the desert iguana. I. The role of the eyes and the pineal.

    PubMed

    Janik, D S; Menaker, M

    1990-04-01

    The pineal and the eyes are known to be important components in the circadian system of some species of lizards; their effects may be mediated by the hormone melatonin. We examined the role played by these structures in the desert iguana (Dipsosaurus dorsalis). Surgical removal of the pineal had no effect on circadian locomotor rhythms, even though this procedure abolished the circadian rhythm of melatonin in the blood. Furthermore, when the isolated pineal of Dipsosaurus was studied in organ culture, it showed no circadian rhythm of melatonin secretion, as do pineals of some other lizard species, although it did produce large quantities of this hormone. Bilateral ocular enucleation had only small effects on the freerunning period of locomotor rhythms, without affecting melatonin levels in the blood. Behavioral circadian rhythms persisted in desert iguanas subjected to both enucleation and pinealectomy. These data suggest that neither the pineal nor the eyes are central components of the circadian pacemaking system in Dipsosaurus, nor is melatonin critically involved in maintaining its organization. PMID:2359054

  4. Effect of Spaceflight on the Circadian Rhythm, Lifespan and Gene Expression of Drosophila melanogaster

    PubMed Central

    Xu, Kanyan

    2015-01-01

    Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China’s Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight. PMID:25798821

  5. Circadian rhythms synchronise intracellular calcium dynamics and ATP production for facilitating Arabidopsis pollen tube growth

    PubMed Central

    Yue, Xun; Gao, Xin-Qi; Zhang, Xian Sheng

    2015-01-01

    Experimental evidences support that the circadian rhythm regulates the transcription levels of genes encoding the enzymes involved in plant metabolism. However, there is no paper to refer the correlation of the circadian rhythms and the metabolic processes for facilitating pollen tube growth. In this study, we found that many central components of the circadian clock were highly enriched and specifically present in the in vivo grown Arabidopsis pollen tubes. Our analysis also identified the significant differentially expressed genes encoding co-expressed enzymes in the consecutive steps of fatty acid β-oxidation II, pentose phosphate pathway (oxidative branch) and phosphatidic acid biosynthesis pathway in the in vivo grown Arabidopsis pollen tubes during pollination. Thus, it is implicated that the circadian rhythms of pollen tube may be adjusted and have a greater probability of the direct or indirect functional relationship with enhanced intracellular Ca2+ dynamics and ATP production for facilitating pollen tube growth in vivo. PMID:26039479

  6. Circadian rhythm of RNA N6-methyladenosine and the role of cryptochrome.

    PubMed

    Wang, Chao-Yung; Yeh, Jih-Kai; Shie, Shian-Sen; Hsieh, I-Chang; Wen, Ming-Shien

    2015-09-11

    Methylation of RNA N(6)-methyladenosine has fundamental cellular functions, including translation regulation, RNA export, and stem cells renewal. However, the regulation of RNA N(6)-methyladenosine methylation is poorly understood. Here, we observed a robust circadian rhythm in N(6)-methyladenosine modifications of RNA. Deficiency of core mammalian clock genes, cryptochromes, decreased the levels of N(6)-methyladenosine in RNA. Cryptochrome1/2 knockout mice had significantly lower N(6)-methyladenosine methylation of RNA and lost the circadian rhythm of N(6)-methyladenosine levels in RNA. Global analysis of the circadian methylomes of N(6)-methyladenosine in RNA revealed that gene transcription, translation regulation, and RNA metabolism were highly correlated with N(6)-methyladenosine oscillation. Our findings extended a fundamental link between the circadian rhythm and N(6)-methyladenosine modification of RNA and suggested that this link is critical in controlling post-transcriptional gene expression and RNA metabolism. PMID:26239657

  7. Identification of a circadian output circuit for rest:activity rhythms in Drosophila

    PubMed Central

    Cavanaugh, Daniel J.; Geratowski, Jill D.; Wooltorton, Julian R. A.; Spaethling, Jennifer M.; Hector, Clare E.; Zheng, Xiangzhong; Johnson, Erik C.; Eberwine, James H.; Sehgal, Amita

    2014-01-01

    SUMMARY Though much is known about the cellular and molecular components of the circadian clock, output pathways that couple clock cells to overt behaviors have not been identified. We conducted a screen for circadian-relevant neurons in the Drosophila brain, and report here that cells of the pars intercerebralis (PI), a functional homologue of the mammalian hypothalamus, comprise an important component of the circadian output pathway for rest:activity rhythms. GRASP analysis demonstrates that PI cells are connected to the clock through a polysynaptic circuit extending from pacemaker cells to PI neurons. Molecular profiling of relevant PI cells identified the corticotropin releasing factor (CRF) homologue, DH44, as a circadian output molecule that is specifically expressed by PI neurons and required for normal rest:activity rhythms. Notably, selective activation or ablation of just 6 DH44+ PI cells causes arrhythmicity. These findings delineate a circuit through which clock cells can modulate locomotor rhythms. PMID:24766812

  8. Individual variation in circadian rhythms of sleep, EEG, temperature, and activity among monkeys - Implications for regulatory mechanisms.

    NASA Technical Reports Server (NTRS)

    Crowley, T. J.; Halberg, F.; Kripke, D. F.; Pegram, G. V.

    1971-01-01

    Investigation of circadian rhythms in a number of variables related to sleep, EEG, temperature, and motor activity in rhesus monkeys on an LD 12:12 schedule. Circadian rhythms were found to appear in each of 15 variables investigated. Statistical procedures assessed the variables for evidence of common regulation in these aspects of their circadian rhythms: acrophase (timing), amplitude (extent of change), and level (24-hr mean value). Patterns appearing in the data suggested that the circadian rhythms of certain variables are regulated in common. The circadian modulation of activity in the beta and sigma frequency bands of the EEG was correlated with statistical significance in acrophase, level, and amplitude. The delta frequency band appeared to be under circadian rhythm regulation distinct from that of the other bands. The circadian rhythm of REM stage sleep was like that of beta activity in level and amplitude. The data indicate that REM stage may share some common regulation of circadian timing with both stage 3-4 sleep and with temperature. Generally, however, the circadian rhythm of temperature appeared to bear little relation to the circadian rhythms of motor activity, EEG, or sleep.

  9. Circadian rhythms in axillary skin surface pH.

    PubMed

    Burry, J; Coulson, H F; Roberts, G

    2001-08-01

    Sweat and skin surface pH are critical parameters in determining the performance of antiperspirants. The mechanism of action, the so-called 'plug theory' first proposed by Reller and Luedders, involves the expression of eccrine sweat onto the surface of the skin into which the solid antiperspirant salts, typically an aluminium chlorohydrate or zirconium aluminium glycine, dissolve. The resultant acidic 'solution' then diffuses with time into the sweat glands, where it hydrolyses in more alkaline sweat and forms an amorphous metal hydroxide agglomerate that physically plugs the ducts some 20-100 mum into the glands. It is therefore important to understand whether diurnal variations in skin surface pH exist in the axilla, as these may influence strongly the time of day at which antiperspirant should be applied in order to yield maximal protection. Clinical studies demonstrate a significant fall in axillary skin surface pH between the morning (pH = 5.87 +/- 0.23) and the evening (pH = 5.49 +/- 0.23). This diurnal variation in skin surface pH suggests that antiperspirant efficacy will be optimal when products are applied in the morning. In addition, the data suggest a circadian rhythm in axillary skin barrier function, indicating that chronopharmacology, the timing of administration of medication, could be used to optimize treatment of axillary hyperhidrotics using topical administration of anticholinergic drugs. PMID:18498460

  10. Comparison of hormone and electrolyte circadian rhythms in male and female humans

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Winget, C. M.; Goodwin, A. E.; Reilly, T.

    1977-01-01

    Circadian rhythm characteristics in healthy male and female humans were studied at 4-hour intervals for urine volume, cortisol, 5-hydroxyindoleacetic acid (5-HIAA), Na, K, Na/K ratios in the urine, as well as plasma cortisol. While plasma and urinary cortisol rhythms were very similar in both sexes, the described rhythms in urine volume, electrolyte, and 5-HIAA excretion differ for the two sexes. The results suggest that sex differences exist in the circadian patterns of important hormone and metabolic functions and that the internal synchrony of circadian rhythms differs for the two sexes. The results seem to indicate that the rhythmical secretion of cortisol does not account for the pattern of Na and K excretion.

  11. Circadian rhythms and memory: not so simple as cogs and gears

    PubMed Central

    Eckel-Mahan, Kristin L; Storm, Daniel R

    2009-01-01

    The influence of circadian rhythms on memory has long been studied; however, the molecular prerequisites for their interaction remain elusive. The hippocampus, which is a region of the brain important for long-term memory formation and temporary maintenance, shows circadian rhythmicity in pathways central to the memory-consolidation process. As neuronal plasticity is the translation of numerous inputs, illuminating the direct molecular links between circadian rhythms and memory consolidation remains a daunting task. However, the elucidation of how clock genes contribute to synaptic plasticity could provide such a link. Furthermore, the idea that memory training could actually function as a zeitgeber for hippocampal neurons is worth consideration, based on our knowledge of the entrainment of the circadian clock system. The integration of many inputs in the hippocampus affects memory consolidation at both the cellular and the systems level, leaving the molecular connections between circadian rhythmicity and memory relatively obscure but ripe for investigation. PMID:19465890

  12. Dim light at night disrupts molecular circadian rhythms and increases body weight.

    PubMed

    Fonken, Laura K; Aubrecht, Taryn G; Meléndez-Fernández, O Hecmarie; Weil, Zachary M; Nelson, Randy J

    2013-08-01

    With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption. PMID:23929553

  13. A Long Noncoding RNA Perturbs the Circadian Rhythm of Hepatoma Cells to Facilitate Hepatocarcinogenesis12

    PubMed Central

    Cui, Ming; Zheng, Minying; Sun, Baodi; Wang, Yue; Ye, Lihong; Zhang, Xiaodong

    2015-01-01

    Clock circadian regulator (CLOCK)/brain and muscle arnt-like protein-1 (BMAL1) complex governs the regulation of circadian rhythm through triggering periodic alterations of gene expression. However, the underlying mechanism of circadian clock disruption in hepatocellular carcinoma (HCC) remains unclear. Here, we report that a long noncoding RNA (lncRNA), highly upregulated in liver cancer (HULC), contributes to the perturbations in circadian rhythm of hepatoma cells. Our observations showed that HULC was able to heighten the expression levels of CLOCK and its downstream circadian oscillators, such as period circadian clock 1 and cryptochrome circadian clock 1, in hepatoma cells. Strikingly, HULC altered the expression pattern and prolonged the periodic expression of CLOCK in hepatoma cells. Mechanistically, the complementary base pairing between HULC and the 5' untranslated region of CLOCK mRNA underlay the HULC-modulated expression of CLOCK, and the mutants in the complementary region failed to achieve the event. Moreover, immunohistochemistry staining and quantitative real-time polymerase chain reaction validated that the levels of CLOCK were elevated in HCC tissues, and the expression levels of HULC were positively associated with those of CLOCK in clinical HCC samples. In functional experiments, our data exhibited that CLOCK was implicated in the HULC-accelerated proliferation of hepatoma cells in vitro and in vivo. Taken together, our data show that an lncRNA, HULC, is responsible for the perturbations in circadian rhythm through upregulating circadian oscillator CLOCK in hepatoma cells, resulting in the promotion of hepatocarcinogenesis. Thus, our finding provides new insights into the mechanism by which lncRNA accelerates hepatocarcinogenesis through disturbing circadian rhythm of HCC. PMID:25622901

  14. Sustained Circadian Rhythms in Continuous Light in Synechocystis sp. PCC6803 Growing in a Well-Controlled Photobioreactor

    PubMed Central

    van Alphen, Pascal; Hellingwerf, Klaas J.

    2015-01-01

    The cyanobacterial circadian clock has been well-studied and shown to be both robust and a dominant factor in the control of gene expression in Synechococcus elongatus PCC7942. In Synechocystis sp. PCC6803, the circadian clock is assumed to function similarly, yet appears to control transcription to a far lesser extent and its circadian rhythm was reported to not be sustained, or at least rapidly damped, under continuous illumination. One of the feedback loops that governs the clock in S. elongatus in addition to the core oscillator, i.e., the transcriptional-translation regulation loop hinging on KaiC-dependent expression of kaiBC, appears to be missing in Synechocystis, which would account for this difference. Here, we show that the clock in Synechocystis fulfills all criteria of a circadian clock: 1) a free-running period of approximately 24 h, 2) temperature compensation, and 3) being able to be entrained. A remarkably stable rhythm is generated despite the fact that the organism grows with a doubling time of less than 24 h in a photobioreactor run in turbidostat mode. No damping of the free-running circadian oscillation was observed in 2 weeks, suggesting that the clock in individual cells stays synchronized within a culture despite the apparent lack of a transcriptional-translation regulation loop. Furthermore, the dependence of chlorophyll synthesis on the presence of O2 was demonstrated. PMID:26030367

  15. Robust Circadian Rhythms of Gene Expression in Brassica rapa Tissue Culture1[W][OA

    PubMed Central

    Xu, Xiaodong; Xie, Qiguang; McClung, C. Robertson

    2010-01-01

    Circadian clocks provide temporal coordination by synchronizing internal biological processes with daily environmental cycles. To date, study of the plant circadian clock has emphasized Arabidopsis (Arabidopsis thaliana) as a model, but it is important to determine the extent to which this model applies in other species. Accordingly, we have investigated circadian clock function in Brassica rapa. In Arabidopsis, analysis of gene expression in transgenic plants in which luciferase activity is expressed from clock-regulated promoters has proven a useful tool, although technical challenges associated with the regeneration of transgenic plants has hindered the implementation of this powerful tool in B. rapa. The circadian clock is cell autonomous, and rhythmicity has been shown to persist in tissue culture from a number of species. We have established a transgenic B. rapa tissue culture system to allow the facile measurement and manipulation of clock function. We demonstrate circadian rhythms in the expression of several promoter:LUC reporters in explant-induced tissue culture of B. rapa. These rhythms are temperature compensated and are reset by light and temperature pulses. We observe a strong positive correlation in period length between the tissue culture rhythm in gene expression and the seedling rhythm in cotyledon movement, indicating that the circadian clock in B. rapa tissue culture provides a good model for the clock in planta. PMID:20406912

  16. An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila

    PubMed Central

    Kumar, Shailesh; Chen, Dechun; Jang, Christopher; Nall, Alexandra; Zheng, Xiangzhong; Sehgal, Amita

    2014-01-01

    Summary Little is known about molecular links between circadian clocks and steroid hormone signaling although both are important for normal physiology. Here we report a circadian function for a nuclear receptor, Ecdysone Induced Protein 75 (Eip75/E75), which we identify through a gain-of-function screen for circadian genes in Drosophila melanogaster. Overexpression or knockdown of E75 in clock neurons disrupts rest:activity rhythms and dampens molecular oscillations. E75 represses expression of the gene encoding the transcriptional activator, CLOCK (CLK), and may also affect circadian output. PER inhibits the activity of E75 on the Clk promoter, thereby providing a mechanism for a previously proposed de-repressor effect of PER on Clk transcription. The ecdysone receptor is also expressed in central clock cells and manipulations of its expression produce effects similar to those of E75 on circadian rhythms. We find that E75 protects rhythms under stressful conditions, suggesting a function for steroid signaling in the maintenance of circadian rhythms in Drosophila. PMID:25511299

  17. Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on Innate Immunity.

    PubMed

    Dengler, Viola; Westphalen, Kristin; Koeppen, Michael

    2015-01-01

    The earth rotates on its axis around the sun, creating a day and night cycle, that caused the development of circadian rhythms. The circadian rhythm is primarily entrained by light, which is detected by the retina. Retinal ganglion cells project to a part of the hypothalamus termed suprachiasmatic nucleus. Here, we find the master molecular clock, composed of a transcription-translation-loop at its core. The master clock indirectly influences the innate immune system via different biological systems. Also, the master clock controls the peripheral clocks, which are present in innate immune cells. Here, circadian rhythm proteins influence the response of immune cells to pathogens. Furthermore, the master clock influences our sleep-pattern, the most important restorative physiological function. In critically ill patients the circadian rhythm is substantially altered, supporting a dysfunctional innate immune response. This review discusses recent basic science findings on the interaction of the circadian rhythm and the innate immune system. Furthermore we give an outlook on potential future therapeutic strategies. PMID:26144943

  18. Functional diversities of two activity components of circadian rhythm in genetical splitting mice (CS strain).

    PubMed

    Abe, H; Honma, S; Honma, K; Suzuki, T; Ebihara, S

    1999-03-01

    CS mice, an inbred strain, showed two distinctive characteristics in the circadian rhythm of locomotor activity: (1) large variation in the freerunning period, and (2) spontaneous rhythm splitting under continuous darkness. In the splitting rhythm there was a positive correlation between the freerunning period of the evening component and the activity time of the morning component. The phase-shifting effect of a 15-min light pulse was examined on the two activity components of the splitting rhythm. There were significant differences in the amount of light-induced phase response between the two components. A light pulse during the late subjective night induced a phase advance shift only in the morning component, while a light pulse during the early subjective night induced a phase delay shift only in the evening component. These results indicate functional diversities of the two activity components in the circadian locomotor rhythm of CS mice, and suggest that the circadian system in CS mice consists of two mutually coupled oscillators which have different circadian periods and different responsiveness to light. The CS mouse is a useful model to explore a genetic background of oscillator coupling in the circadian system of nocturnal rodents. PMID:10319444

  19. Lighting, sleep and circadian rhythm: An intervention study in the intensive care unit.

    PubMed

    Engwall, Marie; Fridh, Isabell; Johansson, Lotta; Bergbom, Ingegerd; Lindahl, Berit

    2015-12-01

    Patients in an intensive care unit (ICU) may risk disruption of their circadian rhythm. In an intervention research project a cycled lighting system was set up in an ICU room to support patients' circadian rhythm. Part I aimed to compare experiences of the lighting environment in two rooms with different lighting environments by lighting experiences questionnaire. The results indicated differences in advantage for the patients in the intervention room (n=48), in perception of daytime brightness (p=0.004). In nighttime, greater lighting variation (p=0.005) was found in the ordinary room (n=52). Part II aimed to describe experiences of lighting in the room equipped with the cycled lighting environment. Patients (n=19) were interviewed and the results were presented in categories: "A dynamic lighting environment", "Impact of lighting on patients' sleep", "The impact of lighting/lights on circadian rhythm" and "The lighting calms". Most had experiences from sleep disorders and half had nightmares/sights and circadian rhythm disruption. Nearly all were pleased with the cycled lighting environment, which together with daylight supported their circadian rhythm. In night's actual lighting levels helped patients and staff to connect which engendered feelings of calm. PMID:26215384

  20. Mother-Infant Circadian Rhythm: Development of Individual Patterns and Dyadic Synchrony

    PubMed Central

    Thomas, Karen A.; Burr, Robert L.; Spieker, Susan; Lee, Jungeun; Chen, Jessica

    2014-01-01

    Background Mutual circadian rhythm is an early and essential component in the development of maternal-infant physiological synchrony. Aims To examine the longitudinal pattern of maternal-infant circadian rhythm and rhythm synchrony as measured by rhythm parameters. Study Design In-home dyadic actigraphy monitoring at infant age 4, 8, and 12 weeks. Subjects Forty-three healthy mother-infant pairs. Outcome Measures Circadian parameters derived from cosinor and non-parametric analysis including mesor, magnitude, acrophase, L5 and M10 midpoints (midpoint of lowest 5 and highest 10 hours of activity), amplitude, interdaily stability (IS), and intradaily variability (IV). Results Mothers experienced early disruption of circadian rhythm, with re-establishment of rhythm over time. Significant time effects were noted in increasing maternal magnitude, amplitude, and IS and decreasing IV (p < .001). Infants demonstrated a developmental trajectory of circadian pattern with significant time effects for increasing mesor, magnitude, amplitude, L5, IS, and IV (p < .001). By 12 weeks, infant phase advancement was evidenced by mean acrophase and M10 midpoint occurring 60 and 43 minutes (respectively) earlier than at 4 weeks. While maternal acrophase remained consistent over time, infants became increasingly phase advanced relative to mother and mean infant acrophase at 12 weeks occurred 60 minutes before mother. Mother-infant synchrony was evidenced in increasing correspondence of acrophase at 12 weeks (r = 0.704), L5 (r = 0.453) and M10 (r = 0.479) midpoints. Conclusions Development of mother-infant synchrony reflects shared elements of circadian rhythm. PMID:25463836

  1. Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants

    PubMed Central

    Ivars, Katrin; Nelson, Nina; Theodorsson, Annette; Theodorsson, Elvar; Ström, Jakob O.; Mörelius, Evalotte

    2015-01-01

    Background Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life. Methods 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist. Results A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life. Conclusions Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants. PMID:26086734

  2. Melanopsin resets circadian rhythms in cells by inducing clock gene Period1

    NASA Astrophysics Data System (ADS)

    Yamashita, Shuhei; Uehara, Tomoe; Matsuo, Minako; Kikuchi, Yo; Numano, Rika

    2014-02-01

    The biochemical, physiological and behavioral processes are under the control of internal clocks with the period of approximately 24 hr, circadian rhythms. The expression of clock gene Period1 (Per1) oscillates autonomously in cells and is induced immediately after a light pulse. Per1 is an indispensable member of the central clock system to maintain the autonomous oscillator and synchronize environmental light cycle. Per1 expression could be detected by Per1∷luc and Per1∷GFP plasmid DNA in which firefly luciferase and Green Fluorescence Protein were rhythmically expressed under the control of the mouse Per1 promoter in order to monitor mammalian circadian rhythms. Membrane protein, MELANOPSIN is activated by blue light in the morning on the retina and lead to signals transduction to induce Per1 expression and to reset the phase of circadian rhythms. In this report Per1 induction was measured by reporter signal assay in Per1∷luc and Per1∷GFP fibroblast cell at the input process of circadian rhythms. To the result all process to reset the rhythms by Melanopsin is completed in single cell like in the retina projected to the central clock in the brain. Moreover, the phase of circadian rhythm in Per1∷luc cells is synchronized by photo-activated Melanopsin, because the definite peak of luciferase activity in one dish was found one day after light illumination. That is an available means that physiological circadian rhythms could be real-time monitor as calculable reporter (bioluminescent and fluorescent) chronological signal in both single and groups of cells.

  3. Development of the cortisol circadian rhythm in the light of stress early in life.

    PubMed

    Simons, Sterre S H; Beijers, Roseriet; Cillessen, Antonius H N; Weerth, Carolina de

    2015-12-01

    The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood. PMID:26352482

  4. Disturbed mouse circadian rhythm before the Kobe EQ in 1995

    NASA Astrophysics Data System (ADS)

    Yokoi, Sayoko

    2013-04-01

    Legends of macro-anomalies before large earthquakes have been passed down for generations in Asia. Most of the statements on earthquake precursors are considered unreliable afterthoughts by traditional scientists. However, disturbed biological rhythms in mice were observed before the Kobe EQ in 1995 (Yokoi et al, 2003). The records of unusual mouse behavior before the earthquake were obtained to study biological clock at Institute for Protein Research, Osaka University. It is clarified that the disturbance was very rare phenomena statistically. Similar phenomenon was observed before the Wenchuan earthquake in 2008, too (Li et al, 2009). In the presentation, I will discuss the phenomena as one example of preseismic unusual animal behaviors.

  5. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson’s disease

    PubMed Central

    Videnovic, Aleksandar; Noble, Charleston; Reid, Kathryn J.; Peng, Jie; Turek, Fred W.; Marconi, Angelica; Rademaker, Alfred W.; Simuni, Tanya; Zadikoff, Cindy; Zee, Phyllis C.

    2014-01-01

    Importance Diurnal fluctuations of motor and non-motor symptoms and high prevalence of sleep/wake disturbances in Parkinson’s disease (PD) suggest a role of the circadian system in the modulation of these symptoms. Yet, surprisingly little is known regarding circadian function in PD, and whether circadian dysfunction is involved in the development of sleep/wake disturbances in PD. Objective The objective of this study was to determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness and disease metrics. Design A cross-sectional study, (2009–2012). Setting PD and Movement Disorders Center, Northwestern University, Chicago. Participants Twenty PD patients on stable dopaminergic therapy and 15 age-matched controls underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions. Main Outcome Measure(s) Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index (PSQI)) and daytime sleepiness (Epworth Sleepiness Scale (ESS)), circadian markers of the melatonin rhythm, including the amplitude, area-under-the-curve (AUC), and phase of the 24-hour rhythm. Results Participants with PD had a blunted circadian rhythms of melatonin secretion compared to controls; both the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD participants compared with controls (p<0.001). Markers of circadian phase were not significantly different between the two groups. Among PD participants, those with excessive daytime sleepiness (ESS score ?10) had a significantly lower amplitude of the melatonin rhythm and the 24-hour melatonin AUC compared with PD participants without excessive sleepiness (p=0.001). Disease duration, UPDRS scores, levodopa equivalent dose and global PSQI scores in the PD group were not significantly related to measures of the melatonin circadian rhythm. Conclusion and Relevance These results indicate that circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be further explored in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed bright light and exercise, might potentially serve as complementary therapies for the non-motor manifestations of PD. PMID:24566763

  6. Analysis of Circadian Rhythms in the Basal Filamentous Ascomycete Pyronema confluens

    PubMed Central

    Traeger, Stefanie; Nowrousian, Minou

    2015-01-01

    Many organisms use circadian clocks to adapt to daily changes in the environment. Major insights into the molecular mechanisms of circadian oscillators have been gained through studies of the model organism Neurospora crassa; however, little is known about molecular components of circadian clocks in other fungi. An important part of the N. crassa circadian clock is the frequency (frq) gene, homologs of which can be found in Sordariomycetes, Dothideomycetes, and Leotiomycetes, but not Eurotiomycetes. Recently, we identified a frq homolog in Pyronema confluens, a member of the early-diverging Pezizomycete lineage of filamentous ascomycetes. The P. confluens FRQ shares many conserved domains with the N. crassa FRQ. However, there is no known morphological phenotype showing overt circadian rhythmicity in P. confluens. To investigate whether a molecular clock is present, we analyzed frq transcription in constant darkness, and found circadian oscillation of frq with a peak in the subjective morning. This rhythm was temperature compensated. To identify additional clock-controlled genes, we performed RNA sequencing of two time points (subjective morning and evening). Circadian expression of two morning-specific genes was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) over a full time course, whereas expression of two putative morning-specific and five putative evening-specific genes could not be verified as circadian. frq expression was synchronized, but not entrained by light. In summary, we have found evidence for two of the three main properties of circadian rhythms (free-running rhythm, temperature compensation) in P. confluens, suggesting that a circadian clock with rhythmically expressed frq is present in this basal filamentous ascomycete. PMID:26254031

  7. Analysis of Circadian Rhythms in the Basal Filamentous Ascomycete Pyronema confluens.

    PubMed

    Traeger, Stefanie; Nowrousian, Minou

    2015-10-01

    Many organisms use circadian clocks to adapt to daily changes in the environment. Major insights into the molecular mechanisms of circadian oscillators have been gained through studies of the model organism Neurospora crassa; however, little is known about molecular components of circadian clocks in other fungi. An important part of the N. crassa circadian clock is the frequency (frq) gene, homologs of which can be found in Sordariomycetes, Dothideomycetes, and Leotiomycetes, but not Eurotiomycetes. Recently, we identified a frq homolog in Pyronema confluens, a member of the early-diverging Pezizomycete lineage of filamentous ascomycetes. The P. confluens FRQ shares many conserved domains with the N. crassa FRQ. However, there is no known morphological phenotype showing overt circadian rhythmicity in P. confluens. To investigate whether a molecular clock is present, we analyzed frq transcription in constant darkness, and found circadian oscillation of frq with a peak in the subjective morning. This rhythm was temperature compensated. To identify additional clock-controlled genes, we performed RNA sequencing of two time points (subjective morning and evening). Circadian expression of two morning-specific genes was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) over a full time course, whereas expression of two putative morning-specific and five putative evening-specific genes could not be verified as circadian. frq expression was synchronized, but not entrained by light. In summary, we have found evidence for two of the three main properties of circadian rhythms (free-running rhythm, temperature compensation) in P. confluens, suggesting that a circadian clock with rhythmically expressed frq is present in this basal filamentous ascomycete. PMID:26254031

  8. Circadian rhythms. Atomic-scale origins of slowness in the cyanobacterial circadian clock.

    PubMed

    Abe, Jun; Hiyama, Takuya B; Mukaiyama, Atsushi; Son, Seyoung; Mori, Toshifumi; Saito, Shinji; Osako, Masato; Wolanin, Julie; Yamashita, Eiki; Kondo, Takao; Akiyama, Shuji

    2015-07-17

    Circadian clocks generate slow and ordered cellular dynamics but consist of fast-moving bio-macromolecules; consequently, the origins of the overall slowness remain unclear. We identified the adenosine triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock. Crystal structures of the ATPase revealed that the slowness of this ATPase arises from sequestration of a lytic water molecule in an unfavorable position and coupling of ATP hydrolysis to a peptide isomerization with high activation energy. The slow ATPase is coupled with another ATPase catalyzing autodephosphorylation in the carboxyl-terminal half of KaiC, yielding the circadian response frequency of intermolecular interactions with other clock-related proteins that influences the transcription and translation cycle. PMID:26113637

  9. Circadian regulation gene polymorphisms are associated with sleep disruption and duration, and circadian phase and rhythm in adults with HIV.

    PubMed

    Lee, Kathryn A; Gay, Caryl; Byun, Eeeseung; Lerdal, Anners; Pullinger, Clive R; Aouizerat, Bradley E

    2015-01-01

    Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep-wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72?h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep-wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep-wake behavior patterns. PMID:26512752

  10. Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Depression

    PubMed Central

    Salgado-Delgado, Roberto; Tapia Osorio, Araceli; Saderi, Nadia; Escobar, Carolina

    2011-01-01

    Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationship between the biological clock and the incidence of depressive symptoms is far from being understood. The efficiency and the timing of treatments based on chronotherapy (e.g., light treatment, sleep deprivation, and scheduled medication) indicate that the circadian system is an essential target in the therapy of depression. The aim of the present review is to analyze the biological and clinical data that link depression with the disruption of circadian rhythms, emphasizing the contribution of circadian desynchrony. Therefore, we examine the conditions that may lead to circadian disruption of physiology and behavior as described in depressive states, and, according to this approach, we discuss therapeutic strategies aimed at treating the circadian system and depression. PMID:21845223

  11. Therapeutic strategies for circadian rhythm and sleep disturbances in Huntington disease.

    PubMed

    van Wamelen, Daniel J; Roos, Raymund Ac; Aziz, Nasir A

    2015-12-01

    Aside from the well-known motor, cognitive and psychiatric signs and symptoms, Huntington disease (HD) is also frequently complicated by circadian rhythm and sleep disturbances. Despite the observation that these disturbances often precede motor onset and have a high prevalence, no studies are available in HD patients which assess potential treatments. In this review, we will briefly outline the nature of circadian rhythm and sleep disturbances in HD and subsequently focus on potential treatments based on findings in other neurodegenerative diseases with similarities to HD, such as Parkinson and Alzheimer disease. The most promising treatment options to date for circadian rhythm and sleep disruption in HD include melatonin (agonists) and bright light therapy, although further corroboration in clinical trials is warranted. PMID:26621387

  12. A circadian rhythm in optic nerve impulses from an isolated eye in darkness.

    NASA Technical Reports Server (NTRS)

    Jacklet, J. W.

    1971-01-01

    Study of the circadian rhythm of optic nerve potentials recorded from the isolated eye of the sea hare Aplysia. The optic nerve activity in constant conditions is found to be clearly circadian and to obey the circadian rule for diurnal animals. In addition, the period length depends on the in vitro culturing solution. In seawater it is about 22 hr, but in culture medium it is 27 hr. The rhythm can be completely phase-shifted in one trial if the phase of the LD 12:12 Zeitgeber is advanced or delayed 4 hr. The rhythm in one eye can be phase-shifted in vivo independently of the other eye and in vitro independently of the rest of the animal. Thus, in the animal, the eye oscillators are, at most, only slightly influenced by each other or by other oscillators in the animal.

  13. Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room light

    NASA Technical Reports Server (NTRS)

    Boivin, D. B.; Czeisler, C. A.

    1998-01-01

    The present study was designed to investigate whether a weak photic stimulus can reset the endogenous circadian rhythms of plasma melatonin and plasma cortisol in human subjects. A stimulus consisting of three cycles of 5 h exposures to ordinary room light (approximately 180 lux), centered 1.5 h after the endogenous temperature nadir, significantly phase-advanced the plasma melatonin rhythm in eight healthy young men compared with the phase delays observed in eight control subjects who underwent the same protocol but were exposed to darkness (p < or = 0.003). After light-induced phase advances, the circadian rhythms of plasma melatonin and plasma cortisol maintained stable temporal relationships with the endogenous core body temperature cycle, consistent with the conclusion that exposure to ordinary indoor room light had shifted a master circadian pacemaker.

  14. The possible long-term effects of early-life circadian rhythm disturbance on social behavior.

    PubMed

    Kohyama, Jun

    2014-07-01

    Sleep loss impairs brain function. As late sleep onset can reduce sleep, this sleep/circadian rhythm disturbance may cause brain impairment. Specific data on the long-term effects of sleep/circadian rhythm disturbance on subsequent brain function are lacking. Japan, a sleep-deprived society from infancy to adulthood, provides an ideal platform to investigate the association of these disturbances in early life with subsequent functioning. In this article, several current problematic behaviors among youth in Japan (dropping out from high school, school absenteeism, early resignation from employment, and suicide) are discussed in relation to early life sleep/circadian rhythm patterns. We hypothesize that daily habits of modern society during early stages of life produce unfavorable effects on brain function resulting in problematic behaviors in subsequent years. PMID:24902476

  15. Adaptation of sleep and circadian rhythms to the Antarctic summer - A question of zeitgeber strength

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Macdonald, John A.; Montgomery, John C.; Paulin, Michael G.

    1991-01-01

    Adaptation of sleep and circadian rhythms was examined in three temperate zone dwellers arriving in Antarctica during summer. Rectal temperature, wrist activity, and heart rate were monitored continuously, sleep timing and quality noted on awakening, and mood and fatigue rated every 2 h while awake. Sleep was poorer in 2/3 subjects in Antarctica, where all subjects reported more difficulty rising. Sleep occurred at the same clock times in New Zealand and Antarctica, however, the rhythms of temperature, activity, and heart rate underwent a delay of about of 2 h. The subject with the most Antarctic experience had the least difficulty adapting to sleeping during constant daylight. The subject with the most delayed circadian rhythms had the most difficulty. The delay in the circadian system with respect to sleep and clock time is hypothesized to be due to differences in zeitgeber strength and/or zeitgeber exposure between Antarctica and New Zealand.

  16. Controlling Circadian Rhythms by Dark-Pulse Perturbations in Arabidopsis thaliana

    PubMed Central

    Fukuda, Hirokazu; Murase, Haruhiko; Tokuda, Isao T.

    2013-01-01

    Plant circadian systems are composed of a large number of self-sustained cellular circadian oscillators. Although the light-dark signal in the natural environment is known to be the most powerful Zeitgeber for the entrainment of cellular oscillators, its effect is too strong to control the plant rhythm into various forms of synchrony. Here, we show that the application of pulse perturbations, i.e., short-term injections of darkness under constant light, provides a novel technique for controlling the synchronized behavior of plant rhythm in Arabidopsis thaliana. By destroying the synchronized cellular activities, circadian singularity was experimentally induced. The present technique is based upon the theory of phase oscillators, which does not require prior knowledge of the detailed dynamics of the plant system but only knowledge of its phase and amplitude responses to the pulse perturbation. Our approach can be applied to diverse problems of controlling biological rhythms in living systems. PMID:23524981

  17. [Circadian rhythms and temperature homeostasis in monkeys during a flight on the Kosmos 1514 biosatellite

    NASA Technical Reports Server (NTRS)

    Klimovitskui, V. Ia; Alpatov, A. M.; Salzman, F. M.; Fuller, C. A.; Moore-Ede, M. S.

    1987-01-01

    In the course of a 5-day space flight of two rhesus-monkeys the following parameters were recorded at an interval of 16 min: core body temperature (Tc), skin temperature (Ts), and motor activity (MA). The telemetric Tc sensor was implanted subcutaneously in the right axilla, Ts thermistor was attached to the right ankle, and the MA piezotape was fixed to the inner side of the vest. Circadian rhythms of Tc varied with a period of 24 hours in one monkey and 25 hours in the other. The daily Tc decreased on the average by 0.5 degrees C, Ts fell immediately after launch and remained close to the lower limit throughout the flight. The Ts amplitude decreased 5-fold. Phases of the circadian rhythms of Ts changed and circadian rhythms of MA remained unchanged and equal to 24 hours.

  18. Circadian rhythm of temperature preference and its neural control in Drosophila

    PubMed Central

    Kaneko, Haruna; Head, Lauren M.; Ling, Jinli; Tang, Xin; Liu, Yilin; Hardin, Paul E.; Emery, Patrick; Hamada, Fumika N.

    2012-01-01

    A daily body temperature rhythm (BTR) is critical for the maintenance of homeostasis in mammals. While mammals use internal energy to regulate body temperature, ectotherms typically regulate body temperature behaviorally [1]. Some ectotherms maintain homeostasis via a daily temperature preference rhythm (TPR) [2], but the underlying mechanisms are largely unknown. Here, we show that Drosophila exhibit a daily circadian clock dependent TPR that resembles mammalian BTR. Pacemaker neurons critical for locomotor activity are not necessary for TPR; instead, the dorsal neuron 2s (DN2s), whose function was previously unknown, is sufficient. This indicates that TPR, like BTR, is controlled independently from locomotor activity. Therefore, the mechanisms controlling temperature fluctuations in fly TPR and mammalian BTR may share parallel features. Taken together, our results reveal the existence of a novel DN2- based circadian neural circuit that specifically regulates TPR; thus, understanding the mechanisms of TPR will shed new light on the function and neural control of circadian rhythms. PMID:22981774

  19. Circadian rhythms and mood: Opportunities for multi-level analyses in genomics and neuroscience

    PubMed Central

    Li, Jun Z

    2014-01-01

    In the healthy state, both circadian rhythm and mood are stable against perturbations, yet they are capable of adjusting to altered internal cues or ongoing changes in external conditions. The dual demands of stability and flexibility are met by the collective properties of complex neural networks. Disruption of this balance underlies both circadian rhythm abnormality and mood disorders. However, we do not fully understand the network properties that govern the crosstalk between the circadian system and mood regulation. This puzzle reflects a challenge at the center of neurobiology, and its solution requires the successful integration of existing data across all levels of neural organization, from molecules, cells, circuits, network dynamics, to integrated mental function. This essay discusses several open questions confronting the cross-level synthesis, and proposes that circadian regulation, and its role in mood, stands as a uniquely tractable system to study the causal mechanisms of neural adaptation. PMID:24853393

  20. Robust Circadian Rhythm and Parathyroid Hormone-Induced Resetting during Hypertrophic Differentiation in ATDC5 Chondroprogenitor Cells

    PubMed Central

    Hosokawa, Toshihiro; Tsuchiya, Yoshiki; Okubo, Naoki; Kunimoto, Tatsuya; Minami, Yoichi; Fujiwara, Hiroyoshi; Umemura, Yasuhiro; Koike, Nobuya; Kubo, Toshikazu; Yagita, Kazuhiro

    2015-01-01

    Cartilage tissues possess intrinsic circadian oscillators, which influence chondrocyte function and chondrocyte specific gene expression. However, it is not fully understood how chondrogenesis influences the circadian clock, and vice versa. Thus, we established ATDC5 cells which were stably transfected with the Bmal1:luc reporter and revealed robust circadian rhythms in ATDC5 cells during differentiation. Moreover, the circadian clock in ATDC5 cells was strongly reset by PTH in a circadian time-dependent manner. This assay system is expected to be useful for investigating the role of the circadian clock in chondrogenic differentiation and the precise molecular mechanisms underlying PTH action on the chondrocyte circadian clock. PMID:26855448

  1. Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

    PubMed Central

    Chiu, Joanna C.; Low, Kwang Huei; Pike, Douglas H.; Yildirim, Evrim; Edery, Isaac

    2010-01-01

    Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (≡24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal's endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties. PMID:20972399

  2. Self-arrangement of cellular circadian rhythms through phase-resetting in plant roots

    NASA Astrophysics Data System (ADS)

    Fukuda, Hirokazu; Ukai, Kazuya; Oyama, Tokitaka

    2012-10-01

    We discovered a striped pattern of gene expression with circadian rhythms in growing plant roots using bioluminescent imaging of gene expression. Our experimental analysis revealed that the stripe wave in the bioluminescent image originated at the root tip and was caused by a continuous phase resetting of circadian oscillations. Some complex stripe waves containing arrhythmic regions were also observed. We succeeded in describing the formation mechanisms of these patterns using a growing phase oscillator network with a phase-resetting boundary condition.

  3. Sex differences in human circadian rhythms: intrinsic periods and sleep fractions.

    PubMed

    Wever, R A

    1984-11-15

    The period of freerunning circadian rhythms is significantly shorter and the fraction of sleep is significantly larger in human females than in males, as long as the rhythms run internally synchronized. The sex difference in the period could be a property either of the whole circadian system or of only one of the oscillators in a multi-oscillator system. The sex difference in the sleep fraction could be a fixed property of the sleep-wake rhythm or could depend on interactions in the multi-oscillator system. To investigate these questions, a sample of 33 long-term experiments, in which the rhythms ran internally synchronized in one section and internally desynchronized in another section, were analyzed. The periods of rhythms in rectal temperature were different in females and males during internal synchronization, but became identical during internal desynchronization. In contrast, sex differences in sleep-wake periods were more pronounced when the rhythms were desynchronized than when they were internally synchronized. This result provides evidence that the sex difference in periodicity is a property only of the sleep-wake rhythm; the intrinsic periods of temperature rhythms are identical in females and males, whereas those of sleep-wake rhythms are distinctly shorter in females than in males. In the state of internal synchronization, the joint period is a compromise between the intrinsic periods of the rhythms involved, and therefore it shows a small but significant sex difference. Moreover, the transition from internally synchronized to desynchronized rhythms is combined with a highly significant reduction in the sleep fraction, which is considerably greater in females than in males. These results suggest that the occurrence of internal desynchronization strongly affects the sleep-wake rhythm, and that the influence of rhythm disorders is considerably greater in females than in males. PMID:6500007

  4. Circadian Rhythms of PER2::LUC in Individual Primary Mouse Hepatocytes and Cultures

    PubMed Central

    Molyneux, Penny C.; Yu, Jimmy K.; Li, Alexander S.; Leise, Tanya L.; Harrington, Mary E.

    2014-01-01

    Background Hepatocytes, the parenchymal cells of the liver, express core clock genes, such as Period2 and Cryptochrome2, which are involved in the transcriptional/translational feedback loop of the circadian clock. Whether or not the liver is capable of sustaining rhythms independent of a central pacemaker is controversial. Whether and how circadian information may be shared among cells in the liver in order to sustain oscillations is currently unknown. Results In this study we isolated primary hepatocytes from transgenic Per2Luc mice and used bioluminescence as a read-out of the state of the circadian clock. Hepatocytes cultured in a collagen gel sandwich configuration exhibited persistent circadian rhythms for several weeks. The amplitude of the rhythms damped, but medium changes consistently reset the phase and amplitude of the cultures. Cry2?/? Per2Luc cells oscillated robustly and expressed a longer period. Co-culturing with wildtype cells did not significantly shorten the period, indicating that coupling among hepatocytes is insufficient to synchronize cells with significantly differing periods. However, spatial patterns revealed by cellular imaging of wildtype cultures provided evidence of weak local coupling among the hepatocytes. Conclusions Our results with primary hepatocyte cultures demonstrate that cultured hepatocytes are weakly coupled. While this coupling is not sufficient to sustain global synchrony, it does increase local synchrony, which may stabilize the circadian rhythms of peripheral oscillators, such as the liver, against noise in the entraining signals. PMID:24498336

  5. Circadian Rhythms of Crawling and Swimming in the Nudibranch Mollusc Melibe leonina

    PubMed Central

    NEWCOMB, JAMES M.; KIROUAC, LAUREN E.; NAIMIE, AMANDA A.; BIXBY, KIMBERLY A.; LEE, COLIN; MALANGA, STEPHANIE; RAUBACH, MAUREEN; WATSON, WINSOR H.

    2015-01-01

    Daily rhythms of activity driven by circadian clocks are expressed by many organisms, including molluscs. We initiated this study, with the nudibranch Melibe leonina, with four goals in mind: (1) determine which behaviors are expressed with a daily rhythm; (2) investigate which of these rhythmic behaviors are controlled by a circadian clock; (3) determine if a circadian clock is associated with the eyes or optic ganglia of Melibe, as it is in several other gastropods; and (4) test the hypothesis that Melibe can use extraocular photoreceptors to synchronize its daily rhythms to natural light-dark cycles. To address these goals, we analyzed the behavior of 55 animals exposed to either artificial or natural light-dark cycles, followed by constant darkness. We also repeated this experiment using 10 animals that had their eyes removed. Individuals did not express daily rhythms of feeding, but they swam and crawled more at night. This pattern of locomotion persisted in constant darkness, indicating the presence of a circadian clock. Eyeless animals also expressed a daily rhythm of locomotion, with more locomotion at night. The fact that eyeless animals synchronized their locomotion to the light-dark cycle suggests that they can detect light using extraocular photoreceptors. However, in constant darkness, these rhythms deteriorated, suggesting that the clock neurons that influence locomotion may be located in, or near, the eyes. Thus, locomotion in Melibe appears to be influenced by both ocular and extraocular photoreceptors, although the former appear to have a greater influence on the expression of circadian rhythms. PMID:25572214

  6. Circadian rhythm of leaf movement in Capsicum annuum observed during centrifugation

    NASA Technical Reports Server (NTRS)

    Chapman, D. K.; Brown, A. H.; Dahl, A. O.

    1975-01-01

    Plant circadian rhythms of leaf movement in seedlings of the pepper plant (Capsicum annuum L., var. Yolo Wonder) were observed at different g-levels by means of a centrifuge. Except for the chronically imposed g-force all environmental conditions to which the plants were exposed were held constant. The circadian period, rate of change of amplitude of successive oscillations, symmetry of the cycles, and phase of the rhythm all were found not to be significantly correlated with the magnitude of the sustained g-force.

  7. Cortisol-mediated synchronization of circadian rhythm in urinary potassium excretion

    NASA Technical Reports Server (NTRS)

    Moore-Ede, M. C.; Schmelzer, W. S.; Kass, D. A.; Herd, J. A.

    1977-01-01

    Conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 hr daily (LD 12:12) display a prominent circadian rhythm in renal potassium excretion. The characteristics of this rhythm were reproduced in adrenalectomized monkeys by infusing 5 mg cortisol and 0.001 mg aldosterone, or 5 mg cortisol alone, between 0800 and 0900 kr daily. When the timing of cortisol administration (with or without aldosterone) was phase-delayed by 8 hr, the urinary potassium rhythm resynchronized by 80% of the cortisol phase shift, but only after a transient response lasting 3-4 days. With the same daily dose of adrenal steroids given as a continuous infusion throughout each 24 hr, urinary potassium excretion showed free-running oscillations no longer synchronized to the light-dark cycle. These results indicate that the circadian rhythm of plasma cortisol concentration acts as an internal mediator in the circadian timing system, synchronizing a potentially autonomous oscillation in renal potassium excretion to environmental time cues and to other circadian rhythms within the animal.

  8. Circadian rhythms of locomotor activity in the Nile tilapia Oreochromis niloticus.

    PubMed

    Vera, Luisa Maria; Cairns, Louise; Sánchez-Vázquez, Francisco Javier; Migaud, Hervé

    2009-05-01

    Behavioral rhythms of the Nile tilapia were investigated to better characterize its circadian system. To do so, the locomotor activity patterns of both male and female tilapia reared under a 12:12 h light-dark (LD) cycle were studied, as well as in males the existence of endogenous rhythmicity under free-running conditions (DD and 45 min LD pulses). When exposed to an LD cycle, the daily pattern of activity differed between individuals: some fish were diurnal, some nocturnal, and a few displayed an arrhythmic pattern. This variability would be typical of the plastic circadian system of fish. Moreover, reproductive events clearly affected the behavioral rhythms of female tilapia, a mouth-brooder teleost species. Under DD, 50% (6 of 12) of male fish showed circadian rhythms with an average period (tau) of 24.1+/-0.2 h, whereas under the 45 min LD pulses, 58% (7 of 12) of the fish exhibited free-running activity rhythms with an average tau of 23.9+/-0.5 h. However, interestingly in this case, activity was always confined to the dark phase. Furthermore, when the LD cycle was reversed, a third of the fish showed gradual resynchronization to the new phase, taking 7-10 days to be completely re-entrained. Taken together, these results suggest the existence of an endogenous circadian oscillator that controls the expression of locomotor activity rhythms in the Nile tilapia, although its anatomical localization remains unknown. PMID:19444748

  9. No time to lose: workshop on circadian rhythms and metabolic disease

    PubMed Central

    Silva, Corinne M.; Sato, Sheryl; Margolis, Ronald N.

    2010-01-01

    The objective of the workshop was to gain a better understanding of the link between circadian rhythms and human health and disease. The impacts of circadian rhythms on metabolic gene regulation, as well as the effect of nutrient uptake and balance on the molecular components of the clock, were discussed. Topics included the neural circuitry underlying the central clock; the effect of the environment and diet on the central clock as well as peripheral, tissue-specific clocks; and the transcriptional, post-transcriptional, and post-translational (e.g., epigenomic) mechanisms through which these signals are transduced. Evidence presented during the meeting demonstrated that circadian rhythms and metabolism are intricately linked, and that disruption in these rhythms have profound consequences—many times leading to metabolic disease. The mechanisms by which circadian rhythms are maintained and the cross-talk with metabolic signaling are just beginning to be elucidated. However, the interactions between these fields and the knowledge learned will clearly have a profound impact on our understanding of metabolic disease and lead to novel therapeutic approaches in the future PMID:20634312

  10. Circadian foraging rhythms of bumblebees monitored by radio-frequency identification.

    PubMed

    Jürgen Stelzer, Ralph; Stanewsky, Ralf; Chittka, Lars

    2010-08-01

    Circadian clocks enable organisms to anticipate changes of environmental conditions. In social insects, the colony as a superorganism has a foraging rhythm aligned to the diurnal patterns of resource availability. Within this colony rhythm, the diurnal patterns of individuals are embedded, and various tasks within the colony are performed at different times by different individuals to best serve the colony as a whole. Recent studies have shown that social cues influence the traits of the circadian clock in social insects, but keeping track of the activity of individual workers is not an easy task. Here the authors use fully automatic radio-frequency identification (RFID) to analyze the circadian rhythms of bumblebee foragers (Bombus terrestris) in the normal social context of their nest. They monitored their foraging patterns under different light conditions in the laboratory, including light:dark cycles (LD) as well as constant darkness (DD) and constant light conditions (LL). Their results show that the majority of bumblebee foragers exhibit robust circadian rhythms in LD under laboratory conditions, while they show free-running rhythms both in DD and LL, with free-running periods being significantly shorter in LL conditions. The authors also found that bumblebee workers show an increased level of arrhythmic activity ("death dance") in the hours or days before their death. PMID:20679495

  11. Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo

    SciTech Connect

    Rubin, N.H.

    1982-01-01

    Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, to a lesser extent, degree of recovery.

  12. Comparison of synchronization of primate circadian rhythms by light and food

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Fuller, C. A.; Moore-Ede, M. C.

    1978-01-01

    It is a well-documented fact that cycles of light and dark (LD) are the major entraining agent or 'zeitgeber' for circadian rhythms and that cycles of eating and fasting (EF) are capable of synchronizing a few circadian rhythms in the squirrel monkey. In this paper, by contrasting how these rhythms are timed by LD and EF cycles, the differential coupling to the oscillating system within adult male squirrel monkeys is examined. The variables measured are the rhythms of drinking, colonic temperature, and urinary potassium and water excretion. Attention is given to a comparison of the reproducibility of the averaged waveforms of the rhythms, the stability of the timing of a phase reference point, and the rate of resynchronization of these rhythms following an abrupt 8-hr phase delay in the zeitgeber. It is shown that the colonic temperature rhythm is more tightly controlled by LD than EF cycles, and that the drinking and urinary rhythms are more tightly coupled to EF than LD cycles.

  13. Modulation of metabolic and clock gene mRNA rhythms by pineal and retinal circadian oscillators

    PubMed Central

    Karaganis, Stephen P.; Bartell, Paul A.; Shende, Vikram R.; Moore, Ashli F.; Cassone, Vincent M.

    2009-01-01

    Avian circadian organization involves interactions between three neural pacemakers: the suprachiasmatic nuclei (SCN), pineal, and retina. Each of these structures is linked within a neuroendocrine loop to influence downstream processes and peripheral oscillations. However, the contribution of each structure to drive or synchronize peripheral oscillators or circadian outputs in avian species is largely unknown. To explore these interactions in the chick, we measured 2-deoxy[14C]-glucose (2DG) uptake and mRNA expression of the chick clock genes bmal1, cry1, and per3 in three brain areas and in two peripheral organs in chicks that underwent pinealectomy, enucleation, or sham surgery. We found that 2DG uptake rhythms damp under constant darkness in intact animals, while clock gene mRNA levels continue to cycle, demonstrating that metabolic rhythms are not directly driven by clock gene transcription. Moreover, 2DG rhythms are not phase-locked to rhythms of clock gene mRNA. However, pinealectomy and enucleation had similar disruptive effects on both metabolic and clock gene rhythms, suggesting that both of these oscillators act similarly to reinforce molecular and physiological rhythms in the chicken. Finally, we show that the relative phasing of at least one clock gene, cry1, varies between central and peripheral oscillators in a tissue specific manner. These data point to a complex, differential orchestration of central and peripheral oscillators in the chick, and, importantly, indicate a disconnect between canonical clock gene regulation and circadian control of metabolism. PMID:19136000

  14. Cell Cycle-related and Endogenously Controlled Circadian Photosynthetic Rhythms in Euglena1

    PubMed Central

    Laval-Martin, Danielle L.; Shuch, David J.; Edmunds, Leland N.

    1979-01-01

    The data presented for three strains of Euglena gracilis corroborate previous reports of a diel rhythm in photosynthetic capacity in division-synchronized cultures of this alga and extend these studies to free running, dividing and nondividing (stationary) cultures maintained in either 24-hour or 40-minute cycles of light and darkness. During synchronous growth entrained by LD: 12,12 or free running under LD: 1/3,1/3, photosynthetic CO2 fixation was rhythmic with a period (24.0 or about 30 hours) corresponding to the period of the cell division rhythm in the population. Furthermore, the rhythm in CO2 fixation (per cell) found in nondividing cultures maintained in LD: 12,12 persisted in LD: 1/3,1/3 for weeks with a free running, circadian period of approximately 30 hours. An endogenous, circadian rhythm in cellular chlorophyll was found to exist, independently of cell division, under both light regimens and in each individual experiment; this observation could reflect changes in the functional role of the pigment. In cultures maintained in LD: 1/3,1/3, the phase relationship between the rhythm of photosynthetic capacity and that of chlorophyll content varied, suggesting the possibility of desynchronization among circadian rhythms in a multioscillator, unicellular organism. PMID:16660755

  15. Melatonin Entrains PER2::LUC Bioluminescence Circadian Rhythm in the Mouse Cornea

    PubMed Central

    Baba, Kenkichi; Davidson, Alec J.; Tosini, Gianluca

    2015-01-01

    Purpose Previous studies have reported the presence of a circadian rhythm in PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence in mouse photoreceptors, retina, RPE, and cornea. Melatonin (MLT) modulates many physiological functions in the eye and it is believed to be one of the key circadian signals within the eye. The aim of the present study was to investigate the regulation of the PER2::LUC circadian rhythm in mouse cornea and to determine the role played by MLT. Methods Corneas were obtained from PER2::LUC mice and cultured to measure bioluminescence rhythmicity in isolated tissue using a Lumicycle or CCD camera. To determine the time-dependent resetting of the corneal circadian clocks in response to MLT or IIK7 (a melatonin type 2 receptor, MT2, agonist) was added to the cultured corneas at different times of the day. We also defined the location of the MT2 receptor within different corneal layers using immunohistochemistry. Results A long-lasting bioluminescence rhythm was recorded from cultured PER2::LUC cornea and PER2::LUC signal was localized to the corneal epithelium and endothelium. MLT administration in the early night delayed the cornea rhythm, whereas administration of MLT at late night to early morning advanced the cornea rhythm. Treatment with IIK7 mimicked the MLT phase-shifting effect. Consistent with these results, MT2 immunoreactivity was localized to the corneal epithelium and endothelium. Conclusions Our work demonstrates that MLT entrains the PER2::LUC bioluminescence rhythm in the cornea. Our data indicate that the cornea may represent a model to study the molecular mechanisms by which MLT affects the circadian clock. PMID:26207312

  16. Circadian rhythm of the Leydig cells endocrine function is attenuated during aging.

    PubMed

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Bjelic, Maja M; Radovic, Sava M; Andric, Silvana A; Kostic, Tatjana S

    2016-01-01

    Although age-related hypofunction of Leydig cells is well illustrated across species, its circadian nature has not been analyzed. Here we describe changes in circadian behavior in Leydig cells isolated from adult (3-month) and aged (18- and 24-month) rats. The results showed reduced circadian pattern of testosterone secretion in both groups of aged rats despite unchanged LH circadian secretion. Although arrhythmic, the expression of Insl3, another secretory product of Leydig cells, was decreased in both groups. Intracellular cAMP and most important steroidogenic genes (Star, Cyp11a1 and Cyp17a1), together with positive steroidogenic regulator (Nur77), showed preserved circadian rhythm in aging although rhythm robustness and expression level were attenuated in both aged groups. Aging compromised cholesterol mobilization and uptake by Leydig cells: the oscillatory transcription pattern of genes encoding HDL-receptor (Scarb1), hormone sensitive lipase (Lipe, enzyme that converts cholesterol esters from lipid droplets into free cholesterol) and protein responsible for forming the cholesterol esters (Soat2) were flattened in 24-month group. The majority of examined clock genes displayed circadian behavior in expression but only a few of them (Bmal1, Per1, Per2, Per3 and Rev-Erba) were reduced in 24-month-old group. Furthermore, aging reduced oscillatory expression pattern of Sirt1 and Nampt, genes encoding key enzymes that connect cellular metabolism and circadian network. Altogether circadian amplitude of Leydig cell's endocrine function decreased during aging. The results suggest that clock genes are more resistant to aging than genes involved in steroidogenesis supporting the hypothesis about peripheral clock involvement in rhythm maintenance during aging. PMID:26547053

  17. The circadian cycle: daily rhythms from behaviour to genes

    PubMed Central

    Merrow, Martha; Spoelstra, Kamiel; Roenneberg, Till

    2005-01-01

    The daily recurrence of activity and rest are so common as to seem trivial. However, they reflect a ubiquitous temporal programme called the circadian clock. In the absence of either anatomical clock structures or clock genes, the timing of sleep and wakefulness is disrupted. The complex nature of circadian behaviour is evident in the fact that phasing of the cycle during the day varies widely for individuals, resulting in extremes colloquially called 'larks' and 'owls'. These behavioural oscillations are mirrored in the levels of physiology and gene expression. Deciphering the underlying mechanisms will provide important insights into how the circadian clock affects health and disease. PMID:16222241

  18. Circadian Rhythms and Mood Regulation: Insights from Pre-Clinical Models

    PubMed Central

    McClung, Colleen A.

    2011-01-01

    Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes that associate with these disorders. Thus, there appears to be a strong association between the circadian system and mood regulation, although the mechanisms that underlie this association are unclear. Recently, a number of studies in animal models have begun to shed light on the complex interactions between circadian genes and mood-related neurotransmitter systems, the effects of light manipulation on brain circuitry, the impact of chronic stress on rhythms, and the ways in which antidepressant and mood-stabilizing drugs alter the clock. This review will focus on the recent advances that have been gleaned from the use of pre-clinical models to further our understanding of how the circadian system regulates mood. PMID:21835596

  19. Urinary Cortisol Circadian Rhythm in a Group of High-Functioning Children with Autism.

    ERIC Educational Resources Information Center

    Richdale, Amanda L.; Prior, Margot R.

    1992-01-01

    This study found no evidence for abnormal temporal placement of the basal urinary cortisol circadian rhythm in a group of 18 high-functioning children (ages 4-14) with autism. There was a tendency toward cortisol hypersecretion during the day, predominantly in autistic children who were integrated into the normal school system. (Author/JDD)

  20. A Comparative Study of Circadian Rhythm Functioning and Sleep in People with Asperger Syndrome

    ERIC Educational Resources Information Center

    Hare, Dougal Julian; Jones, Steven; Evershed, Kate

    2006-01-01

    The circadian rhythm functioning and sleep patterns of 10 adults with Asperger syndrome were investigated using actigraphy. When compared with data from neurotypical adults, both statistical and clinically significant differences were found between the two groups, with the adults with Asperger syndrome showing marked abnormalities in both the…

  1. Dark pulses affect the circadian rhythm of activity in hamsters kept in constant light.

    PubMed

    Ellis, G B; McKlveen, R E; Turek, F W

    1982-01-01

    We compared the effects of light pulses in constant darkness (DD) and dark pulses in constant light (LL) on the free-running rhythm of locomotor activity in male golden hamsters. Light pulses yielded advances, delays, or no change in the rhythm of activity. These data conform to a typical phase-response curve; this curve was unaffected by pinealectomy. Dark pulses occurring either late in the subjective night or early in the subjective day had little effect. In contrast, dark pulses occurring either late in the subjective day or early in the subjective night altered the rhythm in one of three ways: advance of the rhythm; splitting into two components; or induction of a new component, in phase with the pulse. Because dark pulses in LL perturb the circadian system in a different manner than do light pulses in DD, they may have value in identifying heretofore unknown aspects of circadian systems. As such, the use of dark pulses to perturb circadian rhythmicity will be a useful tool in examining the formal properties of circadian systems. PMID:7058930

  2. Darwin, Earthworms & Circadian Rhythms: A Fertile Field for Science Fair Experiments

    ERIC Educational Resources Information Center

    Burns, John T.; Scurti, Paul J.; Furda, Amy M.

    2009-01-01

    This article discusses why the study of earthworms has fascinated many scientists, and why earthworms make ideal experimental animals for students to test in the laboratory. Although earthworms may appear to be primitive, they are governed by both circadian and seasonal rhythms, just as more advanced organisms are. They possess an intelligence…

  3. A Comparative Study of Circadian Rhythm Functioning and Sleep in People with Asperger Syndrome

    ERIC Educational Resources Information Center

    Hare, Dougal Julian; Jones, Steven; Evershed, Kate

    2006-01-01

    The circadian rhythm functioning and sleep patterns of 10 adults with Asperger syndrome were investigated using actigraphy. When compared with data from neurotypical adults, both statistical and clinically significant differences were found between the two groups, with the adults with Asperger syndrome showing marked abnormalities in both the…

  4. Circadian rhythms of body temperature and metabolic rate in naked mole-rats.

    PubMed

    Riccio, A P; Goldman, B D

    Body temperature (T(b)) and metabolic rate (O(2) consumption) were measured continuously in naked mole-rats. Circadian rhythms were observed for both parameters. Body temperature increased at the end of the light phase in a 12L:12D cycle in three of four animals. The remaining animal exhibited a freerunning rhythm of T(b). When animals had access to running wheels, the time of elevated T(b) coincided closely with the time of increased running wheel activity. Rhythms of T(b) continued following removal of the wheels, but the duration of increased T(b) was decreased as compared to the duration of T(b) elevation in the presence of wheels. Metabolic rate was increased at the same circadian phase as the increase in T(b) and running wheel activity. These observations extend our earlier findings on circadian rhythms of locomotor activity in naked mole-rats and suggest that the circadian system may have significant physiological functions in this subterranean rodent. PMID:11134680

  5. CIRCADIAN RHYTHMS OF FEEDING, OVIPOSITION, AND EMERGENCE OF THE BOLL WEEVIL (COLEOPTERA: CURCULIONIDAE)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythm of feeding, oviposition, and emergence of boll weevil adults were determined at 5 different photophases (24, 14, 12, 10 and 0 hours) and a constant 27 deg C temperature, 65% RH in the laboratory. Squares from petri dishes, where they were exposed to boll weevil females, were remove...

  6. Darwin, Earthworms & Circadian Rhythms: A Fertile Field for Science Fair Experiments

    ERIC Educational Resources Information Center

    Burns, John T.; Scurti, Paul J.; Furda, Amy M.

    2009-01-01

    This article discusses why the study of earthworms has fascinated many scientists, and why earthworms make ideal experimental animals for students to test in the laboratory. Although earthworms may appear to be primitive, they are governed by both circadian and seasonal rhythms, just as more advanced organisms are. They possess an intelligence…

  7. The Circadian Clock in the Regulation of Renal Rhythms.

    PubMed

    Solocinski, Kristen; Gumz, Michelle L

    2015-12-01

    Since the kidney is integral to maintenance of fluid and ion homeostasis, and therefore blood pressure regulation, its proper function is paramount. Circadian fluctuations in blood pressure, renal blood flow, glomerular filtration rate, and sodium and water excretion have been documented for decades, if not longer. Recent studies on the role of circadian clock proteins in the regulation of a variety of renal transport genes suggest that the molecular clock in the kidney controls circadian fluctuations in renal function. The circadian clock appears to be a critical regulator of renal function with important implications for the treatment of renal pathologies, which include chronic kidney disease and hypertension. The development, regulation, and mechanism of the kidney clock are reviewed here. PMID:26527094

  8. Circadian regulation of prion protein messenger RNA in the rat forebrain: a widespread and synchronous rhythm.

    PubMed

    Cagampang, F R; Whatley, S A; Mitchell, A L; Powell, J F; Campbell, I C; Coen, C W

    1999-01-01

    Although the expression of the normal prion protein in the host is critical to the development of transmissible spongiform encephalopathies, the physiological role of this protein and the processes regulating its expression remain obscure. We now report that the messenger RNA for the prion protein is regulated in the rat brain in a marked circadian manner not only in the suprachiasmatic nuclei, the principal site for the generation of mammalian circadian rhythms, but also in other forebrain regions. The data show a remarkable consistency in the concurrence of a single peak of prion protein messenger RNA at each of the sites early in the animal's phase of increased locomotor activity; behavioural arousal does not, however, appear to affect this expression. We believe this to be the first study demonstrating that the expression of prion protein messenger RNA can change over a relatively short period in vivo. The results are discussed with reference to the range of recently discovered "clock-related" transcripts which also have widespread tissue expression; these include the messenger RNAs for D-box binding protein and thyroid embryonic factor, transcription factors which bind to the prion protein promoter. PMID:10391428

  9. Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders

    PubMed Central

    Morgenthaler, Timothy I.; Lee-Chiong, Teofilo; Alessi, Cathy; Friedman, Leah; Aurora, R. Nisha; Boehlecke, Brian; Brown, Terry; Chesson, Andrew L.; Kapur, Vishesh; Maganti, Rama; Owens, Judith; Pancer, Jeffrey; Swick, Todd J.; Zak, Rochelle

    2007-01-01

    The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses “exogenous” circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the “endogenous” circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non–24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from “Option” to “Guideline,” depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs (Guideline). A range of therapeutic interventions were considered including planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics, stimulants, and alerting agents. Planned or prescribed sleep schedules are indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly-demented/nursing home residents), and FRD (Option). Specifically dosed and timed light exposure is indicated for each of the circadian disorders with variable success (Option). Timed melatonin administration is indicated for JLD (Standard); SWD, DSPD, and FRD in unsighted persons (Guideline); and for ASPD, FRD in sighted individuals, and for ISWR in children with moderate to severe psychomotor retardation (Option). Hypnotic medications may be indicated to promote or improve daytime sleep among night shift workers (Guideline) and to treat jet lag-induced insomnia (Option). Stimulants may be indicated to improve alertness in JLD and SWD (Option) but may have risks that must be weighed prior to use. Modafinil may be indicated to improve alertness during the night shift for patients with SWD (Guideline). Citation: Morgenthaler TI; Lee-Chiong T; Alessi C; Friedman L; Aurora N; Boehlecke B; Brown T; Chesson AL; Kapur V; Maganti R; Owens J; Pancer J; Swick TJ; Zak R; Standards of Practice Committee of the AASM. Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders. SLEEP 2007;30(11):1445-1459. PMID:18041479

  10. Circadian locomotor rhythms in the desert iguana. II. Effects of electrolytic lesions to the hypothalamus.

    PubMed

    Janik, D S; Pickard, G E; Menaker, M

    1990-04-01

    Desert iguanas, Dipsosaurus dorsalis, displaying freerunning circadian locomotor rhythms in conditions of constant darkness and temperature received electrolytic lesions to the hypothalamus. The locomotor activity of those lizards (N = 9) which sustained 80% or more damage to the suprachiasmatic nucleus (SCN) became arrhythmic whereas all animals that sustained less than 35% damage to the SCN remained rhythmic, even though they sustained significant damage to nearby regions of the hypothalamus and preoptic area. These results suggest strongly that the SCN plays a role in the regulation of circadian rhythms in the desert iguana. Taken together with other evidence, they support the view that this structure is homologous to the mammalian SCN, which acts as a pacemaker in the circadian system. PMID:2359055

  11. Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons

    PubMed Central

    Wang, Tongfei A.; Yu, Yanxun V.; Govindaiah, Gubbi; Ye, Xiaoying; Artinian, Liana; Coleman, Todd P.; Sweedler, Jonathan V.; Cox, Charles L.; Gillette, Martha U.

    2012-01-01

    Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are orchestrated by a central circadian clock in the brain, the suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to metabolic changes in reduction and oxidation (redox); however, circadian cycles in protein oxidation have been reported in anucleate cells, where no transcription occurs. We tested whether the SCN also expresses redox cycles and how such metabolic oscillations might affect neuronal physiology. We detected self-sustained circadian rhythms of SCN redox state that required the molecular clockwork. The redox oscillation could determine the excitability of SCN neurons through non-transcriptional modulation of multiple K+ channels. Thus, dynamic regulation of SCN excitability appears to be closely tied to metabolism that engages the clockwork machinery. PMID:22859819

  12. The genetic background of individual variations of circadian-rhythm periods in healthy human adults.

    PubMed Central

    Ashkenazi, I E; Reinberg, A; Bicakova-Rocher, A; Ticher, A

    1993-01-01

    As a group phenomenon, human variables exhibit a rhythm with a period (tau) equal to 24 h. However, healthy human adults may differ from one another with regard to the persistence of the 24-h periods of a set of variables' rhythms within a given individual. Such an internal desynchronization (or individual circadian dyschronism) was documented during isolation experiments without time cues, both in the present study involving 78 male shift workers and in 20 males and 19 females living in a natural setting. Circadian rhythms of sleep-wake cycles, oral temperature, grip strength of both hands, and heart rate were recorded, and power-spectra analyses of individual time series of about 15 days were used to quantify the rhythm period of each variable. The period of the sleep-wake cycle seldom differed from 24 h, while rhythm periods of the other variables exhibited a trimodal distribution (tau = 24 h, tau > 24 h, tau < 24 h). Among the temperature rhythm periods which were either < 24 h or > 24 h, none was detected between 23.2 and 24 h or between 24 and 24.8 h. Furthermore, the deviations from the 24-h period were predominantly grouped in multiples of +/- 0.8 h. Similar results were obtained when the rhythm periods of hand grip strength were analyzed (for each hand separately). In addition, the distribution of grip strength rhythm periods of the left hand exhibited a gender-related difference. These results suggested the presence of genetically controlled variability. Consequently, the distribution pattern of the periods was analyzed to elucidate its compatibility with a genetic control consisting of either a two-allele system, a multiple-allele system, or a polygenic system. The analysis resulted in structuring a model which integrates the function of a constitutive (essential) gene which produces the exact 24-h period (the Dian domain) with a set of (inducible) polygenes, the alleles of which, contribute identical time entities to the period. The time entities which affected the rhythm periods of the variables examined were in the magnitude of +/- 0.8 h. Such an assembly of genes may create periods ranging from 20 to 28 h (the Circadian domain). The model was termed by us "The Dian-Circadian Model." This model can also be used to explain the beat phenomena in biological rhythms, the presence of 7-d and 30-d periods, and interindividual differences in sensitivity of rhythm characteristics (phase shifts, synchronization, etc.) to external (and environmental) factors. PMID:8503453

  13. Circadian rhythms constrain leaf and canopy gas exchange in an Amazonian forest

    NASA Astrophysics Data System (ADS)

    Doughty, Christopher E.; Goulden, Michael L.; Miller, Scott D.; da Rocha, Humberto R.

    2006-08-01

    We used a controlled-environment leaf gas-exchange system and the micrometeorological technique eddy covariance to determine whether circadian rhythms constrain the rates of leaf and canopy gas exchange in an Amazonian forest over a day. When exposed to continuous and constant light for 20 to 48 hours leaves of eleven of seventeen species reduced their photosynthetic rates and closed their stomata during the normally dark period and resumed active gas exchange during the normally light period. Similarly, the rate of whole-forest CO2 uptake at a predetermined irradiance declined during the late afternoon and early morning and increased during the middle of the day. We attribute these cycles to circadian rhythms that are analogous to ones that have been reported for herbaceous plants in the laboratory. The importance of endogenous gas exchange rhythms presents a previously unrecognized challenge for efforts to both interpret and model land-atmosphere energy and mass exchange.

  14. Circadian rhythms of visual accommodation responses and physiological correlations.

    NASA Technical Reports Server (NTRS)

    Murphy, M. R.; Randle, R. J.; Williams, B. A.

    1972-01-01

    Use of a recently developed servocontrolled infrared optometer to continuously record the state of monocular focus while subjects viewed a visual target for which the stimulus to focus was systematically varied. Calculated parameters form recorded data - e.g., speeds of accommodation to approaching and receding targets, magnitude of accommodation to step changes in target distance, and amplitude and phase lag of response to sinusoidally varying stimuli were submitted to periodicity analyses. Ear canal temperature (ECT) and heart rate (HR) rhythms were also recorded for physiological correlation with accommodation rhythms. HR demonstrated a 24-hr rhythm, but ECT data did not.

  15. Alteration of Daily and Circadian Rhythms following Dopamine Depletion in MPTP Treated Non-Human Primates

    PubMed Central

    Fifel, Karim; Vezoli, Julien; Dzahini, Kwamivi; Claustrat, Bruno; Leviel, Vincent; Kennedy, Henry; Procyk, Emmanuel; Dkhissi-Benyahya, Ouria; Gronfier, Claude; Cooper, Howard M.

    2014-01-01

    Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([11C]-PE2I) and post-mortem TH and DAT quantification. In a light?dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed. PMID:24465981

  16. Coupling circadian rhythms of metabolism and chromatin remodelling.

    PubMed

    Masri, S; Orozco-Solis, R; Aguilar-Arnal, L; Cervantes, M; Sassone-Corsi, P

    2015-09-01

    The circadian clock controls a large variety of neuronal, endocrine, behavioural and physiological responses in mammals. This control is exerted in large part at the transcriptional level on genes expressed in a cyclic manner. A highly specialized transcriptional machinery based on clock regulatory factors organized in feedback autoregulatory loops governs a significant portion of the genome. These oscillations in gene expression are paralleled by critical events of chromatin remodelling that appear to provide plasticity to circadian regulation. Specifically, the nicotinamide adenine dinucleotide (NAD)(+) -dependent deacetylases SIRT1 and SIRT6 have been linked to circadian control of gene expression. This, and additional accumulating evidence, shows that the circadian epigenome appears to share intimate links with cellular metabolic processes and has remarkable plasticity showing reprogramming in response to nutritional challenges. In addition to SIRT1 and SIRT6, a number of chromatin remodellers have been implicated in clock control, including the histone H3K4 tri-methyltransferase MLL1. Deciphering the molecular mechanisms that link metabolism, epigenetic control and circadian responses will provide valuable insights towards innovative strategies of therapeutic intervention. PMID:26332964

  17. Circadian rhythms and sleep have additive effects on respiration in the rat.

    PubMed

    Stephenson, R; Liao, K S; Hamrahi, H; Horner, R L

    2001-10-01

    1. We tested two hypotheses: that respiration and metabolism are subject to circadian modulation in wakefulness, non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep; and that the effects of sleep on breathing vary as a function of time of day. 2. Electroencephalogram (EEG), neck electromyogram (EMG) and abdominal body temperature (T(b)) were measured by telemetry in six male Sprague-Dawley rats. The EEG and EMG were used to identify sleep-wake states. Ventilation (V(I)) and metabolic rate (V(CO2)) were measured by plethysmography. Recordings were made over 24 h (12:12 h light:dark) when rats were in established states of wakefulness, NREM sleep and REM sleep. 3. Statistically significant circadian rhythms were observed in V(I) and V(CO2) in each of the wakefulness, NREM sleep and REM sleep states. Amplitudes and phases of the circadian rhythms were similar across sleep-wake states. 4. The circadian rhythm in V(I) was mediated by a circadian rhythm in respiratory frequency (f(R)). Tidal volume (V(T)) was unaffected by time of day in all three sleep-wake states. 5. The 24 h mean V(I) was significantly greater during wakefulness (363.5 +/- 18.5 ml min(-1)) than during NREM sleep (284.8 +/- 11.1 ml min(-1)) and REM sleep (276.1 +/- 13.9 ml min(-1)). V(CO2) and V(T) each significantly decreased from wakefulness to NREM sleep to REM sleep. f(R) was significantly lower in NREM sleep than in wakefulness and REM sleep. 6. These data confirm that ventilation and metabolism exhibit circadian rhythms during wakefulness, and NREM and REM sleep, and refute the hypothesis that state-related effects on breathing vary as a function of time of day. We conclude that the effects of circadian rhythms and sleep-wake state on respiration and metabolic rate are additive in the rat. PMID:11579171

  18. Proteomics and circadian rhythms: It’s all about signaling!

    PubMed Central

    Mauvoisin, Daniel; Dayon, Loïc; Gachon, Frédéric; Kussmann, Martin

    2014-01-01

    1. Abstract Proteomic technologies using mass spectrometry (MS) offer new perspectives in circadian biology, in particular the possibility to study posttranslational modifications (PTMs). To date, only very few studies have been carried out to decipher the rhythmicity of protein expression in mammals with large-scale proteomics. Although signaling has been shown to be of high relevance, comprehensive characterization studies of PTMs are even more rare. This review aims at describing the actual landscape of circadian proteomics and the opportunities and challenges appearing on the horizon. Emphasis was given to signaling processes for their role in metabolic heath as regulated by circadian clocks and environmental factors. Those signaling processes are expected to be better and more deeply characterized in the coming years with proteomics. PMID:25103677

  19. Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers.

    PubMed

    Al-Turk, Walid; Al-Dujaili, Emad A S

    2016-02-01

    There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non-consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00h. In young males DHEA reduced from 541.1±101.3 (mean±sd) at 8.00h to 198.9±90.7pg/mL at 18.00h; p<0.0001, and young females from 401.6±149.5 to 215.4±95.3pg/mL; p<0.001. In older males DHEA reduced from 267.5±32.4 to 132.5±46.7pg/mL; p<0.001, and older females from 147.7±78.1 to 89.5±29.1pg/mL; p=0.05. DHEA levels on 2 non-consecutive days showed some variations but this was not significant. Aerobic exercise has significantly increased DHEA levels at 2 time points of the day (p=0.05) in male subjects. In conclusion, our study showed a clear daily circadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups. PMID:26686899

  20. Circadian rhythm of maternal blood pressure and fetal growth.

    PubMed

    Maggioni, C; Cornélissen, G; Otsuka, K; Halberg, F; Consonni, D; Nicolini, U

    2005-10-01

    This study aimed at examining any relation between the circadian variation in blood pressure (BP) in human pregnancy and fetal growth. A prospective study included 52 pregnant women monitored during the third trimester of pregnancy. There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19 pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at birth (Group 2). Ten women (five in each group) had pregnancy-induced hypertension. All women were hospitalized and followed a similar daily routine. BP was recorded with an automatic wearable device. Measurements were obtained every 20 min for 24 +/- 1 h. BP profiles were analyzed by conventional statistical methods and by cosinor, involving the least squares fit of cosine curves with an anticipated period (24 h) to the data. BP parameters, fetal outcome, demographic and obstetric characteristics were compared between the two groups. Logistic regression and multivariate analyses were used to assess factors putatively associated with fetal outcome. The circadian amplitude of diastolic BP was found to be larger in normotensive women with IUGR. As gauged by odds ratios (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1-2.8; P = 0.03) and hematocrit (OR = 1.4, 95% CI: 1.0-1.9; P = 0.04) were the only variables positively and independently associated with IUGR. In the presence of maternal hypertension, the circadian amplitude of systolic BP was negatively associated with IUGR (OR = 0.7, 95% CI: 0.5-1.0; P = 0.03). A larger circadian variation in diastolic BP, rather than a difference in the mean value of systolic or diastolic BP, was found to be statistically significantly associated with IUGR. This study adds another condition in which the circadian BP amplitude constitutes a harbinger of elevated risk, apart from an association with a shortened lifespan in the absence or presence of malignant hypertension and with an increased risk of stroke and nephropathy reported earlier. PMID:16275513

  1. Fractional desynchronization of human circadian rhythms. A method for evaluating entrainment limits and functional interdependencies.

    PubMed

    Wever, R A

    1983-02-01

    Under the influence of artificial zeitgebers, human circadian rhythms can be entrained only within limited ranges of periods; different overt rhythms may show different entrainment limits. When the period of a zeitgeber is varied slowly but continuously, entrainment limits can be evaluated precisely. An overt rhythm is synchronized to the zeitgeber only up to a certain day, or period respectively, until it breaks away from the zeitgeber and starts to freerun. The interindividual comparison among different subjects shows that the range of entrainment is positioned nearly symmetrically around the freerunning period. Its width depends strongly on the freerunning period; it increases with lengthening freerunning period. As the consequence, subjects with a freerunning period only slightly shorter than 23 h would fail to become synchronized to the natural 24-h day, whereas subjects with a freerunning period even slightly longer 28 h would become synchronized. In the intraindividual comparison, overt rhythms of different variables show different entrainment limits. For instance, rhythms in urinary excretion of different electrolytes can be dissociated for several days; the same is true with the rhythms of deep body temperature and performance. This temporal separation excludes the possibility of functional interdependencies between the variables under consideration. Consequently, results obtained with this method of fractional desynchronization do not only assist in evaluating properties of the circadian system, but also assist in the search for physiological interconnections between different variables. PMID:6835816

  2. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus

    PubMed Central

    Guilding, Clare; Hughes, Alun TL; Brown, Timothy M; Namvar, Sara; Piggins, Hugh D

    2009-01-01

    Background In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN) enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc) now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH), a site pivotal for optimal internal homeostatic regulation. Results Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc) and dorsomedial nuclei (DMH). Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2::LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT). A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT. Conclusion Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism. PMID:19712475

  3. DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression

    PubMed Central

    Sato, Fuyuki; Bhawal, Ujjal K.; Yoshimura, Tomohiro; Muragaki, Yasuteru

    2016-01-01

    Clock genes, major regulators of circadian rhythm, are involved in tumor progression. We have shown that clock genes basic helix-loop-helix (BHLH) transcription factors, differentiated embryonic chondrocyte gene 1 (DEC1/BHLHE40/Sharp2/Stra13) and DEC2 (BHLHE41/Sharp1) play important roles in circadian rhythm, cell proliferation, apoptosis, hypoxia response, various stresses, and epithelial-to-mesenchymal transition (EMT) of tumor cells. Various stresses, such as exposure to transforming growth factor-beta (TGF-β), hypoxia, cytokines, serum-free, and anti-tumor drugs affect DEC1 and DEC2 expression. An increased or decreased expression of DEC1 and DEC2 regulated tumor progression. However, DEC1 and DEC2 have opposite effects in tumor progression, where the reason behind remains unclear. We found that DEC2 has circadian expression in implanted mouse sarcoma cells, suggesting that DEC2 regulates tumor progression under circadian rhythm. In addition to that, we showed that DEC1 and DEC2 regulate target genes via positive or negative feedback system in tumor progression. We propose that DEC1 and DEC2 act as an accelerator or a brake in tumor progression. In this review, we summarize current progress of knowledge in the function of DEC1 and DEC2 genes in tumor progression. PMID:26819638

  4. Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value

    PubMed Central

    Bloch, Guy; Barnes, Brian M.; Gerkema, Menno P.; Helm, Barbara

    2013-01-01

    Circadian rhythms are ubiquitous in many organisms. Animals that are forced to be active around the clock typically show reduced performance, health and survival. Nevertheless, we review evidence of animals showing prolonged intervals of activity with attenuated or nil overt circadian rhythms and no apparent ill effects. We show that around-the-clock and ultradian activity patterns are more common than is generally appreciated, particularly in herbivores, in animals inhabiting polar regions and habitats with constant physical environments, in animals during specific life-history stages (such as migration or reproduction), and in highly social animals. The underlying mechanisms are diverse, but studies suggest that some circadian pacemakers continue to measure time in animals active around the clock. The prevalence of around-the-clock activity in diverse animals and habitats, and an apparent diversity of underlying mechanisms, are consistent with convergent evolution. We suggest that the basic organizational principles of the circadian system and its complexity encompass the potential for chronobiological plasticity. There may be trade-offs between benefits of persistent daily rhythms versus plasticity, which for reasons still poorly understood make overt daily arrhythmicity functionally adaptive only in selected habitats and for selected lifestyles. PMID:23825202

  5. Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value.

    PubMed

    Bloch, Guy; Barnes, Brian M; Gerkema, Menno P; Helm, Barbara

    2013-08-22

    Circadian rhythms are ubiquitous in many organisms. Animals that are forced to be active around the clock typically show reduced performance, health and survival. Nevertheless, we review evidence of animals showing prolonged intervals of activity with attenuated or nil overt circadian rhythms and no apparent ill effects. We show that around-the-clock and ultradian activity patterns are more common than is generally appreciated, particularly in herbivores, in animals inhabiting polar regions and habitats with constant physical environments, in animals during specific life-history stages (such as migration or reproduction), and in highly social animals. The underlying mechanisms are diverse, but studies suggest that some circadian pacemakers continue to measure time in animals active around the clock. The prevalence of around-the-clock activity in diverse animals and habitats, and an apparent diversity of underlying mechanisms, are consistent with convergent evolution. We suggest that the basic organizational principles of the circadian system and its complexity encompass the potential for chronobiological plasticity. There may be trade-offs between benefits of persistent daily rhythms versus plasticity, which for reasons still poorly understood make overt daily arrhythmicity functionally adaptive only in selected habitats and for selected lifestyles. PMID:23825202

  6. Circadian rhythms of isoprene biosynthesis in grey poplar leaves.

    PubMed

    Loivamäki, Maaria; Louis, Sandrine; Cinege, Gyöngyi; Zimmer, Ina; Fischbach, Robert J; Schnitzler, Jörg-Peter

    2007-01-01

    Isoprene (2-methyl-1,3-butadiene) emission varies diurnally in different species. In poplar (Populus spp.), it has recently been shown that the gene encoding the synthesizing enzyme for isoprene, isoprene synthase (ISPS), displays diurnal variation in expression. Working on shoot cultures of Grey poplar (Populus x canescens) placed under a different light regime in phytochambers, we showed that these variations in PcISPS gene expression, measured by quantitative real-time polymerase chain reaction, are not only due to day-night changes, but also are linked to an internal circadian clock. Measurement of additional selected isoprenoid genes revealed that phytoene synthase (carotenoid pathway) displays similar fluctuations, whereas 1-deoxy-d-xylulose 5-phosphate reductoisomerase, possibly the first committed enzyme of the 1-deoxy-d-xylulose 5-phosphate pathway, only shows light regulation. On the protein level, it appeared that PcISPS activity and protein content became reduced under constant darkness, whereas under constant light, activity and protein content of this enzyme were kept high. In contrast, isoprene emission rates under continuous irradiation displayed circadian changes as is the case for gene expression of PcISPS. Furthermore, binding assays with Arabidopsis (Arabidopsis thaliana) late elongated hypocotyl, a transcription factor of Arabidopsis involved in circadian regulation, clearly revealed the presence of circadian-determining regulatory elements in the promoter region of PcISPS. PMID:17122071

  7. Circadian Rhythms of Isoprene Biosynthesis in Grey Poplar Leaves1

    PubMed Central

    Loivamäki, Maaria; Louis, Sandrine; Cinege, Gyöngyi; Zimmer, Ina; Fischbach, Robert J.; Schnitzler, Jörg-Peter

    2007-01-01

    Isoprene (2-methyl-1,3-butadiene) emission varies diurnally in different species. In poplar (Populus spp.), it has recently been shown that the gene encoding the synthesizing enzyme for isoprene, isoprene synthase (ISPS), displays diurnal variation in expression. Working on shoot cultures of Grey poplar (Populus × canescens) placed under a different light regime in phytochambers, we showed that these variations in PcISPS gene expression, measured by quantitative real-time polymerase chain reaction, are not only due to day-night changes, but also are linked to an internal circadian clock. Measurement of additional selected isoprenoid genes revealed that phytoene synthase (carotenoid pathway) displays similar fluctuations, whereas 1-deoxy-d-xylulose 5-phosphate reductoisomerase, possibly the first committed enzyme of the 1-deoxy-d-xylulose 5-phosphate pathway, only shows light regulation. On the protein level, it appeared that PcISPS activity and protein content became reduced under constant darkness, whereas under constant light, activity and protein content of this enzyme were kept high. In contrast, isoprene emission rates under continuous irradiation displayed circadian changes as is the case for gene expression of PcISPS. Furthermore, binding assays with Arabidopsis (Arabidopsis thaliana) late elongated hypocotyl, a transcription factor of Arabidopsis involved in circadian regulation, clearly revealed the presence of circadian-determining regulatory elements in the promoter region of PcISPS. PMID:17122071

  8. Circadian Rhythms in Cognitive Processes: Implications for School Learning

    ERIC Educational Resources Information Center

    Valdez, Pablo; Ramírez, Candelaria; García, Aída

    2014-01-01

    Circadian variations have been found in cognitive processes, such as attention, working memory, and executive functions, which may explain oscillations in the performance of many tasks. These cognitive processes improve during the day and decrease during the night and early hours of the morning. Sleep deprivation further decreases these cognitive…

  9. Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

    NASA Technical Reports Server (NTRS)

    Dijk, D. J.; Neri, D. F.; Wyatt, J. K.; Ronda, J. M.; Riel, E.; Ritz-De Cecco, A.; Hughes, R. J.; Elliott, A. R.; Prisk, G. K.; West, J. B.; Czeisler, C. A.

    2001-01-01

    Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

  10. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.

    PubMed

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-11-24

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5'-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  11. Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights.

    PubMed

    Dijk, D J; Neri, D F; Wyatt, J K; Ronda, J M; Riel, E; Ritz-De Cecco, A; Hughes, R J; Elliott, A R; Prisk, G K; West, J B; Czeisler, C A

    2001-11-01

    Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep. PMID:11641138

  12. Clocks for sex: loss of circadian rhythms in ants after mating?

    NASA Astrophysics Data System (ADS)

    Sharma, Vijay Kumar; Lone, Shahnaz Rahman; Goel, Anubhuthi

    This paper describes experiments on the locomotor activity rhythm of queens of the ant species Camponotus compressus, which were performed to investigate the consequences of mating on circadian clocks. Locomotor activity rhythm of virgin and mated queens was monitored individually under constant conditions of the laboratory. The locomotor activity rhythm of virgin queens entrained to a 24 h (12:12 h) laboratory light/dark (LD) cycle and free-ran under constant dim red light (RR) with a free-running period (?) of approximately 24 h. The locomotor activity of the mated queens on the other hand was arrhythmic during the period when they were laying eggs, and robust rhythmicity appeared soon after the egg-laying phase was over. The ? of the locomotor activity rhythm of mated queens was significantly greater than that of virgin queens. These results are contrary to the commonly held belief that the role of circadian clocks in ant queens ceases after mating flights, thus suggesting that circadian clocks of ant queens are adaptively plastic and display activity patterns, perhaps depending on their physiological state and tasks in the colony.

  13. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

    PubMed Central

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-01-01

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  14. Liraglutide Activates AMPK Signaling and Partially Restores Normal Circadian Rhythm and Insulin Secretion in Pancreatic Islets in Diabetic Mice.

    PubMed

    Wang, Kexin; Sun, Yu; Lin, Peng; Song, Jun; Zhao, Ruxing; Li, Wenjuan; Hou, Xinguo; Wang, Chuan; Wang, Lingshu; Zhu, Ping; Chen, Li

    2015-01-01

    ?-Cell insufficiency plays an important role in the development of diabetes. Environmental factors, including lifestyle, play a critical role in ?-cell dysfunction. Modern lifestyles affect the inherent circadian clock in central and peripheral organs. Recent studies have demonstrated that the normal intrinsic circadian clock in islets was essential for the viability of ? cells and their insulin secretory function. Overall, however, the data are inconclusive. Our study demonstrated that the disrupted circadian rhythm of islets in streptozotocin induced type1 diabetic mice may be associated with impaired ?-cell function and glucose intolerance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, could partially restore the normal circadian rhythm and activate the 5' AMP-activated protein kinase (AMPK) signaling pathway. Our study provided evidence demonstrating that Liraglutide might restore ?-cell function and protect against the development of diabetes in a mouse model by attenuating the disruption of the intrinsic circadian rhythm in islets and by activating AMPK signaling. PMID:26040899

  15. A dynamic model of circadian rhythms in rodent tail skin temperature for comparison of drug effects

    PubMed Central

    2012-01-01

    Menopause-associated thermoregulatory dysfunction can lead to symptoms such as hot flushes severely impairing quality of life of affected women. Treatment effects are often assessed by the ovariectomized rat model providing time series of tail skin temperature measurements in which circadian rhythms are a fundamental ingredient. In this work, a new statistical strategy is presented for analyzing such stochastic-dynamic data with the aim of detecting successful drugs in hot flush treatment. The circadian component is represented by a nonlinear dynamical system which is defined by the van der Pol equation and provides well-interpretable model parameters. Results regarding the statistical evaluation of these parameters are presented. PMID:22221596

  16. Long-Lasting Effects of Sepsis on Circadian Rhythms in the Mouse

    PubMed Central

    O'Callaghan, Emma K.; Anderson, Sean T.; Moynagh, Paul N.; Coogan, Andrew N.

    2012-01-01

    Daily patterns of activity and physiology are termed circadian rhythms and are driven primarily by an endogenous biological timekeeping system, with the master clock located in the suprachiasmatic nucleus. Previous studies have indicated reciprocal relationships between the circadian and the immune systems, although to date there have been only limited explorations of the long-term modulation of the circadian system by immune challenge, and it is to this question that we addressed ourselves in the current study. Sepsis was induced by peripheral treatment with lipopolysaccharide (5 mg/kg) and circadian rhythms were monitored following recovery. The basic parameters of circadian rhythmicity (free-running period and rhythm amplitude, entrainment to a light/dark cycle) were unaltered in post-septic animals compared to controls. Animals previously treated with LPS showed accelerated re-entrainment to a 6 hour advance of the light/dark cycle, and showed larger phase advances induced by photic stimulation in the late night phase. Photic induction of the immediate early genes c-FOS, EGR-1 and ARC was not altered, and neither was phase-shifting in response to treatment with the 5-HT-1a/7 agonist 8-OH-DPAT. Circadian expression of the clock gene product PER2 was altered in the suprachiasmatic nucleus of post-septic animals, and PER1 and PER2 expression patterns were altered also in the hippocampus. Examination of the suprachiasmatic nucleus 3 months after treatment with LPS showed persistent upregulation of the microglial markers CD-11b and F4/80, but no changes in the expression of various neuropeptides, cytokines, and intracellular signallers. The effects of sepsis on circadian rhythms does not seem to be driven by cell death, as 24 hours after LPS treatment there was no evidence for apoptosis in the suprachiasmatic nucleus as judged by TUNEL and cleaved-caspase 3 staining. Overall these data provide novel insight into how septic shock exerts chronic effects on the mammalian circadian system. PMID:23071720

  17. Involvement of the Circadian Rhythm and Inflammatory Cytokines in the Pathogenesis of Rheumatoid Arthritis

    PubMed Central

    Yoshida, Kohsuke; Hashimoto, Teppei; Sakai, Yoshitada; Hashiramoto, Akira

    2014-01-01

    Among the symptoms of patients with rheumatoid arthritis (RA), joint stiffness is influenced by diurnal rhythm and reaches peak in the morning, which is a common complaint and reflects the circadian nature of disease manifestation. In addition, inflammatory cytokines, which reach peak secretion early in the morning are major players causing the morning stiffness. In this review, we explore the link between the circadian clock and inflammation, focusing on the interactions of various clock genes with the immune-pathways underlying the pathology of rheumatoid arthritis. PMID:24901009

  18. Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response

    PubMed Central

    Luna, Augustin; McFadden, Geoffrey B.; Aladjem, Mirit I.; Kohn, Kurt W.

    2015-01-01

    The circadian clock is a set of regulatory steps that oscillate with a period of approximately 24 hours influencing many biological processes. These oscillations are robust to external stresses, and in the case of genotoxic stress (i.e. DNA damage), the circadian clock responds through phase shifting with primarily phase advancements. The effect of DNA damage on the circadian clock and the mechanism through which this effect operates remains to be thoroughly investigated. Here we build an in silico model to examine damage-induced circadian phase shifts by investigating a possible mechanism linking circadian rhythms to metabolism. The proposed model involves two DNA damage response proteins, SIRT1 and PARP1, that are each consumers of nicotinamide adenine dinucleotide (NAD), a metabolite involved in oxidation-reduction reactions and in ATP synthesis. This model builds on two key findings: 1) that SIRT1 (a protein deacetylase) is involved in both the positive (i.e. transcriptional activation) and negative (i.e. transcriptional repression) arms of the circadian regulation and 2) that PARP1 is a major consumer of NAD during the DNA damage response. In our simulations, we observe that increased PARP1 activity may be able to trigger SIRT1-induced circadian phase advancements by decreasing SIRT1 activity through competition for NAD supplies. We show how this competitive inhibition may operate through protein acetylation in conjunction with phosphorylation, consistent with reported observations. These findings suggest a possible mechanism through which multiple perturbations, each dominant during different points of the circadian cycle, may result in the phase advancement of the circadian clock seen during DNA damage. PMID:26020938

  19. On the Role of Histamine Receptors in the Regulation of Circadian Rhythms

    PubMed Central

    Rozov, Stanislav V.; Porkka-Heiskanen, Tarja; Panula, Pertti

    2015-01-01

    Several lines of evidence suggest a regulatory role of histamine in circadian rhythms, but little is known about signaling pathways that would be involved in such a putative role. The aim of this study was to examine whether histamine mediates its effects on the circadian system through Hrh1 or Hrh3 receptors. We assessed both diurnal and free-running locomotor activity rhythms of Hrh1-/- and Hrh3-/- mice. We also determined the expression of Per1, Per2 and Bmal1 genes in the suprachiasmatic nuclei, several areas of the cerebral cortex and striatum under symmetric 24 h light-dark cycle at zeitgeber times 14 and 6 by using radioactive in situ hybridization. We found no differences between Hrh1-/- and wild type mice in the length, amplitude and mesor of diurnal and free-running activity rhythms as well as in expression of Per1, Per2 and Bmal1 genes in any of the examined brain structures. The amplitude of free-running activity rhythm of the Hrh3-/- mice was significantly flattened, whereas the expression of the clock genes in Hrh3-/- mice was similar to the wild type animals in all of the assessed brain structures. Therefore, the knockout of Hrh1 receptor had no effects on the circadian rhythm of spontaneous locomotion, and a knockout of Hrh3 receptor caused a substantial reduction of free-running activity rhythm amplitude, but none of these knockout models affected the expression patterns of the core clock genes in any of the studied brain structures. PMID:26660098

  20. Effects of microgravity on circadian rhythms in insects

    NASA Technical Reports Server (NTRS)

    Alpatov, A. M.; Hoban-Higgins, T. M.; Fuller, C. A.; Lazarev, A. O.; Rietveld, W. J.; Tschernyshev, V. B.; Tumurova, E. G.; Wassmer, G.; Zotov, V. A.

    1998-01-01

    The desert beetle Trigonoscelis gigas Reitt. was used as a biological model in studies that examined the effects of space flight on the circadian timing system. Results from studies aboard the Bion-10, Bion-11, and Photon-11 missions are reported. The control study is an ongoing Mir experiment. The studies indicate that the free-running period in beetles may be longer during space flight.

  1. Synchronization of Biological Clock Neurons by Light and Peripheral Feedback Systems Promotes Circadian Rhythms and Health

    PubMed Central

    Ramkisoensing, Ashna; Meijer, Johanna H.

    2015-01-01

    In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude of the SCN’s electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise) has a positive effect on amplitude. Given that the amplitude of the SCN’s electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-h rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders. PMID:26097465

  2. Synchronization of Biological Clock Neurons by Light and Peripheral Feedback Systems Promotes Circadian Rhythms and Health.

    PubMed

    Ramkisoensing, Ashna; Meijer, Johanna H

    2015-01-01

    In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude of the SCN's electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise) has a positive effect on amplitude. Given that the amplitude of the SCN's electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-h rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders. PMID:26097465

  3. Working around the clock: circadian rhythms and skeletal muscle

    PubMed Central

    Zhang, Xiping; Dube, Thomas J.

    2009-01-01

    The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to understand the contribution of circadian factors to normal metabolism, metabolic responses to muscle training, and contribution of the molecular clock in muscle-to-muscle disease (e.g., insulin resistance). Consistent with the potential for the skeletal muscle molecular clock modulating skeletal muscle physiology, there are findings in the literature that there is significant time-of-day effects for strength and metabolism. Additionally, there is some recent evidence that temporal specificity is important for optimizing training for muscular performance. While these studies do not prove that the molecular clock in skeletal muscle is important, they are suggestive of a circadian contribution to skeletal muscle function. The application of well-established models of skeletal muscle research in function and metabolism with available genetic models of molecular clock disruption will allow for more mechanistic understanding of potential relationships. PMID:19696362

  4. Robust and tunable circadian rhythms from differentially sensitive catalytic domains

    PubMed Central

    Phong, Connie; Markson, Joseph S.; Wilhoite, Crystal M.; Rust, Michael J.

    2013-01-01

    Circadian clocks are ubiquitous biological oscillators that coordinate an organism’s behavior with the daily cycling of the external environment. To ensure synchronization with the environment, the period of the clock must be maintained near 24 h even as amplitude and phase are altered by input signaling. We show that, in a reconstituted circadian system from cyanobacteria, these conflicting requirements are satisfied by distinct functions for two domains of the central clock protein KaiC: the C-terminal autokinase domain integrates input signals through the ATP/ADP ratio, and the slow N-terminal ATPase acts as an input-independent timer. We find that phosphorylation in the C-terminal domain followed by an ATPase cycle in the N-terminal domain is required to form the inhibitory KaiB•KaiC complexes that drive the dynamics of the clock. We present a mathematical model in which this ATPase-mediated delay in negative feedback gives rise to a compensatory mechanism that allows a tunable phase and amplitude while ensuring a robust circadian period. PMID:23277568

  5. Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels.

    PubMed

    Baird, A L; Coogan, A N; Siddiqui, A; Donev, R M; Thome, J

    2012-10-01

    Attention-deficit hyperactivity disorder (ADHD) in adults is associated with impaired sleep, and it has been postulated that this impairment may contribute to the psychopathology of this common condition. One key driver of sleep/wake cycles is the circadian system, which at the molecular level consists of a series of transcriptional feedback loops of clock genes, which in turn produce endocrine, physiological and behavioural outputs with a near 24 h periodicity. We set out to examine circadian rhythms at the behavioural, endocrine and molecular levels in ADHD. Adults with ADHD as well as age- and sex-matched controls were recruited. Circadian rhythms were measured by means of actigraphy for the determination of gross motor patterns, by self-sampling of oral mucosa for assessment of rhythmic expression of the clock genes BMAL1 and PER2, and by estimation of salivary cortisol and melatonin levels. Actigraphic analysis revealed significant diurnal and nocturnal hyperactivity in the ADHD group, as well as a significant shorter period of best fit for the locomotor circadian rhythm in ADHD. BMAL1 and PER2 showed circadian rhythmicity in controls with this being lost in the ADHD group. Cortisol rhythms were significantly phase delayed in the ADHD group. These findings indicate that adult ADHD is accompanied by significant changes in the circadian system, which in turn may lead to decreased sleep duration and quality in the condition. Further, modulation of circadian rhythms may represent a novel therapeutic avenue in the management of ADHD. PMID:22105622

  6. A statistical model of the human core-temperature circadian rhythm

    NASA Technical Reports Server (NTRS)

    Brown, E. N.; Choe, Y.; Luithardt, H.; Czeisler, C. A.

    2000-01-01

    We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

  7. Profiling molecular and behavioral circadian rhythms in the non-symbiotic sea anemone Nematostella vectensis

    PubMed Central

    Oren, Matan; Tarrant, Ann M.; Alon, Shahar; Simon-Blecher, Noa; Elbaz, Idan; Appelbaum, Lior; Levy, Oren

    2015-01-01

    Endogenous circadian clocks are poorly understood within early-diverging animal lineages. We have characterized circadian behavioral patterns and identified potential components of the circadian clock in the starlet sea anemone, Nematostella vectensis: a model cnidarian which lacks algal symbionts. Using automatic video tracking we showed that Nematostella exhibits rhythmic circadian locomotor activity, which is persistent in constant dark, shifted or disrupted by external dark/light cues and maintained the same rate at two different temperatures. This activity was inhibited by a casein kinase 1δ/ε inhibitor, suggesting a role for CK1 homologue(s) in Nematostella clock. Using high-throughput sequencing we profiled Nematostella transcriptomes over 48 hours under a light-dark cycle. We identified 180 Nematostella diurnally-oscillated transcripts and compared them with previously established databases of adult and larvae of the symbiotic coral Acropora millepora, revealing both shared homologues and unique rhythmic genes. Taken together, this study further establishes Nematostella as a non-symbiotic model organism to study circadian rhythms and increases our understanding about the fundamental elements of circadian regulation and their evolution within the Metazoa PMID:26081482

  8. Circadian Nature of a Rhythm Expressed by an Invertaseless Strain of Neurospora crassa1

    PubMed Central

    Sargent, Malcolm L.; Briggs, Winslow R.; Woodward, Dow O.

    1966-01-01

    A new strain of Neurospora crassa which exhibits a rhythm of conidiation when growing along an agar surface in a growth tube is described. The rhythm has been shown to be circadian for it meets the following criteria: A) the period under constant environmental conditions in the dark is about 24 hours (22.7 hours at 25°); B) the period is relatively temperature-independent (Q10 is between 0.95 and 1.21 for temperature range of 18 to 35°); C) the rhythm persists in continuous darkness at constant temperature for a minimum of 14 days without damping out; and D) the phase of the rhythm can be shifted by a single brief exposure to light. The sensitivity of this strain to light has been demonstrated further by the entrainment of the rhythm to a period of 24.0 hours using a suitable light-dark regime, and by the inhibition by light of the appearance of a rhythm; i.e., continuous conidiation occurs when the strain is subjected to continuous light. The new strain is compared to 2 other strains of Neurospora which also express a rhythm, patch and clock. Images Fig. 1 Fig. 2 Fig. 7 Fig. 8 PMID:5978549

  9. Developmental Alcohol Exposure Alters Light-Induced Phase Shifts of the Circadian Activity Rhythm in Rats

    PubMed Central

    Farnell, Yuhua Z.; West, James R.; Chen, Wei-Jung A.; Allen, Gregg C.; Earnest, David J.

    2009-01-01

    Background Developmental alcohol (EtOH) exposure produces long-term changes in the photic regulation of rat circadian behavior. Because entrainment of circadian rhythms to 24-hr light/dark cycles is mediated by phase shifting or resetting the clock mechanism, we examined whether developmental EtOH exposure also alters the phase-shifting effects of light pulses on the rat activity rhythm. Methods Artificially reared Sprague-Dawley rat pups were exposed to EtOH (4.5 g/kg/day) or an isocaloric milk formula (gastrostomy control; GC) on postnatal days 4 to 9. At 2 months of age, rats from the EtOH, GC, and suckle control groups were housed individually, and wheel-running behavior was continuously recorded first in a 12-hr light/12-hr dark photoperiod for 10 to 14 days and thereafter in constant darkness (DD). Once the activity rhythm was observed to stably free-run in DD for at least 14 days, animals were exposed to a 15-min light pulse at either 2 or 10 hr after the onset of activity [i.e., circadian time (CT) 14 or 22, respectively], because light exposure at these times induces maximal phase delays or advances of the rat activity rhythm. Results EtOH-treated rats were distinguished by robust increases in their phase-shifting responses to light. In the suckle control and GC groups, light pulses shifted the activity rhythm as expected, inducing phase delays of approximately 2 hr at CT 14 and advances of similar amplitude at CT 22. In contrast, the same light stimulus produced phase delays at CT 14 and advances at CT 22 of longer than 3 hr in EtOH-treated rats. The mean phase delay at CT 14 and advance at CT 22 in EtOH rats were significantly greater (p < 0.05) than the light-induced shifts observed in control animals. Conclusions The data indicate that developmental EtOH exposure alters the phase-shifting responses of the rat activity rhythm to light. This finding, coupled with changes in the circadian period and light/dark entrainment observed in EtOH-treated rats, suggests that developmental EtOH exposure may permanently alter the clock mechanism in the suprachiasmatic nucleus and its regulation of circadian behavior. PMID:15252288

  10. Involvement of 5-HT? receptors in vortioxetine's modulation of circadian rhythms and episodic memory in rodents.

    PubMed

    Westrich, Ligia; Haddjeri, Nasser; Dkhissi-Benyahya, Ouria; Sánchez, Connie

    2015-02-01

    Since poor circadian synchrony and cognitive dysfunction have been linked to affective disorders, antidepressants that target key 5-HT (serotonin) receptor subtypes involved in circadian rhythm and cognitive regulation may have therapeutic utility. Vortioxetine is a multimodal antidepressant that inhibits 5-HT1D, 5-HT3, 5-HT7 receptor activity, 5-HT reuptake, and enhances the activity of 5-HT1A and 5-HT1B receptors. In this study, we investigated the effects of vortioxetine on the period length of PER2::LUC expression, circadian behavior, and episodic memory, using tissue explants from genetically modified PER2::LUC mice, locomotor activity rhythm monitoring, and the object recognition test, respectively. Incubation of tissue explants from the suprachiasmatic nucleus of PER2::LUC mice with 0.1 ?M vortioxetine increased the period length of PER2 bioluminescence. Monitoring of daily wheel-running activity of Sprague-Dawley rats treated with vortioxetine (10 mg/kg, s.c.), alone or in combination with the 5-HT1A receptor agonist flesinoxan (2.5 mg/kg, s.c.) or the 5-HT7 receptor antagonist SB269970 (30 mg/kg, s.c.), just prior to activity onset revealed significant delays in wheel-running behavior. The increase in circadian period length and the phase delay produced by vortioxetine were abolished in the presence of the 5-HT7 receptor partial agonist AS19. Finally, in the object recognition test, vortioxetine (10 mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this effect was prevented by AS19 (5 mg/kg, i.p.). In conclusion, the present study shows that vortioxetine, partly via its 5-HT7 receptor antagonism, induced a significant effect on circadian rhythm and presented promnesic properties in rodents. PMID:25446573

  11. Toward a classification of medications for sleep and circadian rhythm disorders

    PubMed Central

    Thorpy, Michael J; Roth, Thomas

    2013-01-01

    While some systems classify medications according to therapeutic class, others are based on the mechanism of action of the drugs. The two main classifications of medications used to treat patients in the United States are those of the United States Pharmacopeia and US Food and Drug Administration, and they vary in their organization of the medication categories. Here we propose a taxonomy for medications used to treat sleep and circadian rhythm disorders based on symptoms and disorders. PMID:24363563

  12. A school-refuser: his rest-activity rhythm involved multiple circadian components.

    PubMed

    Chiba, Y

    1984-01-01

    In a 950-day observation, a school- refuser showed a freerunning circadian rest-activity rhythm of 24.5 h interrupted intermittently by days of irregular rest-activity cycle. The interruption may be explained by an interaction between two desynchronized rhythmic components; one is freerunning and the other is of 24.0 h. The symptoms of emotional disorder were observed more frequently during days of interruption. PMID:6723473

  13. Circadian rhythms: influences of internal and external factors on the period measured in constant conditions.

    PubMed

    Aschoff, J

    1979-03-01

    The article reviews most of the data available on the period tau of freerunning circadian rhythms, measured in constant conditions. Emphasis is placed on the effects of light intensity and ambient temperature on tau, with references to influences of other external as well as internal factors. In the introduction, examples are given of spontaneous and induced variations in tau and its dependence on the experimental history. The discussion concentrates largely on results obtained from arthropods and vertebrates. PMID:386643

  14. [Smith-Magenis syndrome is an association of behavioral and sleep/wake circadian rhythm disorders].

    PubMed

    Poisson, A; Nicolas, A; Sanlaville, D; Cochat, P; De Leersnyder, H; Rigard, C; Franco, P; des Portes, V; Edery, P; Demily, C

    2015-06-01

    Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features. PMID:25934608

  15. Phase-shifting human circadian rhythms: influence of sleep timing, social contact and light exposure

    NASA Technical Reports Server (NTRS)

    Duffy, J. F.; Kronauer, R. E.; Czeisler, C. A.

    1996-01-01

    1. Both the timing of behavioural events (activity, sleep and social interactions) and the environmental light-dark cycle have been reported to contribute to entrainment of human circadian rhythms to the 24 h day. Yet, the relative contribution of those putative behavioural synchronizers to that of light exposure remains unclear. 2. To investigate this, we inverted the schedule of rest, sedentary activity and social contact of thirty-two young men either with or without exposure to bright light. 3. On this inverted schedule, the endogenous component of the core temperature rhythm of subjects who were exposed to bright light showed a significant phase shift, demonstrating that they were adapting to the new schedule. In contrast, the core temperature rhythm of subjects who were not exposed to bright light moved on average 0.2 h later per day and after 10 days had not significantly adapted to the new schedule. 4. The direction of phase shift in the groups exposed to bright light was dependent on the time of bright light exposure, while control subjects drifted to a later hour regardless of the timing of their schedule of sleep timing, social contact and meals. 5. These results support the concept that the light-dark cycle is the most important synchronizer of the human circadian system. They suggest that inversion of the sleep-wake, rest-activity and social contact cycles provides relatively minimal drive for resetting the human circadian pacemaker. 6. These data indicate that interventions designed to phase shift human circadian rhythms for adjustment to time zone changes or altered work schedules should focus on properly timed light exposure.

  16. Sleep and circadian rhythms in long duration space flight - Antarctica as an analogue environment

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.

    1992-01-01

    The feasibility of using Antarctica as an environment for studying the impact of unusual 24 h environmental cycles (zeitgebers) on the circadian system is discussed. Adaptation of circadian rhythms and sleep of three scientists travelling from New Zealand to Antarctica during summer (which is analogous to arrival at a lunar base during the lunar day) has been studied. Data obtained indicate that sleep occurred at the same clock time, but sleep quality was poorer in Antarctica, which can be explained by the fact that the circadian system delayed by about 2 h in Antarctica, as would be expected in a weaker zeitgeber environment. It is suggested that sleep could be improved by altering patterns of exposure to the available zeitgebers to increase their effective strength.

  17. Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism

    PubMed Central

    Gnocchi, Davide; Pedrelli, Matteo; Hurt-Camejo, Eva; Parini, Paolo

    2015-01-01

    Disorders of lipid and lipoprotein metabolism and transport are responsible for the development of a large spectrum of pathologies, ranging from cardiovascular diseases, to metabolic syndrome, even to tumour development. Recently, a deeper knowledge of the molecular mechanisms that control our biological clock and circadian rhythms has been achieved. From these studies it has clearly emerged how the molecular clock tightly regulates every aspect of our lives, including our metabolism. This review analyses the organisation and functioning of the circadian clock and its relevance in the regulation of physiological processes. We also describe metabolism and transport of lipids and lipoproteins as an essential aspect for our health, and we will focus on how the circadian clock and lipid metabolism are greatly interconnected. Finally, we discuss how a deeper knowledge of this relationship might be useful to improve the recent spread of metabolic diseases. PMID:25665169

  18. Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio).

    PubMed

    Zhao, Yanbin; Fent, Karl

    2016-01-01

    Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals. PMID:26899944

  19. Cognitive Performance as a Zeitgeber: Cognitive Oscillators and Cholinergic Modulation of the SCN Entrain Circadian Rhythms

    PubMed Central

    Gritton, Howard J.; Stasiak, Ashley M.; Sarter, Martin; Lee, Theresa M.

    2013-01-01

    The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF) cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s) outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior. PMID:23441168

  20. Eyeless Mexican Cavefish Save Energy by Eliminating the Circadian Rhythm in Metabolism

    PubMed Central

    Moran, Damian; Softley, Rowan; Warrant, Eric J.

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea. PMID:25251018

  1. Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio)

    PubMed Central

    Zhao, Yanbin; Fent, Karl

    2016-01-01

    Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7–742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals. PMID:26899944

  2. The Development and Course of Bipolar Spectrum Disorders: An Integrated Reward and Circadian Rhythm Dysregulation Model

    PubMed Central

    Alloy, Lauren B.; Nusslock, Robin; Boland, Elaine M.

    2014-01-01

    In this article, we present and review the evidence for two major biopsychosocial theories of the onset and course of bipolar spectrum disorders (BSDs) that integrate behavioral, environmental, and neurobiological mechanisms: the reward hypersensitivity and the social and circadian rhythm disruption models. We describe the clinical features, spectrum, age of onset, and course of BSDs. We then discuss research designs relevant to demonstrating whether a hypothesized mechanism represents a correlate, vulnerability, or predictor of the course of BSDs, as well as important methodological issues. We next present the reward hypersensitivity model of BSD, followed by the social/circadian rhythm disruption model of BSD. For each model, we review evidence regarding whether the proposed underlying mechanism is associated with BSDs, provides vulnerability to the onset of BSDs, and predicts the course of BSDs. We then present a new integrated reward/circadian rhythm (RCR) dysregulation model of BSD and discuss how the RCR model explains the symptoms, onset, and course of BSDs. We end with recommendations for future research directions. PMID:25581235

  3. Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio)

    NASA Astrophysics Data System (ADS)

    Zhao, Yanbin; Fent, Karl

    2016-02-01

    Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7–742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals.

  4. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

    PubMed

    Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

    2015-12-15

    Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms. PMID:25662277

  5. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

    NASA Astrophysics Data System (ADS)

    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

    2015-06-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants.

  6. Nonentrained circadian rhythms of melatonin in submariners scheduled to an 18-hour day.

    PubMed

    Kelly, T L; Neri, D F; Grill, J T; Ryman, D; Hunt, P D; Dijk, D J; Shanahan, T L; Czeisler, C A

    1999-06-01

    The human circadian timing system has previously been shown to free run with a period slightly longer than 24 h in subjects living in the laboratory under conditions of forced desynchrony. In forced desynchrony, subjects are shielded from bright light and periodic time cues and are required to live on a day length outside the range of circadian entrainment. The work schedule used for most personnel aboard American submarines is 6 h on duty alternating with 12 h off duty. This imposed 18-h cycle is too short for human circadian synchronization, especially given that there is no bright-light exposure aboard submarines. However, crew members are exposed to 24-h stimuli that could mediate synchronization, such as clocks and social contacts with personnel who are living on a 24-h schedule. The authors investigated circadian rhythms of salivary melatonin in 20 crew members during a prolonged voyage on a Trident nuclear submarine. The authors found that in crew members living on the 18-h duty cycle, the endogenous rhythm of melatonin showed an average period of 24.35 h (n = 12, SD = 0.18 h). These data indicate that social contacts and knowledge of clock time are insufficient for entrainment to a 24-h period in personnel living by an 18-h rest-activity cycle aboard a submarine. PMID:10452330

  7. Circadian Rhythms and Breast Cancer: The Role of Per2 in Doxorubicin-Induced Cell Death

    PubMed Central

    Mitchell, Megan I.; Engelbrecht, Anna-Mart

    2015-01-01

    Mammalian circadian rhythms form an integral physiological system allowing for the synchronisation of all metabolic processes to daily light/dark cycles, thereby optimising their efficacy. Circadian disruptions have been implicated in the onset and progression of various cancers, including those arising in the breast. Several links between the circadian protein Per2 and DNA damage responses exist. Aberrant Per2 expression results in potent downstream effects on both cell cycle and apoptotic targets, suggestive of a tumour suppressive role for Per2. Due to the severe dose limiting side effects associated with current chemotherapeutic strategies, including the use of doxorubicin, a need for more effective adjuvant therapies to increase cancer cell susceptibility has arisen. This study was therefore aimed at characterizing the role of Per2 in normal breast epithelia (MCF-12A) and in ER? breast cancer cells (MDA-MB-231) and also at determining the role of Per2 in doxorubicin-induced cell death. In both cell lines Per2 protein expression displayed a 24-hour circadian rhythm in both cell lines. Per2 was located predominantly in the cytoplasm, with nuclear localization observed with lower cytoplasmic fluorescent intensities. Our results show that Per2 silencing effectively sensitizes the chemoresistant MDA-MB-231 breast cancer cells to the cytotoxic effects of doxorubicin. PMID:26347774

  8. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

    PubMed Central

    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

    2015-01-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

  9. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging.

    PubMed

    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y; Yang, Jian-Bo; Zheng, Lei

    2015-01-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R(2), 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

  10. [Effect of Earth magnetic field on circadian rhythm of total antioxidant capacity of human saliva in the North].

    PubMed

    Borisenkov, M F

    2007-01-01

    In the inhabitants of the North during increase of geomagnetic activity and during magnetic calm the decrease of amplitude of circadian rhythm of total antioxidant capacity of saliva is observed. The most favorable conditions to display the circadian rhythm are observed at Kp from 0,5 up to 2. The long residing in the North is connected to influence of irregularly varying geomagnetic activity causing disturbance of function of circadian and antioxidant systems that, probably, is one of the reasons of acceleration of process of aging at northerner and of higher risk of occurrence in them the age associated diseases. PMID:18383711

  11. Circadian rhythms and post-transcriptional regulation in higher plants

    PubMed Central

    Romanowski, Andrés; Yanovsky, Marcelo J.

    2015-01-01

    The circadian clock of plants allows them to cope with daily changes in their environment. This is accomplished by the rhythmic regulation of gene expression, in a process that involves many regulatory steps. One of the key steps involved at the RNA level is post-transcriptional regulation, which ensures a correct control on the different amounts and types of mRNA that will ultimately define the current physiological state of the plant cell. Recent advances in the study of the processes of regulation of pre-mRNA processing, RNA turn-over and surveillance, regulation of translation, function of lncRNAs, biogenesis and function of small RNAs, and the development of bioinformatics tools have helped to vastly expand our understanding of how this regulatory step performs its role. In this work we review the current progress in circadian regulation at the post-transcriptional level research in plants. It is the continuous interaction of all the information flow control post-transcriptional processes that allow a plant to precisely time and predict daily environmental changes. PMID:26124767

  12. Pinealectomy shortens resynchronisation times of house sparrow ( Passer domesticus) circadian rhythms

    NASA Astrophysics Data System (ADS)

    Kumar, Vinod; Gwinner, Eberhard

    2005-09-01

    In many birds periodic melatonin secretion by the pineal organ is essential for the high-amplitude self-sustained output of the circadian pacemaker, and thus for the persistence of rhythmicity in 24 h oscillations controlled by it. The elimination of the pineal melatonin rhythm, or a reduction of its amplitude, renders the circadian pacemaker a less self-sustained, often highly damped, oscillatory system. A reduction in the degree of self-sustainment of a rhythm should not only increase its range of entrainment but also shorten the resynchronization times following phase-shifts of the zeitgeber. This hypothesis has not yet been directly tested. We therefore carried out the present study in which house sparrows (Passer domesticus) were subjected to both 6-h advance and 6-h delay phase-shifts of the light-dark cycle before and after the pinealectomy, and the rhythms in locomotion and feeding were recorded. The results indicate that following the delay, but not the advance, phase shift, resynchronization times were significantly shorter after pinealectomy. The dependence of resynchronization times on the presence or absence of the pineal organ is not only of theoretical interest but might also be of functional significance in the natural life of birds. A reduction or elimination of the amplitude of the melatonin secretion rhythm by the pineal organ might be responsible for faster adjustment to changes in zeitgeber conditions in nature.

  13. Does 'anchor sleep' entrain circadian rhythms? Evidence from constant routine studies.

    PubMed Central

    Minors, D S; Waterhouse, J M

    1983-01-01

    Experiments have been performed in an isolation unit to investigate the effects of abnormal sleep-waking schedules upon circadian rhythms of renal excretion and deep-body temperature. In confirmation of previous work, nychthemeral rhythms appeared to be 'anchored' to a 24 h period if 4 h sleep was taken regularly each day, even though another 4 h was taken irregularly. The endogenous components were investigated by assessing circadian rhythmicity under constant routine conditions, that is, when rhythmic influences in the environment and sleep-waking pattern had been minimized. Analysis of the constant routine data indicated the presence of a rhythmic component which had been stabilized to a period of 24 h by the 'anchor sleep'. In addition, a delayed component was also present. The starting time of the constant routines produced a direct effect upon the rhythms, which was presumed to result from removing the 'masking' effect that sleep normally exerts upon rhythms. There was some evidence that the relative importance of the masking effect and the delayed component depended upon the variable under consideration. The implications of these findings, in terms of the effects of anchor sleep, the presence of more than one internal clock and the usefulness of constant routines, are discussed. PMID:6663508

  14. Hypoxia disrupts the expression levels of circadian rhythm genes in hepatocellular carcinoma.

    PubMed

    Yu, Chao; Yang, Sheng-Li; Fang, Xiefan; Jiang, Jian-Xin; Sun, Cheng-Yi; Huang, Tao

    2015-05-01

    Disturbance in the expression of circadian rhythm genes is a common feature in certain types of cancer, however the mechanisms mediating this disturbance remain to be elucidated. The present study aimed to investigate the effect of hypoxia on the expression of circadian rhythm genes in liver cancer cells and to identify the mechanisms underlying this effect in hepatocellular carcinoma (HCC). The HCC cell line, PLC/PRF/5. was treated with either a vehicle control or CoCl2 at 50, 100 or 200 µ? for 24 h. Following treatment, the protein expression levels of hypoxia?inducible factor (HIF)?1? and HIF?2? were detected by western blotting and the mRNA expression levels of circadian rhythm genes, including circadian locomotor output cycles kaput (Clock), brain and muscle Arnt?like 1 (Bmal1), period (Per)1, Per2, Per3, cryptochrome (Cry)1, Cry2 and casein kinase I? (CKI?), were detected by reverse transcription quantitative polymerase chain reaction (RT?qPCR). Expression plasmids containing HIF?1? or HIF?2? were transfected into the PLC/PRF/5 cells using liposomes and RT?qPCR was used to determine the effects of the transfections on the expression levels of circadian rhythm genes. Following treatment with CoCl2, the protein expression levels of HIF?1? and HIF?2? were upregulated in a CoCl2 concentration?dependent manner. The mRNA expression levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and CKI? were decreased following CoCl2 treatment (P<0.05). In the PLC/PRF/5 cells transfected with the plasmid containing HIF?1?, the mRNA expression levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and CKI? were decreased. In the PLC/PRF/5 cells transfected with the plasmid containing HIF?2?, the mRNA expression levels of Clock, Bmal1, Per1, Cry1, Cry2 and CKI? were upregulated, and the mRNA expression levels of Per2 and Per3 were downregulated (P<0.05). A hypoxic microenvironment may contribute to the disturbance in the expression of circadian genes in HCC. HIF?1? and HIF?2? are involved in this process and have redundant, but not identical effects. PMID:25591621

  15. Convergent Rhythm Generation from Divergent Cellular Mechanisms

    PubMed Central

    Rodriguez, Jason C.; Blitz, Dawn M.

    2013-01-01

    Different modulatory inputs commonly elicit distinct rhythmic motor patterns from a central pattern generator (CPG), but they can instead elicit the same pattern. We are determining the rhythm-generating mechanisms in this latter situation, using the gastric mill (chewing) CPG in the crab (Cancer borealis) stomatogastric ganglion, where stimulating the projection neuron MCN1 (modulatory commissural neuron 1) or bath applying CabPK (C. borealis pyrokinin) peptide elicits the same gastric mill motor pattern, despite configuring different gastric mill circuits. In both cases, the core rhythm generator includes the same reciprocally inhibitory neurons LG (lateral gastric) and Int1 (interneuron 1), but the pyloric (food-filtering) circuit pacemaker neuron AB (anterior burster) is additionally necessary only for CabPK rhythm generation. MCN1 drives this rhythm generator by activating in the LG neuron the modulator-activated inward current (IMI), which waxes and wanes periodically due to phasic feedback inhibition of MCN1 transmitter release. Each buildup of IMI enables the LG neuron to generate a self-terminating burst and thereby alternate with Int1 activity. Here we establish that CabPK drives gastric mill rhythm generation by activating in the LG neuron IMI plus a slowly activating transient, low-threshold inward current (ITrans-LTS) that is voltage, time, and Ca2+ dependent. Unlike MCN1, CabPK maintains a steady IMI activation, causing a subthreshold depolarization in LG that facilitates a periodic postinhibitory rebound burst caused by the regular buildup and decay of the availability of ITrans-LTS. Thus, different modulatory inputs can use different rhythm-generating mechanisms to drive the same neuronal rhythm. Additionally, the same ionic current (IMI) can play different roles under these different conditions, while different currents (IMI, ITrans-LTS) can play the same role. PMID:24227716

  16. High throughput and quantitative approaches for measuring circadian rhythms in cyanobacteria using bioluminescence

    PubMed Central

    Shultzaberger, Ryan K.; Paddock, Mark L.; Katsuki, Takeo; Greenspan, Ralph J.; Golden, Susan S.

    2016-01-01

    The temporal measurement of a bioluminescent reporter has proven to be one of the most powerful tools for characterizing circadian rhythms in the cyanobacterium Synechococcus elongatus. Primarily, two approaches have been used to automate this process: (1) detection of cell culture bioluminescence in 96-well plates by a photomultiplier tube-based plate-cycling luminometer (TopCount Microplate Scintillation and Luminescence Counter, Perkin Elmer) and (2) detection of individual colony bioluminescence by iteratively rotating a Petri dish under a cooled CCD camera using a computer-controlled turntable. Each approach has distinct advantages. The TopCount provides a more quantitative measurement of bioluminescence, enabling the direct comparison of clock output levels among strains. The computer-controlled turntable approach has a shorter set-up time and greater throughput, making it a more powerful phenotypic screening tool. While the latter approach is extremely useful, only a few labs have been able to build such an apparatus because of technical hurdles involved in coordinating and controlling both the camera and the turntable, and in processing the resulting images. This protocol provides instructions on how to construct, use, and process data from a computer-controlled turntable to measure the temporal changes in bioluminescence of individual cyanobacterial colonies. Furthermore, we describe how to prepare samples for use with the TopCount to minimize experimental noise, and generate meaningful quantitative measurements of clock output levels for advanced analysis. PMID:25662451

  17. Nonlinear dynamics of the CAM circadian rhythm in response to environmental forcing.

    PubMed

    Hartzell, Samantha; Bartlett, Mark S; Virgin, Lawrence; Porporato, Amilcare

    2015-03-01

    Crassulacean acid metabolism (CAM) photosynthesis functions as an endogenous circadian rhythm coupled to external environmental forcings of energy and water availability. This paper explores the nonlinear dynamics of a new CAM photosynthesis model (Bartlett et al., 2014) and investigates the responses of CAM plant carbon assimilation to different combinations of environmental conditions. The CAM model (Bartlett et al., 2014) consists of a Calvin cycle typical of C3 plants coupled to an oscillator of the type employed in the Van der Pol and FitzHugh-Nagumo systems. This coupled system is a function of environmental variables including leaf temperature, leaf moisture potential, and irradiance. Here, we explore the qualitative response of the system and the expected carbon assimilation under constant and periodically forced environmental conditions. The model results show how the diurnal evolution of these variables entrains the CAM cycle with prevailing environmental conditions. While constant environmental conditions generate either steady-state or periodically oscillating responses in malic acid uptake and release, forcing the CAM system with periodic daily fluctuations in light exposure and leaf temperature results in quasi-periodicity and possible chaos for certain ranges of these variables. This analysis is a first step in quantifying changes in CAM plant productivity with variables such as the mean temperature, daily temperature range, irradiance, and leaf moisture potential. Results may also be used to inform model parametrization based on the observed fluctuating regime. PMID:25542971

  18. High-throughput and quantitative approaches for measuring circadian rhythms in cyanobacteria using bioluminescence.

    PubMed

    Shultzaberger, Ryan K; Paddock, Mark L; Katsuki, Takeo; Greenspan, Ralph J; Golden, Susan S

    2015-01-01

    The temporal measurement of a bioluminescent reporter has proven to be one of the most powerful tools for characterizing circadian rhythms in the cyanobacterium Synechococcus elongatus. Primarily, two approaches have been used to automate this process: (1) detection of cell culture bioluminescence in 96-well plates by a photomultiplier tube-based plate-cycling luminometer (TopCount Microplate Scintillation and Luminescence Counter, Perkin Elmer) and (2) detection of individual colony bioluminescence by iteratively rotating a Petri dish under a cooled CCD camera using a computer-controlled turntable. Each approach has distinct advantages. The TopCount provides a more quantitative measurement of bioluminescence, enabling the direct comparison of clock output levels among strains. The computer-controlled turntable approach has a shorter set-up time and greater throughput, making it a more powerful phenotypic screening tool. While the latter approach is extremely useful, only a few labs have been able to build such an apparatus because of technical hurdles involved in coordinating and controlling both the camera and the turntable, and in processing the resulting images. This protocol provides instructions on how to construct, use, and process data from a computer-controlled turntable to measure the temporal changes in bioluminescence of individual cyanobacterial colonies. Furthermore, we describe how to prepare samples for use with the TopCount to minimize experimental noise and generate meaningful quantitative measurements of clock output levels for advanced analysis. PMID:25662451

  19. Circadian rhythm of mechanically mediated differentiation of osteoblasts

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Klingler, E.

    1984-01-01

    The differential of osteoblasts in response to orthodontic pressure in the periodontal ligament of the maxillary-first-molar periodontal ligaments of 12-h-light/dark-entrained 7-wk-old male Simonsen outbred rats is measured by (H-3)-Thymidine nuclear-volume morphometry (Roberts et al., 1983) at hourly intervals throughout the circadian cycle. The results are presented in graphs and discussed. Preosteoblast large nuclei (D-cells) are found to synthesize DNA mainly in light and to divide in the following dark period, while small-nucleus osteoprogenitors (A-cells) synthesize in darkness and divide in light. These findings are seen as consistent with a model in which the sequence of proliferation and differentiation requires at least 60 h (five 12-h periods) and the shift from A to D cells lasts about 19 h.

  20. Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing.

    PubMed

    Fernandez, Fabian; Lu, Derek; Ha, Phong; Costacurta, Patricia; Chavez, Renee; Heller, H Craig; Ruby, Norman F

    2014-11-14

    Chronic circadian dysfunction impairs declarative memory in humans but has little effect in common rodent models of arrhythmia caused by clock gene knockouts or surgical ablation of the suprachiasmatic nucleus (SCN). An important problem overlooked in these translational models is that human dysrhythmia occurs while SCN circuitry is genetically and neurologically intact. Siberian hamsters (Phodopus sungorus) are particularly well suited for translational studies because they can be made arrhythmic by a one-time photic treatment that severely impairs spatial and recognition memory. We found that once animals are made arrhythmic, subsequent SCN ablation completely rescues memory processing. These data suggest that the inhibitory effects of a malfunctioning SCN on cognition require preservation of circuitry between the SCN and downstream targets that are lost when these connections are severed. PMID:25395537

  1. Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

    PubMed Central

    2013-01-01

    Background Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. PMID:23521808

  2. [Peculiarities of circadian rhythms in plants from different geographical latitudes].

    PubMed

    Mayer, W

    1966-09-01

    1 Two species of plants (Taraxacum arcticum and Arnica angustifolia), collected in Spitsbergen (geogr. latitude 76-80 degrees) exhibit endogenous circadian leaf movements but also movements with shorter periods. Astragalus frigidus, A. alpinus and Hedysarum hedysaroides, collected in arctic regions of continental Europe, also show endogenous diurnal leaf movements. 2. In most of the species tested, there was no difference in the length of the free running periods of plants from arctic and Central-European regions. This is also the case when individuals of the same species collected in different regions are compared. However, in Taraxacum arcticum the period is shorter than in T. officinale In general, under constant conditions the circadian oscillations of arctic plants persist for a shorter period than those of other plants. 3. The free running periods of several of the investigated species from tropical regions are much longer than 24 hours, i.e., much longer than those of species from Central-European and arctic regions. 4. The free running periods of several tropical species are temperature-independent (Erythrina senegalensis, Albizzia lophanta, Rhynchosia memmonia, Vigna catjang, Phaseolus multiflorus). In other tropical species, however, the periods decrease rather strongly with increasing temperature (Phaseolus mungo, Canavalia obtusifolia, Clitoria ternatea, Dolichos lablab, Vigna sesquipedalis, Dolichos zebra). The temperature does not influence the amplitudes in Phaseolus mungo and Vigna sesquipedalis, but it strongly influences the amplitudes in Erythrina senegalensis, in LD-cycles as well as in continuous light. 5. The arctic plant Astragalus frigidus still shows free running oscillations at 12°C, whereas several tropical species oscillate only at temperatures above 17°C. 6. The differences in the periods of tropical and non-tropical species (see under [3]) disappear if the plants are compared not at the same temperature but at temperatures which are optimal for them. If tropical plants are tested 27°C and Central-European and arctic species at 17°C, the periods always approach the value of 24 hours. PMID:24557984

  3. Circadian and ultradian temperature rhythms of lactating dairy cows.

    PubMed

    Bitman, J; Lefcourt, A; Wood, D L; Stroud, B

    1984-05-01

    Thermistors were implanted in the right front quarter of udder and peritoneal cavity of six lactating Holstein cows to investigate whether udder temperature is regulated independently of deep body temperature. Sequential measurements of udder, body, chamber, and outdoor temperatures were every 1.4 min (1024 readings/probe per 24 h) by digital computer. Cows were housed (except for short exercise periods) in a chamber at 16.7 +/- .3 degrees C, lights on 0730 to 1630 and 2100 to 0200 h. Temperature was monitored continuously for 5 days in three cows in early lactation and in three cows in late lactation. Udder temperature was closely correlated with body temperature (body and udder temperatures were 38.8 +/- .1 degree C). Five of six cows showed two patterns of temperature variation: a 24-h pattern with two troughs each day--minimum at 0930 to 1100 h, increase 1.0 degree C by 1200 to 1300 h, decline 1 degree C from 2000 to 2200 h, second minimum by 2100 to 2200 h, and constant elevation from 2300 to 0800 h (peak to trough, 1.23 +/- .09 degrees C); and superimposed upon the 24-h rhythm was an ultradian rhythm with an approximate 90 min period (peak to trough, .5 +/- .03 degrees C). Rhythmicity of udder and body temperatures should be considered in research on the chronobiology of milk secretion and mastitis. PMID:6736397

  4. Circadian sleep-wake rhythm of older adults with intellectual disabilities.

    PubMed

    Maaskant, Marijke; van de Wouw, Ellen; van Wijck, Ruud; Evenhuis, Heleen M; Echteld, Michael A

    2013-04-01

    The circadian sleep-wake rhythm changes with aging, resulting in a more fragmented sleep-wake pattern. In individuals with intellectual disabilities (ID), brain structures regulating the sleep-wake rhythm might be affected. The aims of this study were to compare the sleep-wake rhythm of older adults with ID to that of older adults in the general population, and to investigate which factors are associated with the sleep-wake rhythm in older adults with ID. This study is part of the 'Healthy Aging and Intellectual Disabilities' study (HA-ID). We applied actigraphy in 551 persons with ID and 58 persons in the general population, aged 50 years and over. Outcome measures were stability (interdaily stability), fragmentation (intradaily variability) and amplitude (relative amplitude) of the sleep-wake rhythm. Compared to older adults in the general population, the sleep-wake rhythm of older adults with ID was significantly less stable (p=0.03), more fragmented (p<0.001) and had a lower relative amplitude (p<0.001). Multivariate regression analysis revealed that higher age, dementia, depression, visual impairment, severe hearing impairment, epilepsy and spasticity are independently associated with a more disturbed sleep-wake rhythm in this group. The sleep-wake rhythm is more stable in females and those living at a setting for more intensive care. Higher physical activity levels are strongly associated with both a less fragmented (p<0.001) and a more stable (p<0.001) sleep-wake rhythm. Higher age, dementia and depression are also associated with the sleep-wake rhythm in the general population. Neurological and sensory impairments that were associated with the sleep-wake rhythm in older adults with ID, are frequent known conditions in the ID population. Further research should focus on which factors specifically influence the sleep-wake rhythm in older adults with ID, and on the effects of more physical daytime activity on the sleep-wake rhythm in this population. PMID:23376049

  5. Microglia modulate respiratory rhythm generation and autoresuscitation.

    PubMed

    Lorea-Hernández, Jonathan-Julio; Morales, Teresa; Rivera-Angulo, Ana-Julia; Alcantara-Gonzalez, David; Peña-Ortega, Fernando

    2016-04-01

    Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBötzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation. GLIA 2016;64:603-619. PMID:26678570

  6. Masking of the circadian rhythms of heart rate and core temperature by the rest-activity cycle in man

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Connell, Linda J.; Graeber, R. Curtis

    1986-01-01

    Experiments were conducted to estimate the magnitude of the masking effect produced in humans by alternate periods of physical activity and rest or sleep on the circadian rhythms of heart rate and core temperature. The heart rate, rectal temperature, and nondominant wrist activity were monitored in 12 male subjects during 6 days of normal routine at home and during 6 days of controlled bed-rest regimen. The comparisons of averaged waveforms for the activity, heart rate, and temperature indicated that about 45 percent of the range of the circadian heart rate rhythm during normal routine and about 14 percent of the range of the circadian temperature rhythm were attributable to the effects of activity. The smaller effect of activity on the temperature rhythm may be partially attributable to the fact that core temperature is being more rigorously conserved than heart rate, at least during moderate exercise.

  7. The Effects of Hydrogen Peroxide on the Circadian Rhythms of Microcystis aeruginosa

    PubMed Central

    Yu, Shuqiong; Pan, Xiangjie; Wu, Tao; Fu, Zhengwei

    2012-01-01

    Background The cyanobacterium Microcystis aeruginosa is one of the principal bloom-forming cyanobacteria present in a wide range of freshwater ecosystems. M. aeruginosa produces cyanotoxins, which can harm human and animal health. Many metabolic pathways in M. aeruginosa, including photosynthesis and microcystin synthesis, are controlled by its circadian rhythms. However, whether xenobiotics affect the cyanobacterial circadian system and change its growth, physiology and biochemistry is unknown. We used real-time PCR to study the effect of hydrogen peroxide (H2O2) on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD) cycle. Results The results revealed that H2O2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA) and significantly decreases the transcript levels of kaiB, kaiC and sasA. H2O2 treatment also decreased the transcription of circadian genes, such as photosynthesis-related genes (psaB, psbD1 and rbcL) and microcystin-related genes (mcyA, mcyD and mcyH), and changed their circadian expression patterns. Moreover, the physiological functions of M. aeruginosa, including its growth and microcystin synthesis, were greatly influenced by H2O2 treatment during LD. These results indicate that changes in the cyanobacterial circadian system can affect its physiological and metabolic pathways. Conclusion Our findings show that a xenobiotic can change the circadian expression patterns of its clock genes to influence clock-controlled gene regulation, and these influences are evident at the level of cellular physiology. PMID:22413018

  8. Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man

    SciTech Connect

    Pooler, P.A.; Duane, W.C.

    1988-09-01

    In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from (26-14C)cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man.

  9. Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

    PubMed Central

    Seroka, Cheryl D; Johnson, Cynthia E; Heideman, Paul D

    2008-01-01

    Background Variation in circadian rhythms and nocturnality may, hypothetically, be related to or independent of genetic variation in photoperiodic mediation of seasonal changes in physiology and behavior. We hypothesized that strain variation in photoperiodism between photoperiodic F344 rats and nonphotoperiodic Harlan Sprague Dawley (HSD) rats might be caused by underlying variation in clock function. We predicted that HSD rats would have more activity during the day or subjective day, longer free-running rhythms, poor entrainment to short day length, and shorter duration of activity, traits that have been associated with nonphotoperiodism in other laboratory rodent species, relative to F344 rats. An alternative hypothesis, that differences are due to variation in melatonin secretion or responses to melatonin, predicts either no such differences or inconsistent combinations of differences. Methods We tested these predictions by examining activity rhythms of young male F344 and HSD rats given access to running wheels in constant dark (DD), short day length (L8:D16; SD), and long day length (L16:D8; LD). We compared nocturnality (the proportion of activity during night or subjective night), duration of activity (alpha), activity onset and offset, phase angle of entrainment, and free running rhythms (tau) of F344 and HSD rats. Results HSD rats had significantly greater activity during the day, were sometimes arrhythmic in DD, and had significantly longer tau than F344 rats, consistent with predictions. However, HSD rats had significantly longer alpha than F344 rats and both strains entrained to SD, inconsistent with predictions. Conclusion The ability of HSD rats to entrain to SD, combined with longer alpha than F344 rats, suggests that the circadian system of HSD rats responds correctly to SD. These data offer best support for the alternative hypothesis, that differences in photoresponsiveness between F344 and HSD rats are caused by non-circadian differences in melatonin secretion or the response to melatonin. PMID:18782448

  10. Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability.

    PubMed

    Yamamoto, Naomune; Otsuka, Kuniaki; Kubo, Yutaka; Hayashi, Mitsutoshi; Mizuno, Koh; Ohshima, Hiroshi; Mukai, Chiaki

    2015-04-01

    We evaluated their circadian rhythms using data from electrocardiographic records and examined the change in circadian period related to normal RR intervals for astronauts who completed a long-term (?6-month) mission in space. The examinees were seven astronauts, five men and two women, from 2009 to 2010. Their mean?±?SD age was 52.0?±?4.2 years (47-59?yr). Each stayed in space for more than 160 days; their average length of stay was 172.6?±?14.6 days (163-199 days). We conducted a 24-h Holter electrocardiography before launch (Pre), at one month after launch (DF1), at two months after launch (DF2), at two weeks before return (DF3), and at three months after landing (Post), comparing each index of frequency-domain analysis and 24-h biological rhythms of the NN intervals (normal RR intervals). Results show that the mean period of Normal Sinus (NN) intervals was within 24?±?4?h at each examination. Inter-individual variability differed among the stages, being significantly smaller at DF3 (Pre versus DF1 versus DF3 versus Post?=?22.36?±?2.50 versus 25.46?±?4.37 versus 22.46?±?1.75 versus 26.16?±?7.18?h, p?circadian rhythms were disturbed until one month had passed in space, well-scheduled sleep and wake rhythms and meal times served as synchronizers. PMID:25392280

  11. Effects of Circadian Rhythm on Power, Force, and Hormonal Response in Young Men.

    PubMed

    Hatfield, Disa L; Nicoll, Justin X; Kraemer, William J

    2016-03-01

    Hatfield, DL, Nicoll, JX, and Kraemer, WJ. Effects of circadian rhythm on power, force, and hormonal response in young men. J Strength Cond Res 30(3): 725-732, 2016-Circadian rhythms (CRs) persist in many physiological systems related to performance. The effects of circadian patterns on dynamic muscular power are minimal and conflicting. Furthermore, no study to date has investigated the effect of CR on bench press throws (BPTs) despite its popularity as a modality to increase muscular power. The purpose of this study was to examine the effects of circadian variations on muscular power output and hormonal changes in men. College aged men (n = 7, age: 23.6 ± 1.3 years, height: 179.9 ± 5.4 cm, and body mass: 81.5 ± 19.7 kg.) were recruited for this repeated measures study. Testing occurred at 4 different times of day (04:00, 10:00, 16:00, and 22:00 hours). Testosterone (T) and cortisol (C) hand dynamometer strength (GS), heart rate (HR), mental readiness (MR), BPT and squat jumps (SJs), power (P), and force (F) were measured at each time point. Statistical significance was set at (p ≤ 0.05). There were no significant differences in HR, MR, and GS among all time points. There were no decrements in P or F in BPT or SJ among any time point (p ≥ 0.05). Testosterone and C decreased significantly throughout the day (p ≤ 0.05). Although P and F output differed at various percentages of 1 repetition maximum, they were not affected by circadian pattern, such that muscular performance was not impaired at any time point. Practical implications of these data indicate that high force and power exercises using BPT or SJ may be performed any time of day without detrimental decreases in acute performance. PMID:26466129

  12. Altered circadian rhythms of natural killer (NK) cell activity in patients with autoimmune rheumatic diseases.

    PubMed

    Masera, R G; Carignola, R; Staurenghi, A H; Sartori, M L; Lazzero, A; Griot, G; Angeli, A

    1994-01-01

    Natural Killer (NK) cells are a lymphocyte subset actively involved in cytotoxicity against tumor-transformed and virus-infected cells; they are a reliable model for the study of neuroendocrine-immune interactions. In previous works we demonstrated that in healthy subjects NK activity of peripheral blood mononuclear cells (PBMC) and susceptibility to endogenous modifiers display statistically validated circadian rhythms. In rheumatoid arthritis (RA) and in other autoimmune rheumatic diseases abnormalities of the circadian rhythm of serum cortisol and altered levels of NK cell activity have been reported. We evaluated the circadian pattern of NK cell activity in 7 hospitalized patients with autoimmune rheumatic diseases (4 RA, 1 scleroderma, 2 mixed connective tissue disease). Temporal variations of in vitro responses to either positive recombinant (immune interferon, r IFN-gamma IFN-gamma: 650 IU/ml; recombinant interleukin-2, r IL-2 IL-2: 100 IU/ml) or negative (cortisol: 10(-6) M) modifiers were also studied. Blood was drawn at 4h intervals for 24 h, starting at 0800. PBMC preparations were immediately separated and incubated for 20h in the presence or absence of modifiers. NK activity was assessed with a direct non-radiometric 4h cytolytic assay, using K 562 cells as targets. Significant circadian variations of spontaneous NK activity were documented only in women with RA, with a peak in the evening hours and a minimum in the night or in the early morning (p < 0.05, PR 51.5%, phi 1829). Population-mean cosinor analysis did not yield detection of significant circadian variations of in vitro responsiveness to modifiers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7924633

  13. Circadian Disruption Alters the Effects of Lipopolysaccharide Treatment on Circadian and Ultradian Locomotor Activity and Body Temperature Rhythms of Female Siberian Hamsters.

    PubMed

    Prendergast, Brian J; Cable, Erin J; Stevenson, Tyler J; Onishi, Kenneth G; Zucker, Irving; Kay, Leslie M

    2015-12-01

    The effect of circadian rhythm (CR) disruption on immune function depends on the method by which CRs are disrupted. Behavioral and thermoregulatory responses induced by lipopolysaccharide (LPS) treatment were assessed in female Siberian hamsters in which circadian locomotor activity (LMA) rhythms were eliminated by exposure to a disruptive phase-shifting protocol (DPS) that sustains arrhythmicity even when hamsters are housed in a light-dark cycle. This noninvasive treatment avoids genome manipulations and neurological damage associated with other models of CR disruption. Circadian rhythmic (RHYTH) and arrhythmic (ARR) hamsters housed in a 16L:8D photocycle were injected with bacterial LPS near the onset of the light (zeitgeber time 1; ZT1) or dark (ZT16) phase. LPS injections at ZT16 and ZT1 elicited febrile responses in both RHYTH and ARR hamsters, but the effect was attenuated in the arrhythmic females. In ZT16, LPS inhibited LMA in the dark phase immediately after injection but not on subsequent nights in both chronotypes; in contrast, LPS at ZT1 elicited more enduring (~4 day) locomotor hypoactivity in ARR than in RHYTH hamsters. Power and period of dark-phase ultradian rhythms (URs) in LMA and Tb were markedly altered by LPS treatment, as was the power in the circadian waveform. Disrupted circadian rhythms in this model system attenuated responses to LPS in a trait- and ZT-specific manner; changes in UR period and power are novel components of the acute-phase response to infection that may affect energy conservation. PMID:26566981

  14. Ecdysis behaviors and circadian rhythm of ecdysis in the stick insect, Carausius morosus

    PubMed Central

    Wadsworth, Tracy; Carriman, Andrew; Gutierrez, Alba A.; Moffatt, Christopher; Fuse, Megumi

    2014-01-01

    Successful ecdysis in insects depends on proper timing and sequential activation of an elaborate series of motor programs driven by a relatively conserved network of neuropeptides. The behaviors must be activated at the appropriate times to ensure successful loosening and shedding of the old cuticle, and can be influenced by environmental cues in the form of immediate sensory feedback and by circadian rhythms. We assessed the behaviors, components of the neural network and the circadian basis of ecdysis in the stick insect, Carausius morosus. C. morosus showed many of the characteristic pre-ecdysis and ecdysis behaviors previously described in crickets and locusts. Ecdysis was described in three phases, namely the (i) preparatory or pre-ecdysis phase, (ii) the ecdysial phase, and (iii) the post-ecdysis or exuvial phase. The frequencies of pushups and sways during the preparatory phase were quantified as well as durations of all the phases. The regulation of ecdysis appeared to act via elevation of cGMP, as described in many other insects, although eclosion hormone-like immunoreactivity was not noted using a lepidopteran antiserum. Finally, C. morosus showed a circadian rhythm to the onset of ecdysis, with ecdysis occurring just prior or at lights on. Ecdysis could be induced precociously with mechanical stimulation. PMID:25450561

  15. Altered Circadian Rhythm and Metabolic Gene Profile in Rats Subjected to Advanced Light Phase Shifts

    PubMed Central

    Herrero, Laura; Valcarcel, Lorea; da Silva, Crhistiane Andressa; Albert, Nerea; Diez-Noguera, Antoni; Cambras, Trinitat; Serra, Dolors

    2015-01-01

    The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level. PMID:25837425

  16. Circadian cycles are the dominant transcriptional rhythm in the intertidal mussel Mytilus californianus

    PubMed Central

    Connor, Kwasi M.; Gracey, Andrew Y.

    2011-01-01

    Residents in the marine intertidal, the zone where terrestrial and marine habitats converge, inhabit an environment that is subject to both the 24-h day and night daily rhythm of the terrestrial earth and also the 12.4-h ebb and flow of the tidal cycle. Here, we investigate the relative contribution of the daily and tidal cycle on the physiology of intertidal mussels, Mytilus californianus, by monitoring rhythms of gene expression in both simulated and natural tidal environments. We report that >40% of the transcriptome exhibits rhythmic gene expression, and that depending on the specific tidal conditions, between 80% and 90% of the rhythmic transcripts follow a circadian expression pattern with a period of 24 to 26 h. Consistent with the dominant effect of the circadian cycle we show that the expression of clock genes oscillates with a 24-h period. Our data indicate that the circadian 24-h cycle is the dominant driver of rhythmic gene expression in this intertidal inhabitant despite the profound environmental and physiological changes associated with aerial exposure during tidal emergence. PMID:21911390

  17. Effects of square-wave and simulated natural light-dark cycles on hamster circadian rhythms

    NASA Technical Reports Server (NTRS)

    Tang, I. H.; Murakami, D. M.; Fuller, C. A.

    1999-01-01

    Circadian rhythms of activity (Act) and body temperature (Tb) were recorded from male Syrian hamsters under square-wave (LDSq) and simulated natural (LDSN, with dawn and dusk transitions) light-dark cycles. Light intensity and data sampling were under the synchronized control of a laboratory computer. Changes in reactive and predictive onsets and offsets for the circadian rhythms of Act and Tb were examined in both lighting conditions. The reactive Act onset occurred 1.1 h earlier (P < 0.01) in LDSN than in LDSq and had a longer alpha-period (1.7 h; P < 0.05). The reactive Tb onset was 0.7 h earlier (P < 0.01) in LDSN. In LDSN, the predictive Act onset advanced by 0.3 h (P < 0.05), whereas the Tb predictive onset remained the same as in LDSq. The phase angle difference between Act and Tb predictive onsets decreased by 0.9 h (P < 0.05) in LDSN, but the offsets of both measures remained unchanged. In this study, animals exhibited different circadian entrainment characteristics under LDSq and LDSN, suggesting that gradual and abrupt transitions between light and dark may provide different temporal cues.

  18. Circadian rhythms of clock gene expression in the cerebellum of serotonin-deficient Pet-1 knockout mice.

    PubMed

    Paulus, Erin V; Mintz, Eric M

    2016-01-01

    Serotonin plays an important role in the central regulation of circadian clock function. Serotonin levels are generally higher in the brain during periods of high activity, and these periods are in turn heavily regulated by the circadian clock located in the suprachiasmatic nucleus. However, the role of serotonin as a regulator of circadian rhythms elsewhere in the brain has not been extensively examined. In this study, we examined circadian rhythms of clock gene expression in the cerebellum in mice lacking the Pet-1 transcription factor, which results in a developed brain that is deficient in serotonin neurons. If serotonin helps to synchronize rhythms in brain regions other than the suprachiasmatic nucleus, we would expect to see differences in clock gene expression in these serotonin deficient mice. We found minor differences in the expression of Per1 and Per2 in the knockout mice as compared to wild type, but these differences were small and of questionable functional importance. We also measured the response of cerebellar clocks to injections of the serotonin agonist 8-OH-DPAT during the early part of the night. No effect on clock genes was observed, though the immediate-early gene Fos showed increased expression in wild type mice but not the knockouts. These results suggest that serotonin is not an important mediator of circadian rhythms in the cerebellum in a way that parallels its regulation of the circadian clock in the suprachiasmatic nucleus. PMID:26529643

  19. Mistimed wheel running interferes with re-entrainment of circadian Per1 rhythms in the mouse skeletal muscle and lung.

    PubMed

    Yamanaka, Yujiro; Honma, Sato; Honma, Ken-Ichi

    2016-03-01

    Previously, we showed the acceleration of re-entrainment to 8-h phase-advanced light/dark cycles (LD) in the circadian Per1 expression rhythms of the mouse lung and skeletal muscle by 3-h wheel running (WR) at the beginning of shifted dark phase. In the present study, the effects of WR at the end of shifted dark phase were examined on the re-entrainment in mice. LD was advanced by shortening and was delayed by lengthening the first light period in the phase-advance and phase-delay protocol, respectively. Shifted LD was continued for 4 days, which was followed by constant darkness (DD). Per1 expression was measured in the cultured tissues obtained on the first day of DD from mice carrying a bioluminescence reporter of Per1 expression. In the phase-advance protocol, re-entrainment was not influenced by WR in any circadian rhythm examined. In the phase-delay protocol, re-entrainment of the circadian locomotor rhythm was not affected by WR. However, re-entrainment of circadian Per1 rhythm was significantly decelerated in the skeletal muscle and lung. These findings indicate that the effects of WR on re-entrainment depend on the time of day and the peripheral tissues. Mistimed WR interferes with re-entrainment of circadian rhythms in the lung and skeletal muscle. PMID:26818910

  20. Disruption of cardiovascular circadian rhythms in mice post myocardial infarction: relationship with central angiotensin II receptor expression

    PubMed Central

    Mousa, Tarek M.; Schiller, Alicia M.; Zucker, Irving H.

    2014-01-01

    Abstract Angiotensin II (Ang II) is well known to participate in the abnormal autonomic cardiovascular control that occurs during the development of chronic heart failure (CHF). Disrupted cardiovascular circadian rhythm in CHF is also well accepted; however, the mechanisms underlying and the role of central Ang II type 1 receptors (AT1R) and oxidative stress in mediating such changes are not clear. In a post myocardial infarction (MI) CHF mouse model we investigated the circadian rhythm for mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS) following MI. The cardiovascular parameters represent the middle 6?h averages during daytime (6:00–18:00) and nighttime (18:00–6:00). HR increased with the severity of CHF reaching its maximum by 12 weeks post?MI; loss of circadian HR and BRS rhythms were observed as early as 4 weeks post?MI in conjunction with a significant blunting of the BRS and an upregulation in the AT1R and gp91phox proteins in the brainstem. Loss of MAP circadian rhythm was observed 8 weeks post?MI. Circadian AT1R expression was demonstrated in sham animals but was lost 8 weeks following MI. Losartan reduced AT1R expression in daytime (1.18 ± 0.1 vs. 0.85 ± 0.1; P < 0.05) with a trend toward a reduction in the AT1R mRNA expression in the nighttime (1.2 ± 0.1 vs. 1.0 ± 0.1; P > 0.05) but failed to restore circadian variability. The disruption of circadian rhythm for HR, MAP and BRS along with the upregulation of AT1 and gp91phox suggests a possible role for central oxidative stress as a mediator of circadian cardiovascular parameters in the post?MI state. PMID:25413327

  1. Corkscrews and singularities in fruitflies - Resetting behavior of the circadian eclosion rhythm.

    NASA Technical Reports Server (NTRS)

    Winfree, A. T.

    1971-01-01

    Description of experiments undertaken to define the phase-resetting behavior of the circadian rhythm of pupal eclosion in populations of fruitflies. An attempt is made to determine how and why the resetting response depends on the duration of a standard perturbation as well as on the time at which it is given. Plotting a three-dimensional graph of the measured emergence centroids vs the stimulus variables, the data are found to spiral up around a vertical rotation axis. Using a computer, a smooth surface, called the resetting surface, which approximately fits the helicoidal cloud of data points, is obtained and is shown to be best described as a vertical corkscrew linking together tilted planes. This corkscrew feature of the resetting surface is taken to indicate that there is an isolated perturbation following which there is either no circadian rhythm of emergence in the steady state, or one of unpredictable phase. A hypothesis concerning the clock dynamics underlying the eclosion rhythm is briefly sketched which encompasses the main features of known resetting data using single discrete pulses of any perturbing agent.

  2. Tick-tock-tick-tock: the impact of circadian rhythm disorders on cardiovascular health and wellness.

    PubMed

    Gamaldo, Charlene E; Chung, Youjin; Kang, Yu Min; Salas, Rachel Marie E

    2014-12-01

    Humans spend a third of their lives asleep. A well-balanced synchrony between sleep and wakefulness is needed to maintain a healthy lifestyle. Optimal sleep is based on an individual's inherent sleep requirement and circadian rhythm. If either one or both of these critical elements are disrupted, daytime dysfunction, non-restorative sleep, and/or reduced sense of well-being may result. While the medical community is more familiar with sleep disorders such as sleep apnea, insomnia, and narcolepsy, circadian rhythm sleep wake disorders (CRSWDs) are less known, despite these being common within the general population. CRSWDs are comprised of the following: shiftwork disorder, delayed sleep phase disorder, advanced sleep phase disorder, jet lag disorder, non-24-hour sleep-wake disorder, and irregular sleep-wake rhythm disorder. In general, a CRSWD results when there is misalignment between the sleep pattern and the desired sleep schedule, dictated by work, family, and social schedules. Subsequently, patients have difficulty falling asleep, maintaining sleep, and/or experience poor quality sleep predisposing them to insomnia or excessive sleepiness. In this article, we review the core concepts related to sleep, and sleep deprivation in the context of CRSWDs. PMID:25492836

  3. The parathyroid hormone circadian rhythm is truly endogenous--a general clinical research center study

    NASA Technical Reports Server (NTRS)

    el-Hajj Fuleihan, G.; Klerman, E. B.; Brown, E. N.; Choe, Y.; Brown, E. M.; Czeisler, C. A.

    1997-01-01

    While circulating levels of PTH follow a diurnal pattern, it has been unclear whether these changes are truly endogenous or are dictated by external factors that themselves follow a diurnal pattern, such as sleep-wake cycles, light-dark cycles, meals, or posture. We evaluated the diurnal rhythm of PTH in 11 normal healthy male volunteers in our Intensive Physiologic Monitoring Unit. The first 36 h spent under baseline conditions were followed by 28-40 h of constant routine conditions (CR; enforced wakefulness in the strict semirecumbent position, with the consumption of hourly snacks). During baseline conditions, PTH levels followed a bimodal diurnal rhythm with an average amplitude of 4.2 pg/mL. A primary peak (t1max) occurred at 0314 h, and the secondary peak (t2max) occurred at 1726 h, whereas the primary and secondary nadirs (t1min and t2min) took place, on the average, at 1041 and 2103 h, respectively. This rhythm was preserved under CR conditions, albeit with different characteristics, thus confirming its endogenous nature. The serum ionized calcium (Cai) demonstrated a rhythm in 3 of the 5 subjects studied that varied widely between individuals and did not have any apparent relation to PTH. Urinary calcium/creatinine (UCa/Cr), phosphate/Cr (UPO4/Cr), and sodium/Cr (UNa/Cr) ratios all followed a diurnal rhythm during the baseline day. These rhythms persisted during the CR, although with different characteristics for the first two parameters, whereas that of UNa/Cr was unchanged. In general, the temporal pattern for the UCa/Cr curve was a mirror image of the PTH curve, whereas the UPO4/Cr pattern moved in parallel with the PTH curve. In conclusion, PTH levels exhibit a diurnal rhythm that persists during a CR, thereby confirming that a large component of this rhythm is an endogenous circadian rhythm. The clinical relevance of this rhythm is reflected in the associated rhythms of biological markers of PTH effect at the kidney, namely UCa/Cr and UPO4/Cr.

  4. Drosophila circadian rhythms in seminatural environments: Summer afternoon component is not an artifact and requires TrpA1 channels.

    PubMed

    Green, Edward W; O'Callaghan, Emma K; Hansen, Celia N; Bastianello, Stefano; Bhutani, Supriya; Vanin, Stefano; Armstrong, James Douglas; Costa, Rodolfo; Kyriacou, Charalambos P

    2015-07-14

    Under standard laboratory conditions of rectangular light/dark cycles and constant warm temperature, Drosophila melanogaster show bursts of morning (M) and evening (E) locomotor activity and a "siesta" in the middle of the day. These M and E components have been critical for developing the neuronal dual oscillator model in which clock gene expression in key cells generates the circadian phenotype. However, under natural European summer conditions of cycling temperature and light intensity, an additional prominent afternoon (A) component that replaces the siesta is observed. This component has been described as an "artifact" of the TriKinetics locomotor monitoring system that is used by many circadian laboratories world wide. Using video recordings, we show that the A component is not an artifact, neither in the glass tubes used in TriKinetics monitors nor in open-field arenas. By studying various mutants in the visual and peripheral and internal thermo-sensitive pathways, we reveal that the M component is predominantly dependent on visual input, whereas the A component requires the internal thermo-sensitive channel transient receptor potential A1 (TrpA1). Knockdown of TrpA1 in different neuronal groups reveals that the reported expression of TrpA1 in clock neurons is unlikely to be involved in generating the summer locomotor profile, suggesting that other TrpA1 neurons are responsible for the A component. Studies of circadian rhythms under seminatural conditions therefore provide additional insights into the molecular basis of circadian entrainment that would otherwise be lost under the usual standard laboratory protocols. PMID:26124142

  5. Drosophila circadian rhythms in seminatural environments: Summer afternoon component is not an artifact and requires TrpA1 channels

    PubMed Central

    Green, Edward W.; O’Callaghan, Emma K.; Hansen, Celia N.; Bastianello, Stefano; Bhutani, Supriya; Vanin, Stefano; Armstrong, James Douglas; Costa, Rodolfo; Kyriacou, Charalambos P.

    2015-01-01

    Under standard laboratory conditions of rectangular light/dark cycles and constant warm temperature, Drosophila melanogaster show bursts of morning (M) and evening (E) locomotor activity and a “siesta” in the middle of the day. These M and E components have been critical for developing the neuronal dual oscillator model in which clock gene expression in key cells generates the circadian phenotype. However, under natural European summer conditions of cycling temperature and light intensity, an additional prominent afternoon (A) component that replaces the siesta is observed. This component has been described as an “artifact” of the TriKinetics locomotor monitoring system that is used by many circadian laboratories world wide. Using video recordings, we show that the A component is not an artifact, neither in the glass tubes used in TriKinetics monitors nor in open-field arenas. By studying various mutants in the visual and peripheral and internal thermo-sensitive pathways, we reveal that the M component is predominantly dependent on visual input, whereas the A component requires the internal thermo-sensitive channel transient receptor potential A1 (TrpA1). Knockdown of TrpA1 in different neuronal groups reveals that the reported expression of TrpA1 in clock neurons is unlikely to be involved in generating the summer locomotor profile, suggesting that other TrpA1 neurons are responsible for the A component. Studies of circadian rhythms under seminatural conditions therefore provide additional insights into the molecular basis of circadian entrainment that would otherwise be lost under the usual standard laboratory protocols. PMID:26124142

  6. The Optic Lobes Regulate Circadian Rhythms of Olfactory Learning and Memory in the Cockroach.

    PubMed

    Lubinski, Alexander J; Page, Terry L

    2016-04-01

    The cockroach, Leucophaea maderae, can be trained in an associative olfactory memory task by either classical or operant conditioning. When trained by classical conditioning, memory formation is regulated by a circadian clock, but once the memory is formed, it can be recalled at any circadian time. In contrast, when trained via operant conditioning, animals can learn the task at any circadian phase, but the ability to recall the long-term memory is tied to the phase of training. The optic lobes of the cockroach contain a circadian clock that drives circadian rhythms of locomotor activity, mating behavior, sensitivity of the compound eye to light, and the sensitivity of olfactory receptors in the antennae. To evaluate the role of the optic lobes in regulating learning and memory processes, the authors examined the effects of surgical ablation of the optic lobes on memory formation in classical conditioning and memory recall following operant conditioning. The effect of optic lobe ablation was to "rescue" the deficit in memory acquisition at a time the animals normally cannot learn and "rescue" the animal's ability to recall a memory formed by operant conditioning at a phase where memory was not normally expressed. The results suggested that the optic lobe pacemaker regulates these processes through inhibition at "inappropriate" times of day. As a pharmacological test of this hypothesis, the authors showed that injections of fipronil, an antagonist of GABA and glutamate-activated chloride channels, had the same effects as optic lobe ablation on memory formation and recall. The data suggest that the optic lobes contain the circadian clock(s) that regulate learning and memory processes via inhibition of neural processes in the brain. PMID:26714872

  7. Does Disruption of Circadian Rhythms Contribute to Beta-Cell Failure in Type 2 Diabetes?

    PubMed Central

    Rakshit, Kuntol; Thomas, Anthony P.

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by the loss of beta-cell secretory function and mass. The pathophysiology of beta-cell failure in T2DM involves a complex interaction between genetic susceptibilities and environmental risk factors. One environmental condition that is gaining greater appreciation as a risk factor for T2DM is the disruption of circadian rhythms (eg, shift-work and sleep loss). In recent years, circadian disruption has become increasingly prevalent in modern societies and consistently shown to augment T2DM susceptibility (partly mediated through its effects on pancreatic beta-cells). Since beta-cell failure is essential for development of T2DM, we will review current work from epidemiologic, clinical, and animal studies designed to gain insights into the molecular and physiological mechanisms underlying the predisposition to beta-cell failure associated with circadian disruption. Elucidating the role of circadian clocks in regulating beta-cell health will add to our understanding of T2DM pathophysiology and may contribute to the development of novel therapeutic and preventative approaches. PMID:24532160

  8. Hopf Bifurcations in a Model for Circadian Rhythms in Arabidopsis Thaliana

    NASA Astrophysics Data System (ADS)

    Shindell, Orrin; Tagg, Randall

    2011-03-01

    Arabidopsis thaliana is a plant used for many fundamental studies, including circadian rhythms. Numerically integrating the 7-equation kinetic model of Locke et al. [J. Theor. Bio. 234 (2005) 383], we have mapped regions of parameter space where circadian expression of key mRNA and proteins undergoes limit cycle oscillation. We seek to relate this to the work of Fukuda et al. [Phys. Rev. Lett. 99 (2007) 098102], where a coupled system of cells individually described by Stuart-Landau equations is used phenomenologically to describe experimentally observed spatio-temporal patterns in the plant leaves. To that end we have done a weakly nonlinear analysis of the system of kinetic equations. We also comment on possible experimental directions to further connect the kinetic models to dynamics in this multi-cellular system.

  9. Influences of horizontal hypokinesia on performance and circadian physiological rhythms in female humans

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Deroshia, C. W.; Sandler, H.

    1982-01-01

    Eight females from 35-45 yr of age were subjected to seven days of ambulatory control, seven days of bed rest, and a five day recovery period, with 30 min of centrifugation on day seven of bedrest to determine the effects of weightlessness on the circadian rhythms of females in that age group. Heart rate and rectal temperature (RT) were monitored and each subject was tested in a flight simulator twice a day in conditions of varying levels of turbulence. The flight simulations were run during the morning and acrophase of the circadian RT and performance errors wery monitored for 6 min. No significant differences were detected in the group performance data pre-, during, and post-bedrest, although better performance in the simulator was observed after the centrifuge exposure. An RT phase shift was statistically significant between pre- and during bedrest stages.

  10. Dynamics of three coupled van der Pol oscillators with application to circadian rhythms

    NASA Astrophysics Data System (ADS)

    Rompala, Kevin; Rand, Richard; Howland, Howard

    2007-08-01

    In this work we study a system of three van der Pol oscillators. Two of the oscillators are identical, and are not directly coupled to each other, but rather are coupled via the third oscillator. We investigate the existence of the in-phase mode in which the two identical oscillators have the same behavior. To this end we use the two variable expansion perturbation method (also known as multiple scales) to obtain a slow flow, which we then analyze using the computer algebra system MACSYMA and the numerical bifurcation software AUTO. Our motivation for studying this system comes from the presence of circadian rhythms in the chemistry of the eyes. We model the circadian oscillator in each eye as a van der Pol oscillator. Although there is no direct connection between the two eyes, they are both connected to the brain, especially to the pineal gland, which is here represented by a third van der Pol oscillator.

  11. The role of clock genes and circadian rhythm in the development of cardiovascular diseases.

    PubMed

    Takeda, Norihiko; Maemura, Koji

    2015-09-01

    The time of onset of cardiovascular disorders such as myocardial infarctions or ventricular arrhythmias exhibits a circadian rhythm. Diurnal variations in autonomic nervous activity, plasma cortisol level or renin-angiotensin activity underlie the pathogenesis of cardiovascular diseases. Transcriptional-translational feedback loop of the clock genes constitute a molecular clock system. In addition to the central clock in the suprachiasmatic nucleus, clock genes are also expressed in a circadian fashion in each organ to make up the peripheral clock. The peripheral clock seems to be beneficial for anticipating external stimuli and thus contributes to the maintenance of organ homeostasis. Loss of synchronization between the central and peripheral clocks also augments disease progression. Moreover, accumulating evidence shows that clock genes affect inflammatory and intracellular metabolic signaling. Elucidating the roles of the molecular clock in cardiovascular pathology through the identification of clock controlled genes will help to establish a novel therapeutic approach for cardiovascular disorders. PMID:25972277

  12. Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

    NASA Technical Reports Server (NTRS)

    Ede, M. C. M.

    1975-01-01

    The mechanisms that underlie the circadian variations in electrolyte content in body fluid compartments were investigated, and the mechanisms that control the oscillations were studied in order to investigate what effects internal desynchronization in such a system would have during manned space flight. The studies were performed using volunteer human subjects and squirrel monkeys. The intercompartmental distribution of potassium was examined when dietary intake, activity, and posture are held constant throughout each 24-hour day. A net flux of potassium was observed out of the body cell mass during the day and a reverse flux from the extracellular fluid into the body cell mass during the night, counterbalanced by changes in urinary potassium excretion. Experiments with monkeys provided evidence for the synchronization of renal potassium excretion by the rhythm of cortisol secretion with the light-dark cycle. Three models of the circadian timing system were formalized.

  13. Effect of feeding and temperature on the circadian rhythms of cortisol, thyroxine and triiodothyronine in pigs

    SciTech Connect

    Becker, B.A.; Nienaber, J.A.; Ford, J.J.; Hahn, G.L.

    1986-03-05

    An experiment was conducted to evaluate the circadian rhythms of cortisol, thyroxine (T/sub 4/) and triiodothyronine (T/sub 3/) in pigs under two temperature and feeding regimes. Twenty-eight barrows were randomly assigned to one of the following: 1) ad-libitum fed at 5/sup 0/C(AL-5); 2) ad-libitum fed at 20/sup 0/C(AL-20); 3) meal fed at 5/sup 0/C(M-5); and 4) meal fed at 20/sup 0/C(M-20). M-5 and M-20 animals were fed at 0730 and 1400 hrs. Lights were on from 0600 to 2000 hrs. After 5 wks, blood samples were collected for 27 hrs. Serum cortisol, T/sub 4/ and T/sub 3/ concentrations were determined by RIA. No significant differences were found in the mesors, amplitudes or acrophases for cortisol. The mesors for T/sub 4/ (p<.01) were 60.6 +/- 5.6, 40.2 +/- 5.6, 61.2 +/- 5.6 and 49.1 +/- 5.0 ng/ml for AL-5, AL-20, M-5, and M-20, respectively. The mesors for T/sub 3/ (p<.01) were .85 +/- .06, .69 +/- .06, .92 +/- .06 and .66 +/- .05 ng/ml for AL-5, AL-20, M-5, and M-20 respectively. No differences in the amplitudes or acrophases for T/sub 3/ or T/sub 4/ were found. These data show that temperature and feeding regimes do not entrain the circadian rhythm of cortisol in pigs. The circadian rhythms of T/sub 4/ and T/sub 3/ are also not altered by feeding regimes but are affected by temperature.

  14. Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.

    PubMed

    Lech, Karolina; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

    2016-02-01

    The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERB? in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings. PMID:26527095

  15. Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival.

    PubMed

    Lévi, Francis; Dugué, Pierre-Antoine; Innominato, Pasquale; Karaboué, Abdoulaye; Dispersyn, Garance; Parganiha, Arti; Giacchetti, Sylvie; Moreau, Thierry; Focan, Christian; Waterhouse, Jim; Spiegel, David

    2014-10-01

    The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (I < O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I < O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for those with a lower I < O (Log-rank p < 0.001). Multivariate analyses retained continuous I < O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (p < 0.001) and 0.970 (p < 0.001) for each 1% increase in I < O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker I < O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms. PMID:24927369

  16. Pharmacology of Myopia and Potential Role for Intrinsic Retinal Circadian Rhythms

    PubMed Central

    Stone, Richard A.; Pardue, Machelle T.; Iuvone, P. Michael; Khurana, Tejvir S.

    2013-01-01

    Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetycholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine’s role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors. PMID:23313151

  17. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    PubMed Central

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  18. Circadian Rhythms of Chloroplast Orientation and Photosynthetic Capacity in Ulva123

    PubMed Central

    Britz, Steven J.; Briggs, Winslow R.

    1976-01-01

    Ulva lactuca L. var. latissima (L.) Decandolle and var. rigida (C. Agardh) Le Jolis and U. mutabilis Foyn have a circadian rhythm of chloroplast orientation which results in large changes in the light-absorption properties of the thallus. During the day, the chloroplasts cover the outer face of the cells and absorbance is high. At night, the chloroplasts are along the side walls and absorbance is low. Enteromorpha linza (L.) J. Agardh, E. intestinalis (L.) Link, E. sp., and Monostroma grevillei (Thuret) Wittrock, members of the Ulvales, were not observed to have this rhythmic movement. Chloroplasts, when in the face position, could not be induced to move to the sides by high intensity light up to 80,000 lux. Unrelated to chloroplast position per se and light-absorption efficiency, there is a rhythm of photosynthetic capacity which peaks just before midday and which continues in constant darkness. Images PMID:16659613

  19. In synch but not in step: Circadian clock circuits regulating plasticity in daily rhythms.

    PubMed

    Evans, J A; Gorman, M R

    2016-04-21

    The suprachiasmatic nucleus (SCN) is a network of neural oscillators that program daily rhythms in mammalian behavior and physiology. Over the last decade much has been learned about how SCN clock neurons coordinate together in time and space to form a cohesive population. Despite this insight, much remains unknown about how SCN neurons communicate with one another to produce emergent properties of the network. Here we review the current understanding of communication among SCN clock cells and highlight a collection of formal assays where changes in SCN interactions provide for plasticity in the waveform of circadian rhythms in behavior. Future studies that pair analytical behavioral assays with modern neuroscience techniques have the potential to provide deeper insight into SCN circuit mechanisms. PMID:26861419

  20. Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²⁺ rhythms in vivo.

    PubMed

    Liang, Xitong; Holy, Timothy E; Taghert, Paul H

    2016-02-26

    In Drosophila, molecular clocks control circadian rhythmic behavior through a network of ~150 pacemaker neurons. To explain how the network's neuronal properties encode time, we performed brainwide calcium imaging of groups of pacemaker neurons in vivo for 24 hours. Pacemakers exhibited daily rhythmic changes in intracellular Ca(2+) that were entrained by environmental cues and timed by molecular clocks. However, these rhythms were not synchronous, as each group exhibited its own phase of activation. Ca(2+) rhythms displayed by pacemaker groups that were associated with the morning or evening locomotor activities occurred ~4 hours before their respective behaviors. Loss of the receptor for the neuropeptide PDF promoted synchrony of Ca(2+) waves. Thus, neuropeptide modulation is required to sequentially time outputs from a network of synchronous molecular pacemakers. PMID:26917772

  1. A Novel Quantitative Trait Locus on Mouse Chromosome 18, “era1,” Modifies the Entrainment of Circadian Rhythms

    PubMed Central

    Wisor, Jonathan P.; Striz, Martin; DeVoss, Jason; Murphy, Greer M.; Edgar, Dale M.; O'Hara, Bruce F.

    2007-01-01

    Study Objectives: The mammalian circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus conveys 24-h rhythmicity to sleep-wake cycles, locomotor activity, and other behavioral and physiological processes. The timing of rhythms relative to the light/dark (LD12:12) cycle is influenced in part by the endogenous circadian period and the time of day specific sensitivity of the clock to light. We now describe a novel circadian rhythm phenotype, and a locus influencing that phenotype, in a segregating population of mice. Methods: By crossbreeding 2 genetically distinct nocturnal strains of mice (Cast/Ei and C57BL/6J) and backcrossing the resulting progeny to Cast/Ei, we have produced a novel circadian phenotype, called early runner mice. Results: Early runner mice entrain to a light/dark cycle at an advanced phase, up to 9 hours before dark onset. This phenotype is not significantly correlated with circadian period in constant darkness and is not associated with disruption of molecular circadian rhythms in the SCN, as assessed by analysis of period gene expression. We have identified a genomic region that regulates this phenotype—a major quantitative trait locus on chromosome 18 (near D18Mit184) that we have named era1 for Early Runner Activity locus one. Phase delays caused by light exposure early in the subjective night were of smaller magnitude in backcross offspring that were homozygous Cast/Ei at D18Mit184 than in those that were heterozygous at this locus. Conclusion: Genetic variability in the circadian response to light may, in part, explain the variance in phase angle of entrainment in this segregating mouse population. Citation: Wisor JP; Striz M; DeVoss J; Murphy GM; Edgar DM; O'Hara BF. A novel quantitative trait locus on mouse chromosome 18, “era1,” modifies the entrainment of circadian rhythms. SLEEP 2007;30(10):1255-1263. PMID:17969459

  2. The dependence of onset and duration of sleep on th circadian rhythm of rectal temperature.

    PubMed

    Zulley, J; Wever, R; Aschoff, J

    1981-10-01

    The sleep-wake cycle and the circadian rhythm of rectal temperature were recorded in subjects who lived singly in an isolation unit. In 10 subjects, the freerunning rhythms remained internally synchronized, 10 other subjects showed internal desynchronization. Times of onset and end of bedrest ("sleep") were determined in each cycle and referred to the phase of the temperature rhythm. In the synchronized subjects, onset of sleep occurred, on the average, 1.34 h before the minimum of temperature, and end of sleep 6.94 h thereafter, with narrow distributions. The desynchronized subjects had a broad bimodal distribution of sleep onsets (peaks 6.3 and 1.3 h before the minimum); the duration of sleep varied between more than 15 h when sleep began about 10 h before the temperature minimum, and less than 4 h when sleep began several hours after the minimum. The dependence of sleep duration on body temperature is interpreted as a continuing action of the coupling forces between the two rhythms after mutual synchronization is lost. PMID:7312563

  3. Clock Genes may Influence Bipolar Disorder Susceptibility and Dysfunctional Circadian Rhythm

    PubMed Central

    Shi, Jiajun; Wittke-Thompson, Jacqueline K.; Badner, Judith A.; Hattori, Eiji; Potash, James B.; Willour, Virginia L; McMahon, Francis J.; Gershon, Elliot S.; Liu, Chunyu

    2008-01-01

    Several previous studies suggest that dysfunction of circadian rhythms may increase susceptibility to bipolar disorder (BP). We conducted an association study of five circadian genes (CRY2, PER1-3, and TIMELESS) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CSNK1D, CSNK1E, DBP, and NR1D1) in an extended family collection of 70 trios and 237 quads (Sample II), which includes the same 114 families but not necessarily the same individuals as Sample I. In Sample II, the Sibling-Transmission Disequilibrium Test (sib-tdt) analysis showed nominally significant association of BP with three SNPs within or near the CLOCK gene (rs534654, p = 0.0097; rs6850524, p = 0.012; rs4340844, p = 0.015). In addition, SNPs in the ARNTL2, CLOCK, DBP, and TIMELESS genes and haplotypes in the ARNTL, CLOCK, CSNK1E, and TIMELESS genes showed suggestive evidence of association with several circadian phenotypes identified in BP patients. However, none of these associations reached gene-wide or experiment-wide significance after correction for multiple-testing. A multi-locus interaction between rs6442925 in the 5? upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3? end of the CLOCK gene, however, is significantly associated with BP (p = 0.00000172). It remains significant after correcting for multiple testing using the False Discovery Rate method. Our results indicate an interaction between three circadian genes in susceptibility to bipolar disorder. PMID:18228528

  4. Time-Specific Fear Acts as a Non-Photic Entraining Stimulus of Circadian Rhythms in Rats

    PubMed Central

    Pellman, Blake A.; Kim, Earnest; Reilly, Melissa; Kashima, James; Motch, Oleksiy; de la Iglesia, Horacio O.; Kim, Jeansok J.

    2015-01-01

    Virtually all animals have endogenous clock mechanisms that “entrain” to the light-dark (LD) cycle and synchronize psychophysiological functions to optimal times for exploring resources and avoiding dangers in the environment. Such circadian rhythms are vital to human mental health, but it is unknown whether circadian rhythms “entrained” to the LD cycle can be overridden by entrainment to daily recurring threats. We show that unsignaled nocturnal footshock caused rats living in an “ethological” apparatus to switch their natural foraging behavior from the dark to the light phase and that this switch was maintained as a free-running circadian rhythm upon removal of light cues and footshocks. Furthermore, this fear-entrained circadian behavior was dependent on an intact amygdala and suprachiasmatic nucleus. Thus, time-specific fear can act as a non-photic entraining stimulus for the circadian system, and limbic centers encoding aversive information are likely part of the circadian oscillator network that temporally organizes behavior. PMID:26468624

  5. Entrainment of the Circadian Rhythm in Egg Hatching of the Crab Dyspanopeus sayi by Chemical Cues from Ovigerous Females.

    PubMed

    Forward, Richard B; Sanchez, Kevin G; Riley, Paul P

    2016-02-01

    The subtidal crab Dyspanopeus sayi has a circadian rhythm in larval release with a free-running period of 24.1 h. Under constant conditions, eggs hatch primarily in the 4-h interval after the time of sunset. The study tested the new model for entrainment in subtidal crabs, which proposes that the female perceives the environmental cycles and entrains the endogenous rhythm in the embryos. Results verified the model for D. sayi. Hatching by embryos collected from the field when they had not yet developed eye pigments, and were kept in constant conditions attached to their mother, exhibited the circadian hatching rhythm. Attached embryos could also be entrained to a new photoperiod in the laboratory before they developed eye pigments. Further, mature embryos removed from the female hatched rhythmically, indicating that a circadian rhythm resides in the embryos. However, if mature embryos with eye pigments were removed from the female and exposed to a new light-dark cycle, they could not be entrained to the new cycle; rather, they hatched according to the timing of the original light-dark cycle. Nevertheless, detached, mature embryos would entrain to a new light-dark cycle if they were in chemical, but not physical, contact with the female. Thus, the female perceives the light-dark cycle, and uses chemical cues to entrain the circadian rhythm of hatching by the embryos. PMID:26896174

  6. Light masking of circadian rhythms of heat production, heat loss, and body temperature in squirrel monkeys

    NASA Technical Reports Server (NTRS)

    Robinson, E. L.; Fuller, C. A.

    1999-01-01

    Whole body heat production (HP) and heat loss (HL) were examined to determine their relative contributions to light masking of the circadian rhythm in body temperature (Tb). Squirrel monkey metabolism (n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of body temperature and activity. Feeding was also measured. Responses to an entraining light-dark (LD) cycle (LD 12:12) and a masking LD cycle (LD 2:2) were compared. HP and HL contributed to both the daily rhythm and the masking changes in Tb. All variables showed phase-dependent masking responses. Masking transients at L or D transitions were generally greater during subjective day; however, L masking resulted in sustained elevation of Tb, HP, and HL during subjective night. Parallel, apparently compensatory, changes of HL and HP suggest action by both the circadian timing system and light masking on Tb set point. Furthermore, transient HL increases during subjective night suggest that gain change may supplement set point regulation of Tb.

  7. Passive cigarette smoking changes the circadian rhythm of clock genes in rat intervertebral discs.

    PubMed

    Numaguchi, Shumpei; Esumi, Mariko; Sakamoto, Mika; Endo, Michiko; Ebihara, Takayuki; Soma, Hirotoki; Yoshida, Akio; Tokuhashi, Yasuaki

    2016-01-01

    We aimed to elucidate the molecular changes in intervertebral discs (IVDs) caused by passive smoking. Rats were subjected to 8 weeks of passive smoking; thereafter, their lumbar vertebrae were harvested. The annulus fibrosus and cartilage endplate (AF/CEP) were harvested together, and the nucleus pulposus (NP) was isolated separately. The expression of 27,342 rat genes was analyzed. In 3 "nonsmoking" rats, 96 of 112 genes whose expression varied ?10-fold between the AF/CEP and NP were more highly expressed in the AF/CEP. With these differentially expressed genes, we uncovered novel AF/CEP and NP marker genes and indicated their possible novel functions. Although passive smoking induced less marked alteration in the gene expression profiles of both the AF/CEP and NP, multiple clock-related genes showed altered expression. These genes were expressed with a circadian rhythm in IVD cells, and most genes showed a phase shift of -6 to -9?h induced by passive smoking. Some clock-related genes showed abolished oscillation in the NP. Passive smoking also changed the expression levels of proteases and protease inhibitors and reduced the expression of NP marker genes. Thus, passive smoking induces changes in the circadian rhythm of a peripheral clock (IVD clock) that might be involved in molecular events related to IVD degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:39-47, 2016. PMID:25939642

  8. Evidence for clock genes circadian rhythms in human full-term placenta.

    PubMed

    Pérez, Silvia; Murias, Lucía; Fernández-Plaza, Catalina; Díaz, Irene; González, Celestino; Otero, Jesús; Díaz, Elena

    2015-12-01

    Biological rhythms are driven by endogenous biological clocks; in mammals, the master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This master pacemaker can synchronize other peripheral oscillators in several tissues such as some involved in endocrine or reproductive functions. The presence of an endogenous placental clock has received little attention. In fact, there are no studies in human full-term placentas. To test the existence of an endogenous pacemaker in this tissue we have studied the expression of circadian locomoter output cycles kaput (Clock), brain and muscle arnt-like (Bmal)1, period (Per)2, and cryptochrome (Cry)1 mRNAs at 00, 04, 08, 12, 16, and 20 hours by qPCR. The four clock genes studied are expressed in full-term human placenta. The results obtained allow us to suggest that a peripheral oscillator exists in human placenta. Data were analyzed using Fourier series where only the Clock and Bmal1 expression shows a circadian rhythm. PMID:26247999

  9. Circadian rhythms in vitamin B12 content of the rat brain.

    PubMed

    Ikeda, M; Inoué, S

    1997-06-01

    The whole brain content of vitamin B12 (VB12) in the rat was assayed by the chemiluminescent immunoassay at 4 h intervals in 12:12 h light-dark cycles (LD) and five different circadian times (CTs) under constant dim illumination (dim LL). In LD-entrained rats, the content of VB12 exhibited a day-night rhythm with a peak 2 h after the dark onset time and a trough 2 h before the light onset time. In freerunning rats under dim LL, the content of VB12 also exhibited a circadian variation with a peak ca. 2 h after the activity onset time (CT14) and a trough ca. 12 h after the activity onset time (CT 0). These findings clearly indicate that the brain VB12 content decreased during the active phase and increased during the resting phase regardless of the lighting schedule. On the other hand, the drinking behavior, as an index of the intake activity, was observed less frequently in the light phase of LD cycles and the resting phase of dim LL. Since most of the digested VB12 is known to be continuously stored in the liver, it is demonstrated that the rhythm of the brain content of VB12 may be caused by brain consumption of VB12 during the active phase and the transportation from the peripheral storage during the resting phase, independent of intake activities. PMID:9209116

  10. A novel multi-unit tablet for treating circadian rhythm diseases.

    PubMed

    Liu, Qi; Gong, Yinhua; Shi, Yun; Jiang, Liqun; Zheng, Chunli; Ge, Liang; Liu, Jianping; Zhu, Jiabi

    2013-06-01

    This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit(®) NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease(®) were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases. PMID:23649996

  11. Circadian Rhythm Genes CLOCK and PER3 Polymorphisms and Morning Gastric Motility in Humans

    PubMed Central

    Yamaguchi, Mitsue; Kotani, Kazuhiko; Tsuzaki, Kokoro; Takagi, Ayaka; Motokubota, Naoko; Komai, Naho; Sakane, Naoki; Moritani, Toshio; Nagai, Narumi

    2015-01-01

    Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut. PMID:25775462

  12. A circadian rhythm in skill-based errors in aviation maintenance.

    PubMed

    Hobbs, Alan; Williamson, Ann; Van Dongen, Hans P A

    2010-07-01

    In workplaces where activity continues around the clock, human error has been observed to exhibit a circadian rhythm, with a characteristic peak in the early hours of the morning. Errors are commonly distinguished by the nature of the underlying cognitive failure, particularly the level of intentionality involved in the erroneous action. The Skill-Rule-Knowledge (SRK) framework of Rasmussen is used widely in the study of industrial errors and accidents. The SRK framework describes three fundamental types of error, according to whether behavior is under the control of practiced sensori-motor skill routines with minimal conscious awareness; is guided by implicit or explicit rules or expertise; or where the planning of actions requires the conscious application of domain knowledge. Up to now, examinations of circadian patterns of industrial errors have not distinguished between different types of error. Consequently, it is not clear whether all types of error exhibit the same circadian rhythm. A survey was distributed to aircraft maintenance personnel in Australia. Personnel were invited to anonymously report a safety incident and were prompted to describe, in detail, the human involvement (if any) that contributed to it. A total of 402 airline maintenance personnel reported an incident, providing 369 descriptions of human error in which the time of the incident was reported and sufficient detail was available to analyze the error. Errors were categorized using a modified version of the SRK framework, in which errors are categorized as skill-based, rule-based, or knowledge-based, or as procedure violations. An independent check confirmed that the SRK framework had been applied with sufficient consistency and reliability. Skill-based errors were the most common form of error, followed by procedure violations, rule-based errors, and knowledge-based errors. The frequency of errors was adjusted for the estimated proportion of workers present at work/each hour of the day, and the 24 h pattern of each error type was examined. Skill-based errors exhibited a significant circadian rhythm, being most prevalent in the early hours of the morning. Variation in the frequency of rule-based errors, knowledge-based errors, and procedure violations over the 24 h did not reach statistical significance. The results suggest that during the early hours of the morning, maintenance technicians are at heightened risk of "absent minded" errors involving failures to execute action plans as intended. PMID:20653456

  13. Weaker Circadian Activity Rhythms are Associated with Poorer Executive Function in Older Women

    PubMed Central

    Walsh, Christine M.; Blackwell, Terri; Tranah, Gregory J.; Stone, Katie L.; Ancoli-Israel, Sonia; Redline, Susan; Paudel, Misti; Kramer, Joel H.; Yaffe, Kristine

    2014-01-01

    Study Objectives: Older adults and patients with dementia often have disrupted circadian activity rhythms (CARs). Disrupted CARs are associated with health declines and could affect cognitive aging. We hypothesized that among older women, weaker CARs would be associated with poorer cognitive function 5 y later. Design: Prospective observational study. Setting: Three US clinical sites. Participants: There were 1,287 community-dwelling older women (82.8 ± 3.1 y) participating in an ongoing prospective study who were free of dementia at the baseline visit. Measurements and Results: Baseline actigraphy was used to determine CAR measures (amplitude, mesor, and rhythm robustness, analyzed as quartiles; acrophase analyzed by peak activity time < 13:34 and > 15:51). Five years later, cognitive performance was assessed with the Modified Mini-Mental Status Examination (3MS), California Verbal Learning Task (CVLT), digit span, Trail Making Test B (Trails B), categorical fluency, and letter fluency. We compared cognitive performance with CARs using analyses of covariance adjusted for a number of health factors and comorbidities. Women in the lowest quartile for CAR amplitude performed worse on Trails B and categorical fluency compared to women in the highest quartile (group difference (d) = 30.42 sec, d = -1.01 words respectively, P < 0.05). Women in the lowest quartile for mesor performed worse on categorical fluency (d = -0.86 words, P < 0.05). Women with a later acrophase performed worse on categorical fluency (d = -0.69 words, P < 0.05). Controlling for baseline Mini-Mental State Examination and sleep factors had little effect on our results. Conclusions: Weaker circadian activity rhythm patterns are associated with worse cognitive function, especially executive function, in older women without dementia. Further investigation is required to determine the etiology of these relationships. Citation: Walsh CM, Blackwell T, Tranah GJ, Stone KL, Ancoli-Israel S, Redline S, Paudel M, Kramer JH, Yaffe K. Weaker circadian activity rhythms are associated with poorer executive function in older women. SLEEP 2014;37(12):2009-2016. PMID:25337947

  14. Coordinated regulation of circadian rhythms and homeostasis by the suprachiasmatic nucleus

    PubMed Central

    Nakagawa, Hachiro; Okumura, Nobuaki

    2010-01-01

    We have demonstrated that in rats activities of various enzymes related to gluconeogenesis and amino acid metabolism show circadian rhythms. Based on these results, we have explored the molecular mechanisms underlying circadian oscillation and phase response to light of the master clock located in the dorsomedial subdivision of the suprachiasmatic nucleus (SCN) and found various proteins closely related to phase response such as BIT/SHPS-1 and those of circadian oscillation, some of which are involved in protein-tyrosine phosphorylation. On the other hand, we have presented several lines of evidence that the ventrolateral subdivision of the SCN includes not only the control center of energy supply to the brain, but also that of homeostasis such as blood glucose, blood pressure, water balance, and body temperature. We have also shown that besides these functions, the latter subdivision is involved in the regulations of hormone secretions such as insulin, glucagon, corticosterone and vasopressin. It has been also shown by electrophysiological means that light exposure to rat eye enhances sympathetic nerve activity, whereas it depresses parasympathetic nerve activity. Thus, environmental light is implicated not only in the phase-shift through the retinohypthalamic tract (RHT), but also control of autonomic nerve activities through the RHT, It is also discussed in this review how the two divisions are interconnected and how environmental light is involved in this interconnection. PMID:20431263

  15. Light-sampling behavior in photoentrainment of a rodent circadian rhythm.

    PubMed

    DeCoursey, P J

    1986-08-01

    Behavioral aspects of photoentrainment of circadian locomotor activity rhythms were recorded for a nocturnal den-dwelling rodent, the flying squirrel, Glaucomys volans. Methods included both telemetric monitoring and infrared observations of animals under constant dark (DD) or light-dark (LD) schedules in either standard wheel cages or in newly developed simulated den cages. By means of the den cages, several aspects of a circadian activity cycle could be simultaneously measured emphasizing the arousal from rest, the light-sampling behavior by which a squirrel assessed the environmental photoregimen, and the phase-shifting by which photoentrainment was achieved. Each animal in a den cage remained for 12 or more hours of its rest period almost exclusively in the darkened nest box, then at an abrupt arousal time moved to the light-sampling porthole. In darkness each animal initiated wheel activity immediately after arousal; light at arousal time, however, induced a return to the nest box for a nap and a delay phase-shift in onset of activity of approximately 40 min. On subsequent days, each animal appeared to be free-running (tau FR less than 24 h) until onset again advanced into the light period. A squirrel usually viewed only a few minutes light per day, and on free-running days occasionally saw none of the 12-h light period. The significance of these data for theories of circadian photoentrainment is discussed. PMID:3761222

  16. Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy.

    PubMed

    De Rui, M; Middleton, B; Sticca, A; Gatta, A; Amodio, P; Skene, D J; Montagnese, S

    2015-02-01

    Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline. PMID:25135598

  17. Habitual moderate alcohol consumption desynchronizes circadian physiologic rhythms and affects reaction-time performance.

    PubMed

    Reinberg, Alain; Touitou, Yvan; Lewy, Hadas; Mechkouri, Mohamed

    2010-10-01

    The authors studied longitudinally four healthy young adults to explore if habitual evening intake of a "moderate" amount of wine alters parameters, including period (?) of circadian rhythms. Subjects, synchronized by diurnal activity from 07.30?h?±?60?min to 23.00?h?±?90?min and nocturnal rest, were studied during a continuous 22-day span: 11 days without alcohol (control) and 11 days with a glass (200?mL) of wine nightly at supper (alcohol). The amount of alcohol ingested with dinner ranged from 0.28 to 0.42?g/kg/24?h/participant and the estimated evening blood alcohol level ranged from 0.02 to 0.10?g/L/participant. Single reaction time (SRT; yellow light signal), three-choice reaction time (CRT) (red, green, and yellow signals) of both hands, related cumulated errors (c-errors), as well as oral temperature (OT) and grip strength (GS) were measured four to seven times/24?h. Time series were analyzed individually to quantify 24-h means (M), circadian ? (power spectra), and cosinor, and correlation, ?(2), and t tests were performed. The sleep-wake ? (actography) was 24?h in every subject for both conditions. With alcohol, all subjects showed an OT circadian ? shorter than the control one. The SRT circadian M was longer (poorer performance) with wine versus control in three subjects, while CRT was longer with wine versus control in only one subject. Correlation analyses also showed the detrimental effect of alcohol on the same variables. Number of days with <2 c-errors was predominant in control and decreased with alcohol, especially for SRT. The desynchronization of the 10 different documented rhythms was greater with alcohol with reference to control in two of the four studied subjects. This work shows that habitual "moderate" wine drinking at supper reduces the performance of subjects, increases the level of c-errors/24?h, especially for SRT, suggesting a "moderate" amount of alcohol has the potential to increase accident risk, and it can also desynchronize circadian time organization. PMID:20969532

  18. Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans.

    PubMed

    Cuesta, Marc; Boudreau, Philippe; Dubeau-Laramée, Geneviève; Cermakian, Nicolas; Boivin, Diane B

    2016-03-15

    Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers. PMID:26873990

  19. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

    PubMed Central

    Sletten, Tracey L.; Segal, Ahuva Y.; Flynn-Evans, Erin E.; Lockley, Steven W.; Rajaratnam, Shantha M. W.

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID:26043207

  20. Adjustment of sleep and the circadian temperature rhythm after flights across nine time zones

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Myhre, Grete; Graeber, R. Curtis; Lauber, John K.; Andersen, Harald T.

    1989-01-01

    The adjustment of sleep-wake patterns and the circadian temperature rhythm was monitored in nine Royal Norwegian Airforce volunteers operating P-3 aircraft during a westward training deployment across nine time zones. Subjects recorded all sleep and nap times, rated nightly sleep quality, and completed personality inventories. Rectal temperature, heart rate, and wrist activity were continuously monitored. Adjustment was slower after the return eastward flight than after the outbound westward flight. The eastward flight produced slower readjustment of sleep timing to local time and greater interindividual variability in the patterns of adjustment of sleep and temperature. One subject apparently exhibited resynchronization by partition, with the temperature rhythm undergoing the reciprocal 15-h delay. In contrast, average heart rates during sleep were significantly elevated only after westward flight. Interindividual differences in adjustment of the temperature rhythm were correlated with some of the personality measures. Larger phase delays in the overall temperature waveform (as measured on the 5th day after westward flight) were exhibited by extraverts, and less consistently by evening types.

  1. Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice.

    PubMed

    Gallardo, Christian M; Darvas, Martin; Oviatt, Mia; Chang, Chris H; Michalik, Mateusz; Huddy, Timothy F; Meyer, Emily E; Shuster, Scott A; Aguayo, Antonio; Hill, Elizabeth M; Kiani, Karun; Ikpeazu, Jonathan; Martinez, Johan S; Purpura, Mari; Smit, Andrea N; Patton, Danica F; Mistlberger, Ralph E; Palmiter, Richard D; Steele, Andrew D

    2014-01-01

    Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output. PMID:25217530

  2. Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice

    PubMed Central

    Gallardo, Christian M; Darvas, Martin; Oviatt, Mia; Chang, Chris H; Michalik, Mateusz; Huddy, Timothy F; Meyer, Emily E; Shuster, Scott A; Aguayo, Antonio; Hill, Elizabeth M; Kiani, Karun; Ikpeazu, Jonathan; Martinez, Johan S; Purpura, Mari; Smit, Andrea N; Patton, Danica F; Mistlberger, Ralph E; Palmiter, Richard D; Steele, Andrew D

    2014-01-01

    Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output. DOI: http://dx.doi.org/10.7554/eLife.03781.001 PMID:25217530

  3. Stochastic models of cellular circadian rhythms in plants help to understand the impact of noise on robustness and clock structure.

    PubMed

    Guerriero, Maria L; Akman, Ozgur E; van Ooijen, Gerben

    2014-01-01

    Rhythmic behavior is essential for plants; for example, daily (circadian) rhythms control photosynthesis and seasonal rhythms regulate their life cycle. The core of the circadian clock is a genetic network that coordinates the expression of specific clock genes in a circadian rhythm reflecting the 24-h day/night cycle. Circadian clocks exhibit stochastic noise due to the low copy numbers of clock genes and the consequent cell-to-cell variation: this intrinsic noise plays a major role in circadian clocks by inducing more robust oscillatory behavior. Another source of noise is the environment, which causes variation in temperature and light intensity: this extrinsic noise is part of the requirement for the structural complexity of clock networks. Advances in experimental techniques now permit single-cell measurements and the development of single-cell models. Here we present some modeling studies showing the importance of considering both types of noise in understanding how plants adapt to regular and irregular light variations. Stochastic models have proven useful for understanding the effect of regular variations. By contrast, the impact of irregular variations and the interaction of different noise sources are less well studied. PMID:25374576

  4. Stochastic models of cellular circadian rhythms in plants help to understand the impact of noise on robustness and clock structure

    PubMed Central

    Guerriero, Maria L.; Akman, Ozgur E.; van Ooijen, Gerben

    2014-01-01

    Rhythmic behavior is essential for plants; for example, daily (circadian) rhythms control photosynthesis and seasonal rhythms regulate their life cycle. The core of the circadian clock is a genetic network that coordinates the expression of specific clock genes in a circadian rhythm reflecting the 24-h day/night cycle. Circadian clocks exhibit stochastic noise due to the low copy numbers of clock genes and the consequent cell-to-cell variation: this intrinsic noise plays a major role in circadian clocks by inducing more robust oscillatory behavior. Another source of noise is the environment, which causes variation in temperature and light intensity: this extrinsic noise is part of the requirement for the structural complexity of clock networks. Advances in experimental techniques now permit single-cell measurements and the development of single-cell models. Here we present some modeling studies showing the importance of considering both types of noise in understanding how plants adapt to regular and irregular light variations. Stochastic models have proven useful for understanding the effect of regular variations. By contrast, the impact of irregular variations and the interaction of different noise sources are less well studied. PMID:25374576

  5. Age-Related Sleep Disruption and Reduction in the Circadian Rhythm of Urine Output: Contribution to Nocturia?

    PubMed

    Duffy, Jeanne F; Scheuermaier, Karine; Loughlin, Kevin R

    2016-01-01

    Aging is associated with a marked increase in sleep complaints, and one factor causing sleep disruption is waking to void (nocturia). Urological surveys have found that few young adults report nocturia symptoms, but about half of those in their 60's and nearly 80% of older age groups are affected. Sleep surveys have found nocturia is a major cause of sleep disruption, with a majority of older adults with sleep disruption citing the need to void as the cause of their awakening. While much of the urological literature implies that nocturia causes sleep disruption, age-related changes in sleep depth and continuity may make it more likely that an older adult will wake in response to a filling bladder, or that an older adult will wake for another reason and then decide to void. There is also evidence that age-related changes in the amplitude of circadian rhythms contribute to nocturia. There is a well-described circadian rhythm in urine output, and evidence of circadian rhythmicity in some diuretic and anti-diuretic hormones. In this article, we describe how age-related changes in sleep depth and continuity and age-related changes in circadian rhythm amplitude may contribute to nocturia, and how nocturia in turn leads to sleep disruption. Better understanding of how changes in sleep and circadian rhythmicity impact nocturia may lead to improved treatments and better quality of life for older adults. PMID:26632430

  6. Circadian Rhythms in Executive Function during the Transition to Adolescence: The Effect of Synchrony between Chronotype and Time of Day

    ERIC Educational Resources Information Center

    Hahn, Constanze; Cowell, Jason M.; Wiprzycka, Ursula J.; Goldstein, David; Ralph, Martin; Hasher, Lynn; Zelazo, Philip David

    2012-01-01

    To explore the influence of circadian rhythms on executive function during early adolescence, we administered a battery of executive function measures (including a Go-Nogo task, the Iowa Gambling Task, a Self-ordered Pointing task, and an Intra/Extradimensional Shift task) to Morning-preference and Evening-preference participants (N = 80) between…

  7. Circadian Rhythms in Executive Function during the Transition to Adolescence: The Effect of Synchrony between Chronotype and Time of Day

    ERIC Educational Resources Information Center

    Hahn, Constanze; Cowell, Jason M.; Wiprzycka, Ursula J.; Goldstein, David; Ralph, Martin; Hasher, Lynn; Zelazo, Philip David

    2012-01-01

    To explore the influence of circadian rhythms on executive function during early adolescence, we administered a battery of executive function measures (including a Go-Nogo task, the Iowa Gambling Task, a Self-ordered Pointing task, and an Intra/Extradimensional Shift task) to Morning-preference and Evening-preference participants (N = 80) between…

  8. A Failure to Detect an Influence of Magnetic Fields on the Growth Rate and Circadian Rhythm of Neurospora crassa1

    PubMed Central

    Bitz, D. Michael; Sargent, Malcolm L.

    1974-01-01

    Low strength magnetic fields, 6.36 and 32.25 gauss, were found to have no effect, with one questionable exception, on the circadian rhythm and growth rate of Neurospora crassa. This was true whether the fields were continuous, pulsed 20 minutes daily, or on a 12: 12, on-off cycle. PMID:16658667

  9. Lithium and genetic inhibition of GSK3beta enhance the effect of methamphetamine on circadian rhythms in the mouse.

    PubMed

    Mohawk, Jennifer A; Miranda-Anaya, Manuel; Tataroglu, Ozgur; Menaker, Michael

    2009-03-01

    Lithium, a drug commonly used to treat mood disorders, and the psychostimulant methamphetamine are both capable of altering circadian rhythmicity. Although the actions of lithium on the circadian system are thought to occur through inhibition of glycogen synthase kinase-3beta (GSK3beta), the mechanism by which methamphetamine alters circadian rhythms is unknown. We tested the effects of concurrent methamphetamine and lithium treatment on the circadian wheel-running behavior of mice. Methamphetamine alone lengthened both the active duration and the free-running period of locomotor activity in animals housed in constant conditions. Administering lithium enhanced the period-lengthening effects of methamphetamine in animals housed in constant darkness. This effect was even more pronounced when animals were housed in constant light. Lithium increased both methamphetamine intake and serum levels of methamphetamine, possibly contributing to the effects on circadian behavior. We also tested the effect of methamphetamine in mutant mice possessing only one allele for Gsk3beta. These animals, when treated with methamphetamine, responded like wild-type mice treated with a combination of methamphetamine and lithium, displaying long, free-running rhythms. These data, together with many others in the literature, point to a complicated interaction between the circadian system and the development and possible treatment of psychopathologies such as bipolar disorder and drug addiction. PMID:19339873

  10. Body weight gain in rats by a high-fat diet produces chronodisruption in activity/inactivity circadian rhythm.

    PubMed

    Bravo, Rafael; Cubero, Javier; Franco, Lourdes; Mesa, Mónica; Galán, Carmen; Rodríguez, Ana Beatriz; Jarne, Carlos; Barriga, Carmen

    2014-04-01

    In the last few decades, obesity has become one of the most important public health problems. Adipose tissue is an active endocrine tissue which follows a rhythmic pattern in its functions and may produce alterations in certain circadian rhythms. Our aim was to evaluate whether the locomotor activity circadian rhythm could be modified by a hypercaloric diet in rodents. Two groups were considered in the experiment: 16 rats were used as a control group and were fed standard chow; the other group comprised 16 rats fed a high-fat diet (35.8% fat, 35% glucides). The trial lasted 16 weeks. Body weight was measured every week, and a blood sample was extracted every two weeks to quantify triglyceride levels. The activity/inactivity circadian rhythm was logged through actimetry throughout the trial, and analysed using the DAS 24© software package. At the end of the experiment, the high-fat fed rats had obese-like body weights and high plasma triglyceride levels, and, compared with the control group, increased diurnal activity, decreased nocturnal activity, reductions in amplitude, midline estimating statistic of rhythm, acrophase and interdaily stability, and increases in intradaily variability of their activity rhythms. The results thus show how obesity can lead to symptoms of chronodisruption in the body similar to those of ageing. PMID:24304409

  11. Repeated psychosocial stress at night affects the circadian activity rhythm of male mice.

    PubMed

    Bartlang, Manuela S; Oster, Henrik; Helfrich-Förster, Charlotte

    2015-06-01

    We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2. PMID:25900040

  12. Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

    PubMed Central

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J.

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n?=?24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm?2 s?1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n?=?8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P?=?0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  13. [Development of the mammalian circadian system].

    PubMed

    Laurinová, Kristýna; Sumová, Alena

    2006-01-01

    Many behavioral, physiological and molecular processes exhibit diurnal rhythms. Endogenous rhythms with period close to 24 hours are called circadian rhythms. Light entrains circadian rhythms to a 24 period of solar day. Circadian system consists of pacemaker, which is in mammals located in the suprachiasmatic nuclei of hypothalamus (SCN), its input and output pathways and peripheral clocks in numerous tissues. The generation of circadian rhytmicity is based on interactive transcription-translational feedback loops in SCN. These feedback loops consist of so called clock genes and their protein products which positively or negatively regulate their own transcription. Studies in rodent embros and neonates demonstrate that individual components of circadian system matures gradually during prenatal and postnatal period Mechanism of light entrainment of the circadian system develops postnatally. During early postnatal period, the developing circadian system is synchronized mainly by maternal cues. PMID:17685020

  14. Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol

    NASA Technical Reports Server (NTRS)

    Chavarri, M.; Ganguly, A.; Luetscher, J. A.; Zager, P. G.

    1977-01-01

    Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.

  15. Hierarchy of models: From qualitative to quantitative analysis of circadian rhythms in cyanobacteria

    NASA Astrophysics Data System (ADS)

    Chaves, M.; Preto, M.

    2013-06-01

    A hierarchy of models, ranging from high to lower levels of abstraction, is proposed to construct "minimal" but predictive and explanatory models of biological systems. Three hierarchical levels will be considered: Boolean networks, piecewise affine differential (PWA) equations, and a class of continuous, ordinary, differential equations' models derived from the PWA model. This hierarchy provides different levels of approximation of the biological system and, crucially, allows the use of theoretical tools to more exactly analyze and understand the mechanisms of the system. The Kai ABC oscillator, which is at the core of the cyanobacterial circadian rhythm, is analyzed as a case study, showing how several fundamental properties—order of oscillations, synchronization when mixing oscillating samples, structural robustness, and entrainment by external cues—can be obtained from basic mechanisms.

  16. Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways

    PubMed Central

    Jenwitheesuk, Anorut; Nopparat, Chutikorn; Mukda, Sujira; Wongchitrat, Prapimpun; Govitrapong, Piyarat

    2014-01-01

    Brain aging is linked to certain types of neurodegenerative diseases and identifying new therapeutic targets has become critical. Melatonin, a pineal hormone, associates with molecules and signaling pathways that sense and influence energy metabolism, autophagy, and circadian rhythms, including insulin-like growth factor 1 (IGF-1), Forkhead box O (FoxOs), sirtuins and mammalian target of rapamycin (mTOR) signaling pathways. This review summarizes the current understanding of how melatonin, together with molecular, cellular and systemic energy metabolisms, regulates epigenetic processes in the neurons. This information will lead to a greater understanding of molecular epigenetic aging of the brain and anti-aging mechanisms to increase lifespan under healthy conditions. PMID:25247581

  17. Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways.

    PubMed

    Jenwitheesuk, Anorut; Nopparat, Chutikorn; Mukda, Sujira; Wongchitrat, Prapimpun; Govitrapong, Piyarat

    2014-01-01

    Brain aging is linked to certain types of neurodegenerative diseases and identifying new therapeutic targets has become critical. Melatonin, a pineal hormone, associates with molecules and signaling pathways that sense and influence energy metabolism, autophagy, and circadian rhythms, including insulin-like growth factor 1 (IGF-1), Forkhead box O (FoxOs), sirtuins and mammalian target of rapamycin (mTOR) signaling pathways. This review summarizes the current understanding of how melatonin, together with molecular, cellular and systemic energy metabolisms, regulates epigenetic processes in the neurons. This information will lead to a greater understanding of molecular epigenetic aging of the brain and anti-aging mechanisms to increase lifespan under healthy conditions. PMID:25247581

  18. Regularity of daily life in relation to personality, age, gender, sleep quality and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Petrie, S. R.; Hayes, A. J.; Kupfer, D. J.

    1994-01-01

    A diary-like instrument to measure lifestyle regularity (the 'Social Rhythm Metric'-SRM) was given to 96 subjects (48 women, 48 men), 39 of whom repeated the study after at least one year, with additional objective measures of rest/activity. Lifestyle regularity as measured by the SRM related to age, morningness, subjective sleep quality and time-of-day variations in alertness, but not to gender, extroversion or neuroticism. Statistically significant test-retest correlations of about 0.4 emerged for SRM scores over the 12-30 month delay. Diary-based estimates of bedtime and waketime appeared fairly reliable. In a further study of healthy young men, 4 high SRM scorers ('regular') had a deeper nocturnal body temperature trough than 5 low SRM scorers ('irregular'), suggesting a better functioning circadian system in the 'regular' group.

  19. Stocking density affects circadian rhythms of locomotor activity in African catfish, Clarias gariepinus.

    PubMed

    Vera, Luisa Mar A; Al-Khamees, Sami; Herv, Migaud

    2011-11-01

    The effect of stocking density on the locomotor activity of African catfish C. gariepinus under different light regimes was investigated. C. gariepinus were stocked under different densities (1, 5, or 10 fish/tank), and their locomotor activity recorded under light-dark (LD), constant light (LL), constant darkness (DD), and LD-reversed (DL) regimens. Under the LD cycle, catfish showed a crepuscular activity pattern, irrespective of stocking density, with most of the daily activity concentrated around the light-onset and light-offset times. When fish were subjected to DD, all 4 tanks with medium (5 fish) and high (10 fish) stocking densities showed circadian rhythmicity, with an average period (?) of 23.3???0.5 and 24.6???0.5?h, respectively. In contrast, only 2 low (1 fish) density tanks showed free-running rhythms. Under LL, activity levels decreased significantly in comparison with levels observed under LD and DD. Moreover, fish of 1, 2, and 3 out of the 4 tanks with low, medium, and high densities, respectively, showed free-running rhythms under these conditions. When the photocycle was reversed (DL), fish of 3, 2, and 4 out of the 4 tanks with low, medium, and high stocking densities, respectively, showed gradual resynchronization to the new phase, and transient cycles of activity were observed. These results suggest that stocking density of fish affected the display of circadian rhythmicity and the intensity of activity levels. Thus, fish kept in higher densities showed more robust rhythmicity and higher levels of daily activity, indicating that social interactions may have an influence on behavioral patterns in the African catfish. PMID:21895490

  20. An ASMT variant associated with bipolar disorder influences sleep and circadian rhythms: a pilot study.

    PubMed

    Geoffroy, P A; Boudebesse, C; Henrion, A; Jamain, S; Henry, C; Leboyer, M; Bellivier, F; Etain, B

    2014-03-01

    Patients with bipolar disorder (BD) experience persistent circadian rhythm and sleep abnormalities during periods of remission, and biological studies have shown that these patients have abnormal melatonin secretion profiles or reactivity to light. We previously reported the association with BD of a common polymorphism (rs4446909) of the promoter of the acetylserotonin O-methyltransferase (ASMT) gene, encoding one of the two enzymes involved in melatonin biosynthesis. This variant was associated with weaker transcription and lower levels of ASMT activity in lymphoblastoid cell lines. Actigraphy, based on the use of a mobile portable device for the analysis of sleep/wake cycles in natural conditions, may be useful for studies of carriers of the at-risk allele. We studied the association between the ASMT rs4446909 variant and sleep/activity, as assessed with the Pittsburgh Sleep Quality Index (PSQI) and by actigraphy, in 53 subjects (25 patients with BD in remission and 28 healthy controls). The two groups were similar for age, sex ratio, current mood symptoms, body mass index and risk of sleep apnea syndrome. In the total sample, the GG at-risk genotype was associated with longer sleep duration (P?=?0.03), greater activity in active periods of sleep (P?=?0.015) and greater interday stability (P?=?0.003). These associations remained significant when disease status was included in the model. Only the association with interday stability remained significant after correction for multiple testing. This pilot study thus shows that a BD-associated functional variant involved in the melatonin synthesis pathway influences sleep and circadian rhythms in bipolar patients in remission and controls. PMID:24308489

  1. Circadian rhythm of onset of stroke - in 50 cases of ischemic stroke.

    PubMed

    Uddin, M S; Hoque, M I; Uddin, M K; Kamol, S A; Chowdhury, R H

    2015-01-01

    Stroke is a leading cause of death and disability worldwide. While the immediate consequence of stroke include permanent cognitive deficits, paralysis, visual impairment and sensory disturbances; stroke also results in long term dysregulation of sleep and mood, which may be equally disabling. The influence of ischemic stroke on circadian rhythm regulation, which is strongly linked to sleep and mood, may thus potentially influence long term recovery in stroke patients. Stroke induces immediate changes in the timing of pineal melatonin secretion, indicating that cortical and basal ganglia infarction impacts the timing of melatonin rhythms. This study was done to find out the time of onset of most of the ischemic stroke attack and to determine the outcome of ischemic stroke during hospital stay. All ischemic stroke patients admitted in Medicine wards in Comilla Medical College Hospital during the period of 1st November 2010 to 30th April 2011 included in this study. After admission, a careful history and a thorough clinical examination was carried out. Data collection was done on a preset questionnaire which involved to identify the risk factors, the time of onset of ischemic stroke, and outcome during hospital stay. All the cases were investigated. Among the 50 ischemic stroke patients, 68% were male and 32% female. Maximum age groups were 61-70 years (50%). By occupational category, maximum were retired persons (46%); 68% were hypertensive, 38% smoker and 16% had diabetes. Dyslipidemia was present in 44% patients. Most of the ischemic stroke (44%) occurred in the morning to late morning (6:01AM-12:00PM) and majority (80%) of the patients was discharged with residual neurological dysfunction. This study supports the presence of a circadian pattern in the onset of ischemic stroke, with higher risk in the morning to late morning. Most of the patients were discharged with residual neurological dysfunction. PMID:25725678

  2. A Circadian Clock in Antarctic Krill: An Endogenous Timing System Governs Metabolic Output Rhythms in the Euphausid Species Euphausia superba

    PubMed Central

    Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

    2011-01-01

    Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9–12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9–12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle. PMID:22022521

  3. A circadian clock in Antarctic krill: an endogenous timing system governs metabolic output rhythms in the euphausid species Euphausia superba.

    PubMed

    Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

    2011-01-01

    Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9-12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9-12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle. PMID:22022521

  4. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet.

    PubMed

    Kc, Ranjan; Li, Xin; Forsyth, Christopher B; Voigt, Robin M; Summa, Keith C; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W; Meng, Qing-Jun; Im, Hee-Jeong

    2015-01-01

    A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications. PMID:26584570

  5. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet

    PubMed Central

    Kc, Ranjan; Li, Xin; Forsyth, Christopher B.; Voigt, Robin M.; Summa, Keith C.; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W.; Meng, Qing-Jun; Im, Hee-Jeong

    2015-01-01

    A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications. PMID:26584570

  6. The effects of feedback lighting on the circadian drinking rhythm in the diurnal new world primate Saimiri sciureus

    NASA Technical Reports Server (NTRS)

    Ferraro, J. S.; Sulzman, F. M.

    1988-01-01

    Feedback lighting provides illumination primarily during the subjective night (i.e., the photosensitive portion of the circadian cycle) in response to a given behavior. This technique has previously been used to test the nonparametric model of entrainment in nocturnal rodents. In three species (Rattus norvegicus, Mesocricetus auratus, and Mus musculus), the free-running period of the locomotor activity rhythm was similar whether the animals were exposed to continuous light or discrete light pulses occurring essentially only during the subjective night (i.e., feedback lighting). In the current experiments, feedback lighting was presented to squirrel monkeys so that light fell predominantly during the subjective night. Feedback lighting was linked to the drinking behavior in this diurnal primate so that when the animal drank, the lights went out. Despite the seemingly adverse predicament, the monkeys maintained regular circadian drinking rhythms. Furthermore, just as the period of the free-running activity rhythms of nocturnal rodents exposed to continuous light or feedback lighting were similar, the period of the drinking rhythms of the squirrel monkeys in continuous light and feedback lighting were comparable (25.6 +/- 0.1 and 25.9 +/- 0.1 hours, respectively), despite a substantial decrease in the total amount of light exposure associated with feedback lighting. The free-running period of monkeys exposed to continuous dark (24.5 +/- 0.1 hours) was significantly shorter than either of the two lighting conditions (P < 0.001). The results presented for the drinking rhythm were confirmed by examination of the temperature and activity rhythms. Therefore, discrete light pulses given predominately during the subjective night are capable of simulating the effects of continuous light on the free-running period of the circadian rhythms of a diurnal primate. The response of squirrel monkeys to feedback lighting thus lends further support for the model and suggests that the major entrainment mechanisms are similar in nocturnal rodents and diurnal primates.

  7. Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats

    NASA Technical Reports Server (NTRS)

    McDonald, R. B.; Hoban-Higgins, T. M.; Ruhe, R. C.; Fuller, C. A.; Horwitz, B. A.

    1999-01-01

    We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

  8. The expression of locomotor circadian rhythm in female German cockroach, Blattella germanica (L.).

    PubMed

    Lin, T M; Lee, H J

    1996-07-01

    Fifteen percent of intact female German cockroaches (n = 13), Blattella germanica (L.) (Dictyoptera: Blattellidae), had weak free-running locomotor rhythmicity under 28 degrees C and constant darkness conditions. However, 86% of ovariectomized females (n = 14) showed a strong free-running rhythm under the same conditions with a circadian period of 23.60 +/- 0.15 h, similar to the male's period of 23.45 +/- 0.03 h. In addition, the locomotory activities occurred mainly during the subjective night under DD conditions as was the case in males. These results indicated that female locomotion was under the control of a circadian oscillator, which was masked by the existence of ovaries. This internal masking effect could be removed by the existence of males, but females had no effect on the locomotor pattern of another female. Since the male failed to entrain female locomotion, its role as a zeitgeber was excluded. That the locomotory pattern of the females still coincided with their reproductive cycle when exposed to male odor suggests that exposure to a male only partially removed the internal masking effects. PMID:8877117

  9. Phase Shift of the Circadian Rhythm of Lemna Caused by Pulses of a Leucine Analog, Trifluoroleucine

    PubMed Central

    Kondo, Takao

    1988-01-01

    Pulses of a fluorinated analog of leucine, 5?,5?,5?-trifluoroleucine, reset the phase of the circadian rhythm of K+ uptake in Lemna gibba G3 under continuous light conditions. The trifluoroleucine pulse caused the largest delay phase-shifts during the early subjective phase but it caused only small phase advances. The action of trifluoroleucine was investigated and the following results were obtained. (a) The uptake of trifluoroleucine was essentially the same at all circadian phases, even though phase shifting was dramatically different at different phases. At effective phases, the magnitude of phase shifting was well correlated with the amount of trifluoroleucine taken up by the duckweed. (b) The trifluoroleucine pulse lowered the endogenous content of valine and leucine but these decreases did not correlate with phase shifting. (c) Protein synthesis was not affected by trifluoroleucine pulses which caused large phase shifts. (d) Pulses of 4-azaleucine, a different structural analog of leucine, also caused phase shifting. However, neither the direction nor the effective times of phase shifting were similar to those of trifluoroleucine. Taken together, these results negate the proposition that trifluoroleucine and azaleucine caused phase shift by disturbing amino acid metabolism and/or inhibiting protein synthesis, but they suggest instead that these analogs are incorporated into some protein(s) which are necessary for normal clock operation. PMID:16666410

  10. The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

    NASA Astrophysics Data System (ADS)

    Qin, Chuanjie; Shao, Ting

    2015-05-01

    The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene ( Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%-88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.

  11. Biochemical genetics of the circadian rhythm in Neurospora crassa: studies on the cel strain

    SciTech Connect

    Lakin-Thomas, P.L.

    1985-01-01

    In Neurospora crassa, the cel mutation lengthens the period of the circadian rhythm when the medium is supplemented with linoleic acid (18:2). Double mutant strains were constructed between cel and the clock mutants prd-1 and four alleles at the frq locus. It was found that: (1) the effect of 18:2 on cel was blocked by prd-1, i.e., prd-1 is epistatic to cel. (2) cel and frq interact such that the percent increase in the period produced by 18:2 was inversely proportional to the period of the frq parent. (3) Data from the literature on period effects in double mutant strains support a multiplicative rather than an additive model. A biochemical interpretation of these interactions is discussed, based on the control of flux through metabolic pathways. Because the cel strain is known to be deficient in the pantothenate derivative normally attached to the fatty acid synthetase (FAS) complex, the possibility that cel may affect other pantothenate-modified proteins was investigated. It was found that in the cel/sup +/ strain, five proteins of molecular weights (M/sub r/) 9000, 19,000, 22,000, 140,000, and 200,000 were labelled with (/sup 14/C)pantothenate. In the cel strain, only the 200 k (FAS) label was reduced in amount. Therefore, there is no evidence that cel affects circadian rhythmicity through any deficiency other than FAS. A biochemical model for circadian rhythmicity in Neurospora is presented. Oscillations in cytoplasmic and mitochondrial Ca/sup 2 +/ are proposed; clock mutations are postulated to affect Ca/sup 2 +/ transporters and the mitochondrial membrane; and phase-shifting effects are accounted for by changes in Ca/sup 2 +/ or ATP levels.

  12. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    PubMed

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-08-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light. PMID:26203935

  13. Light Cycles Given During Development Affect Freerunning Period of Circadian Locomotor Rhythm of period Mutants in Drosophila melanogaster.

    PubMed

    MATSUMOTO, N; UWOZUMI, K; TOMIOKA, K

    1997-03-01

    We reared wild type (Canton-S) and period mutant flies, i.e., per(S) and per(L), of Drosophila melanogaster in constant darkness, constant light or 24h light dark cycles with various light to dark ratios throughout the development from embryo to early adult. The locomotor activity rhythms of newly eclosed individuals were subsequently monitored in the lighting conditions, in which they had been reared, for several days and then in constant darkness. Circadian rhythms were clearly exhibited in constant darkness even in flies reared in constant light and constant darkness as well as flies reared in light-dark cycles, but the freerunning period differed among groups. The results suggest that the circadian clock is assembled without any cyclical photic information, and that the light influences the developing circadian clock of Drosophila to alter the freerunning period. The effects of light on the rhythm differed in some aspects between per(L) flies and the other two strains. Possible mechanisms through which light affects the developing circadian clock are discussed. Copyright 1997 Elsevier Science Ltd. All rights reserved PMID:12769914

  14. Rhythms.

    ERIC Educational Resources Information Center

    Online-Offline, 2000

    2000-01-01

    Presents selected resources for elementary and secondary education that relate to rhythms, including literary rhythms, natural rhythms, and musical rhythms. Includes Web sites, CD-ROMs and software, videos, books, audio materials, magazines, professional resources, and suggested classroom activities. (LRW)

  15. Differential regulation of circadian melatonin rhythm and sleep-wake cycle by bright lights and nonphotic time cues in humans.

    PubMed

    Yamanaka, Yujiro; Hashimoto, Satoko; Masubuchi, Satoru; Natsubori, Akiyo; Nishide, Shin-Ya; Honma, Sato; Honma, Ken-Ichi

    2014-09-01

    Our previous study demonstrated that physical exercise under dim lights (<10 lux) accelerated reentrainment of the sleep-wake cycle but not the circadian melatonin rhythm to an 8-h phase-advanced sleep schedule, indicating differential effects of physical exercise on the human circadian system. The present study examined the effects of bright light (>5,000 lux) on exercise-induced acceleration of reentrainment because timed bright lights are known to reset the circadian pacemaker. Fifteen male subjects spent 12 days in temporal isolation. The sleep schedule was advanced from habitual sleep times by 8 h for 4 days, which was followed by a free-run session. In the shift session, bright lights were given during the waking time. Subjects in the exercise group performed 2-h bicycle running twice a day. Subjects in the control kept quiet. As a result, the sleep-wake cycle was fully entrained by the shift schedule in both groups. Bright light may strengthen the resetting potency of the shift schedule. By contrast, the circadian melatonin rhythm was phase-advanced by 6.9 h on average in the exercise group but only by 2.0 h in the control. Thus physical exercise prevented otherwise unavoidable internal desynchronization. Polysomnographical analyses revealed that deterioration of sleep quality by shift schedule was protected by physical exercise under bright lights. These findings indicate differential regulation of sleep-wake cycle and circadian melatonin rhythm by physical exercise in humans. The melatonin rhythm is regulated primarily by bright lights, whereas the sleep-wake cycle is by nonphotic time cues, such as physical exercise and shift schedule. PMID:24944250

  16. Effects of restricted daily feeding on freerunning circadian rhythms in rats.

    PubMed

    Honma, K; von Goetz, C; Aschoff, J

    1983-06-01

    Male rats were kept in conditions of constant dim illumination and alternately fed ad lib or for 2 or 4 hr per day only. Locomotor activity was recorded as wheel running and as activity in the cage by a microphone system. At selected days before, during and after restricted feeding (RF) blood samples were taken from the tail in 4-hr intervals for the determination of plasma corticosterone. Under both schedules of RF, the circadian rhythms of activity and of plasma corticosterone continued to freerun without significant changes in period or phase while the feeding times were anticipated by increases in activity and in plasma corticosterone. After the termination of RF, the anticipatory components persisted for several days and merged into the freerunning rhythms through transients. The results support the concept of two systems with oscillatory capacities: the freerunning system which is driven by a pacemaker and not affected by RF, and the anticipatory system which can be uncoupled from the freerunning system by an entraining feeding cycle. PMID:6611695

  17. Sensitivity to Stimulation, a Component of the Circadian Rhythm in Luminescence in Gonyaulax1

    PubMed Central

    Christianson, Roger; Sweeney, Beatrice M.

    1972-01-01

    A new method for the stimulation of bioluminescence in the dinoflagellate Gonyaulax polyedra is described. With this technique, in which cells flow through a capillary coil, it is possible to graduate the intensity of the stimulus by varying the flow rate. In continuous darkness, the threshold stimulus for cells in the middle of the day phase is greater than that for cells in the middle of the night phase. Some evidence suggests heterogeneity of sensitivity to stimulation among either cells or individual luminescent sources within a cell. At stimulus intensities much above threshold, the luminescence of both day- and night-phase cells is proportional to the number of cells within the capillary coil. Night-phase cells emit about 14 times as much light as do day-phase cells in continuous darkness. Single bioluminescent flashes from cells were recorded with a high speed camera. No significant difference in flash kinetics was found between cells in the day and the night phase in continuous darkness. Cells in the night phase emit a flash three to five times brighter than that from day-phase cells. About twice as many flashes are recorded in a given time from a population of night-phase cells. The activity of both luciferin and luciferase have been shown to vary rhythmically. The differences in threshold and number of flahses are evidence for a second component of the circadian rhythm in luminescence, a rhythm in sensitivity to stimulation. PMID:16658099

  18. Maximum entropy spectral analysis for circadian rhythms: theory, history and practice.

    PubMed

    Dowse, Harold B

    2013-01-01

    There is an array of numerical techniques available to estimate the period of circadian and other biological rhythms. Criteria for choosing a method include accuracy of period measurement, resolution of signal embedded in noise or of multiple periodicities, and sensitivity to the presence of weak rhythms and robustness in the presence of stochastic noise. Maximum Entropy Spectral Analysis (MESA) has proven itself excellent in all regards. The MESA algorithm fits an autoregressive model to the data and extracts the spectrum from its coefficients. Entropy in this context refers to "ignorance" of the data and since this is formally maximized, no unwarranted assumptions are made. Computationally, the coefficients are calculated efficiently by solution of the Yule-Walker equations in an iterative algorithm. MESA is compared here to other common techniques. It is normal to remove high frequency noise from time series using digital filters before analysis. The Butterworth filter is demonstrated here and a danger inherent in multiple filtering passes is discussed. PMID:23844660

  19. Maximum entropy spectral analysis for circadian rhythms: theory, history and practice

    PubMed Central

    2013-01-01

    There is an array of numerical techniques available to estimate the period of circadian and other biological rhythms. Criteria for choosing a method include accuracy of period measurement, resolution of signal embedded in noise or of multiple periodicities, and sensitivity to the presence of weak rhythms and robustness in the presence of stochastic noise. Maximum Entropy Spectral Analysis (MESA) has proven itself excellent in all regards. The MESA algorithm fits an autoregressive model to the data and extracts the spectrum from its coefficients. Entropy in this context refers to “ignorance” of the data and since this is formally maximized, no unwarranted assumptions are made. Computationally, the coefficients are calculated efficiently by solution of the Yule-Walker equations in an iterative algorithm. MESA is compared here to other common techniques. It is normal to remove high frequency noise from time series using digital filters before analysis. The Butterworth filter is demonstrated here and a danger inherent in multiple filtering passes is discussed. PMID:23844660

  20. Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

    NASA Technical Reports Server (NTRS)

    Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)

    1999-01-01

    The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

  1. Circadian rhythms are not involved in the regulation of circannual reproductive cycles in a sub-tropical bird, the spotted munia.

    PubMed

    Budki, Puja; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

    2014-07-15

    Circannual rhythms regulate seasonal reproduction in many vertebrates. The present study investigated whether circannual reproductive phenotypes (rhythms in growth of gonads and molt) were generated independently of the circadian clocks in the subtropical non-photoperiodic spotted munia (Lonchura punctulata). Birds were subjected to light:dark (LD) cycles with identical light but varying dark hours, such that the period of LD cycle (T) equaled 16 h (T16; 12 h L:4 h D), 21 h (T21; 12 h L:9 h D), 24 h (T24; 12 h L:12 h D) and 27 h (T27; 12 h L:15 h D), or to continuous light (LL, 24 h L:0 h D) at ~18°C. During the ~21 month exposure, munia underwent at least two cycles of gonadal development and molt; changes in body mass were not rhythmic. This was similar to the occurrence of annual cycles in reproduction and molt observed in wild birds. A greater asynchrony between circannual cycles of gonad development and molt indicated their independent regulation. Females showed reproductive rhythms with similar circannual periods, whilst in males, circannual periods measured between peak gonadal size were longer in T21 and T24 than in T16 or T27. This suggested a sex-dependent timing of annual reproduction in the spotted munia. Also, food availability periods may not influence the circannual timing of reproduction, as shown by the results on the rhythm in gonadal growth and regression in munia under T-photocycles and LL that provided differential light (feeding) hours. Further, a short-term experiment revealed that activity-rest patterns in munia were synchronized with T-photocycles, but were arrhythmic under LL. We conclude that circadian rhythms are not involved in the timing of the annual reproductive cycle in the spotted munia. PMID:24803462

  2. Complex effects of melatonin on human circadian rhythms in constant dim light.

    PubMed

    Middleton, B; Arendt, J; Stone, B M

    1997-10-01

    In humans, the pineal hormone melatonin can phase shift a number of circadian rhythms (e.g., "fatigue", endogenous melatonin, core body temperature) together with the timing of prolactin secretion. It is uncertain, however, whether melatonin can fully entrain all human circadian rhythms. In this study, the authors investigated the effects of daily melatonin administration on sighted individuals kept in continuous very dim light. A total of 10 normal, healthy males were maintained in two separate groups in partial temporal isolation under constant dim light (< 8 lux) with attenuated sound and ambient temperature variations but with knowledge of clock time for two periods of 30 days. In these circumstances, the majority of individuals free run with a mean period of 24.3 h. In a double-blind, randomized crossover design, subjects received 5 mg melatonin at 20:00 h on Days 1 to 15 (Melatonin 1st) followed by placebo on Days 16 to 30 (Placebo 2nd) or vice versa (Placebo 1st, Melatonin 2nd) during Leg 1 with treatment reversed in Leg 2. The variables measured were melatonin (as 6-sulphatoxymelatonin), rectal temperature, activity, and sleep (actigraphy and logs). In the experiment, 9 of the 10 subjects free ran with Placebo 1st, whereas Melatonin 1st stabilized the sleep-wake cycle to 24 h in 8 of 10 individuals. In addition, 2 individuals showed irregular sleep with this treatment. In some subjects, there was a shortening of the period of the temperature rhythm without synchronization. Melatonin 2nd induced phase advances (5 of 9 subjects), phase delays (2 of 9 subjects), and stabilization (2 of 9 subjects) of the sleep-wake cycle with subsequent synchronization to 24 h in the majority of individuals (7 of 9). Temperature continued to free run in 4 subjects. Maximum phase advances in core temperature were seen when the first melatonin treatment was given approximately 2 h after the temperature acrophase. These results indicate that melatonin was able to phase shift sleep and core temperature but was unable to synchronize core temperature consistently. In the majority of subjects, the sleep-wake cycle could be synchronized. PMID:9376645

  3. A tunable artificial circadian clock in clock-defective mice

    PubMed Central

    D'Alessandro, Matthew; Beesley, Stephen; Kim, Jae Kyoung; Chen, Rongmin; Abich, Estela; Cheng, Wayne; Yi, Paul; Takahashi, Joseph S.; Lee, Choogon

    2015-01-01

    Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators. PMID:26617050

  4. Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms

    PubMed Central

    St. Hilaire, Melissa A.; Lockley, Steven W.

    2015-01-01

    Objective/Background Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep–wake disorder. Patients/Methods Three totally blind males (63.0?±?7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48?h every 1–2 weeks. Participants completed daily sleep–wake logs, and rated their alertness and mood using nine-point scales every ~2–4?h while awake on urine sampling days. Caffeine capsules (150?mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period ? and compared to placebo (n?=?2) or no treatment (n?=?1) in a single-masked manner. Results Non-24-h aMT6s rhythms were confirmed in all three participants (? range?=?24.32–24.57?h). Daily administration of 150?mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p?circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep–Wake Disorder in the blind appropriately. PMID:25891543

  5. Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation

    NASA Technical Reports Server (NTRS)

    Millet, C.; Custaud, M. A.; Allevard, A. M.; Zaouali-Ajina, M.; Monk, T. H.; Arnaud, S. B.; Claustrat, B.; Gharib, C.; Gauquelin-Koch, G.

    2001-01-01

    We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450 (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of the aldosterone rhythm.

  6. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day

    NASA Technical Reports Server (NTRS)

    Wyatt, J. K.; Ritz-De Cecco, A.; Czeisler, C. A.; Dijk, D. J.

    1999-01-01

    The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15-24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

  7. Time dictates: emerging clinical analyses of the impact of circadian rhythms on diagnosis, prognosis and treatment of disease.

    PubMed

    Nagy, Andras D; Reddy, Akhilesh B

    2015-12-01

    Since the advent of modern molecular tools, researchers have extensively shown that essential cellular machineries have robust circadian (roughly 24 hours) variations in their pace. This molecular rhythmicity translates directly into time-of-day-dependent variation in physiology in most organ systems, which in turn provides the mechanistic rationale for why timing on a daily basis should matter in many aspects of human health. However, these basic science findings have been slow to move from bench to bedside because clinical studies are still lacking to demonstrate the importance of timing. Therefore, it has not been clear how physicians should incorporate knowledge of natural 24-hour rhythms into routine practice. This review is a brief summary of results from recently completed clinical studies on hypertension, myocardial infarction, diabetes mellitus, and adrenal dysfunction that highlights new evidence for the emerging importance of circadian rhythms in diagnosis, prognosis and treatment of disease. PMID:26634682

  8. Time dictates: emerging clinical analyses of the impact of circadian rhythms on diagnosis, prognosis and treatment of disease

    PubMed Central

    Nagy, Andras D.; Reddy, Akhilesh B.

    2016-01-01

    Since the advent of modern molecular tools, researchers have extensively proven that essential cellular machineries show robust circadian (~24 hour) variations in their pace. This molecular rhythmicity translates in most organ systems directly into time of day dependent variation in physiology, which in turn provides the mechanistic rationale for why timing on a daily basis should matter in many aspects of human health. However, these basic science findings have been slow to move from bench to bedside since clinical studies are still lacking to demonstrate the importance of timing. Therefore, it has not been clear how physicians might incorporate knowledge of our natural 24 hour rhythms into their routine practise. This review is a brief summary of results from recently completed clinical studies on hypertension, myocardial infarction, diabetes mellitus, and adrenal dysfunction to highlight new evidence on the emerging importance of circadian rhythms in diagnosis, prognosis and treatment of disease. PMID:26634682

  9. The effects on human sleep and circadian rhythms of 17 days of continuous bedrest in the absence of daylight

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Billy, B. D.; Kennedy, K. S.; Kupfer, D. J.

    1997-01-01

    As part of a larger bedrest study involving various life science experiments, a study was conducted on the effects of 17 days of continuous bedrest and elimination of daylight on circadian rectal temperature rhythms, mood, alertness, and sleep (objective and diary) in eight healthy middle-aged men. Sleep was timed from 2300 to 0700 hours throughout. Three 72-hour measurement blocks were compared: ambulatory prebedrest, early bedrest (days 5-7), and late bedrest (days 15-17). Temperature rhythms showed reduced amplitude and later phases resulting from the bedrest conditions. This was associated with longer nocturnal sleep onset latencies and poorer subjectively rated sleep but with no reliable changes in any of the other sleep parameters. Daily changes in posture and/or exposure to daylight appear to be important determinants of a properly entrained circadian system.

  10. The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

    NASA Technical Reports Server (NTRS)

    DeRoshia, Charles W.; Colletti, Laura C.; Mallis, Melissa M.

    2008-01-01

    This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

  11. Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Cederholm, Tommy; Sjögren, Per; Lindholm, Bengt; Ärnlöv, Johan; Carrero, Juan Jesús

    2015-01-01

    Background Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. Methods This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). Results UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m2) in its association with the changes of both night-time systolic BP (SBP) and night–day SBP ratio. After stratification, UAER strongly predicted night–day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER. Conclusions UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations. PMID:26413281

  12. Circadian rhythm in the pineal organ of the yellow-bellied toad, Bombina variegata (L.), under laboratory conditions.

    PubMed

    Sura, P

    1992-01-01

    A circadian morphological rhythm of the pineal organ, as judged by changes in the nuclear volume of the photoreceptor cells, was found in sexually mature male Yellow-bellied toads (Bombina variegata) maintained continuously at 26 degrees C and on a 17L/7D illumination cycle. The greatest nuclear volume occurred at the photophase (16.00 h), and the lowest at the end of the scotophase (4.00 h). PMID:1306508

  13. Daily Rhythms of Hunger and Satiety in Healthy Men during One Week of Sleep Restriction and Circadian Misalignment.

    PubMed

    Sargent, Charli; Zhou, Xuan; Matthews, Raymond W; Darwent, David; Roach, Gregory D

    2016-01-01

    The impact of sleep restriction on the endogenous circadian rhythms of hunger and satiety were examined in 28 healthy young men. Participants were scheduled to 2 × 24-h days of baseline followed by 8 × 28-h days of forced desynchrony during which sleep was either moderately restricted (equivalent to 6 h in bed/24 h; n = 14) or severely restricted (equivalent to 4 h in bed/24 h; n = 14). Self-reported hunger and satisfaction were assessed every 2.5 h during wake periods using visual analogue scales. Participants were served standardised meals and snacks at regular intervals and were not permitted to eat ad libitum. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. Both hunger and satiety exhibited a marked endogenous circadian rhythm. Hunger was highest, and satiety was lowest, in the biological evening (i.e., ~17:00-21:00 h) whereas hunger was lowest, and satiety was highest in the biological night (i.e., 01:00-05:00 h). The results are consistent with expectations based on previous reports and may explain in some part the decrease in appetite that is commonly reported by individuals who are required to work at night. Interestingly, the endogenous rhythms of hunger and satiety do not appear to be altered by severe-as compared to moderate-sleep restriction. PMID:26840322

  14. Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization

    PubMed Central

    2013-01-01

    Introduction Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34+ cell yields when collected in the afternoon compared with the morning. Methods A prospective study was conducted to directly examine the number of peripheral blood CD34+ and CD34+CD38– progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 ?g/kg/day in the morning) mobilization in 11 allogeneic donors. Data were analyzed using mixed-model analysis of repeated measures. Results Whereas we observed a significant increase in CD34+ cell counts toward the evening, counts were then sustained on the morning of day 5. The correlation between CD34+CD38– cell counts and the less defined CD34+ populations was weak. Conclusions Our results suggest that the pharmacodynamic activity and timing of G-CSF may alter endogenous progenitor rhythms. Donor age, medical history, and medications may also impact circadian rhythm. Further studies should examine the circadian rhythm at the peak of G-CSF mobilization and should consider potential confounders such as the time of G-CSF administration and the age of the subjects. PMID:23514984

  15. Daily Rhythms of Hunger and Satiety in Healthy Men during One Week of Sleep Restriction and Circadian Misalignment

    PubMed Central

    Sargent, Charli; Zhou, Xuan; Matthews, Raymond W.; Darwent, David; Roach, Gregory D.

    2016-01-01

    The impact of sleep restriction on the endogenous circadian rhythms of hunger and satiety were examined in 28 healthy young men. Participants were scheduled to 2 × 24-h days of baseline followed by 8 × 28-h days of forced desynchrony during which sleep was either moderately restricted (equivalent to 6 h in bed/24 h; n = 14) or severely restricted (equivalent to 4 h in bed/24 h; n = 14). Self-reported hunger and satisfaction were assessed every 2.5 h during wake periods using visual analogue scales. Participants were served standardised meals and snacks at regular intervals and were not permitted to eat ad libitum. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. Both hunger and satiety exhibited a marked endogenous circadian rhythm. Hunger was highest, and satiety was lowest, in the biological evening (i.e., ~17:00–21:00 h) whereas hunger was lowest, and satiety was highest in the biological night (i.e., 01:00–05:00 h). The results are consistent with expectations based on previous reports and may explain in some part the decrease in appetite that is commonly reported by individuals who are required to work at night. Interestingly, the endogenous rhythms of hunger and satiety do not appear to be altered by severe—as compared to moderate—sleep restriction. PMID:26840322

  16. A study on circadian rhythm disorder of rat lung tissue caused by mechanical ventilation induced lung injury.

    PubMed

    Li, Huan; Wang, Chunxiao; Hu, Jiaqi; Tan, Junyuan

    2014-02-01

    Ventilator-induced lung injury (VILI), the most serious complication of mechanical ventilation therapy, is an excessive inflammatory response in lung tissue characterized by infiltration of inflammatory cells and overproduction of inflammatory mediators. The pathogenesis of VILI is very complex. It is becoming increasingly evident that disruption of circadian rhythm affects the immune response. Whether the pathogenesis of VILI is associated with circadian rhythm disruption has not been reported. In this study, we establish VILI model in SD rat by performing an endotracheal intubation and placing the rat on a mechanical ventilator (tidal volume of 40 ml/kg or 10 ml/kg without positive end-expiratory pressure). To examine the effect of VILI on clock gene expression, real-time quantitative PCR was performed to measure bmal1, clock, per2 and Rev-erb? mRNA expression. We found that Rev-erb? mRNA was significantly decreased in high tide volume mechanical ventilation group compared with spontaneous group, the same as REV-ERB? protein product which was tested by Western blot approach. Stimulation of REV-ERB? activity by SR9009 greatly diminished VILI-induced lung edema, inflammatory cell infiltration and the production of the pro-inflammatory cytokine TNF-?. Collectively, our findings are the first to show that REV-ERB? plays an important role in VILI and inflammation, and circadian rhythm disorder in inflammation response may be a novel pathogenesis of VILI. PMID:24355794

  17. Effects of growth hormone therapy on circadian osteocalcin rhythms in idiopathic short stature.

    PubMed

    Markowitz, M E; DiMartino-Nardi, J; Gasparini, F; Fishman, K; Rosen, J F; Saenger, P

    1989-08-01

    The effects of GH administration on the circadian osteocalcin (Oc) rhythm were determined in four prepubertal children with idiopathic short stature (height, less than 5th percentile; growth velocity, less than 50th percentile for age). Each child underwent 24-h sequential blood sampling on three occasions: immediately before the initiation of GH treatment, 6 months later, and at the end of 12 months of treatment. The growth rate increased more than 50% over baseline in three of the four children during at least one of the 6-month periods. Insulin-like growth factor-I levels increased during treatment in all of the children. Twenty-four-hour Oc levels increased on 7 of the 8 treatment days evaluated. When mean 24-h Oc patterns for each of the 3 study days were derived by averaging across individual subjects at each time point and then compared, we noted an upward shift in the entire pattern during treatment (t = 13.2 at P less than 0.001 and t = 5.9 at P less than 0.001 for 6 and 12 month comparisons vs. the pretreatment day, respectively). This was more easily appreciated after the data were smoothed using the method of running means. There was, in addition, a progressive improvement in the shape of the Oc pattern compared to a normative model derived from a study of healthy adult men. The correlation between the model and the pre-GH day was 0.46, that between the model and the 6 months of GH day was 0.77, and that between the model and the 12 months of GH day was 0.96. Cross-correlation analyses showed that the peak correlation between the 2 treatment days and the m