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Sample records for activity circadian rhythms

  1. Circadian Rhythms

    ... microbes. The study of circadian rhythms is called chronobiology. Are circadian rhythms the same thing as biological ... the eyes cross. Do circadian rhythms have a genetic component? Yes. Researchers have already identified genes that ...

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

    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.

  3. Circadian activity rhythms in the spiny mouse, Acomys cahirinus.

    Weber, E T; Hohn, V M

    2005-11-15

    Circadian locomotor rhythms were examined in adult common spiny mice, Acomys cahirinus. Spiny mice demonstrated nocturnal activity, with onset of activity coinciding promptly with onset of darkness. Re-entrainment to 6-h delays of the light-dark cycle was accomplished faster than to 6-h advances. Access to running wheels yielded significant changes in period and duration of daily activity. Novelty-induced wheel running had no effect on phase of activity rhythms. Circadian responses to light at various times of the circadian cycle were temporally similar to those observed in other nocturnal rodent species. No gender differences were observed in any of the parameters measured.

  4. Circadian activity rhythms for mothers with an infant in ICU

    Shih-Yu eLee

    2010-12-01

    Full Text Available Circadian rhythms influence sleep and wakefulness. Circadian activity rhythms (CAR are altered in individuals with dementia or seasonal affective disorder. To date, studies exploring CAR and sleep in postpartum women are rare. The purpose of this report is to describe relationships between CAR, sleep disturbance, and fatigue among 72 first-time mothers during their 2nd week postpartum while their newborn remain hospitalized in intensive care unit (ICU. Seventy two mothers were included in this secondary data analysis sample from three separate studies. Participants completed the General Sleep Disturbance Scale (GSDS, Numerical Rating Scale for Fatigue (NRS-F, and a sleep diary. The objective sleep data included total sleep time (TST, wake after sleep onset (WASO, and CAR determined by the circadian quotient (amplitude/mesor averaged from at least 48-hours of wrist actigraphy monitoring. The TST of mothers who self-reported as poor sleepers was 354 minutes (SEM= 21.9, with a mean WASO of 19.5% (SEM= 2.8. The overall sleep quality measured by the GSDS was clinically, significantly disrupted (M= 5.5, SD= 1.2. The mean score for morning fatigue was 5.8 (SD= 2.0, indicating moderate fatigue severity. The CAR was .62 (SEM= .04, indicating poor synchronization. The self-reported good sleepers (GSDS < 3 had better CAR (M= .71, SEM= .02 than poor sleepers (GSDS > 3 (t [70] = 2.0, p< .05. A higher circadian equation was associated with higher TST (r= .83, p<.001, less WASO (r= -.50, p< .001, lower self-reported sleep disturbance scores (r= -.35, p= .01, and less morning fatigue (r= -.26. Findings indicate that mothers with a hospitalized infant have both nocturnal sleep problems and disturbed circadian activity rhythms. Factors responsible for these sleep and rhythm disturbances, the adverse effects on mother’s physical and mental well-being, and mother-infant relationship require further study.

  5. Calculating activation energies for temperature compensation in circadian rhythms

    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.

  6. Circadian activity rhythms for mothers with an infant in ICU.

    Lee, Shih-Yu; Lee, Kathryn A; Aycock, Dawn; Decker, Michael

    2010-01-01

    Circadian rhythms influence sleep and wakefulness. Circadian activity rhythms (CAR) are altered in individuals with dementia or seasonal affective disorder. To date, studies exploring CAR and sleep in postpartum women are rare. The purpose of this report is to describe relationships between CAR, sleep disturbance, and fatigue among 72 first-time mothers during their second week postpartum while their newborn remain hospitalized in intensive care unit. Seventy-two mothers were included in this secondary data analysis sample from three separate studies. Participants completed the general sleep disturbance scale (GSDS), numerical rating scale for fatigue, and a sleep diary. The objective sleep data included total sleep time (TST), wake after sleep onset (WASO), and CAR determined by the circadian quotient (amplitude/mesor) averaged from at least 48-h of wrist actigraphy monitoring. The TST of mothers who self-reported as poor sleepers was 354 min (SEM = 21.9), with a mean WASO of 19.5% (SEM = 2.8). The overall sleep quality measured by the GSDS was clinically, significantly disrupted (M = 5.5, SD = 1.2). The mean score for morning fatigue was 5.8 (SD = 2.0), indicating moderate fatigue severity. The CAR was 0.62 (SEM = 0.04), indicating poor synchronization. The self-reported good sleepers (GSDS  3) (t[70] = 2.0, p sleep disturbance scores (r = -0.35, p = 0.01), and less morning fatigue (r = -0.26). Findings indicate that mothers with a hospitalized infant have both nocturnal sleep problems and disturbed circadian activity rhythms. Factors responsible for these sleep and rhythm disturbances, the adverse effects on mother's physical and mental well-being, and mother-infant relationship require further study.

  7. Forced desynchrony of circadian rhythms of body temperature and activity in rats

    Strijkstra, AM; Meerlo, P; Beersma, DGM

    1999-01-01

    The daily rhythm in body temperature is thought to be the result of the direct effects of activity and the effects of an endogenous circadian clock. Forced desynchrony (FD) is a tool used in human circadian rhythm research to disentangle endogenous and activity-related effects on daily rhythms. In t

  8. Circadian Rhythm Sleep Disorders

    Erhan Akinci

    2016-06-01

    Full Text Available The circadian rhythm sleep disorders define the clinical conditions where sleep and ndash;wake rhythm is disrupted despite optimum environmental and social conditions. They occur as a result of the changes in endogenous circadian hours or non-compatibility of environmental factors or social life with endogenous circadian rhythm. The sleep and ndash;wake rhythm is disrupted continuously or in repeating phases depending on lack of balance between internal and external cycles. This condition leads to functional impairments which cause insomnia, excessive sleepiness or both in people. Application of detailed sleep anamnesis and sleep diary with actigraphy record, if possible, will be sufficient for diagnosis. The treatment aims to align endogenous circadian rhythm with environmental conditions. The purpose of this article is to review pathology, clinical characteristics, diagnosis and treatment of circadian rhythm disorder. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 178-189

  9. Maternal and infant activity: Analytic approaches for the study of circadian rhythm.

    Thomas, Karen A; Burr, Robert L; Spieker, Susan

    2015-11-01

    The study of infant and mother circadian rhythm entails choice of instruments appropriate for use in the home environment as well as selection of analytic approach that characterizes circadian rhythm. While actigraphy monitoring suits the needs of home study, limited studies have examined mother and infant rhythm derived from actigraphy. Among this existing research a variety of analyses have been employed to characterize 24-h rhythm, reducing ability to evaluate and synthesize findings. Few studies have examined the correspondence of mother and infant circadian parameters for the most frequently cited approaches: cosinor, non-parametric circadian rhythm analysis (NPCRA), and autocorrelation function (ACF). The purpose of this research was to examine analytic approaches in the study of mother and infant circadian activity rhythm. Forty-three healthy mother and infant pairs were studied in the home environment over a 72h period at infant age 4, 8, and 12 weeks. Activity was recorded continuously using actigraphy monitors and mothers completed a diary. Parameters of circadian rhythm were generated from cosinor analysis, NPCRA, and ACF. The correlation among measures of rhythm center (cosinor mesor, NPCRA mid level), strength or fit of 24-h period (cosinor magnitude and R(2), NPCRA amplitude and relative amplitude (RA)), phase (cosinor acrophase, NPCRA M10 and L5 midpoint), and rhythm stability and variability (NPCRA interdaily stability (IS) and intradaily variability (IV), ACF) was assessed, and additionally the effect size (eta(2)) for change over time evaluated. Results suggest that cosinor analysis, NPCRA, and autocorrelation provide several comparable parameters of infant and maternal circadian rhythm center, fit, and phase. IS and IV were strongly correlated with the 24-h cycle fit. The circadian parameters analyzed offer separate insight into rhythm and differing effect size for the detection of change over time. Findings inform selection of analysis and

  10. Effect of melatonin on antioxidant status and circadian activity rhythm during hepatocarcinogenesis in mice

    Devi Verma; Onn Haji Hashim; Jaime Jacqueline Jayapalan; Perumal Subramanian

    2014-01-01

    Aim: Alteration of circadian systems can cause cancer and affects its development and response to therapeutics. The present study investigates whether cancer can disrupt circadian locomotor rhythms and evaluated the influence of melatonin (MLT) and oxaliplatin on the levels of antioxidants and circadian locomotor activity rhythms in N-nitrosodiethylamine (NDEA)-induced liver tumor in Indian field mouse (Mus booduga). Materials and Methods: Effects of NDEA, NDEA, and MLT, as well as NDEA an...

  11. Glutamate phase shifts circadian activity rhythms in hamsters

    Meijer, J.H.; van der Zee, E.A.; Dietz, M.

    1988-01-01

    The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Photic entrainment of this pacemaker can be accomplished via the direct retino-hypothalamic tract (RHT). Glutamate is a putative transmitter of the RHT. In the present study it is demonstrated

  12. Circadian rhythm of rest activity and autonomic nervous system activity at different stages in Parkinson's disease.

    Niwa, Fumitoshi; Kuriyama, Nagato; Nakagawa, Masanori; Imanishi, Jiro

    2011-12-01

    Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, including sleep and autonomic dysfunctions, controlled by circadian regulation. To evaluate the alteration of circadian rhythm in PD patients, we investigated both rest activities and autonomic functions. Twenty-seven patients with idiopathic PD and 30 age-matched control subjects were recruited. Group comparisons of controls (mean age: 68.93 years), early-PD patients classified as Hoehn-Yahr (HY) stage 1&2 (mean age: 70.78 years), and advanced-PD as HY 3&4 (mean age: 68.61 years) were conducted. Measurement of rest activities was performed using Actigraph for 7 continuous days, and included measuring rhythm patterns (activity patterns recorded in or out of bed) and circadian rhythm amplitudes (power of the cycle being closest to 24h). A power spectral analysis of heart rate variability (HRV) using 24-hour ambulatory ECG was also performed. The actigraphic measurements indicated that statistically PD patients have lower activity levels when out of bed and higher activity levels when in bed, and that, the circadian rest-activity rhythm in PD decreases with disease severity. The HRV analysis showed that the total frequency component and low frequency/high frequency ratio were low in PD patients, suggesting that autonomic activities and the circadian rhythm of the sympathetic nervous system are attenuated in PD. This study elucidated the disorganization in the rest activities and HRV of PD patients as well as the gradual alterations in the circadian rhythm. The circadian rhythm disturbances are important to consider the mechanism of non-motor symptoms that occur from early stage of PD.

  13. Circadian rhythms in microalgae production

    Winter, de L.

    2015-01-01

    Abstract Thesis: Circadian rhythms in microalgae production Lenneke de Winter The sun imposes a daily cycle of light and dark on nearly all organisms. The circadian clock evolved to help organisms program their activities at an appropriate time during this daily cycle. For example,

  14. Circadian rhythm of activity during the annual phases in the European quail, Coturnix coturnix.

    Lumineau, S; Guyomarc'h, C

    2000-09-01

    Migratory birds, such as the European quail, present an annual cycle with the following phases: moult, fattening, migration and reproduction. This study aimed at determining how variations in the circadian rhythm of feeding during the annual cycle took endogenous rhythmic characteristics into account. The birds (n = 8) were maintained under constant dim light from the age of 1 to 9 months. Feeding activity was recorded using infra-red detectors. The birds expressed all the phases, except migration. Activity was arrhythmic when they were moulting. A circadian rhythm of feeding activity appeared during the fattening phase. In males, the circadian period lengthened and the clarity of the rhythm increased during sexual development. These results appear to confirm the effects of physiological state on the temporal organisation of activity. Variations of the circadian rhythm could influence the ability to synchronize with exogenous cycles such as the alternation of day and night.

  15. Circadian rhythm sleep disorders

    Morgenthaler TI

    2012-05-01

    Full Text Available Bhanu P Kolla,1,2 R Robert Auger,1,2 Timothy I Morgenthaler11Mayo Center for Sleep Medicine, 2Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Misalignment between endogenous circadian rhythms and the light/dark cycle can result in pathological disturbances in the form of erratic sleep timing (irregular sleep–wake rhythm, complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type, delayed sleep timing (delayed sleep phase disorder, or advanced sleep timing (advanced sleep phase disorder. Whereas these four conditions are thought to involve predominantly intrinsic mechanisms, circadian dysrhythmias can also be induced by exogenous challenges, such as those imposed by extreme work schedules or rapid transmeridian travel, which overwhelm the ability of the master clock to entrain with commensurate rapidity, and in turn impair approximation to a desired sleep schedule, as evidenced by the shift work and jet lag sleep disorders. This review will focus on etiological underpinnings, clinical assessments, and evidence-based treatment options for circadian rhythm sleep disorders. Topics are subcategorized when applicable, and if sufficient data exist. The length of text associated with each disorder reflects the abundance of associated literature, complexity of management, overlap of methods for assessment and treatment, and the expected prevalence of each condition within general medical practice.Keywords: circadian rhythm sleep disorders, assessment, treatment

  16. Dopaminergic regulation of circadian food anticipatory activity rhythms in the rat.

    Andrea N Smit

    Full Text Available Circadian activity rhythms are jointly controlled by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN and by food-entrainable circadian oscillators (FEOs located elsewhere. The SCN mediates synchrony to daily light-dark cycles, whereas FEOs generate activity rhythms synchronized with regular daily mealtimes. The location of FEOs generating food anticipation rhythms, and the pathways that entrain these FEOs, remain to be clarified. To gain insight into entrainment pathways, we developed a protocol for measuring phase shifts of anticipatory activity rhythms in response to pharmacological probes. We used this protocol to examine a role for dopamine signaling in the timing of circadian food anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats then received the D2 agonist quinpirole (1 mg/kg IP alone or after pretreatment with the dopamine synthesis inhibitor α-methylparatyrosine (AMPT. By comparison with vehicle injections, quinpirole administered 1-h before lights-off (19h before mealtime induced a phase delay of activity onset prior to the next meal. Delay shifts were larger in rats pretreated with AMPT, and smaller following quinpirole administered 4-h after lights-on. A significant shift was not observed in response to the D1 agonist SKF81297. These results provide evidence that signaling at D2 receptors is involved in phase control of FEOs responsible for circadian food anticipatory rhythms in rats.

  17. [Circadian rhythm sleep disorder].

    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.

  18. Circadian rhythms regulate amelogenesis.

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

    2013-07-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization.

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

    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.

  20. Sleep and activity rhythms in mice: a description of circadian patterns and unexpected disruptions in sleep.

    Mitler, M M; Lund, R; Sokolove, P G; Pittendrigh, C S; Dement, W C

    1977-08-05

    Studies on daily and circadian rhythms in wheel running and electrographically defined wakefulness, NREM sleep, and REM sleep in M. musculus were done to gather data on the temporal distribution of activity and sleep. Generally, peaks in NREM and sleep tended to coincide and to alternate with the coincident peaks of wakefulness and wheel running. However, during the active phase of the circadian wheel running cycle some NREM and REM sleep did occur; conversely, during its rest phase, wakefulness was often present. The most striking finding was that in mice with clearly entrained or free-running activity onsets, the circadian peak-through patterns in wakefulness, NREM, and REM sleep were not always distinct--they could be damped and/or polyphasic. Several explanations of these phenomena are considered.

  1. Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

    2008-01-01

    Abstract 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 d...

  2. SNC 80, a delta-opioid agonist, elicits phase advances in hamster circadian activity rhythms.

    Byku, M; Gannon, R L

    2000-05-15

    Non-photic stimuli administered to hamsters during the subjective day can cause phase advances in circadian wheel running activity. It is believed that afferent projections from the intergeniculate leaflet of the thalamus to circadian pacemaker cells within the suprachiasmatic nucleus mediate the phase shifting effects of some non-photic stimuli. In hamsters, many of the intergeniculate leaflet afferents contain enkephalin, yet the role of opioids in producing non-photic phase shifts in hamsters has not been reported. In the present study, we show that SNC 80, an agonist for the delta opioid receptor subtype, will phase advance hamster wheel running activity rhythms when administered late in the subjective day. These results indicate that opioids may be involved in modulating the circadian pacemaker in hamsters.

  3. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on

    Baandrup, Lone; Fasmer, Ole Bernt; Glenthøj, Birte Yding

    2016-01-01

    BACKGROUND: Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short......-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction...... is associated with changes in circadian rhythm parameters. METHOD: Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg) or matching placebo, and usual benzodiazepine dosage...

  4. Role of proinflammatory cytokines on lipopolysaccharide-induced phase shifts in locomotor activity circadian rhythm.

    Leone, M Juliana; Marpegan, Luciano; Duhart, José M; Golombek, Diego A

    2012-07-01

    We previously reported that early night peripheral bacterial lipopolysaccharide (LPS) injection produces phase delays in the circadian rhythm of locomotor activity in mice. We now assess the effects of proinflammatory cytokines on circadian physiology, including their role in LPS-induced phase shifts. First, we investigated whether differential systemic induction of classic proinflammatory cytokines could explain the time-specific behavioral effects of peripheral LPS. Induction levels for plasma interleukin (IL)-1α, IL-1β, IL-6, or tumor necrosis factor (TNF)-α did not differ between animals receiving a LPS challenge in the early day or early night. We next tested the in vivo effects of central proinflammatory cytokines on circadian physiology. We found that intracerebroventricular (i.c.v.) delivery of TNF-α or interleukin IL-1β induced phase delays on wheel-running activity rhythms. Furthermore, we analyzed if these cytokines mediate the LPS-induced phase shifts and found that i.c.v. administration of soluble TNF-α receptor (but not an IL-1β antagonistic) prior to LPS stimulation inhibited the phase delays. Our work suggests that the suprachiasmatic nucleus (SCN) responds to central proinflammatory cytokines in vivo, producing phase shifts in locomotor activity rhythms. Moreover, we show that the LPS-induced phase delays are mediated through the action of TNF-α at the central level, and that systemic induction of proinflammatory cytokines might be necessary, but not sufficient, for this behavioral outcome.

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

    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.

  6. Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

    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

  7. Circadian Rhythm Management System Project

    National Aeronautics and Space Administration — The value of measuring sleep-wake cycles is significantly enhanced by measuring other physiological signals that depend on circadian rhythms (such as heart rate and...

  8. Masking of the circadian rhythms of heart rate and core temperature by the rest-activity cycle in man

    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.

  9. Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.

    Naoto Hayasaka

    Full Text Available Regulators of G protein signaling (RGS are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs of G protein α-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.

  10. Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

    Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M; Rogers, Courtney O; Johnson, Russell L; Young, Martin E; Gamble, Karen L

    2015-04-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3β isoform. Whether phosphorylation of the other primary isoform (GSK3α) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (α and β) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN.

  11. Oestradiol Exposure Early in Life Programs Daily and Circadian Activity Rhythms in Adult Mice.

    Royston, S E; Bunick, D; Mahoney, M M

    2016-01-01

    Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity. However, the timing of when developmental oestrogens modify the timekeeping system is poorly understood. To test the hypothesis that alterations in postnatal oestrogenic signalling organise adult daily activity rhythms, we utilised aromatase knockout mice (ArKO), which lack the enzyme required for oestradiol synthesis. ArKO and wild-type (WT) males and females were administered either oestradiol (E) or oil (OIL) daily for the first 5 postnatal days (p1-5E and p1-5OIL , respectively) because this time encompasses the emergence of clock gene rhythmicity and light responsiveness in the suprachiasmatic nucleus, a bilateral hypothalamic structure regarded as the 'master oscillator'. After sexual maturation, gonadectomy and exogenous oestradiol supplementation, locomotor parameters were assessed. We determined that altered oestrogenic signalling in early life exerts organisational control over the expression of daily and circadian activity rhythms in adult mice. Specifically, p1-5E reduced total wheel running activity in male and female ArKO and female WT mice but had no effect on WT male activity levels. In females, wheel running was consolidated by p1-5E to the early versus late evening, a phenomenon characteristic of male mice. The time of peak activity was advanced by p1-5E in WT and ArKO females but not males. P1-5E shortened the length of the active phase (alpha) in WT males but had no effect on ArKO males or females of either genotypes. Finally, p1-5E altered the magnitude of photic-induced shifts, suggesting that developmental oestrogenic signalling impacts adult circadian functions. In the present study, we further define both a critical period of development of the adult timekeeping system and the role that oestrogenic signalling plays in the expression of daily and

  12. Effect of melatonin on endogenous circadian rhythm

    XU Feng; WANG Min; ZANG Ling-he

    2008-01-01

    Objective To further authenticate the role of melatonin on endogenous biologic clock system. Methods Pinealectomized mice were used in the experiments, a series of circadian rhythm of physiology index, such as glucocorticoid, amino acid neurotransmitter, immune function, sensitivity of algesia and body temperature were measured. Results Effects of melatonin on endogenous circadian rhythm roughly appeared four forms: 1) The model of inherent rhythm was invariant, but midvalue was removed. 2) Pacing function: pinealectomy and melatonin administration changed amplitude of the circadian vibration of aspartate, peripheral blood WBC and serum hemolysin. 3) Phase of rhythm changed, such as the effects on percentage of lymphocyte and sensitivity of algesia. 4) No effect, the circadian rhythm of body temperature belong to this form Conclusions Melatonin has effects some circadian rhythm, and it can adjust endogenous inherent rhythm and make the rhythm keep step with environmental cycle. Melatonin may be a kind of Zeitgeber, Pineal gland might being a rhythm bearing organ to some circadian rhythm.

  13. Circadian rhythms of women with fibromyalgia

    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.

  14. Circadian Disruption Alters the Effects of Lipopolysaccharide Treatment on Circadian and Ultradian Locomotor Activity and Body Temperature Rhythms of Female Siberian Hamsters.

    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.

  15. Chronotype influences activity circadian rhythm and sleep: differences in sleep quality between weekdays and weekend.

    Vitale, Jacopo A; Roveda, Eliana; Montaruli, Angela; Galasso, Letizia; Weydahl, Andi; Caumo, Andrea; Carandente, Franca

    2015-04-01

    Several studies have shown the differences among chronotypes in the circadian rhythm of different physiological variables. Individuals show variation in their preference for the daily timing of activity; additionally, there is an association between chronotype and sleep duration/sleep complaints. Few studies have investigated sleep quality during the week days and weekends in relation to the circadian typology using self-assessment questionnaires or actigraphy. The purpose of this study was to use actigraphy to assess the relationship between the three chronotypes and the circadian rhythm of activity levels and to determine whether sleep parameters respond differently with respect to time (weekdays versus the weekend) in Morning-types (M-types), Neither-types (N-types) and Evening-types (E-types). The morningness-eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16 M-types, 15 N-types and 19 E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth® actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To compare the amplitude and the acrophase among the three chronotypes, we used a one-way ANOVA followed by the Tukey-Kramer post-hoc test. To compare the Midline Estimating Statistic of Rhythm (MESOR) among the three chronotypes, we used a Kruskal-Wallis non-parametric test followed by pairwise comparisons that were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. The analysis of each sleep parameter was conducted using the mixed ANOVA procedure. The results showed that the chronotype was influenced by sex (χ(2) with p = 0.011) and the photoperiod at birth (χ(2) with p sleep parameters: Sleep end, Assumed Sleep, Immobility Time and Sleep Efficiency. Sleep Efficiency showed the same patterns as did Assumed Sleep and Immobility Time: the Sleep

  16. ADHD, circadian rhythms and seasonality

    Wynchank, Dora S.; Bijlenga, Denise; Lamers, Femke; Bron, Tannetje I.; Winthorst, Wim H.; Vogel, Suzan W.; Penninx, Brenda W.; Beekman, Aartjan T.; Kooij, J. Sandra

    2016-01-01

    Objective: We evaluated whether the association between Adult Attention-Deficit/Hyperactivity Disorder (ADHD) and Seasonal Affective Disorder (SAD) was mediated by the circadian rhythm. Method: Data of 2239 persons from the Netherlands Study of Depression and Anxiety (NESDA) were used. Two groups we

  17. Circadian rhythm and its role in malignancy

    Rana, Sobia; Mahmood, Saqib

    2010-01-01

    Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circ...

  18. Circadian rhythms of PERIOD1 expression in the dorsomedial hypothalamic nucleus in the absence of entrained food-anticipatory activity rhythms in rats.

    Verwey, Michael; Lam, Germain Y M; Amir, Shimon

    2009-06-01

    When food availability is restricted to a single time of day, circadian rhythms of behavior and physiology in rodents shift to anticipate the predictable time of food arrival. It has been hypothesized that certain food-anticipatory rhythms are linked to the induction and entrainment of rhythms in clock gene expression in the dorsomedial hypothalamic nucleus (DMH), a putative food-entrained circadian oscillator. To study this concept further, we made food availability unpredictable by presenting the meal at a random time each day (variable restricted feeding, VRF), either during the day, night or throughout the 24-h cycle. Wheel running activity and the expression of the clock protein, Period1 (PER1), in the DMH and the suprachiasmatic nucleus (SCN) were assessed. Rats exhibited increased levels of activity during the portion of the day when food was randomly presented but, as expected, failed to entrain anticipatory wheel running activity to a single time of day. PER1 expression in the SCN was unchanged by VRF schedules. In the DMH, PER1 expression became rhythmic, peaking at opposite times of day in rats fed only during the day or during the night. In rats fed randomly throughout the entire 24-h cycle, PER1 expression in the DMH remained arrhythmic, but was elevated. These results demonstrate that VRF schedules confined to the day or night can induce circadian rhythms of clock gene expression in the DMH. Such feeding schedules cannot entrain behavioral rhythms, thereby showing that food-entrainment of behavior and circadian rhythms of clock gene expression in the DMH are dissociable.

  19. Circadian rhythm of spontaneous locomotor activity in the bed bug, Cimex lectularius L.

    Romero, Alvaro; Potter, Michael F; Haynes, Kenneth F

    2010-11-01

    Bed bugs must avoid detection when finding hosts and returning to hidden harborages. Their stealthy habits include foraging when hosts are asleep. Characteristics of spontaneous locomotor activity rhythm of bed bugs with different feeding histories were studied. In the absence of host stimuli, adults and nymphs were much more active in the dark than in the light. The onset of activity in the scotophase commenced soon after lights-off. The free-running period (tau) for all stages was longer in continuous darkness (DD) than in continuous light (LL). The lengthening of tau in DD is an exception for the circadian rule that predicts the opposite in nocturnal animals. Activity in all stages was entrained to reverse L:D regimes within four cycles. Short-term starved adults moved more frequently than recently fed adults. While bed bugs can survive for a year or more without a blood meal, we observed a reduction in activity in insects held for five weeks without food. We suggest that bed bugs make a transition to host-stimulus dependent searching when host presence is not predictable. Such a strategy would enable bed bugs to maximize reproduction when resources are abundant and save energy when resources are scarce.

  20. S20098 affects the free-running rhythms of body temperature and activity and decreases light-induced phase delays of circadian rhythms of the rat

    Tuma, J; Strubbe, JH; Mocaer, E.; KOOLHAAS, JM; Koolhaas, Jaap M.

    2001-01-01

    Mammalian endogenous circadian rhythms are entrained to the environmental day-night cycle by light exposure. Melatonin is involved in this entrainment by signaling the day-night information to the endogenous circadian pacemaker. Furthermore, melatonin is known to affect the circadian rhythm of body temperature directly. A striking property of the endogenous melatonin signal is its synthesis pattern, characterized by long-term elevated melatonin levels throughout the night. In the present stud...

  1. Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

    Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

  2. Development of cortisol circadian rhythm in infancy.

    Weerth, C. de; Zijl, R.H.

    2003-01-01

    BACKGROUND AND AIMS: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agr

  3. Drugs of Abuse Can Entrain Circadian Rhythms

    Ann E. K. Kosobud

    2007-01-01

    Full Text Available Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.

  4. Temperature compensation and entrainment in circadian rhythms

    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.

  5. Circadian rhythms synchronize mitosis in Neurospora crassa

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

    2014-01-01

    Circadian rhythms provide temporal information to other cellular processes, such as metabolism. We investigate the coupling between the cell cycle and the circadian clock using mathematical modeling and experimentally validate model-driven predictions with a model filamentous fungus, Neurospora crassa. We demonstrate a conserved coupling mechanism between the cell cycle and the circadian clock in Neurospora as in mammals, which results in circadian clock-gated mitotic cycles. Furthermore, we ...

  6. Zebrafish temperature selection and synchronization of locomotor activity circadian rhythm to ahemeral cycles of light and temperature.

    López-Olmeda, Jose Fernando; Sánchez-Vázquez, Francisco Javier

    2009-02-01

    In addition to light cycles, temperature cycles are among the most important synchronizers in nature. Indeed, both clock gene expression and circadian activity rhythms entrain to thermocycles. This study aimed to extend our knowledge of the relative strength of light and temperature as zeitgebers for zebrafish locomotor activity rhythms. When the capacity of a 24:20 degrees C (thermophase:cryophase, referred to as TC) thermocycle to synchronize activity rhythms under LL was evaluated, it was found that most groups (78%) synchronized to these conditions. Under LD, when zebrafish were allowed to select the water temperature (24 degrees C vs. 20 degrees C), most fish selected the higher temperature and showed diurnal activity, while a small (25%) percentage of fish that preferred the lower temperature displayed nocturnal activity. Under conflicting LD and TC cycles, fish showed diurnal activity when the zeitgebers were in phase or in antiphase, with a high percentage of activity displayed around dawn and dusk (22% and 34% of the total activity for LD/TC and LD/CT, respectively). Finally, to test the relative strength of each zeitgeber, fish were subjected to ahemeral cycles of light (T=25 h) and temperature (T=23 h). Zebrafish synchronized mostly to the light cycle, although they displayed relative coordination, as their locomotor activity increased when light and thermophase coincided. These findings show that although light is a stronger synchronizer than temperature, TC cycles alone can entrain circadian rhythms and interfere in their light synchronization, suggesting the existence of both light- and temperature-entrainable oscillators that are weakly coupled.

  7. Chemical composition, circadian rhythm and antibacterial activity of essential oils of piper divaricatum: a new source of safrole

    Queila P. S. Barbosa

    2012-01-01

    Full Text Available The essential oils from leaves, stems and fruits of Piper divaricatum were analyzed by GC-MS. The tissues showed high safrole content: leaves (98%, fruits (87% and stems (83%, with yields of 2.0, 4.8 and 1.7%, respectively. This is a new alternative source of safrole, a compound widely used as a flavoring agent and insecticide. The leaf's oil showed antibacterial activity against gram-negative bacteria while safrole was active against Salmonella Typhimurium and Pseudomonas aeruginosa. In addition, the study of circadian rhythm of the safrole concentration in the essential oils of leaves showed a negligible variation of 92 to 98%.

  8. Circadian Rhythm in Cytokines Administration.

    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.

  9. Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin.

    Ying Wu

    2008-11-01

    induces rhythmic action potential bursts and depolarized plateau potentials. These in vitro and in vivo electrophysiological effects of membrane-tethered delta-ACTX-Hv1a are consistent with the effects of soluble delta-ACTX-Hv1a purified from venom on Na(+ channel physiological and biophysical properties in cockroach neurons. Membrane-tethered delta-ACTX-Hv1a expression in the PDF-secreting subset of clock neurons induces an approximately 4-h phase advance of the rhythm of PDF accumulation in their terminals relative to both the phase of the day:night cycle and the phase of the circadian transcriptional feedback loops. As a consequence, the morning anticipatory peak of locomotor activity preceding dawn, which has been shown to be driven by the clocks of the PDF-secreting subset of clock neurons, phase advances coordinately with the phase of the PDF rhythm of the PDF-secreting clock neurons, rather than maintaining its phase relationship with the day:night cycle and circadian transcriptional feedback loops. These results (1 validate the tethered-toxin technology for cell-autonomous modulation of ion channel biophysical properties in vivo in transgenic Drosophila, (2 demonstrate that the kinetics of para Na(+ channel inactivation is a key parameter for determining the phase relationship between circadian transcriptional feedback oscillation and PDF secretion, and (3 provide experimental support for the hypothesis that PDF-secreting clock neurons entrain the phase of organismal rhythms via the temporal patterning of secreted PDF signals.

  10. Timekeeping through social contacts: social synchronization of circadian locomotor activity rhythm in the carpenter ant Camponotus paria.

    Lone, Shahnaz Rahman; Sharma, Vijay Kumar

    2011-12-01

    In ant colonies a large proportion of individuals remain inside nests for most of their lives and come out only when necessary. It is not clear how, in a nest of several thousand individuals, information about local time is communicated among members of the colony. Central to this seem to be circadian clocks, which have an intrinsic ability to keep track of local time by entraining to environmental light-dark, temperature, and social cycles. Here, the authors report the results of their study aimed at understanding the role of cyclic social interactions in circadian timekeeping of a day-active species of carpenter ant Camponotus paria. The authors found that daily social interactions with visitors (worker ants) was able to synchronize the circadian locomotor activity rhythm of host worker ants and queens, in one-on-one (pair-wise) and multi-individual (group-wise) interactions. Interestingly, the outcome of cyclic social interactions was context specific; when visitor workers socially interacted with host workers one-on-one, host workers considered the time of interaction as subjective day, but when visitor workers interacted with a group of workers and queens, the hosts considered the time of interaction as subjective night. These results can be taken to suggest that members of the ant species C. paria keep track of local time by socially interacting with workers (foragers) who shuttle in and out of the colony in search of food. (Author correspondence: vsharma@jncasr.ac.in ).

  11. A New Perspective for Parkinson's Disease: Circadian Rhythm.

    Li, Siyue; Wang, Yali; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

    2017-02-01

    Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

  12. Circadian rhythm of outside-nest activity in wild (WWCPS, albino and pigmented laboratory rats.

    Rafał Stryjek

    Full Text Available The domestication process of the laboratory rat has been going on for several hundred generations in stable environmental conditions, which may have affected their physiological and behavioural functions, including their circadian system. Rats tested in our ethological experiments were laboratory-bred wild Norway rats (WWCPS, two strains of pigmented laboratory rats (Brown Norway and Long Evans, and two strains of albino rats (Sprague-Dawley and Wistar. Rats were placed in purpose-built enclosures and their cycle of activity (time spent actively outside the nest has been studied for one week in standard light conditions and for the next one in round-the-clock darkness. The analysis of circadian pattern of outside-nest activity revealed differences between wild, pigmented laboratory, and albino laboratory strains. During daytime, albino rats showed lower activity than pigmented rats, greater decrease in activity when the light was turned on and greater increase in activity when the light was switched off, than pigmented rats. Moreover albino rats presented higher activity during the night than wild rats. The magnitude of the change in activity between daytime and nighttime was also more pronounced in albino rats. Additionaly, they slept outside the nest more often during the night than during the day. These results can be interpreted in accordance with the proposition that intense light is an aversive stimulus for albino rats, due to lack of pigment in their iris and choroid, which reduces their ability to adapt to light. Pigmented laboratory rats were more active during lights on, not only in comparison to the albino, but also to the wild rats. Since the difference seems to be independent of light intensity, it is likely to be a result of the domestication process. Cosinor analysis revealed a high rhythmicity of circadian cycles in all groups.

  13. Neurobiology of Circadian Rhythm Regulation.

    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.

  14. [Circadian rhythm of human lymphocyte subpopulations].

    Pasqualetti, P; Colantonio, D; Casale, R; Colangeli, S; Natali, G

    1988-01-01

    Circadian rhythm of lymphocyte subsets was investigated in four healthy subjects, males, aged 35-58 years old. After a period of ambiental synchronization, venous blood samples were taken during a span of a day at 0.00 a.m., 4.00 a.m., 8.00 a.m., noon, 4.00 p.m. and 8.00 p.m. Lymphocyte subsets (OKT3, OKT4, OKT8, OKB7, OKJa1) were determined by monoclonal antibodies method, and serum level of cortisol by radioimmunoassay method. The OKT4/OKT8 ratio was also calculated. Data were analyzed by chronograms (mean +/- 1SD) and by cosinor method. Results show a significant circadian rhythm for each lymphocyte subset and for serum cortisol levels. The lowest levels of all circulating subsets were seen between noon and 4.00 p.m. and the highest levels around midnight, inversely related with the circadian rhythm of serum cortisol. The OKT4/OKT8 ratio, on the contrary, was relatively constant during the day, without a significant circadian rhythm. These observations have laboratoristic, clinical, and therapeutic implications and should be considered in the course of immunological studies.

  15. Relationships between circadian rhythms and ethanol intake in mice

    Trujillo, Jennifer L.

    2009-01-01

    This dissertation integrates methods from alcohol and circadian rhythms research to explore relationships between ethanol and circadian rhythms in mice. Ingesting alcohol at certain times of day differentially affects the body; circadian rhythms also impact preference for drinking alcohol at different times of day. The influence of circadian timing on development and maintenance of ethanol drinking patterns was studied in Chapter 2. This showed how establishing a history of ethanol exposure a...

  16. Circadian rhythms in floral scent emission

    Myles eFenske

    2016-04-01

    Full Text Available To successfully recruit pollinators, plants often release attractive floral scents at specific times of day to coincide with pollinator foraging. This timing of scent emission is thought to be evolutionarily beneficial to maximize resource efficiency while attracting only useful pollinators. Temporal regulation of scent emission is tied to the activity of the specific metabolic pathways responsible for scent production. Although floral volatile profiling in various plants indicated a contribution by the circadian clock, the mechanisms by which the circadian clock regulates timing of floral scent emission remained elusive. Recent studies using two species in the Solanaceae family provided initial insight into molecular clock regulation of scent emission timing. In Petunia hybrida, the benzenoid/phenylpropanoid (FVBP pathway is the major metabolic pathway that produces floral volatiles. Three MYB-type transcription factors, ODORANT1 (ODO1, EMISSION OF BENZENOIDS I (EOBI, and EOBII, all of which show diurnal rhythms in mRNA expression, act as positive regulators for several enzyme genes in the FVBP pathway. Recently, in P. hybrida and Nicotiana attenuata, homologs of the Arabidopsis clock gene LATE ELONGATED HYPOCOTYL (LHY have been shown to have a similar role in the circadian clock in these plants, and to also determine the timing of scent emission. In addition, in P. hybrida, PhLHY directly represses ODO1 and several enzyme genes in the FVBP pathway during the morning as an important negative regulator of scent emission. These findings facilitate our understanding of the relationship between a molecular timekeeper and the timing of scent emission, which may influence reproductive success.

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

    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.

  18. Circadian rhythms synchronize mitosis in Neurospora crassa.

    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

    2014-01-28

    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 frq(ko) 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.

  19. Circadian Rhythm Shapes the Gut Microbiota Affecting Host Radiosensitivity.

    Cui, Ming; Xiao, Huiwen; Luo, Dan; Zhang, Xin; Zhao, Shuyi; Zheng, Qisheng; Li, Yuan; Zhao, Yu; Dong, Jiali; Li, Hang; Wang, Haichao; Fan, Saijun

    2016-10-26

    Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

  20. Circadian rhythm and cell population growth

    Clairambault, Jean; Lepoutre, Thomas

    2010-01-01

    Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictate rhythms of approximately 24 hours (circa diem) to many physiological processes. This includes metabolism (e.g., temperature, hormonal blood levels) and cell proliferation. It has been observed in tumor-bearing laboratory rodents that a severe disruption of these physiological rhythms results in accelerated tumor growth. The question of accurately representing the control exerted by circadian clocks on healthy and tumour tissue proliferation to explain this phenomenon has given rise to mathematical developments, which we review. The main goal of these previous works was to examine the influence of a periodic control on the cell division cycle in physiologically structured cell populations, comparing the effects of periodic control with no control, and of different periodic controls between them. We state here a general convexity result that may give a theoretical justification to the concept of cancer chronothera...

  1. Mechanisms by which circadian rhythm disruption may lead to cancer

    L. C. Roden

    2010-02-01

    Full Text Available Humans have evolved in a rhythmic environment and display daily (circadian rhythms in physiology, metabolism and behaviour that are in synchrony with the solar day. Modern lifestyles have compromised the exposure to bright light during the day and dark nights, resulting in the desynchronisation of endogenously generated circadian rhythms from the external environment and loss of coordination between rhythms within the body. This has detrimental effects on physical and mental health, due to the misregulation and uncoupling of important cellular and physiological processes. Long-term shift workers who are exposed to bright light at night experience the greatest disruption of their circadian rhythms. Studies have shown an association between exposure to light at night, circadian rhythm disruption and an increased risk of cancer. Previous reviews have explored the relevance of light and melatonin in cancer, but here we explore the correlation of circadian rhythm disruption and cancer in terms of molecular mechanisms affecting circadian gene expression and melatonin secretion.

  2. The association of quality of life with potentially remediable disruptions of circadian sleep/activity rhythms in patients with advanced lung cancer

    Braun Donald P

    2011-05-01

    Full Text Available Abstract Background Cancer patients routinely develop symptoms consistent with profound circadian disruption, which causes circadian disruption diminished quality of life. This study was initiated to determine the relationship between the severity of potentially remediable cancer-associated circadian disruption and quality of life among patients with advanced lung cancer. Methods We concurrently investigated the relationship between the circadian rhythms of 84 advanced lung cancer patients and their quality of life outcomes as measured by the EORTC QLQ C30 and Ferrans and Powers QLI. The robustness and stability of activity/sleep circadian daily rhythms were measured by actigraphy. Fifty three of the patients in the study were starting their definitive therapy following diagnosis and thirty one patients were beginning second-line therapy. Among the patients who failed prior therapy, the median time between completing definitive therapy and baseline actigraphy was 4.3 months, (interquartile range 2.1 to 9.8 months. Results We found that circadian disruption is universal and severe among these patients compared to non-cancer-bearing individuals. We found that each of these patient's EORTC QLQ C30 domain scores revealed a compromised capacity to perform the routine activities of daily life. The severity of several, but not all, EORTC QLQ C30 symptom items correlate strongly with the degree of individual circadian disruption. In addition, the scores of all four Ferrans/Powers QLI domains correlate strongly with the degree of circadian disruption. Although Ferrans/Powers QLI domain scores show that cancer and its treatment spared these patients' emotional and psychological health, the QLI Health/Function domain score revealed high levels of patients' dissatisfaction with their health which is much worse when circadian disruption is severe. Circadian disruption selectively affects specific Quality of Life domains, such as the Ferrans/Powers Health

  3. Isochron-Based Phase Response Analysis of Circadian Rhythms

    Gunawan, Rudiyanto; Doyle, Francis J.

    2006-01-01

    Circadian rhythms possess the ability to robustly entrain to the environmental cycles. This ability relies on the phase synchronization of circadian rhythm gene regulation to different environmental cues, of which light is the most obvious and important. The elucidation of the mechanism of circadian entrainment requires an understanding of circadian phase behavior. This article presents two phase analyses of oscillatory systems for infinitesimal and finite perturbations based on isochrons as ...

  4. Torpor shortens the period of Siberian hamster circadian rhythms.

    Thomas, E M; Jewett, M E; Zucker, I

    1993-10-01

    We investigated the influence of ambient and body temperature (Ta and Tb) on circadian rhythms of gonadectomized male Siberian hamsters. Animals that entered torpor (Tb circadian periods (tau s) than did nontorpid hamsters at a Ta of 13 degrees C (24.17 +/- 0.05 vs. 24.33 +/- 0.04 h). The tau s of homeothermic hamsters were not affected by Ta change. Short-term decreases in Tb, rather than changes in Ta, appear to affect tau. Access to activity wheels inhibited expression of torpor in short daylengths and was associated with significant increases in body mass. Running wheel activity can mask or block specific short-day responses.

  5. Exploration of Circadian Rhythms in Patients with Bilateral Vestibular Loss.

    Tristan Martin

    Full Text Available New insights have expanded the influence of the vestibular system to the regulation of circadian rhythmicity. Indeed, hypergravity or bilateral vestibular loss (BVL in rodents causes a disruption in their daily rhythmicity for several days. The vestibular system thus influences hypothalamic regulation of circadian rhythms on Earth, which raises the question of whether daily rhythms might be altered due to vestibular pathology in humans. The aim of this study was to evaluate human circadian rhythmicity in people presenting a total bilateral vestibular loss (BVL in comparison with control participants.Nine patients presenting a total idiopathic BVL and 8 healthy participants were compared. Their rest-activity cycle was recorded by actigraphy at home over 2 weeks. The daily rhythm of temperature was continuously recorded using a telemetric device and salivary cortisol was recorded every 3 hours from 6:00AM to 9:00PM over 24 hours. BVL patients displayed a similar rest activity cycle during the day to control participants but had higher nocturnal actigraphy, mainly during weekdays. Sleep efficiency was reduced in patients compared to control participants. Patients had a marked temperature rhythm but with a significant phase advance (73 min and a higher variability of the acrophase (from 2:24 PM to 9:25 PM with no correlation to rest-activity cycle, contrary to healthy participants. Salivary cortisol levels were higher in patients compared to healthy people at any time of day.We observed a marked circadian rhythmicity of temperature in patients with BVL, probably due to the influence of the light dark cycle. However, the lack of synchronization between the temperature and rest-activity cycle supports the hypothesis that the vestibular inputs are salient input to the circadian clock that enhance the stabilization and precision of both external and internal entrainment.

  6. Entrainment of circadian rhythm by ambient temperature cycles in mice.

    Refinetti, Roberto

    2010-08-01

    Much is known about how environmental light-dark cycles synchronize circadian rhythms in animals. The ability of environmental cycles of ambient temperature to synchronize circadian rhythms has also been investigated extensively but mostly in ectotherms. In the present study, the synchronization of the circadian rhythm of running-wheel activity by environmental cycles of ambient temperature was studied in laboratory mice. Although all mice were successfully entrained by a light-dark cycle, only 60% to 80% of the mice were entrained by temperature cycles (24-32 degrees C or 24-12 degrees C), and attainment of stable entrainment seemed to take longer under temperature cycles than under a light-dark cycle. This suggests that ambient temperature cycles are weaker zeitgebers than light-dark cycles, which is consistent with the results of the few previous studies using mammalian species. Whereas 80% of the mice were entrained by 24-h temperature cycles, only 60% were entrained by 23-h cycles, and none was entrained by 25-h cycles. The results did not clarify whether entrainment by temperature cycles is caused directly by temperature or indirectly through a temperature effect on locomotor activity, but it is clear that the rhythm of running-wheel activity in mice can be entrained by ambient temperature cycles in the nonnoxious range.

  7. Altered Circadian Food Anticipatory Activity Rhythms in PACAP Receptor 1 (PAC1) Deficient Mice.

    Hannibal, Jens; Georg, Birgitte; Fahrenkrug, Jan

    2016-01-01

    Light signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) entrain the circadian clock and regulate negative masking. Two neurotransmitters, glutamate and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP), found in the ipRGCs transmit light signals to the brain via glutamate receptors and the specific PACAP type 1 (PAC1) receptor. Light entrainment occurs during the twilight zones and has little effect on clock phase during daytime. When nocturnal animals have access to food only for a few hours during the resting phase at daytime, they adapt behavior to the restricted feeding (RF) paradigm and show food anticipatory activity (FAA). A recent study in mice and rats demonstrating that light regulates FAA prompted us to investigate the role of PACAP/PAC1 signaling in the light mediated regulation of FAA. PAC1 receptor knock out (PAC1-/-) and wild type (PAC1+/+) mice placed in running wheels were examined in a full photoperiod (FPP) of 12:12 h light/dark (LD) and a skeleton photoperiod (SPP) 1:11:1:11 h L:DD:L:DD at 300 and 10 lux light intensity. Both PAC1-/- mice and PAC1+/+ littermates entrained to FPP and SPP at both light intensities. However, when placed in RF with access to food for 4-5 h during the subjective day, a significant change in behavior was observed in PAC1-/- mice compared to PAC1+/+ mice. While PAC1-/- mice showed similar FAA as PAC1+/+ animals in FPP at 300 lux, PAC1-/- mice demonstrated an advanced onset of FAA with a nearly 3-fold increase in amplitude compared to PAC1+/+ mice when placed in SPP at 300 lux. The same pattern of FAA was observed at 10 lux during both FPP and SPP. The present study indicates a role of PACAP/PAC1 signaling during light regulated FAA. Most likely, PACAP found in ipRGCs mediating non-image forming light information to the brain is involved.

  8. Altered Circadian Food Anticipatory Activity Rhythms in PACAP Receptor 1 (PAC1 Deficient Mice.

    Jens Hannibal

    Full Text Available Light signals from intrinsically photosensitive retinal ganglion cells (ipRGCs entrain the circadian clock and regulate negative masking. Two neurotransmitters, glutamate and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP, found in the ipRGCs transmit light signals to the brain via glutamate receptors and the specific PACAP type 1 (PAC1 receptor. Light entrainment occurs during the twilight zones and has little effect on clock phase during daytime. When nocturnal animals have access to food only for a few hours during the resting phase at daytime, they adapt behavior to the restricted feeding (RF paradigm and show food anticipatory activity (FAA. A recent study in mice and rats demonstrating that light regulates FAA prompted us to investigate the role of PACAP/PAC1 signaling in the light mediated regulation of FAA. PAC1 receptor knock out (PAC1-/- and wild type (PAC1+/+ mice placed in running wheels were examined in a full photoperiod (FPP of 12:12 h light/dark (LD and a skeleton photoperiod (SPP 1:11:1:11 h L:DD:L:DD at 300 and 10 lux light intensity. Both PAC1-/- mice and PAC1+/+ littermates entrained to FPP and SPP at both light intensities. However, when placed in RF with access to food for 4-5 h during the subjective day, a significant change in behavior was observed in PAC1-/- mice compared to PAC1+/+ mice. While PAC1-/- mice showed similar FAA as PAC1+/+ animals in FPP at 300 lux, PAC1-/- mice demonstrated an advanced onset of FAA with a nearly 3-fold increase in amplitude compared to PAC1+/+ mice when placed in SPP at 300 lux. The same pattern of FAA was observed at 10 lux during both FPP and SPP. The present study indicates a role of PACAP/PAC1 signaling during light regulated FAA. Most likely, PACAP found in ipRGCs mediating non-image forming light information to the brain is involved.

  9. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

    Skene, Debra J.; Arendt, Josephine; Cade, Janet E.; Grant, Peter J.; Hardie, Laura J.

    2016-01-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important. PMID:27763782

  10. Circadian rhythms of photorefractory siberian hamsters remain responsive to melatonin.

    Butler, Matthew P; Paul, Matthew J; Turner, Kevin W; Park, Jin Ho; Driscoll, Joseph R; Kriegsfeld, Lance J; Zucker, Irving

    2008-04-01

    Short day lengths increase the duration of nocturnal melatonin (Mel) secretion, which induces the winter phenotype in Siberian hamsters. After several months of continued exposure to short days, hamsters spontaneously revert to the spring-summer phenotype. This transition has been attributed to the development of refractoriness of Mel-binding tissues, including the suprachiasmatic nucleus (SCN), to long-duration Mel signals. The SCN of Siberian hamsters is required for the seasonal response to winter-like Mel signals, and becomes refractory to previously effective long-duration Mel signals restricted to this area. Acute Mel treatment phase shifts circadian locomotor rhythms of photosensitive Siberian hamsters, presumably by affecting circadian oscillators in the SCN. We tested whether seasonal refractoriness of the SCN to long-duration Mel signals also renders the circadian system of Siberian hamsters unresponsive to Mel. Males manifesting free-running circadian rhythms in constant dim red light were injected with Mel or vehicle for 5 days on a 23.5-h T-cycle beginning at circadian time 10. Mel injections caused significantly larger phase advances in activity onset than did the saline vehicle, but the magnitude of phase shifts to Mel did not differ between photorefractory and photosensitive hamsters. Similarly, when entrained to a 16-h light/8-h dark photocycle, photorefractory and photosensitive hamsters did not differ in their response to Mel injected 4 h before the onset of the dark phase. Activity onset in Mel-injected hamsters was masked by light but was revealed to be significantly earlier than in vehicle-injected hamsters upon transfer to constant dim red light. The acute effects of melatonin on circadian behavioral rhythms are preserved in photorefractory hamsters.

  11. Circadian rhythms, the molecular clock, and skeletal muscle.

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

    2011-01-01

    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(Δ19) 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.

  12. Circadian rhythms and new options for novel anticancer therapies

    Prosenc Zmrzljak U

    2015-01-01

    Full Text Available Ursula Prosenc ZmrzljakFaculty of Medicine, Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, University of Ljubljana, Ljubljana, SloveniaAbstract: The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.Keywords: circadian rhythms, cancer, chronotherapy, detoxification metabolism

  13. Exposure to T-cycles of 22 and 23 h during lactation modifies the later dissociation of motor activity and temperature circadian rhythms in rats.

    Anglès-Pujolràs, Montserrat; Díez-Noguera, Antoni; Cambras, Trinitat

    2007-01-01

    Early environmental conditions may affect the development and manifestation of circadian rhythms. This study sought to determine whether the maintenance of rats under different T-cycles during lactation influences the subsequent degree of dissociation of the circadian rhythms of motor activity and core body temperature. Two groups of 22 day-old Wistar rats were kept after weaning under T-cycles of 22 h (T22) or 23 h (T23) for 70 days. Subsequently, they were kept in constant darkness (DD). Half of the animals in each group were born and reared under these experimental conditions, while the other half were reared until weaning under 24 h LD cycles (T24). Rats transferred from T24 to T22 or T23 showed two circadian components in motor activity and temperature, one entrained by light and the other free-running. In T22, there was also desynchronization between temperature and motor activity. Rats submitted to T23 from birth showed higher stability of the 23 h component than rats transferred from T24 to T23 after weaning. However, in comparison to rats born under T24 and subsequently changed to T22, animals submitted to T22 from birth showed shorter values of the period of the non-light-dependent component during T22, more aftereffects when transferred to DD, and a lack of desynchronization between motor activity and temperature. The results suggest that T-cycles in the early environment may modify overt rhythms by altering the internal coupling of the circadian pacemaker.

  14. Activity, sleep and ambient light have a different impact on circadian blood pressure, heart rate and body temperature rhythms.

    Gubin, D G; Weinert, D; Rybina, S V; Danilova, L A; Solovieva, S V; Durov, A M; Prokopiev, N Y; Ushakov, P A

    2017-02-16

    The aim of the present study was to investigate the impact of endogenous and exogenous factors for the expression of the daily rhythms of body temperature (BT), blood pressure (BP) and heart rate (HR). One hundred and seventy-three young adults (YA), 17-24 years old (y.o.), of both genders were studied under a modified constant-routine (CR) protocol for 26 h. Participants were assigned randomly to groups with different lighting regimens: CR-LD, n = 77, lights (>400 l×) on from 09:00 to 17:00 h and off (400 l×) during the whole experimental session; CR-DD, n = 15, constant dim light (measured every 2 h. For comparison, the results of the former studies performed under conditions of regular life with an activity period from 07:00 to 23:00 h and sleep from 23:00 till 07:00 h (Control) were reanalyzed. Seven-day Ambulatory Blood Pressure Monitoring (ABPM) records from 27 YA (16-38 y.o.) and BT self-measurement data from 70 YA (17-30 y.o.) taken on ≥ 3 successive days at 08:00, 11:00, 14:00, 17:00, 20:00, 23:00 and 03:00 were available. The obtained daily patterns were different between Control and CR-DD groups, due to effects of activity, sleep and light. The comparison of Control and CR-LD groups allowed the effects of sleep and activity to be estimated since the lighting conditions were similar. The activity level substantially elevated SBP, but not DBP. Sleep, on the other hand, lowered the nighttime DBP, but has no effect on SBP. HR was affected both by activity and sleep. In accordance with previous studies, these results confirm that the steep BP increase in the morning is not driven by the circadian clock, but rather by sympathoadrenal factors related to awakening and corresponding anticipatory mechanisms. The effect on BT was not significant. To investigate the impact of light during the former dark time and darkness during the former light time, the CR-LL and CR-DD groups were each compared with the CR-LD group. Light delayed the evening decrease of BT

  15. Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats.

    Mairesse, Jerome; Silletti, Viviana; Laloux, Charlotte; Zuena, Anna Rita; Giovine, Angela; Consolazione, Michol; van Camp, Gilles; Malagodi, Marithe; Gaetani, Silvana; Cianci, Silvia; Catalani, Assia; Mennuni, Gioacchino; Mazzetta, Alessandro; van Reeth, Olivier; Gabriel, Cecilia; Mocaër, Elisabeth; Nicoletti, Ferdinando; Morley-Fletcher, Sara; Maccari, Stefania

    2013-03-01

    Agomelatine is a novel antidepressant acting as an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist. Because of its peculiar pharmacological profile, this drug caters the potential to correct the abnormalities of circadian rhythms associated with mood disorders, including abnormalities of the sleep/wake cycle. Here, we examined the effect of chronic agomelatine treatment on sleep architecture and circadian rhythms of motor activity using the rat model of prenatal restraint stress (PRS) as a putative 'aetiological' model of depression. PRS was delivered to the mothers during the last 10 d of pregnancy. The adult progeny ('PRS rats') showed a reduced duration of slow wave sleep, an increased duration of rapid eye movement (REM) sleep, an increased number of REM sleep events and an increase in motor activity before the beginning of the dark phase of the light/dark cycle. In addition, adult PRS rats showed an increased expression of the transcript of the primary response gene, c-Fos, in the hippocampus just prior to the beginning of the dark phase. All these changes were reversed by a chronic oral treatment with agomelatine (2000 ppm in the diet). The effect of agomelatine on sleep was largely attenuated by treatment with the MT1/MT2 melatonin receptor antagonist, S22153, which caused PRS-like sleep disturbances on its own. These data provide the first evidence that agomelatine corrects sleep architecture and restores circadian homeostasis in a preclinical model of depression and supports the value of agomelatine as a novel antidepressant that resynchronizes circadian rhythms under pathological conditions.

  16. Persistence, entrainment, and function of circadian rhythms in polar vertebrates.

    Williams, Cory T; Barnes, Brian M; Buck, C Loren

    2015-03-01

    Polar organisms must cope with an environment that periodically lacks the strongest time-giver, or zeitgeber, of circadian organization-robust, cyclical oscillations between light and darkness. We review the factors influencing the persistence of circadian rhythms in polar vertebrates when the light-dark cycle is absent, the likely mechanisms of entrainment that allow some polar vertebrates to remain synchronized with geophysical time, and the adaptive function of maintaining circadian rhythms in such environments.

  17. Neuroimaging, cognition, light and circadian rhythms

    Giulia eGaggioni

    2014-07-01

    Full Text Available 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.

  18. A circadian rhythm regulating hyphal melanization in Cercospora kikuchii.

    Bluhm, Burton H; Burnham, A Michele; Dunkle, Larry D

    2010-01-01

    Many metabolic and developmental processes in fungi are controlled by biological rhythms. Circadian rhythms approximate a daily (24 h) cycle and have been thoroughly studied in the model fungus, Neurospora crassa. However relatively few examples of true circadian rhythms have been documented among other filamentous fungi. In this study we describe a circadian rhythm underlying hyphal melanization in Cercospora kikuchii, an important pathogen of soybean. After growth in light or light : dark cycles, colonies transferred to darkness produced zonate bands of melanized hyphae interspersed with bands of hyaline hyphae. Rhythmic production of bands was remarkably persistent in the absence of external cues, lasting at least 7 d after transfer to darkness, and was compensated over a range of temperatures. As in N. crassa, blue light but not red light was sufficient to entrain the circadian rhythm in C. kikuchii, and a putative ortholog of white collar-1, one of the genes required for light responses in N. crassa, was identified in C. kikuchii. Circadian regulation of melanization is conserved in other members of the genus: Similar rhythms were identified in another field isolate of C. kikuchii as well as field isolates of C. beticola and C. sorghi, but not in wild-type strains of C. zeae-maydis or C. zeina. This report represents the first documented circadian rhythm among Dothideomycete fungi and provides a new opportunity to dissect the molecular basis of circadian rhythms among filamentous fungi.

  19. Worsening of rest-activity circadian rhythm and quality of life in female breast cancer patients along progression of chemotherapy cycles.

    Sultan, Armiya; Choudhary, Vivek; Parganiha, Arti

    2017-02-16

    Chemotherapy and its associated side effects can induce the disruption of circadian rest-activity rhythm and may have negative consequences on health-related quality of life (HRQoL) of cancer patients. In the current study, repeated-measures cross-sectional design was implemented to determine the status of circadian rest-activity rhythm and to assess the HRQoL of newly diagnosed female breast cancer patients those were planned to receive six cycles of chemotherapy. Rest activity and HRQoL were assessed in twenty-five patients during chemotherapy cycles 1st (C1), 3rd (C3), and 6th (C6) immediately after they reported to the outdoor ward of the Regional Cancer Center, Pt. J.N.M. Medical College, Dr. B.R. Ambedkar Memorial Hospital, Raipur, India. Wrist actigraphs for consecutive spans of 3-4 days were used to record the rest-activity rhythm, and its parameters were computed with the help of Cosinor Rhythmometry. Quality of life (QoL) parameters were assessed using EORTC QLQ-C30 and QLQ-BR23. Results revealed that average scores of all rhythm parameters, such as MESOR, amplitude, acrophase, rhythm quotient, circadian quotient, peak activity, dichotomy index, and autocorrelation coefficient; and all functional scales of QLQ-C30, such as physical, role, emotional, cognitive, and social, and global quality of life statistically significantly decreased with the increasing number of chemotherapy cycles (C1 to C3 and C6). Scores of symptom scales of QLQ-C30, such as fatigue, pain, dyspnoea, insomnia, appetite loss, and diarrhea increased significantly from C1 to C6. Among the QLQ-BR23 scales, scores of sexual functioning, sexual enjoyment, breast symptoms, and arm symptoms significantly decreased, whereas scores of systemic therapy side effects, and upset by hair loss significantly increased across the chemotherapy cycles. We conclude that rest-activity rhythm disrupted and HRQoL of breast cancer patients worsened along the increasing number of chemotherapy cycles. We

  20. Sleep, Wakefulness and Circadian Rhythm

    1979-09-01

    Regardless which of the two reactions occur first, the catecholamines are degrcdec to the comon metabolite vanillylmandelic acid (VMA). In addition...been shown to be a peptide containing 36 amino acid residues of which the 24 on the amino-terminus of the molecule are required for activity. It has... acids , sterols, and others) Vlth the foregoing cmts as bacbgraund, it is now appropriate to consider the individual steps leading to glucocorticoid

  1. Pathophysiology and pathogenesis of circadian rhythm sleep disorders

    Hida Akiko

    2012-03-01

    Full Text Available Abstract Metabolic, physiological and behavioral processes exhibit 24-hour rhythms in most organisms, including humans. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues. The transcription and translation feedback loops of multiple clock genes are involved in the molecular mechanism of the circadian system. Disturbed circadian rhythms are known to be closely related to many diseases, including sleep disorders. Advanced sleep phase type, delayed sleep phase type and nonentrained type of circadian rhythm sleep disorders (CRSDs are thought to result from disorganization of the circadian system. Evaluation of circadian phenotypes is indispensable to understanding the pathophysiology of CRSD. It is laborious and costly to assess an individual's circadian properties precisely, however, because the subject is usually required to stay in a laboratory environment free from external cues and masking effects for a minimum of several weeks. More convenient measurements of circadian rhythms are therefore needed to reduce patients' burden. In this review, we discuss the pathophysiology and pathogenesis of CRSD as well as surrogate measurements for assessing an individual's circadian phenotype.

  2. Social memory in the rat: circadian variation and effect of circadian rhythm disruption

    Reijmers, L.G.J.E.; Leus, I.E.; Burbach, J.P.H.; Spruijt, B.M.; Ree, van J.M.

    2001-01-01

    Disruption of circadian rhythm can impair long-term passive avoidance memory of rats and mice. The present study investigated whether disruption of circadian rhythm can also impair social memory of male rats. Social memory was assessed using the social discrimination test, in which a short-term olfa

  3. Circadian Rhythms of Locomotor Activity in Captive Birds and Mammals : Their Variations with Season and Latitude

    Daan, Serge; Aschoff, Jürgen

    1975-01-01

    1. The seasonal variations in time of daily onset and end of locomotor activity are described for 3 species of mammals and 5 species of birds kept in captivity at the arctic circle and at lower latitude. These variations are most pronounced at high latitude. 2. The duration of daily activity plotted

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

    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.

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

    Ron Weiss

    2014-04-01

    Full Text Available 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.

  6. Circadian rhythms in cognitive performance: implications for neuropsychological assessment

    Valdez P

    2012-12-01

    Full Text Available Pablo Valdez, Candelaria Ramírez, Aída GarcíaLaboratory of Psychophysiology, School of Psychology, University of Nuevo León, Monterrey, Nuevo León, MéxicoAbstract: Circadian variations have been found in human performance, including the efficiency to execute many tasks, such as sensory, motor, reaction time, time estimation, memory, verbal, arithmetic calculations, and simulated driving tasks. Performance increases during the day and decreases during the night. Circadian rhythms have been found in three basic neuropsychological processes (attention, working memory, and executive functions, which may explain oscillations in the performance of many tasks. The time course of circadian rhythms in cognitive performance may be modified significantly in patients with brain disorders, due to chronotype, age, alterations of the circadian rhythm, sleep deprivation, type of disorder, and medication. This review analyzes the recent results on circadian rhythms in cognitive performance, as well as the implications of these rhythms for the neuropsychological assessment of patients with brain disorders such as traumatic head injury, stroke, dementia, developmental disorders, and psychiatric disorders.Keywords: human circadian rhythms, cognitive performance, neuropsychological assessment, attention, working memory, executive functions

  7. Circadian rhythms of crawling and swimming in the nudibranch mollusc Melibe leonina.

    Newcomb, James M; Kirouac, Lauren E; Naimie, Amanda A; Bixby, Kimberly A; Lee, Colin; Malanga, Stephanie; Raubach, Maureen; Watson, Winsor H

    2014-12-01

    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.

  8. Effects of square-wave and simulated natural light-dark cycles on hamster circadian rhythms

    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 circadian entrainment characteristics under LDSq and LDSN, suggesting that gradual and abrupt transitions between light and dark may provide different temporal cues.

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

    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.

  10. A stochastic model for circadian rhythms from coupled ultradian oscillators

    Illner Reinhard

    2007-01-01

    Full Text Available Abstract Background Circadian rhythms with varying components exist in organisms ranging from humans to cyanobacteria. A simple evolutionarily plausible mechanism for the origin of such a variety of circadian oscillators, proposed in earlier work, involves the non-disruptive coupling of pre-existing ultradian transcriptional-translational oscillators (TTOs, producing "beats," in individual cells. However, like other TTO models of circadian rhythms, it is important to establish that the inherent stochasticity of the protein binding and unbinding does not invalidate the finding of clear oscillations with circadian period. Results The TTOs of our model are described in two versions: 1 a version in which the activation or inhibition of genes is regulated stochastically, where the 'unoccupied" (or "free" time of the site under consideration depends on the concentration of a protein complex produced by another site, and 2 a deterministic, "time-averaged" version in which the switching between the "free" and "occupied" states of the sites occurs so rapidly that the stochastic effects average out. The second case is proved to emerge from the first in a mathematically rigorous way. Numerical results for both scenarios are presented and compared. Conclusion Our model proves to be robust to the stochasticity of protein binding/unbinding at experimentally determined rates and even at rates several orders of magnitude slower. We have not only confirmed this by numerical simulation, but have shown in a mathematically rigorous way that the time-averaged deterministic system is indeed the fast-binding-rate limit of the full stochastic model.

  11. AtHESPERIN: a novel regulator of circadian rhythms with poly(A)-degrading activity in plants

    Delis, Costas; Krokida, Afrodite; Tomatsidou, Anastasia; Tsikou, Daniela; Beta, Rafailia A.A.; Tsioumpekou, Maria; Moustaka, Julietta; Stravodimos, Georgios; Leonidas, Demetres D.; Balatsos, Nikolaos A. A.; Papadopoulou, Kalliope K.

    2016-01-01

    ABSTRACT We report the identification and characterization of a novel gene, AtHesperin (AtHESP) that codes for a deadenylase in Arabidopsis thaliana. The gene is under circadian clock-gene regulation and has similarity to the mammalian Nocturnin. AtHESP can efficiently degrade poly(A) substrates exhibiting allosteric kinetics. Size exclusion chromatography and native electrophoresis coupled with kinetic analysis support that the native enzyme is oligomeric with at least 3 binding sites. Knockdown and overexpression of AtHESP in plant lines affects the expression and rhythmicity of the clock core oscillator genes TOC1 and CCA1. This study demonstrates an evolutionary conserved poly(A)-degrading activity in plants and suggests deadenylation as a mechanism involved in the regulation of the circadian clock. A role of AtHESP in stress response in plants is also depicted. PMID:26619288

  12. Suprachiasmatic nuclei and Circadian rhythms. The role of suprachiasmatic nuclei on rhythmic activity of neurons in the lateral hypothalamic area, ventromedian nuclei and pineal gland

    Nishino, H.

    1977-01-01

    Unit activity of lateral hypothalamic area (LHA) and Ventromedian nuclei (VMN) was recorded in urethane anesthetized male rats. A 5 to 10 sec. a 3-5 min and a circadian rhythmicity were observed. In about 15% of all neurons, spontaneous activity of LHA and VMN showed reciprocal relationships. Subthreshold stimuli applied at a slow rate in the septum and the suprachiasmatic nuclei (SCN) suppressed the rhythms without changing firing rates. On the other hand, stimulation of the optic nerve at a rate of 5 to 10/sec increased firing rates in 1/3 of neurons of SCN. Iontophoretically applied acetylcholine increased 80% of tested neurons of SCN, whereas norepinephrine, dopamine and 5 HT inhibited 64, 60 and 75% of SCN neurons respectively. These inhibitions were much stronger in neurons, the activity of which was increased by optic nerve stimulation. Stimulation of the SCN inhibited the tonic activity in cervical sympathetic nerves.

  13. Glucocorticoids play a key role in circadian cell cycle rhythms.

    Thomas Dickmeis

    2007-04-01

    Full Text Available Clock output pathways play a pivotal role by relaying timing information from the circadian clock to a diversity of physiological systems. Both cell-autonomous and systemic mechanisms have been implicated as clock outputs; however, the relative importance and interplay between these mechanisms are poorly understood. The cell cycle represents a highly conserved regulatory target of the circadian timing system. Previously, we have demonstrated that in zebrafish, the circadian clock has the capacity to generate daily rhythms of S phase by a cell-autonomous mechanism in vitro. Here, by studying a panel of zebrafish mutants, we reveal that the pituitary-adrenal axis also plays an essential role in establishing these rhythms in the whole animal. Mutants with a reduction or a complete absence of corticotrope pituitary cells show attenuated cell-proliferation rhythms, whereas expression of circadian clock genes is not affected. We show that the corticotrope deficiency is associated with reduced cortisol levels, implicating glucocorticoids as a component of a systemic signaling pathway required for circadian cell cycle rhythmicity. Strikingly, high-amplitude rhythms can be rescued by exposing mutant larvae to a tonic concentration of a glucocorticoid agonist. Our work suggests that cell-autonomous clock mechanisms are not sufficient to establish circadian cell cycle rhythms at the whole-animal level. Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part.

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

    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.

  15. Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle.

    Chen, Wenfeng; Liu, Zhenxing; Li, Tianjiao; Zhang, Ruifeng; Xue, Yongbo; Zhong, Yang; Bai, Weiwei; Zhou, Dasen; Zhao, Zhangwu

    2014-11-24

    MicroRNA-mediated post-transcriptional regulations are increasingly recognized as important components of the circadian rhythm. Here we identify microRNA let-7, part of the Drosophila let-7-Complex, as a regulator of circadian rhythms mediated by a circadian regulatory cycle. Overexpression of let-7 in clock neurons lengthens circadian period and its deletion attenuates the morning activity peak as well as molecular oscillation. Let-7 regulates the circadian rhythm via repression of CLOCKWORK ORANGE (CWO). Conversely, upregulated cwo in cwo-expressing cells can rescue the phenotype of let-7-Complex overexpression. Moreover, circadian prothoracicotropic hormone (PTTH) and CLOCK-regulated 20-OH ecdysteroid signalling contribute to the circadian expression of let-7 through the 20-OH ecdysteroid receptor. Thus, we find a regulatory cycle involving PTTH, a direct target of CLOCK, and PTTH-driven miRNA let-7.

  16. CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila.

    Kim, Minkyung; Lee, Hoyeon; Hur, Jin-Hoe; Choe, Joonho; Lim, Chunghun

    2016-08-31

    Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species.

  17. Synchronous circadian voltage rhythms with asynchronous calcium rhythms in the suprachiasmatic nucleus.

    Enoki, Ryosuke; Oda, Yoshiaki; Mieda, Michihiro; Ono, Daisuke; Honma, Sato; Honma, Ken-Ichi

    2017-03-07

    The suprachiasmatic nucleus (SCN), the master circadian clock, contains a network composed of multiple types of neurons which are thought to form a hierarchical and multioscillator system. The molecular clock machinery in SCN neurons drives membrane excitability and sends time cue signals to various brain regions and peripheral organs. However, how and at what time of the day these neurons transmit output signals remain largely unknown. Here, we successfully visualized circadian voltage rhythms optically for many days using a genetically encoded voltage sensor, ArcLightD. Unexpectedly, the voltage rhythms are synchronized across the entire SCN network of cultured slices, whereas simultaneously recorded Ca(2+) rhythms are topologically specific to the dorsal and ventral regions. We further found that the temporal order of these two rhythms is cell-type specific: The Ca(2+) rhythms phase-lead the voltage rhythms in AVP neurons but Ca(2+) and voltage rhythms are nearly in phase in VIP neurons. We confirmed that circadian firing rhythms are also synchronous and are coupled with the voltage rhythms. These results indicate that SCN networks with asynchronous Ca(2+) rhythms produce coherent voltage rhythms.

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

    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 exerci...

  19. Inositols affect the mating circadian rhythm of Drosophila melanogaster

    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

  20. Inositols affect the mating circadian rhythm of Drosophila melanogaster

    Kazuki eSakata

    2015-06-01

    Full Text Available Accumulating evidence indicates that the molecular circadian clock underlies the mating behavior of D. 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 Drosophila 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.

  1. Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

    Harrison, Elizabeth M; Walbeek, Thijs J; Sun, Jonathan; Johnson, Jeremy; Poonawala, Qays; Gorman, Michael R

    2016-12-08

    The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24 h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturnal illumination (entrainment. Continuation of dim light is unnecessary for T15/30 behavioral entrainment following bifurcation. Finally, neither dim light alone nor a shortened night is sufficient for the extraordinary entrainment observed under bifurcation. Thus, we demonstrate in a non-pharmacological, non-genetic manipulation that the circadian system is far more flexible than previously thought. These findings challenge the current conception of entrainment and its underlying principles, and reveal new potential targets for circadian interventions.

  2. CMYB1 Encoding a MYB Transcriptional Activator Is Involved in Abiotic Stress and Circadian Rhythm in Rice

    Min Duan

    2014-01-01

    Full Text Available Through analysis of cold-induced transcriptome, a novel gene encoding a putative MYB transcription factor was isolated and designated Cold induced MYB 1 (CMYB1. Tissue-specific gene expression analysis revealed that CMYB1 was highly expressed in rice stems and nodes. qRT-PCR assay indicated that CMYB1 was dramatically induced by cold stress (>100-folds and induced by exogenous ABA and osmotic stress. Interestingly, CMYB1 showed rhythmic expression profile in rice leaves at different developmental stages. Subcellular localization assay suggested that CMYB1-GFP (green fluorescent protein fusion protein was localized in the nuclei. Moreover, CMYB1 exhibited the transcriptional activation activity when transiently expressed in rice protoplast cells. Taken together, CMYB1 probably functions as a transcriptional activator in mediating stress and rhythm responsive gene expression in rice.

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

    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.

  4. Circadian rhythms of fetal liver transcription persist in the absence of canonical circadian clock gene expression rhythms in vivo.

    Chengwei Li

    Full Text Available The cellular circadian clock and systemic cues drive rhythmicity in the transcriptome of adult peripheral tissues. However, the oscillating status of the circadian clocks in fetal tissues, and their response to maternal cues, are less clear. Most clock genes do not cycle in fetal livers from mice and rats, although tissue level rhythms rapidly emerge when fetal mouse liver explants are cultured in vitro. Thus, in the fetal mouse liver, the circadian clock does not oscillate at the cellular level (but is induced to oscillate in culture. To gain a comprehensive overview of the clock status in the fetal liver during late gestation, we performed microarray analyses on fetal liver tissues. In the fetal liver we did not observe circadian rhythms of clock gene expression or many other transcripts known to be rhythmically expressed in the adult liver. Nevertheless, JTK_CYCLE analysis identified some transcripts in the fetal liver that were rhythmically expressed, albeit at low amplitudes. Upon data filtering by coefficient of variation, the expression levels for transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to undergo synchronized daily fluctuations at high amplitudes. These results suggest that maternal cues influence the fetal liver, despite the fact that we did not detect circadian rhythms of canonical clock gene expression in the fetal liver. These results raise important questions on the role of the circadian clock, or lack thereof, during ontogeny.

  5. Monitoring cell-autonomous circadian clock rhythms of gene expression using luciferase bioluminescence reporters.

    Ramanathan, Chidambaram; Khan, Sanjoy K; Kathale, Nimish D; Xu, Haiyan; Liu, Andrew C

    2012-09-27

    In mammals, many aspects of behavior and physiology such as sleep-wake cycles and liver metabolism are regulated by endogenous circadian clocks (reviewed). The circadian time-keeping system is a hierarchical multi-oscillator network, with the central clock located in the suprachiasmatic nucleus (SCN) synchronizing and coordinating extra-SCN and peripheral clocks elsewhere. Individual cells are the functional units for generation and maintenance of circadian rhythms, and these oscillators of different tissue types in the organism share a remarkably similar biochemical negative feedback mechanism. However, due to interactions at the neuronal network level in the SCN and through rhythmic, systemic cues at the organismal level, circadian rhythms at the organismal level are not necessarily cell-autonomous. Compared to traditional studies of locomotor activity in vivo and SCN explants ex vivo, cell-based in vitro assays allow for discovery of cell-autonomous circadian defects. Strategically, cell-based models are more experimentally tractable for phenotypic characterization and rapid discovery of basic clock mechanisms. Because circadian rhythms are dynamic, longitudinal measurements with high temporal resolution are needed to assess clock function. In recent years, real-time bioluminescence recording using firefly luciferase as a reporter has become a common technique for studying circadian rhythms in mammals, as it allows for examination of the persistence and dynamics of molecular rhythms. To monitor cell-autonomous circadian rhythms of gene expression, luciferase reporters can be introduced into cells via transient transfection or stable transduction. Here we describe a stable transduction protocol using lentivirus-mediated gene delivery. The lentiviral vector system is superior to traditional methods such as transient transfection and germline transmission because of its efficiency and versatility: it permits efficient delivery and stable integration into the host

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

    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.

  7. My Path from Chemistry to Phytochrome and Circadian Rhythms

    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

  8. Studies on circadian rhythm disturbances and melatonin in delirium

    de Jonghe, A.-M.

    2014-01-01

    The circadian sleep/wake rhythm disturbances that are seen in delirium and the role of melatonin supplementation provide a new angle in delirium research. More research is needed to determine the role of melatonin in the pathophysiological mechanisms of delirium and to determine whether the restorat

  9. Circadian clock proteins in prokaryotes: hidden rhythms?

    Maria eLoza-Correa

    2010-12-01

    Full Text Available Circadian clock genes are vital features of eukaryotes that have evolved such that organisms can adapt to our planet’s rotation in order to anticipate the coming day or night as well as unfavorable seasons. This circadian clock uses oscillation as a timekeeping element. However, circadian clock mechanisms exist also in prokaryotes. The circadian clock of Cyanobacteria is well studied. It is regulated by a cluster of three genes: kaiA, kaiB and kaiC. In this review, we will discuss the circadian system in cyanobacteria, and provide an overview and up-dated phylogenetic analysis of prokaryotic organisms that contain the main circadian genes. It is evident that the evolution of the kai genes has been influenced by lateral transfers but further and deeper studies are needed to get an in depth understanding of the exact evolutionary history of these genes. Interestingly, Legionella pneumophila an environmental bacterium and opportunistic human pathogen that parasitizes protozoa in fresh water environments also contains kaiB and kaiC, but their functions are not known. All of the residues described for the biochemical functions of the main pacemaker KaiC in Synechoccous elongates are also conserved in the L. pneumophila KaiC protein.

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

    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

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

    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

  12. Host-seeking activity of bluetongue virus vectors: endo/exophagy and circadian rhythm of Culicoides in Western Europe.

    Elvina Viennet

    Full Text Available Feeding success of free-living hematophagous insects depends on their ability to be active when hosts are available and to reach places where hosts are accessible. When the hematophagous insect is a vector of pathogens, determining the components of host-seeking behavior is of primary interest for the assessment of transmission risk. Our aim was to describe endo/exophagy and circadian host-seeking activity of Palaearctic Culicoides species, which are major biting pests and arbovirus vectors, using drop traps and suction traps baited with four sheep, as bluetongue virus hosts. Collections were carried out in the field, a largely-open stable and an enclosed stable during six collection periods of 24 hours in April/May, in late June and in September/October 2010 in western France. A total of 986 Culicoides belonging to 13 species, mainly C. brunnicans and C. obsoletus, was collected on animal baits. Culicoides brunnicans was clearly exophagic, whereas C. obsoletus was able to enter stables. Culicoides brunnicans exhibited a bimodal pattern of host-seeking activity with peaks just after sunrise and sunset. Culicoides obsoletus was active before sunset in spring and autumn and after sunset in summer, thus illustrating influence of other parameters than light, especially temperature. Description of host-seeking behaviors allowed us to discuss control strategies for transmission of Culicoides-borne pathogens, such as bluetongue virus. However, practical vector-control recommendations are difficult to provide because of the variation in the degree of endophagy and time of host-seeking activity.

  13. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver.

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2015-12-05

    Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LFD). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% down-regulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver.

  14. Endocrine (plasma cortisol and glucose) and behavioral (locomotor and self-feeding activity) circadian rhythms in Senegalese sole (Solea senegalensis Kaup 1858) exposed to light/dark cycles or constant light.

    Oliveira, Catarina C V; Aparício, Rocio; Blanco-Vives, Borja; Chereguini, Olvido; Martín, Ignacio; Javier Sánchez-Vazquez, F

    2013-06-01

    The existence of daily rhythms under light/dark (LD) cycles in plasma cortisol, blood glucose and locomotor and self-feeding activities, as well as their persistence (circadian nature) under constant light (LL), was investigated in Senegalese sole (Solea senegalensis). For the cortisol and glucose rhythms study, 48 soles were equally distributed in 8 tanks and exposed to a 12:12 LD cycle and natural water temperature (experiment 1). After an acclimation period, blood was sampled every 3 h until a 24-h cycle was completed. Blood glucose levels were measured immediately after sampling, while plasma cortisol was measured later by ELISA. In experiment 2, the fish were exposed to LL for 11 days, and after this period, the same sampling procedure was repeated. For the study of locomotor and self-feeding rhythms (experiment 3), two groups of sole were used: one exposed to LD and the other to LL. Each group was distributed within 3 tanks equipped with infrared photocells for the record of locomotor activity, and self-feeders for feeding behavior characterization. The results revealed a marked oscillation in cortisol concentrations during the daily cycle under LD, with a peak (35.65 ± 3.14 ng/ml) in the afternoon (15:00 h) and very low levels during the night (5.30 ± 1.09 ng/ml). This cortisol rhythm persisted under LL conditions, with lower values (mean cortisol concentration = 7.12 ± 1.11 ng/ml) and with the peak shifted by 3 h. Both rhythms were confirmed by COSINOR analysis (p circadian cortisol and behavioral circadian rhythms in flat fish. Such results revealed the importance of taking into account the time of day when assessing stress responses and evaluating physiological indicators of stress in fish.

  15. Microarray analysis of natural socially regulated plasticity in circadian rhythms of honey bees.

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

    2012-02-01

    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 being 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.

  16. When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias

    Seenivasan, Pavithraa; Sridhar, S; Sinha, Sitabhra

    2016-01-01

    It has recently been observed that the occurrence of sudden cardiac death has a close statistical relationship with the time of day, viz., ventricular fibrillation is most likely to occur between 12 am-6 am, with 6 pm-12 am being the next most likely period. Consequently there has been significant interest in understanding how cardiac activity is influenced by the circadian clock, i.e., temporal oscillations in physiological activity with a period close to 24 hours and synchronized with the day-night cycle. Although studies have identified the genetic basis of circadian rhythms at the intracellular level, the mechanisms by which they influence cardiac pathologies are not yet fully understood. Evidence has suggested that diurnal variations in the conductance properties of ion channel proteins that govern the excitation dynamics of cardiac cells may provide the crucial link. In this paper, we investigate the relationship between the circadian rhythm as manifested in modulations of ion channel properties and the...

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

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

    2015-04-20

    Cell-autonomous circadian rhythms allow organisms to temporally orchestrate their internal state to anticipate and/or resonate with the external environment. 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. 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. 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. Rhythmic oscillations in cellular redox state are another universal feature of circadian timekeeping, e.g., over-oxidation cycles of abundant peroxiredoxin proteins. 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. 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.

  18. Evolution of circadian rhythms in Drosophila melanogaster populations reared in constant light and dark regimes for over 330 generations.

    Shindey, Radhika; Varma, Vishwanath; Nikhil, K L; Sharma, Vijay Kumar

    2017-02-03

    Organisms are believed to have evolved circadian clocks as adaptations to deal with cyclic environmental changes, and therefore it has been hypothesized that evolution in constant environments would lead to regression of such clocks. However, previous studies have yielded mixed results, and evolution of circadian clocks under constant conditions has remained an unsettled topic of debate in circadian biology. In continuation of our previous studies, which reported persistence of circadian rhythms in Drosophila melanogaster populations evolving under constant light, here we intended to examine whether circadian clocks and the associated properties evolve differently under constant light and constant darkness. In this regard, we assayed activity-rest, adult emergence and oviposition rhythms of D. melanogaster populations which have been maintained for over 19 years (~330 generations) under three different light regimes - constant light (LL), light-dark cycles of 12:12 h (LD) and constant darkness (DD). We observed that while circadian rhythms in all the three behaviors persist in both LL and DD stocks with no differences in circadian period, they differed in certain aspects of the entrained rhythms when compared to controls reared in rhythmic environment (LD). Interestingly, we also observed that DD stocks have evolved significantly higher robustness or power of free-running activity-rest and adult emergence rhythms compared to LL stocks. Thus, our study, in addition to corroborating previous results of circadian clock evolution in constant light, also highlights that, contrary to the expected regression of circadian clocks, rearing in constant darkness leads to the evolution of more robust circadian clocks which may be attributed to an intrinsic adaptive advantage of circadian clocks and/or pleiotropic functions of clock genes in other traits.

  19. [Circadian rhythm and stress in the elderly: a study using salivary cortisol levels as an indicator].

    Fujibayashi, S; Koizumi, A

    1989-10-01

    Biological response to stress was studied in the healthy elderly by fluctuations of their circadian rhythms using salivary cortisol levels as an indicator. Social activities per se may not be stressors, but may serve as a "eustress" to the elderly when they are in good health because their rhythm is maintained. Concerning the occupations of the subjects, the rhythms of elderly watchmen showed no disturbance when they slept for three hours between 23:00 and 2:00. However, those who were unable to sleep showed disturbed rhythms. We concluded that disturbance of a rhythm that has been established on the basis of being active during the day time and sleeping at night could be a stressor to the elderly rather than stress due to working as a guard.

  20. [Effect of Earth magnetic field on circadian rhythm of total antioxidant capacity of human saliva in the North].

    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.

  1. Delayed Circadian Rhythm in Adults with Attention-Deficit/Hyperactivity Disorder and Chronic Sleep-Onset Insomnia

    Kooij, J. J. Sandra; Boonstra, A. Marije; Gordijn, Marijke C. M.; Van Someren, Eus J. W.

    2010-01-01

    Background: Previous studies suggest circadian rhythm disturbances in children with attention-deficit/hyperactivity disorder (ADHD) and sleep-onset insomnia (SOI). We investigate here sleep and rhythms in activity and melatonin in adults with ADHD. Methods: Sleep logs and actigraphy data were collec

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

    Simons, S.S.H.; Beijers, R.; Cillessen, A.H.N.; Weerth, C. de

    2015-01-01

    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

  3. Links between circadian rhythms and psychiatric disease

    Ilia N Karatsoreos

    2014-05-01

    Full Text Available 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.

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

    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. Mat...

  5. Pregnancy-induced changes in ultradian rhythms persist in circadian arrhythmic Siberian hamsters.

    Wang, Z Yan; Cable, Erin J; Zucker, Irving; Prendergast, Brian J

    2014-07-01

    The impact of pregnancy and lactation on ultradian rhythms (URs) and circadian rhythms (CRs) of locomotor activity was assessed in circadian rhythmic and arrhythmic Siberian hamsters maintained in a long-day photoperiod (16h light/day). Progressive decrements in CR robustness and amplitude over the course of gestation were accompanied by enhanced URs. Dark-phase UR period and amplitude increased during early gestation and complexity and robustness increased during late gestation. The persistence of pregnancy-associated enhancements of URs in circadian arrhythmic (ARR) hamsters suggests that reproductive modulation of the UR waveform is not dependent on coherent circadian organization. The increased incidence of dark-phase URs appeared more rapidly in ARR dams than entrained (ENTR) dams. Throughout gestation, the percentage of dams with dark-phase URs was significantly greater in the ARR group. Gestational increases in UR complexity and robustness emerged earlier and were greater in ARR than ENTR dams. The attenuation of CRs during lactation is correlated with increased expression of URs. Relaxation of circadian control of the dam's behavior may increase fitness by permitting more efficient interactions with circadian arrhythmic pups.

  6. Circadian Rhythms, Metabolism, and Chrononutrition in Rodents and Humans123

    Johnston, Jonathan D; Scheer, Frank A; Turek, Fred W

    2016-01-01

    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

  7. Prolactin circadian rhythm persists throughout lactation in women.

    Stern, J M; Reichlin, S

    1990-01-01

    To determine whether the prolactin (PRL) circadian rhythm, with its characteristic nocturnal rise, persists during the hyperprolactinemia of lactation, PRL levels were analyzed in blood samples collected hourly for 24 h from 20 mothers, 4-46 months postpartum. The circadian rhythm of PRL persisted throughout lactation as manifested by: (1) significantly higher mean nighttime than daytime PRL levels in the whole sample, despite higher daytime nursing durations; (2) the distribution of zenith levels which most frequently occur between 23.00 and 07.00 h, when nursing duration is lowest, and which are almost absent between 07.00 and 23.00 h, when nursing duration is highest, and of nadir levels, which have an opposite pattern; (3) spontaneous PRL surges that are more frequent, longer, and of higher magnitude at night than during the day, and (4) the larger magnitude of suckling-induced PRL release from late afternoon through the night compared to the morning in some women. Our data suggest that the mechanisms responsible for the circadian rhythm in PRL secretion are relatively independent of the mechanisms of suckling-induced release. We propose that the nocturnal rise in PRL during lactation functions to ensure a robust milk supply during an extensive nonsuckling interval.

  8. Study of SCN Neurochemistry using In Vivo Microdialysis in the Conscious Brain: Correlation with Circadian Activity Rhythms.

    1992-12-29

    and calcium channel blockers avoid damage to the nuclei [coordinates: anterior/posterior (AP) = (diltiazem HCI 200 tiM, verapamil 200 pM, cinnarizine ...significantly affected by calcium channel with serotonin during the dark phase (starting at 03.00 h) blockers (N-type, cinnarizine and flunarizine and L...synthesis and cycle. Perfusion with 5 p.M TIX for 60 min during the light degradation [ 15-201 on behavioral and endocrine rhythms phase (starting at

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

    Videnovic, A.; Lazar, A.S.; Barker, R.A.; Overeem, S.

    2014-01-01

    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 neurodeg

  10. Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

    Elliott Jeffrey A

    2005-06-01

    Full Text Available Abstract Background In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion and for the day (e.g., rest and low melatonin secretion. Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. Results Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. Conclusion The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges.

  11. Circadian rhythm of C-reactive protein in patients with rheumatoid arthritis.

    Herold, M; Günther, R

    1987-01-01

    Ten men with classic rheumatoid arthritis were studied for 23 days in Badgastein, Austria, in August, 1980. One man (patient 07) showed a marked increase of disease activity after a few days. C-reactive protein (CRP) concentrations increased from 8.7 mg/dl on day 2 to 13.0 mg/dl on day 16. CRP values expressed as percent mean of a day showed a significant circadian rhythm with the acrophase at -30 degrees. For the same patient we also found significant circadian rhythms in grip strength and pearl stringing with acrophases in the evening and a circadian rhythm in walking time with the acrophase in the early morning. Seven of the ten men in the study had elevated CRP concentrations during the 3 weeks of observation. Population-mean cosinor results of CRP, grip strength, pearl stringing, and walking time revealed acrophases similar to the single cosinor results of patient 07. Our results suggest that inflammation in rheumatoid arthritis is a circadian rhythmic process with lowest disease activity in the evening.

  12. Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter.

    Goya, María Eugenia; Romanowski, Andrés; Caldart, Carlos S; Bénard, Claire Y; Golombek, Diego A

    2016-11-29

    Circadian rhythms are based on endogenous clocks that allow organisms to adjust their physiology and behavior by entrainment to the solar day and, in turn, to select the optimal times for most biological variables. Diverse model systems-including mice, flies, fungi, plants, and bacteria-have provided important insights into the mechanisms of circadian rhythmicity. However, the general principles that govern the circadian clock of Caenorhabditis elegans have remained largely elusive. Here we report robust molecular circadian rhythms in C elegans recorded with a bioluminescence assay in vivo and demonstrate the main features of the circadian system of the nematode. By constructing a luciferase-based reporter coupled to the promoter of the suppressor of activated let-60 Ras (sur-5) gene, we show in both population and single-nematode assays that C elegans expresses ∼24-h rhythms that can be entrained by light/dark and temperature cycles. We provide evidence that these rhythms are temperature-compensated and can be re-entrained after phase changes of the synchronizing agents. In addition, we demonstrate that light and temperature sensing requires the photoreceptors LITE and GUR-3, and the cyclic nucleotide-gated channel subunit TAX-2. Our results shed light on C elegans circadian biology and demonstrate evolutionarily conserved features in the circadian system of the nematode.

  13. Circadian rhythms and endocrine functions in adult insects.

    Bloch, Guy; Hazan, Esther; Rafaeli, Ada

    2013-01-01

    Many behavioral and physiological processes in adult insects are influenced by both the endocrine and circadian systems, suggesting that these two key physiological systems interact. We reviewed the literature and found that experiments explicitly testing these interactions in adult insects have only been conducted for a few species. There is a shortage of measurements of hormone titers throughout the day under constant conditions even for the juvenile hormones (JHs) and ecdysteroids, the best studied insect hormones. Nevertheless, the available measurements of hormone titers coupled with indirect evidence for circadian modulation of hormone biosynthesis rate, and the expression of genes encoding proteins involved in hormone biosynthesis, binding or degradation are consistent with the hypothesis that the circulating levels of many insect hormones are influenced by the circadian system. Whole genome microarray studies suggest that the modulation of farnesol oxidase levels is important for the circadian regulation of JH biosynthesis in honey bees, mosquitoes, and fruit flies. Several studies have begun to address the functional significance of circadian oscillations in endocrine signaling. The best understood system is the circadian regulation of Pheromone Biosynthesis Activating Neuropeptide (PBAN) titers which is important for the temporal organization of sexual behavior in female moths. The evidence that the circadian and endocrine systems interact has important implications for studies of insect physiology and behavior. Additional studies on diverse species and physiological processes are needed for identifying basic principles underlying the interactions between the circadian and endocrine systems in insects.

  14. Circadian rhythms differ between sexes and closely related species of Nasonia wasps.

    Rinaldo C Bertossa

    Full Text Available Activity rhythms in 24 h light-dark cycles, constant darkness, and constant light conditions were analyzed in four different Nasonia species for each sex separately. Besides similarities, clear differences are evident among and within Nasonia species as well as between sexes. In all species, activity in a light-dark cycle is concentrated in the photophase, typical for diurnal organisms. Contrary to most diurnal insect species so far studied, Nasonia follows Aschoff's rule by displaying long (>24 h internal rhythms in constant darkness but short (<24 h in constant light. In constant light, N. vitripennis males display robust circadian activity rhythms, whereas females are usually arrhythmic. In contrast to other Nasonia species, N. longicornis males display anticipatory activity, i.e. activity shortly before light-on in a light-dark cycle. As expected, N. oneida shows activity patterns similar to those of N. giraulti but with important differences in key circadian parameters. Differences in circadian activity patterns and parameters between species may reflect synchronization of specific life-history traits to environmental conditions. Scheduling mating or dispersion to a specific time of the day could be a strategy to avoid interspecific hybridization in Nasonia species that live in sympatry.

  15. Postnatal constant light compensates Cryptochrome1 and 2 double deficiency for disruption of circadian behavioral rhythms in mice under constant dark.

    Daisuke Ono

    Full Text Available Clock genes Cryptochrome (Cry1 and Cry2 are essential for expression of circadian rhythms in mice under constant darkness (DD. However, circadian rhythms in clock gene Per1 expression or clock protein PER2 are detected in the cultured suprachiasmatic nucleus (SCN of neonatal Cry1 and Cry2 double deficient (Cry1 (-/-/Cry2 (-/- mice. A lack of circadian rhythms in adult Cry1 (-/-/Cry2 (-/- mice is most likely due to developmentally disorganized cellular coupling of oscillating neurons in the SCN. On the other hand, neonatal rats exposed to constant light (LL developed a tenable circadian system under prolonged LL which was known to fragment circadian behavioral rhythms. In the present study, Cry1 (-/-/Cry2 (-/- mice were raised under LL from postnatal day 1 for 7 weeks and subsequently exposed to DD for 3 weeks. Spontaneous movement was monitored continuously after weaning and PER2::LUC was measured in the cultured SCN obtained from mice under prolonged DD. Surprisingly, Chi square periodogram analysis revealed significant circadian rhythms of spontaneous movement in the LL-raised Cry1 (-/-/Cry2 (-/- mice, but failed to detect the rhythms in Cry1 (-/-/Cry2 (-/- mice raised under light-dark cycles (LD. By contrast, prolonged LL in adulthood did not rescue the circadian behavioral rhythms in the LD raised Cry1 (-/-/Cry2 (-/- mice. Visual inspection disclosed two distinct activity components with different periods in behavioral rhythms of the LL-raised Cry1(-/-/Cry2(-/- mice under DD: one was shorter and the other was longer than 24 hours. The two components repeatedly merged and separated. The patterns resembled the split behavioral rhythms of wild type mice under prolonged LL. In addition, circadian rhythms in PER2::LUC were detected in some of the LL-raised Cry1(-/-/Cry2(-/- mice under DD. These results indicate that neonatal exposure to LL compensates the CRY double deficiency for the disruption of circadian behavioral rhythms under DD in

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

    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.

  17. Biotelemetry transmitter implantation in rodents: impact on growth and circadian rhythms.

    Leon, Lisa R; Walker, Larry D; DuBose, David A; Stephenson, Lou A

    2004-05-01

    The implantation of a biotelemetry transmitter for core body temperature (T(c)) and motor activity (MA) measurements is hypothesized to have effects on growth and circadian rhythmicity depending on animal body-to-transmitter (B:T) size ratio. This study examined the impact of transmitter implantation (TM) on body weight, food intake (FI), water intake (WI), and circadian T(c) and MA rhythms in mice (23.8 +/- 0.04 g) and rats (311.5 +/- 5.1 g) receiving no treatment (NT), anesthesia, laparotomy (LAP), and TM. The B:T size ratio was 6:1 and 84:1 for mice and rats, respectively. In mice, body weight required 14 days to recover to presurgical levels and never attained the level of the other groups. FI recovered in 3 days, whereas WI never reached presurgical levels. Rat body weight did not decrease below presurgical levels. FI and WI recovered to presurgical levels in rats by day 2 postsurgery. Anesthesia decreased mouse body weight for 1 wk, but was without effect in rats. LAP significantly decreased body weight for 5 days in mice and 1 day in rats, showing a significant effect of the surgical procedure in the absence of TM in both species. Circadian T(c) and MA rhythms were evident within the first week in both species, indicating dissociation between circadian rhythmicity and recovery of growth variables. Cosinor analysis showed a TM effect on T(c) min, T(c) max, mesor, amplitude, and period of mice, whereas only the amplitude of the rhythm was affected in rats. These data indicate that a large B:T size ratio is associated with minimization of the adverse effects of surgical implantation. We recommend that B:T size ratio, recovery of presurgical body weight, and display of a robust circadian T(c) and MA rhythm be established before collection of biotelemetry data collection under an experimental paradigm.

  18. Circadian rhythm of glycoprotein secretion in the vas deferens of the moth, Spodoptera littoralis

    Gvakharia B

    2002-09-01

    Full Text Available Abstract Background Reproductive systems of male moths contain circadian clocks, which time the release of sperm bundles from the testis to the upper vas deferens (UVD and their subsequent transfer from the UVD to the seminal vesicles. Sperm bundles are released from the testis in the evening and are retained in the vas deferens lumen overnight before being transferred to the seminal vesicles. The biological significance of periodic sperm retention in the UVD lumen is not understood. In this study we asked whether there are circadian rhythms in the UVD that are correlated with sperm retention. Results We investigated the carbohydrate-rich material present in the UVD wall and lumen during the daily cycle of sperm release using the periodic acid-Shiff reaction (PAS. Males raised in 16:8 light-dark cycles (LD showed a clear rhythm in the levels of PAS-positive granules in the apical portion of the UVD epithelium. The peak of granule accumulation occurred in the middle of the night and coincided with the maximum presence of sperm bundles in the UVD lumen. These rhythms persisted in constant darkness (DD, indicating that they have circadian nature. They were abolished, however, in constant light (LL resulting in random patterns of PAS-positive material in the UVD wall. Gel-separation of the UVD homogenates from LD moths followed by detection of carbohydrates on blots revealed daily rhythms in the abundance of specific glycoproteins in the wall and lumen of the UVD. Conclusion Secretory activity of the vas deferens epithelium is regulated by the circadian clock. Daily rhythms in accumulation and secretion of several glycoproteins are co-ordinated with periodic retention of sperm in the vas deferens lumen.

  19. The circadian activity rhythm of mosquitoes through men-net-bait and CO2 lamp-trapping%入帐诱与CO2灯诱对蚊蚋种群昼夜活动节律的研究

    党荣理; 董言德; 郑重; 郭晓霞; 张映梅; 张桂林; 赵彤言

    2011-01-01

    Objective To understand the circadian activity rhythm of mosquitoes in three environments of Beiwan region through men-net-bait and C02 lamp - trapping. Methods The circadian activity rhythm of mosquitoes through men-net-bait and C02 lamp-trapping were carried out in three different environment. Results The same result were obtained as for the species and population composition between men-net-bait and C02 lamp-trapping, and Si. Mculatum showed a little more harmful than mosquito in three environments. Aedes vexans was predominant species with a proportion of over 95% , both An. Maculatum and Ae. Caspius were very few. The same circadian activity rhythm was obtained for Aedes vexans between two methods, and the circadian activity rhythm for Si. Mculatum with a complicated activity curves were very different in three environments. Conclusion Both men-net-bait and C02 lamp - trapping are available for the research on the circadian activity rhythm of mosquitoes, further studies remain to be done with using C02 lamp-trapping to investigate the circadian activity rhythm and population for blackfly.%目的 研究人帐诱法和CO2灯诱法对北湾地区蚊、蚋种群昼夜活动的变化规律.方法 选取3种不同生境同时采用入帐诱法和CO2灯诱法进行昼夜数量动态的调查.结果 2种方法对于危害种类及组成调查结果一致,在3种生境中班布蚋的危害均大于蚊虫,刺扰伊蚊为当地的优势蚊虫,组成占到95%以上,里海伊蚊和米赛按蚊数量很少;对于种群昼夜活动节律,刺扰伊蚊2种方法结果一致,都具有晨峰和昏峰,昏峰明显,数量多,晨峰数量较少,班布蚋的活动曲线较为复杂,不同生境变化较大,但一般具有4个高峰,两种方法调查结果差异较大.结论 人帐诱和CO2灯诱都可作为蚊虫种群数量及活动节律的调查方法,但对于蚋种群CO2灯诱法是否能作为数量及活动节律的调查方法,还需做进一步的研究.

  20. Therapeutic applications of circadian rhythms for the cardiovascular system

    Elena V Tsimakouridze

    2015-04-01

    Full Text Available 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 towards 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.

  1. Acute light exposure suppresses circadian rhythms in clock gene expression.

    Grone, Brian P; Chang, Doris; Bourgin, Patrice; Cao, Vinh; Fernald, Russell D; Heller, H Craig; Ruby, Norman F

    2011-02-01

    Light can induce arrhythmia in circadian systems by several weeks of constant light or by a brief light stimulus given at the transition point of the phase response curve. In the present study, a novel light treatment consisting of phase advance and phase delay photic stimuli given on 2 successive nights was used to induce circadian arrhythmia in the Siberian hamster ( Phodopus sungorus). We therefore investigated whether loss of rhythms in behavior was due to arrhythmia within the suprachiasmatic nucleus (SCN). SCN tissue samples were obtained at 6 time points across 24 h in constant darkness from entrained and arrhythmic hamsters, and per1, per2 , bmal1, and cry1 mRNA were measured by quantitative RT-PCR. The light treatment eliminated circadian expression of clock genes within the SCN, and the overall expression of these genes was reduced by 18% to 40% of entrained values. Arrhythmia in per1, per2, and bmal1 was due to reductions in the amplitudes of their oscillations. We suggest that these data are compatible with an amplitude suppression model in which light induces singularity in the molecular circadian pacemaker.

  2. Identified Circadian Rhythm Genes of Ciliary Epithelium with Differential Display

    Yanxia Li; Dongcheng Lu; Jian Ge; Yanna Li; Yehong Zhuo; Sears ML

    2001-01-01

    Purpose:To identify differential genes expressed in the rabbit ciliary epithelium duringthe circadian cycle of aqueous flow.Methods: Total RNA from ciliary epithelium of rabbits at 8AM (light on 1 hour) and8PM(light off 1 hour) were compared by differential display reverse transcription-polymerase chain reaetion(DD RT-PCR), using 6 % denaturing polyacrylamide electro-phoresis, choose differential display bands, cut and reamplify with the same primer, cloneand sequence. Search the database of Genbank, prolong them with 5' RACE and 3'RACE technique then clone, sequence and search database of Genbank.Results: 93 Significant differences gene expression were detected between light on andlight off in the rabbit ciliary epithelium.Conclusion: Differential display is a powerful tool to screen differentially expressedgenes in circadian rhythm of ciliary epithelium.

  3. Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

    Sunil, S A; Srikanth, M V; Rao, N Sreenivasa; Uhumwangho, M U; Latha, K; Murthy, K V Ramana

    2011-11-01

    The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

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

    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.

  5. Synchronization of circadian Per2 rhythms and HSF1-BMAL1:CLOCK interaction in mouse fibroblasts after short-term heat shock pulse.

    Teruya Tamaru

    Full Text Available Circadian rhythms are the general physiological processes of adaptation to daily environmental changes, such as the temperature cycle. A change in temperature is a resetting cue for mammalian circadian oscillators, which are possibly regulated by the heat shock (HS pathway. The HS response (HSR is a universal process that provides protection against stressful conditions, which promote protein-denaturation. Heat shock factor 1 (HSF1 is essential for HSR. In the study presented here, we investigated whether a short-term HS pulse can reset circadian rhythms. Circadian Per2 rhythm and HSF1-mediated gene expression were monitored by a real-time bioluminescence assay for mPer2 promoter-driven luciferase and HS element (HSE; HSF1-binding site-driven luciferase activity, respectively. By an optimal duration HS pulse (43°C for approximately 30 minutes, circadian Per2 rhythm was observed in the whole mouse fibroblast culture, probably indicating the synchronization of the phases of each cell. This rhythm was preceded by an acute elevation in mPer2 and HSF1-mediated gene expression. Mutations in the two predicted HSE sites adjacent (one of them proximally to the E-box in the mPer2 promoter dramatically abolished circadian mPer2 rhythm. Circadian Per2 gene/protein expression was not observed in HSF1-deficient cells. These findings demonstrate that HSF1 is essential to the synchronization of circadian rhythms by the HS pulse. Importantly, the interaction between HSF1 and BMAL1:CLOCK heterodimer, a central circadian transcription factor, was observed after the HS pulse. These findings reveal that even a short-term HS pulse can reset circadian rhythms and cause the HSF1-BMAL1:CLOCK interaction, suggesting the pivotal role of crosstalk between the mammalian circadian and HSR systems.

  6. Disrupted reproduction, estrous cycle, and circadian rhythms in female mice deficient in vasoactive intestinal peptide.

    Loh, D H; Kuljis, D A; Azuma, L; Wu, Y; Truong, D; Wang, H B; Colwell, C S

    2014-10-01

    The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP)-expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle, but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produce about half the offspring of their wild-type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle; that is, ovulation occurs less frequently and results in the release of fewer oocytes compared with controls. Circadian rhythms of wheel-running activity are disrupted in the female mutant mice, as is the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibits lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator, which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success.

  7. On the Effect of Lengthening Circadian Rhythm by Heavy Water

    Akhmedov T. R.

    2014-01-01

    Full Text Available The problem of time sensor of biological clock (BC attracts interest of many scientists, and a great number of experiments are being conducted to stud y the influence of vari- ous physical and chemical factors on functioning of BC. Special attention is drawn to studying the influence of heavy water (D 2 O on functioning of BC that always leads to lengthening of circadian rhythms (CR. This work presents theoretical consideration of lengthening of CR, when hydrogen (H 2 in water is replaced by deuterium (D 2 , that is based on spacial difference of energy levels with similar principle quantum numbers.

  8. Circadian Rhythm of Neuron R15 of Aplysia californica: In Vivo Photoentrainment.

    Audesirk, G; Strumwasser, F

    1975-06-01

    (1) The neuron R15 in the parietovisceral ganglion of Aplysia has a circadian rhythm of spiking activity when recorded in the isolated ganglion. The rhythm is entrained in vivo by light-dark cycles. (2) The phase of the R15 rhythm is a function not only of the entraining light schedule, but also of the time of dissection. Changes in the dissection time during the light portion of the light-dark cycle yield little change in the subsequent R15 peak time. Dissections during the dark portion produce peak times that vary with dissection time with a slope that is approximately one. (3) The circadian rhythm of R15 can be phase-shifted in vivo by changes in the phase of the entraining light-dark cycle in one to two weeks. R15 neurons of blinded Aplysia, however, show little or no phase shift in this time. (4) It is concluded that the eyes are important as receptors for the photoentrainment of the R15 rhythm in vivo, but that neural connections from the eyes to R15 are not required.

  9. Air Travel, Circadian Rhythms/Hormones, and Autoimmunity.

    Torres-Ruiz, J; Sulli, A; Cutolo, M; Shoenfeld, Y

    2017-02-27

    Biological rhythms are fundamental for homeostasis and have recently been involved in the regulatory processes of various organs and systems. Circadian cycle proteins and hormones have a direct effect on the inflammatory response and have shown pro- or anti-inflammatory effects in animal models of autoimmune diseases. The cells of the immune system have their own circadian rhythm, and the light-dark cycle directly influences the inflammatory response. On the other hand, patients with autoimmune diseases characteristically have sleep disorders and fatigue, and in certain disease, such as rheumatoid arthritis (RA), a frank periodicity in the signs and symptoms is recognized. The joint symptoms predominate in the morning, and apparently, subjects with RA have relative adrenal insufficiency, with a cortisol peak unable to control the late night load of pro-inflammatory cytokines. Transatlantic flights represent a challenge in the adjustment of biological rhythms, since they imply sleep deprivation, time zone changes, and potential difficulties for drug administration. In patients with autoimmune diseases, the use of DMARDs and prednisone at night is probably best suited to lessen morning symptoms. It is also essential to sleep during the trip to improve adaptation to the new time zone and to avoid, as far as possible, works involving flexible or nocturnal shifts. The study of proteins and hormones related to biological rhythms will demonstrate new pathophysiological pathways of autoimmune diseases, which will emphasize the use of general measures for sleep respect and methods for drug administration at key daily times to optimize their anti-inflammatory and immune modulatory effects.

  10. Circadian rhythm of heart rate and heart rate variability

    Massin, M; Maeyns, K.; Withofs, N.; Ravet, F.; Gerard, P.; Healy, M.

    2000-01-01

    BACKGROUND—Measurements of heart rate variability (HRV) are increasingly used as markers of cardiac autonomic activity.
AIM—To examine circadian variation in heart rate and HRV in children.
SUBJECTS—A total of 57 healthy infants and children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter recording. Monitoring was also performed on five teenagers with diabetes mellitus and subclinical vagal neuropathy in order to identify the origin of the circadian variat...

  11. Cycles of circadian illuminance are sufficient to entrain and maintain circadian locomotor rhythms in Drosophila

    Cho, Eunjoo; Oh, Ji Hye; Lee, Euna; Do, Young Rag; Kim, Eun Young

    2016-11-01

    Light at night disrupts the circadian clock and causes serious health problems in the modern world. Here, we show that newly developed four-package light-emitting diodes (LEDs) can provide harmless lighting at night. To quantify the effects of light on the circadian clock, we employed the concept of circadian illuminance (CIL). CIL represents the amount of light weighted toward the wavelengths to which the circadian clock is most sensitive, whereas visual illuminance (VIL) represents the total amount of visible light. Exposure to 12 h:12 h cycles of white LED light with high and low CIL values but a constant VIL value (conditions hereafter referred to as CH/CL) can entrain behavioral and molecular circadian rhythms in flies. Moreover, flies re-entrain to phase shift in the CH/CL cycle. Core-clock proteins are required for the rhythmic behaviors seen with this LED lighting scheme. Taken together, this study provides a guide for designing healthful white LED lights for use at night, and proposes the use of the CIL value for estimating the harmful effects of any light source on organismal health.

  12. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    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

  13. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    Maria Angeles Bonmati-Carrion

    2014-12-01

    Full Text Available 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.

  14. Integration of light signaling with photoperiodic flowering and circadian rhythm

    Min NI

    2005-01-01

    Plants become photosynthetic through de-etiolation, a developmental process regulated by red/far-red light-absorbing phytochromes and blue/ultraviolet A light-absorbing cryptochromes. Genetic screens have identified in the last decade many far-red light signaling mutants and several red and blue light signaling mutants, suggesting the existence of distinct red, far-red, or blue light signaling pathways downstream of phytochromes and cryptochromes. However, genetic screens have also identified mutants with defective de-etiolation responses under multiple wavelengths. Thus, the optimal de-etiolation responses of a plant depend on coordination among the different light signaling pathways. This review intends to discuss several recently identified signaling components that have a potential role to integrate red, far-red, and blue light signalings. This review also highlights the recent discoveries on proteolytic degradation in the desensitization of light signal transmission, and the tight connection of light signaling with photoperiodic flowering and circadian rhythm. Studies on the controlling mechanisms of de-etiolation, photoperiodic flowering, and circadian rhythm have been the fascinating topics in Arabidopsis research. The knowledge obtained from Arabidopsis can be readily applied to food crops and ornamental species, and can be contributed to our general understanding of signal perception and transduction in all organisms.

  15. Circadian and Ultradian Rhythms of Free Glucocorticoid Hormone Are Highly Synchronized between the Blood, the Subcutaneous Tissue, and the Brain

    Qian, Xiaoxiao; Droste, Susanne K.; Lightman, Stafford L.; Reul, Johannes M. H. M.

    2012-01-01

    Total glucocorticoid hormone levels in plasma of various species, including humans, follow a circadian rhythm that is made up from an underlying series of hormone pulses. In blood most of the glucocorticoid is bound to corticosteroid-binding globulin and albumin, resulting in low levels of free hormone. Although only the free fraction is biologically active, surprisingly little is known about the rhythms of free glucocorticoid hormones. We used single-probe microdialysis to measure directly the free corticosterone levels in the blood of freely behaving rats. Free corticosterone in the blood shows a distinct circadian and ultradian rhythm with a pulse frequency of approximately one pulse per hour together with an increase in hormone levels and pulse height toward the active phase of the light/dark cycle. Similar rhythms were also evident in the subcutaneous tissue, demonstrating that free corticosterone rhythms are transferred from the blood into peripheral target tissues. Furthermore, in a dual-probe microdialysis study, we demonstrated that the circadian and ultradian rhythms of free corticosterone in the blood and the subcutaneous tissue were highly synchronized. Moreover, free corticosterone rhythms were also synchronous between the blood and the hippocampus. These data demonstrate for the first time an ultradian rhythm of free corticosterone in the blood that translates into synchronized rhythms of free glucocorticoid hormone in peripheral and central tissues. The maintenance of ultradian rhythms across tissue barriers in both the periphery and the brain has important implications for research into aberrant biological rhythms in disease and for the development of improved protocols for glucocorticoid therapy. PMID:22822164

  16. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

    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.

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

    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…

  18. When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias

    Seenivasan, Pavithraa; Menon, Shakti N.; Sridhar, S.; Sinha, Sitabhra

    2016-10-01

    It has recently been observed that the occurrence of sudden cardiac death has a close statistical relationship with the time of day, viz., ventricular fibrillation is most likely to occur between 12am-6am, with 6pm-12am being the next most likely period. Consequently there has been significant interest in understanding how cardiac activity is influenced by the circadian clock, i.e., temporal oscillations in physiological activity with a period close to 24 hours and synchronized with the day-night cycle. Although studies have identified the genetic basis of circadian rhythm at the intracellular level, the mechanisms by which they influence cardiac pathologies are not yet fully understood. Evidence has suggested that diurnal variations in the conductance properties of ion channel proteins that govern the excitation dynamics of cardiac cells may provide the crucial link. In this paper, we investigate the relationship between the circadian rhythm as manifested in modulations of ion channel properties and the susceptibility to cardiac arrhythmias by using a mathematical model that describes the electrical activity in ventricular tissue. We show that changes in the channel conductance that lead to extreme values for the duration of action potentials in cardiac cells can result either in abnormally high-frequency reentrant activity or spontaneous conduction block of excitation waves. Both phenomena increase the likelihood of wavebreaks that are known to initiate potentially life- threatening arrhythmias. Thus, disruptive cardiac excitation dynamics are most likely to occur in time-intervals of the day-night cycle during which the channel properties are closest to these extreme values, providing an intriguing relation between circadian rhythms and cardiac pathologies.

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

    Noheon Park

    Full Text Available 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 (Bmal1GTΔC allele. The homozygous mutant (Bmal1GTΔC/GTΔC mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (Bmal1+/GTΔC mice displayed a gradual loss of rhythms, in contrast to Bmal1+/- mice where rhythms were sustained. Bmal1GTΔC/GTΔC 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 Bmal1GTΔC/GTΔC mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in Bmal1+/GTΔC and Bmal1GTΔC/GTΔC mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1GTΔC 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 Bmal1GTΔC mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1.

  20. Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality.

    Souêtre, E; Salvati, E; Belugou, J L; Pringuey, D; Candito, M; Krebs, B; Ardisson, J L; Darcourt, G

    1989-06-01

    Circadian rhythms of body temperature, plasma cortisol, norepinephrine (NE), thyroid stimulating hormone (TSH), and melatonin were compared in 16 endogenously depressed, 15 recovered (after 3 weeks of anti-depressant treatment), and 16 normal subjects. The depressed patients showed clear circadian rhythm abnormalities, consisting mainly in amplitude reduction. This amplitude reduction was significantly correlated with the patients' Hamilton depression scores. Normal circadian profiles were restored after recovery when amplitude, in particular, was increased. Features of the circadian rhythms observed in remission may be associated with antidepressant drug effects, whereas those observed in depression resemble the circadian rhythms observed in normal subjects living under conditions of temporal isolation and those of blind subjects. Our findings suggest that depression may be related both to a weakening of the coupling processes between internal pacemakers and to an abnormal sensitivity to environmental information.

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

    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).

  2. Vasoactive intestinal polypeptide mediates circadian rhythms in mammalian olfactory bulb and olfaction.

    Miller, Jae-Eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E; Herzog, Erik D

    2014-04-23

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system.

  3. Circadian rhythms in biologically closed electrical circuits of plants.

    Volkov, Alexander; Waite, Astian J; Wooten, Joseph D; Markin, Vladislav S

    2012-02-01

    The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. Here, we discuss the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. Plants are able to memorize daytime and nighttime. Even at continuous light or darkness, plants recognize nighttime or daytime and change the input resistance. The circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge, and the speed of transmission of electrical energy from the electrostimulator to plants.

  4. Effects of Photoperiods on Circadian Rhythm and Activity of Mandarin Voles and Kunming Mice%光周期对棕色田鼠和昆明小鼠昼夜节律及活动的影响

    任修涛; 杨艳艳; 张宁; 王振龙; 李扬威; 路纪琪

    2011-01-01

    Photoperiods plays an important role in circadian rhythm formation and maintenance. However,random and rhythmic active circadian rhythms occurs in subterranean rodents. By using video recording and focal animal sampling methods, we tested the effect of dark-light cycles on activity rhythm in Mandarin Voles (Lasiopodomys mandarinus) and Kunming (KM) Mice (Mus musculus). The results showed that: 1 ) light duration of 28 d did not significantly influence body mass of L. mandarinus and M. musculus, respectively; 2)there were significant differences in daily activity rhythm between the two rodent species under situation of light to dark 12 h: 12 h; Mandarin Voles were active in both dark and light duration and Kunming Mice were mainly active in dark period; 3 ) L. mandarinus were little more active during time period with light, while Kunmin Mice reduced their activity frequency when light was on although both species did not change their active rhythms under full dark treatment; 4 ) M. musculus behaved a strict circadian rhythm while L. mandarinus showed a random active rhythm. The results from our research indicated that L. mandarinus has evolutionarily adapted to subterranean environment than M. musculus which derived from ground-lived ancestor.%光周期对动物昼夜节律的维持具有重要的影响,地下鼠的生活方式导致其昼夜活动节律产生变化,分化出随机活动和节律型两种模式.本文采用录像观察记录的方法,测定了棕色田鼠(Lasioposomys mandarinus)和昆明小鼠(Mus musculus)在不同光暗周期下的昼夜节律变化.结果表明:28 d的光周期变化对棕色田鼠和昆明小鼠的体重影响不显著.在12L:12D光照处理条件下,棕色田鼠的昼夜活动节律不明显,昼夜均有活动,表现为随机的活动节律模式;昆明小鼠则主要在暗周期活动,光周期极少活动,2种鼠的昼夜活动节律差异极显著.无光处理未改变棕色田鼠和昆明小鼠的同有昼夜活动节

  5. Effects of (± 3,4-Methylenedioxymethamphetamine (MDMA on Sleep and Circadian Rhythms

    Una D. McCann

    2007-01-01

    Full Text Available Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA, may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in normal sleep regulation. In particular, MDMA has been found to damage brain serotonin (5-HT neurons in a variety of animal species, including nonhuman primates, with growing evidence that humans are also susceptible to MDMA-induced brain 5-HT neurotoxicity. 5-HT is an important modulator of sleep and circadian rhythms and, therefore, individuals who sustain MDMA-induced 5-HT neurotoxicity may be at risk for developing chronic abnormalities in sleep and circadian patterns. In turn, such abnormalities could play a significant role in other alterations reported in abstinent in MDMA users (e.g., memory disturbance. This paper will review preclinical and clinical studies that have explored the effects of prior MDMA exposure on sleep, circadian activity, and the circadian pacemaker, and will highlight current gaps in knowledge and suggest areas for future research.

  6. Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

    Landry, Glenn J; Kent, Brianne A; Patton, Danica F; Jaholkowski, Mark; Marchant, Elliott G; Mistlberger, Ralph E

    2011-01-01

    The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

  7. Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

    Glenn J Landry

    Full Text Available The dorsomedial hypothalamus (DMH is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

  8. Coupled Oscillations and Circadian Rhythms in Molecular Replication Networks.

    Wagner, Nathaniel; Alasibi, Samaa; Peacock-Lopez, Enrique; Ashkenasy, Gonen

    2015-01-02

    Living organisms often display rhythmic and oscillatory behavior. We investigate here a challenge in contemporary Systems Chemistry, that is, to construct "bottom-up" molecular networks that display such complex behavior. We first describe oscillations during self-replication by applying kinetic parameters relevant to peptide replication in an open environment. Small networks of coupled oscillators are then constructed in silico, producing various functions such as logic gates, integrators, counters, triggers, and detectors. These networks are finally utilized to simulate the connectivity and network topology of the Kai proteins circadian clocks from the S. elongatus cyanobacteria, thus producing rhythms whose constant frequency is independent of the input intake rate and robust toward concentration fluctuations. We suggest that this study helps further reveal the underlying principles of biological clocks and may provide clues into their emergence in early molecular evolution.

  9. A Neural Network Underlying Circadian Entrainment and Photoperiodic Adjustment of Sleep and Activity in Drosophila

    Schlichting, Matthias; Menegazzi, Pamela; Lelito, Katharine R.; Yao, Zepeng; Buhl, Edgar; Dalla Benetta, Elena; Bahle, Andrew; Denike, Jennifer; Hodge, James John; Helfrich-Förster, Charlotte; Shafer, Orie Thomas

    2016-01-01

    A sensitivity of the circadian clock to light/dark cycles ensures that biological rhythms maintain optimal phase relationships with the external day. In animals, the circadian clock neuron network (CCNN) driving sleep/activity rhythms receives light input from multiple photoreceptors, but how these

  10. Do Urgent Caesarean Sections Have a Circadian Rhythm?

    Doğru, Serkan; Doğru, Hatice Yılmaz; Karaman, Tuğba; Şahin, Aynur; Tapar, Hakan; Karaman, Serkan; Arıcı, Semih; Özsoy, Asker Zeki; Çakmak, Bülent; İşgüder, Çiğdem Kunt; Delibaş, İlhan Bahri; Karakış, Alkan

    2016-01-01

    Objective The primary goal of the present study was to demonstrate the existence of a possible circadian variation in urgent operative deliveries. Methods All urgent caesarean sections between 1 January 2014 and 1 January 2015 with known exact onset times of operation were included in this retrospective study. Cases that were previously scheduled for elective caesarean section were excluded. Information regarding age, delivery date, onset time of operation and type of anaesthesia was collected from the database. Analyses were completed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) version 20.0 software. The statistical significance for all analyses was set at p<0.05. Results A total of 285 urgent caesarean section deliveries were included in the study. There were 126 (44.2%) deliveries during the day shift and 159 (55.8%) during the night shift. 80 patients (28.1%) received general anaesthesia and 65 (22.8%) received spinal anaesthesia in the morning shift, whereas 54 patients (18.9%) received general anaesthesia and 86 (30.2%) received spinal anaesthesia during the night shift. Conclusion The present study suggested that urgent caesarean sections revealed a circadian rhythm during the day. PMID:27366574

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

    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.

  12. Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock transcription.

    Chaves, Inês; van der Horst, Gijsbertus T J; Schellevis, Raymond; Nijman, Romana M; Koerkamp, Marian Groot; Holstege, Frank C P; Smidt, Marten P; Hoekman, Marco F M

    2014-06-02

    Circadian rhythms are responsive to external and internal cues, light and metabolism being among the most important. In mammals, the light signal is sensed by the retina and transmitted to the suprachiasmatic nucleus (SCN) master clock [1], where it is integrated into the molecular oscillator via regulation of clock gene transcription. The SCN synchronizes peripheral oscillators, an effect that can be overruled by incoming metabolic signals [2]. As a consequence, peripheral oscillators can be uncoupled from the master clock when light and metabolic signals are not in phase. The signaling pathways responsible for coupling metabolic cues to the molecular clock are being rapidly uncovered [3-5]. Here we show that insulin-phosphatidylinositol 3-kinase (PI3K)-Forkhead box class O3 (FOXO3) signaling is required for circadian rhythmicity in the liver via regulation of Clock. Knockdown of FoxO3 dampens circadian amplitude, an effect that is rescued by overexpression of Clock. Subsequently, we show binding of FOXO3 to two Daf-binding elements (DBEs) located in the Clock promoter area, implicating Clock as a transcriptional target of FOXO3. Transcriptional oscillation of both core clock and output genes in the liver of FOXO3-deficient mice is affected, indicating a disrupted hepatic circadian rhythmicity. Finally, we show that insulin, a major regulator of FOXO activity [6-9], regulates Clock levels in a PI3K- and FOXO3-dependent manner. Our data point to a key role of the insulin-FOXO3-Clock signaling pathway in the modulation of circadian rhythms.

  13. Medical Students Circadian Sleep Rhythms and Academic Performance

    Isabel Pérez-Olmos

    2006-10-01

    Full Text Available Objective: to evaluate, with a preliminarystudy, the distribution of circadian rhythms, sleepschedule patterns and their relationship withacademic performance on medical students.Methodology: in this descriptive study, a 10 itemoriginal questionnaire about sleep rhythms andacademic performance was applied to medicalstudents from different semesters. Week (classtime and weekend schedules, preferences,daytime somnolence and academic performancewere asked. Three chronotypes (morningness,intermediate and eveningness were definedamong waking-sleeping preference, difficulty tosleep early, exam preparation preference hour and real sleep schedule. The sleep hour deficit perweek night was also calculated. Results: Of the318 medical students that answered the questionnaire,62.6% corresponded to intermediatechronotypes, 8.8% to evening-type and 28.7%to morning-type. Significant difference wasfound among the two chronotype tails (p=0.000,Chi-square 31.13. No correlation was foundbetween academic performance and age, sex,chronotype, week sleep deficit and sleep hours inweek and weekends. A 71.1% of the students slept6 or fewer hours during class time and 78% hada sleep deficit (more frequent in the eveningchronotype. Conclusions: No relation was foundbetween sleep chronotype and academic performance.Students tend to morningness. Fewstudies have been made on equatorial zones orwithout seasons.

  14. Conservation of retinal circadian rhythms during cavefish eye degeneration.

    Espinasa, Luis; Jeffery, William R

    2006-01-01

    Regressive evolution of morphological features is a common evolutionary event. However, the relationship between structural degeneration and loss of physiological function is often unclear because the ancestral and derived states of a character are usually not available for comparison. Here, we report studies on retinomotor rhythms during development of the blind cavefish Astyanax mexicanus, a single teleost species consisting of a sighted surface-dwelling form (surface fish) and several blind cave-dwelling (cavefish) forms. The eyed and blind forms of Astyanax diverged from a common sighted ancestor within the past million years. Despite the absence of functional eyes in cavefish adults, optic primordia are formed in embryos, but then gradually arrest in development, degenerate, and sink into the orbits. Although a layered retina is formed in cavefish embryos, it is deficient in photoreceptor cells, and in some cases the retinal pigment epithelium has lost its pigmentation. We show that the capacity to exhibit light-entrained retinomotor rhythms has been conserved in the degenerating embryonic eyes of two different Astyanax cavefish populations. The results indicate that loss of circadian retinal function does not precede and is therefore not required for eye degeneration in the blind cavefish.

  15. Circadian rhythms of ocular melatonin in the wrasse Halichoeres tenuispinnis, a labrid teleost.

    Iigo, Masayuki; Ikeda, Emi; Sato, Masaru; Kawasaki, Shigekatsu; Noguchi, Fumitaka; Nishi, Genjirou

    2006-01-01

    Using in vivo and in vitro methods we studied the regulation of ocular melatonin rhythms in the wrasse Halichoeres tenuispinnis, by either light or the circadian clock. Rhythmic changes in ocular melatonin levels under light-dark (LD) cycles were persistent under constant darkness (DD), and had a circadian periodicity of approximately 24h. However, ocular melatonin levels remained low under constant light conditions. When wrasse were exposed to a single 6-h light pulse at three different circadian phases under DD, phase-dependent phase shifts in the circadian rhythms of ocular melatonin were observed. When eyecups were prepared during mid-light periods or at the onset of darkness, and incubated in vitro in either light or dark periods, both time and light conditions affected melatonin release. These results indicate that the melatonin rhythms in the wrasse eye are driven by an ocular circadian clock that is entrained to LD cycles via local photoreceptors.

  16. Circadian rhythm in plasma noradrenaline of healthy sleep-deprived subjects.

    Candito, M; Pringuey, D; Jacomet, Y; Souêtre, E; Salvati, E; Ardisson, J L; Chambon, P; Darcourt, G

    1992-12-01

    Under normal sleep-wake conditions, noradrenaline (NA) secretions in supine subjects exhibit a weak circadian variation with a peak that occurs around noon; the sleep span is characterized by reduced NA secretion. Some investigators have reported that the circadian NA rhythm is completely obliterated during sleep deprivation. In our laboratory, plasma NA was assayed every hour for 24 h in nine healthy men 20-23 years of age. All men were deprived of sleep and were required to eat and walk around every hour to prevent sleep. However, subjects remained supine for 20 min before blood samples were collected to eliminate the effect of activity. Persistence of a slight decrease in the night concentration in several subjects, despite sleep deprivation, suggests that NA secretion may be influenced by a biological clock whose activity becomes visible when the influence of posture is removed.

  17. Evolutionary Endocrinology of Hormonal Rhythms: Juvenile Hormone Titer Circadian Polymorphism in Gryllus firmus.

    Zera, Anthony J

    2016-08-01

    Daily rhythms for hormonal traits are likely widespread and important aspects of organismal (e.g., life history) adaptation. Yet they remain substantially understudied, especially with respect to variable rhythms within species. The cricket, Gryllus firmus, exhibits a genetically polymorphic circadian rhythm for the blood titer of the key hormone, juvenile hormone (JH). Gryllus firmus is also wing-polymorphic, consisting of a dispersing morph that delays reproduction and a flightless morph with substantially enhanced egg production. JH circadian phenotype strongly covaries with morph type: The blood JH titer is strongly rhythmic in multiple populations artificially-selected for the dispersing morph (LW(f) = long wings with functional flight muscles) and is essentially arrhythmic in populations selected for the SW (short-winged) morph. Association between JH titer cycle and LW(f) morph is also found in natural populations of G. firmus and in several related species in the field. This is one of the very few studies of endocrine titer variation in natural populations of an insect. The morph-specific cycle is underlain by a circadian rhythm in hormone biosynthesis, which in turn is underlain by a rhythm in a brain neuropeptide regulator of JH biosynthesis. The morph-specific JH titer circadian cycle is also strongly correlated with a morph-specific daily rhythm in global gene expression. This is currently the only example of a genetically-variable hormone circadian rhythm in both the laboratory and field that is strongly associated with an ecologically important polymorphism. The extensive information on the underlying causes of the morph-specific JH titer rhythm, coupled with the strong association between the JH circadian rhythm and wing polymorphism makes this system in G. firmus an exceptional experimental model to investigate the mechanisms underlying circadian hormonal adaptations. Genetic polymorphism for the JH titer circadian rhythm in G. firmus is discussed

  18. Use of melatonin in circadian rhythm disorders and following phase shifts

    Skene, DJ; Deacon, S; Arendt, J.

    1996-01-01

    Following abrupt phase shifts (real or simulated time zone changes, night shift work) there is desynchronisation between the internal circadian rhythms (including melatonin) and the external environment with consequent disturbances in sleep, mood and performance. In humans the pineal hormone melatonin has phase-shifting and resynchronising properties with regard to a number of circadian rhythms. Suitably timed melatonin adrninstration hastened adaptation to phase shift and significantly impro...

  19. Treadmill Exercise Improves Memory Function Depending on Circadian Rhythm Changes in Mice

    Hwang, Dong Sup; Kwak, Hyo Bum; Ko, Il Gyu; Kim, Sung Eun; Jin, Jun Jang; Ji, Eun Sang; Choi, Hyun Hee; Kwon, Oh Young

    2016-01-01

    Purpose Exercise enhances memory function by increasing neurogenesis in the hippocampus, and circadian rhythms modulate synaptic plasticity in the hippocampus. The circadian rhythm-dependent effects of treadmill exercise on memory function in relation with neurogenesis were investigated using mice. Methods The step-down avoidance test was used to evaluate short-term memory, the 8-arm maze test was used to test spatial learning ability, and 5-bromo-2’-deoxyuridine immunofluorescence was used t...

  20. Circadian Rhythms: The Effects of Global Market Integration in the Currency Trading Industry

    Srilata Zaheer

    1995-01-01

    This essay assesses the impact of global market integration in the currency trading industry as the market interfaces with states, with firms and with individuals, and raises questions for research from a variety of disciplines. Issues discussed include the question of state control in global markets, the impact of globalization on firm structures and processes, how firms can derive competitive advantage from global circadian rhythms, and the influences of the circadian rhythms of the global ...

  1. Social interaction and sex differences influence rat temperature circadian rhythm under LD cycles and constant light.

    Cambras, T; Castejón, L; Díez-Noguera, A

    2011-06-01

    Circadian rhythms produce an efficient organization of animal behaviour over the 24h day. In some species, social cues have been found to have a role as synchronizers of these rhythms. Here, the influence of social interaction on rat circadian behaviour was investigated, addressing the question of whether cohabitation would produce a delay in the appearance of arrhythmicity under constant light conditions. To this end, the circadian rhythms of male and female rat body temperature were studied for 10days under light-dark conditions, followed by 33days under constant bright light. Half of the animals were maintained in individual cages, whilst the others were maintained in larger cages in groups of three rats of the same sex. Results showed that individual circadian rhythms under 24hour light-dark (LD) cycles were more stable and with higher amplitude in grouped than in isolated animals, and higher in males than in females. During the first days under constant light (LL), the stability of the rhythm was also higher in males than in females, but there were no differences according to the group. Moreover, we did not find significant differences in the time of circadian rhythm loss under LL, since high individual variability was found for this variable. On the other hand, female rats living in isolation showed a delayed acrophase in the circadian rhythm under LD conditions compared with those living in groups. These results suggest that cohabitation increases the internal coherence of circadian behaviour, and could be interpreted as indicating that living in isolation may induce a level of stress that disturbs manifestation of the circadian rhythm, especially in females, which are also more reactive than males to external signals.

  2. Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells.

    Julia Hoffmann

    Full Text Available 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.

  3. LUX ARRHYTHMO encodes a Myb domain protein essential for circadian rhythms.

    Hazen, Samuel P; Schultz, Thomas F; Pruneda-Paz, Jose L; Borevitz, Justin O; Ecker, Joseph R; Kay, Steve A

    2005-07-19

    In higher plants, the circadian clock orchestrates fundamental processes such as light signaling and the transition to flowering. We isolated mutants of the circadian clock from an Arabidopsis thaliana mutagenized reporter line by screening for seedlings with long hypocotyl phenotypes and subsequently assaying for abnormal clock-regulated CAB2::LUC expression. This screen identified five mutant alleles of a clock gene, LUX ARRHYTHMO (LUX), that significantly affect amplitude and robustness of rhythms in both constant white light and dark conditions. In addition, the transition from vegetative to floral development is accelerated and hypocotyl elongation is accentuated in these mutants under light:dark cycles. We genetically mapped the mutations by bulk segregant analysis with high-density oligonucleotide array genotyping to a small putative Myb transcription factor related to other clock components and response regulators in Arabidopsis. The negative arm of the Arabidopsis circadian clock, CIRCADIAN CLOCK ASSOCIATED (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), is repressed in the lux mutants, whereas TIMING OF CAB2 EXPRESSION (TOC1) is activated. We demonstrate that CCA1 and LHY bind to the evening element motif in the LUX promoter, which strongly suggests that these proteins repress LUX expression, as they do TOC1. The data are also consistent with LUX being necessary for activation of CCA1 and LHY expression.

  4. Molecular circadian rhythm shift due to bright light exposure before bedtime is related to subthreshold bipolarity.

    Cho, Chul-Hyun; Moon, Joung-Ho; Yoon, Ho-Kyoung; Kang, Seung-Gul; Geum, Dongho; Son, Gi-Hoon; Lim, Jong-Min; Kim, Leen; Lee, Eun-Il; Lee, Heon-Jeong

    2016-08-22

    This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression.

  5. Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

    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.

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

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

    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 relationsh...

  7. Melatonin attenuates photic disruption of circadian rhythms in Siberian hamsters.

    Ruby, N F; Kang, T; Heller, H C

    1997-10-01

    Body temperature (Tb) was recorded via a biotelemetry system from 28 adult male Siberian hamsters maintained in a light-dark (LD) cycle of 16 h light/day for several months. After Tb was recorded for 3 wk, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8 LD cycle for the remainder of the experiment. Hamsters were injected daily with melatonin or vehicle solution for several weeks, beginning either 2 mo after (experiment 1) or on the day of (experiment 2) the phase shift; injections occurred within 30 min of dark onset. In experiment 1, 75% of animals free ran with circadian periods >24 h, beginning on the day of the phase shift, and never reentrained to the LD cycle; no hamsters unambiguously entrained to daily injections. In contrast, 78% of animals in experiment 2 entrained to melatonin injections, and 71% of those animals subsequently reentrained to the photocycle when the injection regimen ended. No vehicle-treated animals entrained to the injection schedule. Melatonin had no effect on daily mean Tb and Tb rhythm amplitude in either experiment; however, melatonin doubled the duration of a hyperthermic response that occurred after each injection. Thus melatonin can prevent loss of entrainment induced by a phase shift of the LD cycle but cannot restore entrainment to free-running animals. Failure to reentrain in the presence of two appropriately coordinated entraining agents also suggests that a phase shift of the photocycle can diminish the sensitivity of the circadian system to both photic and nonphotic input.

  8. Circadian rhythms in electrical circuits of Clivia miniata.

    Volkov, Alexander G; Wooten, Joseph D; Waite, Astian J; Brown, Corydon R; Markin, Vladislav S

    2011-10-15

    The biological clock regulates a wide range of physiological processes in plants. Here we show circadian variation of the Clivia miniata responses to electrical stimulation. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), which regulate its physiology, were analyzed in vivo using the charge stimulation method. The electrostimulation was provided with different voltages and electrical charges. Resistance between Ag/AgCl electrodes in the leaf of C. miniata was higher at night than during the day or the following day in the darkness. The biologically closed electrical circuits with voltage gated ion channels in C. miniata are activated the next day, even in the darkness. C. miniata memorizes daytime and nighttime. At continuous light, C. miniata recognizes nighttime and increases the input resistance to the nighttime value even under light. These results show that the circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate voltage gated ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge and speed of transmission of electrical energy from the electrostimulator to the C. miniata leaves. We present the equivalent electrical circuits in C. miniata and its circadian variation to explain the experimental data.

  9. The circadian rhythm of cortisol in the saliva of young pigs

    Ekkel, E.D.; Dieleman, S.J.; Schouten, W.G.P.; Portela, A.; Cornelissen, G.; Tielen, M.J.M.; Hallberg, F.

    1996-01-01

    Single and population-mean cosinor analyses document a circadian rhythm in salivary cortisol of pigs (p < 0.001). The midline estimated statistic of rhythm, the MESOR (M), is 1.50 +/- 0.07 ng/ml. For the group of 14 pigs studied there was a predictable variation of 64% around this mean in salivary c

  10. Stretch, Shrink, and Shatter the Rhythms: The Intrinsic Circadian Period in Mania and Depression.

    Martynhak, Bruno Jacson; Pereira, Marcela; de Souza, Camila Pasquini; Andreatini, Roberto

    2015-01-01

    Disturbances in the circadian rhythms have long been associated with depression and mania. Animal models of mania and depression exhibit differential effects upon the intrinsic circadian period and the same occurs with antidepressants and mood stabilizers treatment. The intrinsic circadian period is expressed when there are no time clues or when the light/dark cycle length is beyond the capacity of synchronization. In summary, while there is no clear association between the circadian period and mania, depressive-like behaviour is generally associated either with lengthening of the circadian period or with arrythmicity, and the improvement of depressive-like behaviour is associated with shortening of the circadian period. Thus, this review is an attempt to summarize data regarding these correlations and find a putative role of the circadian intrinsic period in mood regulation, particularly concerning the switch from depression to mania.

  11. Tired of diabetes genetics? Circadian rhythms and diabetes: the MTNR1B story?

    Nagorny, Cecilia; Lyssenko, Valeriya

    2012-12-01

    Circadian rhythms are ubiquitous in biological systems and regulate metabolic processes throughout the body. Misalliance of these circadian rhythms and the systems they regulate has a profound impact on hormone levels and increases risk of developing metabolic diseases. Melatonin, a hormone secreted by the pineal gland, is one of the major signaling molecules used by the master circadian oscillator to entrain downstream circadian rhythms. Several recent genetic studies have pointed out that a common variant in the gene that encodes the melatonin receptor 2 (MTNR1B) is associated with impaired glucose homeostasis, reduced insulin secretion, and an increased risk of developing type 2 diabetes. Here, we try to review the role of this receptor and its signaling pathways in respect to glucose homeostasis and development of the disease.

  12. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism

    Feng, Dan; Liu, Tao; Sun, Zheng;

    2011-01-01

    Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when...... HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes...... hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis....

  13. Pineal photoreceptor cells are required for maintaining the circadian rhythms of behavioral visual sensitivity in zebrafish.

    Xinle Li

    Full Text Available In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity.

  14. A circadian clock in Antarctic krill: an endogenous timing system governs metabolic output rhythms in the euphausid species Euphausia superba.

    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.

  15. A circadian clock in Antarctic krill: an endogenous timing system governs metabolic output rhythms in the euphausid species Euphausia superba.

    Mathias Teschke

    Full Text Available 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.

  16. [Sleep and the circadian rhythm of cortisol in transsexuals].

    Puca, F M; Specchio, L M; Minervini, M G; Zaccaro, F; Todarello, O; Dello Russo, G; Giorgino, R; Abbaticchio, G; Lattanzi, V

    1983-09-30

    Polygraphic recordings of nocturnal sleep and hormonal behavior were studied in three male and two female transexual subjects, aged 17 to 26 years, who had required a surgical sex reassignment. The transexual state was assayed by psychological investigations according to the law. All subjects appeared healthy at physical examination and no abnormalities were revealed by basal laboratory data. Chromosomal picture was in accordance with sexual characteristics. Pituitary sella enlargements were excluded by radiographic examination. In each patient two adjustment days were followed by polygraphic recording (EEG,EOG,EMG of chin muscles) of nocturnal sleep and blood drawing for cortisol assay. Blood samples were drawn at 30 minutes intervals for 24 hours, starting from the bedding-time. Hormonal blood concentration were determined by radioimmunoassay. Cosinor method was employed in the analysis of circadian rhythm. In transexual subjects the percentage of sleep intermediate phase, or ambiguous sleep, with reference to total sleep time, was significantly higher than in matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Disruption of circadian rhythm increases the risk of cancer, metabolic syndrome and cardiovascular disease

    Vignesh Shanmugam

    2013-03-01

    Full Text Available Incidents of non-communicable diseases (NCD like cardiovascular diseases, cancer, diabetes, and chronic respiratory disease have increased dramatically and are currently the leading causes of death worldwide. Their rising incidents coincide with the dramatic changes in industrialization and development of societies over the past few hundred years. Therefore, current lifestyle practices should be further explored to uncover novel risk factors for certain cancers (i.e. colon, prostate, and breast cancer, metabolic syndrome (i.e. diabetes and obesity, and cardiovascular disease (i.e. coronary artery disease. This review discusses how a disruption of the “biological clock” or circadian rhythms could be involved in the development of these diseases as circadian rhythms control multiple physiological processes such as wake/sleep cycles, hormonal levels, body temperature, metabolism, and immune system.Several environmental factors that disrupt circadian rhythms can be identified including exposure to artificial light and electromagnetic (EM waves, unbalanced diet and night shift work. The mechanisms of how these “chronodisruptors” are associated with NCDs will be discussed. Furthermore, the involvement of genetic factors in the disturbance of circadian rhythms and predisposition to NCDs will be highlighted.Overall there is strong evidence from animal models and epidemiological studies underlining that circadian disruption is a significant player in several diseases particularly the multifactorial diseases that pose a significant public health challenge in contemporary society. A circadian disruption-based model of cancer, metabolic syndrome and cardiovascular disease etiology can be proposed. But, to fully understand the complex interactions of the different components in the network of disease development due to disruption of circadian rhythms, more investigations are needed to unravel the causal relationship between modern lifestyle

  18. Phase advance of circadian rhythms in Smith-Magenis syndrome: a case study in an adult man.

    Kocher, Laurence; Brun, Jocelyne; Devillard, Françoise; Azabou, Eric; Claustrat, Bruno

    2015-01-12

    Melatonin secretion is usually increased during the daytime and decreased at night in Smith-Magenis syndrome (SMS) and consequently is not a pertinent marker of the circadian phase of the clock in these cases. No data on temperature rhythm is available in SMS, another reliable marker of circadian clock activity. For this reason, we assessed the 24h profiles of core temperature, sleep-wake cycle, hormones (plasma cortisol and melatonin) and plasma and urine 6sulfatoxy-melatonin, the main hepatic melatonin metabolism in a 31-year-old man diagnosed with a SMS. All circadian rhythms, especially temperature rhythm showed a phase-advance, associated with reverse melatonin secretion. Plasma and urine 6sulfatoxy-melatonin profiles showed normal melatonin catabolism and confirmed the reversed melatonin secretion. Taking in consideration the reverse melatonin secretion and the phase-advanced temperature rhythm, which is driven by the suprachiasmatic nucleus, we hypothesize that the central clock is more sensitive to afternoon than to morning melatonin. This different responsiveness to melatonin according to the time of the day (i.e. chronaesthesia) corroborates the phase response curve of melatonin secretion to exogenous melatonin.

  19. Impact of dispersed coupling strength on the free running periods of circadian rhythms

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

    2016-03-01

    The dominant endogenous clock, named the suprachiasmatic nucleus (SCN), regulates circadian rhythms of behavioral and physiological activity in mammals. One of the main characteristics of the SCN is that the animal maintains a circadian rhythm with a period close to 24 h in the absence of a daily light-dark cycle (called the free running period). The free running period varies among species due to heterogeneity of the SCN network. Previous studies have shown that the heterogeneity in cellular coupling as well as in intrinsic neuronal periods shortens the free running period. Furthermore, as derived from experiments, one neuron's coupling strength is negatively associated with its period. It is unknown what the effects of this association between coupling strength and period are on the free running period and how the heterogeneity in coupling strength influences this free running period. In the present study we found that in the presence of a negative relationship between one neuron's coupling strength and its period, surprisingly, the dispersion of coupling strengths increases the free running period. Our present finding may shed new light on the understanding of the heterogeneous SCN network and provides an alternative explanation for the diversity of free running periods between species.

  20. The Effect of Acute Training and Circadian Rhythm on Blood Hemostasis in Female Athletes

    Salimeh Mahmoodinezhad

    2016-06-01

    Full Text Available Background: Circadian rhythm and physical activity are factors that influence the homeostasis of blood. This study aimed to investigate the effect of exhaustive exercise in the morning and evening on the blood hemostasis in female athletes. Methods: In the present quasi-experimental study, 30 female athletes aged 18-25 were selected by convenience sampling method and randomly divided into two groups (morning and afternoon exercises. The standard Bruce protocol test was used. In the present study, platelets, fibrinogen, and thromboplastin time were measured as indicators of blood coagulation before and after testing. Paired t-test and covariance analysis were used to analyze the measured indices and P ≤ 0.05 was considered significant. Results: An acute exhausting aerobic training session in both groups significantly increased platelet and fibrinogen levels, but a significant decrease was observed in thromboplastin time. Considering the training time, significant difference was observed in the blood thromboplastin time in the morning in comparison with the afternoon. Conclusion: According to the results of this study, the circadian rhythm and acute exhausting aerobic training are effective factors on the blood coagulation and a training session in the morning compared with the evening training has a greater effect on the blood coagulation.

  1. Light masking of circadian rhythms of heat production, heat loss, and body temperature in squirrel monkeys

    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.

  2. Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2

    Yaoming Yang

    2012-06-01

    Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock feedback mechanism. Previous work has focused on the role of ubiquitin ligases in the clock mechanism. Here we show a role for the rhythmically-expressed deubiquitinating enzyme ubiquitin specific peptidase 2 (USP2 in clock function. Mice with a deletion of the Usp2 gene (Usp2 KO display a longer free-running period of locomotor activity rhythms and altered responses of the clock to light. This was associated with altered expression of clock genes in synchronized Usp2 KO mouse embryonic fibroblasts and increased levels of clock protein PERIOD1 (PER1. USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it. Interestingly, this deubiquitination does not alter PER1 stability. Taken together, our results identify USP2 as a new core component of the clock machinery and demonstrate a role for deubiquitination in the regulation of the circadian clock, both at the level of the core pacemaker and its response to external cues.

  3. Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy.

    Chan, Sharon; Debono, Miguel

    2010-06-01

    Cortisol has one of the most distinct and fascinating circadian rhythms in human physiology. This is regulated by the central clock located in the suprachiasmatic nucleus of the hypothalamus. It has been suggested that cortisol acts as a secondary messenger between central and peripheral clocks, hence its importance in the synchronization of body circadian rhythms. Conventional immediate-release hydrocortisone, either at twice- or thrice-daily doses, is not capable of replicating physiological cortisol circadian rhythm and patients with adrenal insufficiency or congenital adrenal hyperplasia still suffer from a poor quality of life and increased mortality. Novel treatments for replacement therapy are therefore essential. Proof-of-concept studies using hydrocortisone infusions suggest that the circadian delivery of hydrocortisone may improve biochemical control and life quality in patients lacking cortisol with an impaired cortisol rhythm. Recently oral formulations of modified-release hydrocortisone are being developed and it has been shown that it is possible to replicate cortisol circadian rhythm and also achieve better control of morning androgen levels. These new drug therapies are promising and potentially offer a more effective treatment with less adverse effects. Definite improvements clearly need to be established in future clinical trials.

  4. Modeling the emergence of circadian rhythms in a clock neuron network.

    Luis Diambra

    Full Text Available Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i the control of net entrance of PER into the nucleus and (ii the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.

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

    Katrin Ivars

    Full Text Available 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.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.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.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.

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

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

    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.

  7. Crosstalk between circadian rhythmicity, mitochondrial dynamics and macrophage bactericidal activity

    Oliva-Ramírez, Jacqueline; Moreno-Altamirano, María Maximina B; Pineda-Olvera, Benjamín; Cauich-Sánchez, Patricia; Sánchez-García, F Javier

    2014-01-01

    Biological functions show rhythmic fluctuations with 24-hr periodicity regulated by circadian proteins encoded by the so-called ‘clock’ genes. The absence or deregulation of circadian proteins in mice leads to metabolic disorders and in vitro models have shown that the synthesis of pro-inflammatory cytokines by macrophages follows a circadian rhythm so showing a link between circadian rhythmicity, metabolism and immunity. Recent evidence reveals that mitochondrial shape, position and size, collectively referred to as mitochondrial dynamics, are related to both cell metabolism and immune function. However, studies addressing the simultaneous crosstalk between circadian rhythm, mitochondrial dynamics and cell immune function are scarce. Here, by using an in vitro model of synchronized murine peritoneal macrophages, we present evidence that the mitochondrial dynamics and the mitochondrial membrane potential (Δψm) follow a circadian rhythmic pattern. In addition, it is shown that the fusion of mitochondria along with high Δψm, indicative of high mitochondrial activity, precede the highest phagocytic and bactericidal activity of macrophages on Salmonella typhimurium. Taken together, our results suggest a timely coordination between circadian rhythmicity, mitochondrial dynamics, and the bactericidal capacity of macrophages. PMID:24903615

  8. Is vertical migration in Antarctic krill (Euphausia superba) influenced by an underlying circadian rhythm?

    Edward Gaten; Geraint Tarling; Harold Dowse; Charalambos Kyriacou; Ezio Rosato

    2008-12-01

    Antarctic krill (Euphausia superba) is a keystone species in the southern ocean ecosystem where it is the main consumer of phytoplankton and constitutes the main food item of many higher predators. Both food and predators are most abundant at the surface, thus krill hide in the depth of the ocean during the day and migrate to the upper layers at night, to feed at a time when the predatory risk is lowest. Although the functional significance of this diel vertical migration (DVM) is clear and its modulation by environmental factors has been described, the involvement of an endogenous circadian clock in this behaviour is as yet not fully resolved. We have analysed the circadian behaviour of Euphausia superba in a laboratory setting and here we present the first description of locomotor activity rhythms for this species. Our results are in agreement with the hypothesis that the circadian clock plays a key role in DVM. They also suggest that the interplay between food availability, social cues and the light:dark cycle acts as the predominant Zeitgeber for DVM in this species.

  9. A circadian rhythm in skill-based errors in aviation maintenance.

    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

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

    Roberto Salgado-Delgado

    2011-01-01

    Full Text Available 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.

  11. Disruption of circadian rhythms: a crucial factor in the etiology of depression.

    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.

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

    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.

  13. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review.

    Jonghe, A. de; Korevaar, J.C.; Munster, B.C. van; Rooij, S.E. de

    2010-01-01

    Objective: Circadian rhythm disturbances, like sundowning, are seen in dementia. Because the circadian rhythm is regulated by the biological clock, melatonin might be effective in the treatment of these disturbances. We systematically studied the effect of melatonin treatment in patients with dement

  14. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? : A systematic review

    de Jonghe, A; Korevaar, J C; van Munster, B C; de Rooij, S E

    2010-01-01

    OBJECTIVE: Circadian rhythm disturbances, like sundowning, are seen in dementia. Because the circadian rhythm is regulated by the biological clock, melatonin might be effective in the treatment of these disturbances. We systematically studied the effect of melatonin treatment in patients with dement

  15. Enhancement and suppression of ultradian and circadian rhythms across the female hamster reproductive cycle.

    Prendergast, Brian J; Beery, Annaliese K; Paul, Matthew J; Zucker, Irving

    2012-06-01

    The impact of ovarian hormones on hamster ultradian rhythms (URs) is unknown. We concurrently monitored URs and circadian rhythms (CRs) of home cage locomotor activity during the estrous cycle, pregnancy, and lactation of Syrian hamsters. URs with a mean period of 4-5 h were evident during the dark phase in more than 90% of females on days 1 and 2 of the estrous cycle but were significantly less prevalent on cycle days 3 and 4. The period of the UR did not vary as a function of estrous cycle stage, but at all stages, the UR period was longer in the dark than the light phase. The UR acrophase occurred significantly earlier on cycle day 4 than on days 1 and 2, and UR robustness and amplitude were reduced on days 3 and 4. Robustness, mesor, and amplitude of CRs were greater during cycle days 3 and 4; timing of the CR acrophase was delayed on day 4 relative to all other cycle days. Effects of the estrous cycle on URs were evident only during the dark phase. The proportion of hamsters displaying dark phase URs increased significantly during early and late gestation and decreased during lactation. Pregnancy significantly increased UR complexity, robustness, and amplitude. The emergence of URs over gestation was paralleled by decrements in the robustness and amplitude of CRs, which also were absent in a significant proportion of dams during lactation but re-emerged at weaning of litters. The changing endocrine profile of the estrous cycle, hormonal dynamics of pregnancy and lactation, and nursing demands placed on dams are each associated with alterations in the expression of ultradian and circadian locomotor rhythms. Diminution of CRs and augmentation of URs may afford greater behavioral flexibility during life stages when interactions with mates and offspring are less predictable.

  16. Circadian rhythms of Per2::Luc in individual primary mouse hepatocytes and cultures.

    Casey J Guenthner

    Full Text Available 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 Per2(Luc 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(-/- Per2(Luc 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.

  17. Rethinking the clockwork: redox cycles and non-transcriptional control of circadian rhythms.

    Wu, Lisa; Reddy, Akhilesh B

    2014-02-01

    Circadian rhythms are a hallmark of living organisms, observable in all walks of life from primitive bacteria to highly complex humans. They are believed to have evolved to co-ordinate the timing of biological and behavioural processes to the changing environmental needs brought on by the progression of day and night through the 24-h cycle. Most of the modern study of circadian rhythms has centred on so-called TTFLs (transcription-translation feedback loops), wherein a core group of 'clock' genes, capable of negatively regulating themselves, produce oscillations with a period of approximately 24 h. Recently, however, the prevalence of the TTFL paradigm has been challenged by a series of findings wherein circadian rhythms, in the form of redox reactions, persist in the absence of transcriptional cycles. We have found that circadian cycles of oxidation and reduction are conserved across all domains of life, strongly suggesting that non-TTFL mechanisms work in parallel with the canonical genetic processes of timekeeping to generate the cyclical cellular and behavioural phenotypes that we commonly recognize as circadian rhythms.

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

    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.

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

    Zhao NB

    2013-01-01

    Full Text Available Ningbo Zhao,* Hong Tang,* Kai Yang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China*These authors contributed equally to this workBackground: 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

  20. Constitutive expression of the Period1 gene impairs behavioral and molecular circadian rhythms.

    Numano, Rika; Yamazaki, Shin; Umeda, Nanae; Samura, Tomonori; Sujino, Mitsugu; Takahashi, Ri-ichi; Ueda, Masatsugu; Mori, Akiko; Yamada, Kazunori; Sakaki, Yoshiyuki; Inouye, Shin-ichi T; Menaker, Michael; Tei, Hajime

    2006-03-07

    Three mammalian Period (Per) genes, termed Per1, Per2, and Per3, have been identified as structural homologues of the Drosophila circadian clock gene, period (per). The three Per genes are rhythmically expressed in the suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals. The phases of peak mRNA levels for the three Per genes in the SCN are slightly different. Light sequentially induces the transcripts of Per1 and Per2 but not of Per3 in mice. These data and others suggest that each Per gene has a different but partially redundant function in mammals. To elucidate the function of Per1 in the circadian system in vivo, we generated two transgenic rat lines in which the mouse Per1 (mPer1) transcript was constitutively expressed under the control of either the human elongation factor-1alpha (EF-1alpha) or the rat neuron-specific enolase (NSE) promoter. The transgenic rats exhibited an approximately 0.6-1.0-h longer circadian period than their wild-type siblings in both activity and body temperature rhythms. Entrainment in response to light cycles was dramatically impaired in the transgenic rats. Molecular analysis revealed that the amplitudes of oscillation in the rat Per1 (rPer1) and rat Per2 (rPer2) mRNAs were significantly attenuated in the SCN and eyes of the transgenic rats. These results indicate that either the level of Per1, which is raised by overexpression, or its rhythmic expression, which is damped or abolished in over expressing animals, is critical for normal entrainment of behavior and molecular oscillation of other clock genes.

  1. Evaluating the influence of sleep deprivation upon circadian rhythms of exercise metabolism.

    Montelpare, W J; Plyley, M J; Shephard, R J

    1992-06-01

    Cardiorespiratory and gas exchange responses to a moderate, standardized treadmill walking task showed a weak circadian rhythm, with larger superimposed peaks attributable to feeding. However, both rhythms became progressively attenuated during a period of sleep deprivation. A method of exploring this phenomenon is illustrated by an analysis of data on walking heart rate, respiratory minute volume, oxygen intake, and rating of perceived exertion, collected on 11 young men at 3-hr intervals during 60 hours of sleep deprivation.

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

    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

  3. An ASMT variant associated with bipolar disorder influences sleep and circadian rhythms: a pilot study.

    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.

  4. The effects of combining serotonin reuptake inhibition and 5-HT7 receptor blockade on circadian rhythm regulation in rodents.

    Westrich, Ligia; Sprouse, Jeffrey; Sánchez, Connie

    2013-02-17

    Disruption of circadian rhythms may lead to mood disorders. The present study investigated the potential therapeutic utility of combining a 5-HT7 antagonist with a selective serotonin (5-HT) reuptake inhibitor (SSRI), the standard of care in depression, on circadian rhythm regulation. In tissue explants of the suprachiasmatic nucleus (SCN) from PER2::LUC mice genetically modified to report changes in the expression of a key clock protein, the period length of PER2 bioluminescence was shortened in the presence of AS19, a 5-HT7 partial agonist. This reduction was blocked by SB269970, a selective 5-HT7 antagonist. The SSRI, escitalopram, had no effect alone on period length, but a combination with SB269970, yielded significant increases. Dosed in vivo, escitalopram had little impact on the occurrence of activity onsets in rats given access to running wheels, whether the drug was given acutely or sub-chronically. However, preceding the escitalopram treatment with a single acute dose of SB269970 produced robust phase delays, in keeping with the in vitro explant data. Taken together, these findings suggest that the combination of an SSRI and a 5-HT7 receptor antagonist has a greater impact on circadian rhythms than that observed with either agent alone, and that such a multimodal approach may be of therapeutic value in treating patients with poor clock function.

  5. Tasimelteon, a melatonin agonist for the treatment of insomnia and circadian rhythm sleep disorders.

    Hardeland, Rüdiger

    2009-07-01

    Tasimelteon, developed by Vanda Pharmaceuticals Inc under license from Bristol-Myers Squibb Co, is a melatonin receptor agonist. Because of the high density of melatonin receptors in the circadian pacemaker, the suprachiasmatic nucleus, melatonergic actions can phase-shift circadian rhythms and promote sleep. Tasimelteon was effective in reducing sleep onset latency (in phase II and III clinical trials) and in resetting the circadian melatonin rhythm (in phase II trials), which indicated its potential suitability as treatment for jet lag, shift work and circadian rhythm sleep disorders. Statistically significant improvements in sleep maintenance have also been observed with the drug. Tasimelteon has been claimed to be useful in the treatment of depression, and preclinical evidence in this respect is to be confirmed in a phase II clinical trial, which was ready to be initiated at the time of publication. It is plausible that the drug may be effective in the treatment of depressive disorders, at least those that are related to circadian dysfunction, and that it may attenuate sleep problems in depressed patients of different subtypes. A general suitability in mitigating other symptoms of major depressive disorder cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1 and MT2. The drug is well tolerated, does not induce impairment of next-day functioning or dependence, and seems to be safe in short-term treatment; however, toxicological data would be required for assessing its long-term safety.

  6. Importance of radioimmunoassays in studies of physiological circadian rhythms of children in health and disease

    Korolyuk, I.P.; Katricheva, L.V.; Kel' tsev, V.A. (Kujbyshevskij Meditsinskij Inst. (USSR))

    1982-08-01

    A study was made of the circadian activity of the thyroid gland, adrenal gland and hypophysis in 42 children, of them 23 suffered from rheumatic fever, 11 from the articular and articular-visceral forms of rhematoid arthritis, and 8 children were practically healthy. The concentration of T/sub 3/, T/sub 4/, TTH, AKTH and hydrocortisone was determined in the blood serum using standard kits for in vitro diagnosis. Certain rhythmicality is noted in the functioning of the endocrine glands in healthy children. This rhythm is simultaneous with sleep. The circadian activity of the endocrine glands gets distorted in children with rheumatic diseases: the more severe the process the more marked desynchronosis. The same type of changes in the level of hormones in the blood of children with rheumatic fever and rheumatoid arthritis presupposes some identical mechanism of the compensatory-adaptive reaction of the body to disturbances of the hormonal homeostasis that should be considered in the treatment of such patients.

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

    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…

  8. Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2

    Yang, Yaoming; Duguay, David; Bédard, Nathalie

    2012-01-01

    Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock...

  9. Effect of cataract surgery on regulation of circadian rhythms

    Erichsen, Jesper Høiberg; Brøndsted, Adam E; Kessel, Line

    2015-01-01

    improved regulation of circadian rhythms measured by the PSQI questionnaire, but the clinical relevance is uncertain. There was no difference between the effect of the 2 IOL types. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned....

  10. Fugue G Minor: Getting the Lymph Node Ensemble Together with Circadian Rhythm.

    Silva-Sanchez, Aaron; Randall, Troy D

    2017-01-17

    A fugue is characterized by the systematic repetition of a principal theme in simultaneous melodic lines. In this issue of Immunity, Druzd et al. (2017) show that a similar phenomenon occurs in lymph nodes (LNs), in which lymphocyte entry and exit is governed by repetitive circadian rhythms.

  11. Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease

    Wu, Y.-H.; Swaab, D.F.

    2007-01-01

    Circadian rhythm disturbances, such as sleep disorders, are frequently seen in aging and are even more pronounced in Alzheimer's disease (AD). Alterations in the biological clock, the suprachiasmatic nucleus (SCN), and the pineal gland during aging and AD are considered to be the biological basis fo

  12. Resonance of about-weekly human heart rate rhythm with solar activity change.

    Cornelissen, G; Halberg, F; Wendt, H W; Bingham, C; Sothern, R B; Haus, E; Kleitman, E; Kleitman, N; Revilla, M A; Revilla, M; Breus, T K; Pimenov, K; Grigoriev, A E; Mitish, M D; Yatsyk, G V; Syutkina, E V

    1996-12-01

    In several human adults, certain solar activity rhythms may influence an about 7-day rhythm in heart rate. When no about-weekly feature was found in the rate of change in sunspot area, a measure of solar activity, the double amplitude of a circadian heart rate rhythm, approximated by the fit of a 7-day cosine curve, was lower, as was heart rate corresponds to about-weekly features in solar activity and/or relates to a sunspot cycle.

  13. Time-Specific Fear Acts as a Non-Photic Entraining Stimulus of Circadian Rhythms in Rats.

    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.

  14. Circadian rhythms of feeding, oviposition, and emergence of the boll weevil (Coleoptera: Curculionidae)

    SHOIL M.GREENBERG; J.SCOTT ARMSTRONG; MAMOUDOU S(E)TAMOU; THOMAS W.SAPPINGTON; RANDY J.COLEMAN; TONG-XIAN LIU

    2006-01-01

    Circadian rhythm of feeding,oviposition,and emergence of boll weevil adults were determined at five different photophases (24,14,12,10,and 0 hours) and a constant 27℃ temperature,65% RH in the laboratory. Squares from Petri dishes,where they were exposed to boll weevil females,were removed and examined for feeding and oviposition punctures every 4 hours during daylight (0700-1900 h) and every 12 h at night (1900-0700 h) over eight consecutive days. Cohorts of randomly selected egg-punctured squares were sampled from ovipositing females at 0700,1100,1500,and 1900 during 24 hours and under different photophase treatments,and maintained in Petri dishes at 27 ± 1℃,65% RH.Dishes were observed twice daily (1900 and 0700 h) for adults emerging at day or night.Circadian rhythm of oviposition was not affected by the length of the photophase. The boll weevil has round-the-clock circadian rhythm of oviposition,with a daytime preference. We observed that 82.4%-86.0% of the boll weevil eggs were deposited between 0700 and 1900 h,and 14.0%-17.6% between 1900 and 0700 h during a 24-h period. Feeding of boll weevil females in photoperiods 24:0 h (complete light) and 0:24 h (complete darkness) did not significantly change between 0700-1900 h versus 1900-0700 h,while the daily cycle of light and darkness in other photoperiods significantly increased the feeding punctures from 0700-1900 compared with 1900-0700 h. The circadian rhythm of emergence depended significantly on the time of oviposition and the length of the photophase. Investigation of boll weevil circadian rhythm provides a better understanding of boll weevil ecology and reveals potential weak links for improving control technologies targeting their reproductive strategies.

  15. Circadian Mechanisms of Food Anticipatory Rhythms in Rats Fed Once or Twice Daily: Clock Gene and Endocrine Correlates

    Patton, Danica F.; Katsuyama, Ângela M.; Pavlovski, Ilya; Michalik, Mateusz; Patterson, Zachary; Parfyonov, Maksim; Smit, Andrea N.; Marchant, Elliott G.; Chung, John; Abizaid, Alfonso; Storch, Kai-Florian; de la Iglesia, Horacio; Mistlberger, Ralph E.

    2014-01-01

    Circadian clocks in many brain regions and peripheral tissues are entrained by the daily rhythm of food intake. Clocks in one or more of these locations generate a daily rhythm of locomotor activity that anticipates a regular mealtime. Rats and mice can also anticipate two daily meals. Whether this involves 1 or 2 circadian clocks is unknown. To gain insight into how the circadian system adjusts to 2 daily mealtimes, male rats in a 12∶12 light-dark cycle were fed a 2 h meal either 4 h after lights-on or 4 h after lights-off, or a 1 h meal at both times. After 30 days, brain, blood, adrenal and stomach tissue were collected at 6 time points. Multiple clock genes from adrenals and stomachs were assayed by RT-PCR. Blood was assayed for corticosterone and ghrelin. Bmal1 expression was quantified in 14 brain regions by in situ hybridization. Clock gene rhythms in adrenal and stomach from day-fed rats oscillated in antiphase with the rhythms in night-fed rats, and at an intermediate phase in rats fed twice daily. Corticosterone and ghrelin in 1-meal rats peaked at or prior to the expected mealtime. In 2-meal rats, corticosterone peaked only prior the nighttime meal, while ghrelin peaked prior to the daytime meal and then remained elevated. The olfactory bulb, nucleus accumbens, dorsal striatum, cerebellum and arcuate nucleus exhibited significant daily rhythms of Bmal1 in the night-fed groups that were approximately in antiphase in the day-fed groups, and at intermediate levels (arrhythmic) in rats anticipating 2 daily meals. The dissociations between anticipatory activity and the peripheral clocks and hormones in rats anticipating 2 daily meals argue against a role for these signals in the timing of behavioral rhythms. The absence of rhythmicity at the tissue level in brain regions from rats anticipating 2 daily meals support behavioral evidence that circadian clock cells in these tissues may reorganize into two populations coupled to different meals. PMID:25502949

  16. Circadian rhythm and profile in patients with juvenile myoclonic epilepsy and temporal lobe epilepsy

    Aya Fukuda

    2015-01-01

    Full Text Available Objective This study intended to compare the circadian rhythm and circadian profile between patients with juvenile myoclonic epilepsy (JME and patients with temporal lobe epilepsy (TLE. Method We enrolled 16 patients with JME and 37 patients with TLE from the Outpatient Clinic of UNICAMP. We applied a questionnaire about sleep-wake cycle and circadian profile. Results Fourteen (87% out of 16 patients with JME, and 22 out of 37 (59% patients with TLE reported that they would sleep after seizure (p < 0.05. Three (19% patients with JME, and 17 (46% reported to be in better state before 10:00 AM (p < 0.05. Conclusion There is no clear distinct profile and circadian pattern in patients with JME in comparison to TLE patients. However, our data suggest that most JME patients do not feel in better shape early in the day.

  17. Entrainment of circadian rhythms to irregular light/dark cycles: a subterranean perspective.

    Flôres, Danilo E F L; Jannetti, Milene G; Valentinuzzi, Veronica S; Oda, Gisele A

    2016-10-04

    Synchronization of biological rhythms to the 24-hour day/night has long been studied with model organisms, under artificial light/dark cycles in the laboratory. The commonly used rectangular light/dark cycles, comprising hours of continuous light and darkness, may not be representative of the natural light exposure for most species, including humans. Subterranean rodents live in dark underground tunnels and offer a unique opportunity to investigate extreme mechanisms of photic entrainment in the wild. Here, we show automated field recordings of the daily light exposure patterns in a South American subterranean rodent, the tuco-tuco (Ctenomys aff. knighti ). In the laboratory, we exposed tuco-tucos to a simplified version of this natural light exposure pattern, to determine the minimum light timing information that is necessary for synchronization. As predicted from our previous studies using mathematical modeling, the activity rhythm of tuco-tucos synchronized to this mostly simplified light/dark regimen consisting of a single light pulse per day, occurring at randomly scattered times within a day length interval. Our integrated semi-natural, lab and computer simulation findings indicate that photic entrainment of circadian oscillators is robust, even in face of artificially reduced exposure and increased phase instability of the synchronizing stimuli.

  18. Disrupting circadian rhythms in rats induces retrograde amnesia

    Fekete, Mátyás; Ree, J.M. van; Niesink, Raymond J.M.; Wied, D. de

    1985-01-01

    Disrupting circadian organization in rats by phase-shifting the illumination cycle or by exposure to a reversed day/night cycle or to continuous light, resulted in retrograde amnesia for passive avoidance behavior. This retrograde amnesia induced by phase-shifting lasted at least 2 days, and gradual

  19. Circadian rhythms in the cell cycle and biomass composition of Neochloris oleoabundans under nitrogen limitation.

    de Winter, Lenneke; Schepers, Lutz W; Cuaresma, Maria; Barbosa, Maria J; Martens, Dirk E; Wijffels, René H

    2014-10-10

    The circadian clock schedules processes in microalgae cells at suitable times in the day/night cycle. To gain knowledge about these biological time schedules, Neochloris oleoabundans was grown under constant light conditions and nitrogen limitation. Under these constant conditions, the only variable was the circadian clock. The results were compared to previous work done under nitrogen-replete conditions, in order to determine the effect of N-limitation on circadian rhythms in the cell cycle and biomass composition of N. oleoabundans. The circadian clock was not affected by nitrogen-limitation, and cell division was timed in the natural night, despite of constant light conditions. However, because of nitrogen-limitation, not the entire population was able to divide every day. Two subpopulations were observed, which divided alternately every other day. This caused oscillations in biomass yield and composition. Starch and total fatty acids (TFA) were accumulated during the day. Also, fatty acid composition changed during the cell cycle. Neutral lipids were built up during the day, especially in cells that were arrested in their cell cycle (G2 and G3). These findings give insight in the influence of circadian rhythms on the cell cycle and biomass composition.

  20. Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

    Mingrone, G; Nolfe, G; Gissey, G Castagneto;

    2009-01-01

    AIMS/HYPOTHESIS: We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. METHODS: Ten morbidly obese participants, five with normal glucose tolerance ...

  1. The nuclear receptor genes HR3 and E75 are required for the circadian rhythm in a primitive insect.

    Kamae, Yuichi; Uryu, Outa; Miki, Taiki; Tomioka, Kenji

    2014-01-01

    Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim) and period (per). Although the transcriptional regulation of Clock (Clk) has been profoundly studied, little is known about the regulation of cycle (cyc). Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes.

  2. The nuclear receptor genes HR3 and E75 are required for the circadian rhythm in a primitive insect.

    Yuichi Kamae

    Full Text Available Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim and period (per. Although the transcriptional regulation of Clock (Clk has been profoundly studied, little is known about the regulation of cycle (cyc. Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes.

  3. Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.

    Gérard, Claude; Goldbeter, Albert

    2012-05-01

    The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values.

  4. Continuous exposure to a novel stressor based on water aversion induces abnormal circadian locomotor rhythms and sleep-wake cycles in mice.

    Koyomi Miyazaki

    Full Text Available Psychological stressors prominently affect diurnal rhythms, including locomotor activity, sleep, blood pressure, and body temperature, in humans. Here, we found that a novel continuous stress imposed by the perpetual avoidance of water on a wheel (PAWW affected several physiological diurnal rhythms in mice. One week of PAWW stress decayed robust circadian locomotor rhythmicity, while locomotor activity was evident even during the light period when the mice are normally asleep. Daytime activity was significantly upregulated, whereas nighttime activity was downregulated, resulting in a low amplitude of activity. Total daily activity gradually decreased with increasing exposure to PAWW stress. The mice could be exposed to PAWW stress for over 3 weeks without adaptation. Furthermore, continuous PAWW stress enhanced food intake, but decreased body weight and plasma leptin levels, indicating that sleep loss and PAWW stress altered the energy balance in these mice. The diurnal rhythm of corticosterone levels was not severely affected. The body temperature rhythm was diurnal in the stressed mice, but significantly dysregulated during the dark period. Plasma catecholamines were elevated in the stressed mice. Continuous PAWW stress reduced the duration of daytime sleep, especially during the first half of the light period, and increased nighttime sleepiness. Continuous PAWW stress also simultaneously obscured sleep/wake and locomotor activity rhythms compared with control mice. These sleep architecture phenotypes under stress are similar to those of patients with insomnia. The stressed mice could be entrained to the light/dark cycle, and when they were transferred to constant darkness, they exhibited a free-running circadian rhythm with a timing of activity onset predicted by the phase of their entrained rhythms. Circadian gene expression in the liver and muscle was unaltered, indicating that the peripheral clocks in these tissues remained intact.

  5. Continuous exposure to a novel stressor based on water aversion induces abnormal circadian locomotor rhythms and sleep-wake cycles in mice.

    Miyazaki, Koyomi; Itoh, Nanako; Ohyama, Sumika; Kadota, Koji; Oishi, Katsutaka

    2013-01-01

    Psychological stressors prominently affect diurnal rhythms, including locomotor activity, sleep, blood pressure, and body temperature, in humans. Here, we found that a novel continuous stress imposed by the perpetual avoidance of water on a wheel (PAWW) affected several physiological diurnal rhythms in mice. One week of PAWW stress decayed robust circadian locomotor rhythmicity, while locomotor activity was evident even during the light period when the mice are normally asleep. Daytime activity was significantly upregulated, whereas nighttime activity was downregulated, resulting in a low amplitude of activity. Total daily activity gradually decreased with increasing exposure to PAWW stress. The mice could be exposed to PAWW stress for over 3 weeks without adaptation. Furthermore, continuous PAWW stress enhanced food intake, but decreased body weight and plasma leptin levels, indicating that sleep loss and PAWW stress altered the energy balance in these mice. The diurnal rhythm of corticosterone levels was not severely affected. The body temperature rhythm was diurnal in the stressed mice, but significantly dysregulated during the dark period. Plasma catecholamines were elevated in the stressed mice. Continuous PAWW stress reduced the duration of daytime sleep, especially during the first half of the light period, and increased nighttime sleepiness. Continuous PAWW stress also simultaneously obscured sleep/wake and locomotor activity rhythms compared with control mice. These sleep architecture phenotypes under stress are similar to those of patients with insomnia. The stressed mice could be entrained to the light/dark cycle, and when they were transferred to constant darkness, they exhibited a free-running circadian rhythm with a timing of activity onset predicted by the phase of their entrained rhythms. Circadian gene expression in the liver and muscle was unaltered, indicating that the peripheral clocks in these tissues remained intact.

  6. Counting circadian cycles to determine the period of a circasemilunar rhythm in a marine insect.

    Soong, Keryea; Chang, Yin-Hao

    2012-12-01

    Semilunar and lunar rhythms are often controlled endogenously, but the mechanisms of their respective free-run periods, when external factors are absent, are mostly unclear. In this investigation, the authors studied the mechanism controlling the period of the circasemilunar emergence rhythm of a marine midge, Pontomyia oceana, in southern Taiwan. Experimental approaches were adopted with various artificial light-dark (LD) periods, or T, from 22 to 28 h per cycle in the first experiment, and 18 to 30 h per cycle in the second experiment, as treatments on the same cohorts of midge larvae. The responses in emergence days were directly proportional to the magnitude of the treatments, just as that predicted by the frequency demultiplication hypothesis. A counting mechanism is thus the only hypothesis supported by this finding. To further test whether it is endogenous oscillations that are counted, submultiples as well as multiples of 24 h, i.e., 6, 12, 24, and 48 h per cycle, were used as T. The midges under all these treatments emerged at similar days. This result supports the hypothesis that endogenous circadian oscillations, not external LD cycles, are counted in this circasemilunar emergence rhythm of the marine midge. This paper reports a first case supporting the frequency demultiplication hypothesis in a circasemilunar rhythm that is based on counting the cycles of endogenous circadian rhythms.

  7. Effects of microgravity on circadian rhythms in insects

    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.

  8. [New hypnotics ramelteon for the treatment of insomniacs with circadian rhythm disturbance].

    Mishima, Kazuo

    2012-06-01

    Ramelteon is a new class of sleep agent that selectively binds to the melatonin type 1 (MT1) and type 2 (MT2) receptors in the suprachiasmatic nucleus (SCN), instead of binding to GABA-A receptors such as with traditional hypnotics benzodiazepines. Ramelteon exhibits not only acute sleep-promoting effect but also circadian phase-shifting effect via MT1 and MT2 receptors respectively, and has been revealed to contribute to the treatment of acute and chronic insomnia in patients with circadian rhythm sleep disorders(sleep-wake rhythm disorders) or with inappropriate timing of sleep habits. Optimal administration plan for insomniac patients to induce these characteristic sleep-modulating effects by ramelteon was discussed.

  9. Adipose circadian rhythms: translating cellular and animal studies to human physiology.

    Johnston, Jonathan D

    2012-02-05

    Emerging links between circadian rhythms and metabolism promise much for the understanding of metabolic physiology and pathophysiology, in which white adipose tissue (WAT) plays a prominent role. Many WAT endocrine molecules, termed adipokines, display rhythmic plasma concentration. Moreover, similar to most other tissues, WAT exhibits widespread 24-h variation in gene expression, with approximately 20% of the murine adipose transcriptome estimated to undergo daily variation. A major limitation to human chronobiology research is the availability of physiologically defined peripheral tissues. To date most analyses of in vivo human peripheral clocks has been limited to blood leucocytes. However, subcutaneous adipose tissue represents a novel opportunity to study peripheral molecular rhythms that are of clearly defined metabolic relevance. This review summarises basic concepts of circadian and metabolic physiology before then comparing alternative protocols used to analyse the rhythmic properties of human adipose tissue.

  10. A Low-Cost Computerized System to Monitor Running Performance and Circadian Rhythms of Twenty Mice Simultaneously.

    Van Leenen, Dik; Bijvoet, Agnes G. A.; Visser, Pim; Heuvelsland, Gerard F. M.; Verkerk, Anton; Van Der Horst, Gijsbertus T. J.; Reuser, Arnold J. J.

    1999-11-01

    This paper describes the design and functioning of a low-cost computerized system for monitoring the voluntary activity of mice in running wheels. The required software is written in Turbo Pascal(r) and provided via the Internet (http://www.eur.nl/fgg/ch1/rodent.html). The system accommodates the simultaneous monitoring of 20 animals over a virtually unlimited period. Two applications of the system are presented; one monitors the circadian rhythm of mice, and the other tests muscle strength and endurance.

  11. Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep-wake cycles.

    Nakamaru-Ogiso, Eiko; Miyamoto, Hiroyuki; Hamada, Kozo; Tsukada, Koji; Takai, Katsuji

    2012-06-01

    Serotonin (5-HT) neurons have been implicated in the modulation of many physiological functions, including mood regulation, feeding, and sleep. Impaired or altered 5-HT neurotransmission appears to be involved in depression and anxiety symptoms, as well as in sleep disorders. To investigate brain 5-HT functions in sleep, we induced 5-HT deficiency through acute tryptophan depletion in rats by intraperitoneally injecting a tryptophan-degrading enzyme called tryptophan side chain oxidase I (TSOI). After the administration of TSOI (20 units), plasma tryptophan levels selectively decreased to 1-2% of those of controls within 2 h, remained under 1% for 12-24 h, and then recovered between 72 and 96 h. Following plasma tryptophan levels, brain 5-HT levels decreased to ∼30% of the control level after 6 h, remained at this low level for 20-30 h, and returned to normal after 72 h. In contrast, brain norepinephreine and dopamine levels remained unchanged. After TSOI injection, the circadian rhythms of the sleep-wake cycle and locomotive activity were lost and broken into minute(s) ultradian alternations. The hourly slow-wave sleep (SWS) time significantly increased at night, but decreased during the day, whereas rapid eye movement sleep was significantly reduced during the day. However, daily total (cumulative) SWS time was retained at the normal level. As brain 5-HT levels gradually recovered 48 h after TSOI injection, the circadian rhythms of sleep-wake cycles and locomotive activity returned to normal. Our results suggest that 5-HT with a rapid turnover rate plays an important role in the circadian rhythm of sleep-wake cycles.

  12. The circadian rhythm induced by the heterogeneous network structure of the suprachiasmatic nucleus

    Gu, Changgui; Yang, Huijie

    2016-05-01

    In mammals, the master clock is located in the suprachiasmatic nucleus (SCN), which is composed of about 20 000 nonidentical neuronal oscillators expressing different intrinsic periods. These neurons are coupled through neurotransmitters to form a network consisting of two subgroups, i.e., a ventrolateral (VL) subgroup and a dorsomedial (DM) subgroup. The VL contains about 25% SCN neurons that receive photic input from the retina, and the DM comprises the remaining 75% SCN neurons which are coupled to the VL. The synapses from the VL to the DM are evidently denser than that from the DM to the VL, in which the VL dominates the DM. Therefore, the SCN is a heterogeneous network where the neurons of the VL are linked with a large number of SCN neurons. In the present study, we mimicked the SCN network based on Goodwin model considering four types of networks including an all-to-all network, a Newman-Watts (NW) small world network, an Erdös-Rényi (ER) random network, and a Barabási-Albert (BA) scale free network. We found that the circadian rhythm was induced in the BA, ER, and NW networks, while the circadian rhythm was absent in the all-to-all network with weak cellular coupling, where the amplitude of the circadian rhythm is largest in the BA network which is most heterogeneous in the network structure. Our finding provides an alternative explanation for the induction or enhancement of circadian rhythm by the heterogeneity of the network structure.

  13. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.

    Bienert, Agnieszka; Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

    2010-06-01

    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

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

    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

  15. Circadian rhythm in pain, stiffness, and manual dexterity in rheumatoid arthritis: relation between discomfort and disability.

    Bellamy, N; Sothern, R B; Campbell, J.; Buchanan, W W

    1991-01-01

    Fourteen patients with rheumatoid arthritis (RA) self rated their pain and stiffness on separate 10 cm visual analogue scales and performed bead intubation coordinometry (BIC) on six occasions each day for seven consecutive days. In addition, 14 healthy controls matched for age and sex also performed BIC measurements according to the same schedule. Data were analysed using least squares and cosine vector techniques. Significant circadian rhythms in patients with RA were detected in pain, stif...

  16. Eyeless Mexican cavefish save energy by eliminating the circadian rhythm in metabolism.

    Damian Moran

    Full Text Available 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.

  17. Demonstration of Circadian Rhythm in Heart Rate Turbulence using Novel Application of Correlator Functions

    Watanabe, M; Barthel, P; Bauer, A; Schmidt, G; Schneider, R; Stein, P; Alford, Mark; Barthel, Petra; Bauer, Axel; Schmidt, Georg; Schneider, Raphael; Stein, Phyllis; Watanabe, Mari

    2006-01-01

    Background: It has been difficult to demonstrate circadian rhythm in the two parameters of heart rate turbulence, turbulence onset (TO) and turbulence slope (TS). Objective: To devise a new method for detecting circadian rhythm in noisy data, and apply it to selected Holter recordings from two post-myocardial infarction databases, Cardiac Arrhythmia Suppression Trial (CAST, n=684) and Innovative Stratification of Arrhythmic Risk (ISAR, n=327). Methods: For each patient, TS and TO were calculated for each hour with >4 VPCs. An autocorrelation function Corr(Delta t) = was then calculated, and averaged over all patients. Positive Corr(Delta t) indicates that TS at a given hour and Delta t hours later are similar. TO was treated likewise. Simulations and mathematical analysis showed that circadian rhythm required Corr(Delta t) to have a U-shape consisting of positive values near Delta t=0 and 23, and negative values for intermediate Delta t. Significant deviation of Corr(Delta t) from the correlator function of ...

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

    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.

  19. Effects of controllable vs. uncontrollable stress on circadian temperature rhythms.

    Kant, G J; Bauman, R A; Pastel, R H; Myatt, C A; Closser-Gomez, E; D'Angelo, C P

    1991-03-01

    The effects of sustained stress on body temperature were investigated in rats implanted with mini-transmitters that permitted remote measurement of body temperature. Temperature was first monitored during control conditions. Following the control period, rats were either shaped to avoid/escape signalled around-the-clock intermittent footshock (controllable stress) or yoked to the controlling rats such that the controlling rat and the yoked rat received shock of the same duration, but only the controlling rat could terminate shock by pulling a ceiling chain. Under control conditions, rats demonstrated regular rhythms in body temperature which averaged 1 degree higher during the 12-h dark cycle than the light cycle. Stress disrupted the rhythm and markedly decreased the night-day difference in temperature, especially in the yoked rats in which almost no difference between light and dark cycle temperature was seen. The disruption was most marked for the first days of stress. A regular temperature rhythm was reestablished following about 5 days of stress although the stress condition continued. Leverpressing for food was also affected by the stress conditions with both stress groups leverpressing less than controls and the uncontrollable stress group pressing less than the controllable stress group. These data offer additional evidence of the increased pathophysiological effects of uncontrollable as compared to controllable stress.

  20. Changing the waveform of circadian rhythms: considerations for shift-work

    Elizabeth M Harrison

    2012-05-01

    Full Text Available Circadian disruption in shift-work is common and has deleterious effects on health and performance. Current efforts to mitigate these harms reasonably focus on the phase of the circadian pacemaker, which unfortunately in humans, shifts slowly and often incompletely. Temporal reorganization of rhythmic waveform (i.e. the shape of its 24 h oscillation, rather than phase, however, may better match performance demands of shift-workers and can be quickly and feasibly implemented in animals. In fact, a bifurcated pacemaker waveform may permit stable entrainment of a bimodal sleep/wake rhythm promoting alertness in both night and daylight hours. Although bifurcation has yet to be formally assessed in humans, evidence of conserved properties of circadian organization and plasticity predict its occurrence: humans respond to conventional manipulations of waveform (e.g., photoperiodism; behaviorally, the sleep/wake rhythm is adaptable; and finally, the human circadian system likely derives from the same multiple cellular oscillators that permit waveform flexibility in the rodent pacemaker. In short, investigation into untried manipulations of waveform in humans to facilitate adjustment to challenging schedules is justified.

  1. Changing the waveform of circadian rhythms: considerations for shift-work.

    Harrison, Elizabeth M; Gorman, Michael R

    2012-01-01

    Circadian disruption in shift-work is common and has deleterious effects on health and performance. Current efforts to mitigate these harms reasonably focus on the phase of the circadian pacemaker, which unfortunately in humans, shifts slowly and often incompletely. Temporal reorganization of rhythmic waveform (i.e., the shape of its 24 h oscillation), rather than phase, however, may better match performance demands of shift-workers and can be quickly and feasibly implemented in animals. In fact, a bifurcated pacemaker waveform may permit stable entrainment of a bimodal sleep/wake rhythm promoting alertness in both night and daylight hours. Although bifurcation has yet to be formally assessed in humans, evidence of conserved properties of circadian organization and plasticity predict its occurrence: humans respond to conventional manipulations of waveform (e.g., photoperiodism); behaviorally, the sleep/wake rhythm is adaptable; and finally, the human circadian system likely derives from the same multiple cellular oscillators that permit waveform flexibility in the rodent pacemaker. In short, investigation into untried manipulations of waveform in humans to facilitate adjustment to challenging schedules is justified.

  2. Review article: chronobiology: influence of circadian rhythms on the therapy of severe pain.

    Junker, Uwe; Wirz, Stefan

    2010-06-01

    Modern pain therapy widely follows the WHO (World Health Organization) guidelines using a three-step 'ladder' for pain relief. This escalating step scheme includes the administration in the order nonopioids, mild opioids and strong opioids, and adjuvants at any step. Analgesics should be given 'by the clock' rather than 'on demand'. However, the chronobiological parameters circadian pain rhythm, circadian efficacy of analgesics, and individual circadian need for analgesics are to be considered. The results of a multitude of studies in chronobiology are not consistent. Therefore, further studies with standardized protocols are needed that allow to assign more consistent rhythms to diseases, pain causes, and analgesic efficacy of opioids. In many cases, each patient perceives pain and its intensity individually during the time of day. By administration of analgesics over a constant or continuous dosage time fluctuations in pain perception and the outcomes of many studies in chronobiology are ignored that prove the influence of biological rhythms on the pharmacokinetic and pharmacodynamic aspects of analgesics. As different types of pain show different rhythms (highest pain intensities arising at different times of the day) analgesics should be dosed flexibly. It is also very important that drug therapy can be adjusted individually to the pain rhythm of the patient as well as to the type and cause of pain. In severe pain, therapy should be particularly careful. A flexible dosage depending on pain intensity and rapid dose adjustment are essentials of a modern pain therapy. Therefore, opioids that are flexible to use are better suited to treat the individual pain of the patient than rigid modified release oral or transdermal systems.

  3. Demand-feeding rhythms and feeding-entrainment of locomotor activity rhythms in tench (Tinca tinca).

    Herrero, M J; Pascual, M; Madrid, J A; Sánchez-Vázquez, F J

    2005-03-31

    Tench (Tinca tinca) has been described as a strictly nocturnal species whose locomotor activity rhythms, albeit strongly synchronised by light, have an endogenous nature. Aside from light, a number of other environmental factors, such as mealtime, can act as circadian system synchronisers in fish; however, there is a scarcity of information on tench feeding rhythms. This study describes daily self-feeding rhythms in tench, and analyses the role of feeding time on synchronisation of locomotor activity rhythms. Tench were able to operate string sensor-activated self-feeders, and they displayed a strictly nocturnal behavior, both under indoor and outdoor conditions. Locomotor activity remained strictly nocturnal irrespective of whether tench were fed only during the scotophase (D-feeding) or the photophase (L-feeding). However, no statistically significant differences were detected between both groups in terms of food intake or growth performance. Furthermore, unlike L-feeding, D-feeding elicited a clear anticipatory activity (FAA). When tench were given the possibility of feeding at both times of the day, they showed a clear preference for D-feeding. Finally, in fish exposed to constant darkness (DD), feeding time acted as a true zeitgeber and FAA was observed. When animals were fasted under DD conditions, locomotor activity free-run and 6 out of 12 individuals yielded significant results in the periodogram analysis. Under DD, fish resynchronised when regular food was resumed, with some tench displaying FAA. The obtained results indicated the existence of a feeding-entrainable oscillator (FEO) in tench.

  4. Locomotor activity rhythm in the Japanese eel Anguilla japonica elvers

    2007-01-01

    Under artificial LD cycles (6, 12, 18 L), the elvers of Japanese eel, Anguilla japonica, showed a 24 h cycle of locomotor activity rhythm being most active at light transitions: the eels' activity rose to a primary peak after lights-off, followed by a quiescent period during which they buried into the shelters or lying motionlessly on sand for most of the time, and then reached a secondary peak before lights-on. Elvers could resynchronize their activity rhythm with a new photo cycle within 4 d. Moreover, their activity level at dark phase significantly increased as the light period was prolonged: higher activity levels during shorter dark period. However, the elvers did not display clearly the existence of a circadian rhythm under constant light or dark conditions. The timing of daily activity rhythm evidenced in the Japanese eels may occur through the action of the LD cycles with a weak participation of an endogenous circadian system. In all the LD cycles, over 99% of the activity occurred in the dark phase, indicating that the eels were always nocturnally active no matter what time of day it might be. Under 12 L conditions, the eels' activity level and the time outside sand were significantly elevated both at light and dark phases as temperature increased from 10~15 to 20~25 ℃. The activity rhythm pattern (i.e., two peaks occurring around light transitions) did not apparently change among temperatures. However, in contrast with the primary activity peaks immediately after lights-off at 20 and 25 ℃, the timing of the primary peaks at 10 and 15 ℃ showed a latency of a few hours following lights-off, indicating the inhibiting effect of low temperature on the eels' activity.

  5. The effects of feedback lighting on the circadian drinking rhythm in the diurnal new world primate Saimiri sciureus

    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 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.

  6. Pinealectomy shortens resynchronisation times of house sparrow ( Passer domesticus) circadian rhythms

    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.

  7. The Pathophysiology of Circadian and Ultradian Rhythm Disturbances on Behavioral and Visceral Functions, Stress Response, and Disease Susceptibility.

    1987-12-01

    ofdata School of Medicinc)- Hunger and satiety in eating had been evaluated. disorders F. J. McGU)GAN. A. DOLLINS (United States Inter- G. BIGELOW...those animals living in long days, those living in short days lost their circadian hormone rhythms. - -, 20 DISTRIBUTION/AVAILABILITY OF ABSTRACT 21...34Free running performance rhythms in monkeys .. ................... 12 "Adrenal, thyroid, and testicular hormonal rhythms in male Syrian hamsters on long

  8. Chronic electromyographic analysis of circadian locomotor activity in crayfish.

    Tomina, Yusuke; Kibayashi, Akihiro; Yoshii, Taishi; Takahata, Masakazu

    2013-07-15

    Animals generally exhibit circadian rhythms of locomotor activity. They initiate locomotor behavior not only reflexively in response to external stimuli but also spontaneously in the absence of any specific stimulus. The neuronal mechanisms underlying circadian locomotor activity can, therefore, be based on the rhythmic changes in either reflexive efficacy or endogenous activity. In crayfish Procambarus clarkii, it can be determined by analyzing electromyographic (EMG) patterns of walking legs whether the walking behavior is initiated reflexively or spontaneously. In this study, we examined quantitatively the leg muscle activity that underlies the locomotor behavior showing circadian rhythms in crayfish. We newly developed a chronic EMG recording system that allowed the animal to freely behave under a tethered condition for more than 10 days. In the LD condition in which the animals exhibited LD entrainment, the rhythmic burst activity of leg muscles for stepping behavior was preceded by non-rhythmic tonic activation that lasted for 1323±488ms when the animal initiated walking. In DD and LL free-running conditions, the pre-burst activation lasted for 1779±31 and 1517±39ms respectively. In the mechanical stimulus-evoked walking, the pre-burst activation ended within 79±6ms. These data suggest that periodic changes in the crayfish locomotor activity under the condition of LD entrainment or free-running are based on activity changes in the spontaneous initiation mechanism of walking behavior rather than those in the sensori-motor pathway connecting mechanoreceptors with leg movements.

  9. Crayfish Procambarus clarkii retina and nervous system exhibit antioxidant circadian rhythms coupled with metabolic and luminous daily cycles.

    Fanjul-Moles, María Luisa; Prieto-Sagredo, Julio; López, Dario Santiago; Bartolo-Orozco, Ramón; Cruz-Rosas, Hugo

    2009-01-01

    Based on previous work in which we proposed midgut as a putative peripheral oscillator responsible for circadian reduced glutathione (GSH) crayfish status, herein we investigated the retina and optic lobe-brain (OL-B) circadian GSH system and its ability to deal with reactive oxygen species (ROS) produced as a consequence of metabolic rhythms and light variations. We characterized daily and antioxidant circadian variations of the different parameters of the glutathione system, including GSH, oxidized glutathione (GSSG), glutathione reductase (GR) and glutathione peroxidase (GPx), as well as metabolic and lipoperoxidative circadian oscillations in retina and OL-B, determining internal and external GSH-system synchrony. The results demonstrate statistically significant bi- and unimodal daily and circadian rhythms in all GSH-cycle parameters, substrates and enzymes in OL-B and retina, as well as an apparent direct effect of light on these rhythms, especially in the retina. The luminous condition appears to stimulate the GSH system to antagonize ROS and lipid peroxidation (LPO) daily and circadian rhythms occurring in both structures, oscillating with higher LPO under dark conditions. We suggest that the difference in the effect of light on GSH rhythmic mechanisms of both structures for antagonizing ROS could be due to differences in glutathione-system coupling strength with the circadian clock.

  10. Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing.

    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.

  11. Treatment of Sleep Deprivation-induced Circadian Rhythm Disorder by Applying Garlic Cream on Acupoint Shenque(CV 8)

    WU Dong; SHI Na; ZHU Chong-tian; HUANG Yong; ZHU Zhong-chun

    2007-01-01

    To observe the regulative effect of applying garlic cream on acupoint Shenque (CV8) on circadian rhythm disorder induced by sleep deprivation.Methods:Twenty healthy adult men were randomly divided into normal group(group A),sleep deprivation group (group B) and treatment group (group C).Subjects in group B and C received 48-hour sleep deprivation,and in the meantime subjects in group C were treated by applying garlic cream on acupoint Shenque(CV8),while subjects in group A received no any treatment,then contents of serum noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were detected.Results:The contents of NA in three groups all appeared typical circadian rhythm(P<0.01 when group A is compared with group C,and P<0.05 when group A is compared with group B).The peak value in group A was 158.377 and appeared at 10:56,peak value in group B was 291.529 and appeared at 19:44,peak value in group C was 255.964 and appeared at 17:06.The peak phase in group B shifted more obviously when compared with group A,and the peak phase in group C recovered slightly when compared with group B.The contents of 5-HT in group A showed typical circadian rhythm (P<0.01) and the circadian rhythms in group B and C disappeared (P>0.05).the peak value in group A was 196.563 and appeared at about13:10.Conclusion:The application of garlic cream on acupoint Shenque (CV8) Can adjust the disturbed circadian rhythm and accelerate the recovery of circadian rhythm.It is a simple and effective therapeutic method for adjusting circadian rhythm disorder.

  12. The effects of hydrogen peroxide on the circadian rhythms of Microcystis aeruginosa.

    Haifeng Qian

    Full Text Available 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 (H(2O(2 on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD cycle. RESULTS: The results revealed that H(2O(2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA and significantly decreases the transcript levels of kaiB, kaiC and sasA. H(2O(2 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 H(2O(2 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.

  13. Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man

    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.

  14. Circadian rhythm disturbance after radiotherapy for brain tumor in infantile period; Clinical effect of L-thyroxine and vitamin B[sub 12

    Kubota, Masaya; Shinozaki, Masako (Metropolitan Medical Center for the Severely Handicapped, Fuchu, Tokyo (Japan)); Sasaki, Hideo

    1993-08-01

    We report a 19-year-old man suffering from circadian sleep-wake (S-W) rhythm disturbance after total tumor resection and whole brain irradiation. The patient was diagnosed as having astrocytoma in the right temporal lobe by CT scan and angiography at the age of 6 months. After total tumor resection and whole brain irradiation ([sup 60]Co 60 Gy), he showed profound psychomotor retardation, endoclinologic dysfunction including hypothyroidism and growth hormone deficiency, and S-W rhythm disturbance. At age 19, brain MRI revealed asymmetrical low intensity in the hypothalamic region. On endoclinological examination panhypopituitarism due to primary hypothalamic lesion was evident. His S-W rhythm was disturbed; i.e., sleep periods were dispersedly distributed throughout 24 hours. He showed a lethargic tendency in the daytime. All-day polysomnography revealed abnormal sleep structure such as the absence of sleep spindle and hump, peripheral apnea, snoring and low oxygen saturation. After L-thyroxine supplementation his daily activity improved gradually. The decrease in short time sleep and tendency of a free-running rhythm were observed and oxygen saturation improved remarkably. Peripheral apnea and snoring disappeared. This wakening effect of L-thyroxine administration may be due to improvement of hypothyroidism symptom such as myxoedematous pharynx. It also seems related to the alteration of the central S-W rhythm regulation, because free-running rhythm appeared after L-thyroxine administration. Vitamin B[sub 12] (VB[sub 12]), which has been reported to be effective for S-W rhythm disorders, was not effective for our patient's free-running rhythm. Compared with the patients responding to VB[sub 12], our patient's organic brain damage was more evident radiologically and endoclinologically. Following the hypothesis that VB[sub 12] has a potential to reinforce the entrainment of circadian rhythm, our patient's organic brain damage may include entrainment

  15. Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

    Laura Herrero

    Full Text Available 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.

  16. Dynamic mechanistic explanation: computational modeling of circadian rhythms as an exemplar for cognitive science.

    Bechtel, William; Abrahamsen, Adele

    2010-09-01

    We consider computational modeling in two fields: chronobiology and cognitive science. In circadian rhythm models, variables generally correspond to properties of parts and operations of the responsible mechanism. A computational model of this complex mechanism is grounded in empirical discoveries and contributes a more refined understanding of the dynamics of its behavior. In cognitive science, on the other hand, computational modelers typically advance de novo proposals for mechanisms to account for behavior. They offer indirect evidence that a proposed mechanism is adequate to produce particular behavioral data, but typically there is no direct empirical evidence for the hypothesized parts and operations. Models in these two fields differ in the extent of their empirical grounding, but they share the goal of achieving dynamic mechanistic explanation. That is, they augment a proposed mechanistic explanation with a computational model that enables exploration of the mechanism's dynamics. Using exemplars from circadian rhythm research, we extract six specific contributions provided by computational models. We then examine cognitive science models to determine how well they make the same types of contributions. We suggest that the modeling approach used in circadian research may prove useful in cognitive science as researchers develop procedures for experimentally decomposing cognitive mechanisms into parts and operations and begin to understand their nonlinear interactions.

  17. Circadian cycles are the dominant transcriptional rhythm in the intertidal mussel Mytilus californianus.

    Connor, Kwasi M; Gracey, Andrew Y

    2011-09-20

    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.

  18. A Study of Circadian Rhythm and Meteorological Factors Influencing Acute Myocardial Infarction

    Selvam, A M; Mody, S M S

    1998-01-01

    The circadian rhythm in the occurrence of acute myocardial infarction (AMI) was assessed in three hundred and twenty three patients admitted with AMI during the two-year period June 1992 to May 1994. The influence of the following meteorological, solar-geophysical and cosmic parameters in the causation of an infarct was also considered : (1) surface pressure (2) maximum temperature (3) minimum temperature (4) relative humidity (5) cosmic ray index (6) geomagnetic aa index (7) solar flares and (8) sunspot number. A well pronounced diurnal variability in AMI with a peak in the morning hours (6-12 a.m.) was seen. Further analysis of the data by considering one-hour periods revealed the presence of a smaller evening (10 p.m.) increase in incidence, i.e., the existence of a bimodal circadian rhythm. The simultaneous occurrence of the well documented semi-diurnal rhythm in surface pressure and incidence of acute myocardial infarction were evident. This may be one of the factors involved in the causation of the smal...

  19. Circadian rhythm and the influence of physical activity on circulating surfactant protein D in early and long-standing rheumatoid arthritis

    Christensen, A F; Hoegh, S V; Lottenburger, T;

    2011-01-01

    Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed...... diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P exercise levels in both...... ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP...

  20. Free access to a running-wheel advances the phase of behavioral and physiological circadian rhythms and peripheral molecular clocks in mice.

    Yuki Yasumoto

    Full Text Available Behavioral and physiological circadian rhythms are controlled by endogenous oscillators in animals. Voluntary wheel-running in rodents is thought to be an appropriate model of aerobic exercise in humans. We evaluated the effects of chronic voluntary exercise on the circadian system by analyzing temporal profiles of feeding, core body temperature, plasma hormone concentrations and peripheral expression of clock and clock-controlled genes in mice housed under sedentary (SED conditions or given free access to a running-wheel (RW for four weeks. Voluntary wheel-running activity advanced the circadian phases of increases in body temperature, food intake and corticosterone secretion in the mice. The circadian expression of clock and clock-controlled genes was tissue- and gene-specifically affected in the RW mice. The temporal expression of E-box-dependent circadian clock genes such as Per1, Per2, Nr1d1 and Dbp were slightly, but significantly phase-advanced in the liver and white adipose tissue, but not in brown adipose tissue and skeletal muscle. Peak levels of Per1, Per2 and Nr1d1 expression were significantly increased in the skeletal muscle of RW mice. The circadian phase and levels of hepatic mRNA expression of the clock-controlled genes that are involved in cholesterol and fatty acid metabolism significantly differed between SED and RW mice. These findings indicated that endogenous clock-governed voluntary wheel-running activity provides feedback to the central circadian clock that systemically governs behavioral and physiological rhythms.

  1. Circadian regulation of food-anticipatory activity in molecular clock-deficient mice.

    Nana N Takasu

    Full Text Available In the mammalian brain, the suprachiasmatic nucleus (SCN of the anterior hypothalamus is considered to be the principal circadian pacemaker, keeping the rhythm of most physiological and behavioral processes on the basis of light/dark cycles. Because restriction of food availability to a certain time of day elicits anticipatory behavior even after ablation of the SCN, such behavior has been assumed to be under the control of another circadian oscillator. According to recent studies, however, mutant mice lacking circadian clock function exhibit normal food-anticipatory activity (FAA, a daily increase in locomotor activity preceding periodic feeding, suggesting that FAA is independent of the known circadian oscillator. To investigate the molecular basis of FAA, we examined oscillatory properties in mice lacking molecular clock components. Mice with SCN lesions or with mutant circadian periods were exposed to restricted feeding schedules at periods within and outside circadian range. Periodic feeding led to the entrainment of FAA rhythms only within a limited circadian range. Cry1(-/- mice, which are known to be a "short-period mutant," entrained to a shorter period of feeding cycles than did Cry2(-/- mice. This result indicated that the intrinsic periods of FAA rhythms are also affected by Cry deficiency. Bmal1(-/- mice, deficient in another essential element of the molecular clock machinery, exhibited a pre-feeding increase of activity far from circadian range, indicating a deficit in circadian oscillation. We propose that mice possess a food-entrainable pacemaker outside the SCN in which canonical clock genes such as Cry1, Cry2 and Bmal1 play essential roles in regulating FAA in a circadian oscillatory manner.

  2. Circadian regulation of food-anticipatory activity in molecular clock-deficient mice.

    Takasu, Nana N; Kurosawa, Gen; Tokuda, Isao T; Mochizuki, Atsushi; Todo, Takeshi; Nakamura, Wataru

    2012-01-01

    In the mammalian brain, the suprachiasmatic nucleus (SCN) of the anterior hypothalamus is considered to be the principal circadian pacemaker, keeping the rhythm of most physiological and behavioral processes on the basis of light/dark cycles. Because restriction of food availability to a certain time of day elicits anticipatory behavior even after ablation of the SCN, such behavior has been assumed to be under the control of another circadian oscillator. According to recent studies, however, mutant mice lacking circadian clock function exhibit normal food-anticipatory activity (FAA), a daily increase in locomotor activity preceding periodic feeding, suggesting that FAA is independent of the known circadian oscillator. To investigate the molecular basis of FAA, we examined oscillatory properties in mice lacking molecular clock components. Mice with SCN lesions or with mutant circadian periods were exposed to restricted feeding schedules at periods within and outside circadian range. Periodic feeding led to the entrainment of FAA rhythms only within a limited circadian range. Cry1(-/-) mice, which are known to be a "short-period mutant," entrained to a shorter period of feeding cycles than did Cry2(-/-) mice. This result indicated that the intrinsic periods of FAA rhythms are also affected by Cry deficiency. Bmal1(-/-) mice, deficient in another essential element of the molecular clock machinery, exhibited a pre-feeding increase of activity far from circadian range, indicating a deficit in circadian oscillation. We propose that mice possess a food-entrainable pacemaker outside the SCN in which canonical clock genes such as Cry1, Cry2 and Bmal1 play essential roles in regulating FAA in a circadian oscillatory manner.

  3. Maternal obesity disrupts circadian rhythms of clock and metabolic genes in the offspring heart and liver.

    Wang, Danfeng; Chen, Siyu; Liu, Mei; Liu, Chang

    2015-06-01

    Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Pparα, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-α, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood.

  4. Hepatitis B virus X protein disrupts the balance of the expression of circadian rhythm genes in hepatocellular carcinoma.

    Yang, Sheng-Li; Yu, Chao; Jiang, Jian-Xin; Liu, Li-Ping; Fang, Xiefan; Wu, Chao

    2014-12-01

    The human circadian rhythm is controlled by at least eight circadian clock genes and disruption of the circadian rhythm is associated with cancer development. The present study aims to elucidate the association between the expression of circadian clock genes and the development of hepatocellular carcinoma (HCC), and also to reveal whether the hepatitis B virus X protein (HBx) is the major regulator that contributes to the disturbance of circadian clock gene expression. The mRNA levels of circadian clock genes in 30 HCC and the paired peritumoral tissues were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A stable HBx-expressing cell line, Bel-7404-HBx, was established through transfection of HBx plasmids. The mRNA level of circadian clock genes was also detected by RT-qPCR in these cells. Compared with the paired peritumoral tissues, the mRNA levels of the Per1, Per2, Per3 and Cry2 genes in HCC tissue were significantly lower (P0.05). Compared with Bel-7404 cells, the mRNA levels of the CLOCK, Per1 and Per2 genes in Bel-7404-HBx cells were significantly increased, while the mRNA levels of the BMAL1, Per3, Cry1, Cry2 and CKIɛ genes were decreased (Pgenes is common in HCC. HBx disrupts the expression of circadian clock genes and may, therefore, induce the development of HCC.

  5. Circadian and dark-pulse activation of orexin/hypocretin neurons

    Marston Oliver J

    2008-12-01

    Full Text Available Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH. Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock.

  6. Circadian rhythm sleep disorder, free-running type in a sighted male with severe depression, anxiety, and agoraphobia.

    Brown, Mark A; Quan, Stuart F; Eichling, Philip S

    2011-02-15

    Circadian rhythm sleep disorder, free-running type (CRSD, FRT) is a disorder in which the intrinsic circadian rhythm is no longer entrained to the 24-hour schedule. A unique case of CRSD, FRT in a 67-year-old sighted male is presented. The patient had a progressively delayed time in bed (TIB) each night, so that he would cycle around the 24-h clock approximately every 30 days. This was meticulously documented each night by the patient over the course of 22 years. The patient's CRSD, FRT was associated with severe depression, anxiety, and agoraphobia. The agoraphobia may have exacerbated the CRSD, FRT. Entrainment and stabilization of his circadian rhythm was accomplished after treatment that included melatonin, light therapy, and increased sleep structure.

  7. Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue.

    Bratsun, D A; Merkuriev, D V; Zakharov, A P; Pismen, L M

    2016-01-01

    We propose a multiscale chemo-mechanical model of cancer tumor development in epithelial tissue. The model is based on the transformation of normal cells into a cancerous state triggered by a local failure of spatial synchronization of the circadian rhythm. The model includes mechanical interactions and a chemical signal exchange between neighboring cells, as well as a division of cells and intercalation that allows for modification of the respective parameters following transformation into the cancerous state. The numerical simulations reproduce different dephasing patterns--spiral waves and quasistationary clustering, with the latter being conducive to cancer formation. Modification of mechanical properties reproduces a distinct behavior of invasive and localized carcinoma.

  8. A study around the clock: human circadian rhythms, mechanisms, role in cancer and chronotherapy

    2014-01-01

    Dissertação de Mestrado apresentada à Faculdade de Medicina da Universidade de Coimbra com vista à obtenção do grau de Mestre no âmbito do ciclo de estudos de Mestrado Integrado em Medicina Objective: The goal of this paper is to discuss biological rhythms, focusing on chronotherapy in cancer. The objectives are to: (1) briefly describe the circadian timing system, its physiology and networks; (2) address causal issues that have prompt progress toward an understanding of mechanisms underly...

  9. The molecular basis of metabolic cycles and their relationship to circadian rhythms.

    Mellor, Jane

    2016-12-06

    Metabolic cycles result from the partitioning of oxidative and reductive metabolism into rhythmic phases of gene expression and oscillating post-translational protein modifications. Relatively little is known about how these switches in gene expression are controlled, although recent studies have suggested that transcription itself may play a central role. This review explores the molecular basis of the metabolic and gene-expression oscillations in the yeast Saccharomyces cerevisiae, as well as how they relate to other biological time-keeping mechanisms, such as circadian rhythms.

  10. Circadian rhythms, metabolism, and insulin sensitivity: transcriptional networks in animal models.

    Kitazawa, Masashi

    2013-04-01

    Homeostatic systems have adapted to respond to the diurnal light/dark cycle. Numerous physiological pathways, including metabolism, are coordinated by this 24-h cycle. Animals with mutations in clock genes show abnormal glucose and lipid metabolism, indicating a critical relationship between the circadian clock and metabolism. Energy homeostasis is achieved through circadian regulation of the expression and activity of several key metabolic enzymes. Temporal organization of tissue metabolism is coordinated by reciprocal cross-talk between the core clock mechanism and key metabolic enzymes and transcriptional activators. The aim of this review is to define the role of the circadian clock in the regulation of insulin sensitivity by describing the interconnection between the circadian clock and metabolic pathways.

  11. Circadian fluctuations in circulating plasminogen activator inhibitor-1 are independent of feeding cycles in mice.

    Oishi, Katsutaka; Ohkura, Naoki; Yasumoto, Yuki; Yamamoto, Saori

    2017-01-01

    To evaluate the involvement of the day-night feeding cycle in the circadian regulation of circulating plasminogen activator inhibitor-1 (PAI-1) concentrations, mice were fed with a diet for eight hours during either daytime (DF) or nighttime (NF) for one week. The reversed feeding cycle did not affect the circadian phases of plasma PAI-1 levels as well as the nocturnal wheel-running activity, although the phase of Pai-1 mRNA expression was significantly advanced for 8.6 hours in the livers of DF, compared with NF mice. The day-night feeding cycle is not a critical Zeitgeber for circadian rhythm of circulating PAI-1.

  12. Postoperative circadian disturbances

    Gögenur, Ismail

    2010-01-01

    in patients with lower than median pain levels for a three days period after laparoscopic cholecystectomy. In the series of studies included in this thesis we have systematically shown that circadian disturbances are found in the secretion of hormones, the sleep-wake cycle, core body temperature rhythm......An increasing number of studies have shown that circadian variation in the excretion of hormones, the sleep wake circle, the core body temperature rhythm, the tone of the autonomic nervous system and the activity rhythm are important both in health and in disease processes. An increasing attention...... has also been directed towards the circadian variation in endogenous rhythms in relation to surgery. The attention has been directed to the question whether the circadian variation in endogenous rhythms can affect postoperative recovery, morbidity and mortality. Based on the lack of studies where...

  13. Blood pressure circadian rhythm and obesity: Blood pressure variations and obesity

    Despotović Nebojša

    2002-01-01

    Full Text Available Introduction The association between obesity and arterial hypertension has been established in a great number of studies. Our objective was to investigate whether circadian rhythm of blood pressure is disturbed among obese people. Material and methods In this cross-sectional, randomized study, Schiller BR-102 device was used for ambulatory blood pressure monitoring. One hundred and twenty outpatients were divided into three randomized groups: obese body mass index 30 kg/m2 (52 patients, overweight (28 patients, with body mass index 25,0-29,9 kg/m2 and normal weight (control group (48 patients, with body mass index 18,5-24,9 kg/m2. In all patients we investigated the following blood pressure parameters: average blood pressure (total, day-time and night-time, maximal blood pressure and dipping or non-dipping blood pressure pattern during night (for systolic and diastolic blood pressure, respectively. Results In body mass index beyond 30 kg/m2 only systolic blood pressure parameters were significantly higher - average blood pressure - during daytime (P=0.034 and during night (P=0.014; maximal blood pressure (P=0.001. In body mass index beyond 30 kg/m2, absence of normal blood pressure during night was significantly more often registered (P=0.007. Discussion and Conclusion The non-dipping blood pressure pattern and increase of systolic blood pressure only reveal hyper activation of sympathetic nervous system as a leading pathophysiological mechanism causing arterial hypertension in obese patients.

  14. Traffic crash accidents in Tehran, Iran: Its relation with circadian rhythm of sleepiness

    Khosro Sadeghniiat-Haghighi; Zohreh Yazdi; Mohsen Moradinia; Omid Aminian; Alireza Esmaili

    2015-01-01

    Purpose:Road traffic accidents are one of main problems in Iran.Multiple factors cause traffic accidents and the most important one is sleepiness.This factor,however,is given less attention in our country.Road traffic accidents relevant to sleepiness are studied.Methods:In this cross-sectional study,all road traffic accidents relevant to sleepiness,which were reported by police,were studied in Tehran province in 2009.Results:The risk of road traffic accidents due to sleepiness was increased by more than sevenfold (odds ratio =7.33) in low alertness hours (0:00-6:00) compared to other time of day.The risk of road traffic accidents due to sleepiness was decreased by 0.15-fold (odds ratio-0.15) in hours with maximum of alertness (18:00-22:00) of circadian rhythm compared to other time of day.Conclusion:The occurrence of road traffic accidents due to sleepiness has significant statistical relations with driving during lowest point of alertness of circadian rhythm.

  15. Circadian rhythm in QT interval is preserved in mice deficient of potassium channel interacting protein 2

    Gottlieb, Lisa A; Lubberding, Anniek; Larsen, Anders Peter;

    2016-01-01

    Potassium Channel Interacting Protein 2 (KChIP2) is suggested to be responsible for the circadian rhythm in repolarization duration, ventricular arrhythmias, and sudden cardiac death. We investigated the hypothesis that there is no circadian rhythm in QT interval in the absence of KChIP2. Implanted...... telemetric devices recorded electrocardiogram continuously for 5 days in conscious wild-type mice (WT, n = 9) and KChIP2(-/-) mice (n = 9) in light:dark periods and in complete darkness. QT intervals were determined from all RR intervals and corrected for heart rate (QT100 = QT/(RR/100)(1/2)). Moreover, QT...... intervals were determined from complexes within the RR range of mean-RR ± 1% in the individual mouse (QTmean-RR). We find that RR intervals are 125 ± 5 ms in WT and 123 ± 4 ms in KChIP2(-/-) (p = 0.81), and QT intervals are 52 ± 1 and 52 ± 1 ms, respectively(p = 0.89). No ventricular arrhythmias or sudden...

  16. Effects of Different Electromagnetic Fields on Circadian Rhythms of Some Haematochemical Parameters in Rats

    LAURA CONTALBRIGO; CALOGERO STELLETTA; LAURA FALCIONI; STEFANIA CASELLA; GIUSEPPE PICCION; MORANDO SOFFRITTI; MASSIMO MORGANTE

    2009-01-01

    Objectives To investigate the effects of different electromagnetic fields on some haematochemical parameters of circadian rhythms in Sprague-Dawley rats. Methods The study was carried out in 18 male and 18 female rats in good health conditions exposed to 50 Hz magnetic sinusoid fields at the intensity of 1000μT, 100μT, and 0μT (control group) respectively, and in 18 male and 18 female rats in good health conditions exposed to 1.8 GHz electromagnetic fields at the intensity of 50 V/m, 25 V/m and 0 V/m (control group), respectively. Following haematochemical parameters for glucose, triglycerides, and total cholesterol were measured. Results Different effects of electromagnetic fields on circadian rhythms of both male and female rats were observed. Different changes occurred in some haematochemical parameters for glucose, triglycerides, and total cholesterol (P<0.05). Conclusion Exposure to different electromagnetic fields is responsible for the variations of some haematochemical parameters in rats.

  17. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

    Rie Miyata

    2016-01-01

    Full Text Available Xeroderma pigmentosum group A (XPA is a genetic disorder in DNA nucleotide excision repair (NER with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA. The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

  18. Alterations in circadian rhythms of melatonin and cortisol in patients with bronchial asthma

    Guang-he FEI; Rong-yu LIU; Zhi-hong ZHANG; Jiang-ning ZHOU

    2004-01-01

    AIM: To investigate the possible relationships between alterations in circadian rhythm of melatonin, cortisol and bronchial asthma. METHODS: Salivary melatonin and cortisol were measured simultaneously by radioimmunoassay in 10 mild intermittent or persistent patients, 11 moderate-to-severe persistent asthma patients, and 15 control subjects. Twelve salivary samples were collected in a series during a 24-h period in each subject. RESULTS: The results showed overall lower levels of salivary melatonin in asthma patients compared with control subject (P<0.01). The amplitude, peak-level, and baseline of salivary melatonin were significantly lower in mild intermittent or persistent (P<0.01, P<0.05) and moderate-to-severe persistent asthma patients (P<0.01) compared with control group. The 24-h mean level of salivary cortisol was greatly lower and the acrophase was markedly delayed in patients with mild intermittent or persistent asthma (P<0.01) and moderate-to-severe persistent asthma (P<0.05, P<0.01) compared with control subject. CONCLUSION: Disordered circadian rhythms of salivary melatonin and cortisol were found in asthma patients, which may be involved in the pathogenesis of bronchial asthma.

  19. A novel multi-unit tablet for treating circadian rhythm diseases.

    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.

  20. Modulatory effects of two novel agonists for serotonin receptor 7 on emotion, motivation and circadian rhythm profiles in mice.

    Adriani, Walter; Travaglini, Domenica; Lacivita, Enza; Saso, Luciano; Leopoldo, Marcello; Laviola, Giovanni

    2012-02-01

    Serotonin receptor 7, i.e. 5-HT(7) protein coded by Htr7 gene, was discovered in supra-chiasmatic nucleus (SCN) of the hypothalamus but is widespread in the forebrain. Studies have shown that this receptor is involved in learning/memory, regulation of mood and circadian rhythms. The modulatory effects of two novel agonists, LP-211 and LP-378, were assessed in male adult CD-1 mice with a battery of behavioral tests. Exp. 1 (Black/White Boxes, BWB: Adriani et al., 2009) and Exp. 2 (Dark/Light, D/L; Novelty-seeking, N-S) show: a) that LP-211 administration (acutely, at a 0.25 mg/kg dose i.p.) increases locomotion and BWB exploration; b) that the time spent away from an aversive, lit chamber (i.e., stress-induced anxiety) and in a new environment (i.e., novelty-induced curiosity) are both reduced. Sub-chronic LP-211 (at a 2.5 mg/kg dose i.p.) reveals a sensitization of locomotor-stimulant properties over 4-5 days. In Exp. 3 (BWB), a three- to four-fold dosage (acutely, at 0.83 mg/kg i.p.) is needed with LP-378 to increase locomotion and BWB exploration. In Exp. 4, mice under constant-light conditions reveal the expected spontaneous lengthening (1.5 h per day) of circadian rhythms. A significant phase advance is induced by LP-211 (at a 0.25 mg/kg dose i.p., administered around activity offset), with onset of activity taking place 6 h earlier than in controls. In summary, LP-211 is able to act consistently onto exploratory motivation, anxiety-related profiles, and spontaneous circadian rhythm. In the next future, agonist modulation of 5-HT(7) receptors might turn out to be beneficial for sleep and/or anxiety disorders. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

  1. Pituitary hormone circadian rhythm alterations in cirrhosis patients with subclinical hepatic encephalopathy

    2008-01-01

    AIM: To analyze pituitary hormone and melatonin cir- cadian rhythms, and to correlate hormonal alterations with clinical performance, hepatic disease severity and diagnostic tests used for the detection of hepatic en- cephalopathy in cirrhosis. METHODS: Twenty-six patients with cirrhosis were enrolled in the study. Thirteen patients hospitalized for systemic diseases not affecting the liver were included as controls. Liver disease severity was assessed by the Child-Pugh score. All patients underwent detailed neurological assessment, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), assays of pi- tuitary hormone, cortisol and melatonin, and complete blood chemistry evaluation. RESULTS: Pituitary hormone and melatonin circadian patterns were altered in cirrhosis patients without clinical encephalopathy. Circadian hormone alterations were different in cirrhosis patients compared with con- trois. Although cortisol secretion was not altered in any patient with cirrhosis, the basal cortisol levels were low and correlated with EEG and brain MRI abnormalities. Melatonin was the only hormone associated with the severity of liver insufficiency. CONCLUSION: Abnormal pituitary hormone and mel- atonin circadian patterns are present in cirrhosis before the development of hepatic encephalopathy. These abnormalities may be early indicators of impending hepatic encephalopathy. Factors affecting the human biologic clock at the early stages of liver insufficiency require further study.

  2. EFFECT OF GENDER DIFFERENCE AND CIRCADIAN RHYTHM ON DIASTOLIC BLOOD PRESSURE FOR VOLLEYBALL PLAYERS

    I. Rajagopal

    2011-04-01

    Full Text Available The purpose of the study was to find out the effect of gender difference and circadian rhythm on diastolic blood pressure for volleyball players. METHODS: To achieve the purpose, a total of thirty volleyball players [men (n = 15 and women (n = 15] age between 19 years and 22 years from Einstein College of Engineering, Tamil Nadu, India were selected as subjects. The two independent variables of gender and circadian variations and dependent variable of diastolic blood pressure were selected for this study. The experimental design used was static group factorial design. The data were collected at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours on diastolic blood pressure by using Erkameter during the academic year of 2009 – 2010. Collected data were subjected to statistical analysis by using two-way factorial (2 x 6 Analysis of Variance (ANOVA and Cosinor analysis. RESULTS: There was insignificant difference between genders, significant difference at different times of the day and insignificant circadian rhythmicity exists on diastolic blood pressure for women and significant for men. CONCLUSION: It is recommended to the physical educators to adopt the findings of this study while planning to improve sports skills for the players and athletes.

  3. EFFECT OF GENDER DIFFERENCE AND CIRCADIAN RHYTHM ON TOTAL MOOD DISTURBANCE OF VOLLEYBALL PLAYERS

    Rajagopal I

    2012-08-01

    Full Text Available The purpose of the study was to find out the effect of gender difference and circadian rhythm on total mood disturbance (TMD for volleyball players. METHODS: To achieve the purpose, a total of thirty volleyball players [men (n = 15 and women (n = 15] age between 19 years and 22 years from Einstein College of Engineering, Tamil Nadu, India were selected as subjects. The two independent variables of gender and circadian variations and dependent variable of total mood disturbance were selected for this study. The experimental design used was static group factorial design. The data were collected at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours on total mood disturbance by using profile of mood state (POMS questionnaire during the academic year of 2009 – 2010. Collected data were subjected to statistical analysis by using two-way factorial (2 x 6 Analysis of Variance (ANOVA and Cosinor analysis. RESULTS: 1 There was significant difference in total mood disturbance between genders, 2 significant difference in total mood disturbance at different times of the day irrespective of gender status and 3 significant difference in total mood disturbance for men and women volleyball players at different times of the day. 4 Significant circadian rhythmicity exists on total mood disturbance for women and 5 Insignificant circadian rhythmicity exists on total mood disturbance for men. CONCLUSION: It is recommended to the physical educators to adopt the findings of this study while planning to improve sports skills for the players and athletes.

  4. Stochastic models of cellular circadian rhythms in plants help to understand the impact of noise on robustness and clock structure

    Maria Luisa eGuerriero

    2014-10-01

    Full Text Available 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-hour 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 studied.

  5. Short wavelength light filtering by the natural human lens and IOLs -- implications for entrainment of circadian rhythm

    Brøndsted, Adam Elias; Lundeman, Jesper Holm; Kessel, Line

    2013-01-01

    Photoentrainment of circadian rhythm begins with the stimulation of melanopsin containing retinal ganglion cells that respond directly to blue light. With age, the human lens becomes a strong colour filter attenuating transmission of short wavelengths. The purpose of the study was to examine...

  6. Impact of behavior on central and peripheral circadian clocks in the common vole Microtus arvalis, a mammal with ultradian rhythms

    van der Veen, DR; Le Minh, N; Gos, P; Arneric, M; Gerkema, MP; Schibler, U; Takahashi, Joseph S.

    2006-01-01

    In most mammals, daily rhythms in physiology are driven by a circadian timing system composed of a master pacemaker in the suprachiasmatic nucleus (SCN) and peripheral oscillators in most body cells. The SCN clock, which is phase-entrained by light-dark cycles, is thought to synchronize subsidiary o

  7. A brief history of circadian time: The emergence of redox oscillations as a novel component of biological rhythms

    Lisa Wulund

    2015-12-01

    Full Text Available Circadian rhythms are present in all living organisms. They organise processes such as gene transcription, mitosis, feeding, and rest at different times of day and night. These rhythms are orchestrated by a network of core ‘clock genes’ that are organised into transcription–translation feedback loops (TTFLs, producing oscillations with a period of approximately 24 h. The modern understanding of circadian timekeeping has revolved around the TTFL paradigm. Recently, however, this has been challenged by new findings that redox reactions persist in the absence of gene transcription, and that cycles of oxidation and reduction are conserved across all domain of life. These results suggest that non-transcriptional processes such as metabolic state may interact and work in parallel with the canonical genetic mechanisms of keeping circadian time.

  8. Mitogen-activated protein kinase is a functional component of the autonomous circadian system in the suprachiasmatic nucleus.

    Akashi, Makoto; Hayasaka, Naoto; Yamazaki, Shin; Node, Koichi

    2008-04-30

    The suprachiasmatic nucleus (SCN) is the master circadian pacemaker driving behavioral and physiological rhythms in mammals. Circadian activation of mitogen-activated protein kinase [MAPK; also known as ERK (extracellular signal-regulated kinase)] is observed in vivo in the SCN under constant darkness, although the biological significance of this remains unclear. To elucidate this question, we first examined whether MAPK was autonomously activated in ex vivo SCN slices. Moreover, we investigated the effect of MAPK inhibition on circadian clock gene expression and neuronal firing rhythms using SCN-slice culture systems. We show herein that MAPK is autonomously activated in the SCN, and our data demonstrate that inhibition of the MAPK activity results in dampened rhythms and reduced basal levels in circadian clock gene expression at the SCN single-neuron level. Furthermore, MAPK inhibition attenuates autonomous circadian neuronal firing rhythms in the SCN. Thus, our data suggest that light-independent MAPK activity contributes to the robustness of the SCN autonomous circadian system.

  9. Egg-laying rhythm in Drosophila melanogaster

    T. Manjunatha; Shantala Hari Dass; Vijay Kumar Sharma

    2008-12-01

    Extensive research has been carried out to understand how circadian clocks regulate various physiological processes in organisms. The discovery of clock genes and the molecular clockwork has helped researchers to understand the possible role of these genes in regulating various metabolic processes. In Drosophila melanogaster, many studies have shown that the basic architecture of circadian clocks is multi-oscillatory. In nature, different neuronal subgroups in the brain of D. melanogaster have been demonstrated to control different circadian behavioural rhythms or different aspects of the same circadian rhythm. Among the circadian phenomena that have been studied so far in Drosophila, the egg-laying rhythm is unique, and relatively less explored. Unlike most other circadian rhythms, the egg-laying rhythm is rhythmic under constant light conditions, and the endogenous or free-running period of the rhythm is greater than those of most other rhythms. Although the clock genes and neurons required for the persistence of adult emergence and activity/rest rhythms have been studied extensively, those underlying the circadian egg-laying rhythm still remain largely unknown. In this review, we discuss our current understanding of the circadian egg-laying rhythm in D. melanogaster, and the possible molecular and physiological mechanisms that control the rhythmic output of the egg-laying process.

  10. Circadian rhythms in blood pressure in free-ranging three-toed sloths (Bradypus variegatus

    Duarte D.P.F.

    2003-01-01

    Full Text Available Blood pressure (BP profiles were monitored in nine free-ranging sloths (Bradypus variegatus by coupling one common carotid artery to a BP telemetry transmitter. Animals moved freely in an isolated and temperature-controlled room (24ºC with 12/12-h artificial light-dark cycles and behaviors were observed during resting, eating and moving. Systolic (SBP and diastolic (DBP blood pressures were sampled for 1 min every 15 min for 24 h. BP rhythm over 24 h was analyzed by the cosinor method and the mesor, amplitude, acrophase and percent rhythm were calculated. A total of 764 measurements were made in the light cycle and 721 in the dark cycle. Twenty-four-hour values (mean ± SD were obtained for SBP (121 ± 22 mmHg, DBP (86 ± 17 mmHg, mean BP (MBP, 98 ± 18 mmHg and heart rate (73 ± 16 bpm. The SBP, DBP and MBP were significantly higher (unpaired Student t-test during the light period (125 ± 21, 88 ± 15 and 100 ± 17 mmHg, respectively than during the dark period (120 ± 21, 85 ± 17 and 97 ± 17 mmHg, respectively and the acrophase occurred between 16:00 and 17:45 h. This circadian variation is similar to that observed in cats, dogs and marmosets. The BP decreased during "behavioral sleep" (MBP down from 110 ± 19 to 90 ± 19 mmHg at 21:00 to 8:00 h. Both feeding and moving induced an increase in MBP (96 ± 17 to 119 ± 17 mmHg at 17:00 h and 97 ± 19 to 105 ± 12 mmHg at 15:00 h, respectively. The results show that conscious sloths present biphasic circadian fluctuations in BP levels, which are higher during the light period and are mainly synchronized with feeding.

  11. Circadian rhythms and mood: opportunities for multi-level analyses in genomics and neuroscience: circadian rhythm dysregulation in mood disorders provides clues to the brain's organizing principles, and a touchstone for genomics and neuroscience.

    Li, Jun Z

    2014-03-01

    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. Also watch the Video Abstract. Editor's suggested further reading in BioEssays Major depressive disorder: A loss of circadian synchrony? Abstract.

  12. The circadian cycle : daily rhythms from behaviour to genes - First in the Cycles Review Series

    Merrow, M; Spoelstra, K; Roenneberg, T

    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 c

  13. The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

    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.

  14. Blood pressure circadian rhythm and heart rate turbulence in hypertensive patients: relationship with left ventricular hypertrophy

    Mei Zhu; Mohan Liu; Xinhong Guo; Shiwen Wang

    2009-01-01

    Objective To investigate the relationship of blood pressure circadian rhythm with myocardial hypertrophy and the changes of autonomic nerve function in patients with essential hypertension (EH). Methods Eighty-two female patients with essential hypertension (EH) underwent 24-hours ambulatory blood pressure monitorings (ABPM), dynamic electrocardiogram (Holter) and echocardiography examination. Patients were classified into non-dipping group (n=40) and dipping group (n=42) according to the result of ABPM. Left ventricular mass index (LVMI), heart rate variability (HRV) in time domain (including SDNN, SDANN, rMSSD, PNN50) and heart rate turbulence (HRT) parameters (including turbulence onset [TO] and turbulence slope [TS]) were measured. Results Compared with those in dipping group, patients in non-dipping group have higher incidence of LVH (19.0% vs 52.5%, P<0.01), greater mean LVMI (112.39±12.79 g/m2 vs 121.98±13.35 g/m2, P<0.01), decreased PNN50 and rMSSD. TS value was decreased while TO was increased in non-dipping group compared with those in dipping group (both P <0.01); patients with LVH showed decreased TS and increased TO, compared with those without LVH. Conclusion In female patients with EH, non-dipping blood pressure circadian is associated with higher incidence of LVH. The HRV and HRT were more remarkably blunted in non-dipping patients, as well as those with LVH.

  15. The Role of Circadian Rhythms in Muscular and Osseous Physiology and Their Regulation by Nutrition and Exercise.

    Aoyama, Shinya; Shibata, Shigenobu

    2017-01-01

    The mammalian circadian clock regulates the day and night cycles of various physiological functions. The circadian clock system consists of a central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks in peripheral tissues. According to the results of circadian transcriptomic studies in several tissues, the majority of rhythmic genes are expressed in a tissue-specific manner and are influenced by tissue-specific circadian rhythms. Here we review the diurnal variations of musculoskeletal functions and discuss the impact of the circadian clock on homeostasis in skeletal muscle and bone. Peripheral clocks are controlled by not only photic stimulation from the central clock in the SCN but also by external cues, such as feeding and exercise. In this review, we discuss the effects of feeding and exercise on the circadian clock and diurnal variation of musculoskeletal functions. We also discuss the therapeutic potential of chrono-nutrition and chrono-exercise on circadian disturbances and the failure of homeostasis in skeletal muscle and bone.

  16. Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men.

    Ricardo Mora-Rodríguez

    Full Text Available PURPOSE: To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. METHODS: Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i morning (10:00 a.m. with caffeine ingestion (i.e., 3 mg kg(-1; AM(CAFF trial; ii morning (10:00 a.m. with placebo ingestion (AM(PLAC trial; and iii afternoon (18:00 p.m. with placebo ingestion (PM(PLAC trial. A randomized, double-blind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ and bench press (BP exercises against loads that elicit maximum strength (75% 1RM load and muscle power adaptations (1 m s(-1 load. Isometric maximum voluntary contraction (MVC(LEG and isometric electrically evoked strength of the right knee (EVOK(LEG were measured to identify caffeine's action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone were evaluated at the beginning of each trial (PRE. In addition, plasma norepinephrine (NE and epinephrine were measured PRE and at the end of each trial following a standardized intense (85% 1RM 6 repetitions bout of SQ (POST. RESULTS: In the PM(PLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AM(PLAC treatment (3.0%-7.5%; p≤0.05. During AM(CAFF trial, muscle strength and power output increased above AM(PLAC levels (4.6%-5.7%; p≤0.05 except for BP velocity with 1 m s(-1 load (p = 0.06. During AM(CAFF, EVOK(LEG and NE (a surrogate of maximal muscle sympathetic nerve activation were increased above AM(PLAC trial (14.6% and 96.8% respectively; p≤0.05. CONCLUSIONS: These results indicate that caffeine ingestion reverses the morning neuromuscular declines in highly resistance

  17. Daily patterns of the locomotor activity of Bothrops jararacussu (Serpentes: Viperidae: A response to environmental lighting conditions or an endogenous rhythm?

    Júlia Niehues da Cruz

    2008-12-01

    Full Text Available While most circadian biologists would probably assume that circadian clocks drive activity patterns, it is also well known that environmental stimuli may mask endogenous rhythms by either increasing or suppressing activity. The hypothesis that circadian rhythms are generally entrained by exogenous cycles was experimentally tested in Bothrops jararacussu. In this study, we investigated the locomotor activity under constant light and constant dark conditions for 24 days and compared it to that of control snakes living under a light/dark cycle. Under the light/dark cycle, one peak of activity was observed during the night phase, which is typical of the circadian rhythms of nocturnal species. Constant light on Bothrops jararacussu promoted a significant fragmentation and an overall increase in the amount of locomotor activity, while constant darkness provoked a significant suppression of activity. This circadian rhythm is probably endogenous, primarily synchronized by alternating light and darkness. Constant light induces desynchronization, and constant darkness leads to the blockage of circadian clocks. The functional significance of these circadian changes suggests a small flexibility in circadian organization in response to environmental conditions.

  18. 昼夜节律与衰老的研究%The research of biont in Circadian rhythms and aging degenerative process

    何本进; 贾春媛; 韩晶; 杜建财; 张翻弟; 杨泽; 梁庆华; 胡才友; 孙亮; 朱小泉; 原惠萍; 杨帆; 李星慧; 秦娇琴

    2015-01-01

    多数生物是以24小时或近似24小时为周期而显示出明显的昼夜节律。昼夜节律控制着觉醒与睡眠的更替,即使在全天照明或黑暗的环境条件下也照常运行。尽管在无光照条件下,昼夜节律也能自由运行,但光照对于该节律的设置调整则具有重要作用。通过温度改变、人工光照或人工黑暗条件,监测生物的生理、生化等活动是否会随昼夜节律的改变而发生变化。本文主要就纤细裸藻在温度或光照等条件的改变下,其细胞分裂周期、酶活性、芳香族氨基酸代谢等生理生化活性变化进行了综述。%Most organisms exhibit clear circadian rhythm based on 24h or approximately 24h cycle.Circadian rhythm controls the replacement of wakefulness and sleep,it also runs normally even in light or dark condition throughout the day.However,circadian rhythm is also free-running under the condition of no light,and the setting of illumination to the rhythm plays a key role.Whether the physiological and biological activities of monitoring the organisms will change,following the variation of the circadian rhythm by chan-ges in temperature,subjective light or dark conditions.We review the variations of physiological and biological activities of cell divi-sion cycle, enzymatic activity and aromatic amino acid metabolism in Euglena gracilis Klebs under the change of temperature or illu-mination condition.

  19. Differential regulation of circadian melatonin rhythm and sleep-wake cycle by bright lights and nonphotic time cues in humans.

    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 (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.

  20. Unique food-entrained circadian rhythm in cysteine414-alanine mutant mCRY1 transgenic mice.

    Okano, Satoshi; Yasui, Akira; Hayasaka, Kiyoshi; Nakajima, Osamu

    Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Daily scheduled restricted feeding (RF), in which the food available time is restricted for several hours each day, elicits anticipatory activity. This food-anticipatory activity (FAA) is controlled by a food-entrainable oscillator (FEO) that is distinct from the suprachiasmatic nucleus (SCN), the master pacemaker in mammals. In an earlier report, we described generation of transgenic (Tg) mice ubiquitously overexpressing cysteine414-alanine mutant mCRY1. The Tg mice displayed long locomotor free-running periods (approximately 28 h) with rhythm splitting. Furthermore, their locomotor activity immediately re-adjusted to the advance of light-dark cycles (LD), suggesting some disorder in the coupling of SCN neurons. The present study examined the restricted feeding cycle (RF)-induced entrainment of locomotor activity in Tg mice in various light conditions. In LD, wild-type controls showed both FAA and LD-entrained activities. In Tg mice, almost all activity was eventually consolidated to a single bout before the feeding time. The result suggests a possibility that in Tg mice the feeding cycle dominates the LD cycle as an entrainment agent. In constant darkness (DD), wild-type mice exhibited robust free-run activity and FAA during RF. For Tg mice, only the rhythm entrained to RF was observed in DD. Furthermore, after returning to free feeding, the free-run started from the RF-entrained phase. These results suggest that the SCN of Tg mice is entrainable to RF and that the mCRY1 mutation alters the sensitivity of SCN to the cycle of nonphotic zeitgebers.

  1. Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

    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.

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

    Garaulet, Marta; Ordovás, José M; Gómez-Abellán, Purificación; Martínez, Jose A; Madrid, Juan A

    2011-08-01

    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 including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n=6) were obtained from morbid obese women (BMI≥40 kg/m(2) ). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue.

  3. Postoperative circadian disturbances

    Gögenur, Ismail

    2010-01-01

    An increasing number of studies have shown that circadian variation in the excretion of hormones, the sleep wake circle, the core body temperature rhythm, the tone of the autonomic nervous system and the activity rhythm are important both in health and in disease processes. An increasing attentio...

  4. Circadian rhythms are not involved in the regulation of circannual reproductive cycles in a sub-tropical bird, the spotted munia.

    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.

  5. Lysosomotropic REV-ERB antagonism: A metabolic connection between circadian rhythm and autophagy may tell cancer cells "it's time to die".

    Grimaldi, Benedetto

    2015-01-01

    The discovery that inhibition of a circadian regulator enhances autophagy-dependent cancer cell death reveals potential avenues for the development of new multifunctional anticancer agents. Further studies may elucidate novel crosstalk between circadian rhythm, metabolism, and autophagy that determines cancer cell viability.

  6. Effect of stress and dexamethasone treatment on circadian rhythms of melatonin and corticosterone in ring dove (Streptopelia risoria).

    Barriga, Carmen; Marchena, Jose María; Lea, Robert William; Harvey, Steve; Rodríguez, Ana Beatriz

    2002-03-01

    The possible relationship between the circadian rhythm of blood levels of melatonin and corticosterone in ring dove (Streptopelia risoria) subjected to both immobilization stress and immobilization stress plus dexamethasone treatment were studied. The results show changes in the circadian rhythm of melatonin, with increased daytime levels in situations of stress accompanied by increased corticosterone levels. The highest blood melatonin levels over the 24 h of the study were obtained when the animals were treated with dexamethasone and then subjected to stress. Given the antioxidant role of melatonin, our results support the idea ofmelatonin-corticosterone coupling with the possibility that melatonin released in situations of stress counteracts the adverse effects of glucocorticoids on the organism.

  7. [Reaction of circadian rhythms of the lymphoid system to deep screening from geomagnetic fields of the earth].

    Borodin, Iu I; Letiagin, A Y

    1990-02-01

    C57B1/6 inbred mice were placed in hypomagnetic condition during 14 days constantly. Degree of relaxation of geomagnetic field was 10(4). The increase of the number of eosinophil granulocytes was discovered in peripheral blood of mice. Measures of circadian rhythms of blood's absolute lymphocytosis, absolute number of cells in bone marrow, thymus, spleen and inguinal lymph nodes were safe. Adaptation of lymphoid system to hypomagnetic condition was manifested by desynchronization of circadian rhythmicity on the basis of different sensitivity of lymphoid organs, that realized in strengthening of ultradian rhythms with periods of 15 hours. There are indirect data, that show the increase of speed and/or volume of recirculation of lymphoid cells.

  8. The role of retinal photoreceptors in the regulation of circadian rhythms

    Paul, Ketema N.; Saafir, Talib B.; Tosini, Gianluca

    2009-01-01

    The circadian clock is an evolutionarily, highly conserved feature of most organisms. This internal timing mechanism coordinates biochemical, physiological and behavioral processes to maintain synchrony with the environmental cycles of light, temperature and nutrients. Several studies have shown that light is the most potent cue used by most organisms (humans included) to synchronize daily activities. In mammals, light perception occurs only in the retina; three different types of photorecept...

  9. Correlation between the circadian rhythm of melatonin, phagocytosis, and superoxide anion levels in ring dove heterophils.

    Rodríguez, A B; Marchena, J M; Nogales, G; Durán, J; Barriga, C

    1999-01-01

    A functional role for melatonin is its relationship to circadian timing mechanisms. In addition, there has recently been assumed to be a functional connection between the pineal gland and the immune system in mammals and birds, with some findings showing melatonin to be a free radical scavenger and general antioxidant. The present study investigates the possible relationship between the circadian rhythm of melatonin and the ingestion capacity as well as superoxide anion levels of ring dove (Streptopelia risoria) heterophils. In birds, heterophils, with their ability to ingest and kill different antigens, play a central role in the host defence mechanism. All determinations were made during 24 hr periods at 2 hr intervals. Radioimmunoassay showed an increase of melatonin serum levels during the dark period (from 20:00 to 07:00 hr) with a maximum at 04:00 hr, and a significant decline during the hours of light with a minimum at 16:00 hr. Similarly, the phagocytic index was enhanced during the night, with the maximum at approximately 04:00 hr and the minimum at approximately 18:00 hr. The same was the case in relation to phagocytic percentage. However, the superoxide anion levels were lower during darkness (minimum at 04:00 hr) and higher during the light period (maximum at 14:00 hr). In conclusion, our findings show that one pineal-mediated effect on the immune system may be a direct action of melatonin on phagocytosis and the phagocytic biochemical process, and that this neurohormone might act as an antioxidant.

  10. Daily Rhythms of Hunger and Satiety in Healthy Men during One Week of Sleep Restriction and Circadian Misalignment.

    Sargent, Charli; Zhou, Xuan; Matthews, Raymond W; Darwent, David; Roach, Gregory D

    2016-01-29

    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.

  11. Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

    Mahadevan, Sangeetha K.; Fiorotto, Marta L.; Van den Veyver, Ignatia B.

    2017-01-01

    Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP) or a control protein (20% protein, C) diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein) and single-housed until 8–12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration), depression (tail suspension and forced swim test), sociability (three-chamber), repetitive (marble burying), learning and memory (fear conditioning), and circadian behavior (wheel-running activity during light-dark and constant dark cycles). We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT). Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03), less energy expenditure (P = 0.004), less rearing activity (P = 0.04) and a greater number of night-time rest/sleep bouts (P = 0.03) compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01) but had no learning and memory deficit in fear-conditioning assay (P = 0.02). There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces

  12. Circannual and circadian rhythms of hypothalamic DNA methyltransferase and histone deacetylase expression in male Siberian hamsters (Phodopus sungorus).

    Stevenson, Tyler J

    2017-03-01

    Precise timing of gene transcription is a fundamental component of many biological rhythms. DNA methylation and histone acetylation are two epigenetic modifications that can affect the probability of gene transcription and RNA expression. Enzymes involved in DNA methylation (dnmts) have been shown to exhibit photoperiodic rhythms in expression in the hypothalamus, which coincide with hypothalamic expression of deiodinase type III (dio3), a gene involved in the photoperiodic regulation of reproduction. It is currently unknown whether enzymes involved in histone deacetylation (hdacs) also vary in response to photoperiod, nor have seasonal changes in the circadian waveforms of methylation and/or acetylation enzymes been examined. The present work documents circadian and photoperiodic changes in dnmts and hdacs in whole hypothalamic dissections obtained from male Siberian hamsters (Phodopus sungorus) after 5-6weeks of exposure to SD. The data indicate that short days (SD) markedly inhibit dnmt3a expression, and that SD inhibition of dnmt3a was evident regardless of the alignment of circadian waveforms. Among hdacs, photoperiodic and circadian changes in expression were only observed in hdac4 expression. Recurrent temporal waveforms in epigenetic enzyme expression may provide molecular inputs to the timing systems that reprogram RNA expression to generate daily and annual phenotypic plasticity.

  13. Fine-Tuning Circadian Rhythms: The Importance of Bmal1 Expression in the Ventral Forebrain

    Mieda, Michihiro; Hasegawa, Emi; Kessaris, Nicoletta; Sakurai, Takeshi

    2017-01-01

    Although, the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes has been demonstrated not only in the SCN, but also in peripheral tissues and brain regions outside the SCN. However, the physiological roles of extra-SCN circadian clocks in the brain remain largely elusive. In response, we generated Nkx2.1-Bmal1−/− mice in which Bmal1, an essential clock component, was genetically deleted specifically in the ventral forebrain, including the preoptic area, nucleus of the diagonal band, and most of the hypothalamus except the SCN. In these mice, as expected, PER2::LUC oscillation was drastically attenuated in the explants of mediobasal hypothalamus, whereas it was maintained in those of the SCN. Although, Nkx2.1-Bmal1−/− mice were rhythmic and nocturnal, they showed altered patterns of locomotor activity during the night in a 12:12-h light:dark cycle and during subjective night in constant darkness. Control mice were more active during the first half than the second half of the dark phase or subjective night, whereas Nkx2.1-Bmal1−/− mice showed the opposite pattern of locomotor activity. Temporal patterns of sleep-wakefulness and feeding also changed accordingly. Such results suggest that along with mechanisms in the SCN, local Bmal1–dependent clocks in the ventral forebrain are critical for generating precise temporal patterns of circadian behaviors.

  14. Circadian rhythms and food anticipatory behavior in Wfs1-deficient mice.

    Luuk, Hendrik; Fahrenkrug, Jan; Hannibal, Jens

    2012-08-10

    The dorsomedial hypothalamic nucleus (DMH) has been proposed as a candidate for the neural substrate of a food-entrainable oscillator. The existence of a food-entrainable oscillator in the mammalian nervous system was inferred previously from restricted feeding-induced behavioral rhythmicity in rodents with suprachiasmatic nucleus lesions. In the present study, we have characterized the circadian rhythmicity of behavior in Wfs1-deficient mice during ad libitum and restricted feeding. Based on the expression of Wfs1 protein in the DMH it was hypothesized that Wfs1-deficient mice will display reduced or otherwise altered food anticipatory activity. Wfs1 immunoreactivity in DMH was found almost exclusively in the compact part. Restricted feeding induced c-Fos immunoreactivity primarily in the ventral and lateral aspects of DMH and it was similar in both genotypes. Wfs1-deficiency resulted in significantly lower body weight and reduced wheel-running activity. Circadian rhythmicity of behavior was normal in Wfs1-deficient mice under ad libitum feeding apart from elongated free-running period in constant light. The amount of food anticipatory activity induced by restricted feeding was not significantly different between the genotypes. Present results indicate that the effects of Wfs1-deficiency on behavioral rhythmicity are subtle suggesting that Wfs1 is not a major player in the neural networks responsible for circadian rhythmicity of behavior.

  15. Genetic correlation between the pre-adult developmental period and locomotor activity rhythm in Drosophila melanogaster.

    Takahashi, K H; Teramura, K; Muraoka, S; Okada, Y; Miyatake, T

    2013-04-01

    Biological clocks regulate various behavioural and physiological traits; slower circadian clocks are expected to slow down the development, suggesting a potential genetic correlation between the developmental period and circadian rhythm. However, a correlation between natural genetic variations in the developmental period and circadian rhythm has only been found in Bactrocera cucurbitae. The number of genetic factors that contribute to this genetic correlation is largely unclear. In this study, to examine whether natural genetic variations in the developmental period and circadian rhythm are correlated in Drosophila melanogaster, we performed an artificial disruptive selection on the developmental periods using wild-type strains and evaluated the circadian rhythms of the selected lines. To investigate whether multiple genetic factors mediate the genetic correlation, we reanalyzed previously published genome-wide deficiency screening data based on DrosDel isogenic deficiency strains and evaluated the effect of 438 genomic deficiencies on the developmental periods. We then randomly selected 32 genomic deficiencies with significant effects on the developmental periods and tested their effects on circadian rhythms. As a result, we found a significant response to selection for longer developmental periods and their correlated effects on circadian rhythms of the selected lines. We also found that 18 genomic regions had significant effects on the developmental periods and circadian rhythms, indicating their potential for mediating the genetic correlation between the developmental period and circadian rhythm. The novel findings of our study might lead to a better understanding of how this correlation is regulated genetically in broader taxonomic groups.

  16. Effects of temperature and photoperiod on daily activity rhythms of Lutzomyia longipalpis (Diptera: Psychodidae)

    Rivas, Gustavo BS; Souza,Nataly Araujo de; Peixoto, Alexandre A; Bruno, Rafaela V.

    2014-01-01

    Background Insect vectors have been established as models in Chronobiology for many decades, and recent studies have demonstrated a close relationship between the circadian clock machinery, daily rhythms of activity and vectorial capacity. Lutzomyia longipalpis, the primary vector of Leishmania (Leishmania) infantum in the New World, is reported to have crepuscular/nocturnal activity in the wild. However, most of these studies applied hourly CDC trap captures, which is a good indicative of L....

  17. Short communication: Early modification of the circadian organization of cow activity in relation to disease or estrus.

    Veissier, Isabelle; Mialon, Marie-Madeleine; Sloth, Karen Helle

    2017-03-16

    Biological rhythms are an essential regulator of life. There is evidence that circadian rhythm of activity is disrupted under chronic stress in animals and humans, and it may also be less marked during diseases. Here we investigated whether a detectable circadian rhythm of activity exists in dairy cows in commercial settings using a real-time positioning system. We used CowView (GEA Farm Technologies) to regularly record the individual positions of 350 cows in a Danish dairy farm over 5 mo and to infer the cows' activity (resting, feeding, in alley). We ran a factorial correspondence analysis on the cows' activities and used the first component of this analysis to express the variations in activity. On this axis, the activities obtained the following weights: resting = -0.15; in alleys = +0.12; feeding = +0.34. By applying these weights to the proportions of time each cow spent on each of the 3 activities, we were able to chart a circadian rhythm of activity. We found that average level of activity of a cow on a given day and its variations during that day varied with specific states (i.e., estrus, lameness, mastitis). More specifically, circadian variations in activity appeared to be particularly sensitive and to vary 1 to 2 d before the farmer detected a disorder. These findings offer promising avenues for further research to design models to predict physiological or pathological states of cows from real-time positioning data.

  18. Circadian rhythms in the growth and reproduction of the brown alga Undaria pinnatifida and gametogenesis under different photoperiods

    ZHANG Zhihuai; PANG Shaojun

    2007-01-01

    Circadian growth rhythm of the juvenile sporophyte of the brown alga Undaria pinnatifida was measured with the computer-aided image analysis system in constant florescent white light under constant temperature ( 10 ℃ ). The growth rhythm persisted for 4 d in constant light with a free-running period of 25.6 h. Egg release from filamentous gametophytes pre-cultured in the light - dark regime was evaluated for six consecutive days at fixed time intervals in constant white light and 12 h light per day. Egg release rhythm persisted for 3 d in both regimes, indicating the endogenous nature. Temporal scale of egg release and gametogenesis in 18, 16, 12 and 8 h light per day were evaluated respectively using vegetatively propagated filamentous gametophytes. Egg release occurred 2 h after the onset of dark phase and peaked at midnight. Evaluation of the rates of oogonium formation, egg release or fertilization revealed no significant differences in four light-dark regimes, indicating the great plasticity of sexual reproduction. No photoperiodic effect in gametogenesis in terms of oogonium formation and egg release was found, but fertilization in short days was significantly higher than in long days. Results of this investigation further confirmed the general occurrence of circadian rhythms in intertidal seaweed species.

  19. Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.

    Shechter, Ari; Lespérance, Paul; Ng Ying Kin, N M K; Boivin, Diane B

    2012-01-01

    Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (Pcircadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

  20. High throughput and quantitative approaches for measuring circadian rhythms in cyanobacteria using bioluminescence

    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

  1. Effects of Restricted Fructose Access on Body Weight and Blood Pressure Circadian Rhythms

    Danielle Senador

    2012-01-01

    Full Text Available High-fructose diet is known to produce cardiovascular and metabolic pathologies. The objective was to determine whether the timing of high fructose (10% liquid solution intake affect the metabolic and cardiovascular outcomes. Male C57BL mice with radiotelemetric probes were divided into four groups: (1 24 h water (control; (2 24 h fructose (F24; (3 12 h fructose during the light phase (F12L; (4 12 h fructose during the dark phase (F12D. All fructose groups had higher fluid intake. Body weight was increased in mice on restricted access with no difference in total caloric intake. Fasting glycemia was higher in groups with restricted access. F24 mice showed a fructose-induced blood pressure increase during the dark period. Blood pressure circadian rhythms were absent in F12L mice. Results suggest that the timing of fructose intake is an important variable in the etiology of cardiovascular and metabolic pathologies produced by high fructose consumption.

  2. Circadian Rhythm Influences the Promoting Role of Pulsed Electromagnetic Fields on Sciatic Nerve Regeneration in Rats

    Zhu, Shu; Ge, Jun; Liu, Zhongyang; Liu, Liang; Jing, Da; Ran, Mingzi; Wang, Meng; Huang, Liangliang; Yang, Yafeng; Huang, Jinghui; Luo, Zhuojing

    2017-01-01

    Circadian rhythm (CR) plays a critical role in the treatment of several diseases. However, the role of CR in the treatment of peripheral nerve defects has not been studied. It is also known that the pulsed electromagnetic fields (PEMF) can provide a beneficial microenvironment to quicken the process of nerve regeneration and to enhance the quality of reconstruction. In this study, we evaluate the impact of CR on the promoting effect of PEMF on peripheral nerve regeneration in rats. We used the self-made “collagen-chitosan” nerve conduits to bridge the 15-mm nerve gaps in Sprague-Dawley rats. Our results show that PEMF stimulation at daytime (DPEMF) has most effective outcome on nerve regeneration and rats with DPEMF treatment achieve quickly functional recovery after 12 weeks. These findings indicate that CR is an important factor that determines the promoting effect of PEMF on peripheral nerve regeneration. PEMF exposure in the daytime enhances the functional recovery of rats. Our study provides a helpful guideline for the effective use of PEMF mediations experimentally and clinically. PMID:28360885

  3. CIRCADIAN RHYTHMS IN EXERCISE PERFORMANCE: IMPLICATIONS FOR HORMONAL AND MUSCULAR ADAPTATION

    Weipeng Teo

    2011-12-01

    Full Text Available Almost all physiological and biochemical processes within the human body follow a circadian rhythm (CR. In humans, the suprachiasmatic nucleus regulates sleep- wake cycle and other daily biorhythms in line with solar time. Due to such daily physiological fluctuations, several investigations on neuromuscular performance have reported a distinct CR during exercise. Generally, peak performances have been found to occur in the early evening, at approximately the peak of core body temperature. The increase in core body temperature has been found to increase energy metabolism, improve muscle compliance and facilitate actin-myosin crossbridging. In addition, steroidal hormones such as testosterone (T and cortisol (C also display a clear CR. The role of T within the body is to maintain anabolism through the process of protein synthesis. By contrast, C plays a catabolic function and is involved in the response of stress. Due to the anabolic and catabolic nature of both T and C, it has been postulated that a causal relationship may exist between the CR of T and C and muscular performance. This review will therefore discuss the effects of CR on physical performance and its implications for training. Furthermore, this review will examine the impact of muscular performance on CR in hormonal responses and whether could variations in T and C be potentially beneficial for muscular adaptation

  4. Circadian rhythm modulates long-term potentiation induced at CA1 in rat hippocampal slices.

    Nakatsuka, Hiroki; Natsume, Kiyohisa

    2014-03-01

    Circadian rhythm affects neuronal plasticity. Consistent with this, some forms of synaptic long-term potentiation (LTP) are modulated by the light/dark cycle (LD cycle). For example, this type of modulation is observed in hippocampal slices. In rodents, which are nocturnal, LTP is usually facilitated in the dark phase, but the rat hippocampal CA1 is an exception. The reason why LTP in the dark phase is suppressed in CA1 remains unknown. Previously, LTP was induced with high-frequency stimulation. In this study, we found that in the dark phase, theta-burst stimulation-induced LTP is indeed facilitated in CA1, similar to other regions in the rodent brain. Population excitatory postsynaptic potentials (pEPSP)-LTP and population spikes (PS)-LTP were recorded at CA1. The magnitude of PS-LTP in dark-phase slices was significantly larger than in light-phase slices, while that of pEPSP-LTP was unchanged. Using antidromic-orthodromic stimulation, we found that recurrent inhibition is suppressed in the dark phase. Local gabazine-application to stratum pyramidale in light-phase slices mimicked this disinhibition and facilitated LTP in dark-phase slices. These results suggest that the disinhibition of a GABAA recurrent inhibitory network can be induced in the dark phase, thereby facilitating LTP.

  5. High-throughput and quantitative approaches for measuring circadian rhythms in cyanobacteria using bioluminescence.

    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.

  6. Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.

    Keijzer, Henry; Smits, Marcel G; Duffy, Jeanne F; Curfs, Leopold M G

    2014-08-01

    Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1-2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.

  7. Use of Novel Light Sources and Melatonin Delivery Systems in the Maintenance of Temporal Organization of Physiological and Behavioral Circadian Rhythms

    Winget, C. M.; Singh, M. S.; Syrkin, N. C.; Holley, D. C.

    1998-01-01

    The synchronization of physiological and behavioral rhythms are controlled by an endogenous biological clock. It is generally accepted that environmental lighting is the strongest entrainer of this clock. The pineal gland is an important physiological transducer of environmental lighting via systemic melatonin secretion. We have used a novel light source using light emitting diode (LED) technology to entrain circadian rhythms in rats, and propose a novel percutaneous exogenous melatonin delivery system to entrain rat rhythms. We used 5 groups of Sprague-Dawley rats (175-350 g; N = 8/group) and showed normal entrainment of gross locomotor activity, feeding, and drinking circadian rhythms at light intensities varying from 80 lux to 0.1 lux (22.4 to 0.03 sq cm). To improve the delivery of melatonin across the skin stratum corneum it was formulated in a suitable vehicle in a transdermal drug delivery system. Various saturated and unsaturated fatty acids were used E, akin penetration enhancers. Our best vehicle formulation was achieved with a combination-of ethano1:water (60:40) along with 5% oleic acid as the enhancer. This formulation mixture was studied using Franz diffusion cell (0.636 sq cm diffusional area) and 1 cu cm dorsal skin isolated from Sprague Dawley rats. Our results showed that oleic acid in combination with the water ethanol mixture improved the flux of melatonin by more than 18 fold. The lag time for melatonin permeation was 2-3 hrs and the peak concentrations were achieved in 8-10 hrs. Our approaches in the future will involve the use of our transdermal melatonin delivery system and under the influence of LED light and microgravity.

  8. UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila.

    Bridget C Lear

    Full Text Available In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA, orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to promote behavioral rhythmicity. To better understand the function and regulation of the NA channel, we have characterized two putative auxiliary channel subunits in Drosophila, unc79 (aka dunc79 and unc80 (aka CG18437. We have generated novel unc79 and unc80 mutations that represent strong or complete loss-of-function alleles. These mutants display severe defects in circadian locomotor rhythmicity that are indistinguishable from na mutant phenotypes. Tissue-specific RNA interference and rescue analyses indicate that UNC79 and UNC80 likely function within pacemaker neurons, with similar anatomical requirements to NA. We observe an interdependent, post-transcriptional regulatory relationship among the three gene products, as loss of na, unc79, or unc80 gene function leads to decreased expression of all three proteins, with minimal effect on transcript levels. Yet despite this relationship, we find that the requirement for unc79 and unc80 in circadian rhythmicity cannot be bypassed by increasing NA protein expression, nor can these putative auxiliary subunits substitute for each other. These data indicate functional requirements for UNC79 and UNC80 beyond promoting channel subunit expression. Immunoprecipitation experiments also confirm that UNC79 and UNC80 form a complex with NA in the Drosophila brain. Taken together, these data suggest that Drosophila NA, UNC79, and UNC80 function together in circadian clock neurons to promote rhythmic behavior.

  9. The Effect of Different Photoperiods in Circadian Rhythms of Per3 Knockout Mice

    D. S. Pereira

    2014-01-01

    Full Text Available The aim of this study was to analyse the circadian behavioural responses of mice carrying a functional knockout of the Per3 gene (Per3−/− to different light : dark (L : D cycles. Male adult wild-type (WT and Per3−/− mice were kept under 12-hour light : 12-hour dark conditions (12L : 12D and then transferred to either a short or long photoperiod and subsequently released into total darkness. All mice were exposed to both conditions, and behavioural activity data were acquired through running wheel activity and analysed for circadian characteristics during these conditions. We observed that, during the transition from 12L : 12D to 16L : 8D, Per3−/− mice take approximately one additional day to synchronise to the new L : D cycle compared to WT mice. Under these long photoperiod conditions, Per3−/− mice were more active in the light phase. Our results suggest that Per3−/− mice are less sensitive to light. The data presented here provides further evidence that Per3 is involved in the suppression of behavioural activity in direct response to light.

  10. 2016 Arte Poster Competition First Place Winner: Circadian Rhythm and UV-Induced Skin Damage: An In Vivo Study.

    Guan, Linna; Suggs, Amanda; Ahsanuddin, Sayeeda; Tarrillion, Madeline; Selph, Jacqueline; Lam, Minh; Baron, Elma

    2016-09-01

    Exposure of the skin to ultraviolet (UV) irradiation causes many detrimental effects through mechanisms related to oxidative stress and DNA damage. Excessive oxidative stress can cause apoptosis and cellular dysfunction of epidermal cells leading to cellular senescence and connective tissue degradation. Direct and indirect damage to DNA predisposes the skin to cancer formation. Chronic UV exposure also leads to skin aging manifested as wrinkling, loss of skin tone, and decreased resilience. Fortunately, human skin has several natural mechanisms for combating UV-induced damage. The mechanisms operate on a diurnal rhythm, a cycle that repeats approximately every 24 hours. It is known that the circadian rhythm is involved in many skin physiologic processes, including water regulation and epidermal stem cell function. This study evaluated whether UV damage and the skin's natural mechanisms of inflammation and repair are also affected by circadian rhythm. We looked at UV-induced erythema on seven human subjects irradiated with simulated solar radiation in the morning (at 08:00 h) versus in the afternoon (at 16:00 h). Our data suggest that the same dose of UV radiation induces significantly more inflammation in the morning than in the afternoon. Changes in protein expression relevant to DNA damage, such as xeroderma pigmentosum, complementation group A (XPA), and cyclobutane pyrimidine dimers (CPD) from skin biopsies correlated with our clinical results. Both XPA and CPD levels were higher after the morning UV exposure compared with the afternoon exposure. J Drugs Dermatol. 2016;15(9):1124-1130.

  11. Circadian variation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in swine liver and ileum.

    Rogers, D H; Kim, D N; Lee, K T; Reiner, J M; Thomas, W A

    1981-07-01

    The temporal variation of HMG-CoA reductase activity in the liver and intestine of swine was investigated. The thin-layer chromatographic method widely used in the assay of the reductase was successfully applied to the porcine enzymes. Parallel circadian rhythms were demonstrated in both hepatic and ileal reductases from mash-fed animals. Peak activity occurred approximately 6 hr after feeding, 2.7-fold over the basal level in the liver, and 1.6-fold in the ileum. A milk-cholesterol diet caused a marked depression of both rhythms (90% in liver, 50% in ileum); however, the hourly variation in activity persisted in both organs. Cholestyramine was found to elevate hepatic activity (2.7-fold throughout the rhythm) without affecting that of the intestine. Clofibrate had no effect on either enzyme at any time during the cycle despite a 34% reduction in serum cholesterol concentrations.

  12. Circadian rhythm of salivary cortisol secretion in female zoo-kept African elephants (Loxodonta africana).

    Casares, Miguel; Silván, Gema; Carbonell, Maria Dolores; Gerique, Cati; Martinez-Fernandez, Leticia; Cáceres, Sara; Illera, Juan Carlos

    2016-01-01

    Salivary samples were collected over a 24-hr period from one group of six juvenile (7-12 years) and one group of three adult (24-25 years) African elephant females, Loxodonta africana, and the cortisol concentration was measured in unextracted samples by EIA. Samples were collected during May, June, and November 2012 (n = 147) using cotton swabs at 4-hr intervals from 20:00 to 20:00 of the next day (seven samples per animal in each trial). The animals are kept under standard zoo management: the herd is maintained in their indoor enclosures until 10:00 and then released into the outdoor enclosures until 21:00-21:30 (May/June) and 18:30-19:00 (November). No adult elephant bull was present at the zoo during this time. The results demonstrate a clear diurnal pattern of cortisol secretion with the lowest concentration observed at 20:00 (2.03 ± 0.08 ng/ml saliva) and the peak concentrations at 08:00 (5.26 ± 0.35 ng/ml saliva). Although the cortisol values were higher in the adult cows compared to the juvenile cows in the May-June period, the differences were not significant. However, the values obtained in November from the juvenile group were significantly higher (P < 0.05) than the concentrations measured in this group in June. In conclusion, salivary cortisol in zoo elephants follows a circadian rhythm (sleep-wake cycle) adapted to daily zoo husbandry routines.

  13. Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart.

    Koczor, Christopher A; Ludlow, Ivan; Hight, Robert S; Jiao, Zhe; Fields, Earl; Ludaway, Tomika; Russ, Rodney; Torres, Rebecca A; Lewis, William

    2015-11-01

    MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA's acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy. MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10- or 35-day MDMA, or daily 10-day MDMA followed by 25-day saline washout (10 + 25 days). MDMA treatment caused differential gene expression (p 1.5) in 752 genes following 10 days, 558 genes following 35 days, and 113 genes following 10-day MDMA + 25-day saline washout. Changes in MAPK and circadian rhythm gene expression were identified as early as 10 days. After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was found to be 71% at 10 days, 68% at 35 days, and 91% at 10 + 25 days washout. Differential gene expression paralleled DNA methylation in 22% of genes at 10-day treatment, 17% at 35 days, and 48% at 10 + 25 days washout. We show here that MDMA induced cardiac epigenetic changes in DNA methylation where hypermethylation predominated. Moreover, MDMA induced gene expression of key elements of circadian rhythm regulatory genes. This suggests a fundamental organism-level event to explain some of the etiologies of MDMA dysfunction in the heart.

  14. Circadian rhythms and food anticipatory behavior in Wfs1-deficient mice

    Luuk, Hendrik; Fahrenkrug, Jan; Hannibal, Jens

    2012-01-01

    The dorsomedial hypothalamic nucleus (DMH) has been proposed as a candidate for the neural substrate of a food-entrainable oscillator. The existence of a food-entrainable oscillator in the mammalian nervous system was inferred previously from restricted feeding-induced behavioral rhythmicity...... reduced or otherwise altered food anticipatory activity. Wfs1 immunoreactivity in DMH was found almost exclusively in the compact part. Restricted feeding induced c-Fos immunoreactivity primarily in the ventral and lateral aspects of DMH and it was similar in both genotypes. Wfs1-deficiency resulted...... in significantly lower body weight and reduced wheel-running activity. Circadian rhythmicity of behavior was normal in Wfs1-deficient mice under ad libitum feeding apart from elongated free-running period in constant light. The amount of food anticipatory activity induced by restricted feeding...

  15. Contribution of Drosophila TRPA1-expressing neurons to circadian locomotor activity patterns.

    Youngseok Lee

    Full Text Available In both vertebrates and invertebrates, Transient Receptor Potential (TRP channels are expressed in sensory neurons and mediate environmental stimuli such as light, sound, temperature, and taste. Some of these channels, however, are expressed only in the brain and their functions remain incompletely understood. Using the GAL4/UAS binary system with a line in which the GAL4 had been knocked into the trpA1 locus in Drosophila, we recently reported new insights into TRPA1 localization and function, including its expression in approximately 15% of all circadian neurons. TRPA1 is expressed in lateral posterior neurons (LPNs, which are known to be highly sensitive to entrainment by temperature cycles. Here, I used the bacterial sodium channel, NaChBac, to examine the effects of altering the electrical properties of trpA1 neurons on circadian rhythms. My results indicate that circadian activity of the flies in the morning, daytime, and evening was affected in a temperature-dependent manner following TRPA1 neuronal activation. Remarkably, TRPA1 neuron activation in flies kept at 18°C impacted the morning peak of circadian activity even though TRPA1 is not expressed in morning cells. Taken together, these results suggest that the activation of TRPA1-expressing neurons may differentially coordinate light/dark circadian entrainment, depending on the temperature.

  16. Contribution of Drosophila TRPA1-expressing neurons to circadian locomotor activity patterns.

    Lee, Youngseok

    2013-01-01

    In both vertebrates and invertebrates, Transient Receptor Potential (TRP) channels are expressed in sensory neurons and mediate environmental stimuli such as light, sound, temperature, and taste. Some of these channels, however, are expressed only in the brain and their functions remain incompletely understood. Using the GAL4/UAS binary system with a line in which the GAL4 had been knocked into the trpA1 locus in Drosophila, we recently reported new insights into TRPA1 localization and function, including its expression in approximately 15% of all circadian neurons. TRPA1 is expressed in lateral posterior neurons (LPNs), which are known to be highly sensitive to entrainment by temperature cycles. Here, I used the bacterial sodium channel, NaChBac, to examine the effects of altering the electrical properties of trpA1 neurons on circadian rhythms. My results indicate that circadian activity of the flies in the morning, daytime, and evening was affected in a temperature-dependent manner following TRPA1 neuronal activation. Remarkably, TRPA1 neuron activation in flies kept at 18°C impacted the morning peak of circadian activity even though TRPA1 is not expressed in morning cells. Taken together, these results suggest that the activation of TRPA1-expressing neurons may differentially coordinate light/dark circadian entrainment, depending on the temperature.

  17. Circadian systems biology in Metazoa.

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals.

  18. Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.

    Ari Shechter

    Full Text Available Women with premenstrual dysphoric disorder (PMDD experience mood deterioration and altered circadian rhythms during the luteal phase (LP of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03 worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025 increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05 decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

  19. Circadian rhythm of anti-fungal prenylated chromene in leaves of Piper aduncum.

    Morandim, Andreia de A; Bergamo, Débora Cristina B; Kato, Massuo Jorge; Cavalheiro, Alberto José; Bolzani, Vanderlan da S; Furlan, Maysa

    2005-01-01

    Leaves of Piper aduncum accumulate the anti-fungal chromenes methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (1) and methyl 2,2-dimethyl-8-(3'-methyl-2'-butenyl)-2H-1-chromene-6-carboxylate (2). The enzymatic formation of 2 from dimethylallyl diphosphate and 1 was investigated using cell-free extracts of the title plant. An HPLC assay for the prenylation reaction was developed and the enzyme activity measured in the protein extracts. The prenyltransferase that catalyses the transfer of the dimethylallyl group to C-2' of 1 was soluble and required dimethylallyl diphosphate as the prenyl donor. In the leaves, the biosynthesis of the prenylated chromene 2 was time-regulated and prenyltransferase activity depended upon circadian variation. Preliminary characterisation and purification experiments on the prenyltransferase from P. aduncum have been performed.

  20. Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome.

    Zhang, Yan; Zheng, Wen; Liu, Yuli; Wang, Jue; Peng, Ying; Shang, Haibao; Hou, Ning; Hu, Xiaomin; Ding, Yi; Xiao, Yao; Wang, Can; Zeng, Fanxin; Mao, Jiaming; Zhang, Jun; Ma, Dongwei; Sun, Xueting; Li, Chuanyun; Xiao, Rui-Ping; Zhang, Xiuqin

    2016-04-01

    Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration, and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension.

  1. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity.

    Shelton, Jonathan; Yun, Sujin; Losee Olson, Susan; Turek, Fred; Bonaventure, Pascal; Dvorak, Curt; Lovenberg, Timothy; Dugovic, Christine

    2014-01-01

    Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

  2. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

    Jonathan eShelton

    2015-01-01

    Full Text Available Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6 induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg. Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15 or advance (CT22 wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light-induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

  3. Melatonin promotes circadian rhythm-induced proliferation through Clock/histone deacetylase 3/c-Myc interaction in mouse adipose tissue.

    Liu, Zhenjiang; Gan, Lu; Luo, Dan; Sun, Chao

    2017-05-01

    Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, Pcircadian locomotor output cycles kaput (Clock, Pcycle and increased cell numbers (Pcircadian disruption and promoted adipocyte proliferation in chronic jet-lagged mice and obese mice. Thus, our study found that melatonin promoted adipocyte proliferation by forming a Clock/HDAC3/c-Myc complex and subsequently driving the circadian amplitudes of proliferation genes. Our data reveal a novel mechanism that links circadian rhythm to cell proliferation in adipose tissue. These findings also identify a new potential means for melatonin to prevent and treat sleep deprivation-caused obesity.

  4. A new role for AMP-activated protein kinase in the circadian regulation of L-type voltage-gated calcium channels in late-stage embryonic retinal photoreceptors.

    Huang, Cathy C Y; Shi, Liheng; Lin, Chia-Hung; Kim, Andy Jeesu; Ko, Michael L; Ko, Gladys Y-P

    2015-11-01

    AMP-activated protein kinase (AMPK) is a cellular energy sensor, which is activated when the intracellular ATP production decreases. The activities of AMPK display circadian rhythms in various organs and tissues, indicating that AMPK is involved in the circadian regulation of cellular metabolism. In vertebrate retina, the circadian clocks regulate many aspects of retinal function and physiology, including light/dark adaption, but whether and how AMPK was involved in the retinal circadian rhythm was not known. We hypothesized that the activation of AMPK (measured as phosphorylated AMPK) in the retina was under circadian control, and AMPK might interact with other intracellular signaling molecules to regulate photoreceptor physiology. We combined ATP assays, western blots, immunostaining, patch-clamp recordings, and pharmacological treatments to decipher the role of AMPK in the circadian regulation of photoreceptor physiology. We found that the overall retinal ATP content displayed a diurnal rhythm that peaked at early night, which was nearly anti-phase to the diurnal and circadian rhythms of AMPK phosphorylation. AMPK was also involved in the circadian phase-dependent regulation of photoreceptor L-type voltage-gated calcium channels (L-VGCCs), the ion channel essential for sustained neurotransmitter release. The activation of AMPK dampened the L-VGCC currents at night with a corresponding decrease in protein expression of the L-VGCCα1 pore-forming subunit, while inhibition of AMPK increased the L-VGCC current during the day. AMPK appeared to be upstream of extracellular-signal-regulated kinase and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Hence, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology. We found that in chicken embryonic retina, the activation of AMP-activated protein

  5. Data mining using multivariate The circadian rhythm and visual elements in scorpions: A review

    M. R. Warburg

    2013-12-01

    Full Text Available The purpose of this paper is to review the state of research in this field and to outline future ways how to proceed. The term: "Zeitgeber", implies 'time giver' meaning: synchronizer when an external entrainment factor synchronizes the endogenous rhythm. Is this 'time giver', the chronological date in the sense that it is related to the time of day as reflected in the natural light-dark cycles? Or does it mean cyclic phases of activity as demonstrated in the laboratory? Moreover, is it totally independent of the animal's physiological condition? This subject was studied largely in buthid species (15 of a total of only 30 scorpion species. Moreover, many (over 25% of the studies (19 were done on a single buthid species: Androctonus australis. Species diversity was observed only by one author's work who studied eye structure in seven species. Since he found variability in eye structure it would not be advisable to generalize. The fact that experimenting was carried out irrespective of species diversity, gender, ecological or physiological conditions, and was usually done on animals kept in captivity for some time before the experimenting had started, is a major drawback to this kind of study. The diurnal rhythms is triggered either directly through spontaneous arrhythmic activity in the central nervous system, or by neurosecretory material. It is possible that these differences arise from either different technical treatments or due to basic problems, and these need to be clarified.

  6. An observational study on disturbed peripheral circadian rhythms in hemodialysis patients

    Russcher, Marije; Chaves, Ines; Lech, Karolina; Koch, Birgit C. P.; Nagtegaal, J. Elsbeth; Dorsman, Kira F.; Jong, Anke't; Kayser, Manfred; van Faassen, H. (Martijn) J. R.; Kema, Ido P.; van der Horst, Gijsbertus T. J.; Gaillard, Carlo A. J. M.

    2015-01-01

    The quality of life of hemodialysis (HD) patients is hampered by reduced nocturnal sleep quality and excessive daytime sleepiness. In addition to the sleep/wake cycle, levels of circadian biomarkers (e.g. melatonin) are disturbed in end-stage renal disease (ESRD). This suggests impaired circadian cl

  7. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P

    2015-01-01

    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovari...

  8. Prevalence of Circadian Rhythm Sleep-Wake Disorders and Associated Factors in Euthymic Patients with Bipolar Disorder

    Takaesu, Yoshikazu; Inoue, Yuichi; Murakoshi, Akiko; Komada, Yoko; Otsuka, Ayano; Futenma, Kunihiro; Inoue, Takeshi

    2016-01-01

    Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients. PMID:27442503

  9. Effect of sleep-wake reversal and sleep deprivation on the circadian rhythm of oxygen toxicity seizure susceptibility.

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

    1972-01-01

    Albino Sprague-Dawley rats were exposed in a previously O2 flushed, CO2 free chamber. The exposure began with attainment of 60 psi (gauge) and the end point was the first generalized oxygen toxicity seizure. Animals were exposed to reversal diurnal conditions since weanlings until their sleep-wake cycles had completely reversed, and then divided into four groups of 20 based on the time of day exposed. The time of exposure to oxygen at high pressure prior to seizure was now significantly longer in the group exposed from 1900 to 2000 hr and a reversal of the circadian rhythm of oxygen toxicity seizure susceptibility was noted. Animals maintained on normal diurnal conditions were deprived of sleep on the day of exposure for the 12 hours prior to exposure at 1900 hr, while controls were allowed to sleep. There was no significant differences in the time prior to seizure between the deprived animals and the controls with an n = 40. Thus the inherent threshold in susceptibility to high-pressure oxygen seizures seems not to be a function of sleep itself, but of some biochemical/physiologic event which manifests a circadian rhythm.

  10. Effects of simulated microgravity on circadian rhythm of caudal arterial pressure and heart rate in rats and their underlying mechanism

    Li CHEN

    2016-04-01

    Full Text Available Objective  To explore the effects of simulated microgravity on the circadian rhythm of rats' caudal arterial pressure and heart rate, and their underlying mechanism. Methods  Eighteen male SD rats (aged 8 weeks were randomly assigned to control (CON and tail suspension (SUS group (9 each. Rats with tail suspension for 28 days were adopted as the animal model to simulate microgravity. Caudal arterial pressure and heart rate of rats were measured every 3 hours. The circadian difference of abdominal aorta contraction was measured by aortic ring test. Western blotting was performed to determine and compare the protein expression level of clock genes such as Per2 (Period2, Bmal1 (Aryl hydrocarbon receptor nuclear translocatorlike and dbp (D element binding protein in suprachiasmatic nucleus (SCN and abdominal aorta of rats in CON and SUS group at different time points. Results  Compared with CON group, the caudal arterial pressure, both systolic and diastolic pressure, decreased significantly and the diurnal variability disappeared, meanwhile the heart rate increased obviously and also the diurnal variability disappeared in rats of SUS group. Compared with CON group, the contraction reactivity of abdominal aorta decreased with disappearence of the diurnal variability, and also the clock genes expression in SCN and abdominal aorta showed no diurnal variability in rats of SUS group. Conclusion  Simulated microgravity may lead to circadian rhythm disorders in rats' cardiovascular system, which may be associated with the changes of the clock genes expression. DOI: 10.11855/j.issn.0577-7402.2016.04.06

  11. Polysomnographic Sleep and Circadian Temperature Rhythms as a Function of Prior Shift Work Exposure in Retired Seniors.

    Monk, Timothy H; Buysse, Daniel J; Billy, Bart D; Fletcher, Mary E; Kennedy, Kathy S

    2013-04-29

    In an earlier published telephone interview study (n > 1,000) we have shown that retired shift workers subjectively report worse sleep than retired day workers. This laboratory study sought to determine whether these findings held up when objective polysomnograhic (PSG) measures of sleep were taken and whether retirees' circadian temperature rhythms differed as a function of shift work exposure. All completers of the telephone interview were invited to attend a 36-hour laboratory study for which participants were paid. This involved continuous core body temperature measurement (using an ingestible pill-based system) and 2 nights of PSG. Shift work exposure (plus other measures) was collected by taking a detailed work history. The second laboratory night was scored into sleep stages. Post hoc, we divided participants into 4 shift work exposure groups: 0 years (ie, no exposure to shift work), 1 to 7 years, 7 to 20 years, and >20 years. Sample sizes were 11, 16, 15, and 15, respectively, with approximate equality in mean age (71.7 years of age, 69.1 years of age, 70.0 years of age, and 70.4 years of age, respectively) and percent male (63%, 50%, 67%, and 73%, respectively). Shift work exposure was associated with worse PSG sleep in a dose-related fashion. The percentages of participants with sleep efficiency, 80% for the 0 years, 1 to 7 years, 7 to 20 years, and >20 years groups were 36%, 63%, 67%, and 73%, respectively (P work exposure appeared to result (P = 0.06) in an increased spread of phase angles (difference between habitual bedtime and time of temperature trough). In conclusion, it appears likely that shift work may be related to a scarring of sleep and circadian rhythms. This may be associated with a change in the relationship between habitual sleep timing and the phase of the circadian pacemaker.

  12. The relationship between food metabolism and circadian rhythm%生物钟信号调控的营养学

    孙悦; 吴涛; 诸葛芬; 陆科东; 倪银华; 傅正伟

    2009-01-01

    Circadian rhythms, which generally exist in most organisms, are generated mainly by an internal biological clock. This biological clock is synchronized to the daily periodicities in the physical environment by external factors, such as light-dark cycle, temperature and food availability. Moreover, it has been demonstrated that nutrient substances, such as glucose, cholesterol, adenosine, caffeine, vitamin A and retinoic acid etc., can regulate the biological clock and its circadian outputs by their specific mechanisms. This article briefly reviews recent findings on the relationship of food metabolism and circadian rhythm.%近日节律是生物界普遍存在的一种生理现象,而内源性生物钟是产生近日节律的物质基础,它能使生物体感知并适应环境中的光、温度和食物等周期信号,从而使生物体与外界环境保持周期同步.研究表明,葡萄糖、胆固醇、腺苷、咖啡因、维生素A和视黄酸等营养物质能通过各自不同的方式调控哺乳动物的生物钟,影响其近日节律的信号输出.本文概述了至今为止研究发现的各类与生物钟信号调控相关的营养物质及功能的相关研究进展.

  13. Expanding circadian input, output, and the clock through genomic screens

    2011-01-01

    Many aspects of mammalian physiology display circadian--or once daily--rhythms, such as heart rate, blood pressure, activity levels, metabolism, and liver regeneration. These rhythms are regulated by an entrainable, self-sustaining, cell-autonomous mechanism found in nearly every cell of the body: the circadian clock. The circadian clock itself represents a regulatory network, composed of interlocking negative feedback loops, that in turn is influenced by two other types of regulatory network...

  14. Effects of Resveratrol on Daily Rhythms of Locomotor Activity and Body Temperature in Young and Aged Grey Mouse Lemurs

    Fabien Pifferi

    2013-01-01

    Full Text Available In several species, resveratrol, a polyphenolic compound, activates sirtuin proteins implicated in the regulation of energy balance and biological clock processes. To demonstrate the effect of resveratrol on clock function in an aged primate, young and aged mouse lemurs (Microcebus murinus were studied over a 4-week dietary supplementation with resveratrol. Spontaneous locomotor activity and daily variations in body temperature were continuously recorded. Reduction in locomotor activity onset and changes in body temperature rhythm in resveratrol-supplemented aged animals suggest an improved synchronisation on the light-dark cycle. Resveratrol could be a good candidate to restore the circadian rhythms in the elderly.

  15. Circadian rhythm: a new clue for neuropsychological dysfunction after cardiac surgery

    LUO Ai-lun

    2007-01-01

    @@ In the recent editorial comment, Duboule1 emphasized that "animal development is, in fact, nothing but time".That a circadian timing system is apparently universal in biology is the evidence for the important physiological role that rhythmicity plays.

  16. A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

    Nahum Nolasco

    Full Text Available Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h or day (10:00 h, and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

  17. Sleep deprivation and its impact on circadian rhythms and glucose metabolism

    Jha, P.K.

    2016-01-01

    The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN generates rhythms of behavioural and metabolic processes throughout the body via both endocrine and neuronal outputs. For example, daily rhythms of sleep-wake, fasting-feeding, plasma glucose, glucos

  18. [Circadian rhythms and light responses of clock gene and arylalkylamine N-acetyltransferase gene expressions in the pineal gland of rats].

    Wang, Guo-Qing; Du, Yu-Zhen; Tong, Jian

    2005-02-25

    This study was to investigate the circadian rhythms and light responses of Clock gene and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the 12 h-light : 12 h-dark cycle condition (LD) and constant darkness (DD). Sprague-Dawley rats housed under the light regime of LD (n=36) for 4 weeks and of DD (n=36) for 8 weeks were sampled for the pineal gland once a group (n=6) every 4 h in a circadian day. The total RNA was extracted from each sample and the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine the temporal changes in mRNA levels of Clock and NAT genes during different circadian times or zeitgeber times. The data were analysed by the cosine function software, Clock Lab software and the amplitude F test was used to reveal the circadian rhythm. The main results obtained are as follows. (1) In DD or LD condition, both of Clock and NAT genes mRNA levels in the pineal gland showed robust circadian oscillation (Ppineal gland were significantly reduced (Ppineal gland (P> 0.05). These findings suggest that the expressions of Clock and NAT genes in the pineal gland not only show remarkably synchronous endogenous circadian rhythmic changes, but also response to the ambient light signal in a reduced manner.

  19. Circadian rhythm of Z- and E-2-beta-D: -glucopyranosyloxy-4-methoxy cinnamic acids and herniarin in leaves of Matricaria chamomilla.

    Repcák, Miroslav; Smajda, Benadik; Kovácik, Jozef; Eliasová, Adriana

    2009-07-01

    Chamomile (Matricaria chamomilla) in the above-ground organs synthesizes and accumulates (Z)- and (E)-2-beta-D: -glucopyranosyloxy-4-methoxy cinnamic acids (GMCA), the precursors of phytoanticipin herniarin (7-methoxycoumarin). The diurnal rhythmicity of the sum of GMCA (maximum before daybreak) and herniarin (acrophase at 10 h 21 min of circadian time) was observed under artificial lighting conditions LD 12:12. The acrophase is the time point of the maximum of the sinusoidal curve fitted to the experimental data. In continuous light, the circadian rhythms of both compounds were first described with similar acrophases of endogenous rhythms; a significantly different result from that in synchronized conditions. The rhythms' mesor (the mean value of the sinusoidal curve fitted to the experimental data) under free-running conditions was not influenced. Abiotic stress under synchronized conditions decreased the average content of GMCA to half of the original level and eliminated the rhythmicity. In contrast, the rhythm of herniarin continued, though its content significantly increased. Nitrogen deficiency resulted in a significant increase in GMCA content, which did not manifest any rhythmicity while the rhythm of herniarin continued. Circadian control of herniarin could be considered as a component of the plant's specialized defence mechanisms.

  20. Ultradian rhythms in walking gastric activity.

    Hiatt, J F; Kripke, D F

    1975-01-01

    Ninety to 120 min ultradian rhythms have been described in physiologic and behavioral functions relating to biologic drives. Gastric contractility rhythms were examined in isolated fasting volunteers to supplement behavioral observations of "oral" drives. A clear ultradian rhythms was observed, indicating inherent physiologic oscillation in stomach contractions.

  1. Circadian Clocks in the Immune System.

    Labrecque, Nathalie; Cermakian, Nicolas

    2015-08-01

    The immune system is a complex set of physiological mechanisms whose general aim is to defend the organism against non-self-bodies, such as pathogens (bacteria, viruses, parasites), as well as cancer cells. Circadian rhythms are endogenous 24-h variations found in virtually all physiological processes. These circadian rhythms are generated by circadian clocks, located in most cell types, including cells of the immune system. This review presents an overview of the clocks in the immune system and of the circadian regulation of the function of immune cells. Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24-h rhythm. This has profound impacts on cellular functions, including a daily rhythm in the synthesis and release of cytokines, chemokines and cytolytic factors, the daily gating of the response occurring through pattern recognition receptors, circadian rhythms of cellular functions such as phagocytosis, migration to inflamed or infected tissue, cytolytic activity, and proliferative response to antigens. Consequently, alterations of circadian rhythms (e.g., clock gene mutation in mice or environmental disruption similar to shift work) lead to disturbed immune responses. We discuss the implications of these data for human health and the areas that future research should aim to address.

  2. High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring.

    Sarah J Borengasser

    Full Text Available The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosis, and lipogenic gene expression in the liver at weaning. However, the precise underlying mechanisms leading to metabolic dysregulation in the offspring remains unclear. Using a rat model of overfeeding-induced obesity, we previously demonstrated that exposure to maternal obesity from pre-conception to birth, is sufficient to program increased obesity risk in the offspring. Offspring of obese rat dams gain greater body weight and fat mass when fed high fat diet (HFD as compared to lean dam. Since, disruptions of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver, we examined the hypothesis that maternal obesity leads to perturbations of core clock components and thus energy metabolism in offspring liver. Offspring from lean and obese dams were examined at post-natal day 35, following a short (2 wk HFD challenge. Hepatic mRNA expression of circadian (CLOCK, BMAL1, REV-ERBα, CRY, PER and metabolic (PPARα, SIRT1 genes were strongly suppressed in offspring exposed to both maternal obesity and HFD. Using a mathematical model, we identified two distinct biological mechanisms that modulate PPARα mRNA expression: i decreased mRNA synthesis rates; and ii increased non-specific mRNA degradation rate. Moreover, our findings demonstrate that changes in PPARα transcription were associated with epigenomic alterations in H3K4me3 and H3K27me3 histone marks near the PPARα transcription start site. Our findings indicated that offspring from obese rat dams have detrimental alternations to circadian machinery that may contribute to impaired liver metabolism in response to HFD, specifically via reduced PPAR

  3. SRC-2 Is an Essential Coactivator for Orchestrating Metabolism and Circadian Rhythm

    Erin Stashi

    2014-02-01

    Full Text Available Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2 recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circadian clock.

  4. Mechanism of Sleep Disturbance in Children with Atopic Dermatitis and the Role of the Circadian Rhythm and Melatonin

    Yung-Sen Chang

    2016-03-01

    Full Text Available Sleep disturbance is common in children with atopic dermatitis (AD. It is a major factor leading to impaired quality of life in these patients and could have negative effects on neurocognitive function and behavior. However, the pathophysiology of sleep disturbance in children with AD is poorly understood, and there is no consensus on how to manage sleep problems in these patients. Pruritus and scratching could lead to sleep disruption but is unlikely the sole etiology. The circadian rhythm of cytokines, the immune system, and skin physiology such as transcutaneous water loss and skin blood flow might also play a role. Recent studies have suggested that melatonin could also be involved due to its multiple effects on sleep, immunomodulation, and anti-oxidant ability. Environmental factors should also be considered. In this review, we summarize the current understanding of the pathophysiology of sleep disturbance in children with AD, and discuss possible therapeutic implications.

  5. Mechanism of Sleep Disturbance in Children with Atopic Dermatitis and the Role of the Circadian Rhythm and Melatonin.

    Chang, Yung-Sen; Chiang, Bor-Luen

    2016-03-29

    Sleep disturbance is common in children with atopic dermatitis (AD). It is a major factor leading to impaired quality of life in these patients and could have negative effects on neurocognitive function and behavior. However, the pathophysiology of sleep disturbance in children with AD is poorly understood, and there is no consensus on how to manage sleep problems in these patients. Pruritus and scratching could lead to sleep disruption but is unlikely the sole etiology. The circadian rhythm of cytokines, the immune system, and skin physiology such as transcutaneous water loss and skin blood flow might also play a role. Recent studies have suggested that melatonin could also be involved due to its multiple effects on sleep, immunomodulation, and anti-oxidant ability. Environmental factors should also be considered. In this review, we summarize the current understanding of the pathophysiology of sleep disturbance in children with AD, and discuss possible therapeutic implications.

  6. PDF neuron firing phase-shifts key circadian activity neurons in Drosophila.

    Guo, Fang; Cerullo, Isadora; Chen, Xiao; Rosbash, Michael

    2014-06-17

    Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.

  7. Circadian Regulation of Cortisol Release in Behaviorally Split Golden Hamsters

    2011-01-01

    The master circadian clock located within the hypothalamic suprachiasmatic nucleus (SCN) is necessary for the circadian rhythm of glucocorticoid (GC) release. The pathways by which the SCN sustains rhythmic GC release remain unclear. We studied the circadian regulation of cortisol release in the behaviorally split golden hamster, in which the single bout of circadian locomotor activity splits into two bouts approximately12 h apart after exposing the animals to constant light conditions. We sh...

  8. Disrupted Ultradian Activity Rhythms and Differential Expression of Several Clock Genes in Interleukin-6-Deficient Mice

    Monje, Francisco J.; Cicvaric, Ana; Acevedo Aguilar, Juan Pablo; Elbau, Immanuel; Horvath, Orsolya; Diao, Weifei; Glat, Micaela; Pollak, Daniela D.

    2017-01-01

    The characteristics of the cycles of activity and rest stand out among the most intensively investigated aspects of circadian rhythmicity in humans and experimental animals. Alterations in the circadian patterns of activity and rest are strongly linked to cognitive and emotional dysfunctions in severe mental illnesses such as Alzheimer’s disease (AD) and major depression (MDD). The proinflammatory cytokine interleukin 6 (IL-6) has been prominently associated with the pathogenesis of AD and MDD. However, the potential involvement of IL-6 in the modulation of the diurnal rhythms of activity and rest has not been investigated. Here, we set out to study the role of IL-6 in circadian rhythmicity through the characterization of patterns of behavioral locomotor activity in IL-6 knockout (IL-6 KO) mice and wild-type littermate controls. Deletion of IL-6 did not alter the length of the circadian period or the amount of locomotor activity under either light-entrained or free-running conditions. IL-6 KO mice also presented a normal phase shift in response to light exposure at night. However, the temporal architecture of the behavioral rhythmicity throughout the day, as characterized by the quantity of ultradian activity bouts, was significantly impaired under light-entrained and free-running conditions in IL-6 KO. Moreover, the assessment of clock gene expression in the hippocampus, a brain region involved in AD and depression, revealed altered levels of cry1, dec2, and rev-erb-beta in IL-6 KO mice. These data propose that IL-6 participates in the regulation of ultradian activity/rest rhythmicity and clock gene expression in the mammalian brain. Furthermore, we propose IL-6-dependent circadian misalignment as a common pathogenetic principle in some neurodegenerative and neuropsychiatric disorders.

  9. The role of gene duplication and unconstrained selective pressures in the melanopsin gene family evolution and vertebrate circadian rhythm regulation.

    Rui Borges

    Full Text Available Melanopsin is a photosensitive cell protein involved in regulating circadian rhythms and other non-visual responses to light. The melanopsin gene family is represented by two paralogs, OPN4x and OPN4m, which originated through gene duplication early in the emergence of vertebrates. Here we studied the melanopsin gene family using an integrated gene/protein evolutionary approach, which revealed that the rhabdomeric urbilaterian ancestor had the same amino acid patterns (DRY motif and the Y and E conterions as extant vertebrate species, suggesting that the mechanism for light detection and regulation is similar to rhabdomeric rhodopsins. Both OPN4m and OPN4x paralogs are found in vertebrate genomic paralogons, suggesting that they diverged following this duplication event about 600 million years ago, when the complex eye emerged in the vertebrate ancestor. Melanopsins generally evolved under negative selection (ω = 0.171 with some minor episodes of positive selection (proportion of sites = 25% and functional divergence (θ(I = 0.349 and θ(II = 0.126. The OPN4m and OPN4x melanopsin paralogs show evidence of spectral divergence at sites likely involved in melanopsin light absorbance (200F, 273S and 276A. Also, following the teleost lineage-specific whole genome duplication (3R that prompted the teleost fish radiation, type I divergence (θ(I = 0.181 and positive selection (affecting 11% of sites contributed to amino acid variability that we related with the photo-activation stability of melanopsin. The melanopsin intracellular regions had unexpectedly high variability in their coupling specificity of G-proteins and we propose that Gq/11 and Gi/o are the two G-proteins most-likely to mediate the melanopsin phototransduction pathway. The selection signatures were mainly observed on retinal-related sites and the third and second intracellular loops, demonstrating the physiological plasticity of the melanopsin protein group. Our results provide new

  10. Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in (/sup 3/H)-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

    Scheving, L.E.; Tsai, T.H.; Powell, E.W.; Pasley, J.N.; Halberg, F.; Dunn, J.

    1983-03-01

    Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of (/sup 3/H)-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude.

  11. Secretory patterns of growth hormone in dogs: circannual, circadian, and ultradian rhythms.

    Gobello, Cristina; Corrada, Yanina A; Castex, Gervasio L; de la Sota, Rodolfo L; Goya, Rodolfo G

    2002-04-01

    The objective was to characterize the circannual, circadian, and ultradian secretory patterns of growth hormone (GH) in intact crossbred and purebred dogs. In all experiments, blood samples were collected with minimal stress by direct peripheral venipuncture and GH was measured in plasma by a homologous radioimmunoassay. For circannual studies, samples were collected monthly from 6 male dogs between 15:00 and 17:30 h over a 1-year time span. For circadian studies, blood samples were collected at 145-minute intervals from 09:00 to 06:45 h of the following day in 14 female dogs. In ultradian experiments, blood samples were collected at 15-minute intervals for 2.5 h (15:00 to 17:30 h) in 7 males and 7 females. Plasma GH in male dogs remained without change in summer, autumn, and winter but declined (P < 0.01) in spring (LSM +/- SEM; 6.9 +/- 0.5; 6.0 +/- 0.5; 6.3 +/- 0.5; 4.3 +/- 0.5 ng/mL, respectively). No plasma GH circadian rhythmicity was detected. Nor was any ultradian pattern evident in either males or females. No gender-related differences were observed in ultradian GH plasma profiles. It is concluded that, while basal GH levels show seasonal fluctuations in dogs, neither circadian nor ultradian GH secretory fluctuations were present in the dogs assessed.

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

    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…

  13. Modulation of copper deficiency responses by diurnal and circadian rhythms in Arabidopsis thaliana.

    Perea-García, Ana; Andrés-Bordería, Amparo; Mayo de Andrés, Sonia; Sanz, Amparo; Davis, Amanda M; Davis, Seth J; Huijser, Peter; Peñarrubia, Lola

    2016-01-01

    Copper homeostasis under deficiency is regulated by the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7) transcription factor. The daily oscillating expression of two SPL7-dependent copper deficiency markers, COPPER TRANSPORTER (COPT2) and IRON SUPEROXIDE DISMUTASE (FSD1), has been followed by quantitative PCR and in promoter:LUCIFERASE transgenic plants. Both genes showed circadian and diurnal regulation. Under copper deficiency, their expression decreased drastically in continuous darkness. Accordingly, total copper content was slightly reduced in etiolated seedlings under copper deficiency. The expression of SPL7 and its targets COPT2 and FSD1 was differently regulated in various light signalling mutants. On the other hand, increased copper levels reduced the amplitude of nuclear circadian clock components, such as GIGANTEA (GI). The alteration of copper homeostasis in the COPT1 overexpression line and spl7 mutants also modified the amplitude of a classical clock output, namely the circadian oscillation of cotyledon movements. In the spl7 mutant, the period of the oscillation remained constant. These results suggest a feedback of copper transport on the circadian clock and the integration of rhythmic copper homeostasis into the central oscillator of plants.

  14. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

    Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, A.

    2015-01-01

    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 cl

  15. Screening of Clock Gene Polymorphisms Demonstrates Association of a PER3 Polymorphism with Morningness–Eveningness Preference and Circadian Rhythm Sleep Disorder

    Hida, Akiko; Kitamura, Shingo; Katayose, Yasuko; Kato, Mie; Ono, Hiroko; Kadotani, Hiroshi; Uchiyama, Makoto; Ebisawa, Takashi; Inoue, Yuichi; Kamei, Yuichi; Okawa, Masako; Takahashi, Kiyohisa; Mishima, Kazuo

    2014-01-01

    A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep–wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness–eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes. PMID:25201053

  16. Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder.

    Hida, Akiko; Kitamura, Shingo; Katayose, Yasuko; Kato, Mie; Ono, Hiroko; Kadotani, Hiroshi; Uchiyama, Makoto; Ebisawa, Takashi; Inoue, Yuichi; Kamei, Yuichi; Okawa, Masako; Takahashi, Kiyohisa; Mishima, Kazuo

    2014-09-09

    A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes.

  17. Light activates output from evening neurons and inhibits output from morning neurons in the Drosophila circadian clock.

    Marie Picot

    2007-11-01

    Full Text Available Animal circadian clocks are based on multiple oscillators whose interactions allow the daily control of complex behaviors. The Drosophila brain contains a circadian clock that controls rest-activity rhythms and relies upon different groups of PERIOD (PER-expressing neurons. Two distinct oscillators have been functionally characterized under light-dark cycles. Lateral neurons (LNs that express the pigment-dispersing factor (PDF drive morning activity, whereas PDF-negative LNs are required for the evening activity. In constant darkness, several lines of evidence indicate that the LN morning oscillator (LN-MO drives the activity rhythms, whereas the LN evening oscillator (LN-EO does not. Since mutants devoid of functional CRYPTOCHROME (CRY, as opposed to wild-type flies, are rhythmic in constant light, we analyzed transgenic flies expressing PER or CRY in the LN-MO or LN-EO. We show that, under constant light conditions and reduced CRY function, the LN evening oscillator drives robust activity rhythms, whereas the LN morning oscillator does not. Remarkably, light acts by inhibiting the LN-MO behavioral output and activating the LN-EO behavioral output. Finally, we show that PDF signaling is not required for robust activity rhythms in constant light as opposed to its requirement in constant darkness, further supporting the minor contribution of the morning cells to the behavior in the presence of light. We therefore propose that day-night cycles alternatively activate behavioral outputs of the Drosophila evening and morning lateral neurons.

  18. A comparison of the circadian rhythm of intraocular pressure in primary phronic angle closure glaucoma, primary open angle glaucoma and normal eyes

    Sihota Ramanjit

    2005-01-01

    Full Text Available Purpose: To evaluate the circadian rhythm of intraocular pressure (IOP in primary chronic angle closure glaucoma (PCACG, primary open angle glaucoma (POAG, and normal eyes. Methods: Cross-sectional study of newly diagnosed patients of POAG (60 eyes, PCACG following laser iridotomy (75 eyes, and age and sex matched normal controls (75 eyes. All subjects underwent applanation tonometry at 7 a.m., 10 a.m., 1 p.m., 4 p.m., 7 p.m., and 10 p.m. by a masked observer. Circadian rhythms were classified based upon the timing and presence of peak pressure. Results: Age and gender in all three groups were comparable. Diurnal IOP fluctuations were significantly higher in PCACG (7.69 + 3.03 mmHg and POAG (8.31 + 2.58 mmHg groups compared to normal controls (4.83 + 2.46 mmHg. PCACG eyes and controls had similarly timed circadian rhythms, with PCACG eyes having a consistently higher IOP. At 7 and 10 a.m., IOP peaked more often in POAG eyes compared to PCACG eyes. A plateau type of circadian rhythm was most common in normal eyes. The timing of peak IOP could be significantly correlated with the type of primary glaucoma examined. Conclusion: Afternoon peaks were more common in postiridotomy PCACG eyes, similar to the rhythm in normal eyes. Morning peaks were more frequent in POAG eyes. Diurnal fluctuation > 6 mmHg, associated with an IOP of 21 mmHg or more was never seen in a normal eye.

  19. Unique food-entrained circadian rhythm in cysteine414-alanine mutant mCRY1 transgenic mice

    2016-01-01

    Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Daily scheduled restricted feeding (RF), in which the food available time is restricted for several hours each day, elicits anticipatory activity. This food-anticipatory activity (FAA) is controlled by a food-entrainable oscillator (FEO) that is distinct from the suprachiasmatic nucleus (SCN), the master pacemaker in mammals. In an earlier report, we described generation of transgenic (Tg) mi...

  20. Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

    Lynch Gordon S

    2009-09-01

    Full Text Available Abstract Background Systemic administration of β-adrenoceptor (β-AR agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1-3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic (acute and chronic administration of the β2-AR agonist formoterol. Results Skeletal muscle gene expression (from murine tibialis anterior was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using Illumina 46K mouse BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress. Differentially expressed genes relevant to the regulation of muscle mass and metabolism (in the context of the hypertrophic phenotype were further validated by quantitative RT-PCR to examine gene expression in response to both acute (1-24 h and chronic administration (1-28 days of formoterol at multiple timepoints. In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling (including differential expression of myostatin, activin receptor IIB, phospho-Smad3 etc was observed following acute and chronic administration of formoterol. Acute (but not chronic administration of formoterol also significantly induced the expression of genes involved in oxidative metabolism, including hexokinase 2, sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly, formoterol

  1. Circadian characteristics of spontaneous physical activity and body temperature in narcoleptic patients

    Xing XU

    2016-08-01

    Full Text Available Objective To assess circadian characteristics of spontaneous physical activity and deep body temperature in narcoleptic patients.  Methods Fourteen narcoleptic patients and 14 healthy age- and sex-matched control subjects were enrolled. Nocturnal polysomnography (PSG was recorded, followed by standard multiple sleep latency test (MSLT. Then all subjects were required to wear the actigraphy (actiwatch at home with continuous monitoring of spontaneous physical activity for 1-2 weeks and complete the daily sleep record. All subjects' deep body temperatures were measured at 20 time points.  Results In comparison with control subjects, PSG data suggested narcoleptic patients had significantly longer time in bed at night (P = 0.008, decreased sleep efficiency (P = 0.001, increased awakenings (P = 0.000, extended wake time after sleep onset (P = 0.000 and sleep onset rapid eye movement period (SOREMP, P = 0.002. MSLT data suggested decreased average sleep latency (P = 0.000 and increased SOREMPs (P = 0.000. Actigraphy data suggested increased nocturnal activity and nocturnal activity per hour (P = 0.000, for all, decreased daytime activity and daytime activity per hour (P = 0.000, for all and increased nocturnal activity per hour/daytime activity per hour (P = 0.000, for all. The deep body temperature in both groups showed significant circadian rhythms. The differences in mesor, amplitude and peak phase of deep body temperature between 2 groups had no statistical significance (P = 0.177, 0.730, 0.488.  Conclusions Narcoleptic patients are characterized by impaired circadian rhythm of sleep-wake and spontaneous physical activity. The limited effects on deep body temperature suggest the relative conservation of thermoregulation in narcolepsy. DOI: 10.3969/j.issn.1672-6731.2016.07.010

  2. Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers

    Andersen, Birgitte; Beck-Nielsen, Henning; Højlund, Kurt

    2011-01-01

    Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective...... of this study was to elucidate the 24-h profiling of plasma FGF21 during a 72-h fast....

  3. Adaptive and Pathological Inhibition of Neuroplasticity Associated with Circadian Rhythms and Sleep

    Heller, H. Craig; Ruby, Norman F.; Rolls, Asya; Makam, Megha; Colas, Damien

    2014-01-01

    The circadian system organizes sleep and wake through imposing a daily cycle of sleep propensity on the organism. Sleep has been shown to play an important role in learning and memory. Apart from the daily cycle of sleep propensity, however, direct effects of the circadian system on learning and memory also have been well documented. Many mechanistic components of the memory consolidation process ranging from the molecular to the systems level have been identified and studied. The question that remains is how do these various processes and components work together to produce cycles of increased and decreased learning abilities, and why should there be times of day when neural plasticity appears to be restricted? Insights into this complex problem can be gained through investigations of the learning disabilities caused by circadian disruption in Siberian hamsters and by aneuploidy in Down syndrome mice. A simple working hypothesis that has been explored in this work is that the observed learning disabilities are due to an altered excitation/inhibition balance in the CNS. Excessive inhibition is the suspected cause of deficits in memory consolidation. In this paper we present the evidence that excessive inhibition in these cases of learning disability involves GABAergic neurotransmission, that treatment with GABA receptor inhibitors can reverse the learning disability, and that the efficacy of the treatment is time sensitive coincident with the major daily sleep phase, and that it depends on sleep. The evidence we present leads us to hypothesize that a function of the circadian system is to reduce neuroplasticity during the daily sleep phase when processes of memory consolidation are taking place. PMID:24886189

  4. Detecting KaiC phosphorylation rhythms of the cyanobacterial circadian oscillator in vitro and in vivo

    Kim, Yong-Ick; Boyd, Joseph S.; Espinosa, Javier; Golden, Susan S.

    2016-01-01

    The central oscillator of the cyanobacterial circadian clock is unique in the biochemical simplicity of its components and the robustness of the oscillation. The oscillator is composed of three cyanobacterial proteins, KaiA, KaiB, and KaiC. If very pure preparations of these three proteins are mixed in a test tube in the right proportions and with ATP and MgCl2, the phosphorylation states of KaiC will oscillate with a circadian period and these states can be analyzed simply by SDS-PAGE. The purity of the proteins is critical for obtaining robust oscillation. Contaminating proteases will destroy oscillation by degradation of Kai proteins, and ATPases will attenuate robustness by consumption of ATP. Here, we provide a detailed protocol to obtain pure recombinant proteins from Escherichia coli to construct a robust cyanobacterial circadian oscillator in vitro. In addition, we present a protocol that facilitates analysis of phosphoryation states of KaiC and other phosphorylated proteins from in vivo samples. PMID:25662456

  5. Daily rhythms in mobile telephone communication

    Aledavood, Talayeh; Roberts, Sam G B; Reed-Tsochas, Felix; Moro, Esteban; Dunbar, Robin I M; Saramäki, Jari

    2015-01-01

    Circadian rhythms are known to be important drivers of human activity and the recent availability of electronic records of human behaviour has provided fine-grained data of temporal patterns of activity on a large scale. Further, questionnaire studies have identified important individual differences in circadian rhythms, with people broadly categorised into morning-like or evening-like individuals. However, little is known about the social aspects of these circadian rhythms, or how they vary across individuals. In this study we use a unique 18-month dataset that combines mobile phone calls and questionnaire data to examine individual differences in the daily rhythms of mobile phone activity. We demonstrate clear individual differences in daily patterns of phone calls, and show that these individual differences are persistent despite a high degree of turnover in the individuals' social networks. Further, women's calls were longer than men's calls, especially during the evening and at night, and these calls wer...

  6. Activation of AMPA receptors in the suprachiasmatic nucleus phase-shifts the mouse circadian clock in vivo and in vitro.

    Yasutaka Mizoro

    Full Text Available The glutamatergic neurotransmission in the suprachiasmatic nucleus (SCN plays a central role in the entrainment of the circadian rhythms to environmental light-dark cycles. Although the glutamatergic effect operating via NMDAR (N-methyl D-aspartate receptor is well elucidated, much less is known about a role of AMPAR (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor in circadian entrainment. Here we show that, in the mouse SCN, GluR2 and GluR4 AMPAR subtypes are abundantly expressed in the retinorecipient area. In vivo microinjection of AMPA in the SCN during the early subjective night phase-delays the behavioral rhythm. In the organotypic SCN slice culture, AMPA application induces phase-dependent phase-shifts of core-clock gene transcription rhythms. These data demonstrate that activation of AMPAR is capable of phase-shifting the circadian clock both in vivo and in vitro, and are consistent with the hypothesis that activation of AMPA receptors is a critical step in the transmission of photic information to the SCN.

  7. The Difference of Expression and Activity Circadian Rhythm of Bc1-2 in Tumor Cells of Nude Mice Bearing Lung Adenocarcinoma%荷人肺癌裸鼠上肿瘤细胞Bcl-2表达及其活性生物时间节律差异

    王志东; 刘湘国; 洪秀琴; 田晓彩; 孔春初

    2012-01-01

    目的:探索荷人肺癌裸鼠上肿瘤细胞Bcl-2表达及其活性生物时间节律差异.方法:体外培养A549人肺癌细胞系,移植到裸小鼠身上,10天成瘤后,随机分为6大组,每大组再分2小组,每组4只,一组不给任何处理,设为对照,各组小鼠分别于光照后不同时间点取肿瘤细胞制成细胞悬液,固定染色后,用流式细胞仪以每个样品检测10000个细胞的数量检测单个细胞的荧光强度,用流式细胞仪检测细胞周期情况,单因素方差分析法检验各期细胞在6个时间点差异的显著性,用Cosinor法考察G1,S,G2,M期细胞在24h的分布是否符合余弦函数,即是否有时辰节律.按6个时间点取的肿瘤细胞,匀浆后裂解细胞,Western Blot法测定Bcl-2的表达.结果:1.结果发现肿瘤的生长曲线高峰出现在睡眠期中点,其次在活动期中点;G1、S、G2期细胞变化符合余弦节律;2.Bcl-2的表达在光照后7h和19h达到峰值,变化趋势与肿瘤细胞的周期性改变一致.结论:荷人肺癌裸鼠上肿瘤细胞的细胞周期可能随昼夜交替呈节律性变化,Bcl-2的表达变化与肿瘤细胞的节律性改变一致.%Objective: To explore the difference of the expression of Bcl-2 in tumor cells of nude mice bearing lung neoplasm and its activity circadian rhythm. Methods: Transplanted the A549 lung neoplasm cell lines which were cultured in vitro to nude mice. After tumorigenesis in 10 days, they were divided into 6 groups randomly. And then, every group was subdivided into 2 groups, with 4 mice each. One group served as control, and did not receive any treatments. As for other groups, the tumor cells of each group were made into cell suspension at different time points after irradiation. After fixing dye, 10000 cells in each sample were made out to detect single cell fluorescence intensity and the cell cycle by flow cytometry. Changes at six time-points of cells at each stage were detected by Single factor variance

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

    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.

  9. Circadian clock disruption in neurodegenerative diseases: Cause and effect?

    Erik Steven Musiek

    2015-02-01

    Full Text Available Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer Disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.

  10. Alteration of PHYA expression change circadian rhythms and timing of bud set in Populus.

    Kozarewa, Iwanka; Ibáñez, Cristian; Johansson, Mikael; Ogren, Erling; Mozley, David; Nylander, Eva; Chono, Makiko; Moritz, Thomas; Eriksson, Maria E

    2010-05-01

    In many temperate woody species, dormancy is induced by short photoperiods. Earlier studies have shown that the photoreceptor phytochrome A (phyA) promotes growth. Specifically, Populus plants that over-express the oat PHYA gene (oatPHYAox) show daylength-independent growth and do not become dormant. However, we show that oatPHYAox plants could be induced to set bud and become cold hardy by exposure to a shorter, non-24 h diurnal cycle that significantly alters the relative position between endogenous rhythms and perceived light/dark cycles. Furthermore, we describe studies in which the expression of endogenous Populus tremula x P. tremuloides PHYTOCHROME A (PttPHYA) was reduced in Populus trees by antisense inhibition. The antisense plants showed altered photoperiodic requirements, resulting in earlier growth cessation and bud formation in response to daylength shortening, an effect that was explained by an altered innate period that leads to phase changes of clock-associated genes such as PttCO2. Moreover, gene expression studies following far-red light pulses show a phyA-mediated repression of PttLHY1 and an induction of PttFKF1 and PttFT. We conclude that the level of PttPHYA expression strongly influences seasonally regulated growth in Populus and is central to co-ordination between internal clock-regulated rhythms and external light/dark cycles through its dual effect on the pace of clock rhythms and in light signaling.

  11. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters

    Ibtissam eChakir

    2015-05-01

    Full Text Available Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16h light/08h dark or short photoperiods (08h light/16h dark. Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively. Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state.

  12. Activity/rest rhythm of depressed adolescents undergoing therapy: case studies

    Maria Eugênia Mesquita

    Full Text Available Abstract Introduction: Disorders of circadian rhythms have been reported in studies of both depressed children and of depressed adolescents. The aim of this study was to evaluate whether there is a relationship between the 24-hour spectral power (24h SP of the activity/rest rhythm and the clinical course of depression in adolescents. Methods: Six 14 to 17-year-old adolescents were recruited for the study. They were all suffering from major depressive disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV criteria, as identified by the Schedule for Affective Disorders and Schizophrenia for School Aged Children: Present and Lifetime Version (K-SADS-PL. Depressive symptoms were assessed using the Children's Depression Rating Scale - Revised (CDRS-R and clinical evaluations. Locomotor activity was monitored over a period of 13 consecutive weeks. Activity was measured for 10-minute periods using wrist-worn activity monitors. All patients were prescribed sertraline from after the first week up until the end of the study. Results: We found a relationship between high CDRS values and low 24-hour spectral power. Conclusions: The 24h SP of the activity/rest rhythm correlated significantly (negatively with the clinical ratings of depression.

  13. Circadian Influences on Myocardial Infarction

    Jitka A. I. Virag

    2014-10-01

    Full Text Available Components of circadian rhythm maintenance, or clock genes, are found in all peripheral tissues, including the heart, and influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on cardiovascular disease incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and cardiovascular disease may provide insights into possible preventative and therapeutic strategies for susceptible populations.

  14. Circadian-independent cell mitosis in immortalized fibroblasts.

    Yeom, Mijung; Pendergast, Julie S; Ohmiya, Yoshihiro; Yamazaki, Shin

    2010-05-25

    Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperature-compensated such that the period of the rhythm remains constant (approximately 24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-four-hour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.

  15. Sensory Conflict Disrupts Activity of the Drosophila Circadian Network

    Ross E.F. Harper

    2016-11-01

    Full Text Available Periodic changes in light and temperature synchronize the Drosophila circadian clock, but the question of how the fly brain integrates these two input pathways to set circadian time remains unanswered. We explore multisensory cue combination by testing the resilience of the circadian network to conflicting environmental inputs. We show that misaligned light and temperature cycles can lead to dramatic changes in the daily locomotor activities of wild-type flies during and after exposure to sensory conflict. This altered behavior is associated with a drastic reduction in the amplitude of PERIOD (PER oscillations in brain clock neurons and desynchronization between light- and temperature-sensitive neuronal subgroups. The behavioral disruption depends heavily on the phase relationship between light and temperature signals. Our results represent a systematic quantification of multisensory integration in the Drosophila circadian system and lend further support to the view of the clock as a network of coupled oscillatory subunits.

  16. 近日节律对麻醉药物作用的影响%Effect of circadian rhythms on the action of anaesthetic agents

    曾海波; 尚游; 袁世荧

    2010-01-01

    多数麻醉医生认为,人体是一个非常稳定的有机体.事实上,机体的许多方面因为受到生物节律的影响而会表现出周期性的变化.近日节律是一种重要的生物节律,对动植物乃至人都有诸多重要的影响,这其中也包括对麻醉药物作用的影响.因此,在从事科学研究和临床工作时,近日节律对麻醉药物作用的这种影响不容忽视.%Many anaesthetists assume that humans are homeostatic organisms but in reality we show periodic variations in nearly all facets of our physiology and behaviour, influenced by biologic rhythms. Circadian rhythms is an important biologic rhythm which can affect animals, plants and human beings. Also it make effects on anesthetics, The effects of circadian rhythms should be considered in scientific research of anaesthetic drugs and works of clinical practice of anaesthesia.

  17. Winter Depression: Integrating mood, circadian rhythms, and the sleep/wake and light/dark cycles into a bio-psycho-social-environmental model.

    Lewy, Alfred J; Emens, Jonathan S; Songer, Jeannie B; Sims, Neelam; Laurie, Amber L; Fiala, Steven C; Buti, Allie L

    2009-06-01

    The phase shift hypothesis (PSH) states that most patients with SAD become depressed in the winter because of a delay in circadian rhythms with respect to the sleep/wake cycle: According to the PSH, these patients should preferentially respond to the antidepressant effects of bright light exposure when it is scheduled in the morning so as to provide a corrective phase advance and restore optimum alignment between the circadian rhythms tightly coupled to the endogenous circadian pacemaker and those rhythms that are related to the sleep/wake cycle. Recent support for the PSH has come from studies in which symptom severity was shown to correlate with the degree of circadian misalignment: it appears that a subgroup of patients are phase advanced, not phase delayed; however, the phase-delayed type is predominant in SAD and perhaps in other disorders as well, such as non-seasonal unipolar depression. It is expected that during the next few years the PSH will be tested in these and other conditions, particularly since healthy subjects appear to have more severe symptoms of sub-clinical dysphoria correlating with phase-delayed circadian misalignment; critically important will be the undertaking of treatment trials to investigate the therapeutic efficacy of morning bright light or afternoon/evening low-dose melatonin in these disorders in which symptoms are more severe as the dim light melatonin onset (DLMO) is delayed with respect to the sleep/wake cycle (non-restorative sleep should also be evaluated, as well as bipolar disorder). The possibility that some individuals (and disorders) will be of the phase-advanced type should be considered, taking into account that the correct timing of phase-resetting agents for them will be bright light scheduled in the evening and/or low-dose melatonin taken in the morning. While sleep researchers and clinicians are accustomed to phase-typing patients with circadian-rhythm sleep disorders according to the timing of sleep, phase typing

  18. Effects of music composed by Mozart and Ligeti on blood pressure and heart rate circadian rhythms in normotensive and hypertensive rats.

    Lemmer, Björn

    2008-11-01

    There is continuing discussion on the effect of music ("Mozart effect") on numerous functions in man and experimental animals. Radiotelemetry now allows one to monitor cardiovascular functions in freely-moving unrestrained experimental animals. Radiotelemetry was used to monitor systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and motor activity (MA) in male normotensive WKY and hypertensive SHR animals. Rats were synchronized to a 12 h light (L): 12 h dark (D) regimen in an isolated, ventilated, light-controlled, sound-isolated animal container. Music (Mozart, Symphony # 40; Ligeti, String Quartet # 2) were played for 2 h at 75 dB in the animal cabin starting at the onset of L or D in a cross-over design. Data were collected every 5 min for 24 h under control conditions and during and after music. In addition, plasma concentrations of norepinephrine (NE) were determined in unrestrained animals at 3 h intervals over 24 h. In both WKY and SHR, highly significant circadian rhythms were obtained in SBP, DBP, HR, and MA under control conditions; HR was lower and BP higher in SHR than in WKY. NE was circadian rhythmic in both strains with higher values in D; the increase in NE with immobilization was much more pronounced in SHR than in WKY. The music of Mozart had no effect on either parameter in WKY, neither in L nor in D. In contrast, in SHR, the music of Mozart presented in L significantly decreased HR and left BP unaffected, leading to a small decrease in cardiac output. The music of Ligeti significantly increased BP both in L and in D and reflexively reduced HR in L, the effects being long-lasting over 24 h. Interestingly, white noise at 75 dB had no effect at all on either function in both strains. The effects of both Mozart and Ligeti cannot be attributed to a stress reaction, as stress due to cage switch increased HR and BP both in WKY and SHR. The study clearly demonstrates that music of different character (tempo, rhythm, pitch, tonality) can

  19. Chronobiological studies of chicken IgY: monitoring of infradian, circadian and ultradian rhythms of IgY in blood and yolk of chickens.

    He, Jin-Xin; Thirumalai, Diraviyam; Schade, Rüdiger; Zhang, Xiao-Ying

    2014-08-15

    IgY is the functional equivalent of mammalian IgG found in birds, reptiles and amphibians. Many of its biological aspects have been explored with different approaches. In order to evaluate the rhythmicity of serum and yolk IgY, four chickens were examined and reared under the same conditions. To monitor biological oscillations of IgY in yolk and serum, the eggs and blood samples were collected over a 60 day period and the rhythm of yolk and serum IgY was determined by direct-ELISA. Results indicated that, there is a significant circaseptan rhythm in yolk IgY and circaquattran rhythm in serum IgY. The serum IgY concentration reached a peak in the morning, decreased to a minimum during the daytime and increased again at night revealing a significant circadian rhythm was superimposed by an ultradian rhythm. These data are suited to address the controversies concerning the IgY concentration in egg yolk and blood of laying hens. In addition, this study raised new questions, if the different rhythms in yolk and serum are concerned.

  20. The circadian Clock mutation increases exploratory activity and escape-seeking behavior.

    Easton, A; Arbuzova, J; Turek, F W

    2003-02-01

    Disturbances of circadian rhythms are associated with many types of mood disorders; however, it is unknown whether a dysfunctional circadian pacemaker can be the primary cause of altered emotional behavior. To test this hypothesis, male and female mice carrying a mutation of the circadian gene, Clock, were compared to wild-type mice in an array of behavioral tests used to measure exploratory activity, anxiety, and behavioral despair. Female Clock mutant mice exhibited significantly greater activity and rearing in an open field and a greater number of total arm entries in the elevated plus maze. In addition, female Clock mutant mice spent significantly more time swimming in the forced swim test than wild-type mice on both days of a 2-day test. Male Clock mutant mice also exhibited increased exploration of the open field and increased swimming in the forced swim test; however, behavioral changes were less robust in Clock mutant males compared to Clock mutant females. These changes in behavior were not dependent on the expression of a lengthened free-running period but were more or less striking depending on the testing conditions. These data indicate that the Clock mutation leads to increased exploratory behavior and increased escape-seeking behavior, and, conversely, does not result in increased anxiety or depressive-like behavior. These results suggest that the Clock gene is involved in regulating behavioral arousal, and that Clock may interact with sex hormones to produce these behavioral changes.

  1. The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer.

    Ngoc-Han Ha

    2016-09-01

    Full Text Available Breast cancer mortality is primarily due to metastasis rather than primary tumors, yet relatively little is understood regarding the etiology of metastatic breast cancer. Previously, using a mouse genetics approach, we demonstrated that inherited germline polymorphisms contribute to metastatic disease, and that these single nucleotide polymorphisms (SNPs could be used to predict outcome in breast cancer patients. In this study, a backcross between a highly metastatic (FVB/NJ and low metastatic (MOLF/EiJ mouse strain identified Arntl2, a gene encoding a circadian rhythm transcription factor, as a metastasis susceptibility gene associated with progression, specifically in estrogen receptor-negative breast cancer patients. Integrated whole genome sequence analysis with DNase hypersensitivity sites reveals SNPs in the predicted promoter of Arntl2. Using CRISPR/Cas9-mediated substitution of the MOLF promoter, we demonstrate that the SNPs regulate Arntl2 transcription and affect metastatic burden. Finally, analysis of SNPs associated with ARNTL2 expression in human breast cancer patients revealed reproducible associations of ARNTL2 expression quantitative trait loci (eQTL SNPs with disease-free survival, consistent with the mouse studies.

  2. The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer

    Ha, Ngoc-Han; Long, Jirong; Cai, Qiuyin; Shu, Xiao Ou

    2016-01-01

    Breast cancer mortality is primarily due to metastasis rather than primary tumors, yet relatively little is understood regarding the etiology of metastatic breast cancer. Previously, using a mouse genetics approach, we demonstrated that inherited germline polymorphisms contribute to metastatic disease, and that these single nucleotide polymorphisms (SNPs) could be used to predict outcome in breast cancer patients. In this study, a backcross between a highly metastatic (FVB/NJ) and low metastatic (MOLF/EiJ) mouse strain identified Arntl2, a gene encoding a circadian rhythm transcription factor, as a metastasis susceptibility gene associated with progression, specifically in estrogen receptor-negative breast cancer patients. Integrated whole genome sequence analysis with DNase hypersensitivity sites reveals SNPs in the predicted promoter of Arntl2. Using CRISPR/Cas9-mediated substitution of the MOLF promoter, we demonstrate that the SNPs regulate Arntl2 transcription and affect metastatic burden. Finally, analysis of SNPs associated with ARNTL2 expression in human breast cancer patients revealed reproducible associations of ARNTL2 expression quantitative trait loci (eQTL) SNPs with disease-free survival, consistent with the mouse studies. PMID:27656887

  3. Plant-Pathogen Interaction, Circadian Rhythm, and Hormone-Related Gene Expression Provide Indicators of Phytoplasma Infection in Paulownia fortunei

    Guoqiang Fan

    2014-12-01

    Full Text Available Phytoplasmas are mycoplasma-like pathogens of witches’ broom disease, and are responsible for serious yield losses of Paulownia trees worldwide. The molecular mechanisms of disease development in Paulownia are of considerable interest, but still poorly understood. Here, we have applied transcriptome sequencing technology and a de novo assembly approach to analyze gene expression profiles in Paulownia fortunei infected by phytoplasmas. Our previous researches suggested that methyl methane sulfonated (MMS could reverse the effects of the infection. In this study, leaf samples from healthy, infected, and both infected and methyl methane sulfonate treated plants were analyzed. The results showed that the gene expression profile of P. fortunei underwent dramatic changes after Paulownia witches’ broom (PaWB phytoplasma infection. Genes that encoded key enzymes in plant-pathogen interaction processes were significantly up-regulated in the PaWB-infected Paulownia. Genes involved in circadian rhythm and hormone-related genes were also altered in Paulownia after PaWB infection. However, after the PaWB-infected plants were treated with MMS, the expression profiles of these genes returned to the levels in the healthy controls. The data will help identify potential PaWB disease-resistance genes that could be targeted to inhibit the growth and reproduction of the pathogen and to increase plant resistance.

  4. Plant-pathogen interaction, circadian rhythm, and hormone-related gene expression provide indicators of phytoplasma infection in Paulownia fortunei.

    Fan, Guoqiang; Dong, Yanpeng; Deng, Minjie; Zhao, Zhenli; Niu, Suyan; Xu, Enkai

    2014-12-12

    Phytoplasmas are mycoplasma-like pathogens of witches' broom disease, and are responsible for serious yield losses of Paulownia trees worldwide. The molecular mechanisms of disease development in Paulownia are of considerable interest, but still poorly understood. Here, we have applied transcriptome sequencing technology and a de novo assembly approach to analyze gene expression profiles in Paulownia fortunei infected by phytoplasmas. Our previous researches suggested that methyl methane sulfonated (MMS) could reverse the effects of the infection. In this study, leaf samples from healthy, infected, and both infected and methyl methane sulfonate treated plants were analyzed. The results showed that the gene expression profile of P. fortunei underwent dramatic changes after Paulownia witches' broom (PaWB) phytoplasma infection. Genes that encoded key enzymes in plant-pathogen interaction processes were significantly up-regulated in the PaWB-infected Paulownia. Genes involved in circadian rhythm and hormone-related genes were also altered in Paulownia after PaWB infection. However, after the PaWB-infected plants were treated with MMS, the expression profiles of these genes returned to the levels in the healthy controls. The data will help identify potential PaWB disease-resistance genes that could be targeted to inhibit the growth and reproduction of the pathogen and to increase plant resistance.

  5. Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

    Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

    2015-06-01

    The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rategenes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling.

  6. The electroretinogram as a method for studying circadian rhythms in the mammalian retina

    Morven A. Cameron; Alun R. Barnard; Robert J. Lucas

    2008-12-01

    Circadian clocks are thought to regulate retinal physiology in anticipation of the large variation in environmental irradiance associated with the earth’s rotation upon its axis. In this review we discuss some of the rhythmic events that occur in the mammalian retina, and their consequences for retinal physiology. We also review methods of tracing retinal rhythmicity in vivo and highlight the electroretinogram (ERG) as a useful technique in this field. Principally, we discuss how this technique can be used as a quick and noninvasive way of assessing physiological changes that occur in the retina over the course of the day. We highlight some important recent findings facilitated by this approach and discuss its strengths and limitations.

  7. Spotlight on fish: light pollution affects circadian rhythms of European perch but does not cause stress.

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Preuer, Torsten; Kloas, Werner

    2015-04-01

    Flora and fauna evolved under natural day and night cycles. However, natural light is now enhanced by artificial light at night, particularly in urban areas. This alteration of natural light environments during the night is hypothesised to alter biological rhythms in fish, by effecting night-time production of the hormone melatonin. Artificial light at night is also expected to increase the stress level of fish, resulting in higher cortisol production. In laboratory experiments, European perch (Perca fluviatilis) were exposed to four different light intensities during the night, 0 lx (control), 1 lx (potential light level in urban waters), 10 lx (typical street lighting at night) and 100 lx. Melatonin and cortisol concentrations were measured from water samples every 3h during a 24 hour period. This study revealed that the nocturnal increase in melatonin production was inhibited even at the lowest light level of 1 lx. However, cortisol levels did not differ between control and treatment illumination levels. We conclude that artificial light at night at very low intensities may disturb biological rhythms in fish since nocturnal light levels around 1 lx are already found in urban waters. However, enhanced stress induction could not be demonstrated.

  8. Circadian dysfunction in a rotenone-induced parkinsonian rodent model.

    Lax, Pedro; Esquiva, Gema; Esteve-Rudd, Julian; Otalora, Beatriz Baño; Madrid, Juan Antonio; Cuenca, Nicolás

    2012-03-01

    Parkinson's disease (PD) is a neurodegenerative disorder that also involves circadian rhythm alterations. Modifications of circadian rhythm parameters have been shown to occur in both PD patients and toxin-induced PD animal models. In the latter case, rotenone, a potent inhibitor of mitochondrial complex I (nicotinamide adenine dinucleotide [NADH]-quinone reductase), has been used to elicit degeneration of dopaminergic neurons and development of parkinsonian syndrome. The present work addresses alterations induced by rotenone on both locomotor and body temperature circadian rhythms in rats. Rotenone-treated rats exhibited abnormalities in equilibrium, postural instability, and involuntary movements. Long-term subcutaneous administration of rotenone significantly reduced mean daily locomotor activity in most animals. During rotenone administration, mean body temperatures (BTs) and BT rhythm amplitudes were significantly lower than those observed in the control group. After long-term rotenone administration, the circadian rhythms of both locomotor activity (LA) and BT displayed decreased amplitudes, lower interdaily phase stability, and higher rhythm fragmentation, as compared to the control rats. The magnitude of the LA and BT circadian rhythm alterations induced by rotenone positively correlated with degree of motor impairment. These results indicate that rotenone induces circadian dysfunction in rats through some of the same mechanisms as those responsible for the development of motor disturbances.

  9. Circadian adaptations to meal timing: Neuroendocrine mechanisms

    Danica F Patton

    2013-10-01

    Full Text Available Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus is directly entrained by daily light-dark cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this

  10. Role of circadian rhythm change in the pathogenesis of obesity and diabetes%昼夜节律变化在肥胖和糖尿病发病中的作用

    周丽斌; 陈名道

    2011-01-01

    Increasing clinical evidence shows that modern lifestyle interrupting circadian rhythm contributes to the prevalence of obesity and diabetes.Recent genetic animal models further support the interaction of circadian rhythms and metabolic state.Circadian clock is not limited to be in central nervous system,and is also present in nearly all cells of the body,which constitute hierarchically circadian systems.The molecular circadian clock is evolved to allow organisms to anticipate and prepared for predictable,daily changes in the environment and regulates cellular and tissue function by driving patterns of gene expression and enzymatic activity.At present,basic science in this field has progressed at an extraordinary pace and is expected to continue unraveling the mechanisms linking circadian clocks to metabolism,which is important for understanding the pathophysiology of metabolic diseases such as obesity and diabetes,and provides a conceptual basis for the prevention and therapeutics of these diseases.%不断增长的临床资料表明,影响昼夜节律的现代生活方式增加肥胖和糖尿病的发病风险.最近的遗传性动物模型也进一步证实了昼夜节律与代谢之间的密切相关.昼夜节律生物钟不仅仅存在于中枢神经系统,还存在于机体几乎所有细胞,形成不同层次的昼夜节律系统.分子生物钟通过长期的进化,以使机体能够预见和准备适应环境的每天变化,通过驱动基因表达和酶的活性调控细胞和组织功能.目前在这一领域的基础科学以惊人的速度向前发展,有望不断揭示昼夜节律钟与代谢之间联系的机制,这对于理解糖尿病和肥胖等代谢性疾病的生理和病理机制都有重要意义,并为其防治提供理论基础.

  11. Effects of 5,7-dihydroxytriptamine (5,7-DHT on circadian locomotor activity of the blow fly, Calliphora vicina

    Bronislaw Cymborowski

    2003-05-01

    Full Text Available The biogenic amine serotonin (5-HT is a neuromodulator in both vertebrates and invertebrates. It has been shown that serotonin, apart from its distinct effects on behavior, also plays a morphoregulatory role during the ontogeny of the insect's nervous system. The role of serotonin in modulating circadian locomotor activity of the blow fly, Calliphora vicina was explored. Injection of a specific neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT, into the hemolymph appeared to significantly reduced the level of locomotor activity and lengthened the period (tau of circadian rhythmicity. After drug injection in constant darkness flies continued with their free-running rhythm of a locomotor activity, depending on the time of 5,7-DHT injection. This compound causes phase delay when administered in the early subjective day, and phase advance in the late subjective day. This effect is the opposite of the phase response curve obtained for 5-HT injections. This suggests that 5-HT might act as an entraining agent via the output pathway by feedback to clock neurons in the brain. Some of the injected insects regained their normal level of activity after a few days. These findings suggest a potential role for serotonin as modulator of circadian rhythms in insect including regulation of the level of locomotor activity.

  12. TRiP: Tracking Rhythms in Plants, an automated leaf movement analysis program for circadian period estimation

    Greenham, Kathleen; Lou, Ping; Remsen, Sara E; Farid, Hany; McClung, C. Robertson

    2015-01-01

    Background A well characterized output of the circadian clock in plants is the daily rhythmic movement of leaves. This process has been used extensively in Arabidopsis to estimate circadian period in natural accessions as well as mutants with known defects in circadian clock function. Current methods for estimating circadian period by leaf movement involve manual steps throughout the analysis and are often limited to analyzing one leaf or cotyledon at a time. Results In this study, we describ...

  13. Experimental jetlag disrupts circadian clock genes but improves performance in racehorses after light-dependent rapid resetting of neuroendocrine systems and the rest-activity cycle.

    Tortonese, D J; Preedy, D F; Hesketh, S A; Webb, H N; Wilkinson, E S; Allen, W R; Fuller, C J; Townsend, J; Short, R V

    2011-12-01

    Abrupt alterations in the 24-h light : dark cycle, such as those resulting from transmeridian air travel, disrupt circadian biological rhythms in humans with detrimental consequences on cognitive and physical performance. In the present study, a jetlag-simulated phase shift in photoperiod temporally impaired circadian peaks of peripheral clock gene expression in racehorses but acutely enhanced athletic performance without causing stress. Indices of aerobic and anaerobic capacities were significantly increased by a phase-advance, enabling prolonged physical activity before fatigue occurred. This was accompanied by rapid re-entrainment of the molecular clockwork and the circadian pattern of melatonin, with no disturbance of the adrenal cortical axis, but a timely rise in prolactin, which is a hormone known to target organs critical for physical performance. Subsequent studies showed that, unlike the circadian pattern of melatonin, and in contrast to other species, the daily rhythm of locomotor activity was completely eliminated under constant darkness, but it was restored immediately upon the reintroduction of a light : dark cycle. Resetting of the rhythm of locomotion was remarkably fast, revealing a rapid mechanism of adaptation and a species dependency on light exposure for the expression of daily diurnal activity. These results show that horses are exquisitely sensitive to sudden changes in photoperiod and that, unlike humans, can benefit from them; this appears to arise from powerful effects of light underlying a fast and advantageous process of adjustment to the phase shift.

  14. The timing of the human circadian clock is accurately represented by the core body temperature rhythm following phase shifts to a three-cycle light stimulus near the critical zone

    Jewett, M. E.; Duffy, J. F.; Czeisler, C. A.

    2000-01-01

    A double-stimulus experiment was conducted to evaluate the phase of the underlying circadian clock following light-induced phase shifts of the human circadian system. Circadian phase was assayed by constant routine from the rhythm in core body temperature before and after a three-cycle bright-light stimulus applied near the estimated minimum of the core body temperature rhythm. An identical, consecutive three-cycle light stimulus was then applied, and phase was reassessed. Phase shifts to these consecutive stimuli were no different from those obtained in a previous study following light stimuli applied under steady-state conditions over a range of circadian phases similar to those at which the consecutive stimuli were applied. These data suggest that circadian phase shifts of the core body temperature rhythm in response to a three-cycle stimulus occur within 24 h following the end of the 3-day light stimulus and that this poststimulus temperature rhythm accurately reflects the timing of the underlying circadian clock.

  15. The circadian rhythm of core body temperature (Part I: The use of modern telemetry systems to monitor core body temperature variability

    Słomko Joanna

    2016-06-01

    Full Text Available The best known daily rhythms in humans include: the sleep-wake rhythm, the circadian core body temperature variability, daily fluctuations in arterial blood pressure and heartbeat frequency, and daily changes in hormone secretion: e.g. melatonin, cortisol, growth hormone, prolactin. The core body temperature in humans has a characteristic sinusoidal course, with the maximum value occurring between 3:00-5:00 pm and the minimum between 3:00-5:00 am. Analysis of literature indicates that the obtained results concerning core body temperature are to a large extent influenced by the type of method applied in the measurement. Depending on test protocols, we may apply various methodologies to measuring core body temperature. One of the newest methods of measuring internal and external body temperature consists in the utilisation of remote temperature sensors transmitting the obtained value via a radio signal. The advantages of this method includes the ability to perform: continuous core temperature measurement, observe dynamic changes in core body temperature occurring in circadian rhythm and the repeatability and credibility of the obtained results, which is presented in numerous scientific reports.

  16. Effect of Circadian Rhythm on Peak of Maximal Fat Oxidation on Non-Athletic Men

    Hassan Darvakh; Masoud Nikbakht; Saeed Shakerian; Asieh Sadat Mousavian

    2014-01-01

    4TBackground: The aim of this4T7T 4T7Tstudy is to investigate4T7T 4T7Tthe effect of4T7T 4T7Tcircadian rhythm4T7T 4T7Ton the4T7T 4T7Tmaximal4T7T 4T7Tfat oxidation (4T7TMFO4T7T) and4T7T 4T7TFATMAX4T7T in4T7T students4T7T 4T7Twithout practice. 4TMaterials and Methods: The subjects of this study4T 4Twere4T ten 4Tnon4T9T-athletes9T male students (N=10), with 4Tthe4T9T 4T9Tbody mass index4T 4Tand4T 4Tmaximal oxygen consumption4T 4Tbelow 504T%, who were 4Tselected randomly. Run test was performed...

  17. Non-Alcoholic Fatty Pancreas Disease Pathogenesis: A Role for Developmental Programming and Altered Circadian Rhythms

    Carter, Rebeca; Mouralidarane, Angelina; Soeda, Junpei; Ray, Shuvra; Pombo, Joaquim; Saraswati, Ruma; Novelli, Marco; Fusai, Giuseppe; Rappa, Francesca; Saracino, Chiara; Pazienza, Valerio; Poston, Lucilla; Taylor, Paul D.; Vinciguerra, Manlio; Oben, Jude A.

    2014-01-01

    Objectives Emerging evidence suggests that maternal obesity (MO) predisposes offspring to obesity and the recently described non-alcoholic fatty pancreas disease (NAFPD) but involved mechanisms remain unclear. Using a pathophysiologically relevant murine model, we here investigated a role for the biological clock - molecular core circadian genes (CCG) in the generation of NAFPD. Design Female C57BL6 mice were fed an obesogenic diet (OD) or standard chow (SC) for 6 weeks, prior to pregnancy and throughout gestation and lactation: resulting offspring were subsequently weaned onto either OD (Ob_Ob and Con_Ob) or standard chow (Ob_Con and Con_Con) for 6 months. Biochemical, pro-inflammatory and pro-fibrogenic markers associated with NAFPD were then evaluated and CCG mRNA expression in the pancreas determined. Results Offspring of obese dams weaned on to OD (Ob_Ob) had significantly increased (p≤0.05): bodyweight, pancreatic triglycerides, macrovesicular pancreatic fatty-infiltration, and pancreatic mRNA expression of TNF-α, IL-6, α-SMA, TGF-β and increased collagen compared to offspring of control dams weaned on to control chow (Con_Con). Analyses of CCG expression demonstrated a phase shift in CLOCK (−4.818, p<0.01), REV-ERB-α (−1.4,p<0.05) and Per2 (3.27,p<0.05) in association with decreased amplitude in BMAL-1 (−0.914,p<0.05) and PER2 (1.18,p<0.005) in Ob_Ob compared to Con_Con. 2-way ANOVA revealed significant interaction between MO and post-weaning OD in expression of CLOCK (p<0.005), PER1 (p<0.005) and PER2 (p<0.05) whilst MO alone influenced the observed rhythmic variance in expression of all 5 measured CCG. Conclusions Fetal and neonatal exposure to a maternal obesogenic environment interacts with a post-natal hyper-calorific environment to induce offspring NAFPD through mechanisms involving perturbations in CCG expression. PMID:24657938

  18. Non-alcoholic fatty pancreas disease pathogenesis: a role for developmental programming and altered circadian rhythms.

    Rebeca Carter

    Full Text Available OBJECTIVES: Emerging evidence suggests that maternal obesity (MO predisposes offspring to obesity and the recently described non-alcoholic fatty pancreas disease (NAFPD but involved mechanisms remain unclear. Using a pathophysiologically relevant murine model, we here investigated a role for the biological clock--molecular core circadian genes (CCG in the generation of NAFPD. DESIGN: Female C57BL6 mice were fed an obesogenic diet (OD or standard chow (SC for 6 weeks, prior to pregnancy and throughout gestation and lactation: resulting offspring were subsequently weaned onto either OD (Ob_Ob and Con_Ob or standard chow (Ob_Con and Con_Con for 6 months. Biochemical, pro-inflammatory and pro-fibrogenic markers associated with NAFPD were then evaluated and CCG mRNA expression in the pancreas determined. RESULTS: Offspring of obese dams weaned on to OD (Ob_Ob had significantly increased (p≤0.05: bodyweight, pancreatic triglycerides, macrovesicular pancreatic fatty-infiltration, and pancreatic mRNA expression of TNF-α, IL-6, α-SMA, TGF-β and increased collagen compared to offspring of control dams weaned on to control chow (Con_Con. Analyses of CCG expression demonstrated a phase shift in CLOCK (-4.818, p<0.01, REV-ERB-α (-1.4,p<0.05 and Per2 (3.27,p<0.05 in association with decreased amplitude in BMAL-1 (-0.914,p<0.05 and PER2 (1.18,p<0.005 in Ob_Ob compared to Con_Con. 2-way ANOVA revealed significant interaction between MO and post-weaning OD in expression of CLOCK (p<0.005, PER1 (p<0.005 and PER2 (p<0.05 whilst MO alone influenced the observed rhythmic variance in expression of all 5 measured CCG. CONCLUSIONS: Fetal and neonatal exposure to a maternal obesogenic environment interacts with a post-natal hyper-calorific environment to induce offspring NAFPD through mechanisms involving perturbations in CCG expression.

  19. 24 Hours chronomics of ambulatory blood pressure and its relation with circadian rhythm of 6-sulfatoxy melatonin in night shift health care workers

    B. Anjum

    2015-08-01

    Results: Ambulatory BP and HR were recorded at every 30 min intervals in day time and each hour in night time synchronically with circadian pattern of 6 sulfatoxy melatonin during shift duties. Highly Significant difference was found in double amplitude (2DA of blood pressure between night and day shift (p<0.001. In night shift, hyperbaric index (HBI of mean systolic blood pressure was found to be increased at 00-03 am (midnight while during day shift, peak was found at 06-09 am. Peak melatonin was to be found in early morning as compared to mid night in both the shift. Conclusions: The present study concluded that the desynchronization was appeared during night shift and entrainment of circadian rhythm in the day shift. [Int J Res Med Sci 2015; 3(8.000: 1922-1931

  20. Morph-associated JH titer diel rhythm in Gryllus firmus: Experimental verification of its circadian basis and cycle characterization in artificially selected lines raised in the field.

    Zera, Anthony J; Zhao, Zhangwu

    2009-05-01

    Previous studies demonstrated a high-amplitude, diel cycle for the hemolymph JH titer in the wing-polymorphic cricket, Gryllus firmus. The JH titer rose and fell in the flight-capable morph (long-winged, LW(f)) above and below the relatively temporally invariant JH titer in the flightless (short-winged, SW) morph. The morph-specific JH titer cycle appeared to be primarily driven by a morph-specific diel cycle in the rate of JH biosynthesis. In the present study, cycles of the JH titer and rate of JH biosynthesis in the LW(f) morph persisted in the laboratory under constant darkness with an approximate 24h periodicity. The JH titer cycle also shifted in concert with a shift in the onset of the scotophase, was temperature compensated in constant darkness, and became arrhythmic under constant light. These results provide strong support for the circadian basis of the morph-specific diel rhythm of the JH titer and JH biosynthetic rate. Persistence of the JH titer cycle under constant darkness in multiple LW-selected and SW-selected stocks also provides support for the genetic basis of the morph-associated circadian rhythm. The morph-specific JH titer cycle was observed in these stocks raised in the field, in both males and females, in each of 3 years studied. The onset of the cycle in the LW(f) morph, a few hours before sunset, correlated well with the onset of the cycle, a few hours before lights-off, in the laboratory. The morph-specific JH titer cycle is a general feature of G. firmus, under a variety of environmental conditions, and is not an artifact of specific laboratory conditions or specific genetic stocks. It is a powerful experimental model to investigate the mechanisms underlying endocrine circadian rhythms, their evolution, and their impact on life history evolution.

  1. Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

    Jon C Svendsen

    Full Text Available Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons. Using juvenile lake sturgeon (Acipenser fulvescens, the objective of this study was to test four hypotheses: 1 A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2 A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3 measurements of forced maximum metabolic rate (MMR(F are repeatable in individual fish; and 4 MMR(F correlates positively with spontaneous maximum metabolic rate (MMR(S. Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMR(F. Trials lasting 24 h were used to measure standard metabolic rate (SMR and MMR(S. Repeatability and correlations between MMR(F and MMR(S were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O(2sat, demonstrating oxygen regulation. In contrast, MMR(F was affected by hypoxia and decreased across the range from 100% O(2sat to 70% O(2sat. MMR(F was repeatable in individual fish, and MMR(F correlated positively with MMR(S, but the relationships between MMR(F and MMR(S were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor. Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMR(F and MMR(S support the conjecture that MMR(F represents a measure of organism performance that could be a target of natural selection.

  2. Proteomics of the photoneuroendocrine circadian system of the brain

    Møller, Morten; Lund-Andersen, Casper; Rovsing, Louise

    2010-01-01

    The photoneuroendocrine circadian system of the brain consists of (a) specialized photoreceptors in the retina, (b) a circadian generator located in the forebrain that contains "clock genes," (c) specialized nuclei in the forebrain involved in neuroendocrine secretion, and (d) the pineal gland....... The circadian generator is a nucleus, called the suprachiasmatic nucleus (SCN). The neurons of this nucleus contain "clock genes," the transcription of which exhibits a circadian rhythm. Most circadian rhythms are generated by the neurons of this nucleus and, via neuronal and humoral connections, the SCN...... controls circadian activity of the brain and peripheral tissues. The endogenous oscillator of the SCN is each day entrained to the length of the daily photoperiod by light that reach the retina, and specialized photoreceptors transmit impulses to the SCN via the optic nerves. Mass screening for day...

  3. Chronobiology applied to spawning and gamete withdrawal: importance of daily rhythms

    2011-01-01

    Chronobiology is the field of science which studies the biological rhythms and the mechanisms by which the organisms adapt to a constantly changing environment. Animals synchronize their rhythms with environmental cycles choosing the most suitable moment to feed, reproduce or be active, thereby optimizing biological processes. In fish, the study of circadian activity and feeding rhythms has been profusely investigated lately; however, reproduction rhythms are often neglected. Fish species rep...

  4. Circadian entrainment of Neurospora crassa

    Merrow, M.; Roenneberg, T.

    2007-01-01

    The circadian clock evolved under entraining conditions, yet most circadian experiments and much circadian theory are built around free-running rhythms. The interpretation of entrainment experiments is certainly more complex than that of free-running rhythms due to the relationship between exogenous

  5. Mitogen- and stress-activated protein kinase 1 modulates photic entrainment of the suprachiasmatic circadian clock.

    Cao, Ruifeng; Butcher, Greg Q; Karelina, Kate; Arthur, J Simon; Obrietan, Karl

    2013-01-01

    The master circadian clock in mammals, the suprachiasmatic nucleus (SCN), is under the entraining influence of the external light cycle. At a mechanistic level, intracellular signaling via the p42/44 mitogen-activated protein kinase pathway appears to play a central role in light-evoked clock entrainment; however, the precise downstream mechanisms by which this pathway influences clock timing are not known. Within this context, we have previously reported that light stimulates activation of the mitogen-activated protein kinase effector mitogen-stress-activated kinase 1 (MSK1) in the SCN. In this study, we utilised MSK1(-/-) mice to further investigate the potential role of MSK1 in circadian clock timing and entrainment. Locomotor activity analysis revealed that MSK1 null mice entrained to a 12 h light/dark cycle and exhibited circadian free-running rhythms in constant darkness. Interestingly, the free-running period in MSK1 null mice was significantly longer than in wild-type control animals, and MSK1 null mice exhibited a significantly greater variance in activity onset. Further, MSK1 null mice exhibited a significant reduction in the phase-delaying response to an early night light pulse (100 lux, 15 min), and, using an 8 h phase-advancing 'jet-lag' experimental paradigm, MSK1 knockout animals exhibited a significantly delayed rate of re-entrainment. At the molecular level, early night light-evoked cAMP response element-binding protein (CREB) phosphorylation, histone phosphorylation and Period1 gene expression were markedly attenuated in MSK1(-/-) animals relative to wild-type mice. Together, these data provide key new insights into the molecular mechanisms by which MSK1 affects the SCN clock.

  6. Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver.

    Guillaume Rey

    2011-02-01

    Full Text Available The mammalian circadian clock uses interlocked negative feedback loops in which the heterodimeric basic helix-loop-helix transcription factor BMAL1/CLOCK is a master regulator. While there is prominent control of liver functions by the circadian clock, the detailed links between circadian regulators and downstream targets are poorly known. Using chromatin immunoprecipitation combined with deep sequencing we obtained a time-resolved and genome-wide map of BMAL1 binding in mouse liver, which allowed us to identify over 2,000 binding sites, with peak binding narrowly centered around Zeitgeber time 6. Annotation of BMAL1 targets confirms carbohydrate and lipid metabolism as the major output of the circadian clock in mouse liver. Moreover, transcription regulators are largely overrepresented, several of which also exhibit circadian activity. Genes of the core circadian oscillator stand out as strongly bound, often at promoter and distal sites. Genomic sequence analysis of the sites identified E-boxes and tandem E1-E2 consensus elements. Electromobility shift assays showed that E1-E2 sites are bound by a dimer of BMAL1/CLOCK heterodimers with a spacing-dependent cooperative interaction, a finding that was further validated in transactivation assays. BMAL1 target genes showed cyclic mRNA expression profiles with a phase distribution centered at Zeitgeber time 10. Importantly, sites with E1-E2 elements showed tighter phases both in binding and mRNA accumulation. Finally, analyzing the temporal profiles of BMAL1 binding, precursor mRNA and mature mRNA levels showed how transcriptional and post-transcriptional regulation contribute differentially to circadian expression phase. Together, our analysis of a dynamic protein-DNA interactome uncovered how genes of the core circadian oscillator crosstalk and drive phase-specific circadian output programs in a complex tissue.

  7. Circadian physiology of metabolism.

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark.

  8. Nonphotic entrainment of the human circadian pacemaker

    Klerman, E. B.; Rimmer, D. W.; Dijk, D. J.; Kronauer, R. E.; Rizzo, J. F. 3rd; Czeisler, C. A.

    1998-01-01

    In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals "free run" even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.

  9. Food reward without a timing component does not alter the timing of activity under positive energy balance

    van der Vinne, V.; Akkerman, J.; Lanting, G. D.; Riede, S. J.; Hut, R. A.

    2015-01-01

    Circadian clocks drive daily rhythms in physiology and behavior which allow organisms to anticipate predictable daily changes in the environment. In most mammals, circadian rhythms result in nocturnal activity patterns although plasticity of the circadian system allows activity patterns to shift to

  10. Effect of electric field exposure on melatonin and enzyme circadian rhythms in the rat pineal

    Wilson, B.; Anderson, L.E.; Hilton, D.I.; Phillips, R.D.

    1980-11-01

    The effects of chronic 30-day electric field exposure on pineal serotonin N-acetyl transferase (EC 2.1.15) activity as well as melatonin and 5-methoxy tryptophol (5-MTOL) concentrations in rats, were assessed.

  11. Enhancement of NAD⁺-dependent SIRT1 deacetylase activity by methylselenocysteine resets the circadian clock in carcinogen-treated mammary epithelial cells.

    Fang, Mingzhu; Guo, Wei-Ren; Park, Youngil; Kang, Hwan-Goo; Zarbl, Helmut

    2015-12-15

    We previously reported that dietary methylselenocysteine (MSC) inhibits N-methyl-N-nitrosourea (NMU)-induced mammary tumorigenesis by resetting circadian gene expression disrupted by the carcinogen at the early stage of tumorigenesis. To investigate the underlying mechanism, we developed a circadian reporter system comprised of human mammary epithelial cells with a luciferase reporter driven by the promoter of human PERIOD 2 (PER2), a core circadian gene. In this in vitro model, NMU disrupted cellular circadian rhythm in a pattern similar to that observed with SIRT1-specific inhibitors; in contrast, MSC restored the circadian rhythms disrupted by NMU and protected against SIRT1 inhibitors. Moreover, NMU inhibited intracellular NAD+/NADH ratio and reduced NAD+-dependent SIRT1 activity in a dose-dependent manner, while MSC restored NAD+/NADH and SIRT1 activity in the NMU-treated cells, indicating that the NAD+-SIRT1 pathway was targeted by NMU and MSC. In rat mammary tissue, a carcinogenic dose of NMU also disrupted NAD+/NADH oscillations and decreased SIRT1 activity; dietary MSC restored NAD+/NADH oscillations and increased SIRT1 activity in the mammary glands of NMU-treated rats. MSC-induced SIRT1 activity was correlated with decreased acetylation of BMAL1 and increased acetylation of histone 3 lysine 9 at the Per2 promoter E-Box in mammary tissue. Changes in SIRT1 activity were temporally correlated with loss or restoration of rhythmic Per2 mRNA expression in NMU-treated or MSC-rescued rat mammary glands, respectively. Together with our previous findings, these results suggest that enhancement of NAD+-dependent SIRT1 activity contributes to the chemopreventive efficacy of MSC by restoring epigenetic regulation of circadian gene expression at early stages of mammary tumorigenesis.

  12. Circadian rhythm of heart rate in the rabbit: prolongation of action potential duration by sustained beta adrenoceptor blockade is not due to associated bradycardia.

    Vaughan Williams, E M; Dennis, P D; Garnham, C

    1986-07-01

    Six litters of six young rabbits were injected intraperitoneally, two per litter, with saline, alinidine, or nadolol once or twice daily for two weeks. In four litters successful radiotransmissions of electrocardiograms were recorded once hourly for four days before and during treatment. Alinidine and nadolol produced an overall mean bradycardia in comparison with saline treated animals, the effect of alinidine exceeding that of nadolol. At 48-70 hours after the end of treatment the hearts were used for in vitro electrophysiological study. Nadolol, but not alinidine, induced a prolongation of action potential duration compared with that of saline treated littermates in both atrial and ventricular muscle. An incidental observation was that heart rate in the rabbit followed a circadian rhythm, heart rates being slower in the morning and faster in late afternoon and evening. The circadian rhythm was attenuated but not abolished by alinidine and nadolol. These results suggest that if prolongation of action potential duration by sustained beta blockade in patients after myocardial infarction contributes to protection against sudden death (by a class III antiarrhythmic action) then alinidine would not be expected to provide a comparable prophylaxis.

  13. COMPARATIVE STUDY OF CIRCADIAN RHYTHM OF PEAK EXPIRATORY FLOW RATE IN SOUTH INDIAN HEALTHY FEMALES AND ASTHMATIC FEMALES

    Sindhura

    2016-02-01

    Full Text Available AIM AND OBJECTIVES Cross-sectional study to compare the peak expiratory flow rate with the help of “Mini-Wright” peak flow meter among females, normal healthy subjects and subjects who are asthmatics of age group 20–40 years. METHOD 60 adult females of age group 20-40 years (30-Healthy and 30-Asthmatics for whom baseline pulmonary function testing was done to differentiate normal and asthmatic. All cases were clinically examined to rule-out any obvious cardiopulmonary diseases. Subjects were provided one mini Wright’s peak expiratory flow meter, were individually trained for measuring their own PEFR in L/min and were instructed to record the readings with Wright’s portable peak flow meter at 5:00 am, 8:00 am, 11:00 am, 14:00 pm, 17:00 pm, 20:00 pm and 23:00 pm on two consecutive days. They were instructed to obtain at least three recordings at a time. RESULTS In healthy subjects it is observed that mean PEFR values at morning 5:00 hours was 276.966, which is the lowest value of day and 440.653 at evening 17:00 hour, which is the highest value of the day for this shows there is a progressive rise of about 59.1% in mean PEFR value from early morning till evening and at night 11:00 hours we got a mean value of 340.143, a decline of 22.809% when compared to peak value of the day (17:00 hours. In Asthmatic, early morning mean PEFR value at 5:00 hours was 157.888, which is lowest value of the day and 369.774 at evening at 17:00 hours, which is the highest mean PEFR value of the day. There is a significant rise of about 134.2002% in the mean PEFR value from early morning till evening and at night 11:00 hours we got a mean value of 197.666, a decline of 46.5441% when compared to peak value of the day (17:00 hours. CONCLUSION It is seen that though the circadian rhythm in asthmatics follows a similar pattern, i.e. PEFR dip in morning and PEFR peak in late afternoon, but the swing of PEFR from the mean value is more than in normal subjects. A

  14. Can insulated skin temperature act as a substitute for rectal temperature when studying circadian rhythms?

    Bogh, M; Minors, D S; Waterhouse, J M

    1994-10-01

    We measured rectal, lateral chest wall, and axillary temperature every half hour for at least 24 h while subjects were living normal life-styles and keeping a sleep/activity diary. We then used a purification method to estimate the decrease of temperature due to sleep and the increases due to sitting, standing, walking, or exercising, as well as the parameters of the cosine curve that described the "purified data." Cosinor analysis of raw and purified data showed that the acrophases from both skin sites were much more variable and up to 8 h later than were those from the rectum (particularly if exercise had been taken), even though the acrophases from the two skin sites were similar to each other. For rectal temperature, there was an increase in the size of the masking effect as activity progressed through the sequence: sitting, standing or walking, exercising. In contrast, for both chest wall and axillary temperatures, although sitting produced masking effects similar to those for rectal temperature, masking effects due to standing or walking and exercising were much smaller, and sometimes they were even less than the masking effects due to sitting. These results indicate that our measurements of cutaneous temperature did not act as a substitute for rectal temperature, particularly when the subject was physically active rather than sedentary.

  15. Adaptation to short photoperiods augments circadian food anticipatory activity in Siberian hamsters.

    Bradley, Sean P; Prendergast, Brian J

    2014-06-01

    This article is part of a Special Issue "Energy Balance". Both the light-dark cycle and the timing of food intake can entrain circadian rhythms. Entrainment to food is mediated by a food entrainable circadian oscillator (FEO) that is formally and mechanistically separable from the hypothalamic light-entrainable oscillator. This experiment examined whether seasonal changes in day length affect the function of the FEO in male Siberian hamsters (Phodopus sungorus). Hamsters housed in long (LD; 15 h light/day) or short (SD; 9h light/day) photoperiods were subjected to a timed-feeding schedule for 10 days, during which food was available only during a 5h interval of the light phase. Running wheel activity occurring within a 3h window immediately prior to actual or anticipated food delivery was operationally-defined as food anticipatory activity (FAA). After the timed-feeding interval, hamsters were fed ad libitum, and FAA was assessed 2 and 7 days later via probe trials of total food deprivation. During timed-feeding, all hamsters exhibited increases FAA, but FAA emerged more rapidly in SD; in probe trials, FAA was greater in magnitude and persistence in SD. Gonadectomy in LD did not induce the SD-like FAA phenotype, indicating that withdrawal of gonadal hormones is not sufficient to mediate the effects of photoperiod on FAA. Entrainment of the circadian system to light markedly affects the functional output of the FEO via gonadal hormone-independent mechanisms. Rapid emergence and persistent expression of FAA in SD may reflect a seasonal adaptation that directs behavior toward sources of nutrition with high temporal precision at times of year when food is scarce.

  16. The Progress of Studies on the Relation Between Circadian Rhythm Disruption and Cancer%近日节律紊乱与癌症关系的研究进展

    李胜吾; 吴佳; 胡晓峰

    2012-01-01

    动物实验及流行病学研究结果表明,癌症的发生发展与近日节律的紊乱密切相关.目前关于近日节律紊乱与癌症关系的研究还存在一些局限性:人群流行病学研究目前主要是发现夜间倒班、跨时差飞行等所致的节律紊乱与乳腺癌、前列腺癌发病关系密切,而关于其它癌症的研究报道较少.虽然近日节律失调与癌症的关系已经得到证实,但其机制尚未确定,大多数学者认为,节律紊乱的致癌作用主要与褪黑素分泌的降低和生物钟基因表达的紊乱有关.%Like functions of other organisms, most of the physiological and behavioral functions of human are characterized by day-night rhythms. The rhythms which exhibit approximately 24-hour periodicity are called as circadian rhythms. This review is to summarize the progress of studies on relation of circadian rhythum disruption and cancer. The research results from animal experiments and population-based epidemiological studies have showed that cancer is closly related to circadian rhythm. Although numrous studies have demonstrated the close relation between circadian rhythm disruption and cancer, the mechanism is not yet clear. The current studies attributed decreased level of melatonin secretion and disruption of clock genes expression to the mechanism of carcinogenesis of circadian rhythm disruption.

  17. Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight. Part 2; Metabolism

    Fuller, C. A.; Dotsenko, M. A.; Korolkov, V. I.; Griffin, D. W.; Stein, T. P.

    1994-01-01

    Energy expenditure can be regarded as the sum of two components; the basal metabolic rate and the energy costs of activity. Weight loss is usually associated with an energy deficit. A negative energy balance exists when energy intake is less that energy utilization. The deficit is made up by tissue catabolism (principally fat, but also some protein). By analyzing food and water intake, urine and fecal output, and changes in body weight, the Skylab investigators reached the unexpected conclusion that energy expenditure during spaceflight was about 5% greater than at 1 G (Leonard, 1983; Rambaut et al., 1977). Possible explanations for the human metabolic responses are an increased workload during spaceflight (Leonard, 1983), or as Rambaut and co-workers (1977) suggested, a progressive decrease in metabolic efficiency. It is likely to be very difficult to distinguish between these two possibilities in man because the activity component may be different during spaceflight than it is the ground. The problem is to measure energy expenditure with efficient precision during spaceflight in a non-invasive manner which will not interfere with other investigations or take an time. The doubly labeled water (DLW) method meets these criteria. The DLW method is the only method available for continuously measuring energy expenditure during spaceflight given the severely restricted conditions in the spaceflight environment. Therefore, this study focuses on the development and use of this procedure on nonhuman primates during spaceflight. Energy expenditure and total body water was determined in two Rhesus monkeys by the doubly labeled water (2H2'80) method. Three determinations were made. Monkey B (#2483) was studied twice, during the flight of COSMOS 2044 and during a follow-up ground control study a month later. A second monkey was studied on the ground only (Monkey D, #782).

  18. Cross-talk between the circadian clock and the cell cycle in cancer.

    Soták, Matúš; Sumová, Alena; Pácha, Jiří

    2014-06-01

    The circadian clock is an endogenous timekeeper system that controls the daily rhythms of a variety of physiological processes. Accumulating evidence indicates that genetic changes or unhealthy lifestyle can lead to a disruption of circadian homeostasis, which is a risk factor for severe dysfunctions and pathologies including cancer. Cell cycle, proliferation, and cell death are closely intertwined with the circadian clock, and thus disruption of circadian rhythms appears to be linked to cancer development and progression. At the molecular level, the cell cycle machinery and the circadian clocks are controlled by similar mechanisms, including feedback loops of genes and protein products that display periodic activation and repression. Here, we review the circadian rhythmicity of genes associated with the cell cycle, proliferation, and apoptosis, and we highlight the potential connection between these processes, the circadian clock, and neoplastic transformations. Understanding these interconnections might have potential implications for the prevention and therapy of malignant diseases.

  19. PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator

    Shaul Mezan

    2016-10-01

    Full Text Available Circadian clocks generate 24-hr rhythms in physiology and behavior. Despite numerous studies, it is still uncertain how circadian rhythms emerge from their molecular and neural constituents. Here, we demonstrate a tight connection between the molecular and neuronal circadian networks. Using fluorescent transcriptional reporters in a Drosophila ex vivo brain culture system, we identified a reciprocal negative regulation between the master circadian regulator CLK and expression of pdf, the main circadian neuropeptide. We show that PDF feedback is required for maintaining normal oscillation pattern in CLK-driven transcription. Interestingly, we found that CLK and neuronal firing suppresses pdf transcription, likely through a common pathway involving the transcription factors DHR38 and SR, establishing a direct link between electric activity and the circadian system. In sum, our work provides evidence for the existence of an uncharacterized CLK-PDF feedback loop that tightly wraps together the molecular oscillator with the circadian neuronal network in Drosophila.

  20. The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus.

    Kudo, Takashi; Block, Gene D; Colwell, Christopher S

    2015-01-01

    The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca(2+)]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca(2+)]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca(2+)]i-activated channel is one of the targets.

  1. Circadian regulation of cell cycle: Molecular connections between aging and the circadian clock.

    Khapre, Rohini V; Samsa, William E; Kondratov, Roman V

    2010-09-01

    The circadian clock generates oscillations in physiology and behavior, known as circadian rhythms. Links between the circadian clock genes Periods, Bmal1, and Cryptochromes and aging and cancer are emerging. Circadian clock gene expression is changed in human pathologies, and transgenic mice with mutations in clock genes develop cancer and premature aging. Control of genome integrity and cell proliferation play key roles in the development of age-associated pathologies and carcinogenesis. Here, we review recent data on the connection between the circadian clock and control of the cell cycle. The circadian clock regulates the activity and expression of several critical cell cycle and cell cycle check-point-related proteins, and in turn cell cycle-associated proteins regulate circadian clock proteins. DNA damage can reset the circadian clock, which provides a molecular mechanism for reciprocal regulation between the circadian clock and the cell cycle. This circadian clock-dependent control of cell proliferation, together with other known physiological functions of the circadian clock such as the control of metabolism, oxidative and genotoxic stress response, and DNA repair, opens new horizons for understanding the mechanisms behind aging and carcinogenesis.

  2. Deletion of Metabotropic Glutamate Receptors 2 and 3 (mGlu2 & mGlu3 in Mice Disrupts Sleep and Wheel-Running Activity, and Increases the Sensitivity of the Circadian System to Light.

    David Pritchett

    Full Text Available Sleep and/or circadian rhythm disruption (SCRD is seen in up to 80% of schizophrenia patients. The co-morbidity of schizophrenia and SCRD may in part stem from dysfunction in common brain mechanisms, which include the glutamate system, and in particular, the group II metabotropic glutamate receptors mGlu2 and mGlu3 (encoded by the genes Grm2 and Grm3. These receptors are relevant to the pathophysiology and potential treatment of schizophrenia, and have also been implicated in sleep and circadian function. In the present study, we characterised the sleep and circadian rhythms of Grm2/3 double knockout (Grm2/3-/- mice, to provide further evidence for the involvement of group II metabotropic glutamate receptors in the regulation of sleep and circadian rhythms. We report several novel findings. Firstly, Grm2/3-/- mice demonstrated a decrease in immobility-determined sleep time and an increase in immobility-determined sleep fragmentation. Secondly, Grm2/3-/- mice showed heightened sensitivity to the circadian effects of light, manifested as increased period lengthening in constant light, and greater phase delays in response to nocturnal light pulses. Greater light-induced phase delays were also exhibited by wildtype C57Bl/6J mice following administration of the mGlu2/3 negative allosteric modulator RO4432717. These results confirm the involvement of group II metabotropic glutamate receptors in photic entrainment and sleep regulation pathways. Finally, the diurnal wheel-running rhythms of Grm2/3-/- mice were perturbed under a standard light/dark cycle, but their diurnal rest-activity rhythms were unaltered in cages lacking running wheels, as determined with passive infrared motion detectors. Hence, when assessing the diurnal rest-activity rhythms of mice, the choice of assay can have a major bearing on the results obtained.

  3. Phase Control of Ultradian Feeding Rhythms in the Common Vole (Microtus arvalis) : The Roles of Light and the Circadian System

    Gerkema, Menno P.; Daan, Serge; Wilbrink, Marieke; Hop, Martina W.; Leest, Floris van der

    1993-01-01

    In their ultradian (2- to 3-hr) feeding rhythm, common voles show intraindividual synchrony from day to day, as well as interindividual synchrony between members of the population, even at remote distances. This study addresses the question of how resetting of the ultradian rhythm, a prerequisite fo

  4. Chronotypic action of theophylline and of pentobarbital as circadian zeitgebers in the rat.

    Ehret, C F; Potter, V R; Dobra, K W

    1975-06-20

    In the rat the deep body temperature rhythm, monitored by telemetry, can be reset in a predictable direction by a stimulant (theopylline) and by a depressant (pentobarbital). When the drugs are applied immediately before or during the early active phases of the circadian cycle, the rhythm is set back (phase delay). When applied later, past the thermal peak, theophylline, but not pentobarbital, shifts the rhythm ahead (phase advance). Theophylline and pentobarbital in addition to having a number of already established pharmacological properties are now further identified as chronobiotics: they are drugs that may be used to alter the biological time structure by rephasing a circadian rhythm.

  5. Circadian pattern and burstiness in human communication activity

    Jo, Hang-Hyun; Kertész, János; Kaski, Kimmo

    2011-01-01

    The temporal pattern of human communication is inhomogeneous and bursty, as reflected by the heavy tail distribution of the inter-event times. For the origin of this behavior two main mechanisms have been suggested: a) Externally driven inhomogeneities due to the circadian and weekly activity patterns and b) intrinsic correlation based inhomogeneity rooted deeply in the task handling strategies of humans. Here we address this question by providing systematic de-seasoning methods to remove the circadian and weekly patterns from the time series of communication events. We find that the heavy tails of the inter-event time distributions are robust with respect to this procedure indicating that burstiness is mostly caused by the latter mechanism b). Moreover, we find that our de-seasoning procedure improves the scaling behavior of the distribution.

  6. In the darkness of the polar night, scallops keep on a steady rhythm

    Tran, Damien; Sow, Mohamedou; Camus, Lionel; Ciret, Pierre; Berge, Jorgen; Massabuau, Jean-Charles

    2016-08-01

    Although the prevailing paradigm has held that the polar night is a period of biological quiescence, recent studies have detected noticeable activity levels in marine organisms. In this study, we investigated the circadian rhythm of the scallop Chlamys islandica by continuously recording the animal’s behaviour over 3 years in the Arctic (Svalbard). Our results showed that a circadian rhythm persists throughout the polar night and lasts for at least 4 months. Based on observations across three polar nights, we showed that the robustness and synchronicity of the rhythm depends on the angle of the sun below the horizon. The weakest rhythm occurred at the onset of the polar night during the nautical twilight. Surprisingly, the circadian behaviour began to recover during the darkest part of the polar night. Because active rhythms optimize the fitness of an organism, our study brings out that the scallops C. islandica remain active even during the polar night.

  7. Stability of adult emergence and activity/rest rhythms in fruit flies Drosophila melanogaster under semi-natural condition.

    Nisha N Kannan

    Full Text Available Here we report the results of a study aimed at examining stability of adult emergence and activity/rest rhythms under semi-natural conditions (henceforth SN, in four large outbred fruit fly Drosophila melanogaster populations, selected for emergence in a narrow window of time under laboratory (henceforth LAB light/dark (LD cycles. When assessed under LAB, selected flies display enhanced stability in terms of higher amplitude, synchrony and accuracy in emergence and activity rhythms compared to controls. The present study was conducted to assess whether such differences in stability between selected and control populations, persist under SN where several gradually changing time-cues are present in their strongest form. The study revealed that under SN, emergence waveform of selected flies was modified, with even more enhanced peak and narrower gate-width compared to those observed in the LAB and compared to control populations in SN. Furthermore, flies from selected populations continued to exhibit enhanced synchrony and accuracy in their emergence and activity rhythms under SN compared to controls. Further analysis of zeitgeber effects revealed that enhanced stability in the rhythmicity of selected flies under SN was primarily due to increased sensitivity to light because emergence and activity rhythms of selected flies were as stable as controls under temperature cycles. These results thus suggest that stability of circadian rhythms in fruit flies D. melanogaster, which evolved as a consequence of selection for emergence in a narrow window of time under weak zeitgeber condition of LAB, persists robustly in the face of day-to-day variations in cycling environmental factors of nature.

  8. The influence of the circadian clock genes on 24-hour intraocular pressure rhythm in mice%生物钟对小鼠昼夜眼压节律性的影响

    肖凡; 钟笑; 吴国福; 严璐

    2016-01-01

    Objective To investigate the influence of the circadian clock genes on 24-hour intraocular pressure (IOP) rhythm. Methods C57BL/6J mice were randomly divided into 6 groups (group1,3 and 5,wild-type;group2,4 and 6,Cry-deficient [Cry1-/-Cry2-/-]). IOP was measured at eight time points daily (circadian time [CT] 0,3,6,9,12,15,18,and 21 hours),During the IOP measurements,mice in groups 1 and 2 were maintained in a 12-hour light-dark cycle (LD),mice in groups 3 and 4 were kept in a constant darkness(DD) that started 48 hours before the measurements,mice in groups5 and 6 were kept in a constant lightness (LL) that started 48 hours before the measurements. Analyze the changes of the IOP rhythm. Results In wild-type mice living in LD conditions,pressures measured in the light phase were significantly lower than those in the dark phase. This daily rhythm was maintained under DD and LL conditions. In contrast,Cry-deficient mice did not show significant circadian changes in IOP,regard-less of environmental light conditions. Conclusion Clock oscillatory mechanisms require the activity of clock genes,and it’s im-portant for the generation of a circadian rhythm of IOP.%目的:研究生物钟对小鼠昼夜眼压的影响。方法 C57BL/6J小鼠随机分为6组(组1,3和5为野生型小鼠,组2,4和6为Cry1-/-Cry2-/-双基因敲除小鼠)),每天8次(0,3,6,9,12,15,18和21点)测量双眼眼压。在眼压测量期间,组1和组2的小鼠处于12h光照,12h黑暗(LD)环境;组3和组4的小鼠在眼压测量前的48h一直处于完全黑暗(DD)环境中;组5和组6的小鼠在眼压测量前的48h一直处于完全光照(LL)环境中,分析周期性的眼压变化。结果野生型LD组的光照条件下的眼压明显低于黑暗环境中的眼压,而且在DD和LL环境下仍然保持着眼压的双相性;在LD,DD和LL环境下,Cry基因敲除小鼠的眼压没有表现明显的节律性。结

  9. Stability and fragmentation of the activity rhythm across the sleep-wake cycle: the importance of age, lifestyle, and mental health.

    Luik, Annemarie I; Zuurbier, Lisette A; Hofman, Albert; Van Someren, Eus J W; Tiemeier, Henning

    2013-12-01

    The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96 h (138 ± 14 h, mean ± SD) were collected from 1734 people (age: 62 ± 9.4 yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β = 0.07, p = 0.02), but also with a more fragmented distribution of periods of activity and inactivity (β = 0.20, p < 0.001). Having more depressive symptoms was related to less stable (β = -0.07, p = 0.005) and more fragmented (β = 0.10, p < 0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β = -0.11, p < 0.001; smoking: β = -0.11, p < 0.001) and more fragmented rhythms (BMI: β = 0.09, p < 0.001; smoking: β = 0.11, p < 0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.

  10. Time-dependent effects of dim light at night on re-entrainment and masking of hamster activity rhythms.

    Frank, David W; Evans, Jennifer A; Gorman, Michael R

    2010-04-01

    Bright light has been established as the most ubiquitous environmental cue that entrains circadian timing systems under natural conditions. Light equivalent in intensity to moonlight (circadian function in a number of entrainment paradigms. For example, compared to completely dark nights, dim nighttime illumination accelerated re-entrainment of hamster activity rhythms to 4-hour phase advances and delays of an otherwise standard laboratory photocycle. The purpose of this study was to determine if a sensitive period existed in the night during which dim illumination had a robust influence on speed of re-entrainment. Male Siberian hamsters were either exposed to dim light throughout the night, for half of the night, or not at all. Compared to dark nights, dim illumination throughout the entire night decreased by 29% the time for the midpoint of the active phase to re-entrain to a 4-hour phase advance and by 26% for a 4-hour delay. Acceleration of advances and delays were also achieved with 5 hours of dim light per night, but effects depended on whether dim light was present in the first half, second half, or first and last quarters of the night. Both during phase shifting and steady-state entrainment, partially lit nights also produced strong positive and negative masking effects, as well as entrainment aftereffects in constant darkness. Thus, even in the presence of a strong zeitgeber, light that might be encountered under a natural nighttime sky potently modulates the circadian timing system of hamsters.

  11. Circadian clocks, epigenetics, and cancer

    Masri, Selma

    2015-01-01

    The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work and cancer incidence are linked. Accumulating evidence implicates the circadian clock in cancer survival and proliferation pathways. At the molecular level, multiple control mechanisms have been proposed to link circadian transcription and cell-cycle control to tumorigenesis.The circadian gating of the cell cycle and subsequent control of cell proliferation is an area of active investigation. Moreover, the circadian clock is a transcriptional system that is intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape at the level of histone modifications, DNA methylation, and small regulatory RNAs are differentially controlled in cancer cells. This concept raises the possibility that epigenetic control is a common thread linking the clock with cancer, though little scientific evidence is known to date.This review focuses on the link between circadian clock and cancer, and speculates on the possible connections at the epigenetic level that could further link the circadian clock to tumor initiation or progression.

  12. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice.

    Susie Lee

    Full Text Available BACKGROUND: Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Period1 and 2 (Per or Cryptochrome1 and 2 (Cry are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone. However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: Mice lacking Per1 and 2, Cry1 and 2, or one copy of Bmal1, all show increased spontaneous and radiation-induced tumor development. The neoplastic growth of Per-mutant somatic cells is not controlled cell-autonomously but is dependent upon extracellular mitogenic signals. Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation. Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. CONCLUSIONS/SIGNIFICANCE: Tumor suppression in vivo is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor.

  13. The circadian clock coordinates ribosome biogenesis.

    Céline Jouffe

    Full Text Available Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis.

  14. Rethinking transcriptional activation in the Arabidopsis circadian clock.

    Karl Fogelmark

    2014-07-01

    Full Text Available Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

  15. Rethinking transcriptional activation in the Arabidopsis circadian clock.

    Fogelmark, Karl; Troein, Carl

    2014-07-01

    Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

  16. Circadian regulation of metabolic homeostasis: causes and consequences

    McGinnis GR

    2016-05-01

    Full Text Available Graham R McGinnis, Martin E Young Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Robust circadian rhythms in metabolic processes have been described in both humans and animal models, at the whole body, individual organ, and even cellular level. ­Classically, these time-of-day-dependent rhythms have been considered secondary to fluctuations in energy/nutrient supply/demand associated with feeding/fasting and wake/sleep cycles. Renewed interest in this field has been fueled by studies revealing that these rhythms are driven, at least in part, by intrinsic mechanisms and that disruption of metabolic synchrony invariably increases the risk of cardiometabolic disease. The objectives of this paper are to provide a comprehensive review regarding rhythms in glucose, lipid, and protein/amino acid metabolism, the relative influence of extrinsic (eg, neurohumoral factors versus intrinsic (eg, cell autonomous circadian clocks mediators, the physiologic roles of these rhythms in terms of daily fluctuations in nutrient availability and activity status, as well as the pathologic consequences of dyssynchrony. Keywords: circadian rhythm, circadian clocks, metabolic homeostasis, neurohumoral factors, dyssynchrony, time-of-day-dependent rhythms

  17. Circadian and pharmacological regulation of casein kinase I in the hamster suprachiasmatic nucleus

    Patricia V. Agostino; Santiago A. Plano; Diego A. Golombek

    2008-12-01

    In mammals, the mechanism for the generation of circadian rhythms and entrainment by light–dark (LD) cycles resides in the hypothalamic suprachiasmatic nuclei (SCN), and the principal signal that adjusts this biological clock with environmental timing is the light:dark cycle. Within the SCN, rhythms are generated by a complex of molecular feedback loops that regulate the transcription of clock genes, including per and cry. Posttranslational modification plays an essential role in the regulation of biological rhythms; in particular, clock gene phosphorylation by casein kinase I, both epsilon (CKI) and delta (CKI), regulates key molecular mechanisms in the circadian clock. In this paper, we report for the first time that CKI activity undergoes a significant circadian rhythm in the SCN (peaking at circadian time 12, the start of the subjective night), and its pharmacological inhibition alters photic entrainment of the clock, indicating that CKI may be a key element in this pathway.

  18. The role of chronobiology and circadian rhythms in type 2 diabetes mellitus: implications for management of diabetes

    Kurose T

    2014-07-01

    Full Text Available Takeshi Kurose, Takanori Hyo, Daisuke Yabe, Yutaka Seino Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Fukushima, Osaka, Japan Abstract: Circadian clocks regulate cellular to organic and individual behavior levels of all organisms. Almost all cells in animals have self-sustained clocks entrained by environmental signals. Recent progress in genetic research has included identification of clock genes whose disruption causes metabolic abnormalities such as diabetes, obesity, and hyperlipidemia. Here we review recent advances in research on circadian disruption, shift work, altered eating behaviors, and disrupted sleep-wake cycles, with reference to management of type 2 diabe