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Sample records for underlie circadian rhythms

  1. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 7. Circadian Rhythms - From Daily Rhythms to Biological Clocks. Koustubh M Vaze Vijay Kumar Sharma. Series Article Volume 18 Issue 7 July 2013 pp 662- ... Keywords. Circadian rhythms; biological clocks; geophysical cycles; entrainment.

  2. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    hunger and sleep at the same time as the body would not be in the right state to metabolise food efficiently. Thus, synchronization of internal rhythms is an essential aspect of physiology, and circadian rhythms benefit living beings by bringing about such temporal order. In other words, circadian rhythms are thought to.

  3. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 11. Circadian Rhythms - Circadian Timing Systems: How are they Organized? Koustubh M Vaze Vijay Kumar Sharma. Series Article Volume 18 Issue 11 November 2013 pp 1032-1050 ...

  4. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    significance. (right) Vijay Kumar Sharma is a Professor at the. Evolutionary and. Organismal Biology Unit,. JNCASR, Bangalore. His major research interests presently are in understand- ing circadian organization of fruit flies and ants, adaptive significance of circadian clocks, neurogenetics of circadian egg-laying rhythm.

  5. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    Keywords. Circadian rhythms, biological clocks, geophysical cycles, en- trainment. Living organisms ranging from bacteria to human beings exhibit 24-h rhythms in various behaviours and physiological processes. Matching of the period of such rhythms with that of the daily environmental cycles gives an impression that.

  6. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    rhythms especially their endogenous, self-sustained nature, ability to entrain to environmental cycles and. PRCs, greatly resemble those of self-sustained physical oscillators; which led them to propose that circadian rhythms function like physical oscillators and named such biological oscillators as 'endogenous self- ...

  7. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 2. Circadian Rhythms: Why do Living Organisms Have Them? Koustubh M Vaze K L Nikhil Vijay Kumar Sharma. Series Article Volume 19 Issue 2 February 2014 pp 175-189 ...

  8. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 2 ... Adaptation; fitness; circadian resonance; latitudinal clines; experimental evolution. ... Chronobiology Laboratory Evolutionary and Organismal Biology Unit Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436, ...

  9. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    We all experience robust cycles of light and darkness, occurring as a consequence of continuous rotation of the earth about its axis and we call such a twenty-four hour cycle, 'a day'. Almost all living beings are exposed to such daily environmental cycles and they too exhibit daily rhythms in various biological processes.

  10. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    internal/physiological (endogenous) mechanism that drives them? Such questions have intrigued scientists for several decades and paved the way for the exploration of biological timing systems and their underlying mechanisms. Research on a wide variety of organisms has established that these rhythms are generated by.

  11. Circadian Rhythm Sleep Disorders

    Directory of Open Access Journals (Sweden)

    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

  12. Circadian rhythm and menopause.

    Science.gov (United States)

    Pines, A

    2016-12-01

    Circadian rhythm is an internal biological clock which initiates and monitors various physiological processes with a fixed time-related schedule. The master circadian pacemaker is located in the suprachiasmatic nucleus in the hypothalamus. The circadian clock undergoes significant changes throughout the life span, at both the physiological and molecular levels. This cyclical physiological process, which is very complex and multifactorial, may be associated with metabolic alterations, atherosclerosis, impaired cognition, mood disturbances and even development of cancer. Sex differences do exist, and the well-known sleep disturbances associated with menopause are a good example. Circadian rhythm was detected in the daily pattern of hot flushes, with a peak in the afternoons. Endogenous secretion of melatonin decreases with aging across genders, and, among women, menopause is associated with a significant reduction of melatonin levels, affecting sleep. Although it might seem that hot flushes and melatonin secretion are likely related, there are not enough data to support such a hypothesis.

  13. Circadian Rhythms in Cyanobacteria

    Science.gov (United States)

    Golden, Susan S.

    2015-01-01

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

  14. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    Robertson, Laura; Jones, M. Gail

    2009-01-01

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

  15. [Circadian rhythms and systems biology].

    Science.gov (United States)

    Goldbeter, Albert; Gérard, Claude; Leloup, Jean-Christophe

    2010-01-01

    Cellular rhythms represent a field of choice for studies in system biology. The examples of circadian rhythms and of the cell cycle show how the experimental and modeling approaches contribute to clarify the conditions in which periodic behavior spontaneously arises in regulatory networks at the cellular level. Circadian rhythms originate from intertwined positive and negative feedback loops controlling the expression of several clock genes. Models can be used to address the dynamical bases of physiological disorders related to dysfunctions of the mammalian circadian clock. The cell cycle is driven by a network of cyclin-dependent kinases (Cdks). Modeled in the form of four modules coupled through multiple regulatory interactions, the Cdk network operates in an oscillatory manner in the presence of sufficient amounts of growth factor. For circadian rhythms and the cell cycle, as for other recently observed cellular rhythms, periodic behavior represents an emergent property of biological systems related to their regulatory structure.

  16. Circadian Rhythm Management System Project

    Data.gov (United States)

    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...

  17. Circadian rhythms in microalgae production

    NARCIS (Netherlands)

    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

  18. ADHD, circadian rhythms and seasonality

    NARCIS (Netherlands)

    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

  19. Ischemic stroke destabilizes circadian rhythms

    Directory of Open Access Journals (Sweden)

    Borjigin Jimo

    2008-10-01

    Full Text Available Abstract Background The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis. Methods Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume. Results Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting. Conclusion This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating

  20. Circadian Genes, Rhythms and the Biology of Mood Disorders

    OpenAIRE

    McClung, Colleen A.

    2007-01-01

    For many years, researchers have suggested that abnormalities in circadian rhythms may underlie the development of mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the treatments that are currently employed to treat mood disorders are thought to act by shifting or “resetting” the circadian clock, including total sleep deprivation and bright light therapy. There is also reason to suspect that many of the mood stabilizers and antide...

  1. Development of cortisol circadian rhythm in infancy.

    NARCIS (Netherlands)

    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

  2. Circadian genes, rhythms and the biology of mood disorders.

    Science.gov (United States)

    McClung, Colleen A

    2007-05-01

    For many years, researchers have suggested that abnormalities in circadian rhythms may underlie the development of mood disorders such as bipolar disorder (BPD), major depression and seasonal affective disorder (SAD). Furthermore, some of the treatments that are currently employed to treat mood disorders are thought to act by shifting or "resetting" the circadian clock, including total sleep deprivation (TSD) and bright light therapy. There is also reason to suspect that many of the mood stabilizers and antidepressants used to treat these disorders may derive at least some of their therapeutic efficacy by affecting the circadian clock. Recent genetic, molecular and behavioral studies implicate individual genes that make up the clock in mood regulation. As well, important functions of these genes in brain regions and neurotransmitter systems associated with mood regulation are becoming apparent. In this review, the evidence linking circadian rhythms and mood disorders, and what is known about the underlying biology of this association, is presented.

  3. Circadian Rhythms, the Mesolimbic Dopaminergic Circuit, and Drug Addiction

    OpenAIRE

    McClung, Colleen A.

    2007-01-01

    Drug addiction is a devastating disease that affects millions of individuals worldwide. Through better understanding of the genetic variations that create a vulnerability for addiction and the molecular mechanisms that underlie the progression of addiction, better treatment options can be created for those that suffer from this condition. Recent studies point to a link between abnormal or disrupted circadian rhythms and the development of addiction. In addition, studies suggest a role for spe...

  4. Circadian Rhythm Management System, Phase I

    Data.gov (United States)

    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...

  5. Circadian rhythm and its role in malignancy

    Directory of Open Access Journals (Sweden)

    Mahmood Saqib

    2010-03-01

    Full Text Available Abstract 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 circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer.

  6. Factors influencing circadian rhythms in acetaminophen lethality.

    Science.gov (United States)

    Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

    1984-01-01

    Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

  7. Circadian rhythms of women with fibromyalgia

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2000-01-01

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

  9. The neurobiology of circadian rhythms

    NARCIS (Netherlands)

    Van der Zee, Eddy A.; Boersma, Gretha J.; Hut, Roelof A.

    2009-01-01

    Purpose of review There is growing awareness of the importance of circadian rhythmicity in various research fields. Exciting developments are ongoing in the field of circadian neurobiology linked to sleep, food intake, and memory. With the current knowledge of critical clock genes' (genes found to

  10. Circadian Rhythms, Sleep Deprivation, and Human Performance

    Science.gov (United States)

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

    2014-01-01

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

  11. EFFECTS OF CIRCADIAN RHYTHM ON BALANCE PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Karagul Osman

    2017-09-01

    Full Text Available Introduction. The aim of the study was to examine the effect of circadian rhythm on dynamic balance performance and to determine the role of physical activity level, body temperature, chronotype, and gender in this possible effect. Material and

  12. Circadian rhythms: from genes to behaviour

    Indian Academy of Sciences (India)

    located in the third ventricle of the hypothalamus by two independent groups: F. K. Stephan and Irvin ... levels of biological organization, and we have tried to represent this aspect of our discipline in this special ... nature of circadian rhythm research, because at the core of all these studies lies a genetic architecture which.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Drugs of Abuse Can Entrain Circadian Rhythms

    Directory of Open Access Journals (Sweden)

    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.

  15. Sleep, circadian rhythms, and athletic performance.

    Science.gov (United States)

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

    2015-10-01

    Sleep deprivation and time of day are both known to influence performance. A growing body of research has focused on how sleep and circadian rhythms impact athletic performance. This review provides a systematic overview of this research. We searched three different databases for articles on these issues and inspected relevant reference lists. In all, 113 articles met our inclusion criteria. The most robust result is that athletic performance seems to be best in the evening around the time when the core body temperature typically is at its peak. Sleep deprivation was negatively associated with performance whereas sleep extension seems to improve performance. The effects of desynchronization of circadian rhythms depend on the local time at which performance occurs. The review includes a discussion of differences regarding types of skills involved as well as methodological issues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Work related injuries; impact of circadian rhythm

    Directory of Open Access Journals (Sweden)

    Mostafa Hosseini

    2017-04-01

    Full Text Available Work related injuries make up a major part of traumatic injuries, which inflict a financial burden and huge costs on the family and society. Work related injuries result in loss of a work force of a country on one hand and cause the family to lose its financial support on the other. Therefore, this type of injury has attracted much attention. Although numerous variables play a role in occurrence of these accidents, the effect of physiologic factors cannot be overlooked in this regard. For example interference of night working shifts with the natural circadian rhythm of the body is among these factors. Age, decreased physical strength, tiredness and extent of light are among other factors that affect the level of consciousness in an individual and may lead to work related traumas. In recent years, the role of circadian rhythm in occurrence of work related traumas has been widely considered. Circadian rhythm is formed as a result of a number of clock genes in suprachiasmatic nucleus and other organs of the body. Circadian rhythm is associated with significant changes in hormone secretion and level of consciousness in an individual. Rhythms desynchrony is a phenomenon seen in those that work during the night and sleep during the day and is accompanied by increased risk of work related accidents. For example in a systematic review assessing 13 studies, it was revealed that working night shifts is associated with increased risk of work related accidents. However, there is still controversy regarding the net effect of night shifts in incidence of work related accidents. One question that has not been answered yet is that if an individual works night shifts for a long time, is their circadian rhythm affected or not? On the other hand, can using strategies that improve level of consciousness (such as using blue light in the work place decrease the incidence of these accidents? Are changes in sleep and wake conditions alone able to alter the expression

  17. Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm disturbances in Alzheimer disease

    NARCIS (Netherlands)

    van Someren, E. J.; Scherder, E. J.; Swaab, D. F.

    1998-01-01

    In patients with Alzheimer disease (AD), an irregular day-night rhythm with behavioral restlessness during the night makes a strong demand on caregivers and is among the most important reasons for institutionalization. A dysfunctioning circadian timing system is supposed to underlie the disturbance

  18. Inositol polyphosphates contribute to cellular circadian rhythms: Implications for understanding lithium's molecular mechanism.

    Science.gov (United States)

    Wei, Heather; Landgraf, Dominic; Wang, George; McCarthy, Michael J

    2018-01-11

    Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP 6 ) has effects on circadian rhythms. Using a bioluminescent reporter (Per2::luc) to measure circadian rhythms, we determined that IP 6 increased rhythm amplitude and shortened period in NIH3T3 cells. The IP 6 effect on amplitude was attenuated by selective siRNA knockdown of GSK3B and pharmacological blockade of AKT kinase. However, unlike lithium, IP 6 did not induce serine-9 phosphorylation of GSK3B. The synthesis of IP 6 involves the enzymes inositol polyphosphate multikinase (IPMK) and inositol pentakisphosphate 2-kinase (IPPK). Knockdown of Ippk had effects opposite to those of IP 6 , decreasing rhythm amplitude and lengthening period. Ipmk knockdown had few effects on rhythm alone, but attenuated the effects of lithium on rhythms. However, lithium did not change the intracellular content of IP 6 in NIH3T3 cells or neurons. Pharmacological inhibition of the IP 6 kinases (IP6K) increased rhythm amplitude and shortened period, suggesting secondary effects of inositol pyrophosphates may underlie the period shortening effect, but not the amplitude increasing effect of IP 6 . Overall, we conclude that inositol phosphates, in particular IP 6 have effects on circadian rhythms. Manipulations affecting IP 6 and related inositol phosphates may offer a novel means through which circadian rhythms can be regulated. Published by Elsevier Inc.

  19. Circadian rhythms, sleep, and performance in space.

    Science.gov (United States)

    Mallis, M M; DeRoshia, C W

    2005-06-01

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

  20. Circadian rhythm and sleep influences on digestive physiology and disorders

    OpenAIRE

    Vaughn, Bradley; Rotolo,Sean; Roth,Heidi

    2014-01-01

    Bradley V Vaughn, Sean Rotolo, Heidi L Roth Division of Sleep Medicine, Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Circadian rhythms and sleep influence a variety of physiological functions, including the digestive system. The digestive system also has intrinsic rhythms that interact dynamically with circadian rhythms. New advances in understanding the interaction of these rhythms and sleep provide the prospect of evaluating their...

  1. Peroxiredoxins are conserved markers of circadian rhythms

    Science.gov (United States)

    Edgar, Rachel S.; Green, Edward W.; Zhao, Yuwei; van Ooijen, Gerben; Olmedo, Maria; Qin, Ximing; Xu, Yao; Pan, Min; Valekunja, Utham K.; Feeney, Kevin A.; Maywood, Elizabeth S.; Hastings, Michael H.; Baliga, Nitin S.; Merrow, Martha; Millar, Andrew J.; Johnson, Carl H.; Kyriacou, Charalambos P.; O’Neill, John S.; Reddy, Akhilesh B.

    2012-01-01

    Summary Cellular life emerged ~3.7 billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles due to the Earth’s rotation. The advantage conferred upon organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation-reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterising their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription-translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular time-keeping with redox homeostatic mechanisms following the Great Oxidation Event ~2.5 billion years ago. PMID:22622569

  2. Circadian and infradian rhythms in mood.

    Science.gov (United States)

    Mitsutake, G; Otsuka, K; Cornélissen, G; Herold, M; Günther, R; Dawes, C; Burch, J B; Watson, D; Halberg, F

    2001-01-01

    The aim of this study was to assess any variation in positive, negative and total affect recorded longitudinally; to compare the results with those from prior transverse or hybrid population studies, based on the same or a different method of mood rating; and to test for any association of mood with cardiovascular, hormonal and geophysical variables monitored concomitantly. The study approach was as follows. A clinically healthy 34-year-old man filled out the positive and negative affective scale (PANAS) questionnaire five times a day for 86 days. Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) were also measured automatically at 30-minute intervals with an ambulatory monitor from May 19 to June 29, 2000, while different endpoints of heart rate variability (HRV) were also determined at 5-minute intervals from beat-to-beat electrocardiogram (ECG) monitoring for 42 days between May 3 and June 14, 2000, with only short interruptions while the subject took a shower and changed ECG tapes. Saliva samples were collected at the times of mood ratings for one month for later determination of melatonin and cortisol concentrations. Intervals of 24 hours of the record of each variable displaced in increments of 24 hours were analyzed by chronobiologic serial section at a trial period of 24 hours to assess the circadian characteristics as they changed from one day to another. Estimates of the midline-estimating statistic of rhythm (MESOR) and circadian amplitude and acrophase obtained on consecutive days were correlated among variables to assess any associations. The findings were as follows. Overall, a circadian rhythm was demonstrated for all variables. A positive association was noteworthy between the circadian amplitude of negative affect and the MESOR of both SBP (r= 0.363; P= 0.029) and DBP (r= 0.389; P= 0.019), suggesting that BP is raised in the presence of large swings in negative affect. Needing further validation was a weak association between

  3. Biomarkers for circadian rhythm disruption independent of time of day

    NARCIS (Netherlands)

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

    2015-01-01

    textabstractFrequent shift work causes disruption of the circadian rhythm and might on the long-term result in increased health risk. Current biomarkers evaluating the presence of circadian rhythm disturbance (CRD), including melatonin, cortisol and body temperature, require 24-hr ("around the

  4. Sleep and circadian rhythms in space.

    Science.gov (United States)

    Stampi, C

    1994-05-01

    This paper presents a detailed critical review of the knowledge accumulated in the last three decades concerning research on sleep, work-rest schedules, and circadian rhythms in space. The focus of the paper is preceded by a brief review of the basic principles of the human circadian system and the physiology of the sleep-wake cycle, relevant to understanding the problem of astronaut work-rest scheduling. Much of what is known is based on anecdotal reports, mission log books, and debriefing of astronauts after flights. The broad literature reviewed, which includes studies from American and Soviet space missions, as well as some studies conducted under simulated weightlessness, offers just a handful of objective studies on the physiology of sleep and circadian rhythms in space. Nevertheless, the data are remarkably consistent, and indicate that sleep can be of reasonably good quality in space. The risk of sleep loss and associated performance degradation appears to be a manageable one. However, one clear conclusion arises from this review: whatever the type of mission of flight plan, its success will depend on whether the principles of circadian and sleep-wake regulation have been taken into account during the planning phase of work-rest schedules. That is, satisfactory sleep and alertness is more likely to occur if crews maintain a reasonable (i.e., constant) relation with their normal terrestrial rhythm. This is not as easy a task as it may appear; indeed, unexpected, high-intensity operational demands have been the major cause of acute problems of sleep loss and performance degradation in space. Moreover, the growing complexity of space missions indicate that emergencies will never disappear. Therefore, one of the most important research challenges for future space missions is the development of strategies that could permit astronauts to function closest to maximal efficiency during intensive and prolonged work. Countermeasures for optimizing astronaut

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

    Science.gov (United States)

    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.

  6. Circadian rhythms of hedonic drinking behavior in mice.

    Science.gov (United States)

    Bainier, Claire; Mateo, Maria; Felder-Schmittbuhl, Marie-Paule; Mendoza, Jorge

    2017-05-04

    In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the main circadian clock, synchronized by the light-dark cycle, which generates behavioral rhythms like feeding, drinking and activity. Notwithstanding, the main role of the SCN clock on the control of all circadian rhythms has been questioned due to the presence of clock activity in many brain areas, including those implicated in the regulation of feeding and reward. Moreover, whether circadian rhythms of particular motivated behaviors exist is unknown. Here, we evaluated the spontaneous daily and circadian behavior of consumption of a sweet caloric solution (5-10% sucrose), and the effects of sucrose intake on the expression of clock genes in the mouse brain. Mice showed a daily (in a light-dark cycle) and a circadian (in constant darkness conditions) rhythm in the intake and sucrose preference with a rise for both parameters at night (or subjective night). In addition, we observed changes in the circadian day-night expression of the clock gene Per2 in the SCN, cortex and striatum of animals ingesting sucrose compared to control mice on pure water. Finally, daily rhythms of sucrose intake and preference were abolished in Per2 Brdm1 - and double Per1 -/- Per2 Brdm1 -mutant animals. These data indicate that the expression of circadian rhythms of hedonic feeding behaviors may be controlled by brain circadian clocks and Per gene expression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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    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.

  8. Circadian rhythm in Alzheimer disease after trazodone use.

    Science.gov (United States)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

    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

  10. Recent Advances in Circadian Rhythms in Cardiovascular System

    Directory of Open Access Journals (Sweden)

    Lihong eChen

    2015-04-01

    Full Text Available Growing evidence shows that intrinsic circadian clocks are tightly related to cardiovascular functions. The diurnal changes in blood pressure and heart rate are well known circadian rhythms. Endothelial function, platelet aggregation and thrombus formation exhibit circadian changes as well. The onset of many cardiovascular diseases (CVDs or events, such as myocardial infarction, stroke, arrhythmia, and sudden cardiac death, also exhibits temporal trends. Furthermore, there is strong evidence from animal models and epidemiological studies showing that disruption of circadian rhythms is a significant risk factor for many CVDs, and the intervention of CVDs may have a time dependent effect. In this mini review, we summarized recent advances in our understanding of the relationship between circadian rhythm and cardiovascular physiology and diseases including blood pressure regulation and myocardial infarction.

  11. Rhythms of mammalian body temperature can sustain peripheral circadian clocks.

    Science.gov (United States)

    Brown, Steven A; Zumbrunn, Gottlieb; Fleury-Olela, Fabienne; Preitner, Nicolas; Schibler, Ueli

    2002-09-17

    Low-amplitude temperature oscillations can entrain the phase of circadian rhythms in several unicellular and multicellular organisms, including Neurospora and Drosophila. Because mammalian body temperature is subject to circadian variations of 1 degrees C-4 degrees C, we wished to determine whether these temperature cycles could serve as a Zeitgeber for circadian gene expression in peripheral cell types. In RAT1 fibroblasts cultured in vitro, circadian gene expression could be established by a square wave temperature rhythm with a (Delta)T of 4 degrees C (12 hr 37 degrees C/12 hr 33 degrees C). To examine whether natural body temperature rhythms can also affect circadian gene expression, we first measured core body temperature cycles in the peritoneal cavities of mice by radiotelemetry. We then reproduced these rhythms with high precision in the liquid medium of cultured fibroblasts for several days by means of a homemade computer-driven incubator. While these "in vivo" temperature rhythms were incapable of establishing circadian gene expression de novo, they could maintain previously induced rhythms for multiple days; by contrast, the rhythms of control cells kept at constant temperature rapidly dampened. Moreover, circadian oscillations of environmental temperature could reentrain circadian clocks in the livers of mice, probably via the changes they imposed upon both body temperature and feeding behavior. Interestingly, these changes in ambient temperature did not affect the phase of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. We postulate that both endogenous and environmental temperature cycles can participate in the synchronization of peripheral clocks in mammals.

  12. Endotoxin Disrupts Circadian Rhythms in Macrophages via Reactive Oxygen Species.

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    Yusi Wang

    Full Text Available The circadian clock is a transcriptional network that functions to regulate the expression of genes important in the anticipation of changes in cellular and organ function. Recent studies have revealed that the recognition of pathogens and subsequent initiation of inflammatory responses are strongly regulated by a macrophage-intrinsic circadian clock. We hypothesized that the circadian pattern of gene expression might be influenced by inflammatory stimuli and that loss of circadian function in immune cells can promote pro-inflammatory behavior. To investigate circadian rhythms in inflammatory cells, peritoneal macrophages were isolated from mPer2luciferase transgenic mice and circadian oscillations were studied in response to stimuli. Using Cosinor analysis, we found that LPS significantly altered the circadian period in peritoneal macrophages from mPer2luciferase mice while qPCR data suggested that the pattern of expression of the core circadian gene (Bmal1 was disrupted. Inhibition of TLR4 offered protection from the LPS-induced impairment in rhythm, suggesting a role for toll-like receptor signaling. To explore the mechanisms involved, we inhibited LPS-stimulated NO and superoxide. Inhibition of NO synthesis with L-NAME had no effect on circadian rhythms. In contrast, inhibition of superoxide with Tempol or PEG-SOD ameliorated the LPS-induced changes in circadian periodicity. In gain of function experiments, we found that overexpression of NOX5, a source of ROS, could significantly disrupt circadian function in a circadian reporter cell line (U2OS whereas iNOS overexpression, a source of NO, was ineffective. To assess whether alteration of circadian rhythms influences macrophage function, peritoneal macrophages were isolated from Bmal1-KO and Per-TKO mice. Compared to WT macrophages, macrophages from circadian knockout mice exhibited altered balance between NO and ROS release, increased uptake of oxLDL and increased adhesion and migration

  13. Establishment of human cell lines showing circadian rhythms of bioluminescence.

    Science.gov (United States)

    Yoshikawa, Aki; Shimada, Hiroko; Numazawa, Kahori; Sasaki, Tsukasa; Ikeda, Masaaki; Kawashima, Minae; Kato, Nobumasa; Tokunaga, Katsushi; Ebisawa, Takashi

    2008-11-28

    We have established human retinal pigment epithelial cell lines stably expressing the luciferase gene, driven by the human Bmal1 promoter, to obtain human-derived cells that show circadian rhythms of bioluminescence after dexamethasone treatment. The average circadian period of bioluminescence for the obtained clones was 24.07+/-0.48 h. Lithium (10 mM) in the medium significantly lengthened the circadian period of bioluminescence, which is consistent with previous reports, while 2 mM or 5 mM lithium had no effect. This is the first report on the establishment of human-derived cell lines that proliferate infinitely and show circadian rhythms of bioluminescence, and also the first to investigate the effects of low-dose lithium on the circadian rhythms of human-derived cells in vitro. The established cells will be useful for various in vitro studies of human circadian rhythms and for the development of new therapies for human disorders related to circadian rhythm disturbances.

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

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    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

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

    Science.gov (United States)

    Li, Ying; Liu, Zengrong

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

  16. Circadian rhythm and sleep influences on digestive physiology and disorders

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    Vaughn BV

    2014-09-01

    Full Text Available Bradley V Vaughn, Sean Rotolo, Heidi L Roth Division of Sleep Medicine, Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Circadian rhythms and sleep influence a variety of physiological functions, including the digestive system. The digestive system also has intrinsic rhythms that interact dynamically with circadian rhythms. New advances in understanding the interaction of these rhythms and sleep provide the prospect of evaluating their role in normal physiology and the link of their disruption to pathological conditions. Recent work has demonstrated that sleep and circadian factors influence appetite, nutrient absorption, and metabolism. Disruption of sleep and circadian rhythms may increase vulnerability to digestive disorders, including reflux, ulcers, inflammatory bowel issues, irritable bowel disease, and gastrointestinal cancer. As our knowledge of the link between circadian timing and gastrointestinal physiology grows, so do our opportunities to provide promising diagnostic and therapeutic approaches for gastrointestinal disorders. Keywords: digestion, digestive diseases, gastrointestinal reflux, sleep, circadian rhythm 

  17. Discrepancy between circadian rhythms of inulin and creatinine clearance

    NARCIS (Netherlands)

    van Acker, B. A.; Koomen, G. C.; Koopman, M. G.; Krediet, R. T.; Arisz, L.

    1992-01-01

    To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm

  18. The importance of hormonal circadian rhythms in daily feeding patterns

    NARCIS (Netherlands)

    Boumans, Iris J.M.M.; Boer, de Imke J.M.; Hofstede, Gert Jan; Fleur, la Susanne E.; Bokkers, Eddy

    2017-01-01

    The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is,

  19. Circadian rhythm in succinate dehydrogenase activity in Neurospora crassa

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    Claudia Patricia Álvarez Barón

    2004-07-01

    Full Text Available Neurospora crassa is a widely studied model of circadian rhythmicity. In this fungus, metabolism is controlled by multiple factors which include development, medium characteristics and the circadian clock. The study of the circadian control of metabolism in this fungus could be masked by the use of restrictive media that inhibit growth and development. In this report, the presence of a circadian rhythm in the activity of the enzyme Succinate Dehydrogenase in Neurospora crassa is demonstrated. Rhythmic and arrhythmic Neurospora strains were grown in complete medium without conidiation restriction. A circadian change in the enzymatic activity was found with high values in hours corresponding to the night and a low level during the day. This finding highlights the importance of deeper studies in the circadian control of metabolism in this fungus, given the existence of multiple pathways of regulation of metabolic enzymes and a circadian clock control at the transcriptional and post-transcriptional levels.

  20. Sleep, circadian rhythm and body weight: parallel developments.

    Science.gov (United States)

    Westerterp-Plantenga, Margriet S

    2016-11-01

    Circadian alignment is crucial for body-weight management, and for metabolic health. In this context, circadian alignment consists of alignment of sleep, meal patterns and physical activity. During puberty a significant reduction in sleep duration occurs, and pubertal status is inversely associated with sleep duration. A consistent inverse association between habitual sleep duration and body-weight development occurs, independent of possible confounders. Research on misalignment reveals that circadian misalignment affects sleep-architecture and subsequently disturbs glucose-insulin metabolism, substrate oxidation, leptin- and ghrelin concentrations, appetite, food reward, hypothalamic-pituitary-adrenal-axis activity and gut-peptide concentrations enhancing positive energy balance and metabolic disturbance. Not only aligning meals and sleep in a circadian way is crucial, also regular physical activity during the day strongly promotes the stability and amplitude of circadian rhythm, and thus may serve as an instrument to restore poor circadian rhythms. Endogenicity may play a role in interaction of these environmental variables with a genetic predisposition. In conclusion, notwithstanding the separate favourable effects of sufficient daily physical activity, regular meal patterns, sufficient sleep duration and quality sleep on energy balance, the overall effect of the amplitude and stability of the circadian rhythm, perhaps including genetic predisposition, may integrate the separate effects in an additive way.

  1. Sleep, Circadian Rhythms, and Performance During Space Shuttle Missions

    Science.gov (United States)

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

    2003-01-01

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

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

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    M.A. Quera Salva

    2012-04-01

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

  3. Are circadian rhythms new pathways to understand Autism Spectrum Disorder?

    Science.gov (United States)

    Geoffray, M-M; Nicolas, A; Speranza, M; Georgieff, N

    2016-11-01

    Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep-wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin. This first point raises the hypothesis that circadian rhythms could have an implication in ASD etiology. Moreover, circadian rhythms are generated by auto-regulatory genetic feedback loops, driven by transcription factors CLOCK and BMAL1, who drive transcription daily patterns of a wide number of clock-controlled genes (CCGs) in different cellular contexts across tissues. Among these, are some CCGs coding for synapses molecules associated to ASD susceptibility. Furthermore, evidence emerges about circadian rhythms control of time brain development processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-03-01

    The rotation of the earth and associated alternating cycles of light and dark--the basis of our circadian rhythms--are fundamental to human biology and culture. However, it was not until 1971 that researchers first began to describe the molecular mechanisms for the circadian system. During the past few years, groundbreaking research has revealed a multitude of circadian genes affecting a variety of clinical diseases, including diabetes, obesity, sepsis, cardiac ischemia, and sudden cardiac death. Anesthesiologists, in the operating room and intensive care units, manage these diseases on a daily basis as they significantly affect patient outcomes. Intriguingly, sedatives, anesthetics, and the intensive care unit environment have all been shown to disrupt the circadian system in patients. In the current review, we will discuss how newly acquired knowledge of circadian rhythms could lead to changes in clinical practice and new therapeutic concepts. © The Author(s) 2014.

  5. Synchronization of biological clock neurons by light and peripheral feedback systems promotes circadian rhythms and health

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    Ashna eRamkisoensing

    2015-06-01

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

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

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    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.

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

    Science.gov (United States)

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

    1997-01-01

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

  8. Self-sustained circadian rhythm in cultured human mononuclear cells isolated from peripheral blood.

    Science.gov (United States)

    Ebisawa, Takashi; Numazawa, Kahori; Shimada, Hiroko; Izutsu, Hiroyuki; Sasaki, Tsukasa; Kato, Nobumasa; Tokunaga, Katsushi; Mori, Akio; Honma, Ken-ichi; Honma, Sato; Shibata, Shigenobu

    2010-02-01

    Disturbed circadian rhythmicity is associated with human diseases such as sleep and mood disorders. However, study of human endogenous circadian rhythm is laborious and time-consuming, which hampers the elucidation of diseases. It has been reported that peripheral tissues exhibit circadian rhythmicity as the suprachiasmatic nucleus-the center of the biological clock. We tried to study human circadian rhythm using cultured peripheral blood mononuclear cells (PBMCs) obtained from a single collection of venous blood. Activated human PBMCs showed self-sustained circadian rhythm of clock gene expression, which indicates that they are useful for investigating human endogenous circadian rhythm.

  9. Studies on circadian rhythm disturbances and melatonin in delirium

    NARCIS (Netherlands)

    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

  10. Adaptive Significance of Circadian Rhythms-Biological Clocks and ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 1. Adaptive Significance of Circadian Rhythms - Biological Clocks and Darwinian Fitness in Cyanobacteria. V Sheeba Vijay Kumar Sharma Amitabh Joshi. Research News Volume 4 Issue 1 January 1999 pp 73-75 ...

  11. Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin.

    Science.gov (United States)

    Lopes, C; deLyra, J L; Markus, R P; Mariano, M

    1997-09-01

    Biological rhythms are detected in a variety of physiological and pathological conditions in man and animals, such as rheumatoid arthritis and asthma. Here we describe a circadian rhythm in experimental infectious and non-infectious granuloma. After 30 days of BCG (Bacillus Calmette-Guerin) or nystatin inoculation in the left hind foot of C57B1/6 mice, there is an oscillation with a period of approximately 24 hr in the variation of paw thickness, indicating a circadian rhythm. The acrophase occurred during the light phase, between 9:00 and 13:00 hr, while the nadir occurred in the dark phase, between 21:00 and 01:00 hr. The vascular permeability around the granulomatous lesions was higher at 12:00 hr than at 24:00 hr. This is in agreement with the observation that the thickness of a paw with granulomatous lesion is larger during the light phase. This rhythmic variation was eliminated by either pinealectomy or superior cervical ganglionectomy, which greatly reduce melatonin levels in the blood. Nocturnal replacement of melatonin in pinealectomized mice led to the re-establishment of the circadian rhythm. Thus, the rhythm of the granulomatous lesion is due to the rhythmic melatonin release by the pineal gland. This approach opens new questions regarding the modulation of chronic inflammation in inflammatory diseases that present rhythmic symptoms throughout the day.

  12. Circadian rhythms, time-restricted feeding, and healthy aging.

    Science.gov (United States)

    Manoogian, Emily N C; Panda, Satchidananda

    2017-10-01

    Circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function, and behavior. These endogenous rhythms dampen with age and thus compromise temporal coordination. Feeding-fasting patterns are an external cue that profoundly influence the robustness of daily biological rhythms. Erratic eating patterns can disrupt the temporal coordination of metabolism and physiology leading to chronic diseases that are also characteristic of aging. However, sustaining a robust feeding-fasting cycle, even without altering nutrition quality or quantity, can prevent or reverse these chronic diseases in experimental models. In humans, epidemiological studies have shown erratic eating patterns increase the risk of disease, whereas sustained feeding-fasting cycles, or prolonged overnight fasting, is correlated with protection from breast cancer. Therefore, optimizing the timing of external cues with defined eating patterns can sustain a robust circadian clock, which may prevent disease and improve prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Interaction between circadian rhythms and stress

    Directory of Open Access Journals (Sweden)

    C.E. Koch

    2017-02-01

    Full Text Available Life on earth has adapted to the day-night cycle by evolution of internal, so-called circadian clocks that adjust behavior and physiology to the recurring changes in environmental conditions. In mammals, a master pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus receives environmental light information and synchronizes peripheral tissues and central non-SCN clocks to geophysical time. Regulatory systems such as the hypothalamus-pituitary-adrenal (HPA axis and the autonomic nervous system (ANS, both being important for the regulation of stress responses, receive strong circadian input. In this review, we summarize the interaction of circadian and stress systems and the resulting physiological and pathophysiological consequences. Finally, we critically discuss the relevance of rodent stress studies for humans, addressing complications of translational approaches and offering strategies to optimize animal studies from a chronobiological perspective.

  14. Circadian rhythms in handwriting kinematics and legibility

    NARCIS (Netherlands)

    Jasper, Isabelle; Gordijn, Marijke; Haeussler, Andreas; Hermsdoerfer, Joachim

    The aim of the present study was to analyze the circadian rhythmicity in handwriting kinematics and legibility and to compare the performance between Dutch and German writers. Two subject groups underwent a 40 h sleep deprivation protocol under Constant Routine conditions either in Groningen (10

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Evidence of circadian rhythms in non-photosynthetic bacteria?

    Directory of Open Access Journals (Sweden)

    Soriano María I

    2010-09-01

    Full Text Available Abstract Examples of circadian rhythms have been described in eukaryotic organisms and in photosynthetic bacteria, but direct proof of their existence in other prokaryotes is limited and has been largely ignored. The aim of this article is to review existing evidence and to present preliminary results that suggest that the heterotrophic bacterium Pseudomonas putida shows regular variations in its growth pattern synchronized with light/darkness cycles. We put forward the hypothesis that circadian regulation of certain processes can take place in non-photosynthetic prokaryotes and may represent an adaptative advantage in specific environments.

  17. Circadian rhythms and new options for novel anticancer therapies

    Directory of Open Access Journals (Sweden)

    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

  18. Links between circadian rhythms and psychiatric disease

    Directory of Open Access Journals (Sweden)

    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.

  19. Circadian rhythm of temperature selection in a nocturnal lizard.

    Science.gov (United States)

    Refinetti, R; Susalka, S J

    1997-08-01

    We recorded body temperature and locomotor activity of Tokay geckos (Gekko gecko) with free access to a heat source under a 14:10 light-dark cycle and in constant darkness. Under the light-dark cycle, the lizards selected higher temperatures during the light phase, when locomotor activity was less intense. Rhythmicity in temperature selection was transiently disrupted but later resumed when the animals were placed in constant darkness. These results demonstrate the existence of a circadian rhythm of temperature selection in nocturnal ectotherms and extend previous findings of a temporal mismatch between the rhythms of locomotor activity and temperature selection in nocturnal rodents.

  20. Circadian rhythm of proteinuria: consequences of the use of urinary protein:creatinine ratios

    NARCIS (Netherlands)

    Koopman, M. G.; Krediet, R. T.; Koomen, G. C.; Strackee, J.; Arisz, L.

    1989-01-01

    Proteinuria in patients with glomerular disease has a circadian rhythm, but for creatinine such a rhythm is either absent or of low amplitude. We found in 18 of 23 admitted patients (group I) and in seven outpatients (group II) a marked circadian rhythm of the protein: creatinine ratio. Estimates of

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

    NARCIS (Netherlands)

    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

  2. CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis.

    Science.gov (United States)

    Lin, Ran; Mo, Yan; Zha, Haihong; Qu, Zhipeng; Xie, Pancheng; Zhu, Zheng-Jiang; Xu, Ying; Xiong, Yue; Guan, Kun-Liang

    2017-10-05

    In addition to responding to environmental entrainment with diurnal variation, metabolism is also tightly controlled by cell-autonomous circadian clock. Extensive studies have revealed key roles of transcription in circadian control. Post-transcriptional regulation for the rhythmic gating of metabolic enzymes remains elusive. Here, we show that arginine biosynthesis and subsequent ureagenesis are collectively regulated by CLOCK (circadian locomotor output cycles kaput) in circadian rhythms. Facilitated by BMAL1 (brain and muscle Arnt-like protein), CLOCK directly acetylates K165 and K176 of argininosuccinate synthase (ASS1) to inactivate ASS1, which catalyzes the rate-limiting step of arginine biosynthesis. ASS1 acetylation by CLOCK exhibits circadian oscillation in human cells and mouse liver, possibly caused by rhythmic interaction between CLOCK and ASS1, leading to the circadian regulation of ASS1 and ureagenesis. Furthermore, we also identified NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as acetylation substrates of CLOCK. Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [Seasons, circadian rhythms, sleep and suicidal behaviors vulnerability].

    Science.gov (United States)

    Benard, V; Geoffroy, P A; Bellivier, F

    2015-09-01

    Suicidal behaviors are common in the general population and are so a major public health problem. In order to improve suicide prevention and to reduce the mortality by suicide, it appears essential to better identify suicide risk factors. Seasonality, circadian rhythms and sleep abnormalities have been already associated with numerous psychiatric disorders. This review aimed to characterize the associations between seasonality, circadian rhythms, sleep and suicidal behaviors including suicide attempts and completed suicides. We conducted a literature search between 1973 and 2015 in PubMed databases using the following terms: ("suicide" OR "suicidality" OR "suicide attempts" OR "suicidal behavior") AND ("circadian rhythms" OR "seasons" OR "sleep"). Many studies confirm a specific seasonality for suicide with a higher peak of suicides in spring for both sex and a lower peak in autumn especially for women. This distribution seems to correlate with depressive symptoms (especially for the autumn peak), gender and different types of suicide. Regarding gender and type of suicide differences, males more commonly commit violent suicide with a higher rate of suicides in spring. Suicide behaviors appear to be influenced by climatic and biological factors like sunshine, daylight cycles, temperature, air pollutants, viruses, parasites and aeroallergens. Circadian variations exist in suicide rates depending on age with a morning peak for elder and an evening peak for youth. In addition, completed suicide peak in early morning whereas suicide attempts peak rather in later afternoon. Several biomarkers dysregulation like melatonin, serotonin and cortisol may be implicated in suicide circadian variations. Furthermore, specific sleep disorders like insomnia, nightmares and sleep deprivation are common risk factors of suicide and possibly independently of the presence of depressive symptoms. Finally, the efficacy of chronotherapeutics (such as luminotherapy, dark therapy, sleep

  4. Circadian Rhythm of Osteocalcin in the Maxillomandibular Complex

    Science.gov (United States)

    Gafni, Y.; Ptitsyn, A.A.; Zilberman, Y.; Pelled, G.; Gimble, J.M.; Gazit, D.

    2009-01-01

    The human body displays central circadian rhythms of activity. Recent findings suggest that peripheral tissues, such as bone, possess their own circadian clocks. Studies have shown that osteocalcin protein levels oscillate over a 24-hour period, yet the specific skeletal sites involved and its transcriptional profile remain unknown. The current study aimed to test the hypothesis that peripheral circadian mechanisms regulate transcription driven by the osteocalcin promoter. Transgenic mice harboring the human osteocalcin promoter linked to a luciferase reporter gene were used. Mice of both genders and various ages were analyzed non-invasively at sequential times throughout 24-hour periods. Statistical analyses of luminescent signal intensity of osteogenic activity from multiple skeletal sites indicated a periodicity of ~ 24 hrs. The maxillomandibular complex displayed the most robust oscillatory pattern. These findings have implications for dental treatments in orthodontics and maxillofacial surgery, as well as for the mechanisms underlying bone remodeling in the maxillomandibular complex. PMID:19131316

  5. The Role of Mammalian Glial Cells in Circadian Rhythm Regulation

    Directory of Open Access Journals (Sweden)

    Donají Chi-Castañeda

    2017-01-01

    Full Text Available Circadian rhythms are biological oscillations with a period of about 24 hours. These rhythms are maintained by an innate genetically determined time-keeping system called the circadian clock. A large number of the proteins involved in the regulation of this clock are transcription factors controlling rhythmic transcription of so-called clock-controlled genes, which participate in a plethora of physiological functions in the organism. In the brain, several areas, besides the suprachiasmatic nucleus, harbor functional clocks characterized by a well-defined time pattern of clock gene expression. This expression rhythm is not restricted to neurons but is also present in glia, suggesting that these cells are involved in circadian rhythmicity. However, only certain glial cells fulfill the criteria to be called glial clocks, namely, to display molecular oscillators based on the canonical clock protein PERIOD, which depends on the suprachiasmatic nucleus for their synchronization. In this contribution, we summarize the current information about activity of the clock genes in glial cells, their potential role as oscillators as well as clinical implications.

  6. Familial circadian rhythm disorder in the diurnal primate, Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Irina V Zhdanova

    Full Text Available In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment.

  7. Impacts of nurses’ circadian rhythm sleep disorders, fatigue, and depression on medication administration errors

    Directory of Open Access Journals (Sweden)

    Abdelbaset M. Saleh

    2014-01-01

    Conclusions: Medication administration errors, fatigue and depression were all significantly affected by circadian sleep disorders. An administration’s control of work flow to provide convenient sleep hours will help in improving sleep circadian rhythms and consequently minimize these problems.

  8. Circadian Rhythms and Sleep inDrosophila melanogaster.

    Science.gov (United States)

    Dubowy, Christine; Sehgal, Amita

    2017-04-01

    The advantages of the model organism Drosophila melanogaster , including low genetic redundancy, functional simplicity, and the ability to conduct large-scale genetic screens, have been essential for understanding the molecular nature of circadian (∼24 hr) rhythms, and continue to be valuable in discovering novel regulators of circadian rhythms and sleep. In this review, we discuss the current understanding of these interrelated biological processes in Drosophila and the wider implications of this research. Clock genes period and timeless were first discovered in large-scale Drosophila genetic screens developed in the 1970s. Feedback of period and timeless on their own transcription forms the core of the molecular clock, and accurately timed expression, localization, post-transcriptional modification, and function of these genes is thought to be critical for maintaining the circadian cycle. Regulators, including several phosphatases and kinases, act on different steps of this feedback loop to ensure strong and accurately timed rhythms. Approximately 150 neurons in the fly brain that contain the core components of the molecular clock act together to translate this intracellular cycling into rhythmic behavior. We discuss how different groups of clock neurons serve different functions in allowing clocks to entrain to environmental cues, driving behavioral outputs at different times of day, and allowing flexible behavioral responses in different environmental conditions. The neuropeptide PDF provides an important signal thought to synchronize clock neurons, although the details of how PDF accomplishes this function are still being explored. Secreted signals from clock neurons also influence rhythms in other tissues. SLEEP is, in part, regulated by the circadian clock, which ensures appropriate timing of sleep, but the amount and quality of sleep are also determined by other mechanisms that ensure a homeostatic balance between sleep and wake. Flies have been useful

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

  11. Biomarkers for circadian rhythm disruption independent of time of day.

    Directory of Open Access Journals (Sweden)

    Kirsten C G Van Dycke

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

  12. Therapeutic applications of circadian rhythms for the cardiovascular system

    Science.gov (United States)

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

    2015-01-01

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

  13. SLEEP AND CIRCADIAN RHYTHM DISORDERS IN PARKINSON'S DISEASE.

    Science.gov (United States)

    Gros, Priti; Videnovic, Aleksandar

    2017-09-01

    Sleep disorders are among the most challenging non-motor features of Parkinson's disease (PD) and significantly affect quality of life. Research in this field has gained recent interest among clinicians and scientists and is rapidly evolving. This review is dedicated to sleep and circadian dysfunction associated with PD. Most primary sleep disorders may co-exist with PD; majority of these disorders have unique features when expressed in the PD population. We discuss the specific considerations related to the common sleep problems in Parkinson's disease including insomnia, rapid eye movement sleep behavior disorder, restless legs syndrome, sleep disordered breathing, excessive daytime sleepiness and circadian rhythm disorders. Within each of these sleep disorders, we present updated definitions, epidemiology, etiology, diagnosis, clinical implications and management. Furthermore, areas of potential interest for further research are outlined.

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

    Science.gov (United States)

    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.

  15. Circadian rhythm disorders among adolescents: assessment and treatment options.

    Science.gov (United States)

    Bartlett, Delwyn J; Biggs, Sarah N; Armstrong, Stuart M

    2013-10-21

    Delayed sleep phase disorder (DSPD) - a circadian rhythm sleep disorder - is most commonly seen in adolescents. The differential diagnosis between DSPD and conventional psychophysiological insomnia is important for correct therapeutic intervention. Adolescent DSPD sleep duration is commonly 9 hours or more. Depression may be comorbid with DSPD. DSPD has a negative impact on adolescent academic performance. DSPD treatments include bright light therapy, chronotherapeutic regimens, and administration of melatonin as a chronobiotic (as distinct from a soporific). Attention to non-photic and extrinsic factors including healthy sleep parameters is also important to enable better sleep and mood outcomes in adolescents.

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

    Science.gov (United States)

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

    2017-08-01

    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.

  17. AMPK regulates circadian rhythms in a tissue- and isoform-specific manner.

    Directory of Open Access Journals (Sweden)

    Jee-Hyun Um

    2011-03-01

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

  18. Circadian rhythm of rectal temperature during sleep deprivation with modafinil.

    Science.gov (United States)

    Launay, Jean-Claude; Savourey, Gustave; Guinet, Angélique; Lallement, Guy; Besnard, Yves; Bittel, Jacques

    2002-10-01

    Sleep deprivation (SD) induces many adverse psychological and physiological effects, particularly on vigilance and the thermoregulatory system. The drug modafinil appears to suppress or diminish the harmful effects on vigilance. However, the effects of modafinil combined with SD on the circadian rhythm of core temperature are not well established. We studied the circadian rhythm of rectal temperature (CRTre) during 62 h of SD alone or with three dosage levels of modafinil. Six men underwent repeated SD experiments lasting 7 d each, including a 24-h control period, 62 h of SD, and a 24-h recovery period. Experiments were repeated four times in mixed order for placebo and three levels of modafinil (50, 150, or 300 mg x 24 h(-1)). The Tre was recorded each minute throughout the experiment and the CRTre was studied by the single cosinor method. Independent of modafinil, SD increased the mesor (p modafinil, but not the higher doses, induced a lower mesor (p modafinil on core temperature. The hyperthermic effect reported in the literature for SD with modafinil may actually result from the sleep deprivation alone.

  19. Wavelet-based analysis of circadian behavioral rhythms.

    Science.gov (United States)

    Leise, Tanya L

    2015-01-01

    The challenging problems presented by noisy biological oscillators have led to the development of a great variety of methods for accurately estimating rhythmic parameters such as period and amplitude. This chapter focuses on wavelet-based methods, which can be quite effective for assessing how rhythms change over time, particularly if time series are at least a week in length. These methods can offer alternative views to complement more traditional methods of evaluating behavioral records. The analytic wavelet transform can estimate the instantaneous period and amplitude, as well as the phase of the rhythm at each time point, while the discrete wavelet transform can extract the circadian component of activity and measure the relative strength of that circadian component compared to those in other frequency bands. Wavelet transforms do not require the removal of noise or trend, and can, in fact, be effective at removing noise and trend from oscillatory time series. The Fourier periodogram and spectrogram are reviewed, followed by descriptions of the analytic and discrete wavelet transforms. Examples illustrate application of each method and their prior use in chronobiology is surveyed. Issues such as edge effects, frequency leakage, and implications of the uncertainty principle are also addressed. © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Li, Qianshu; Lang, Xiufeng

    2008-03-15

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

  1. Normalizing effect of bright light therapy on temperature circadian rhythm in patients with eating disorders.

    Science.gov (United States)

    Yamamotová, Anna; Papezová, Hana; Vevera, Jan

    2008-02-01

    Light and food are important synchronizers of circadian rhythmicity. In eating disorders, the circadian rhythms of food intake and temperature are abnormal. We analyzed the effect of the morning light application on the circadian rhythm of tympanic temperature and its association with hunger and mood changes in the sample of 25 female patients hospitalized with DSM-IV diagnosis of eating disorders (14 bulimia nervosa and 11 anorexia nervosa) and in 6 healthy women. Light therapy reduced interindividual variability of the temperature acrophase, synchronized the temperature and hunger rhythms and showed an antidepressant effect on patients with eating disorders. Bright light therapy normalized the circadian rhythm of body temperature in both anorexic and bulimic patients: phase advanced rhythm was delayed and phase delayed rhythm was advanced. In contrast with anorexic patients, the majority of bulimic patients had normal temperature rhythm before the therapy and this rhythm was not changed by the therapy. The light therapy normalized temperature circadian rhythm in patient with eating disorders. We hypothesize that the light therapy can also contribute to improvement of pathological eating pattern because of the functional connections between light and food entrained oscillators. The light may help to restore the irregular circadian rhythmicity induced by chaotic food intake.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. Circadian sleep-wake rhythm of older adults with intellectual disabilities

    NARCIS (Netherlands)

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

    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

  4. Circadian rhythm, sleep pattern, and metabolic consequences: an overview on cardiovascular risk factors.

    Science.gov (United States)

    Machado, Roberta Marcondes; Koike, Marcia Kiyomi

    2014-04-01

    Sleep duration is a risk factor for cardiovascular disease. Alteration in sleep pattern can induce the loss of circadian rhythmicity. Chronically, this desynchronization between endogenous rhythm and behavioral cycles can lead to an adverse metabolic profile, a proinflammatory condition and can increase the risk of cardiovascular disease. The circadian cycle can vary due to environmental cues. The circadian pacemaker is located in the suprachiasmatic nuclei; this central clock coordinates the circadian rhythm in the central nervous system and peripheral tissues. The mechanisms involved in sleep disturbance, circadian misalignment and adverse metabolic effects have yet to be fully elucidated. This review looks over the association among sleep alteration, circadian rhythm and the development of risk factors implicated in cardiovascular disease.

  5. Circadian Rhythm Disturbances in Patients with Alzheimer's Disease: A Review

    Directory of Open Access Journals (Sweden)

    Dawit A. Weldemichael

    2010-01-01

    Full Text Available Circadian Rhythm Disturbances (CRDs affect as many as a quarter of Alzheimer's disease (AD patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients.

  6. Circadian rhythms on skin function of hairless rats: light and thermic influences.

    Science.gov (United States)

    Flo, Ana; Díez-Noguera, Antoni; Calpena, Ana C; Cambras, Trinitat

    2014-03-01

    Circadian rhythms are present in most functions of living beings. We have demonstrated the presence of circadian rhythms in skin variables (transepidermal water loss, TEWL; stratum corneum hydration, SCH; and skin temperature) in hairless rats under different environmental conditions of light and temperature. Circadian rhythms in TEWL and SCH showed mean amplitudes of about 20% and 14% around the mean, respectively, and appeared under light-dark cycles as well as under constant darkness. Environmental temperature was able to override TEWL, but not SCH rhythm, evidencing the dependency of TEWL on the temperature. Mean daily values of TEWL and SCH, and also the amplitude of TEWL rhythm, increased with the age of the animal. Under constant light, situation that induces arrhythmicity in rats, SCH and TEWL were inversely correlated. The results suggest the importance to take into account the functional skin rhythms in research in dermatological sciences. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Gravity and thermoregulation: metabolic changes and circadian rhythms

    Science.gov (United States)

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

    2000-01-01

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

  8. Sleep Disorders: Circadian Rhythm Sleep-Wake Disorders.

    Science.gov (United States)

    Burman, Deepa

    2017-09-01

    Shift work sleep disorder is a common problem in industrialized countries because of the need for occupations and services to continue to function 24 hours/day. Approximately 20% of employed adults in the United States are engaged in shift work. Shift work sleep disorder is diagnosed if there is a report of insomnia or excessive sleepiness for at least 3 months associated with a recurring work schedule that overlaps the usual time for sleep. Shift work is associated with an increased occurrence of metabolic disorders, such as insulin resistance, diabetes, dyslipidemia, and metabolic syndrome, and it has been implicated in weight gain and cognitive impairment. There is evidence of increased absenteeism in night workers compared with day workers. A planned sleep schedule, timed bright light exposure, timed melatonin administration, and stimulants or drugs promoting alertness can be used to manage shift work sleep disorder. Jet lag is characterized by a misalignment between internal circadian rhythms and local time caused by rapid travel across at least two time zones. Not all travelers experience jet lag; risk factors include age, number of time zones crossed, and circadian preference. Management includes timed melatonin along with optional timed and dosed bright light exposure. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  9. Circadian rhythm of breath hydrogen in young women.

    Science.gov (United States)

    Kagaya, M; Iwata, M; Toda, Y; Nakae, Y; Kondo, T

    1998-08-01

    Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of alpha-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21-23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, alpha-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 +/- 3.9 ppm (mean +/- SE), which did not differ from the value for the previous night. Alpha-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 +/- 2.4 ppm (P Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Implications of disturbances in circadian rhythms for cardiovascular health: A new frontier in free radical biology.

    Science.gov (United States)

    Khaper, Neelam; Bailey, Craig D C; Ghugre, Nilesh R; Reitz, Cristine; Awosanmi, Zikra; Waines, Ryan; Martino, Tami A

    2017-11-13

    Cell autonomous circadian "clock" mechanisms are present in virtually every organ, and generate daily rhythms that are important for normal physiology. This is especially relevant to the cardiovascular system, for example the circadian mechanism orchestrates rhythms in heart rate, blood pressure, cardiac contractility, metabolism, gene and protein abundance over the 24-h day and night cycles. Conversely, disturbing circadian rhythms (e.g. via shift work, sleep disorders) increases cardiovascular disease risk, and exacerbates cardiac remodelling and worsens outcome. Notably, reactive oxygen species (ROS) are important contributors to heart disease, especially the pathophysiologic damage that occurs after myocardial infarction (MI, heart attack). However, little is known about how the circadian mechanism, or rhythm desynchrony, is involved in these key pathologic stress responses. This review summarizes the current knowledge on circadian rhythms in the cardiovascular system, and the implications of rhythm disturbances for cardiovascular health. Furthermore, we highlight how free radical biology coincides with the pathogenesis of myocardial repair and remodelling after MI, and indicate a role for the circadian system in the oxidative stress pathways in the heart and brain after MI. This fusion of circadian biology with cardiac oxidative stress pathways is novel, and offers enormous potential for improving our understanding and treatment of heart disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Estimation of Circadian Body Temperature Rhythm Based on Heart Rate in Healthy, Ambulatory Subjects.

    Science.gov (United States)

    Sim, Soo Young; Joo, Kwang Min; Kim, Han Byul; Jang, Seungjin; Kim, Beomoh; Hong, Seungbum; Kim, Sungwan; Park, Kwang Suk

    2017-03-01

    Core body temperature is a reliable marker for circadian rhythm. As characteristics of the circadian body temperature rhythm change during diverse health problems, such as sleep disorder and depression, body temperature monitoring is often used in clinical diagnosis and treatment. However, the use of current thermometers in circadian rhythm monitoring is impractical in daily life. As heart rate is a physiological signal relevant to thermoregulation, we investigated the feasibility of heart rate monitoring in estimating circadian body temperature rhythm. Various heart rate parameters and core body temperature were simultaneously acquired in 21 healthy, ambulatory subjects during their routine life. The performance of regression analysis and the extended Kalman filter on daily body temperature and circadian indicator (mesor, amplitude, and acrophase) estimation were evaluated. For daily body temperature estimation, mean R-R interval (RRI), mean heart rate (MHR), or normalized MHR provided a mean root mean square error of approximately 0.40 °C in both techniques. The mesor estimation regression analysis showed better performance than the extended Kalman filter. However, the extended Kalman filter, combined with RRI or MHR, provided better accuracy in terms of amplitude and acrophase estimation. We suggest that this noninvasive and convenient method for estimating the circadian body temperature rhythm could reduce discomfort during body temperature monitoring in daily life. This, in turn, could facilitate more clinical studies based on circadian body temperature rhythm.

  13. Medical Students Circadian Sleep Rhythms and Academic Performance

    Directory of Open Access Journals (Sweden)

    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. Topological specificity and hierarchical network of the circadian calcium rhythm in the suprachiasmatic nucleus.

    Science.gov (United States)

    Enoki, Ryosuke; Kuroda, Shigeru; Ono, Daisuke; Hasan, Mazahir T; Ueda, Tetsuo; Honma, Sato; Honma, Ken-ichi

    2012-12-26

    The circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is a hierarchical multioscillator system in which neuronal networks play crucial roles in expressing coherent rhythms in physiology and behavior. However, our understanding of the neuronal network is still incomplete. Intracellular calcium mediates the input signals, such as phase-resetting stimuli, to the core molecular loop involving clock genes for circadian rhythm generation and the output signals from the loop to various cellular functions, including changes in neurotransmitter release. Using a unique large-scale calcium imaging method with genetically encoded calcium sensors, we visualized intracellular calcium from the entire surface of SCN slice in culture including the regions where autonomous clock gene expression was undetectable. We found circadian calcium rhythms at a single-cell level in the SCN, which were topologically specific with a larger amplitude and more delayed phase in the ventral region than the dorsal. The robustness of the rhythm was reduced but persisted even after blocking the neuronal firing with tetrodotoxin (TTX). Notably, TTX dissociated the circadian calcium rhythms between the dorsal and ventral SCN. In contrast, a blocker of gap junctions, carbenoxolone, had only a minor effect on the calcium rhythms at both the single-cell and network levels. These results reveal the topological specificity of the circadian calcium rhythm in the SCN and the presence of coupled regional pacemakers in the dorsal and ventral regions. Neuronal firings are not necessary for the persistence of the calcium rhythms but indispensable for the hierarchical organization of rhythmicity in the SCN.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...... cardiac deaths were observed. We find similar diurnal (light:dark) and circadian (darkness) rhythms of RR intervals in WT and KChIP2(-/-) mice. Circadian rhythms in QT100 intervals are present in both groups, but at physiological small amplitudes: 1.6 ± 0.2 and 1.0 ± 0.3 ms in WT and KChIP2...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Perinatal development of human circadian rhythms: role of the foetal biological clock

    NARCIS (Netherlands)

    Mirmiran, M.; Kok, J. H.; Boer, K.; Wolf, H.

    1992-01-01

    The development of circadian rhythms and the neuronal mechanisms underlying their generation (particularly the suprachiasmatic nucleus of the hypothalamus) were reviewed. Based on perinatal animal studies and data from human foetuses and/or preterm infants it was concluded that human circadian

  18. Significance of circadian rhythms in severely brain-injured patients: A clue to consciousness?

    Science.gov (United States)

    Blume, Christine; Lechinger, Julia; Santhi, Nayantara; del Giudice, Renata; Gnjezda, Maria-Teresa; Pichler, Gerald; Scarpatetti, Monika; Donis, Johann; Michitsch, Gabriele; Schabus, Manuel

    2017-05-16

    To investigate the relationship between the presence of a circadian body temperature rhythm and behaviorally assessed consciousness levels in patients with disorders of consciousness (DOC; i.e., vegetative state/unresponsive wakefulness syndrome or minimally conscious state). In a cross-sectional study, we investigated the presence of circadian temperature rhythms across 6 to 7 days using external skin temperature sensors in 18 patients with DOC. Beyond this, we examined the relationship between behaviorally assessed consciousness levels and circadian rhythmicity. Analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3 hours). We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised were closely linked to the integrity of circadian variations in body temperature. Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in 2 out of 8 patients. The study provides evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness. Our findings also make a case for circadian rhythms as a target for treatment as well as the application of diagnostic and therapeutic means at times when cognitive performance is expected to peak. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  19. The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs

    NARCIS (Netherlands)

    Boumans, Iris J. M. M.; de Boer, Imke J. M.; Hofstede, Gert Jan; la Fleur, Susanne E.; Bokkers, Eddie A. M.

    2017-01-01

    The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a

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

    Science.gov (United States)

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

    1998-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Goldstein-Kral Lauren

    2011-01-01

    Full Text Available Abstract Background The mammalian suprachiasmatic nucleus (SCN, located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression. Results We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b and cryptochrome 3 (cry3, in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh and serotonin-N-acetyltransferase (aanat2, involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their

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

    Directory of Open Access Journals (Sweden)

    Sean R. Moore

    2014-09-01

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

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

    NARCIS (Netherlands)

    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

  4. Alterations in the circadian rhythm of salivary melatonin begin during middle-age

    NARCIS (Netherlands)

    Zhou, Jiang-Ning; Liu, Rong-Yu; van Heerikhuize, Joop; Hofman, Michel A.; Swaab, Dick F.

    2003-01-01

    To investigate whether free melatonin may be better suited to reveal age-related changes, we studied the circadian rhythm alterations in saliva melatonin levels during aging. Special attention was paid to the question as to how the free melatonin rhythms change in aging and when such changes take

  5. Indirect bright light improves circadian rest-activity rhythm disturbances in demented patients

    NARCIS (Netherlands)

    van Someren, E. J.; Kessler, A.; Mirmiran, M.; Swaab, D. F.

    1997-01-01

    Light is known to be an important modulator of circadian rhythms. We tested the hypothesis than an enduring increase in the daytime environmental illumination level improves rest-activity rhythm disturbances in demented patients. Actigraphy was performed before, during, and after 4 weeks of

  6. Free-running circadian rhythms of muscle strength, reaction time, and body temperature in totally blind people

    OpenAIRE

    Squarcini, Camila Fabiana Rossi; Pires, Maria Laura Nogueira [UNESP; Lopes, Cleide; Benedito-silva, Ana AmÉlia; Esteves, Andrea Maculano; Cornelissen-guillaume, Germaine; Matarazzo, Carolina; Garcia, Danilo; Silva, Maria Stella Peccin; Tufik, Sergio; Mello, Marco TÚlio

    2013-01-01

    Light is the major synchronizer of circadian rhythms. In the absence of light, as for totally blind people, some variables, such as body temperature, have an endogenous period that is longer than 24 h and tend to be free running. However, the circadian rhythm of muscle strength and reaction time in totally blind people has not been defined in the literature. The objective of this study was to determine the period of the endogenous circadian rhythm of the isometric and isokinetic contraction s...

  7. Evolution of circadian rhythms: from bacteria to human.

    Science.gov (United States)

    Bhadra, Utpal; Thakkar, Nirav; Das, Paromita; Pal Bhadra, Manika

    2017-07-01

    The human body persists in its rhythm as per its initial time zone, and transition always occur according to solar movements around the earth over 24 h. While traveling across different latitudes and longitudes, at the pace exceeding the earth's movement, the changes in the external cues exceed the level of toleration of the body's biological clock. This poses an alteration in our physiological activities of sleep-wake pattern, mental alertness, organ movement, and eating habits, causing them to temporarily lose the track of time. This is further re-synchronized with the physiological cues of the destination over time. The mechanism of resetting of the clocks with varying time zones and cues occur in organisms from bacteria to humans. It is the result of the evolution of different pathways and molecular mechanisms over the time. There has been evolution of numerous comprehensive mechanisms using various research tools to get a deeper insight into the rapid turnover of molecular mechanisms in various species. This review reports insights into the evolution of the circadian mechanism and its evolutionary shift which is vital and plays a major role in assisting different organisms to adapt in different zones and controls their internal biological clocks with changing external cues. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Feng, Dan; Liu, Tao; Sun, Zheng

    2011-01-01

    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......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...... 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....

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

    Science.gov (United States)

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

    1977-01-01

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

  10. Lithium and bipolar disorder: Impacts from molecular to behavioural circadian rhythms.

    Science.gov (United States)

    Moreira, Jeverson; Geoffroy, Pierre Alexis

    2016-01-01

    Bipolar disorder (BD) is a severe and common psychiatric disorder. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. Lithium (Li) is the first-line treatment in BD, and its therapeutic action has been related to its ability to alter circadian rhythms. We systematically searched the PubMed database until January 2016, aiming to critically examine published studies investigating direct and indirect effects of Li on circadian rhythms. The results, from the 95 retained studies, indicated that Li: acts directly on the molecular clocks; delays the phase of sleep-wakefulness rhythms and the peak elevation of diurnal cycle body temperature; reduces the amplitude and shortens the duration of activity rhythms and lengthens free-running rhythms. Chronic Li treatment stabilizes free-running activity rhythms, by improving day-to-day rhythmicity of the activity, with effects that appear to be dose related. Pharmacogenetics demonstrate several associations of Li's response with circadian genes (NR1D1, GSK3β, CRY1, ARNTL, TIM, PER2). Finally, Li acts on the retinal-hypothalamic pineal pathway, influencing light sensitivity and melatonin secretion. Li is a highly investigated chronobiologic agent, and although its chronobiological effects are not completely understood, it seems highly likely that they constitute an inherent component of its therapeutic action in the treatment of mood disorders.

  11. Wheel-running activity modulates circadian organization and the daily rhythm of eating behavior.

    Science.gov (United States)

    Pendergast, Julie S; Branecky, Katrina L; Huang, Roya; Niswender, Kevin D; Yamazaki, Shin

    2014-01-01

    Consumption of high-fat diet acutely alters the daily rhythm of eating behavior and circadian organization (the phase relationship between oscillators in central and peripheral tissues) in mice. Voluntary wheel-running activity counteracts the obesogenic effects of high-fat diet and also modulates circadian rhythms in mice. In this study, we sought to determine whether voluntary wheel-running activity could prevent the proximate effects of high-fat diet consumption on circadian organization and behavioral rhythms in mice. Mice were housed with locked or freely rotating running wheels and fed chow or high-fat diet for 1 week and rhythms of locomotor activity, eating behavior, and molecular timekeeping (PERIOD2::LUCIFERASE luminescence rhythms) in ex vivo tissues were measured. Wheel-running activity delayed the phase of the liver rhythm by 4 h in both chow- and high-fat diet-fed mice. The delayed liver phase was specific to wheel-running activity since an enriched environment without the running wheel did not alter the phase of the liver rhythm. In addition, wheel-running activity modulated the effect of high-fat diet consumption on the daily rhythm of eating behavior. While high-fat diet consumption caused eating events to be more evenly dispersed across the 24 h-day in both locked-wheel and wheel-running mice, the effect of high-fat diet was much less pronounced in wheel-running mice. Together these data demonstrate that wheel-running activity is a salient factor that modulates liver phase and eating behavior rhythms in both chow- and high-fat-diet fed mice. Wheel-running activity in mice is both a source of exercise and a self-motivating, rewarding behavior. Understanding the putative reward-related mechanisms whereby wheel-running activity alters circadian rhythms could have implications for human obesity since palatable food and exercise may modulate similar reward circuits.

  12. Non-peptide oxytocin receptor ligands and hamster circadian wheel running rhythms.

    Science.gov (United States)

    Gannon, Robert L

    2014-10-17

    The synchronization of circadian rhythms in sleep, endocrine and metabolic functions with the environmental light cycle is essential for health, and dysfunction of this synchrony is thought to play a part in the development of many neurological disorders. There is a demonstrable need to develop new therapeutics for the treatment of neurological disorders such as depression and schizophrenia, and oxytocin is currently being investigated for this purpose. There are no published reports describing activity of oxytocin receptor ligands on mammalian circadian rhythms and that, then, is the purpose of this study. Non-peptide oxytocin receptor ligands that cross the blood brain barrier were systemically injected in hamsters to determine their ability to modulate light-induced phase advances and delays of circadian wheel running rhythms. The oxytocin receptor agonist WAY267464 (10 mg/kg) inhibited light induced phase advances of wheel running rhythms by 55%, but had no effect on light-induced phase delays. In contrast, the oxytocin receptor antagonist WAY162720 (10 mg/kg) inhibited light-induced phase delays by nearly 75%, but had no effect on light-induced phase advances. Additionally, WAY162720 was able to antagonize the inhibitory effects of WAY267464 on light-induced phase advances. These results are consistent for a role of oxytocin in the phase-delaying effects of light on circadian activity rhythms early in the night. Therefore, oxytocin may prove to be useful in developing therapeutics for the treatment of mood disorders with a concomitant dysfunction in circadian rhythms. Investigators should also be cognizant that oxytocin ligands may negatively affect circadian rhythms during clinical trials for other conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  16. Effect of cataract surgery on regulation of circadian rhythms

    DEFF Research Database (Denmark)

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

    2015-01-01

    was evaluated based on the principles described in the Grading of Recommendations Assessment, Development, and Evaluation system. A literature search of PubMed, Embase, and Cochrane Library databases was performed, as well as a search for unpublished trials at the U.S. National Institutes of Health Clinical......UNLABELLED: This review looked at the effect of cataract surgery on the regulation of circadian rhythms and compared the effect of blue light-filtering and clear intraocular lenses (IOLs) on circadian rhythms. A systematic review and metaanalysis were performed, and the level of evidence...... 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....

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  2. PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

    International Nuclear Information System (INIS)

    Shirai, Hidenori; Oishi, Katsutaka; Kudo, Takashi; Shibata, Shigenobu; Ishida, Norio

    2007-01-01

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

  3. Reciprocal interactions between sleep, circadian rhythms and Alzheimer's disease: focus on the role of hypocretin and melatonin

    NARCIS (Netherlands)

    Slats, D.; Claassen, J.A.H.R.; Verbeek, M.M.; Overeem, S.

    2013-01-01

    AD, sleep and circadian rhythm physiology display an intricate relationship. On the one hand, AD pathology leads to sleep and circadian disturbances, with a clear negative influence on quality of life. On the other hand, there is increasing evidence that both sleep and circadian regulating systems

  4. Why and how do we model circadian rhythms?

    NARCIS (Netherlands)

    Beersma, DGM

    In our attempts to understand the circadian system, we unavoidably rely on abstractions. Instead of describing the behavior of the circadian system in all its complexity, we try to derive basic features from which we form a global concept on how the system works. Such a basic concept is a model of

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-02-01

    The rhythmic opening/closing and volatile emissions of flowers are known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach has led to the identification of core circadian clock components in Arabidopsis thaliana, the involvement of these clock components in floral rhythms has remained untested, probably because of the weak diurnal rhythms in A. thaliana flowers. Here, we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents and move vertically through a 140° arc. We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission and pedicel movement, but not flower closing. We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known to be core clock components. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  7. Naturally occurring circadian rhythm and sleep duration are related to executive functions in early adulthood.

    Science.gov (United States)

    Kuula, Liisa; Pesonen, Anu-Katriina; Heinonen, Kati; Kajantie, Eero; Eriksson, Johan Gunnar; Andersson, Sture; Lano, Aulikki; Lahti, Jari; Wolke, Dieter; Räikkönen, Katri

    2018-02-01

    Experimental sleep deprivation studies suggest that insufficient sleep and circadian misalignment associates with poorer executive function. It is not known whether this association translates to naturally occurring sleep patterns. A total of 512 of full-term-born members of the Arvo Ylppö Longitudinal Study [mean age = 25.3, standard deviation (SD) = 0.65] (44.3% men) wore actigraphs to define sleep duration, its irregularity and circadian rhythm (sleep mid-point) during a 1-week period (mean 6.9 nights, SD = 1.7). Performance-based executive function was assessed with the Trail-Making Test, Conners' Continuous Performance Test and Stroop. The self-rated adult version of Behavior Rating Inventory of Executive Function was used to assess trait-like executive function. We found that performance-based and self-reported trait-like executive function correlated only modestly (all correlations ≤0.17). Shorter sleep duration associated with more commission errors. Later circadian rhythm associated with poorer trait-like executive function, as indicated by the Brief Metacognitive Index and the Behavior Regulation Index. Those belonging to the group with the most irregular sleep duration performed slower than others in the Trail-Making Test Part A. All associations were adjusted for sex, age, socioeconomic status and body mass index. In conclusion, naturally occurring insufficient sleep and later circadian rhythm showed modest associations with poorer executive function. Shorter habitual sleep duration was associated with lower scores of performance-based tests of executive function, and later circadian rhythm was associated mainly with poorer trait-like executive function characteristics. Our findings suggest additionally that sleep duration and circadian rhythm associate with different domains of executive function, and there are no additive effects between the two. © 2017 European Sleep Research Society.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

  11. The effect of circadian rhythm on the perceived tinnitus severity: A preliminary study.

    Science.gov (United States)

    Zacharia, Thomas; James, Judith; Prakash, Hari; Mohan, Rukmangathan Thurvas; Rajashekhar, Bellur

    2014-01-01

    Hearing sound that does not originate in the world outside the body is an experience every human has at one time or another in life. Circadian rhythm is common for all living organisms and nearly all physiological functions, especially sleep-wake cycles, exhibit circadian rhythmicity. A short survey conducted in the study center revealed that majority of the tinnitus subjects reported a difference in tinnitus severity across the day. So the current study focused on finding out the influence of circadian rhythm on tinnitus severity. Study was conducted on 20 tinnitus subjects irrespective of age, gender, hearing status and type of tinnitus. Kannada version of MEQ was given to all the subjects to classify them to various circadian types. A visual analog scale was also given to rate the severity of the tinnitus in the morning and evening. The result of the current study states that, there was a significant difference in the tinnitus severity for moderate morning type individuals in the morning and evening and not for the intermediate group. So we can conclude that, circadian rhythm has a strong association with the severity of the tinnitus.

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

    NARCIS (Netherlands)

    Chaves, I.; van der Horst, G.T.J.; Schellevis, R.; Nijman, R.M.; Groot Koerkamp, M.; Holstege, F.C.P.; Smidt, M.P.; Hoekman, M.F.M.

    2014-01-01

    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

  13. Circadian rhythms in systemic hemodynamics and renal function in healthy subjects and patients with nephrotic syndrome

    NARCIS (Netherlands)

    Voogel, A. J.; Koopman, M. G.; Hart, A. A.; van Montfrans, G. A.; Arisz, L.

    2001-01-01

    The resemblance of the circadian rhythm of glomerular filtration rate (GFR) to that of arterial blood pressure (BP) suggests that systemic hemodynamic factors contribute to this variation. In the present study, this was investigated using continuous BP monitoring and pulse wave analysis. The study

  14. Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?

    Science.gov (United States)

    Vogel, Suzan W N; Bijlenga, Denise; Tanke, Marjolein; Bron, Tannetje I; van der Heijden, Kristiaan B; Swaab, Hanna; Beekman, Aartjan T F; Kooij, J J Sandra

    2015-11-01

    Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) have a high prevalence of obesity. This is the first study to investigate whether circadian rhythm disruption is a mechanism linking ADHD symptoms to obesity. ADHD symptoms and two manifestations of circadian rhythm disruption: sleep problems and an unstable eating pattern (skipping breakfast and binge eating later in the day) were assessed in participants with obesity (n= 114), controls (n= 154), and adult ADHD patients (n= 202). Participants with obesity had a higher prevalence of ADHD symptoms and short sleep on free days as compared to controls, but a lower prevalence of ADHD symptoms, short sleep on free days, and an unstable eating pattern as compared to ADHD patients.We found that participants with obesity had a similar prevalence rate of an unstable eating pattern when compared to controls. Moreover, mediation analyses showed that both sleep duration and an unstable eating pattern mediated the association between ADHD symptoms and body mass index (BMI). Our study supports the hypothesis that circadian rhythm disruption is a mechanism linking ADHD symptoms to obesity. Further research is needed to determine if treatment of ADHD and circadian rhythm disruption is effective in the prevention and treatment of obesity in patients with obesity and/or ADHD. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Differential Effects of Pinealectomy on Circadian Rhythms of Feeding and Perch Hopping in the European Starling

    NARCIS (Netherlands)

    Gwinner, Eberhard; Subbaraj, Ramanujam; Bluhm, Cynthia K.; Gerkema, Menno

    1987-01-01

    To study the effects of pinealectomy on the circadian rhythms of locomotor activity and feeding, European starlings (Sturnus vulgaris) were held in constant light (0.2 lux and 200 lux) and under constant temperature conditions. Locomotor activity was measured by means of perches with microswitches

  16. The effects of gender on circadian rhythm of human physiological indexes in high temperature environment

    Science.gov (United States)

    Zheng, G. Z.; Li, K.; Bu, W. T.; Lu, Y. Z.; Wang, Y. J.

    2018-03-01

    In the context of frequent high temperature weather in recent years, peoples’ physical health is seriously threatened by the indoor high temperature. The physiological activities of human body show a certain changes of circadian rhythm. In this paper, the circadian rhythms of the physiological indexes in indoor high temperature environment were quantified and compared between the male subjects and female subjects. Ten subjects (five males and five females) were selected. The temperature conditions were set at 28°C, 32°C, 36°C and 38°C, respectively. The blood pressure, heart rate, rectal temperature, eardrum temperature, forehead temperature and mean skin temperature were measured for 24 hours continuously. The medians, amplitudes and acrophases of the circadian rhythms were obtained by the cosinor analysis method. Then the effects of gender on the circadian rhythm of the human body in high temperature environment were analyzed. The results indicate that, compared with the female subjects, the male medians of the systolic pressure and diastolic pressure were higher, and the male medians of heart rate and rectal temperature were lower, however, no significant differences were found between eardrum temperature, forehead temperature and mean skin temperature. This study can provide scientific basis for the health protection of the indoor relevant personnel.

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

    DEFF Research Database (Denmark)

    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...

  18. Identification of circadian brain photoreceptors mediating photic entrainment of behavioural rhythms in lizards.

    NARCIS (Netherlands)

    Pasqualetti, M.; Bertolucci, C.; Ori, M.; Innocenti, A.; Magnone, M.C.; Grip, W.J. de; Nardi, I.; Foa, A.

    2003-01-01

    We have shown previously that in ruin lizards (Podarcis sicula) the ablation of all known photoreceptive structures (lateral eyes, pineal and parietal eye) in the same individual animal does not prevent entrainment of their circadian locomotor rhythms to light. The present study was aimed at

  19. Gastric pH circadian rhythm in the rural Canzibe area of the Eastern ...

    African Journals Online (AJOL)

    Objective: In this study, an attempt has been made to describe the normal circadian rhythm of gastric pH in the dwellers of Canzibe. The high incidence of esophageal cancer in this region is one of the motivating factors to undertake this study. Esophageal impedance studies carried out earlier has supported this finding.

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

    Science.gov (United States)

    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…

  1. Sleep quality and circadian rhythm disruption in the intensive care unit

    DEFF Research Database (Denmark)

    Boyko, Yuliya; Jennum, Poul; Toft, Palle

    2017-01-01

    , medication, as well as the critical illness itself have been reported as important sleep disturbing factors. Secretion of sleep hormone, melatonin, expressing circadian rhythmicity was found abolished or phase delayed in critically ill patients. Various interventions have been tested in several studies...... aiming to improve sleep quality and circadian rhythm in the ICU. The results of these studies were inconclusive due to using the sleep assessment methods other than PSG or the absence of a reliable sleep scoring tool for the analysis of the PSG findings in this patient population. Development of a valid......Sleep and circadian rhythm are reported to be severely abnormal in critically ill patients. Disturbed sleep can lead to the development of delirium and, as a result, can be associated with prolonged stay in the intensive care unit (ICU) and increased mortality. The standard criterion method...

  2. Purinergic Signaling in Neuron-Astrocyte Interactions, Circadian Rhythms, and Alcohol Use Disorder

    Directory of Open Access Journals (Sweden)

    Daniel Lindberg

    2018-02-01

    Full Text Available Alcohol use disorder (AUD is a debilitating condition marked by cyclic patterns of craving, use, and withdrawal. These pathological behaviors are mediated by multiple neurotransmitter systems utilizing glutamate, GABA, dopamine, ATP, and adenosine. In particular, purines such as ATP and adenosine have been demonstrated to alter the phase and function of the circadian clock and are reciprocally regulated by the clock itself. Importantly, chronic ethanol intake has been demonstrated to disrupt the molecular circadian clock and is associated with altered circadian patterns of activity and sleep. Moreover, ethanol has been demonstrated to disrupt purinergic signaling, while dysfunction of the purinergic system has been implicated in conditions of drug abuse such as AUD. In this review, we summarize our current knowledge regarding circadian disruption by ethanol, focusing on the reciprocal relationship that exists between oscillatory neurotransmission and the molecular circadian clock. In particular, we offer detailed explanations and hypotheses regarding the concerted regulation of purinergic signaling and circadian oscillations by neurons and astrocytes, and review the diverse mechanisms by which purinergic dysfuction may contribute to circadian disruption or alcohol abuse. Finally, we describe the mechanisms by which ethanol may disrupt or hijack endogenous circadian rhythms to induce the maladaptive behavioral patterns associated with AUD.

  3. Relationship between circadian rhythm amplitude and stability with sleep quality and sleepiness among shift nurses and health care workers.

    Science.gov (United States)

    Jafari Roodbandi, Akram; Choobineh, Alireza; Daneshvar, Somayeh

    2015-01-01

    Sleep is affected by the circadian cycle and its features. Amplitude and stability of circadian rhythm are important parameters of the circadian cycle. This study aims to examine the relationship between amplitude and stability of circadian rhythm with sleep quality and sleepiness. In this cross-sectional research, 315 shift nurses and health care workers from educational hospitals of Kerman University of Medical Sciences (KUMS), Iran, were selected using a random sampling method. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Circadian Type Inventory (CTI) were used to collect the required data. In this study, 83.2% suffered from poor sleep and one-half had moderate and excessive sleepiness. The results showed that flexibility in circadian rhythm stability, job stress and sleepiness are among the factors affecting quality sleep in shift workers. Those whose circadian rhythm amplitude was languid suffered more from sleepiness and those whose circadian stability was flexible had a better sleep. Variables including circadian rhythm stability (flexible/rigid) and amplitude (languid/vigorous) can act as predictive indices in order to employ people in a shift work system so that sleepiness and a drop in quality of sleep are prevented.

  4. [The influence of age upon circadian rhythm of human pulp sensibility].

    Science.gov (United States)

    Xie, Si-jing; Guo, Bin; Zhou, Xue-dong; Que, Ke-hua; Xu, Zhen; Wang, Zheng-rong; Chen, Xiu-mei

    2007-07-01

    To explore the influence of age on the circadian rhythm of pulp sensibility, guide the diagnosis and treatment of dental and endodontic diseases. The first lower molars of young, middle-aged, and aged volunteers were inspected for the threshold of pulp sensitivity. Each inspection was implemented every 4 hours earlier, totally 7 times during 24 hours. All values of pulp sensibility threshold from each volunteer were analyzed by Halberg methods for cosinor-rhythmometry. The chronobiology characteristics of pulp sensibility were compared among young, middle-aged, and aged. The pulp sensibility threshold values of the young, middle-aged, and aged indicated to have the circadian rhythm alternation in period of 24 hours, with fitting well to a cosine curve. The trend of rhythm curve was similar to all three age groups. The acrophase and bathyphase appeared at 0:00 and 12:00 separately. The values and amplitudes of pulp threshold sensibility showed to be: young>aged> middle-aged. The circadian rhythm of pulp sensibility changes according with age. The pulp sensibility threshold value is lower in aged people than in the young, and the lowest sensibility threshold is in middle-aged people. Besides, the extent of rhythm fluctuation is the least in middle-aged people.

  5. STUDY OF THE RELATIONSHIP BETWEEN CIRCADIAN RHYTHMS AND DRUG RESISTANCE OF BREAST TUMOR CELL LINES

    Directory of Open Access Journals (Sweden)

    A. M. Оgloblina

    2015-01-01

    Full Text Available 10 % of genome mRNA expression is rhythmic and these 24-hrs rhythms are under control of the circadian clock. Epidemiologic studies have revealed a clear link between the disruption of circadian rhythms and cancer development in humans. Growing evidence shows that circadian disruption is associated with development of malignant tumors, including breast cancer. Aim of this study was to investigate: the expression of circadian clock genes in human mammary epithelial cell line MCF10A and breast cancer cell lines MCF-7, ZR-75-1, BT-474 and if the multidrug resistance phenotype of cancer cells is associated with changes in circadian clock genes expression. We have found that Per1 expression significantly reduced in cancer cells. No correlation was detected between the expression of circadian clock genes and cancer breast cell lines drug resistance. Interestingly, the expression of Bmal1, Per1 and Cry1 were increased in multi-drug resistant MCF-7_D cells compare with the parent cells MCF-7 cells, however, if these changes in the expression contribute to the drug-resistance or not is not clear. These results argue for further study.

  6. Circadian Rhythms and Substance Abuse: Chronobiological Considerations for the Treatment of Addiction.

    Science.gov (United States)

    Webb, Ian C

    2017-02-01

    Reward-related learning, including that associated with drugs of abuse, is largely mediated by the dopaminergic mesolimbic pathway. Mesolimbic neurophysiology and motivated behavior, in turn, are modulated by the circadian timing system which generates ∼24-h rhythms in cellular activity. Both drug taking and seeking and mesolimbic dopaminergic neurotransmission can vary widely over the day. Moreover, circadian clock genes are expressed in ventral tegmental area dopaminergic cells and in mesolimbic target regions where they can directly modulate reward-related neurophysiology and behavior. There also exists a reciprocal influence between drug taking and circadian timing as the administration of drugs of abuse can alter behavioral rhythms and circadian clock gene expression in mesocorticolimbic structures. These interactions suggest that manipulations of the circadian timing system may have some utility in the treatment of substance abuse disorders. Here, the literature on bidirectional interactions between the circadian timing system and drug taking is briefly reviewed, and potential chronotherapeutic considerations for the treatment of addiction are discussed.

  7. Mechanisms of social synchrony between circadian activity rhythms in cohabiting marmosets.

    Science.gov (United States)

    Bessa, Zoélia Camila Moura; Melo, Paula Rocha De; Gonçalves, Bruno S B; Azevedo, Carolina V M De

    2018-01-26

    In marmosets, social synchrony between circadian profiles of activity is stronger in animals that cohabit in a family. The activity of three breeding pairs was recorded by actiwatches to investigate the mechanisms involved in the synchrony between the circadian activity profiles during cohabitation in marmoset reproductive pairs. The dyads were submitted to LD 12:12 (21 days) and LL: 1) cohabitation (24 days), 2) removal of the cage mate (20 days), 3) reintroduction of the mate into the cage of the 1 st situation (30 days) and 4) removal of the cage mate (7 days). Next, they were rejoined and maintained in LD 12:12 (11 days). In conditions involving cohabitation of pair, the general and maximum correlation indexes between circadian profiles were higher in cage mates compared to animals of the same or different sex with which they maintain only acoustic and olfactive contact. This strong synchrony between rhythms was accompanied by a stable phase relationship at the activity onset and offset, with identical circadian periods between mates. When the pairs were separated, there was a break in stability in the phase relationships between activity profiles with different circadian periods and a greater phase angle difference between rhythms of cage mates. During separation, two females and one male progressively anticipated the activity onset and offset in a phase similar to that in previous conditions, expressing entrainment to the mate. During the first reintroduction, two pairs exhibited signs of masking in rhythm. Although modulation in the rhythm of some animals has been observed through acoustic cues from animals outside the colony, we suggest that cohabitation favors strong synchrony between the circadian activity profiles of marmoset reproductive pairs involving synchronization by entrainment and masking. Further studies in the absence of external social cues are necessary to clarify the role of these mechanisms on social synchronization in marmosets.

  8. The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs.

    Science.gov (United States)

    Boumans, Iris J M M; de Boer, Imke J M; Hofstede, Gert Jan; la Fleur, Susanne E; Bokkers, Eddie A M

    2017-07-01

    The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

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

    2009-08-27

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

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

    Directory of Open Access Journals (Sweden)

    Guilding Clare

    2009-08-01

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

  13. Circadian rhythm disturbance after radiotherapy for brain tumor in infantile period

    International Nuclear Information System (INIS)

    Kubota, Masaya; Shinozaki, Masako; Sasaki, Hideo.

    1993-01-01

    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 ( 60 Co 60 Gy), he showed profound psychomotor retardation, endoclinologic dysfunction including hypothyroidism and growth hormone deficiency, and S-W rhythm disturbance. At the age of 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. So 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 12 (VB 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 12 , our patient's organic brain damage was more evident radiologically and endoclinologically. Following the hypothesis that VB 12 has a potential to reinforce the entrainment of circadian rhythm, our patient's organic brain damage may include entrainment system. (author)

  14. Circadian rhythm in salivary melatonin in narcoleptic patiens

    Czech Academy of Sciences Publication Activity Database

    Blažejová, K.; Illnerová, Helena; Hájek, Ivan; Nevšímalová, S.

    2008-01-01

    Roč. 437, č. 2 (2008), s. 162-164 ISSN 0304-3940 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : narcolepsy * circadian system * melatonin Subject RIV: FH - Neurology Impact factor: 2.200, year: 2008

  15. The electroretinogram as a method for studying circadian rhythms in ...

    Indian Academy of Sciences (India)

    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 ...

  16. Circadian rhythm gene regulation in the housefly, Musca domestica

    Czech Academy of Sciences Publication Activity Database

    Codd, V.; Doležel, David; Stehlík, Jan; Piccin, A.; Garner, K. J.; Racey, S. N.; Straatman, K. R.; Louis, E. J.; Costa, R.; Šauman, Ivo; Kyriacou, C. P.; Rosato, E.

    2007-01-01

    Roč. 177, č. 3 (2007), s. 1539-1551 ISSN 0016-6731 R&D Projects: GA ČR GA204/04/0862; GA MŠk 2B06129 Institutional research plan: CEZ:AV0Z50070508 Keywords : circadian * evolution * Diptera Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.001, year: 2007

  17. Disrupting circadian rhythms in rats induces retrograde amnesia

    NARCIS (Netherlands)

    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

  18. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology.

    Science.gov (United States)

    Reiter, Russel J; Tan, Dun Xian; Korkmaz, Ahmet; Rosales-Corral, Sergio A

    2014-01-01

    Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her

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

    Science.gov (United States)

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

    2013-01-01

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

  20. Effects of Lithium and 2,4-Dichlorophenol on Zebrafish: Circadian Rhythm Disorder and Molecular Effects.

    Science.gov (United States)

    Xiao, Bo; Cui, Li-Qiang; Ding, Cheng; Wang, Han

    2017-06-01

    The aim of this study was to investigate lithium and 2,4-dichlorophenol (2,4-DCP)-induced circadian rhythm disorder and their genome-wide effects in zebrafish. Zebrafish larvae were exposed to 250 ppm LiCl (n = 40) or 20 ppm 2,4-DCP. RNA was subsequently extracted and determined quantitatively. The mRNA levels of circadian clock-related genes, including clock1a, bmal1b, per2, and per1b, were determined. Microarray datasets were generated and the differentially expressed genes (DEGs) were identified. The mRNA levels of some upregulated and downregulated DEGs were examined by quantitative real-time polymerase chain reaction (RT-PCR). Finally, gene ontology (GO) enrichment analysis was applied to determine the roles of the DEGs. The mRNA expression levels of circadian rhythm-related genes in the daily cycle were significantly affected after incubation of zebrafish with LiCl and 2,4-DCP. Many genes were differentially expressed during the light phase (97 h) and RT-PCR validation tests revealed that the expression patterns of DEGs were in accordance with those obtained by microarray analysis. GO functional enrichment analysis showed that the DEGs in LiCl- and 2,4-DCP-treated groups were associated with signal transduction and development. Collectively, our findings indicate that LiCl and 2,4-DCP could affect signal transduction pathways and immune response, thereby inducing circadian rhythm disorder.

  1. Identification of circadian brain photoreceptors mediating photic entrainment of behavioural rhythms in lizards.

    Science.gov (United States)

    Pasqualetti, Massimo; Bertolucci, Cristiano; Ori, Michela; Innocenti, Augusto; Magnone, Maria C; De Grip, Willem J; Nardi, Irma; Foà, Augusto

    2003-07-01

    We have shown previously that in ruin lizards (Podarcis sicula) the ablation of all known photoreceptive structures (lateral eyes, pineal and parietal eye) in the same individual animal does not prevent entrainment of their circadian locomotor rhythms to light. The present study was aimed at identifying the circadian brain photoreceptors mediating entrainment. For this purpose, we looked for opsin expression in the brain by means of immunocytochemistry. Using anti-cone-opsin antiserum CERN 874 we have localized photoreceptors in the periventricular area of hypothalamus, near the third cerebral ventricle. We also cloned a brain opsin cDNA that, on the basis of the deduced amino acid sequence, appears to belong to the RH2 class of cone-opsins. We named the cloned cone-opsin Ps-RH2. To examine whether brain cone-opsins mediate photic entrainment of circadian locomotor rhythms, we performed post-transcriptional inactivation experiments by injecting an expression eukaryotic vector transcribing the antisense cone-opsin Ps-RH2 mRNA in the third cerebral ventricle of pinealectomized-retinectomized lizards previously entrained to a light-dark (LD) cycle. Injections of the antisense construct abolished photic entrainment of circadian locomotor rhythms of pinealectomized-retinectomized lizards to the LD cycle for 6-9 days. CERN 874 completely failed to label cells within the periventricular area of hypothalamus of brains injected with antisense construct. Thus, abolishment of photic entrainment is due to inactivation of endogenous brain cone-opsins mRNA. The present results demonstrate for the first time in a vertebrate that brain cone-opsins are part of a true circadian brain photoreceptor participating in photic entrainment of behavioural rhythms.

  2. Cancer/testis antigen PIWIL2 suppresses circadian rhythms by regulating the stability and activity of BMAL1 and CLOCK.

    Science.gov (United States)

    Lu, Yilu; Zheng, Xulei; Hu, Wei; Bian, Shasha; Zhang, Zhiwei; Tao, Dachang; Liu, Yunqiang; Ma, Yongxin

    2017-08-15

    Circadian rhythms are regulated by transcriptional and post-translational feedback loops generated by appropriate functions of clock proteins. Rhythmic degradation of the circadian clock proteins is critical for maintenance of the circadian oscillations. Notably, circadian clock does not work during spermatogenesis and can be disrupted in tumors. However, the underlying mechanism that suppresses circadian rhythms in germ cells and cancer cells remains largely unknown. Here we report that the cancer/testis antigen PIWIL2 can repress circadian rhythms both in the testis and cancer cells. By facilitating SRC binding with PI3K, PIWIL2 activates the PI3K-AKT pathway to phosphorylate and deactivate GSK3β, suppressing GSK3β-induced phosphorylation and degradation of circadian protein BMAL1 and CLOCK. Meanwhile, PIWIL2 can bind with E-Box sequences associated with the BMAL1/CLOCK complex to negatively regulate the transcriptional activation activity of promoters of clock-controlled genes. Taken together, our results first described a function for the germline-specific protein PIWIL2 in regulation of the circadian clock, providing a molecular link between spermatogenesis as well as tumorigenesis to the dysfunction of circadian rhythms.

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. The role of melatonin and cortisol circadian rhythms in the pathogenesis of infantile colic.

    Science.gov (United States)

    İnce, Tolga; Akman, Hakkı; Çimrin, Dilek; Aydın, Adem

    2018-03-05

    Despite the high prevalence of infantile colic, the pathogenesis remains incompletely understood. Cortisol and melatonin hormones affect gastrointestinal system development in several ways, and interestingly, both cortisol and melatonin's circadian rhythms begin around the 3rd month in which infantile colic symptoms start to decrease. We hypothesized that infantile colic might associate with desynchronization of normal circadian rhythms of these hormones. In this study, we aimed to investigate the role of melatonin and cortisol in the pathogenesis of infantile colic. Patients who were diagnosed as infantile colic according to Wessel's "rule of three" were enrolled in the colic group. We measured the saliva melatonin and cortisol levels of colic group and control group infants. In both groups, the saliva samples were taken in mornings and at evenings, at the time of diagnosis and 6th month. Fifty-five infants finished the study. Melatonin circadian rhythm developed earlier in the control group than the infantile colic group in our study. We found no significant difference between the daily mean cortisol levels. However, infants with colic had flatter daily cortisol slope than controls which pointed out the probability that they had a less clearly defined cortisol rhythm than infants without colic. We found an association between melatonin levels and infantile colic. However, more research is needed to fully understand the role of hypothalamic-pituitary-adrenal axis and hormone's role on infantile colic physiopathology.

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

    Science.gov (United States)

    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.; hide

    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.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.

    Science.gov (United States)

    Bouchlariotou, Sofia; Liakopoulos, Vassilios; Giannopoulou, Myrto; Arampatzis, Spyridon; Eleftheriadis, Theodoros; Mertens, Peter R; Zintzaras, Elias; Messinis, Ioannis E; Stefanidis, Ioannis

    2014-08-01

    Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, pmelatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Circadian rhythms of body temperature and locomotor activity in the antelope ground squirrel, Ammospermophilus leucurus.

    Science.gov (United States)

    Refinetti, Roberto; Kenagy, G J

    2018-02-01

    We studied circadian rhythms of body temperature and locomotor activity in antelope ground squirrels (Ammospermophilus leucurus) under laboratory conditions of a 12L:12D light-dark cycle and in constant darkness. Antelope ground squirrels are diurnally active and, exceptionally among ground squirrels and other closely related members of the squirrel family in general, they do not hibernate. Daily oscillations in body temperature consisted of a rise in temperature during the daytime activity phase of the circadian cycle and a decrease in temperature during the nighttime rest phase. The body temperature rhythms were robust (71% of maximal strength) with a daily range of oscillation of 4.6°C, a daytime mean of 38.7°C, and a nighttime mean of 34.1°C (24-h overall mean 36.4°C). The body temperature rhythm persisted in continuous darkness with a free-running period of 24.2h. This pattern is similar to that of hibernating species of ground squirrels but with a wave form more similar to that of non-hibernating rodents. Daily oscillations in body temperature were correlated with individual bouts of activity, but daytime temperatures were higher than nighttime temperatures even when comparing short episodes of nocturnal activity that were as intense as diurnal activity. This suggests that although muscular thermogenesis associated with locomotor activity can modify the level of body temperature, the circadian rhythm of body temperature is not simply a consequence of the circadian rhythm of activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms.

    Science.gov (United States)

    Kozlov, Anatoly; Jaumouillé, Edouard; Machado Almeida, Pedro; Koch, Rafael; Rodriguez, Joseph; Abruzzi, Katharine C; Nagoshi, Emi

    2017-07-12

    Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled ( unf ) represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period ( per ) (Jaumouillé et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene CG7837 , which we termed R and B ( Rnb ), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair locomotor rhythms. RNB localizes to the nucleus, and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit. SIGNIFICANCE STATEMENT Circadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons in Drosophila Here, we identified the molecular characteristics

  12. Insulin resistance and circadian rhythm of cardiac autonomic modulation

    Directory of Open Access Journals (Sweden)

    Cai Jianwen

    2010-12-01

    Full Text Available Abstract Background Insulin resistance (IR has been associated with cardiovascular diseases (CVD. Heart rate variability (HRV, an index of cardiac autonomic modulation (CAM, is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. Method Homeostasis models of IR (HOMA-IR, insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M, measures the overall average of a HRV index; amplitude (Â, measures the amplitude of the oscillation of a HRV index; and acrophase time (θ, measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. Results In persons without type diabetes, the multivariate adjusted β (SE of log HOMA-IR and M variable for HRV were -0.251 (0.093, -0.245 (0.078, -0.19 (0.06, -4.89 (1.76, -3.35 (1.31, and 2.14 (0.995, for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P Conclusion Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.

  13. Intensive voluntary wheel running may restore circadian activity rhythms and improves the impaired cognitive performance of arrhythmic Djungarian hamsters

    Czech Academy of Sciences Publication Activity Database

    Weinert, D.; Schöttner, Konrad; Müller, L.; Wienke, A.

    2016-01-01

    Roč. 33, č. 9 (2016), s. 1161-1170 ISSN 0742-0528 Institutional support: RVO:60077344 Keywords : Djungarian hamster * circadian rhythm * arrhythmic activity pattern Subject RIV: ED - Physiology Impact factor: 2.562, year: 2016

  14. Circadian activity rhythms in colonies of 'blind' Molerats, Cryptomys ...

    African Journals Online (AJOL)

    Various activity rhythms (general, feeding, and toilet) were measured under controlled laboratory conditions in two colonies of the Damara molerai Cryptomys damarensis, for 140 consecutive days (following a 30 day test period) under various photoperiod regimes (16:8 LD, 12:12 LD, and constant dark DD). As a general ...

  15. Effects of microgravity on circadian rhythms in insects

    Science.gov (United States)

    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.

  16. Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

    International Nuclear Information System (INIS)

    Demel, A.W.

    1990-12-01

    Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be user for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carb oxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (SCHULZ et al 1990). Using a computerized program (RHYTHM) written by EVE v. CAUTER (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurence of the maximum of a sinusoid fitted to the data). The F acrophase occured between 7:00 and 12:00 h (Mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

  17. Circadian rhythms of melatonin, cortisol, and clock gene expression during simulated night shift work.

    Science.gov (United States)

    James, Francine O; Cermakian, Nicolas; Boivin, Diane B

    2007-11-01

    The synchronization of peripheral circadian oscillators in humans living on atypical sleep/wake schedules is largely unknown. In this night shift work simulation, we evaluate clock gene expression in peripheral blood mononuclear cells (PBMCs) relative to reliable markers of the central circadian pacemaker. Participants were placed on a 10-hr delayed sleep/wake schedule simulating nighttime work followed by a daytime sleep episode. Baseline, intermediate and final circadian evaluations were performed in the temporal isolation laboratory. Five healthy candidates, 18-30 years. Polychromatic white light of (mean +/-SEM) 6,036 +/-326 lux (approximately 17,685 +/-955 W/m2) during night shifts; dim light exposure after each night shift; an 8-hr sleep/darkness episode beginning 2 hrs after the end of each night shift. Melatonin and cortisol in plasma; clock genes HPER1, HPER2 and HBMAL1 RNA in PBMCs. Following 9 days on the night schedule, hormonal rhythms were adapted to the shifted schedule. HPER1 and HPER2 expression in PBMCs displayed significant circadian rhythmicity, which was in a conventional relationship with the shifted sleep/wake schedule. Changes in the pattern of clock gene expression were apparent as of 3 days on the shifted sleep/wake schedule. This preliminary study is the first documentation of the effects of a shifted sleep/wake schedule on the circadian expression of both peripheral circadian oscillators in PBMCs and centrally-driven hormonal rhythms. In light of evidence associating clock gene expression with tissue function, the study of peripheral circadian oscillators has important implications for understanding medical disorders affecting night shift workers.

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

    DEFF Research Database (Denmark)

    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...... the effect the ageing human lens may have for the photoentrainment of circadian rhythm and to compare with intraocular implant lenses (IOLs) designed to block UV radiation, violet or blue light....

  19. A novel algorithm for detecting human circadian rhythms using a thoracic temperature sensor

    Directory of Open Access Journals (Sweden)

    Aly Chkeir

    2017-07-01

    Full Text Available Circadian rhythms undergo high perturbations due to cancer progression and worsening of metabolic diseases. This paper proposes an original method for detecting such perturbations using a novel thoracic temperature sensor. Such an infrared sensor records the skin temperature every five minutes, although some data might be missing. In this pilot study, five control subjects were evaluated over four days of recordings. In order to overcome the problem of missing data, first four different interpolation methods were compared. Using interpolation helps covering the gaps and extending the recordings frequency, subsequently prolonging sensor battery life. Afterwards, a Cosinor model was proposed to characterize circadian rhythms, and extract relevant parameters, with their confidence limits. A divergence study is then performed to detect changes in these parameters. The results are promising, supporting the enlargement of the sample size and warranting further assessment in cancer patients.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    -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...... was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6...

  1. Preliminary evidences of circadian fan activity rhythm in Sabella spallanzanii (Gmelin, 1791 (Polychaeta: Sabellidae

    Directory of Open Access Journals (Sweden)

    Jacopo Aguzzi

    2006-12-01

    Full Text Available The fan activity rhythm of Sabella spallanzanii (Gmelin, 1791 and its entrainment capability to light were studied. Animals were tested under constant darkness (DD followed by two consecutive 24 h light-darkness regimes: a first 11 h light period (LD and a second 9 h light period, with its phase inverted (DL. An infrared analogical video-camera took shots each 30 s. A number of pictures with open fan were counted every 15 min. In DD a weak free-running periodicity in the circadian range was found, thus reinforcing the matching of the 24 h period under study in both photoperiod regimes. A nocturnal activity was characterised with a consistent anticipation to lightOFF (i.e. entrainment. Moreover, this phase of entrainment differed between DL and LD. The presence of endogenous activity rhythm with a variable phase angle of entrainment is a distinctive feature of circadian pacemakers.

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

    Science.gov (United States)

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

    1998-01-01

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

  3. Idiopathic chronic sleep onset insomnia in attention-deficit/hyperactivity disorder: a circadian rhythm sleep disorder.

    Science.gov (United States)

    Van der Heijden, Kristiaan B; Smits, Marcel G; Van Someren, Eus J W; Gunning, W Boudewijn

    2005-01-01

    To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest-activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-naïve children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD-SOI) and 33 children with ADHD without SOI (ADHD-noSOI) referred from community mental health institutions and pediatric departments of non-academic hospitals in The Netherlands. Measurements were 1 wk, 24 h actigraphy recordings and salivary DLMO. The mean (+/-SD) sleep onset time was 21:38 +/- 0:54 h in ADHD-SOI, which was significantly (p insomnia show a delayed sleep phase and delayed DLMO, compared with ADHD children without SOI.

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

    OpenAIRE

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

    2006-01-01

    We used a controlled-environment leaf gas-exchange system and the micrometeorological technique eddy covariance to determine whether circadian rhythms constrain the rates of leaf and canopy gas exchange in an Amazonian forest over a day. When exposed to continuous and constant light for 20 to 48 hours leaves of eleven of seventeen species reduced their photosynthetic rates and closed their stomata during the normally dark period and resumed active gas exchange during the normally light period...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Circadian as well as circannual rhythms of circulating aldosterone have decreased amplitude in aging women.

    Science.gov (United States)

    Cugini, P; Scavo, D; Centanni, M; Halberg, F; Haus, E; Lakatua, D; Schramm, A; Pusch, H J; Franke, H; Kawasaky, T

    1983-02-01

    Age differences in the characteristics of the circadian rhythm in circulating radioimmunoassayable aldosterone were studied on nine 20 to 26 year-old and ten 70 to 78 year-old women and ten 23 to 26 year old and ten 70 to 80 year old men in Würzburg, West Germany. These diurnally active-nocturnally resting subjects were sampled every 3 hours for 15 hours. A classical analysis of variance and a multivariate analysis of rhythm characteristics revealed major effects of age exerted on the circadian aldosterone amplitude in women (p = 0.003) but not in concomitantly sampled men. These observations complement the study of circadian and circannual rhythms in 8 young adults (15-21 years), 10 mature adults (29-36 years) and 10 post-menopausal (44-59 years) North American women, sampled at 100 minute intervals for 24 hours, once in each season, and document that the adrenocortical aldosterone-producing system remains rhythmic with at least two frequencies up to the late decades of human life, although in women it may be characterized by a reduction in the extent of spectral change after 70 years of age.

  8. Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms.

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    Howard J Gritton

    Full Text Available The suprachiasmatic nucleus (SCN is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior.

  9. Circadian Rhythm of Hepatic Cytosolic and Nuclear Estrogen and Androgen Receptors

    Science.gov (United States)

    FRANCAVILLA, ANTONIO; EAGON, PATRICIA K.; DiLEO, ALFREDO; VAN THIEL, DAVID H.; PANELLA, CARMINE; POLIMENO, LORENZO; AMORUSO, CINZIA; INGROSSO, MARCELLO; AQUILINO, A. MARIA; STARZL, THOMAS E.

    2010-01-01

    Mammalian liver is a sex steroid-responsive tissue. The effects of these hormones presumably are mediated by hepatic estrogen receptors (ER) and androgen receptors (AR). Serum levels of sex hormones display circadian rhythms. Further, estrogens and androgens are commonly administered; administration of these agents is associated frequently with liver disease. Therefore, we investigated whether the cytosolic and nuclear sex steroid receptors also display a similar circadian rhythm, and whether variations occurred in the distribution of receptors between cytosolic and nuclear compartments. Animals were killed every 4 h from midnight till the following midnight; cytosolic and nuclear levels of both ER and AR were measured. Cytosolic ER reached a maximum level at 4 AM, and a minimum at 8 PM and midnight of both days. Nuclear ER was highest at 8 AM and lowest at 4 PM and 8 PM, a pattern which parallels variations in serum estradiol levels. Cytosolic AR was highest at 8 PM and lowest at midnight and 4 AM. Nuclear AR was highest at 4 AM and lowest at 4 PM and 8 PM. The highest level of nuclear AR does not correspond to the maximum serum testosterone level, which occurred at 4 PM. The total hepatic content of both ER and AR was not constant over the 24-h period, but varied considerably with time of day. These studies suggest that both ER and AR show a distinct circadian rhythm in subcellular compartmentalization, and that total hepatic content of ER and AR varies significantly during a 24-h period. PMID:3710067

  10. Circadian rhythm abnormalities - Association with the course of inflammatory bowel disease.

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    Sobolewska-Włodarczyk, Aleksandra; Włodarczyk, Marcin; Szemraj, Janusz; Stec-Michalska, Krystyna; Fichna, Jakub; Wiśniewska-Jarosińska, Maria

    2016-08-01

    Crohn's disease (CD) and ulcerative colitis (UC) are the main representatives of inflammatory bowel diseases (IBD), a group of chronic, immune system-mediated inflammatory diseases of the gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions in IBD is not entirely identified and understood: excessive activation of the immune system may come as a result of the interaction of various environmental and infectious factors, genetic predisposition, and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the risk factors for the development of IBD. Currently, there is very little knowledge about circadian rhythm and IBD and there are only a few studies on the relationship between sleep disturbances and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. Furthermore, the relationship between the expression of circadian rhythm genes and severe course of IBD is still unknown. The aim of this review is to show the current state of knowledge about the relationship between circadian rhythm disorders, sleep disturbance and inflammation in the GI tract and to analyze the possibility of employing this knowledge in diagnosis and treatment of IBD. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

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    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

    2015-06-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants.

  12. Scheduled daily mating induces circadian anticipatory activity rhythms in the male rat.

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    Glenn J Landry

    Full Text Available Daily schedules of limited access to food, palatable high calorie snacks, water and salt can induce circadian rhythms of anticipatory locomotor activity in rats and mice. All of these stimuli are rewarding, but whether anticipation can be induced by neural correlates of reward independent of metabolic perturbations associated with manipulations of food and hydration is unclear. Three experiments were conducted to determine whether mating, a non-ingestive behavior that is potently rewarding, can induce circadian anticipatory activity rhythms in male rats provided scheduled daily access to steroid-primed estrous female rats. In Experiment 1, rats anticipated access to estrous females in the mid-light period, but also exhibited post-coital eating and running. In Experiment 2, post-coital eating and running were prevented and only a minority of rats exhibited anticipation. Rats allowed to see and smell estrous females showed no anticipation. In both experiments, all rats exhibited sustained behavioral arousal and multiple mounts and intromissions during every session, but ejaculated only every 2-3 days. In Experiment 3, the rats were given more time with individual females, late at night for 28 days, and then in the midday for 28 days. Ejaculation rates increased and anticipation was robust to night sessions and significant although weaker to day sessions. The anticipation rhythm persisted during 3 days of constant dark without mating. During anticipation of nocturnal mating, the rats exhibited a significant preference for a tube to the mating cage over a tube to a locked cage with mating cage litter. This apparent place preference was absent during anticipation of midday mating, which may reflect a daily rhythm of sexual reward. The results establish mating as a reward stimulus capable of inducing circadian rhythms of anticipatory behavior in the male rat, and reveal a critical role for ejaculation, a modulatory role for time of day, and a

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

    NARCIS (Netherlands)

    van Veen, M.M.; Kooij, J.J.S; Boonstra, A. M.; Gordijn, M.C.M.; van Someren, E.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

  14. Effects of prd circadian clock mutations on FRQ-less rhythms in Neurospora.

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    Li, Sanshu; Lakin-Thomas, Patricia

    2010-04-01

    Rhythmic conidiation (spore formation) in Neurospora crassa provides a model system for investigating the molecular mechanisms of circadian rhythmicity. A feedback loop involving the frq, wc-1, and wc-2 gene products (FRQ/ WCC) is an important component of the mechanism; however, rhythmic conidiation can still be observed when these gene products are absent. The nature of the oscillator(s) that drives this FRQ-less rhythmicity (FLO) is an important question in Neurospora circadian biology. We have looked for interactions between FRQ/WCC and FLO by assaying the effects on FRQ-less rhythms of mutations known to affect the period in the presence of FRQ. We assayed 4 prd mutations (prd-1, prd-2, prd-3, and prd-4) under 2 conditions in frq(null) strains: long-period free-running rhythms in chol-1 strains grown without choline, and heat-entrainable rhythms in choline-sufficient conditions. We found effects of all 4 mutations on both types of FRQ-less rhythms. The greatest effects were seen with prd-1 and prd-2, which abolished free-running rhythms in the chol-1; frq(10) backgrounds and significantly affected entrained peak timing under heat-entrainment conditions in frq( 10) backgrounds. The prd-3 and prd-4 mutations had more subtle effects on period and stability of free-running rhythms in the chol-1; frq(10) backgrounds and had little effect on peak timing under heat-entrainment conditions in frq(10) backgrounds. These results, along with previously published evidence for effects of prd mutations on other FRQ-less rhythms, suggest that either there are common components shared between the FRQ/WCC oscillator and several FRQ-less oscillators or that there is a single oscillator driving all conidiation rhythms. We favor a model of the Neurospora circadian system in which a single FRQ-less oscillator drives conidiation and interacts with the FRQ/WCC feedback loop; the output or amplitude of the FRQ-less oscillator can be affected by many gene products and metabolic

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

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    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.

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

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    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.

  17. Titanium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells.

    Science.gov (United States)

    Hassan, Nathaniel; McCarville, Kirstin; Morinaga, Kenzo; Mengatto, Cristiane M; Langfelder, Peter; Hokugo, Akishige; Tahara, Yu; Colwell, Christopher S; Nishimura, Ichiro

    2017-01-01

    Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated. The Ti biomaterials, which reduced Per1 expression and upregulated Npas2, were further examined with BMSCs harvested from Per1::luc transgenic rats. Next, we addressed the regulatory relationship between Per1 and Npas2 using BMSCs from Npas2 knockout mice. The Npas2 knockout mutation did not rescue the Ti biomaterial-induced Per1 suppression and did not affect Per2, Per3, Bmal1 and Clock expression, suggesting that the Ti biomaterial-induced Npas2 overexpression was likely an independent phenomenon. Previously, vitamin D deficiency was reported to interfere with Ti biomaterial osseointegration. The present study demonstrated that vitamin D supplementation significantly increased Per1::luc expression in BMSCs, though the presence of Ti biomaterials only moderately affected the suppressed Per1::luc expression. Available in vivo microarray data from femurs exposed to Ti biomaterials in vitamin D-deficient rats were evaluated by weighted gene co-expression network analysis. A large co-expression network containing Npas2, Bmal1, and Vdr was observed to form with the Ti biomaterials, which was disintegrated by vitamin D deficiency. Thus, the aberrant BMSC peripheral circadian rhythm may be essential for the integration of Ti biomaterials into bone.

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

    International Nuclear Information System (INIS)

    Pooler, P.A.; Duane, W.C.

    1988-01-01

    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

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

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    Johnson Cynthia E

    2008-09-01

    Full Text Available 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 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

  20. Circadian rhythms of melatonin and cortisol in manifest Huntington's disease and in acute cortical ischemic stroke.

    Science.gov (United States)

    Adamczak-Ratajczak, A; Kupsz, J; Owecki, M; Zielonka, D; Sowinska, A; Checinska-Maciejewska, Z; Krauss, H; Michalak, S; Gibas-Dorna, M

    2017-08-01

    Recent studies indicate disruptions to the circadian system in brain injury and neurodegeneration. The results, however, are often not consistent and limited by measurement of only one circadian marker and by infrequent sampling rates. In this study, we examined diurnal rhythmicity in different stages of Huntington (HD) disease and in patients with acute moderate ischemic stroke (AIS) outside the retinohypothalamic pathway by evaluating serum concentrations of melatonin and cortisol at twelve timepoints. All study participants were subjected to the same study protocol of 12-hour light/dark cycle and controlled room conditions. Using cosinor analysis of data and comparing the results with the controls we found melatonin phase delay with lowered amplitude and mesor in stage III HD patients. These changes coexisted with phase advanced rhythm and elevated values of mesor and amplitude for cortisol. Early and mid-stages of HD showed only a phase advance in cortisol secretion. In AIS the circadian rhythm of serum melatonin was sustained without any phase shift and exhibited more flattened profile (lowered mesor and amplitude values), while advanced rhythm with higher mesor for cortisol was present. In conclusion, 1) abnormal pattern of melatonin release in the late stages of HD and in moderate AIS occurs in conjunction with phase-advanced rhythm of cortisol; 2) changes observed in late stages of HD are similar to those that occur with ageing; 3) brain regions other than the presumptive retinopineal neural pathway may play an important role in the pineal production of melatonin in humans; 4) lesion in extrahypothalamic region is related to the strong adrenal stimulation in response to AIS.

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

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    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.

  2. Altered circadian rhythms of natural killer (NK) cell activity in patients with autoimmune rheumatic diseases.

    Science.gov (United States)

    Masera, R G; Carignola, R; Staurenghi, A H; Sartori, M L; Lazzero, A; Griot, G; Angeli, A

    1994-01-01

    Natural Killer (NK) cells are a lymphocyte subset actively involved in cytotoxicity against tumor-transformed and virus-infected cells; they are a reliable model for the study of neuroendocrine-immune interactions. In previous works we demonstrated that in healthy subjects NK activity of peripheral blood mononuclear cells (PBMC) and susceptibility to endogenous modifiers display statistically validated circadian rhythms. In rheumatoid arthritis (RA) and in other autoimmune rheumatic diseases abnormalities of the circadian rhythm of serum cortisol and altered levels of NK cell activity have been reported. We evaluated the circadian pattern of NK cell activity in 7 hospitalized patients with autoimmune rheumatic diseases (4 RA, 1 scleroderma, 2 mixed connective tissue disease). Temporal variations of in vitro responses to either positive recombinant (immune interferon, r IFN-gamma IFN-gamma: 650 IU/ml; recombinant interleukin-2, r IL-2 IL-2: 100 IU/ml) or negative (cortisol: 10(-6) M) modifiers were also studied. Blood was drawn at 4h intervals for 24 h, starting at 0800. PBMC preparations were immediately separated and incubated for 20h in the presence or absence of modifiers. NK activity was assessed with a direct non-radiometric 4h cytolytic assay, using K 562 cells as targets. Significant circadian variations of spontaneous NK activity were documented only in women with RA, with a peak in the evening hours and a minimum in the night or in the early morning (p < 0.05, PR 51.5%, phi 1829). Population-mean cosinor analysis did not yield detection of significant circadian variations of in vitro responsiveness to modifiers.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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    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.

  4. Differential menopause- versus aging-induced changes in oxidative stress and circadian rhythm gene markers.

    Science.gov (United States)

    Rangel-Zuñiga, Oriol A; Cruz-Teno, Cristina; Haro, Carmen; Quintana-Navarro, Gracia M; Camara-Martos, Fernando; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Garaulet, Marta; Tena-Sempere, Manuel; Lopez-Miranda, Jose; Perez-Jimenez, Francisco; Camargo, Antonio

    2017-06-01

    Menopause is characterized by the depletion of estrogen that has been proposed to cause oxidative stress. Circadian rhythm is an internal biological clock that controls physiological processes. It was analyzed the gene expression in peripheral blood mononuclear cells and the lipids and glucose levels in plasma of a subgroup of 17 pre-menopausal women, 19 men age-matched as control group for the pre-menopausal women, 20 post-menopausal women and 20 men age-matched as control group for the post-menopausal women; all groups were matched by body mass index. Our study showed a decrease in the expression of the oxidative stress-related gene GPX1, and an increase in the expression of SOD1 as consequence of menopause. In addition, we found that the circadian rhythm-related gene PER2 decreased as consequence of menopause. On the other hand, we observed a decrease in the expression of the oxidative stress-related gene GPX4 and an increase in the expression of CAT as a consequence of aging, independently of menopause. Our results suggest that the menopause-induced oxidative stress parallels a disruption in the circadian clock in women, and part of the differences in oxidative stress observed between pre- and post-menopausal women was due to aging, independent of menopause. Clinical Trials.gov.Identifier: NCT00924937. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms.

    Science.gov (United States)

    Rock, Philippa L; Goodwin, Guy M; Wulff, Katharina; McTavish, Sarah F B; Harmer, Catherine J

    2016-03-01

    Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers. Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks. Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times. These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action. © The Author(s) 2016.

  6. Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease.

    Science.gov (United States)

    Versteeg, R I; Serlie, M J; Kalsbeek, A; la Fleur, S E

    2015-08-20

    It is evident that eating in misalignment with the biological clock (such as in shift work, eating late at night and skipping breakfast) is associated with increased risk for obesity and diabetes. The biological clock located in the suprachiasmatic nucleus dictates energy balance including feeding behavior and glucose metabolism. Besides eating and sleeping patterns, glucose metabolism also exhibits clear diurnal variations with higher blood glucose concentrations, glucose tolerance and insulin sensitivity prior to waking up. The daily variation in plasma glucose concentrations in rats, is independent of the rhythm in feeding behavior. On the other hand, feeding itself has profound effects on glucose metabolism, but differential effects occur depending on the time of the day. We here review data showing that a disturbed diurnal eating pattern results in alterations in glucose metabolism induced by a disrupted circadian clock. We first describe the role of central serotonin on feeding behavior and glucose metabolism and subsequently describe the effects of central serotonin on the circadian system. We next explore the interaction between the serotonergic system and the circadian clock in conditions of disrupted diurnal rhythms in feeding and how this might be involved in the metabolic dysregulation that occurs with chronodisruption. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Impacts of shift work on sleep and circadian rhythms.

    Science.gov (United States)

    Boivin, D B; Boudreau, P

    2014-10-01

    Shift work comprises work schedules that extend beyond the typical "nine-to-five" workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2-5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers' health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers' impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts. Copyright © 2014. Published by Elsevier SAS.

  8. Environmental stimuli modulate the circadian rhythm of [3H-methyl]thymidine incorporation into brain DNA of male rats.

    Science.gov (United States)

    Zucconi, G G; Crognale, M C; Bassetti, M A; Giuditta, A

    1990-12-14

    A circadian rhythm of DNA synthesis is present in most organs of adult mammals, with peak levels (acrophase) generally in the rest period. We have recently reported that in the rat brain the acrophase of the rhythm of thymidine incorporation into DNA occurs on the contrary during the active period. To determine whether the brain waking activity was exerting a modulatory action we measured the circadian rhythm of incorporation in the brain and kidney of young adult male rats housed in conditions of sensory and social enrichment or impoverishment for four days. Biochemical and autoradiographic data show that the brain rhythm persists in the enriched condition, but is abolished in the impoverished condition. On the other hand, the rhythm of incorporation in the kidney is maintained in both conditions. These results suggest that the permanence of the brain oscillation is selectively dependent on the complexity of the sensory and social stimulation.

  9. Clock-dependent and system-driven oscillators interact in the suprachiasmatic nuclei to pace mammalian circadian rhythms.

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    Karine Abitbol

    Full Text Available Circadian clocks drive biological rhythms with a period of approximately 24 hours and keep in time with the outside world through daily resetting by environmental cues. While this external entrainment has been extensively investigated in the suprachiasmatic nuclei (SCN, the role of internal systemic rhythms, including daily fluctuations in core temperature or circulating hormones remains debated. Here, we show that lactating mice, which exhibit dampened systemic rhythms, possess normal molecular clockwork but impaired rhythms in both heat shock response gene expression and electrophysiological output in their SCN. This suggests that body rhythms regulate SCN activity downstream of the clock. Mathematical modeling predicts that systemic feedback upon the SCN functions as an internal oscillator that accounts for in vivo and ex vivo observations. Thus we are able to propose a new bottom-up hierarchical organization of circadian timekeeping in mammals, based on the interaction in the SCN between clock-dependent and system-driven oscillators.

  10. Circadian Rhythms and Clock Genes in Reproduction: Insights From Behavior and the Female Rabbit’s Brain

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    Mario Caba

    2018-03-01

    Full Text Available Clock gene oscillations are necessary for a successful pregnancy and parturition, but little is known about their function during lactation, a period demanding from the mother multiple physiological and behavioral adaptations to fulfill the requirements of the offspring. First, we will focus on circadian rhythms and clock genes in reproductive tissues mainly in rodents. Disruption of circadian rhythms or proper rhythmic oscillations of clock genes provoke reproductive problems, as found in clock gene knockout mice. Then, we will focus mainly on the rabbit doe as this mammal nurses the young just once a day with circadian periodicity. This daily event synchronizes the behavior and the activity of specific brain regions critical for reproductive neuroendocrinology and maternal behavior, like the preoptic area. This region shows strong rhythms of the PER1 protein (product of the Per1 clock gene associated with circadian nursing. Additionally, neuroendocrine cells related to milk production and ejections are also synchronized to daily nursing. A threshold of suckling is necessary to entrain once a day nursing; this process is independent of milk output as even virgin does (behaving maternally following anosmia can display circadian nursing behavior. A timing motivational mechanism may regulate such behavior as mesolimbic dopaminergic cells are entrained by daily nursing. Finally, we will explore about the clinical importance of circadian rhythms. Indeed, women in chronic shift-work schedules show problems in their menstrual cycles and pregnancies and also have a high risk of preterm delivery, making this an important field of translational research.

  11. Chronotype differences in circadian rhythms of temperature, melatonin, and sleepiness as measured in a modified constant routine protocol

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    Leon Lack

    2009-11-01

    Full Text Available Leon Lack, Michelle Bailey, Nicole Lovato, Helen WrightSchool of Psychology, Flinders University, Adelaide, South Australia, AustraliaAbstract: Evening chronotypes typically have sleep patterns timed 2–3 hours later than morning chronotypes. Ambulatory studies have suggested that differences in the timing of underlying circadian rhythms as a cause of the sleep period differences. However, differences in endogenous circadian rhythms are best explored in laboratory protocols such as the constant routine. We used a 27-hour modified constant routine to measure the endogenous core temperature and melatonin circadian rhythms as well as subjective and objective sleepiness from hourly 15-minute sleep opportunities. Ten (8f morning type individuals were compared with 12 (8f evening types. All were young, healthy, good sleepers. The typical sleep onset, arising times, circadian phase markers for temperature and melatonin and objective sleepiness were all 2–3 hours later for the evening types than morning types. However, consistent with past studies the differences for the subjective sleepiness rhythms were much greater (5–9 hours. Therefore, the present study supports the important role of subjective alertness/sleepiness in determining the sleep period differences between morning and evening types and the possible vulnerability of evening types to delayed sleep phase disorder.Keywords: chronotype, constant routine, circadian rhythms, sleep propensity, subjective sleepiness

  12. Circadian Rhythms of Melatonin Secretion in Peri- and Postmenopausal Women with Insomnia

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    Irina M. Madaeva

    2017-06-01

    Full Text Available The aim of this study was to assess complaints about sleep quality and to investigate circadian rhythms of melatonin secretion in peri- and postmenopausal women. Material and Methods: A total of 146 climacteric women were examined. All patients were divided into 2 groups: Group1 included 72 perimenopausal women and Group 2 included 74 postmenopausal women. Women were surveyed with special questionnaires: PSQI, FFS, ESS, Daytime Feeling and Functioning Scale. Insomnia Severity Index was calculated. Salivary melatonin content was determined (4 times a day by immunoassay using Microplate Reader EL×808 (USA. Results: Perimenopausal women often complained about difficulties falling asleep (more than 20 minutes from the moment the light was turned off and difficulties awakening in the morning, while postmenopausal women often complained about snoring and frequent awakenings during sleep(≥2 times. ISI was 21.3±0.54 in Group 1 and 24.8±0.31 in Group 2, which corresponded to insomnia. Daily melatonin secretion in perimenopausal patients with insomnia was altered – the maximal level was registered in the morning hours. The circadian rhythms of melatonin secretion in the group of postmenopausal women did not correlate to the occurrence of insomnia. Conclusion: We can recommend administration of melatonin in the evening time and light therapy in the early morning hours in the complex treatment of SDs in perimenopausal women for normalizing and shifting the chronobiological rhythms of melatonin secretion, and specific therapy is aimed to eliminate snoring for postmenopausal women.

  13. Photoperiodism and circadian rhythms in relation to the hazards of environmental pollutants

    International Nuclear Information System (INIS)

    Attia, A.M.; Ali, M.M.; Abdou, M.M.

    1999-01-01

    The duration, intensity and wavelengths of light to which vertebrates and invertebrates are exposed vary widely over a 24-hour period as well as throughout the year. Species, by means of their behavioral patterns, differentially control in part the photoperiodic environment to which they are exposed. It is essential that mammals, probably including humans, adjust their physiology with changes in the makeup of the photoperiod. Numerous body functions undergo variations recurring at about 24-hour intervals in the presence or absence of known environmental changes with similar periods. This applies to continuos but rhythmic phenomena, with a peak and trough repeating itself every 24-hours, as well as to discrete events occurring about once a day. The time intervals separating these consecutive periodic events are similar but often not identical. Such periods are called circadian. Rhythms have been reported in cell growth, hormonal levels, and so on. Rhythms are generally resistant to a variety of chemical substances including stimulants and depressants. photoperiodism and circadian rhythms, in relation to the hazardous effects of environmental pollutants, as pesticides; which may directly or indirectly affect or alter physiologocal processes in living things, are summarized

  14. The Optic Lobes Regulate Circadian Rhythms of Olfactory Learning and Memory in the Cockroach.

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    Lubinski, Alexander J; Page, Terry L

    2016-04-01

    The cockroach, Leucophaea maderae, can be trained in an associative olfactory memory task by either classical or operant conditioning. When trained by classical conditioning, memory formation is regulated by a circadian clock, but once the memory is formed, it can be recalled at any circadian time. In contrast, when trained via operant conditioning, animals can learn the task at any circadian phase, but the ability to recall the long-term memory is tied to the phase of training. The optic lobes of the cockroach contain a circadian clock that drives circadian rhythms of locomotor activity, mating behavior, sensitivity of the compound eye to light, and the sensitivity of olfactory receptors in the antennae. To evaluate the role of the optic lobes in regulating learning and memory processes, the authors examined the effects of surgical ablation of the optic lobes on memory formation in classical conditioning and memory recall following operant conditioning. The effect of optic lobe ablation was to "rescue" the deficit in memory acquisition at a time the animals normally cannot learn and "rescue" the animal's ability to recall a memory formed by operant conditioning at a phase where memory was not normally expressed. The results suggested that the optic lobe pacemaker regulates these processes through inhibition at "inappropriate" times of day. As a pharmacological test of this hypothesis, the authors showed that injections of fipronil, an antagonist of GABA and glutamate-activated chloride channels, had the same effects as optic lobe ablation on memory formation and recall. The data suggest that the optic lobes contain the circadian clock(s) that regulate learning and memory processes via inhibition of neural processes in the brain. © 2015 The Author(s).

  15. Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells

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    Devos Julia

    2011-12-01

    Full Text Available Abstract Background The Magel2 gene is most highly expressed in the suprachiasmatic nucleus of the hypothalamus, where its expression cycles in a circadian pattern comparable to that of clock-controlled genes. Mice lacking the Magel2 gene have hypothalamic dysfunction, including circadian defects that include reduced and fragmented total activity, excessive activity during the subjective day, but they have a normal circadian period. Magel2 is a member of the MAGE family of proteins that have various roles in cellular function, but the specific function of Magel2 is unknown. Methods We used a variety of cell-based assays to determine whether Magel2 modifies the properties of core circadian rhythm proteins. Results Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization. Conclusion Consistent with the blunted circadian rhythm observed in Magel2-null mice, these data suggest that Magel2 normally promotes negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins.

  16. Effects of irradiation on the circadian rhythm in the release of peptides in the suprachiasmatic nucleus culture

    International Nuclear Information System (INIS)

    Saito, Kimihiko

    2000-01-01

    Mammalian circadian rhythms are regulated by the circadian clock which is located in the hypothalamic suprachiasmatic nucleus (SCN). In the present study, we examined the effect of irradiation on the circadian rhythm in the release of arginine-vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in slice cultures of the rat SCN. The effect of irradiation on the glial cell proliferation in the SCN culture was also examined by the immunohistochemical method. In SCN cultures which received irradiation, circadian rhythms in the release of AVP and VIP were detected, as observed in the SCN culture not irradiated. However, the AVP and VIP rhythms showed various phase angle differences in some cultures irradiated, which suggested that irradiation caused a looseness of coupling between AVP and VIP oscillators. On the other hand, the number of glial cells was decreased by irradiation. These results suggested that the dissociation of the two peptide rhythms after irradiation might be due to the inhibition of glial cell proliferation. Furthermore, the radiation changed the amplitude of AVP and VIP rhythms, suggesting that couplings within both AVP and VIP oscillators were influenced by irradiation. (author)

  17. Using Actiwatch to monitor circadian rhythm disturbance in Huntington' disease: A cautionary note.

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    Townhill, Jenny; Hughes, Alis C; Thomas, Benny; Busse, Monica E; Price, Kathy; Dunnett, Stephen B; Hastings, Michael H; Rosser, Anne E

    2016-05-30

    Huntington's disease (HD) is an inherited neurodegenerative disorder that is well recognised as producing progressive deterioration of motor function, including dyskinetic movements, as well as deterioration of cognition and ability to carry out activities of daily living. However, individuals with HD commonly suffer from a wide range of additional symptoms, including weight loss and sleep disturbance, possibly due to disruption of circadian rhythmicity. Disrupted circadian rhythms have been reported in mice models of HD and in humans with HD. One way of assessing an individual's circadian rhythmicity in a community setting is to monitor their sleep/wake cycles, and a convenient method for recording periods of wakefulness and sleep is to use accelerometers to discriminate between varied activity levels (including sleep) during daily life. Here we used Actiwatch(®) Activity monitors alongside ambulatory EEG and sleep diaries to record wake/sleep patterns in people with HD and normal volunteers. We report that periods of wakefulness during the night, as detected by activity monitors, agreed poorly with EEG recordings in HD subjects, and unsurprisingly sleep diary findings showed poor agreement with both EEG recordings and activity monitor derived sleep periods. One explanation for this is the occurrence of 'break through' involuntary movements during sleep in the HD patients, which are incorrectly assessed as wakeful periods by the activity monitor algorithms. Thus, care needs to be taken when using activity monitors to assess circadian activity in individuals with movement disorders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Development of a Measure of Sleep, Circadian Rhythms, and Mood: The SCRAM Questionnaire

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    Jamie E. M. Byrne

    2017-12-01

    Full Text Available Sleep quality, circadian phase, and mood are highly interdependent processes. Remarkably, there is currently no self-report questionnaire that measures all three of these clinically significant functions: The aim of this project was to address this deficit. In Study 1, 720 participants completed a set of potential items was generated from existing questionnaires in each of the three domains and refined to follow a single presentation format. Study 2 used an independent sample (N = 498 to interrogate the latent structure. Exploratory factor analysis was used to identify a parsimonious, three-factor latent structure. Following item reduction, the optimal representation of sleep quality, circadian phase, and mood was captured by a questionnaire with three 5-item scales: Depressed Mood, Morningness, and Good Sleep. Confirmatory factor analysis found the three-scale structure provided adequate fit. In both samples, Morningness and Good Sleep were positively associated, and each was negatively associated with the Depressed Mood scale. Further research is now required to quantify the convergent and discriminant validity of its three face-valid and structurally replicated scales. The new sleep, circadian rhythms, and mood (SCRAM questionnaire is the first instrument to conjointly measure sleep quality, circadian phase, and mood processes, and has significant potential as a clinical tool.

  19. Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome.

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    Trenkwalder, C; Hening, W A; Walters, A S; Campbell, S S; Rahman, K; Chokroverty, S

    1999-01-01

    The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion.

  20. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease.

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    Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-02-19

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.

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

    International Nuclear Information System (INIS)

    Korolyuk, I.P.; Katricheva, L.V.; Kel'tsev, V.A.

    1982-01-01

    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 3 , T 4 , TTH, AKTH and hydrocortisone was determined in the blood serum using standard kits for in vitro diagnosis. Certain rhytmicality 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 shoud be considered in the treatment of such patients

  2. Cryptochromes define a novel circadian clock mechanism in monarch butterflies that may underlie sun compass navigation.

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    Haisun Zhu

    2008-01-01

    Full Text Available The circadian clock plays a vital role in monarch butterfly (Danaus plexippus migration by providing the timing component of time-compensated sun compass orientation, a process that is important for successful navigation. We therefore evaluated the monarch clockwork by focusing on the functions of a Drosophila-like cryptochrome (cry, designated cry1, and a vertebrate-like cry, designated cry2, that are both expressed in the butterfly and by placing these genes in the context of other relevant clock genes in vivo. We found that similar temporal patterns of clock gene expression and protein levels occur in the heads, as occur in DpN1 cells, of a monarch cell line that contains a light-driven clock. CRY1 mediates TIMELESS degradation by light in DpN1 cells, and a light-induced TIMELESS decrease occurs in putative clock cells in the pars lateralis (PL in the brain. Moreover, monarch cry1 transgenes partially rescue both biochemical and behavioral light-input defects in cry(b mutant Drosophila. CRY2 is the major transcriptional repressor of CLOCK:CYCLE-mediated transcription in DpN1 cells, and endogenous CRY2 potently inhibits transcription without involvement of PERIOD. CRY2 is co-localized with clock proteins in the PL, and there it translocates to the nucleus at the appropriate time for transcriptional repression. We also discovered CRY2-positive neural projections that oscillate in the central complex. The results define a novel, CRY-centric clock mechanism in the monarch in which CRY1 likely functions as a blue-light photoreceptor for entrainment, whereas CRY2 functions within the clockwork as the transcriptional repressor of a negative transcriptional feedback loop. Our data further suggest that CRY2 may have a dual role in the monarch butterfly's brain-as a core clock element and as an output that regulates circadian activity in the central complex, the likely site of the sun compass.

  3. Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.

    Science.gov (United States)

    Lech, Karolina; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

    2016-02-01

    The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings. © 2015 The Author(s).

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

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    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.

  5. Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice.

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    Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D; Barandas, Rita; Malinow, Roberto; Welsh, David K

    2016-12-01

    Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

  6. Diurnal and circadian rhythms in the tomato transcriptome and their modulation by cryptochrome photoreceptors.

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    Paolo Facella

    Full Text Available BACKGROUND: Circadian clocks are internal molecular time-keeping mechanisms that provide living organisms with the ability to adjust their growth and physiology and to anticipate diurnal environmental changes. Circadian clocks, without exception, respond to light and, in plants, light is the most potent and best characterized entraining stimulus. The capacity of plants to respond to light is achieved through a number of photo-perceptive proteins including cryptochromes and phytochromes. There is considerable experimental evidence demonstrating the roles of photoreceptors in providing light input to the clock. METHODOLOGY: In order to identify genes regulated by diurnal and circadian rhythms, and to establish possible functional relations between photoreceptors and the circadian clock in tomato, we monitored the temporal transcription pattern in plants entrained to long-day conditions, either by large scale comparative profiling, or using a focused approach over a number of photosensory and clock-related genes by QRT-PCR. In parallel, focused transcription analyses were performed in cry1a- and in CRY2-OX tomato genotypes. CONCLUSIONS: We report a large series of transcript oscillations that shed light on the complex network of interactions among tomato photoreceptors and clock-related genes. Alteration of cryptochrome gene expression induced major changes in the rhythmic oscillations of several other gene transcripts. In particular, over-expression of CRY2 had an impact not only on day/night fluctuations but also on rhythmicity under constant light conditions. Evidence was found for widespread diurnal oscillations of transcripts encoding specific enzyme classes (e.g. carotenoid biosynthesis enzymes as well as for post-transcriptional diurnal and circadian regulation of the CRY2 transcript.

  7. Ovariectomy influences the circadian rhythm of locomotor activity and the photic phase shifts in the volcano mouse.

    Science.gov (United States)

    Juárez-Tapia, Cinthia; Miranda-Anaya, Manuel

    2017-12-01

    Recently, the relationship between the circadian system and female reproduction has been of great interest; ovarian hormones can modify the amount and distribution of daily activity differently in rodent species. The volcano mouse Neotomodon alstoni is a species in which it is possible to study the circadian rhythm of locomotion, and it offers comparative information about the influence of ovaries on the circadian system. In this study, we used infrared crossings to compare free movement in intact and sham-operated or ovariectomized mice. We analyzed behavioral and endocrine changes related to the estrous cycle and locomotor circadian rhythm in free-running mice and photic phase shifting. Evidence shows that intact mice present a scalloped pattern of daily activity during the estrous cycle. In constant darkness, the ovariectomy reduces the total amount of activity, shortens the free-running circadian period of locomotion and increases photic phase shifts during the early subjective night. During entrainment, the ovariectomized mice increased the amplitude of total activity during the scotophase, and delay the time of activity onset. These results suggest that ovarian hormones in N. alstoni modulate the circadian rhythm of locomotor activity in a species-specific manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Circadian Rhythm of Ambient Noise Off the Southeast Coast of India

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    Kannan, R.; Latha, G.; Prashanthi Devi, M.

    An ambient noise system consisting of a vertical linear hydrophone array was deployed in the shallow waters off Chennai, southeast coast of India from 1 August to 16 September 2013 to record ambient ocean noise of frequencies up to 10kHz. Biological sounds, which are broadband, short duration signals resulting from Terapon theraps, a native species, are a prominent feature of the ocean soundscape. Terapon activity peaks at 8pm and 11pm, and its presence is not observed after 12 midnight in both the months. In the other period, the ambient noise fluctuation is due to wind and vessel traffic. Hence, the present study focuses on the description of the ambient noise fluctuation over two 12h periods, i.e., 12 midnight-12 noon considered as period I, and 12 noon-12 midnight as period II in order to show the circadian rhythm of ambient noise. In this study area, Terapon vocalization reached 25dB above the ambient noise level and it dominates the short-term spectra records in the 0.4-4kHz range. All Terapon signals had daily patterns of sound production with highest levels of activity after dusk during the study period. The result shows that the circadian rhythm of ambient noise is mainly of biological sound generated by Terapon and it is reported first time in the shallow waters off the southeast coast of India.

  9. Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis.

    Science.gov (United States)

    Lavtar, Polona; Rudolf, Gorazd; Maver, Aleš; Hodžić, Alenka; Starčević Čizmarević, Nada; Živković, Maja; Šega Jazbec, Saša; Klemenc Ketiš, Zalika; Kapović, Miljenko; Dinčić, Evica; Raičević, Ranko; Sepčić, Juraj; Lovrečić, Luca; Stanković, Aleksandra; Ristić, Smiljana; Peterlin, Borut

    2018-01-01

    Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized that this fact might be partially associated with the influence of latitude on circadian rhythm and consequently that genetic variability of key circadian rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian patients and 1024 healthy controls were compared for genetic signature at 8 SNPs, 4 for each of both genes. We found a statistically significant difference in genotype (ARNTL rs3789327, P = 7.5·10-5; CLOCK rs6811520 P = 0.02) distributions in patients and controls. The ARNTL rs3789327 CC genotype was associated with higher risk for multiple sclerosis at an OR of 1.67 (95% CI 1.35-2.07, P = 0.0001) and the CLOCK rs6811520 genotype CC at an OR of 1.40 (95% CI 1.13-1.73, P = 0.002). The results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis.

  10. The effect of intermittent fasting during Ramadan on sleep, sleepiness, cognitive function, and circadian rhythm.

    Science.gov (United States)

    Qasrawi, Shaden O; Pandi-Perumal, Seithikurippu R; BaHammam, Ahmed S

    2017-09-01

    Studies have shown that experimental fasting can affect cognitive function, sleep, and wakefulness patterns. However, the effects of experimental fasting cannot be generalized to fasting during Ramadan due to its unique characteristics. Therefore, there has been increased interest in studying the effects of fasting during Ramadan on sleep patterns, daytime sleepiness, cognitive function, sleep architecture, and circadian rhythm. In this review, we critically discuss the current research findings in those areas during the month of Ramadan. Available data that controlled for sleep/wake schedule, sleep duration, light exposure, and energy expenditure do not support the notion that Ramadan intermittent fasting increases daytime sleepiness and alters cognitive function. Additionally, recent well-designed studies showed no effect of fasting on circadian rhythms. However, in non-constrained environments that do not control for lifestyle changes, studies have demonstrated sudden and significant delays in bedtime and wake time. Studies that controlled for environmental factors and sleep/wake schedule reported no significant disturbances in sleep architecture. Nevertheless, several studies have consistently reported that the main change in sleep architecture during fasting is a reduction in the proportion of REM sleep.

  11. Circadian Rhythms and Redox State in Plants: Till Stress Do Us Part

    Directory of Open Access Journals (Sweden)

    Carmela R. Guadagno

    2018-03-01

    Full Text Available A growing body of evidence demonstrates a significant relationship between cellular redox state and circadian rhythms. Each day these two vital components of plant biology influence one another, dictating the pace for metabolism and physiology. Diverse environmental stressors can disrupt this condition and, although plant scientists have made significant progress in re-constructing functional networks of plant stress responses, stress impacts on the clock-redox crosstalk is poorly understood. Inter-connected phenomena such as redox state and metabolism, internal and external environments, cellular homeostasis and rhythms can impede predictive understanding of coordinated regulation of plant stress response. The integration of circadian clock effects into predictive network models is likely to increase final yield and better predict plant responses to stress. To achieve such integrated understanding, it is necessary to consider the internal clock not only as a gatekeeper of environmental responses but also as a target of stress syndromes. Using chlorophyll fluorescence as a reliable and high-throughput probe of stress coupled to functional genomics and metabolomics will provide insights on the crosstalk across a wide range of stress severity and duration, including potential insights into oxidative stress response and signaling. We suggest the efficiency of photosystem II in light conditions (Fv′/Fm′ to be the most dynamic of the fluorescence variables and therefore the most reliable parameter to follow the stress response from early sensing to mortality.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  15. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-01-01

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles. PMID:22379191

  16. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators.

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-03-15

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles.

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

    Science.gov (United States)

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

    2014-11-01

    Many behaviors and physiological processes oscillate with circadian rhythms that are synchronized to environmental cues (e.g. light onset), but persist with periods of ~24 h in the absence of such cues. We used a multilevel experimental approach to assess whether circadian rhythms modulate several aspects of the visual physiology and behavior of the praying mantis Hierodula patellifera. We used electroretinograms (ERGs) to assess compound eye sensitivity, colorimetric photographic analyses to assess compound eye color changes (screening pigment migration), behavioral assays of responsiveness to computer-generated prey-like visual stimuli and analyses of locomotor activity patterns on a modified treadmill apparatus. Our results indicate that circadian clocks control and/or modulate each of the target behaviors. Strong rhythms, persisting under constant conditions, with periods of ~24 h were evident in photoreceptor sensitivity to light, appetitive responsiveness to prey-like stimuli and gross locomotor activity. In the first two cases, responsiveness was highest during the subjective night and lowest during the subjective day. Locomotor activity was strongly clustered around the transition time from day to night. In addition, pigment migration and locomotor behavior responded strongly to light:dark cycles and anticipated the light-dark transition, suggesting that the circadian clocks modulating both were entrained to environmental light cues. Together, these data indicate that circadian rhythms operate at the cellular, cellular systems and organismal level in H. patellifera. Our results represent an intriguing first step in uncovering the complexities of circadian rhythms in the Mantodea. © 2014. Published by The Company of Biologists Ltd.

  18. Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

    Science.gov (United States)

    Hadaeghi, Fatemeh; Hashemi Golpayegani, Mohammad Reza; Jafari, Sajad; Murray, Greg

    2016-08-01

    In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this

  19. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    ism to remain in-sync with the external world. While some of .... of chronobiology, Aschoff's Rule Prize and Pittendrigh/Aschoff Lecture Prize is awarded to eminent researchers in chronobiology. ... on Germanium formed the basis for the invention of the first transistor which won the Nobel Prize in Physics in 1956. Meanwhile ...

  20. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    fixation) harboured by the bacteria is sensitive to oxygen. Thus, cyanobacteria have evolved mechanisms to isolate the nitrogenase enzyme from oxygen. The photosynthetic cycle and the nitrogen fixation cycle are temporally segregated such that the vegetative cells produce oxygen through photosynthesis when nitrogen.

  1. Circadian Rhythms

    Indian Academy of Sciences (India)

    K L Nikhil1 Vijay Kumar Sharma2. Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436 Bangalore 560064, India. Chronobiology Laboratory Evolutionary and Organismal Biology Unit Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436 Bangalore 560064, India.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Guerriero, Maria L.; Akman, Ozgur E.; van Ooijen, Gerben

    2014-01-01

    Rhythmic behavior is essential for plants; for example, daily (circadian) rhythms control photosynthesis and seasonal rhythms regulate their life cycle. The core of the circadian clock is a genetic network that coordinates the expression of specific clock genes in a circadian rhythm reflecting the 24-h day/night cycle. Circadian clocks exhibit stochastic noise due to the low copy numbers of clock genes and the consequent cell-to-cell variation: this intrinsic noise plays a major role in circadian clocks by inducing more robust oscillatory behavior. Another source of noise is the environment, which causes variation in temperature and light intensity: this extrinsic noise is part of the requirement for the structural complexity of clock networks. Advances in experimental techniques now permit single-cell measurements and the development of single-cell models. Here we present some modeling studies showing the importance of considering both types of noise in understanding how plants adapt to regular and irregular light variations. Stochastic models have proven useful for understanding the effect of regular variations. By contrast, the impact of irregular variations and the interaction of different noise sources are less well studied. PMID:25374576

  5. The release of a pheromonotropic neuropeptide, PBAN, in the turnip moth Agrotis segetum, exhibits a circadian rhythm

    Czech Academy of Sciences Publication Activity Database

    Závodská, Radka; von Wowern, G.; Löfstedt, C.; Rosén, W. Q.; Šauman, Ivo

    2009-01-01

    Roč. 55, č. 5 (2009), s. 435-440 ISSN 0022-1910 R&D Projects: GA MŠk LC07032 Institutional research plan: CEZ:AV0Z50070508 Keywords : pheromone biosynthesis activating * neuropeptide (PBAN) * circadian rhythm Subject RIV: ED - Physiology Impact factor: 2.235, year: 2009

  6. Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism.

    Science.gov (United States)

    Wells, Audrey M; Ridener, Elysia; Bourbonais, Clinton A; Kim, Woori; Pantazopoulos, Harry; Carroll, F Ivy; Kim, Kwang-Soo; Cohen, Bruce M; Carlezon, William A

    2017-08-09

    Stress plays a critical role in the neurobiology of mood and anxiety disorders. Sleep and circadian rhythms are affected in many of these conditions. Here we examined the effects of chronic social defeat stress (CSDS), an ethological form of stress, on sleep and circadian rhythms. We exposed male mice implanted with wireless telemetry transmitters to a 10 day CSDS regimen known to produce anhedonia (a depressive-like effect) and social avoidance (an anxiety-like effect). EEG, EMG, body temperature, and locomotor activity data were collected continuously during the CSDS regimen and a 5 day recovery period. CSDS affected numerous endpoints, including paradoxical sleep (PS) and slow-wave sleep (SWS), as well as the circadian rhythmicity of body temperature and locomotor activity. The magnitude of the effects increased with repeated stress, and some changes (PS bouts, SWS time, body temperature, locomotor activity) persisted after the CSDS regimen had ended. CSDS also altered mRNA levels of the circadian rhythm-related gene mPer2 within brain areas that regulate motivation and emotion. Administration of the κ-opioid receptor (KOR) antagonist JDTic (30 mg/kg, i.p.) before CSDS reduced stress effects on both sleep and circadian rhythms, or hastened their recovery, and attenuated changes in mPer2 Our findings show that CSDS produces persistent disruptions in sleep and circadian rhythmicity, mimicking attributes of stress-related conditions as they appear in humans. The ability of KOR antagonists to mitigate these disruptions is consistent with previously reported antistress effects. Studying homologous endpoints across species may facilitate the development of improved treatments for psychiatric illness. SIGNIFICANCE STATEMENT Stress plays a critical role in the neurobiology of mood and anxiety disorders. We show that chronic social defeat stress in mice produces progressive alterations in sleep and circadian rhythms that resemble features of depression as it appears in

  7. An endogenous circadian rhythm in sleep inertia results in greatest cognitive impairment upon awakening during the biological night.

    Science.gov (United States)

    Scheer, Frank A J L; Shea, Thomas J; Hilton, Michael F; Shea, Steven A

    2008-08-01

    Sleep inertia is the impaired cognitive performance immediately upon awakening, which decays over tens of minutes. This phenomenon has relevance to people who need to make important decisions soon after awakening, such as on-call emergency workers. Such awakenings can occur at varied times of day or night, so the objective of the study was to determine whether or not the magnitude of sleep inertia varies according to the phase of the endogenous circadian cycle. Twelve adults (mean, 24 years; 7 men) with no medical disorders other than mild asthma were studied. Following 2 baseline days and nights, subjects underwent a forced desynchrony protocol composed of seven 28-h sleep/wake cycles, while maintaining a sleep/wakefulness ratio of 1:2 throughout. Subjects were awakened by a standardized auditory stimulus 3 times each sleep period for sleep inertia assessments. The magnitude of sleep inertia was quantified as the change in cognitive performance (number of correct additions in a 2-min serial addition test) across the first 20 min of wakefulness. Circadian phase was estimated from core body temperature (fitted temperature minimum assigned 0 degrees ). Data were segregated according to: (1) circadian phase (60 degrees bins); (2) sleep stage; and (3) 3rd of the night after which awakenings occurred (i.e., tertiary 1, 2, or 3). To control for any effect of sleep stage, the circadian rhythm of sleep inertia was initially assessed following awakenings from Stage 2 (62% of awakening occurred from this stage; n = 110). This revealed a significant circadian rhythm in the sleep inertia of cognitive performance (p = 0.007), which was 3.6 times larger during the biological night (circadian bin 300 degrees , approximately 2300-0300 h in these subjects) than during the biological day (bin 180 degrees , approximately 1500-1900 h). The circadian rhythm in sleep inertia was still present when awakenings from all sleep stages were included (p = 0.004), and this rhythm could not be

  8. Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael Verwey

    2016-08-01

    Full Text Available Circadian clock proteins form an autoregulatory feedback loop that is central to the endogenous generation and transmission of daily rhythms in behavior and physiology. Increasingly, circadian rhythms in clock gene expression are being reported in diverse tissues and brain regions that lie outside of the suprachiasmatic nucleus (SCN, the master circadian clock in mammals. For many of these extra-SCN rhythms, however, the region-specific implications are still emerging. In order to gain important insights into the potential behavioral, physiological, and psychological relevance of these daily oscillations, researchers have begun to focus on describing the neurochemical, hormonal, metabolic, and epigenetic contributions to the regulation of these rhythms. This review will highlight important sites and sources of circadian control within dopaminergic and striatal circuitries of the brain and will discuss potential implications for psychopathology and disease. For example, rhythms in clock gene expression in the dorsal striatum are sensitive to changes in dopamine release, which has potential implications for Parkinson’s disease and drug addiction. Rhythms in the ventral striatum and limbic forebrain are sensitive to psychological and physical stressors, which may have implications for major depressive disorder. Collectively, a rich circadian tapestry has emerged that forces us to expand traditional views and to reconsider the psychopathological, behavioral, and physiological importance of these region-specific rhythms in brain areas that are not immediately linked with the regulation of circadian rhythms.

  9. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Science.gov (United States)

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  10. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Directory of Open Access Journals (Sweden)

    Ivan Ho Mien

    Full Text Available Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2 s(-1, intermittent red light (1 min on/off, or bright white light (2,500 lux near the onset of nocturnal melatonin secretion (n = 8 in each group. Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69, with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  11. Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

    Directory of Open Access Journals (Sweden)

    Mariam Sabbar

    2017-09-01

    Full Text Available Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p. during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD cycle and in complete darkness (DD. At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir- of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances.

  12. Regularity of daily life in relation to personality, age, gender, sleep quality and circadian rhythms

    Science.gov (United States)

    Monk, T. H.; Petrie, S. R.; Hayes, A. J.; Kupfer, D. J.

    1994-01-01

    A diary-like instrument to measure lifestyle regularity (the 'Social Rhythm Metric'-SRM) was given to 96 subjects (48 women, 48 men), 39 of whom repeated the study after at least one year, with additional objective measures of rest/activity. Lifestyle regularity as measured by the SRM related to age, morningness, subjective sleep quality and time-of-day variations in alertness, but not to gender, extroversion or neuroticism. Statistically significant test-retest correlations of about 0.4 emerged for SRM scores over the 12-30 month delay. Diary-based estimates of bedtime and waketime appeared fairly reliable. In a further study of healthy young men, 4 high SRM scorers ('regular') had a deeper nocturnal body temperature trough than 5 low SRM scorers ('irregular'), suggesting a better functioning circadian system in the 'regular' group.

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

    Science.gov (United States)

    Fei, Guang-he; Liu, Rong-yu; Zhang, Zhi-hong; Zhou, Jiang-ning

    2004-05-01

    To investigate the possible relationships between alterations in circadian rhythm of melatonin, cortisol and bronchial asthma. 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. The results showed overall lower levels of salivary melatonin in asthma patients compared with control subject (Pmelatonin were significantly lower in mild intermittent or persistent (Pcortisol was greatly lower and the acrophase was markedly delayed in patients with mild intermittent or persistent asthma (Pmelatonin and cortisol were found in asthma patients, which may be involved in the pathogenesis of bronchial asthma.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Sudden death circadian rhythm in Chagasic patients compared to non-Chagasic patients.

    Science.gov (United States)

    Marques, Juan; Mendoza, Iván; Suárez, Claudia; Moleiro, Federico; Mendoza-Britto, Iván; Marques-Mejías, Maria

    2017-01-01

    Chagas disease (Ch) affects 8-10 million people in Latin America, most of them are poor. Sudden death (SD) is the major cause of death in patients with Ch. To the best of our knowledge, the present report covers the largest reported series comparing the SD of Ch versus non-Ch patients Objective: To compare the circadian rhythm of SD in Ch versus non-Ch patients. Retrospective analysis of all the cases of SD recorded in our department, including autopsied patients from 1963 until 2011. The pattern of SD of 262 patients (116 Ch and 146 non-Ch), 56.7% men, average age 54, 6 years old, divided into four groups: Group A: Ch with SD (n = 38), Group B: non-Ch with SD (n = 58), Group C. Ch with non SD (n = 89), and Group D: non-Ch with non SD (n = 81). For the statistical analysis, proportion comparison was used. 44.7% (17/38) of SDs in Group A (Ch) occurred between 6 a.m. and 5:59 p.m., while for Group B (not Ch) 70.7% (41 /58) died in that time (p < 0.005). 55.3% (21/38) of the SD in Group A (Ch) occurred between 6 p.m. and 5:59 a.m. compared with 29.3% (17/58) in Group B (p < 0, 005). Circadian rhythm of SD in patient with Ch differs from those with non-Ch. In Ch patients, SD occurs predominantly during the night compared with non-Ch SD that occurs predominantly during the day especially during the morning.

  16. Redundancy of stomatal control for the circadian photosynthetic rhythm in Kalanchoë daigremontiana Hamet et Perrier.

    Science.gov (United States)

    Wyka, T P; Duarte, H M; Lüttge, U E

    2005-03-01

    In continuous light, the Crassulacean acid metabolism plant Kalanchoe daigremontiana Hamet et Perrier has a circadian rhythm of gas exchange with peaks occurring during the subjective night. The rhythm of gas exchange is coupled to a weak, reverse phased rhythm of quantum yield of photosystem II (Phi (PSII)). To test if the rhythm of Phi (PSII) persists in the absence of stomatal control, leaves were coated with a thin layer of translucent silicone grease which prevented CO2 and H2O exchange. In spite of this treatment, the rhythm of Phi (PSII) occurred with close to normal phase timing and with a much larger amplitude than in uncoated leaves. The mechanism underlying the Phi (PSII) rhythm in coated leaves can be explained by a circadian activity of phosphoenolpyruvate carboxylase (PEPC). At peaks of PEPC activity, the small amount of CO2 contained in the coated leaf could have become depleted, preventing the carboxylase activity of Rubisco and causing decreases in electron transport rates (observed as deep troughs of Phi (PSII) at 23-h in LL and at ca. 24-h intervals afterwards). Peaks of Phi (PSII) would be caused by a downregulation of PEPC leading to improved supply of CO2 to Rubisco. Substrate limitation of photochemistry at 23 h (trough of Phi (PSII)) was also suggested by the weak response of ETR in coated leaves to stepwise light enhancement. These results show that photosynthetic rhythmicity in K. daigremontiana is independent of stomatal regulation and may originate in the mesophyll.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    Science.gov (United States)

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-01-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

  19. Circadian sleep/wake rhythm abnormalities as a risk factor of a poststroke apathy.

    Science.gov (United States)

    Cosin, Charlotte; Sibon, Igor; Poli, Mathilde; Allard, Michèle; Debruxelles, Sabrina; Renou, Pauline; Rouanet, François; Mayo, Willy

    2015-07-01

    Poststroke apathy affects 19-55% of patients following stroke and has a negative impact on functional recovery, general health, and quality of life, as well as being a source of significant burden for caregivers. A major clinical issue is the delayed diagnosis of poststroke apathy, and so the aim of our study is to evaluate the relationship between early poststroke alterations of circadian rhythms of sleep/wake cycles and the occurrence of poststroke apathy. Forty-six patients with a recent magnetic resonance imaging confirmed stroke were included. Main exclusion criteria were a mild to severe disability impeding home discharge from the hospital and the presence of apathy or dementia before stroke. Cerebrovascular lesions were evaluated by magnetic resonance imaging. At hospital discharge, an actigraph was used to measure patient's global activity as well as parameters of circadian rhythmicity (relative amplitude, interdaily stability, intradaily variability) and sleep (sleep duration, sleep efficiency, fragmentation index) over seven-days. Apathy was assessed at hospital discharge as well as at three-months using the Apathy Inventory and the Lille Apathy Rating Scale. Of the 46 patients evaluated, 10 (22%) showed apathy three-months after stroke (median Apathy Inventory = 4·5). Before inclusion, these 10 subjects did not differ significantly from other patients concerning their sleep and, at inclusion, they did not differ concerning apathy, anxiety, depression, or cognitive and functional abilities. However, actigraphy measured at discharged identified significant alterations of sleep (P apathy patients exhibited a decrease in sleep efficiency (actual sleep time expressed as a percentage of time in bed) and an increase in the fragmentation index (degree of fragmentation during the sleep period) at three-months. No association was observed between poststroke apathy and the characteristics of cerebrovascular lesions (stroke location, extent of

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

    Science.gov (United States)

    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 (sleep-wake cycle but not the circadian melatonin rhythm to an 8-h phase-advanced sleep schedule, indicating differential effects of physical exercise on the human circadian system. The present study examined the effects of bright light (>5,000 lux) on exercise-induced acceleration of reentrainment because timed bright lights are known to reset the circadian pacemaker. Fifteen male subjects spent 12 days in temporal isolation. The sleep schedule was advanced from habitual sleep times by 8 h for 4 days, which was followed by a free-run session. In the shift session, bright lights were given during the waking time. Subjects in the exercise group performed 2-h bicycle running twice a day. Subjects in the control kept quiet. As a result, the sleep-wake cycle was fully entrained by the shift schedule in both groups. Bright light may strengthen the resetting potency of the shift schedule. By contrast, the circadian melatonin rhythm was phase-advanced by 6.9 h on average in the exercise group but only by 2.0 h in the control. Thus physical exercise prevented otherwise unavoidable internal desynchronization. Polysomnographical analyses revealed that deterioration of sleep quality by shift schedule was protected by physical exercise under bright lights. These findings indicate differential regulation of sleep-wake cycle and circadian melatonin rhythm by physical exercise in humans. The melatonin rhythm is regulated primarily by bright lights, whereas the sleep-wake cycle is by nonphotic time cues, such as physical exercise and shift schedule. Copyright © 2014 the American Physiological Society.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Acute dim light at night increases body mass, alters metabolism, and shifts core body temperature circadian rhythms.

    Science.gov (United States)

    Borniger, Jeremy C; Maurya, Santosh K; Periasamy, Muthu; Nelson, Randy J

    2014-10-01

    The circadian system is primarily entrained by the ambient light environment and is fundamentally linked to metabolism. Mounting evidence suggests a causal relationship among aberrant light exposure, shift work, and metabolic disease. Previous research has demonstrated deleterious metabolic phenotypes elicited by chronic (>4 weeks) exposure to dim light at night (DLAN) (∼ 5 lux). However, the metabolic effects of short-term (body mass, alter whole body metabolism, and display altered body temperature (Tb) and activity rhythms compared to mice maintained in dark nights. Our data largely support these predictions; DLAN mice gained significantly more mass, reduced whole body energy expenditure, increased carbohydrate over fat oxidation, and altered temperature circadian rhythms. Importantly, these alterations occurred despite similar activity locomotor levels (and rhythms) and total food intake between groups. Peripheral clocks are potently entrained by body temperature rhythms, and the deregulation of body temperature we observed may contribute to metabolic problems due to "internal desynchrony" between the central circadian oscillator and temperature sensitive peripheral clocks. We conclude that even relatively short-term exposure to low levels of nighttime light can influence metabolism to increase mass gain.

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

    Science.gov (United States)

    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.

  4. Sleep-wake profiles and circadian rhythms of core temperature and melatonin in young people with affective disorders.

    Science.gov (United States)

    Carpenter, Joanne S; Robillard, Rébecca; Hermens, Daniel F; Naismith, Sharon L; Gordon, Christopher; Scott, Elizabeth M; Hickie, Ian B

    2017-11-01

    While disturbances of the sleep-wake cycle are common in people with affective disorders, the characteristics of these disturbances differ greatly between individuals. This heterogeneity is likely to reflect multiple underlying pathophysiologies, with different perturbations in circadian systems contributing to the variation in sleep-wake cycle disturbances. Such disturbances may be particularly relevant in adolescents and young adults with affective disorders as circadian rhythms undergo considerable change during this key developmental period. This study aimed to identify profiles of sleep-wake disturbance in young people with affective disorders and investigate associations with biological circadian rhythms. Fifty young people with affective disorders and 19 control participants (aged 16-31 years) underwent actigraphy monitoring for approximately two weeks to derive sleep-wake cycle parameters, and completed an in-laboratory assessment including evening dim-light saliva collection for melatonin assay and overnight continuous core body temperature measurement. Cluster analysis based on sleep-wake cycle parameters identified three distinct patient groups, characterised by 'delayed sleep-wake', 'disrupted sleep', and 'long sleep' respectively. The 'delayed sleep-wake' group had both delayed melatonin onset and core temperature nadir; whereas the other two cluster groups did not differ from controls on these circadian markers. The three groups did not differ on clinical characteristics. These results provide evidence that only some types of sleep-wake disturbance in young people with affective disorders are associated with fundamental circadian perturbations. Consequently, interventions targeting endogenous circadian rhythms to promote a phase shift may be particularly relevant in youth with affective disorders presenting with delayed sleep-wake cycles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Circadian rhythm sleep disorders in patients with multiple sclerosis and its association with fatigue: A case-control study

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Najafi

    2013-01-01

    Full Text Available Background: Circadian rhythm sleep disorders are a presentation of sleep disorders in patients with multiple sclerosis (MS. This study aims to compare this problem in MS patients with healthy people and to determine its association with chronic fatigue in MS patients. Materials and Methods: A case-control study was performed on 120 MS patients and 60 healthy subjects matched for age and sex, in 2009 in MS Clinic Alzahra Hospital. Sleep quality, rhythm and fatigue severity were assessed using PSQI (Pittsburgh sleep quality index and FSS (Fatigue severity Scale questionnaires, respectively. Its reliability and validity has been confirmed in several studies (Cronbach′s alpha = 0.83. This index has seven sections including patient′s assessment of his/her sleep, sleep duration, efficacy of routine sleep, sleep disorders, use of hypnotic medication, and dysfunction in daily activities. Results: Circadian rhythm sleep disorder was more frequent in MS patients relative to healthy subjects (P: 0.002. It was higher in MS patients with severe fatigue relative to MS patients with mild fatigue (P: 0.05. Fatigue severity was 49.9 ± 8.2 and 22.5 ± 7.4 in the first and second group, respectively. PSQI index was 7.9 ± 4.5 in patients with severe fatigue and 5.9 ± 4.5 in patients with mild fatigue and 4.5 ± 2.4 in the control group (P: 0.0001. Conclusion: Circadian rhythm sleep disorders are more frequent in MS patients and those with fatigue. Recognition and management of circadian rhythm sleep disorders in MS patients, especially those with fatigue may be helpful in improving care of these patients.

  6. Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms.

    Science.gov (United States)

    St Hilaire, Melissa A; Lockley, Steven W

    2015-06-01

    Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep-wake disorder. Three totally blind males (63.0 ± 7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48 h every 1-2 weeks. Participants completed daily sleep-wake logs, and rated their alertness and mood using nine-point scales every ~2-4 h while awake on urine sampling days. Caffeine capsules (150 mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period τ and compared to placebo (n = 2) or no treatment (n = 1) in a single-masked manner. Non-24-h aMT6s rhythms were confirmed in all three participants (τ range = 24.32-24.57 h). Daily administration of 150 mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p caffeine was able to improve daytime alertness acutely and may therefore provide temporary symptomatic relief, the inability of caffeine to correct the underlying circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep-Wake Disorder in the blind appropriately. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  7. The Quality of Life Analysis with Regard to Circadian and Diurnal Rhythm of Pubescents and Adolescents in Children's Homes in the Region of Pardubice.

    OpenAIRE

    ŠTORKOVÁ, Tereza

    2014-01-01

    This thesis deals with the quality of life of pubescent and adolescent in children's homes in the Pardubice region with regard to circadian and diurnal rhythms. In the theoretical part we define in detail the concept of quality of life, pubescence, and adolescence, biorhythms with a division between circadian and diurnal rhythms, sleep and institutional care. More attention is paid to sleep, its importance, quality and above all sleep cycles that are directly associated with the subsequent re...

  8. The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis

    Czech Academy of Sciences Publication Activity Database

    Luchavová, M.; Zikán, V.; Michalská, D.; Raška, I.; Kuběna, Aleš Antonín; Štěpán, J. J.

    2011-01-01

    Roč. 164, č. 4 (2011), s. 643-648 ISSN 0804-4643 Grant - others:GA MZd(CZ) NS10564 Institutional research plan: CEZ:AV0Z10750506 Keywords : intact parathyroid-hormone * serum cortisol * diurnal rhythm * growth-hormone * in-vivo * resorption * osteoprotegerin * calcium * abnormalities * osteocalcin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.423, year: 2011 http://library.utia.cas.cz/separaty/2011/E/kubena-the effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis .pdf

  9. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day

    Science.gov (United States)

    Wyatt, J. K.; Ritz-De Cecco, A.; Czeisler, C. A.; Dijk, D. J.

    1999-01-01

    The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15-24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

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

    DEFF Research Database (Denmark)

    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)). CONCLUSIONS/INTERPRETATION: An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes....... On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes....

  11. Intensive voluntary wheel running may restore circadian activity rhythms and improves the impaired cognitive performance of arrhythmic Djungarian hamsters.

    Science.gov (United States)

    Weinert, Dietmar; Schöttner, Konrad; Müller, Lisa; Wienke, Andreas

    2016-01-01

    Circadian rhythms are highly important not only for the synchronization of animals and humans with their periodic environment but also for their fitness. Accordingly, the disruption of the circadian system may have adverse consequences. A certain number of animals in our breeding stock of Djungarian hamsters are episodically active throughout the day. Also body temperature and melatonin lack 24-h rhythms. Obviously in these animals, the suprachiasmatic nuclei (SCN) as the central pacemaker do not generate a circadian signal. Moreover, these so-called arrhythmic (AR) hamsters have cognitive deficits. Since motor activity is believed to stabilize circadian rhythms, we investigated the effect of voluntary wheel running. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14 L/10 D lighting regimen. AR animals were selected according to their activity pattern obtained by means of passive infrared motion detectors. In a first step, the daily activity behavior was investigated for 3 weeks each without and with running wheels. To estimate putative photic masking effects, hamsters were exposed to light (LPs) and DPs and also released into constant darkness for a minimum of 3 weeks. A novel object recognition (NOR) test was performed to evaluate cognitive abilities both before and after 3 weeks of wheel availability. The activity patterns of hamsters with low wheel activity were still AR. With more intense running, daily patterns with higher values in the dark time were obtained. Obviously, this was due to masking as LPs did suppress and DPs induced motor activity. When transferred to constant darkness, in some animals the daily rhythm disappeared. In other hamsters, namely those which used the wheels most actively, the rhythm was preserved and free-ran, what can be taken as indication of a reconstitution of circadian rhythmicity. Also, animals showing a 24-h activity pattern after 3 weeks of extensive wheel running were

  12. Rest-activity circadian rhythm and sleep quality in patients with binge eating disorder.

    Science.gov (United States)

    Roveda, E; Montaruli, A; Galasso, L; Pesenti, C; Bruno, E; Pasanisi, P; Cortellini, M; Rampichini, S; Erzegovesi, S; Caumo, A; Esposito, F

    2018-02-01

    Recent findings suggest that altered rest-activity circadian rhythms (RARs) are associated with a compromised health status. RARs abnormalities have been observed also in several pathological conditions, such as cardiovascular, neurological, and cancer diseases. Binge eating disorder (BED) is the most common eating disorder, with a prevalence of 3.5% in women and 2% in men. BED and its associate obesity and motor inactivity could induce RARs disruption and have negative consequences on health-related quality of life. However, the circadian RARs and sleep behavior in patients with BED has been so far assessed only by questionnaires. Therefore, the purpose of this study was to determine RARs and sleep parameters by actigraphy in patients with BED compared to a body mass index-matched control group (Ctrl). Sixteen participants (eight obese women with and eight obese women without BED diagnosis) were recruited to undergo 5-day monitoring period by actigraphy (MotionWatch 8®, CamNtech, Cambridge, UK) to evaluate RARs and sleep parameters. In order to determine the RARs, the actigraphic data were analyzed using the single cosinor method. The rhythmometric parameters of activity levels (MESOR, amplitude and acrophase) were then processed with the population mean cosinor. The Actiwatch Sleep Analysis Software (Cambridge Neurotecnology, Cambridge, UK) evaluated the sleep patterns. In each participant, we considered seven sleep parameters (sleep onset: S-on; sleep offset: S-off; sleep duration: SD; sleep latency: SL; movement and fragmentation index: MFI; immobility time: IT; sleep efficiency: SE) calculated over a period of five nights. The population mean cosinor applied to BED and Ctrl revealed the presence of a significant circadian rhythm in both groups (p < 0.001). The MESOR (170.0 vs 301.6 a.c., in BED and Ctrl, respectively; p < 0.01) and amplitude (157.66 vs 238.19 a.c., in BED and Ctrl, respectively p < 0.05) differed significantly between the two groups

  13. Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

    Science.gov (United States)

    Ajabnoor, Ghada M; Bahijri, Suhad; Borai, Anwar; Abdulkhaliq, Altaf A; Al-Aama, Jumana Y; Chrousos, George P

    2014-01-01

    Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (pRamadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk.

  14. Elucidation of the role of clp protease components in circadian rhythm by genetic deletion and overexpression in cyanobacteria.

    Science.gov (United States)

    Imai, Keiko; Kitayama, Yohko; Kondo, Takao

    2013-10-01

    In the cyanobacterium Synechococcus elongatus PCC7942, KaiA, KaiB, and KaiC are essential elements of the circadian clock, and Kai-based oscillation is thought to be the basic circadian timing mechanism. The Kai-based oscillator coupled with transcription/translation feedback and other intercellular factors maintains the stability of the 24-hour period in vivo. In this study, we showed that disruption of the Clp protease family genes clpP1, clpP2, and clpX and the overexpression of clpP3 cause long-period phenotypes. There were no significant changes in the levels of the clock proteins in these mutants. The overexpression of clpX led to a decrease in kaiBC promoter activity, the disruption of the circadian rhythm, and eventually cell death. However, after the transient overexpression of clpX, the kaiBC gene expression rhythm recovered after a few days. The rhythm phase after recovery was almost the same as the phase before clpX overexpression. These results suggest that the core Kai-based oscillation was not affected by clpX overexpression. Moreover, we showed that the overexpression of clpX sequentially upregulated ribosomal protein subunit mRNA levels, followed by upregulation of other genes, including the clock genes. Additionally, we found that the disruption of clpX decreased the expression of the ribosomal protein subunits. Finally, we showed that the circadian period was prolonged following the addition of a translation inhibitor at a low concentration. These results suggest that translational efficiency affects the circadian period and that clpX participates in the control of translation efficiency by regulating the transcription of ribosomal protein genes.

  15. Should food intake and circadian rhythm be considered when measuring serum calcitonin level?

    Science.gov (United States)

    Zayed, Ayman A; Alzubaidi, Mohammed; Atallah, Sama; Momani, Munther S; Al-Delaimy, Wael K

    2013-01-01

    To investigate the relationship between both food intake and circadian rhythmicity and serum calcitonin in the same individuals. Eighteen healthy subjects, 10 males and 8 females, aged 22 to 24 years, were recruited. Serum calcitonin level was measured three times: at 0800 after a 9-hour overnight fast, at 0900 postprandially, and at 1700 after another 9-hour fast. The same protocol was repeated once. The mean calcitonin levels (at 0800) were 3.92 pg/mL (SD, 2.5 pg/mL) on Day 1 and 3.52 pg/mL (SD, 2.1 pg/mL) on Day 2. Mean postprandial calcitonin (at 0900) was 9.46 pg/mL (SD, 8.6 pg/mL) on Day 1 and 9.91 pg/mL (SD, 6.9 pg/mL) on Day 2. Mean fasting calcitonin in the evening (at 1700) was 6.74 pg/mL (SD, 4.73 pg/mL) on Day 1 and 6.49 pg/mL (SD, 3.57 pg/mL) on Day 2. There was no significant difference in the mean calcitonin level on days 1 and 2 for any of the three time points examined. Statistically significant differences were found between postprandial and evening calcitonin levels and the fasting levels on Day 1 (P = .018 and .015, respectively) and Day 2 (P = .001 and .0009, respectively). These results suggest that serum calcitonin level is significantly influenced by food intake in healthy young subjects and reveal a circadian rhythm, with increased calcitonin level during the afternoon. The timing of blood sampling relative to meals should be integrated into clinical practice and research settings involving serum calcitonin measurements.

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

    Directory of Open Access Journals (Sweden)

    Charli Sargent

    2016-01-01

    Full Text Available 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.

  17. Targeted Recruitment of the Basal Transcriptional Machinery by LNK Clock Components Controls the Circadian Rhythms of Nascent RNAs in Arabidopsis.

    Science.gov (United States)

    Ma, Yuan; Gil, Sergio; Grasser, Klaus D; Mas, Paloma

    2018-04-04

    The rhythms of steady-state mRNA expression pervade nearly all circadian systems. However, the mechanisms behind the rhythmic transcriptional synthesis and its correlation with circadian expression remain fully unexplored, particularly in plants. Here, we discovered a multi-functional protein complex that orchestrates the rhythms of transcriptional activity in Arabidopsis thaliana. The expression of the circadian oscillator genes TOC1 (TIMING OF CAB EXPRESSION1/PSEUDO-RESPONSE REGULATOR1) and PRR5 (PSEUDO-RESPONSE REGULATOR5) initially relies on the modular function of the clock-related factor RVE8: its MYB domain provides the DNA binding specificity, while its LCL domain recruits the clock components, LNKs, to target promoters. LNKs, in turn, specifically interact with RNA Polymerase II and the transcript elongation FACT complex to rhythmically co-occupy the target loci. The functional interaction of these components is central for chromatin status, transcript initiation and elongation, as well as proper rhythms in nascent RNAs. Our findings thus explain how genome readout of environmental information ultimately results in rhythmic changes of gene expression. © 2018 American Society of Plant Biologists. All rights reserved.

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

    Science.gov (United States)

    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.

  19. Circadian and ultradian extrasystole rhythms in healthy individuals at elevated versus lowland altitudes.

    Science.gov (United States)

    Kujanik, Stefan; Mikulecky, Miroslav

    2010-09-01

    We defined chronobiologic norms for supraventricular and ventricular single extrasystoles (SV and VE, respectively) in healthy older males in lowland areas. The study was extended to higher altitudes, where hypobaric hypoxia was expected to increase extrasystole frequency, while perhaps not changing rhythmicity. In healthy men (lowland n = 37, altitude n = 22), aged 49-72 years, mean numbers of SVs and VEs were counted over a 24-h period. Cosinor regression was used to test the 24-h rhythm and its 2nd-10th harmonics. The resulting approximating function for either extrasystole type includes its point, 95% confidence interval of the mean, and 95% tolerance for single measurement estimates. Separate hourly differences (delta) between altitude and lowland (n = 59) were also analysed. Hourly means were significantly higher in the mountains versus lowland, by +0.8 beats/h on average for SVs, and by +0.9 beats/h for VEs. A relatively rich chronogram for VEs in mountains versus lowland exists. Delta VEs clearly display a 24-h component and its 2nd, 3rd, 4th and 7th harmonics. This results in significantly higher accumulation of VEs around 8.00 a.m., 11.00 a.m. and 3.00 p.m. in the mountains. The increase in extrasystole occurrence in the mountains is probably caused by higher hypobaric hypoxia and resulting sympathetic drive. Healthy men at elevated altitudes show circadian and several ultradian rhythms of single VEs dependent on the hypoxia level. This new methodological approach--evaluating the differences between two locations using delta values--promises to provide deeper insight into the occurrence of premature beats.

  20. Melatonin in the Afternoons of a Gradually Advancing Sleep Schedule Enhances the Circadian Rhythm Phase Advance

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2012-01-01

    Rationale We test methods to advance (shift earlier) circadian rhythms without producing misalignment between rhythms and sleep. We previously tested 1) a gradually advancing sleep/dark schedule plus morning bright light and afternoon/evening melatonin; and 2) the same sleep schedule with only morning bright light. Now we report on the same sleep schedule with only afternoon/evening melatonin. Objectives To examine phase advances, sleepiness and performance in response to melatonin compared to placebo. Methods Twelve adults (5 female) aged 20–45 years (mean ± SD = 28.3 ± 7.3 years) completed this within-subjects placebo-controlled counterbalanced study. Participants slept on fixed 8-hour sleep schedules for 9 baseline days. Then, sleep/dark was advanced by 1 h/day for 3 consecutive days of treatment. Participants took 3 mg of melatonin or placebo 11 hours before baseline sleep midpoint (the optimal time to produce phase advances) on the first treatment day and 1 hour earlier each subsequent day. We measured the dim light melatonin onset (DLMO) before and after treatment. Participants rated subjective symptoms throughout the study. They completed the Psychomotor Vigilance Task (PVT) and rated sleepiness from 1 h before pill ingestion until bedtime each treatment day. Results Melatonin produced significantly larger advances (1.3 ± 0.7 h) compared to placebo (0.7 ± 0.7 h); however, in the hours between melatonin ingestion and bed, melatonin caused sleepiness and performance decrements. Conclusions Adding afternoon/evening melatonin to the gradually advancing sleep schedule increased the phase advance, but given the side effects, like sleepiness, it is better to use morning bright light and perhaps a lower dose of melatonin. PMID:23001190

  1. Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life.

    Science.gov (United States)

    Fernandez, Fabian; Nyhuis, Casandra C; Anand, Payal; Demara, Bianca I; Ruby, Norman F; Spanò, Goffredina; Clark, Caron; Edgin, Jamie O

    2017-05-01

    To evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS. A cross-sectional study of 66 infants and young children with DS, aged 5-67 months, and 43 typically developing age-matched controls. Sleep and measures of circadian robustness or timing were quantified using continuous in-home actigraphy recordings performed over seven days. Circadian robustness was quantified via time series analysis of rest-activity patterns. Phase markers of circadian timing were calculated alongside these values. Sleep efficiency was also estimated based on the actigraphy recordings. This study provided further evidence that general sleep quality is poor in infants and toddlers with DS, a population that has sleep apnea prevalence as high as 50% during the preschool years. Despite poor sleep quality, circadian rhythm and phase were preserved in children with DS and displayed similar developmental trajectories in cross-sectional comparisons with a typically developing (TD) cohort. In line with past work, lower sleep efficiency scores were quantified in the group with DS relative to TD children. Infants born with DS exhibited the worst sleep fragmentation; however, in both groups, sleep efficiency and consolidation increased across age. Three circadian phase markers showed that 35% of the recruitment sample with DS was phase-advanced to an earlier morning schedule, suggesting significant within-group variability in the timing of their daily activity rhythms. Circadian rhythms of wake and sleep are robust in children born with DS. The present results suggest that sleep fragmentation and any resultant cognitive deficits are likely not

  2. Delayed circadian rhythm in adults with attention-deficit/hyperactivity disorder and chronic sleep-onset insomnia.

    Science.gov (United States)

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

    2010-06-01

    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. Sleep logs and actigraphy data were collected during 1 week in 40 adults with ADHD, of whom 31 reported SOI. Salivary melatonin levels were assessed during 1 night. Sleep measures, circadian activity variables, and dim light melatonin onset were compared between groups of ADHD adults with and without SOI and with matched healthy control subjects. Compared with control subjects, both groups of ADHD adults had longer sleep-onset latency and lower sleep efficiency. Adults with ADHD and SOI showed a delayed start and end of their sleep period and a delayed melatonin onset compared with adults with ADHD without SOI (p = .006; p = .023; p = .02) and compared with healthy control subjects (p = .014; p = .019; p = .000). Adults with ADHD and SOI also showed an attenuated 24-hour amplitude in their rest-activity pattern, in contrast to those without SOI, who showed a higher day-to-day stability. These findings demonstrate diurnal rhythm deviations during everyday life in the majority of adults with ADHD that have SOI and suggest that potential benefits of rhythm-improving measures should be evaluated. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Importance of regular lifestyle with daytime bright light exposure on circadian rhythm sleep–wake disorders in pervasive developmental disorders

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    Nana N. Takasu

    2011-08-01

    Full Text Available Considerable attention has been paid to individuals showing social maladjustment as well as withdrawal from social situations and activity, a state referred to as “Hikikomori” in Japanese. Recently, social maladjustment and Hikikomori states have also been noted to be highly prevalent among individuals with pervasive developmental disorders (PDDs, which involve abnormalities in social interactions and communication. The individuals with PDDs report a tendency to sleep and wake at irregular or inappropriate times and to suffer from sleep disorders by nature, and they tend to sleep at extreme late night or during the day while experiencing social maladjustment and Hikikomori states. Therefore, it is probable that their oral hygiene might deteriorate due to a circadian rhythm disorder, such as an abnormal salivary secretion rhythm or refusals and noncooperation of dental care due to mood/emotional and social problems, underlying and caused by their sleep and wake patterns. In this review, we describe the importance of regular lifestyle, especially regular sleep–wake rhythm with appropriately timed bright light exposure during daytime, for management of oral health in PDDs via improving their circadian rhythm disorders.

  4. Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones

    OpenAIRE

    Rajaratnam, SMW; Dijk, D-J; Middleton, B; Stone, BM; Arendt, J

    2003-01-01

    The pineal hormone melatonin is a popular treatment for sleep and circadian rhythm disruption. Melatonin administered at optimal times of the day for treatment often results in a prolonged melatonin profile. In photoperiodic (day length-dependent) species, changes in melatonin profile duration influence the timing of seasonal rhythms. We investigated the effects of an artificially prolonged melatonin profile on endogenous melatonin and cortisol rhythms, wrist actigraphy, and reproductive horm...

  5. Circadian Rhythms of Retinomotor Movement in a Marine Megapredator, the Atlantic Tarpon, Megalops atlanticus

    Directory of Open Access Journals (Sweden)

    Kristin L. Kopperud

    2017-09-01

    Full Text Available Many ecologically and economically important marine fish species worldwide spend portions of their lives in coastal regions that are increasingly inundated by artificial light at night. However, while extensive research illustrates the harmful effects of inappropriate light exposure on biological timing in humans, rodents and birds, comparable studies on marine fish are virtually nonexistent. This study aimed to assess the effects of light on biological clock function in the marine fish retina using the Atlantic tarpon (Megalops atlanticus as a model. Using anti-opsin immunofluorescence, we observed robust rhythms of photoreceptor outer segment position (retinomotor movement over the course of the daily light–dark cycle: cone outer segments were contracted toward the inner retina and rods were elongated during the day; the opposite occurred at night. Phase shifting the daily light–dark cycle caused a corresponding shift of retinomotor movement timing, and cone retinomotor movement persisted in constant darkness, indicating control by a circadian clock. Constant light abolished retinomotor movements of both photoreceptor types. Thus, abnormally-timed light exposure may disrupt normal M. atlanticus clock function and harm vision, which in turn may affect prey capture and predator avoidance. These results should help inform efforts to mitigate the effects of coastal light pollution on organisms in marine ecosystems.

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

    International Nuclear Information System (INIS)

    Rubin, N.A.

    1980-01-01

    All mitotically active normal tissues in mammals investigated to date demonstrate a circadian rhythm in cell division. The murine corneal epithelium is a practical and advantageous tissue model for studying this phenomenon. In animals synchronized to a light-dark (LD) schedule, one sees predictably reproducible occurrences of peaks and troughs in the mitotic index (MI) within each 24-hour (h) period. One of the harmful effects of ionizing radiation on dividing cells is mitotic delay, reported to be a G 2 block in cells approaching mitosis. Affected cells are not killed but are inhibited from entering mitosis and are delayed for a span of time reported to be dose and cell cycle dependent. In the classical description of mitotic delay, MI of irradiated cells begins to drop in relation to the control, which is plotted as a straight line, uniform throughout the experiment. After the damage is repaired, delayed cells can enter mitosis along with other cells in the pool unaffected by the radiation, resulting in a MI higher than control levels. The span of delay and the occurrence of recovery are assumed to be constant for a given dose and tissue under similar experimental conditions. First described in asynchronously-dividing tissue culture cells, this concept is also extrapolated to the in vivo situation

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Body temperature circadian rhythm variability corresponds to left ventricular systolic dysfunction in decompensated cardiomyopathic hamsters.

    Science.gov (United States)

    Ahmed, Amany; Gondi, Sreedevi; Cox, Casey; Zheng, Minjuan; Mohammed, Anwarullah; Stupin, Igor V; Wang, Suwei; Vela, Deborah; Brewer, Alan; Elayda, Macarthur A; Buja, L Maximilian; Ward Casscells, S; Wilson, James M

    2011-11-01

    A declining amplitude of body temperature circadian rhythm (BTCR) predicts decompensation or death in cardiomyopathic hamsters. We tested the hypothesis that changes in BTCR amplitude accompany significant changes in left ventricular (LV) size and function. Using intraperitoneal transmitters, we continuously monitored the temperature of 30 male BIO TO-2 Syrian dilated cardiomyopathic hamsters. Cosinor analysis was used to detect significant changes--defined as changes >1 standard deviation from the baseline amplitude for 3 consecutive days--in BTCR amplitude over each hamster's lifespan. The Student t-test was used to compare BTCR variability and LV size and function (as assessed by 2D echocardiography) between baseline and the time that BTCR amplitude declined. All hamsters received 10 mg/kg furosemide daily. At the time of BTCR amplitude decline, functional parameters had changed significantly (P < .0001) from baseline: ejection fraction (0.31 ± 0.09% vs. 0.52 ± 0.08%), LV end-systolic volume (0.11 ± 0.03 vs. 0.05 ± 0.02 cm(3)), and LV end-diastolic volume (0.16 ± 0.04 vs. 0.10 ± 0.03 cm(3)). In decompensated cardiomyopathic hamsters, a decline in BTCR amplitude was associated with progression of heart failure and cardiac decompensation. Variation in BTCR warrants further investigation because of its potential implications for the diagnosis and treatment of cardiovascular disorders. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Circadian mechanisms of food anticipatory rhythms in rats fed once or twice daily: clock gene and endocrine correlates.

    Directory of Open Access Journals (Sweden)

    Danica F Patton

    Full Text Available 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

  13. Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression.

    Science.gov (United States)

    Brivio, Fernando; Fumagalli, Luca; Fumagalli, Gabriele; Pescia, Simonetta; Brivio, Rinaldo; Di Fede, Giuseppe; Rovelli, Franco; Lissoni, Paolo

    2010-01-01

    Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm. The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months. a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD. These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer.

  14. TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.

    Science.gov (United States)

    Kijak, Ewelina; Pyza, Elżbieta

    2017-01-01

    Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly's brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.

  15. Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway-PPAR Gamma, Energy Metabolism and Circadian Rhythms.

    Science.gov (United States)

    Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

    2018-03-23

    Entropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington's disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated. In Alzheimer's disease and Parkinson's disease, WNT/beta-catenin pathway is downregulated while PPAR gamma is upregulated. The dysregulation of the canonical WNT/beta-catenin pathway is responsible for the modification of thermodynamics behaviors of metabolic enzymes. Upregulation of WNT/beta-catenin pathway leads to aerobic glycolysis, named Warburg effect, through activated enzymes, such as glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). Downregulation of WNT/beta-catenin pathway leads to oxidative stress and cell death through inactivation of Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In addition, in NDs, PPAR gamma is dysregulated, whereas it contributes to the regulation of several key circadian genes. NDs show many dysregulation in the mediation of circadian clock genes and so of circadian rhythms. Thermodynamics rhythms operate far-from-equilibrium and partly regulate interactions between WNT/beta-catenin pathway and PPAR gamma. In NDs, metabolism, thermodynamics and circadian rhythms are tightly interrelated.

  16. l-5-hydroxytryptophan resets the circadian locomotor activity rhythm of the nocturnal Indian pygmy field mouse, Mus terricolor

    Science.gov (United States)

    Basu, Priyoneel; Singaravel, Muniyandi; Haldar, Chandana

    2012-03-01

    We report that l-5-hydroxytryptophan (5-HTP), a serotonin precursor, resets the overt circadian rhythm in the Indian pygmy field mouse, Mus terricolor, in a phase- and dose-dependent manner. We used wheel running to assess phase shifts in the free-running locomotor activity rhythm. Following entrainment to a 12:12 h light-dark cycle, 5-HTP (100 mg/kg in saline) was intraperitoneally administered in complete darkness at circadian time (CT)s 0, 3, 6, 9, 12, 15, 18, and 21, and the ensuing phase shifts in the locomotor activity rhythm were calculated. The results show that 5-HTP differentially shifts the phase of the rhythm, causing phase advances from CT 0 to CT 12 and phase delays from CT 12 to CT 21. Maximum advance phase shift was at CT 6 (1.18 ± 0.37 h) and maximum delay was at CT 18 (-2.36 ± 0.56 h). No extended dead zone is apparent. Vehicle (saline) at any CT did not evoke a significant phase shift. Investigations with different doses (10, 50, 100, and 200 mg/kg) of 5-HTP revealed that the phase resetting effect is dose-dependent. The shape of the phase-response curve (PRC) has a strong similarity to PRCs obtained using some serotonergic agents. There was no significant increase in wheel-running activity after 5-HTP injection, ruling out behavioral arousal-dependent shifts. This suggests that this phase resetting does not completely depend on feedback of the overt rhythmic behavior on the circadian clock. A mechanistic explanation of these shifts is currently lacking.

  17. Circadian rhythms of feeding activity in sea bass, Dicentrarchus labrax L.: dual phasing capacity of diel demand-feeding pattern.

    Science.gov (United States)

    Sánchez-Vázquez, F J; Madrid, J A; Zamora, S

    1995-09-01

    The nocturnal versus diurnal feeding patterns of sea bass under controlled experimental conditions were studied in order to investigate the existence of such a dualistic feeding behavior. The animals (six groups of 4 animals and 8 single fish) were held in tanks filled with recirculating salt water and installed in a "chronolab" under constant conditions (23.5 degrees C and 2.4% salinity). The fish were given access to self-demand feeders and first exposed to a photoperiod regime of 12:12 (12 h light, 70 lx, and 12 h dark, complete darkness) and then to light:dark (LD) pulses (40 min light, 40 min dark). The LD 12:12 cycle was reversed by doubling the light period in day 16, and reversed again in day 27 by doubling the dark period. The circadian rhythm of food demand was strongly synchronized with the LD cycle, and fish exhibited both diurnal and nocturnal patterns. In most fish, the shift of the feeding rhythm to the new LD cycle was very fast for each reversal (bringing forward or delaying their feeds 12 h), indicating a weak participation of an endogenous circadian rhythm. However, when submitted to LD pulses, fish began to free-run with a periodicity of about 23 h and kept feeding in the light or dark phase according to their prior behavior. The existence of a dualism in the diel feeding pattern in sea bass was thus clearly demonstrated and it appeared that the diurnal and nocturnal behavior did not depend exclusively on a circadian phase inversion of the feeding rhythms as this pattern of behavior was enhanced under ultradian LD pulses. The ecological implications of such dual capacity and the switch from one type of phasing to another are hitherto unknown and need further field and laboratory investigation.

  18. Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?

    NARCIS (Netherlands)

    Vogel, S.W.; Bijlenga, D.; Tanke, M.; Bron, T.I.; van der Heijden, K.B.; Swaab, H.; Beekman, A.T.; Kooij, J.

    2015-01-01

    Objective: Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) have a high prevalence of obesity. This is the first study to investigate whether circadian rhythmdisruption is a mechanismlinking ADHD symptoms to obesity. Methods: ADHD symptoms and two manifestations of circadian

  19. Functional similarity in relation to the external environment between circadian behavioral and melatonin rhythms in the subtropical Indian weaver bird.

    Science.gov (United States)

    Singh, Jyoti; Rani, Sangeeta; Kumar, Vinod

    2012-04-01

    The present study investigated whether the circadian oscillators controlling rhythms in activity behavior and melatonin secretion shared similar functional relationship with the external environment. We simultaneously measured the effects of varying illuminations on rhythms of movement and melatonin levels in Indian weaver birds under synchronized (experiment 1) and freerunning (experiment 2) light conditions. In experiment 1, weaverbirds were exposed to 12h light: 12h darkness (12L:12D; L = 20 lx, D = 0.1 lx) for 2.5 weeks. Then, the illumination of the dark period was sequentially enhanced to 1-, 5-, 10-, 20- and 100 lx at the intervals of about 2 to 4 weeks. In experiment 2, weaver birds similarly exposed for 2.5 weeks to 12L:12D (L = 100 lx; D = 0.1 lx) were released in constant dim light (LL(dim), 0.1 lx) for 6 weeks. Thereafter, LL(dim) illumination was sequentially enhanced to 1-, 3- and 5 lx at the intervals of about 2 weeks. Whereas the activity of singly housed individuals was continuously recorded, the plasma melatonin levels were measured at two time of the day, once in each light condition. The circadian outputs in activity and melatonin were phase coupled with an inverse phase relationship: melatonin levels were low during the active phase (light period) and high during the inactive phase (dark period). This phase relationship continued in both the synchronized and freerunning states as long as circadian activity and melatonin oscillators subjectively interpreted synchronously the daily light environment, based on illumination intensity and/or photophase contrast, as the times of day and night. There were dissociations between the response of the activity rhythms and melatonin rhythms in light conditions when the contrast between day and night was much reduced (20:10 lx) or became equal. We suggest that circadian oscillators governing activity behavior and melatonin secretion in weaverbirds are phase coupled, but they seem to independently respond to

  20. Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

    Science.gov (United States)

    Reynolds, Thomas H; Soriano, Rachelle A; Obadi, Obadi A; Murkland, Stanley; Possidente, Bernard

    2017-01-01

    Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda), can reduce caloric intake and possibly facilitate weight loss. The purpose of the present study was to examine the effects of the artificial sweetener, rebaudioside A (Reb-A), on circadian rhythms, in vivo insulin action, and the susceptibility to diet-induced obesity. Six month old male C57BL/6 mice were assigned to a control or Reb-A (0.1% Reb-A supplemented drinking water) group for six months. Circadian wheel running rhythms, body weight, caloric intake, insulin action, and susceptibility to diet-induced obesity were assessed. Time of peak physical activity under a 12:12 light-dark (LD) cycle, mean activity levels, and circadian period in constant dark were not significantly different in mice that consumed Reb-A supplemented water compared to normal drinking water, indicating that circadian rhythms and biological clock function were unaltered. Although wheel running significantly reduced body weight in both Reb-A and control mice (P = 0.0001), consuming Reb-A supplemented water did not alter the changes in body weight following wheel running (P = 0.916). In vivo insulin action, as assessed by glucose, insulin, and pyruvate tolerance tests, was not different between mice that consumed Reb-A treated water compared to normal drinking water. Finally, Reb-A does not appear to change the susceptibility to diet-induced obesity as both groups of mice gained similar amounts of body weight when placed on a high fat diet. Our results indicate that consuming Reb-A supplemented water does not promote circadian disruption, insulin

  1. Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

    Directory of Open Access Journals (Sweden)

    Thomas H Reynolds

    Full Text Available Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda, can reduce caloric intake and possibly facilitate weight loss. The purpose of the present study was to examine the effects of the artificial sweetener, rebaudioside A (Reb-A, on circadian rhythms, in vivo insulin action, and the susceptibility to diet-induced obesity. Six month old male C57BL/6 mice were assigned to a control or Reb-A (0.1% Reb-A supplemented drinking water group for six months. Circadian wheel running rhythms, body weight, caloric intake, insulin action, and susceptibility to diet-induced obesity were assessed. Time of peak physical activity under a 12:12 light-dark (LD cycle, mean activity levels, and circadian period in constant dark were not significantly different in mice that consumed Reb-A supplemented water compared to normal drinking water, indicating that circadian rhythms and biological clock function were unaltered. Although wheel running significantly reduced body weight in both Reb-A and control mice (P = 0.0001, consuming Reb-A supplemented water did not alter the changes in body weight following wheel running (P = 0.916. In vivo insulin action, as assessed by glucose, insulin, and pyruvate tolerance tests, was not different between mice that consumed Reb-A treated water compared to normal drinking water. Finally, Reb-A does not appear to change the susceptibility to diet-induced obesity as both groups of mice gained similar amounts of body weight when placed on a high fat diet. Our results indicate that consuming Reb-A supplemented water does not promote circadian disruption

  2. Improvement of a patient's circadian rhythm sleep disorders by aripiprazole was associated with stabilization of his bipolar illness.

    Science.gov (United States)

    Tashiro, Tetsuo

    2017-04-01

    Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the patient's depressive state. Administration of APZ may improve various circadian rhythm sleep disorders, as well as improve and prevent manic-depressive episodes, via augmentation of coupling in the SCN network. © 2017 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

  3. 2016 Arte Poster Competition First Place Winner: Circadian Rhythm and UV-Induced Skin Damage: An In Vivo Study.

    Science.gov (United States)

    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.

  4. Enhanced sodium sensitivity and disturbed circadian rhythm of blood pressure in essential hypertension.

    Science.gov (United States)

    Uzu, Takashi; Kimura, Genjiro; Yamauchi, Atsushi; Kanasaki, Masami; Isshiki, Keiji; Araki, Shin-ichi; Sugiomoto, Toshiro; Nishio, Yoshihiko; Maegawa, Hiroshi; Koya, Daisuke; Haneda, Masakazu; Kashiwagi, Atsunori

    2006-08-01

    To assess whether an association between sodium-sensitive hypertension and metabolic syndrome exists; and whether, in patients with metabolic syndrome, the nocturnal fall of blood pressure decreases and salt restriction affects the circadian blood pressure rhythm. Japanese patients with essential hypertension, who were treated without any antihypertensive agent, were maintained on a high-sodium diet and a low-sodium diet for 1 week each. On the last day of each diet, the 24-h blood pressures were measured. A diagnosis of metabolic syndrome was made according to the International Diabetes Foundation definition Among the 56 patients with essential hypertension, 15 patients were complicated with metabolic syndrome while 41 patients were not. The nocturnal blood pressure fall was significant in patients without metabolic syndrome, while it was not so in patients with metabolic syndrome. Only in patients with metabolic syndrome was the nocturnal blood pressure fall enhanced by sodium restriction. The prevalence of sodium-sensitive hypertension in patients with metabolic syndrome was significantly higher than in those without metabolic syndrome (70.6 versus 36.0%, respectively; P = 0.017). A multiple logistic regression analysis revealed central obesity to be an independent risk factor for sodium-sensitive hypertension (odds ratio, 1.41; 95% confidence interval, 1.04-1.91). In patients with essential hypertension, an inter-relationship exists among metabolic syndrome, enhanced sodium sensitivity of the blood pressure and non-dipping. The elevated risk of cardiovascular diseases in patients with metabolic syndrome may be related to sodium-sensitive hypertension and non-dipping.

  5. Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms.

    Science.gov (United States)

    Arif, I S; Hooper, C L; Greco, F; Williams, A C; Boateng, S Y

    2013-07-01

    Doxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono-optimization by exploiting the diurnal cycle. We determined cell toxicity using MCF-7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study. Doxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1/S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF-7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti-cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 μM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20-fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 μM melatonin) but not in MCF-7 cells. Our data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid-morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart. © 2013 The British Pharmacological Society.

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

    Science.gov (United States)

    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, PMyc (PMyc and then directly stimulated c-Myc transcription. Moreover, Clock physically interacted with histone deacetylase 3 (HDAC3) and formed a complex with c-Myc to promote adipocyte proliferation. Melatonin also attenuated circadian 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. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Urinary iodine concentration follows a circadian rhythm: a study with 3023 spot urine samples in adults and children.

    Science.gov (United States)

    Als, C; Helbling, A; Peter, K; Haldimann, M; Zimmerli, B; Gerber, H

    2000-04-01

    Our overall aim is to monitor iodine supply in a prospective study before and after the September 1998 increase of salt iodide content in Switzerland. Because iodide is supplied by alimentation, we moreover wondered whether urinary iodine concentration (UI) is governed by circadian rhythmicity. Forty-two subjects (18 males and 24 females, including 13 children) collected 3023 urine spots between May 1996 and May 1998, at a rate of three to five samples per month, at any time of the day. The results show that circadian rhythmicity of UI in adults and children was found independent of the individual subject, age, gender, and season. Lowest UI levels were found between 8-11 h. A curve increasing progressively between 12 and 24 h was obtained. UI returned to base-line levels between 21 and 22 h in children only. UI peaks occurred 4-5 h after main meals; children's peaks occurred later than that of adults. Although the existence of a circadian rhythm of UI is probably universal, its profile, however, depends on alimentation. Because nadir of UI is represented by morning spots, this might seem an appropriate collecting period. In view of the significant circadian rhythmicity of UI, studies with restriction of sampling time to morning hours, for example, cannot be directly compared with studies in which urine is sampled all over the day.

  8. Bmal1 is an essential regulator for circadian cytosolic Ca²⁺ rhythms in suprachiasmatic nucleus neurons.

    Science.gov (United States)

    Ikeda, Masayuki; Ikeda, Masaaki

    2014-09-03

    The hypothalamic suprachiasmatic nucleus (SCN) plays a pivotal role in the mammalian circadian clock system. Bmal1 is a clock gene that drives transcriptional-translational feedback loops (TTFLs) for itself and other genes, and is expressed in nearly all SCN neurons. Despite strong evidence that Bmal1-null mutant mice display arrhythmic behavior under constant darkness, the function of Bmal1 in neuronal activity is unknown. Recently, periodic changes in the levels of intracellular signaling messengers, such as cytosolic Ca(2+) and cAMP, were suggested to regulate TTFLs. However, the opposite aspect of how clock gene TTFLs regulate cytosolic signaling remains unclear. To investigate intracellular Ca(2+) dynamics under Bmal1 perturbations, we cotransfected some SCN neurons with yellow cameleon together with wild-type or dominant-negative Bmal1 using a gene-gun applied for mouse organotypic cultures. Immunofluorescence staining for a tag protein linked to BMAL1 showed nuclear expression of wild-type BMAL1 and its degradation within 1 week after transfection in SCN neurons. However, dominant-negative BMAL1 did not translocate into the nucleus and the cytosolic signals persisted beyond 1 week. Consistently, circadian Ca(2+) rhythms in SCN neurons were inhibited for longer periods by dominant-negative Bmal1 overexpression. Furthermore, SCN neurons transfected with a Bmal1 shRNA lengthened, whereas those overexpressing wild-type Bmal1 shortened, the periods of Ca(2+) rhythms, with a significant reduction in their amplitude. BMAL1 expression was intact in the majority of neighboring neurons in organotypic cultures. Therefore, we conclude that proper intrinsic Bmal1 expression, but not passive signaling via cell-to-cell interactions, is the determinant of circadian Ca(2+) rhythms in SCN neurons. Copyright © 2014 the authors 0270-6474/14/3412029-10$15.00/0.

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

    Science.gov (United States)

    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. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. It is not the parts, but how they interact that determines the behaviour of circadian rhythms across scales and organisms.

    Science.gov (United States)

    DeWoskin, Daniel; Geng, Weihua; Stinchcombe, Adam R; Forger, Daniel B

    2014-06-06

    Biological rhythms, generated by feedback loops containing interacting genes, proteins and/or cells, time physiological processes in many organisms. While many of the components of the systems that generate biological rhythms have been identified, much less is known about the details of their interactions. Using examples from the circadian (daily) clock in three organisms, Neurospora, Drosophila and mouse, we show, with mathematical models of varying complexity, how interactions among (i) promoter sites, (ii) proteins forming complexes, and (iii) cells can have a drastic effect on timekeeping. Inspired by the identification of many transcription factors, for example as involved in the Neurospora circadian clock, that can both activate and repress, we show how these multiple actions can cause complex oscillatory patterns in a transcription-translation feedback loop (TTFL). Inspired by the timekeeping complex formed by the NMO-PER-TIM-SGG complex that regulates the negative TTFL in the Drosophila circadian clock, we show how the mechanism of complex formation can determine the prevalence of oscillations in a TTFL. Finally, we note that most mathematical models of intracellular clocks model a single cell, but compare with experimental data from collections of cells. We find that refitting the most detailed model of the mammalian circadian clock, so that the coupling between cells matches experimental data, yields different dynamics and makes an interesting prediction that also matches experimental data: individual cells are bistable, and network coupling removes this bistability and causes the network to be more robust to external perturbations. Taken together, we propose that the interactions between components in biological timekeeping systems are carefully tuned towards proper function. We also show how timekeeping can be controlled by novel mechanisms at different levels of organization.

  11. Effects of sleep loss on the rest-activity circadian rhythm of helpers participating in continuous dogsled races.

    Science.gov (United States)

    Calogiuri, Giovanna; Weydahl, Andi

    2014-04-01

    The Finnmarksløpet dogsled race lasts up to 7 days. Helpers, who keep time, coach, and transport equipment, have to be alert though they have little and fragmented sleep. This study investigated disruptions of the rest-activity rhythm among helpers. 10 helpers were monitored by actigraph a week before, during, and after the race. Sleep logs, sleepiness rate, and self-reported quality of sleep were collected. Nonparametric circadian rhythm analysis showed significant differences between the pre- and postrace interdaily stability and amplitude of rhythm. Compared to prerace, sleepiness at bedtime was increased and number of nocturnal awakenings was reduced postrace, although the actigraphic outputs showed no improvement in sleep quality. Helpers who were engaged in the race for a longer span (5-6 days) had more difficulty recovering from the sleep loss accumulated during the race than those engaged for a shorter time (2-3 days). Poor sleep combined with prolonged and demanding mental focus for 2 days or more has a negative influence upon the rest-activity cycle, though complete restoration of the cycle occurs over 1 week or more. Being in such a condition for ≥ 5 days leads to disruptions of the circadian component of the sleep-wake cycle that hampers the sleep recovery process. Disrupted sleep and demanding mental requirements are common in long-distance sporting events as well as among shift workers. Follow-up intervention should be made in such cases to ensure the return of a healthy rest-activity rhythm and sleep quality.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Daily exposure to a running wheel entrains circadian rhythms in mice in parallel with development of an increase in spontaneous movement prior to running-wheel access.

    Science.gov (United States)

    Yamanaka, Yujiro; Honma, Sato; Honma, Ken-ichi

    2013-12-01

    Entrainment of circadian behavior rhythms by daily exposure to a running wheel was examined in mice under constant darkness. Spontaneous movement was individually monitored for more than 6 mo by a thermal sensor. After establishment of steady-state free running, mice were placed in a different cage equipped with a running-wheel for 3 h once per day at 6 AM. The daily exchange was continued for 80 days. The number of wheel revolutions during exposure to the running wheel was also measured simultaneously with spontaneous movement. In 13 out of 17 mice, circadian behavior rhythm was entrained by daily wheel exposure, showing a period indistinguishable from 24 h. The entrainment occurred in parallel with an increase in spontaneous movement immediately prior to the daily wheel exposure. A similar preexposure increase was observed in only one of four nonentrained mice. The preexposure increase appeared in 19.5 days on average after the start of daily wheel exposure and persisted for 36 days on average after the termination of the exposure schedule. The preexposure increase was detected only when daily wheel exposure came into the activity phase of the circadian behavior rhythm, which was accompanied by an increase in the number of wheel revolutions. These findings indicate that a novel oscillation with a circadian period is induced in mice by daily exposure to a running wheel at a fixed time of day and suggest that the oscillation is involved in the nonphotic entrainment of circadian rhythms in spontaneous movement.

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

    NARCIS (Netherlands)

    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.

    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

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

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    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.

  18. Comparative analysis of the circadian rhythm genes period and timeless in Culex pipiens Linnaeus, 1758 (Diptera, Culicidae)

    Science.gov (United States)

    Shaikevich, Elena V.; Karan, Ludmila S.; Fyodorova, Marina V.

    2016-01-01

    Abstract Nucleotide sequences of the circadian rhythm genes, period and timeless, were studied for the first time in mosquitoes Culex pipiens Linnaeus, 1758. In this work we evaluated variations of the studied genome fragments for the two forms of Culex pipiens (forma “pipiens” – mosquitoes common for aboveground habitats, forma “molestus” – underground mosquitoes). We compared Culex pipiens from Russia with transatlantic Culex pipiens and subtropical Culex quinquefasciatus Say, 1823. Our results show that intraspecies variability is higher for the gene period than for the gene timeless. The revealed substitutions in nucleotide sequences and especially in amino acid sequences grouped the individuals of the two forms into distinct clusters with high significance. The detected fixed amino acid substitutions may appear essential for functioning of the circadian rhythm proteins in Culex pipiens, and may be correlated with adaptations of the taxa within the group Culex pipiens. Our results suggest that natural selection favors fixed mutations and the decrease in diversity of the genes period and timeless in mosquitoes of the Culex pipiens f. “molestus” compared with the Culex pipiens f. “pipiens”, is probably correlated with adaptive features of Culex pipiens f. “molestus”. The studied genome regions may be considered as promising molecular-genetic markers for identification, population and phylogenetic analysis of similar species and forms of the Culex pipiens complex. PMID:28123673

  19. Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder.

    Science.gov (United States)

    Pagani, Lucia; St Clair, Patricia A; Teshiba, Terri M; Service, Susan K; Fears, Scott C; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Makhinson, Juliana; Lopez, Maria C; Montoya, Gabriel; Montoya, Claudia P; Aldana, Ileana; Navarro, Linda; Freimer, Daniel G; Safaie, Brian; Keung, Lap-Woon; Greenspan, Kiefer; Chou, Katty; Escobar, Javier I; Ospina-Duque, Jorge; Kremeyer, Barbara; Ruiz-Linares, Andres; Cantor, Rita M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Bearden, Carrie E; Takahashi, Joseph S; Freimer, Nelson B

    2016-02-09

    Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.

  20. Light interventions: a novel approach for sustaining sleep quality and quantity of elite swimmers under conditions of shifted circadian rhythm

    DEFF Research Database (Denmark)

    Argyraki, Aikaterini; Andersen, Jakob Hildebrandt; Johansen, Lars

    2017-01-01

    For the 2016 Olympics at Rio De Janeiro the Danish swimmers was facing a very important problem, how to maintain a good sleep quality, quantity and high performance potential, while being subject to large shift in circadian rhythm. In the present study we suggest an alternative approach for susta......For the 2016 Olympics at Rio De Janeiro the Danish swimmers was facing a very important problem, how to maintain a good sleep quality, quantity and high performance potential, while being subject to large shift in circadian rhythm. In the present study we suggest an alternative approach...... for sustaining sleep quantity and quality, namely light interventions. A light program, comprising of alternating blue enhanced white light and blue suppressed white light, was designed to complement the activities of elite Danish swimmers after arriving to preparation/training camp; mimicking the conditions......, efficiency, latency, percentages of light, deep or REM sleep were the variables under investigation. The sleep output was modeled (ANOVA) with subject as a random effect and phase as fixed effect. It was observed that the light program during the intervention phase significantly enabled the conservation...

  1. Daily and circadian rhythms of neurotransmitters and related compounds in the hypothalamic suprachiasmatic nuclei of a diurnal vertebrate.

    Science.gov (United States)

    Magnone, Maria Chiara; Bertolucci, Cristiano; Piazza, Francesca; Foà, Augusto

    2003-05-23

    By using immunocytochemistry we tested whether neurotransmitters, and enzymes specific to neurotransmitters synthesis are rhythmically expressed in the suprachiasmatic nuclei of the hypothalamus of Ruin lizards Podarcis sicula either kept in light-dark cycles or constant darkness. Within the suprachiasmatic nuclei, prominent 24 h rhythms under 12:12 light-dark cycles were found for vasoactive intestinal polypeptide (VIP) and for tyrosine hydroxylase (TH). Peaks of both VIP and TH fell in the light phase of the cycle. Rhythmic expression of TH persisted under constant temperature and darkness, demonstrating the existence of circadian rhythms of TH in the suprachiasmatic nuclei. No rhythmic expression of neurotransmitters and related compounds was found in the periventricular nuclei, the supraoptic nuclei, and the rest of the hypothalamus. Our data are the first demonstration of rhythmic expression of neurotransmitters and related compounds in the suprachiasmatic nuclei of a non-mammalian vertebrate. The demonstration of a diurnal peak of VIP in a diurnal reptile-vs. nocturnal peak of VIP typical of nocturnal mammals-provides new information for comparative studies on the circadian physiology of the suprachiasmatic nuclei across vertebrate classes and their adaptation strategies to different temporal niches.

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

    Directory of Open Access Journals (Sweden)

    Yoshikazu Takaesu

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Deciphering the Function of the Blunt Circadian Rhythm of Melatonin in the Newborn Lamb: Impact on Adrenal and Heart.

    Science.gov (United States)

    Seron-Ferre, Maria; Torres-Farfan, Claudia; Valenzuela, Francisco J; Castillo-Galan, Sebastian; Rojas, Auristela; Mendez, Natalia; Reynolds, Henry; Valenzuela, Guillermo J; Llanos, Anibal J

    2017-09-01

    Neonatal lambs, as with human and other neonates, have low arrhythmic endogenous levels of melatonin for several weeks until they start their own pineal rhythm of melatonin production at approximately 2 weeks of life. During pregnancy, daily rhythmic transfer of maternal melatonin to the fetus has important physiological roles in sheep, nonhuman primates, and rats. This melatonin rhythm provides a circadian signal and also participates in adjusting the physiology of several organs in preparation for extrauterine life. We propose that the ensuing absence of a melatonin rhythm plays a role in neonatal adaptation. To test this hypothesis, we studied the effects of imposing a high-amplitude melatonin rhythm in the newborn lamb on (1) clock time-related changes in cortisol and plasma variables and (2) clock time-related changes of gene expression of clock genes and selected functional genes in the adrenal gland and heart. We treated newborn lambs with a daily oral dose of melatonin (0.25 mg/kg) from birth to 5 days of age, recreating a high-amplitude melatonin rhythm. This treatment suppressed clock time-related changes of plasma adrenocorticotropic hormone, cortisol, clock gene expression, and functional genes in the newborn adrenal gland. In the heart, it decreased heart/body weight ratio, increased expression of Anp and Bnp, and resulted in different heart gene expression from control newborns. The interference of this postnatal melatonin treatment with the normal postnatal pattern of adrenocortical function and heart development support a physiological role for the window of flat postnatal melatonin levels during the neonatal transition. Copyright © 2017 Endocrine Society.

  5. Research on sleep, circadian rhythms and aging - Applications to manned spaceflight

    Science.gov (United States)

    Czeisler, Charles A.; Chiasera, August J.; Duffy, Jeanne F.

    1991-01-01

    Disorders of sleep and circadian rhythmicity are characteristic of both advancing age and manned spaceflight. Sleep fragmentation, reduced nocturnal sleep tendency and sleep efficiency, reduced daytime alertness, and increased daytime napping are common to both of these conditions. Recent research on the pathophysiology and treatment of disrupted sleep in older people has led to a better understanding of how the human circadian pacemaker regulates the timing of the daily sleep-wake cycle and how it responds to the periodic changes in the light-dark cycle to which we are ordinarily exposed. These findings have led to new treatments for some of the sleep disorders common to older individuals, using carefully timed exposure to bright light and darkness to manipulate the phase and/or amplitude of the circadian timing system. These insights and treatment approaches have direct applications in the design of countermeasures allowing astronauts to overcome some of the challenges which manned spaceflight poses for the human circadian timing system. We have conducted an operational feasibility study on the use of scheduled exposure to bright light and darkness prior to launch in order to facilitate adaptation of the circadian system of a NASA Space Shuttle crew to the altered sleep-wake schedule required for their mission. The results of this study illustrate how an understanding of the properties of the human circadian timing system and the consequences of circadian disruption can be applied to manned spaceflight.

  6. [Desynchronization of the circadian rhythm of plasma insulin levels and feeding schedules after inversion of periodicity].

    Science.gov (United States)

    Weinert, D; Ulrich, F E; Schuh, J

    1986-01-01

    In experiments with laboratory mice a desynchronisation of daily rhythms in plasma insulin concentration and feeding after inversion of the light-dark periodicity is documented. Whereas the feeding rhythm follows the exogenous Zeitgeber (differences concern above all the quantity of food which decrease after inversion), the acrophase of the hormone rhythm is stable in relation to astronomic time. The daily mean, however, is reduced and the main maximum is split into three components. The results support the hypothesis that rhythms of the two investigated parameters are generated by separate oscillators.

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

    NARCIS (Netherlands)

    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,

  8. Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording

    NARCIS (Netherlands)

    Schaap, J.; Bos, N. P.; de Jeu, M. T.; Geurtsen, A. M.; Meijer, J. H.; Pennartz, C. M.

    1999-01-01

    The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological

  9. Restricted daytime feeding attenuates reentrainment of the circadian melatonin rhythm after an 8-h phase advance of the light-dark cycle

    NARCIS (Netherlands)

    Kalsbeek, A.; Barassin, S.; van Heerikhuize, J. J.; van der Vliet, J.; Buijs, R. M.

    2000-01-01

    It is well established that in the absence of photic cues, the circadian rhythms of rodents can be readily phase-shifted and entrained by various nonphotic stimuli that induce increased levels of locomotor activity (i.e., benzodiazepines, a new running wheel, and limited food access). In the

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Day or night administration of ketamine and pentobarbital differentially affect circadian rhythms of pineal melatonin secretion and locomotor activity in rats.

    Science.gov (United States)

    Mihara, Takahiro; Kikuchi, Tatsuaki; Kamiya, Yoshinori; Koga, Motokazu; Uchimoto, Kazuhiro; Kurahashi, Kiyoyasu; Goto, Takahisa

    2012-10-01

    Surgery with general anesthesia disturbs circadian rhythms, which may lead to postoperative sleep disorders and delirium in patients. However, it is unclear how circadian rhythms are affected by different anesthetics administered at different times during the rest-activity cycle. We hypothesized that pentobarbital (an agonist at the γ-aminobutyric acid A receptors) and ketamine (an antagonist at the N-methyl-d-aspartate receptors) would have differential effects on circadian rhythms, and these effects would also be influenced by the time of their administration (the active versus resting phase). Rats were divided into 4 groups according to the anesthetic administered (pentobarbital or ketamine) and the timing of intraperitoneal administration (active/night phase or resting/day phase). Using online pineal microdialysis, we analyzed pineal melatonin secretion and locomotor activity rhythms in rats under a light/dark (12/12-hour) cycle for 5 days after anesthesia and microdialysis catheter implantation. The data were analyzed for rhythmicity by cosinor analysis. Ketamine administered during the resting phase produced 65- and 153-minute phase advances, respectively, in melatonin secretion and locomotor activity rhythms on the first day after anesthesia. In contrast, ketamine administered during the active phase produced 43- and 235-minute phase delays. Pentobarbital had no effect on the phase of either melatonin secretion or locomotor activity, irrespective of the timing of administration. When administered during the active phase, both anesthetics decreased the amplitude of melatonin secretion on the day after anesthesia; when administered during the resting phase, however, neither anesthetic affected the amplitude. The amplitude of locomotor activity decreased in all animals for 3 days after anesthesia. Ketamine has opposite phase-shifting effects on circadian rhythms according to the time of administration, whereas pentobarbital has no effect. Furthermore, both

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Jim, Heather S.L.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Vierkant, Robert A.; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Schernhammer, Eva; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M.; Kelemen, Linda E.; Ramus, Susan J.; Monteiro, Alvaro N.A.; Goode, Ellen L.; Narod, Steven A.; Gayther, Simon A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    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 ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68–0.90, p = 5.59 × 10−4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. PMID:26807442

  14. Relationships of Blood Pressure Circadian Rhythm and Brain Natriuretic Peptide with Left Ventricular Hypertrophy in the Patients with Primary Hypertension.

    Science.gov (United States)

    Kou, Hui-Juan; Wang, Xin; Gao, Deng-Feng; Dong, Xin; Wei, Jin; Ma, Rui

    2016-10-10

    Objective To investigate the relationships of blood pressure circadian rhythm and brain natriuretic peptide (BNP) with left ventricular hypertrophy (LVH) in patients with primary hypertension. Methods Totally 349 patients (74 with LVH and 275 without LVH) with primary hypertension were enrolled in this study.Echocardiography was performed to determine left ventricular mass index (LVMI) using the Devereux formula. The nocturnal blood pressure decline rate,24-hour blood pressure (24 h PP; especially 24 h mean systolic blood pressure,24 h SBP) and blood pressure index (PPI) were determined by 24 h-ambulatory blood pressure monitoring. These 349 hypertensive patients were divided into four groups including supper-dipper group (defined as≥;20%, n=7),dipper group (defined as 10%- 20%, n=77),non-dipper group (defined as 0- 10%, n=173),and anti-dipper group (defined ashypertension (85.1% vs. 46.9%;χ 2 =34.428,Pblood pressure decline rate [(1.30±8.02)% vs. (5.68±7.25)%; t=-4.510,Phypertensive group had significantly higher BNP level (87.8 pg/ml vs. 28.8 pg/ml; t=2.170,P=0.034) and LVMI (135.1 g/m 2 vs. 88.7 g/m 2 ; t=15.285,Phypertension. Conclusion With the increasing of plasma BNP level,the left ventricular hypertrophy is closely related to abnormal blood pressure circadian rhythm and the grade of hypertension in primary hypertensive patients.

  15. [Influence of sleep habit and nocturnal lifestyle on circadian rhythm of blood pressure among workers in Okinawa].

    Science.gov (United States)

    Sugawara, Mayo; Higashiuesato, Yasushi; Yamane, Nobuhisa

    2012-11-01

    We estimated the influence of sleep habit and nocturnal lifestyle on circadian rhythm of blood pressure by use of ambulatory blood pressure monitoring (ABPM) and self-estimating questionnaire formats. A total of 30 workers aged 21 to 58 years old voluntarily participated. None had any chronic diseases or regular medication. The average subject daily worked for 8 hours, waked-up at 6:00, went-to-bed at 23:45, and had 6.25-hour sleep (median). The subjects were divided into 3 groups according to % dipping of sleep blood pressure; 10 to 20% dipping as a dipper, or = 20% as an extreme-dipper. This characterization resulted in 15 dippers (50%), 8 non-dippers(27%) and 7 extreme-dippers (23%). Of the parameters estimated, (1) sleeping hours of non-dippers were significantly shorter than those of dippers (p=0.02), (2) nighttime blood pressure of extreme-dippers were significantly lower than dippers (p=0.04), (3) the lowest blood pressure in nighttime of non-dippers were significantly higher when compared with the remaining 2 groups, (4) morning surges of blood pressure of non-dippers were the significantly smallest, whereas those of extreme-dippers were the greatest, and (5)refreshing scores of OSA sleep inventory MA version of non-dippers were significantly poorer when compared to extreme-dippers. This study could indicate the significant influence of nocturnal lifestyle with short sleep on circadian rhythm of blood pressure, and the extended prospective-study might be promising for a precise conclusion.

  16. Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus.

    Science.gov (United States)

    Qian, Jingyi; Thomas, Anthony P; Schroeder, Analyne M; Rakshit, Kuntol; Colwell, Christopher S; Matveyenko, Aleksey V

    2017-08-01

    Metabolic state and circadian clock function exhibit a complex bidirectional relationship. Circadian disruption increases propensity for metabolic dysfunction, whereas common metabolic disorders such as obesity and type 2 diabetes (T2DM) are associated with impaired circadian rhythms. Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however, to date, it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo. To address this question, we undertook studies in aged diabetic rats transgenic for human islet amyloid polypeptide, an established nonobese model of T2DM (HIP rat), which develops metabolic defects closely recapitulating those present in patients with T2DM. HIP rats were also cross-bred with a clock gene reporter rat model (Per1:luciferase transgenic rat) to permit assessment of the SCN and the peripheral molecular clock function ex vivo. Utilizing these animal models, we examined effects of diabetes on 1 ) behavioral circadian rhythms, 2 ) photic entrainment of circadian activity, 3 ) SCN and peripheral tissue molecular clock function, and 4 ) melatonin secretion. We report that circadian activity, light-induced entrainment, molecular clockwork, as well as melatonin secretion are preserved in the HIP rat model of T2DM. These results suggest that despite the well-characterized ability of glucose to modulate circadian clock gene expression acutely in vitro, SCN clock function and key behavioral and physiological outputs appear to be preserved under chronic diabetic conditions characteristic of nonobese T2DM. Copyright © 2017 the American Physiological Society.

  17. Mathematical modeling of the circadian rhythm of key neuroendocrine-immune system players in rheumatoid arthritis: a systems biology approach.

    Science.gov (United States)

    Meyer-Hermann, Michael; Figge, Marc Thilo; Straub, Rainer H

    2009-09-01

    Healthy subjects and patients with rheumatoid arthritis (RA) exhibit circadian rhythms of the neuroendocrine-immune system. Understanding circadian dynamics is complex due to the nonlinear behavior of the neuroendocrine-immune network. This study was undertaken to seek and test a mathematical model for studying this network. We established a quantitative computational model to simulate nonlinear interactions between key factors in the neuroendocrine-immune system, such as plasma tumor necrosis factor (TNF), plasma cortisol (and adrenal cholesterol store), and plasma noradrenaline (NA) (and presynaptic NA store). The model was nicely fitted with measured reference data on healthy subjects and RA patients. Although the individual circadian pacemakers of cortisol, NA, and TNF were installed without a phase shift, the relative phase shift between these factors evolved as a consequence of the modeled network interactions. Combined long-term and short-term TNF increase (the "RA model") increased cortisol plasma levels for only a few days, and cholesterol stores started to become markedly depleted. This nicely demonstrated the phenomenon of inadequate cortisol secretion relative to plasma TNF levels, as a consequence of adrenal deficiency. Using the RA model, treatment with glucocorticoids between midnight and 2:00 AM was found to have the strongest inhibitory effect on TNF secretion, which supports recent studies on RA therapy. Long-term reduction of TNF levels by simulation of anti-TNF therapy normalized cholesterol stores under "RA" conditions. These first in silico studies of the neuroendocrine-immune system in rheumatology demonstrate that computational biology in medicine, making use of large collections of experimental data, supports understanding of the pathophysiology of complex nonlinear systems.

  18. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.

    Science.gov (United States)

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J; Foster, Russell G; Peirson, Stuart N; Nolan, Patrick M

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Science.gov (United States)

    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…

  3. Uncovering Physiologic Mechanisms of Circadian Rhythms and Sleep/Wake Regulation Through Mathematical Modeling

    Science.gov (United States)

    2007-06-01

    circadian pacemaker located in the SCN of the hypothalamus . The neural pathway from the retina to the SCN has been identified as the axons of a special set...human functioning. Despite the disparity in approaches, there is a com- mon, shared goal of capturing the rich dynamics of neurophysiology and

  4. Metabolic Rhythms of the Cyanobacterium Cyanothece sp ATCC 51142 Correlate with Modeled Dynamics of Circadian Clock

    Czech Academy of Sciences Publication Activity Database

    Červený, Jan; Nedbal, Ladislav

    2009-01-01

    Roč. 4, č. 24 (2009), s. 295-303 ISSN 0748-7304 R&D Projects: GA ČR(CZ) GA206/09/1284 Institutional research plan: CEZ:AV0Z60870520 Keywords : circadian clock * cyanobacteria * model * photosynthesis * respiration Subject RIV: CE - Biochemistry Impact factor: 4.418, year: 2009

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

    NARCIS (Netherlands)

    Winter, de L.; Schepers, L.W.; Cuaresma Franco, M.; Barbosa, M.J.; Martens, D.E.; Wijffels, R.H.

    2014-01-01

    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

  6. Circadian Rhythms in Fear Conditioning: An Overview of Behavioral, Brain System, and Molecular Interactions

    Directory of Open Access Journals (Sweden)

    Anne Albrecht

    2017-01-01

    Full Text Available The formation of fear memories is a powerful and highly evolutionary conserved mechanism that serves the behavioral adaptation to environmental threats. Accordingly, classical fear conditioning paradigms have been employed to investigate fundamental molecular processes of memory formation. Evidence suggests that a circadian regulation mechanism allows for a timestamping of such fear memories and controlling memory salience during both their acquisition and their modification after retrieval. These mechanisms include an expression of molecular clocks in neurons of the amygdala, hippocampus, and medial prefrontal cortex and their tight interaction with the intracellular signaling pathways that mediate neural plasticity and information storage. The cellular activities are coordinated across different brain regions and neural circuits through the release of glucocorticoids and neuromodulators such as acetylcholine, which integrate circadian and memory-related activation. Disturbance of this interplay by circadian phase shifts or traumatic experience appears to be an important factor in the development of stress-related psychopathology, considering these circadian components are of critical importance for optimizing therapeutic approaches to these disorders.

  7. The circadian rhythm of salivary cortisol in growing pigs : Effects of age, gender, and stress

    NARCIS (Netherlands)

    Ruis, MAW; Brake, JHAT; Engel, B; Ekkel, ED; Buist, WG; Blokhuis, HJ; Koolhaas, JM

    This experiment was designed to examine circadian rhythmicity of cortisol in saliva of growing pigs, in relation to age, gender, and (time of) stressor application. Additionally, the acute cortisol response to a stressor was studied. Five groups, each consisting of 3 barrows and 3 gilts, were

  8. Effects of SCN lesions on circadian blood pressure rhythm in normotensive and transgenic hypertensive rats

    NARCIS (Netherlands)

    Witte, K.; Schnecko, A.; Buijs, R. M.; van der Vliet, J.; Scalbert, E.; Delagrange, P.; Guardiola-Lemaître, B.; Lemmer, B.

    1998-01-01

    Transgenic hypertensive TGR(mREN2)27 (TGR) rats, carrying an additional mouse renin gene, have been found to show inverse circadian blood pressure profiles compared to normotensive Sprague-Dawley rats. In order to evaluate the contributions of the suprachiasmatic nucleus (SCN) and the neurohormone

  9. Roles of eating, rumination, and arterial pressure in determination of the circadian rhythm of renal blood flow in sheep.

    Science.gov (United States)

    Tebot, I; Bonnet, J-M; Junot, S; Ayoub, J-Y; Paquet, C; Cirio, A

    2009-02-01

    To assess the roles of feeding behavior (eating and rumination) and systemic arterial pressure (SAP) on determination of the circadian rhythm of renal blood flow (RBF), 20 sheep fitted with ultrasonic flow-metering probes around both renal arteries and a submandibular balloon to monitor jaw movements (6 of them with a telemetry measurement system into the carotid artery for SAP recording), were successively assigned to 6 feeding patterns: once daily in the morning (0900 to 1100 h), afternoon (1700 to 1900 h), or evening (1900 to 2100 h); twice daily at 0900 to 1100 h and 1700 to 1900 h; ad libitum (food renewed each 2 h); and fasting (40 h). All protocols were carried out in autumn-winter, and the fasting pattern was repeated in spring-summer to evaluate the effect of the daylight length on RBF. In the once-daily feeding patterns, a rapid increase in RBF (P blood pressure and that seemed superimposed on a primary lighting-cycle-dependent RBF rhythm.

  10. Comparison between the impact of morning and evening doses of rivaroxaban on the circadian endogenous coagulation rhythm in healthy subjects.

    Science.gov (United States)

    Brunner-Ziegler, S; Jilma, B; Schörgenhofer, C; Winkler, F; Jilma-Stohlawetz, P; Koppensteiner, R; Quehenberger, P; Seger, C; Weigel, G; Griesmacher, A; Brunner, M

    2016-02-01

    ESSENTIALS: It is unknown whether single rivaroxaban doses should best be administered in the morning or evening. Circadian rhythm of coagulation/fibrinolysis was measured after morning or evening intake of rivaroxaban. Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations. Evening intake of rivaroxaban better matches the morning hypofibrinolysis. A circadian variation of the endogenous coagulation system exists with hypercoagulability and hypofibrinolysis and a corresponding peak of cardiovascular thromboembolic events in the morning. So far, no information is given as to whether single daily doses of the new oral anticoagulant drug rivaroxaban should best be administered in the morning or the evening. Sixteen healthy male or female volunteers with a mean age of 26 ± 7 years were included in this randomized, controlled, analyst-blinded cross-over clinical trial. All subjects were given three morning and three evening single doses of 10 mg rivaroxaban. Circadian rhythms of prothrombin fragment 1 + 2, plasminogen activator inhibitor, and plasmin-antiplasmin complex were measured before any medication intake, as well as after morning or evening medication intake. Rivaroxaban concentrations were determined by an anti-activated factor X assay and liquid chromatography-mass spectrometry. Concentrations of rivaroxaban were higher 12 h after evening intake of rivaroxaban than 12 h after morning intake (53.3 ng mL(-1) [95% confidence interval 46.0-67.8] vs. 23.3 ng mL(-1) [19.4-29.1, respectively]). Rivaroxaban intake in the evening reduced morning F1+2 concentrations better at 8:00 AM than did administration on awakening (85 ± 25 nmol L(-1) vs. 106 ± 34 nmol L(-1) , CI: 9.4-32.1). In addition, this suppression effect was longer lasting after evening intake. Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations and better matches the morning hypofibrinolysis. These results might help to further improve

  11. The Effect Of Reversed Light-Dark Cycle And Restricted Feeding Regime On The Circadian Rhythm Of Cortisol And Serotonin In Male Rats

    International Nuclear Information System (INIS)

    Abdel-Rahman, M.; El-Masry, H.; El-Hennamy, R.E.; Abdel-Kader, S.

    2013-01-01

    Biological clock plays an important role in the regulation of different physiological processes and behaviour. The present study aimed to investigate the effect of the reversed light-dark cycle and restricted feeding regime for one and two weeks on the circadian rhythm of cortisol and serotonin in male rats. Serum cortisol and brain serotonin levels were delayed after exposing rats to a reversed light-dark cycle for one week which may be due to the action of the gene Per2 that delay the phase of the clock. On the other hand, their levels highly elevated and peaked at the same time after two weeks which may be due to continuous stressful events. The serum cortisol reached its highest level at the meal time after one week of restricted feeding while after two weeks, its level was higher at several time intervals, which may be due to the need of the body to energy. The peak of the brain serotonin rhythm was delayed during the day after one week while after two weeks, it exhibited the same pattern of the circadian rhythm of control group. From the present results and previous studies, it could be concluded that the reversed light-dark cycle and restricted feeding regime are able to shift the phase of the circadian rhythm of the studied physiological parameters which led to many mental and physiological disorders

  12. A Role for CHH Methylation in the Parent-of-Origin Effect on Altered Circadian Rhythms and Biomass Heterosis in Arabidopsis Intraspecific Hybrids[W][OPEN

    Science.gov (United States)

    Ng, Danny W.-K.; Miller, Marisa; Yu, Helen H.; Huang, Tien-Yu; Kim, Eun-Deok; Lu, Jie; Xie, Qiguang; McClung, C. Robertson; Chen, Z. Jeffrey

    2014-01-01

    Hybrid plants and animals often show increased levels of growth and fitness, a phenomenon known as hybrid vigor or heterosis. Circadian rhythms optimize physiology and metabolism in plants and animals. In plant hybrids and polyploids, expression changes of the genes within the circadian regulatory network, such as CIRCADIAN CLOCK ASSOCIATED1 (CCA1), lead to heterosis. However, the relationship between allelic CCA1 expression and heterosis has remained elusive. Here, we show a parent-of-origin effect on altered circadian rhythms and heterosis in Arabidopsis thaliana F1 hybrids. This parent-of-origin effect on biomass heterosis correlates with altered CCA1 expression amplitudes, which are associated with methylation levels of CHH (where H = A, T, or C) sites in the promoter region. The direction of rhythmic expression and hybrid vigor is reversed in reciprocal F1 crosses involving mutants that are defective in the RNA-directed DNA methylation pathway (argonaute4 and nuclear RNA polymerase D1a) but not in the maintenance methylation pathway (methyltransferase1 and decrease in DNA methylation1). This parent-of-origin effect on circadian regulation and heterosis is established during early embryogenesis and maintained throughout growth and development. PMID:24894042

  13. A Role for CHH Methylation in the Parent-of-Origin Effect on Altered Circadian Rhythms and Biomass Heterosis in Arabidopsis Intraspecific Hybrids.

    Science.gov (United States)

    Ng, Danny W-K; Miller, Marisa; Yu, Helen H; Huang, Tien-Yu; Kim, Eun-Deok; Lu, Jie; Xie, Qiguang; McClung, C Robertson; Chen, Z Jeffrey

    2014-06-01

    Hybrid plants and animals often show increased levels of growth and fitness, a phenomenon known as hybrid vigor or heterosis. Circadian rhythms optimize physiology and metabolism in plants and animals. In plant hybrids and polyploids, expression changes of the genes within the circadian regulatory network, such as CIRCADIAN CLOCK ASSOCIATED1 (CCA1), lead to heterosis. However, the relationship between allelic CCA1 expression and heterosis has remained elusive. Here, we show a parent-of-origin effect on altered circadian rhythms and heterosis in Arabidopsis thaliana F1 hybrids. This parent-of-origin effect on biomass heterosis correlates with altered CCA1 expression amplitudes, which are associated with methylation levels of CHH (where H = A, T, or C) sites in the promoter region. The direction of rhythmic expression and hybrid vigor is reversed in reciprocal F1 crosses involving mutants that are defective in the RNA-directed DNA methylation pathway (argonaute4 and nuclear RNA polymerase D1a) but not in the maintenance methylation pathway (methyltransferase1 and decrease in DNA methylation1). This parent-of-origin effect on circadian regulation and heterosis is established during early embryogenesis and maintained throughout growth and development. © 2014 American Society of Plant Biologists. All rights reserved.

  14. Circadian Impairment of Distal Skin Temperature Rhythm in Patients With Sleep-Disordered Breathing: The Effect of CPAP.

    Science.gov (United States)

    Martinez-Nicolas, Antonio; Guaita, Marc; Santamaría, Joan; Montserrat, Josep M; Rol, María Ángeles; Madrid, Juan Antonio

    2017-06-01

    Our aim was to evaluate the circadian rhythm of distal skin temperature (DST) in sleep-disordered breathing (SDB), its relation to excessive daytime sleepiness and the effect of continuous positive airway pressure (CPAP) on DST. Eighty SDB patients (53.1 ± 1.2 years old, 27.6% women) and 67 healthy participants (52.3 ± 1.6 years old, 26.9% women) wore a temperature data logger for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test (MWT), Multiple Sleep Latency Test, and Sustained Attention to Response Task protocol to objectively quantify daytime sleepiness. A subset of 21 moderate to severe SDB patients were treated with CPAP during at least 3 months and revaluated with the same procedure. A nonparametric analysis was performed to characterize DST to assess differences between groups and associations among DST, polysomnography, and daytime sleepiness measures. SDB patients showed an unstable, fragmented, flattened, phase-advanced, and less robust DST rhythm as compared to healthy participants. The more severe the SDB, the worse the DST pattern was, as indicated by the correlation coefficient. Sleepiness, according to MWT sleep latencies, was also associated with the higher fragmentation, lower amplitude, and less robustness of the DST rhythm. Treatment with CPAP improved DST pattern regularity and robustness. DST is altered in SDB, exhibiting a direct relationship to the severity of this condition, and improves with CPAP treatment. DST independently correlates with sleepiness, thus, its measurement may contribute to the understanding of the pathophysiology of sleepiness in these patients. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  15. Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

    Directory of Open Access Journals (Sweden)

    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

  16. Independence of genetic geographical variation between photoperiodic diapause, circadian eclosion rhythm, and Thr-Gly repeat region of the period gene in Drosophila littoralis.

    Science.gov (United States)

    Lankinen, P; Forsman, P

    2006-02-01

    Drosophila littoralis is a latitudinally widespread European species of the Drosophila virilis group. The species has ample genetic variation in photoperiodism (adult diapause) and circadian rhythmicity (pupal eclosion rhythm), with adaptive latitudinal clines in both of them. The possible common genetic basis between the variability of photoperiodism and circadian rhythms was studied by a long-term crossing experiment. A northern strain (65 degrees N) having long critical day length (CDL = 19.9 h) for diapause, early phase of the entrained rhythm in LD 3:21 (psi(LD3:21) = 12.3 h), and short period (tau= 18.8 h) of the free-running rhythm for the eclosion rhythm was crossed with a southern strain (42 degrees N) having short CDL (12.4 h), late eclosion phase (psi(LD3:21) = 20.2 h), and long period (tau= 22.8 h). After 54 generations, including free recombination, artificial selection, and genetic drift, a novel strain resulted, having even more "southern" diapause and more "northern" eclosion rhythm characteristics than found in any of the geographical strains. The observed complete separation of eclosion rhythm characteristics from photoperiodism is a new finding in D. littoralis; in earlier studies followed for 16 generations, the changes had been mostly parallel. Evidently, the genes controlling the variability of the eclosion rhythm and photoperiodism in D. littoralis are different but closely linked. To test for the possible gene loci underlying the observed geographical variability, the period gene was studied in 10 strains covering all the known clock variability in D. littoralis. The authors sequenced the most suspected Thr-Gly region, which is known to take part in the adaptive clock variability in Drosophila melanogaster. No coding differences were found in the strains, showing that this region is not included in the adaptive clock variability in D. littoralis.

  17. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease

    OpenAIRE

    Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-01-01

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal ...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans.

    Science.gov (United States)

    Dijk, Derk-Jan; Duffy, Jeanne F; Silva, Edward J; Shanahan, Theresa L; Boivin, Diane B; Czeisler, Charles A

    2012-01-01

    The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity 'room' light (∼90-150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17-94%) and after bright light by 52% (range 12-84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.

  20. Scheduled meals and scheduled palatable snacks synchronize circadian rhythms: consequences for ingestive behavior.

    Science.gov (United States)

    Escobar, Carolina; Salgado, Roberto; Rodriguez, Katia; Blancas Vázquez, Aurea Susana; Angeles-Castellanos, Manuel; Buijs, Ruud M

    2011-09-26

    Food is a potent time signal for the circadian system and has shown to entrain and override temporal signals transmitted by the biological clock, the suprachiasmatic nucleus, which adjusts mainly to the daily light/dark (LD) alternation. Organisms mostly ingest food in their active period and this permits a correct coordination between the LD and the food elicited time signals with the circadian system. Under conditions when feeding opportunities are shifted to the usual resting/sleep phase, the potent entraining force of food, shifts circadian fluctuations in several tissues, organs, and brain structures toward meal time, resulting a desynchrony within the body and between the organism and the external LD cycle. The daily scheduled access to a palatable snack exerts similar changes specifically to brain areas involved in motivation and reward responses. This review describes the phenomenology of food entrainment and entrainment by a palatable snack. It suggests how scheduled feeding can lead to food addiction and how shifted feeding schedules toward the sleep phase can result in altered ingestive behavior, obesity and disturbed metabolic responses. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters

    Directory of Open Access Journals (Sweden)

    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.

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

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    Stryjek, Rafał; Modlińska, Klaudia; Turlejski, Krzysztof; Pisula, Wojciech

    2013-01-01

    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.

  3. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial

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    Lone Baandrup

    2016-10-01

    Full Text Available Abstract 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 was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test. Results A subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance. Conclusion Our data suggest melatonin as an aid during benzodiazepine withdrawal for

  4. Rest-activity circadian rhythms and bone mineral density in elderly men

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    Tara S. Rogers

    2017-12-01

    Conclusions: The data demonstrate modest associations between overall circadian rhythmicity of rest and activity (measured by pseudo F-statistic, as well as daytime to nighttime activity ratio (measured by alpha statistic, aBMD and ΔaBMD, but adjustment for covariates related to lifestyle, BMI and comorbidities attenuated most of these associations. These results suggest that RAR patterns are not independently associated with aBMD or four-year ΔaBMD at the total hip or femoral neck in older men, but additional research is needed.

  5. Circadian rhythms in diet and habitat use in red ruffed lemurs (Varecia rubra) and white-fronted brown lemurs (Eulemur fulvus albifrons).

    Science.gov (United States)

    Vasey, Natalie

    2004-08-01

    Daily variation in niche use among vertebrates is attributed to a variety of factors, including thermoregulatory, reproductive, and nutritional requirements. Lemuriform primates exhibit many behavioral and physiological adaptations related to thermoregulation and sharp, seasonal reproduction, yet they have rarely been subjects of a quantitative analysis of circadian (or daily) rhythms in niche use. In this study, I document daily rhythms in diet and microhabitat use over an annual cycle in two sympatric, frugivorous lemurs, Varecia rubra and Eulemur fulvus albifrons. Data on diet, forest site, and forest height were recorded at 5-min time points on focal animals and divided into three time blocks for analysis (06:00-10:00 hr, 10:00-14:00 hr, and 14:00-18:00 hr). I employed multivariate tests of independence to examine daily rhythms in diet and microhabitat use according to sex, season, and reproductive stage. Throughout the day, V. rubra is frugivorous and dwells in the upper canopy, with notable departures (especially for females) during the hot seasons, gestation, and lactation. E. f. albifrons has heterogeneous daily rhythms of food choice and microhabitat use, particularly across seasons, and both sexes are equally variable. These daily rhythms in diet and microhabitat use appear related to thermoregulatory and nutritional requirements, seasonal food availability and circadian rhythms of plant (and possibly insect) palatability, predator avoidance tactics, and in the case of Varecia, to reproduction. Daily rhythms of food choice in V. rubra support two previously suggested hypotheses explaining why primates consume more nonfruit items late in the day, whereas those of E. f. albifrons are too variable to lend support to these hypotheses. Copyright 2003 Wiley-Liss, Inc.

  6. Biological rhythms

    Science.gov (United States)

    Halberg, F.

    1975-01-01

    An overview is given of basic features of biological rhythms. The classification of periodic behavior of physical and psychological characteristics as circadian, circannual, diurnal, and ultradian is discussed, and the notion of relativistic time as it applies in biology is examined. Special attention is given to circadian rhythms which are dependent on the adrenocortical cycle. The need for adequate understanding of circadian variations in the basic physiological indicators of an individual (heart rate, body temperature, systolic and diastolic blood pressure, etc.) to ensure the effectiveness of prophylactic and therapeutic measures is stressed.

  7. Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging.

    Science.gov (United States)

    Stankiewicz, Alexander J; McGowan, Erin M; Yu, Lili; Zhdanova, Irina V

    2017-10-26

    Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B , and p20 , in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

  8. Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging

    Directory of Open Access Journals (Sweden)

    Alexander J. Stankiewicz

    2017-10-01

    Full Text Available Chronic high caloric intake (HCI is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

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

    Science.gov (United States)

    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.

  10. Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation.

    Science.gov (United States)

    Hampel, Daniela; Shahab-Ferdows, Setareh; Islam, M Munirul; Peerson, Janet M; Allen, Lindsay H

    2017-04-01

    Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake

  11. Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients

    Science.gov (United States)

    Fiorentini, A; Perciaccante, A; Paris, A; Serra, P; Tubani, L

    2005-01-01

    The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance. PMID:16197556

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

    DEFF Research Database (Denmark)

    Luuk, Hendrik; Fahrenkrug, Jan; Hannibal, Jens

    2012-01-01

    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......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...

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

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    Suliman Khan

    2018-01-01

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

  14. Spotlight on fish: light pollution affects circadian rhythms of European perch but does not cause stress.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    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.

  16. Chronobiological studies of chicken IgY: monitoring of infradian, circadian and ultradian rhythms of IgY in blood and yolk of chickens.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain

    International Nuclear Information System (INIS)

    Stankov, B.; Moeller, M.; Lucini, V.; Capsono, S.; Fraschini, F.

    1994-01-01

    Dogs kept under controlled photoperiodic conditions of 12h light and 12h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[ 125 I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in the species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 3-thiotriphosphate led to a consequential decrease in the binding density. Collectively, these data show that the dog possesses all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species. 43 refs. 6 figs., 1 tabs

  18. Participation of endogenous circadian rhythm in photoperiodic time measurement during ovarian responses of the subtropical tree sparrow, Passer montanus.

    Science.gov (United States)

    Singh, Namram Sushindrajit; Dixit, Anand Shanker

    2014-05-01

    Resonance experiment was employed to investigate the mechanism of photoperiodic time measurement during initiation of ovarian growth and functions in the subtropical population of female tree sparrow (Passer montanus) at Shillong (Latitude 25 degrees 34 'N, Longitude 91 degrees 53 'E). Photosensitive birds were subjected to various resonance light dark cycles of different durations such as: 12-(6L:6D), 24-(6L:18D), 36-(6L:30D), 48-(6L:42D), 60-(6L:54D) and 72-(6L:66D) h along with a control group under long days (14L:10D) for 35 days. Birds, exposed to long days, exhibited ovarian growth confirming their photosensitivity at the beginning of the experiment. The birds experiencing resonance light/dark cycles of 12, 36 and 60 h responded well while those exposed to 24, 48 and 72 h cycles did not. Serum levels of estradiol-17beta ran almost parallel to changes in the follicular size. Further, histomorphometric analyses of ovaries of the birds subjected to various resonance light dark cycles revealed distinct correlation with the ovarian growth and the serum levels of estradiol-17beta. No significant change in body weight was observed in the birds under any of the light regimes. The results are in agreement with the avian external coincidence model of photoperiodic time measurement and indicate that an endogenous circadian rhythm is involved during the initiation of the gonadal growth and functions in the female tree sparrow.

  19. The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer.

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    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.

  20. Interactions of cortisol, testosterone, and resistance training: influence of circadian rhythms.

    Science.gov (United States)

    Hayes, Lawrence D; Bickerstaff, Gordon F; Baker, Julien S

    2010-06-01

    Diurnal variation of sports performance usually peaks in the late afternoon, coinciding with increased body temperature. This circadian pattern of performance may be explained by the effect of increased core temperature on peripheral mechanisms, as neural drive does not appear to exhibit nycthemeral variation. This typical diurnal regularity has been reported in a variety of physical activities spanning the energy systems, from Adenosine triphosphate-phosphocreatine (ATP-PC) to anaerobic and aerobic metabolism, and is evident across all muscle contractions (eccentric, isometric, concentric) in a large number of muscle groups. Increased nerve conduction velocity, joint suppleness, increased muscular blood flow, improvements of glycogenolysis and glycolysis, increased environmental temperature, and preferential meteorological conditions may all contribute to diurnal variation in physical performance. However, the diurnal variation in strength performance can be blunted by a repeated-morning resistance training protocol. Optimal adaptations to resistance training (muscle hypertrophy and strength increases) also seem to occur in the late afternoon, which is interesting, since cortisol and, particularly, testosterone (T) concentrations are higher in the morning. T has repeatedly been linked with resistance training adaptation, and higher concentrations appear preferential. This has been determined by suppression of endogenous production and exogenous supplementation. However, the cortisol (C)/T ratio may indicate the catabolic/anabolic environment of an organism due to their roles in protein degradation and protein synthesis, respectively. The morning elevated T level (seen as beneficial to achieve muscle hypertrophy) may be counteracted by the morning elevated C level and, therefore, protein degradation. Although T levels are higher in the morning, an increased resistance exercise-induced T response has been found in the late afternoon, suggesting greater

  1. Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease

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    Si-Yue Li

    2017-01-01

    Conclusions: In the circadian system of advanced PD rat models, circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.

  2. Expression of MEP Pathway Genes and Non-volatile Sequestration Are Associated with Circadian Rhythm of Dominant Terpenoids Emission in Osmanthus fragrans Lour. Flowers

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    Riru Zheng

    2017-10-01

    Full Text Available Osmanthus fragrans Lour. is one of the top 10 traditional ornamental flowers in China famous for its unique fragrance. Preliminary study proved that the terpenoids including ionone, linalool, and ocimene and their derivatives are the dominant aroma-active compounds that contribute greatly to the scent bouquet. Pollination observation implies the emission of aromatic terpenoids may follow a circadian rhythm. In this study, we investigated the variation of volatile terpenoids and its potential regulators. The results showed that both volatile and non-volatile terpenoids presented circadian oscillation with high emission or accumulation during the day and low emission or accumulation during the night. The volatile terpenoids always increased to reach their maximum values at 12:00 h, while free and glycosylated compounds continued increasing throughout the day. The depletion of non-volatile pool might provide the substrates for volatile emission at 0:00–6:00, suggesting the sequestration of non-volatile compounds acted like a buffer regulating emission of terpenoids. Further detection of MEP pathway genes demonstrated that their expressions increased significantly in parallel with the evident increase of both volatile and non-volatile terpenoids during the day, indicating that the gene expressions were also closely associated with terpenoid formation. Thus, the expression of MEP pathway genes and internal sequestration both played crucial roles in modulating circadian rhythm of terpenoid emission in O. fragrans.

  3. Circadian rhythm characteristics, poor sleep quality, daytime sleepiness and common psychiatric disorders among Thai college students.

    Science.gov (United States)

    Haregu, Alazar; Gelaye, Bizu; Pensuksan, Wipawan C; Lohsoonthorn, Vitool; Lertmaharit, Somrat; Rattananupong, Thanapoom; Tadesse, Mahlet G; Williams, Michelle A

    2015-06-01

    To investigate the relationship between common psychiatric disorders (CPDs) and sleep characteristics (evening chronotype, poor sleep quality and daytime sleepiness) among Thai college students. A cross-sectional study was conducted among 2,970 undergraduate students in Thailand. Students were asked to complete a self-administered questionnaire that collected information about lifestyle and demographic characteristics. The Horne and Ostberg Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate circadian preference, sleep quality and daytime sleepiness, respectively. The General Health Questionnaire-12 (GHQ-12) was used to evaluate presence of CPDs. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of CPDs in relation to the covariates of interest. A total of 337 students were classified as having CPDs (11.2%; 95% CI 10.1-12.3%). Evening chronotype (OR = 3.35; 95% CI 2.09-5.37), poor sleep quality (OR = 4.89; 95% CI 3.66-6.54) and excessive daytime sleepiness (OR = 1.95; 95% CI 1.54-2.47) were statistically significantly associated with CPDs. Our study demonstrated that CPDs are common among Thai college students. Further, evening chronotype, poor sleep quality and excessive daytime sleepiness were strongly associated with increased risk of CPDs. These findings highlight the importance of educating students and school administrators about the importance of sleep and their impact on mental health. Copyright © 2014 Wiley Publishing Asia Pty Ltd.

  4. 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

    Science.gov (United States)

    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.

  5. The circadian rhythm of core body temperature (Part I: The use of modern telemetry systems to monitor core body temperature variability

    Directory of Open Access Journals (Sweden)

    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.

  6. Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin, blood pressure, heart rate, skin blood flow, transepidermal water loss, and skin amino acids of healthy young women.

    Science.gov (United States)

    Reinberg, A E; Touitou, Y; Soudant, E; Bernard, D; Bazin, R; Mechkouri, M

    1996-08-01

    Sixteen healthy women users and nonusers of oral contraceptives (OC) volunteered to document a set of circadian rhythms. Nine were taking OC providing ethynyl estradiol (0.03-0.05 mg/24h, 21 days/month) combined with DL- or L-norgestrel or norethisterone. There was no group difference (p > 0.05) in median age (22 years), weight (57 kg), and height (162) cm). Data were obtained at fixed hours, 5 times/24h, during a 48-h span, in November. (Day activity from approximately 08:00 to approximately 23:00 h and night rest). Environmental conditions were controlled, using air-conditioned rooms of constant temperature (26 degrees +/- 0.5) and relative humidity 45% +/- 1. Both cosinor and ANOVA were used for statistical analyses. All circadian rhythms were validated with one exception: that of salivary melatonin was not detected in OC users. The 24h mean (M) exhibited group differences for certain variables: M was greater in OC than non-OC users for systolic blood pressure (p cortisol (p < 0.04) and skin amino acids (p < 0.003). No group difference was detected in any other documented rhythms: diastolic blood pressure, grip strength of both hands, oral temperature, self-rated fatigue, and the skin variables of urea, lactate, triglycerides, and acid phosphatase activity.

  7. Amplitude Reduction and Phase Shifts of Melatonin, Cortisol and Other Circadian Rhythms after a Gradual Advance of Sleep and Light Exposure in Humans

    Science.gov (United States)

    Dijk, Derk-Jan; Duffy, Jeanne F.; Silva, Edward J.; Shanahan, Theresa L.; Boivin, Diane B.; Czeisler, Charles A.

    2012-01-01

    Background The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. Methodology/Principal Findings We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity ‘room’ light (∼90–150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17–94%) and after bright light by 52% (range 12–84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. Conclusions/Significance Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet

  8. Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans.

    Directory of Open Access Journals (Sweden)

    Derk-Jan Dijk

    Full Text Available BACKGROUND: The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity 'room' light (∼90-150 lux or moderate light supplemented with bright light (∼10,000 lux for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h. Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17-94% and after bright light by 52% (range 12-84%, as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. CONCLUSIONS/SIGNIFICANCE: Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift

  9. The Goodwin model: simulating the effect of light pulses on the circadian sporulation rhythm of Neurospora crassa.

    Science.gov (United States)

    Ruoff, P; Vinsjevik, M; Monnerjahn, C; Rensing, L

    2001-03-07

    The Goodwin oscillator is a minimal model that describes the oscillatory negative feedback regulation of a translated protein which inhibits its own transcription. Now, over 30 years later this scheme provides a basic description of the central components in the circadian oscillators of Neurospora, Drosophila, and mammals. We showed previously that Neurospora's resetting behavior by pulses of temperature, cycloheximide or heat shock can be simulated by this model, in which degradation processes play an important role for determining the clock's period and its temperature-compensation. Another important environmental factor for the synchronization is light. In this work, we show that on the basis of a light-induced transcription of the frequency (frq) gene phase response curves of light pulses as well as the influence of the light pulse length on phase shifts can be described by the Goodwin oscillator. A relaxation variant of the model predicts that directly after a light pulse inhibition in frq -transcription occurs, even when the inhibiting factor Z (FRQ) has not reached inhibitory concentrations. This has so far not been experimentally investigated for frq transcription, but it complies with a current model of light-induced transcription of other genes by a phosphorylated white-collar complex. During long light pulses, the relaxational model predicts that the sporulation rhythm is arrested in a steady state of high frq -mRNA levels. However, experimental results indicate the possibility of oscillations around this steady state and more in favor of the results by the original Goodwin model. In order to explain the resetting behavior by two light pulses, a biphasic first-order kinetics recovery period of the blue light receptor or of the light signal transduction pathway has to be assumed. Copyright 2001 Academic Press.

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

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    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.

  11. Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

    Science.gov (United States)

    Svendsen, Jon C; Genz, Janet; Anderson, W Gary; Stol, Jennifer A; Watkinson, Douglas A; Enders, Eva C

    2014-01-01

    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.

  12. Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

    Directory of Open Access Journals (Sweden)

    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.

  13. Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms.

    Science.gov (United States)

    Pantazopoulos, Harry; Wiseman, Jason T; Markota, Matej; Ehrenfeld, Lucy; Berretta, Sabina

    2017-03-15

    Growing evidence points to a key role for somatostatin (SST) in schizophrenia (SZ) and bipolar disorder (BD). In the amygdala, neurons expressing SST play an important role in the regulation of anxiety, which is often comorbid in these disorders. We tested the hypothesis that SST-immunoreactive (IR) neurons are decreased in the amygdala of subjects with SZ and BD. Evidence for circadian SST expression in the amygdala and disrupted circadian rhythms and rhythmic peaks of anxiety in BD suggest a disruption of rhythmic expression of SST in this disorder. Amygdala sections from 12 SZ, 15 BD, and 15 control subjects were processed for immunocytochemistry for SST and neuropeptide Y, a neuropeptide partially coexpressed in SST-IR neurons. Total numbers (N t ) of IR neurons were measured. Time of death was used to test associations with circadian rhythms. SST-IR neurons were decreased in the lateral amygdala nucleus in BD (N t , p = .003) and SZ (N t , p = .02). In normal control subjects, N t of SST-IR neurons varied according to time of death. This pattern was altered in BD subjects, characterized by decreases of SST-IR neurons selectively in subjects with time of death corresponding to the day (6:00 am to 5:59 pm). Numbers of neuropeptide Y-IR neurons were not affected. Decreased SST-IR neurons in the amygdala of patients with SZ and BD, interpreted here as decreased SST expression, may disrupt responses to fear and anxiety regulation in these individuals. In BD, our findings raise the possibility that morning peaks of anxiety depend on a disruption of circadian regulation of SST expression in the amygdala. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Long-Term Effects of Extreme Trauma on Sleep Quality and the Circadian Rhythm of Sleep and Wakefulness: An Actigraphy Study of Utøya Survivors

    OpenAIRE

    Ugland, Kaja Skullerud; Landrø, Heidi

    2015-01-01

    The terror attack at Utøya Island in 2011 was a national tragedy. Most of the survivors were adolescents. The aim of this study was to explore how sleep and circadian rhythm of sleep and wakefulness was affected after the Utøya massacre. In addition we wanted to examine the general sleep pattern among adolescents. Methods: 42 Utøya survivors and 46 control subjects matched on gender, age and socio- demographical variables were studied 18-30 months after the attack. Sleep was assessed by ac...

  15. Circadian Melatonin and Temperature Taus in Delayed Sleep-wake Phase Disorder and Non-24-hour Sleep-wake Rhythm Disorder Patients: An Ultradian Constant Routine Study.

    Science.gov (United States)

    Micic, Gorica; Lovato, Nicole; Gradisar, Michael; Burgess, Helen J; Ferguson, Sally A; Lack, Leon

    2016-08-01

    Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h "days" in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD (p = 0.007, p = 0.06) and control participants (p sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients' persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD

  16. The role of gene duplication and unconstrained selective pressures in the melanopsin gene family evolution and vertebrate circadian rhythm regulation.

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    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

  17. [Study of prevention and control of delirium in ventilated patients by simulating blockage of circadian rhythm with sedative in intensive care unit].

    Science.gov (United States)

    Li, Junyan; Dong, Chenming; Zhang, Hong; Zhang, Hongsong; Song, Ruixia; Yang, Zhaohui; Feng, Fang; Qi, Yan; Yang, Jing

    2016-01-01

    To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. (1) There were no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHEII

  18. Flexibility of the C-terminal, or CII, ring of KaiC governs the rhythm of the circadian clock of cyanobacteria.

    Science.gov (United States)

    Chang, Yong-Gang; Kuo, Nai-Wei; Tseng, Roger; LiWang, Andy

    2011-08-30

    In the cyanobacterial circadian oscillator, KaiA and KaiB alternately stimulate autophosphorylation and autodephosphorylation of KaiC with a periodicity of approximately 24 h. KaiA activates autophosphorylation by selectively capturing the A loops of KaiC in their exposed positions. The A loops and sites of phosphorylation, residues S431 and T432, are located in the CII ring of KaiC. We find that the flexibility of the CII ring governs the rhythm of KaiC autophosphorylation and autodephosphorylation and is an example of dynamics-driven protein allostery. KaiA-induced autophosphorylation requires flexibility of the CII ring. In contrast, rigidity is required for KaiC-KaiB binding, which induces a conformational change in KaiB that enables it to sequester KaiA by binding to KaiA's linker. Autophosphorylation of the S431 residues around the CII ring stabilizes the CII ring, making it rigid. In contrast, autophosphorylation of the T432 residues offsets phospho-S431-induced rigidity to some extent. In the presence of KaiA and KaiB, the dynamic states of the CII ring of KaiC executes the following circadian rhythm: CII STflexible → CIISpTflexible → CIIpSpTrigid → CIIpSTvery-rigid → CIISTflexible. Apparently, these dynamic states govern the pattern of phosphorylation, ST → SpT → pSpT → pST → ST. CII-CI ring-on-ring stacking is observed when the CII ring is rigid, suggesting a mechanism through which the ATPase activity of the CI ring is rhythmically controlled. SasA, a circadian clock-output protein, binds to the CI ring. Thus, rhythmic ring stacking may also control clock-output pathways.

  19. Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.

    Science.gov (United States)

    Mirzaei, Khadijeh; Xu, Min; Qi, Qibin; de Jonge, Lilian; Bray, George A; Sacks, Frank; Qi, Lu

    2014-02-01

    Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis. We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial. The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured. By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ. Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.

  20. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2015-01-01

    OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

  2. Feeding period restriction alters the expression of peripheral circadian rhythm genes without changing body weight in mice.

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    Hagoon Jang

    Full Text Available Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD or a high-fat diet (HFD. In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.

  3. What Are Circadian Rhythms?

    Science.gov (United States)

    ... NICHD Research Information Find a Study More Information Preterm Labor and Birth Condition Information NICHD Research Information ... NIH-funded researchers identify risk factors for sleep apnea during pregnancy NICHD scientists identify molecule that may ...

  4. Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015

    Science.gov (United States)

    Auger, R. Robert; Burgess, Helen J.; Emens, Jonathan S.; Deriy, Ludmila V.; Thomas, Sherene M.; Sharkey, Katherine M.

    2015-01-01

    A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed. Citation: Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015. J Clin Sleep Med 2015;11(10):1199–1236. PMID:26414986

  5. Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks

    Directory of Open Access Journals (Sweden)

    Christina eSchmidt

    2012-07-01

    Full Text Available Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus and the brainstem locus coeruleus (LC. However, how age- related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications to aging in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarise and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviours.

  6. Plasticity of the intrinsic period of the human circadian timing system.

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    Frank A J L Scheer

    2007-08-01

    Full Text Available Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol, which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light ( approximately 450 lux; approximately 1.2 W/m(2 for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration.

  7. Circadian Regulation of Synaptic Plasticity

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    Marcos G. Frank

    2016-07-01

    Full Text Available Circadian rhythms refer to oscillations in biological processes with a period of approximately 24 h. In addition to the sleep/wake cycle, there are circadian rhythms in metabolism, body temperature, hormone output, organ function and gene expression. There is also evidence of circadian rhythms in synaptic plasticity, in some cases driven by a master central clock and in other cases by peripheral clocks. In this article, I review the evidence for circadian influences on synaptic plasticity. I also discuss ways to disentangle the effects of brain state and rhythms on synaptic plasticity.

  8. Review of the possible relationship and hypothetical links between attention deficit hyperactivity disorder (ADHD) and the simple sleep related movement disorders, parasomnias, hypersomnias, and circadian rhythm disorders.

    Science.gov (United States)

    Walters, Arthur S; Silvestri, Rosalia; Zucconi, Marco; Chandrashekariah, Ranju; Konofal, Eric

    2008-12-15

    Recent evidence has been accumulating that the sleep of individuals with attention deficit hyperactivity disorder (ADHD) is not only disrupted in a nonspecific way but that ADHD has an increased association with simple sleep related movement disorders such as restless legs syndrome/periodic limb movements in sleep (RLS/PLMS), rhythmic movement disorder (body rocking and head banging), and parasomnias, such as disorders of partial arousal (sleep walking, sleep terrors, and confusional arousals). In addition increased associations have been reported between ADHD and hypersomnias such as narcolepsy and sleep apnea as well as circadian rhythm disorders, such as delayed sleep phase syndrome. These relationships are reviewed and the implications for such associations are explored. Patients with sleep disorders should be queried about the symptoms of ADHD and vice versa.

  9. The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization.

    Science.gov (United States)

    Korge, Sandra; Maier, Bert; Brüning, Franziska; Ehrhardt, Lea; Korte, Thomas; Mann, Matthias; Herrmann, Andreas; Robles, Maria S; Kramer, Achim

    2018-01-01

    Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics. Among them was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose knockdown and knockout led to short circadian periods. TNPO1 was found in endogenous clock protein complexes and particularly binds to PER1 regulating its (but not PER2's) nuclear localization. While PER1 is also transported to the nucleus by the classical, Importin β-mediated pathway, TNPO1 depletion slowed down PER1 nuclear import rate as revealed by fluorescence recovery after photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated nuclear import may constitute a novel input pathway of how cellular redox state signals to the clock, since redox stress increases binding of TNPO1 to PER1 and decreases its nuclear localization. Together, our RNAi screen knocking down import carriers (but also export carriers) results in short and long circadian periods indicating that the regulatory pathways that control the timing of clock protein subcellular localization are far more complex than previously assumed. TNPO1 is one of the novel players essential for normal circadian periods and potentially for redox regulation of the clock.

  10. The frequency of hippocampal theta rhythm is modulated on a circadian period and is entrained by food availability.

    Directory of Open Access Journals (Sweden)

    Robert Gordon Keith Munn

    2015-03-01

    Full Text Available The hippocampal formation plays a critical role in the generation of episodic memory. While the encoding of the spatial and contextual components of memory have been extensively studied, how the hippocampus encodes temporal information, especially at long time intervals, is less well understood. The activity of place cells in hippocampus has previously been shown to be modulated at a circadian time-scale, entrained by a behavioral stimulus, but not entrained by light. The experimental procedures used in the previous study of this phenomenon, however, necessarily conflated two alternative entraining stimuli, the exposure to the recording environment and the availability of food, making it impossible to distinguish between these possibilities. Here we demonstrate that the frequency of theta-band hippocampal EEG varies with a circadian period in freely moving animals and that this periodicity mirrors changes in the firing rate of hippocampal neurons. Theta activity serves, therefore, as a proxy of circadian-modulated hippocampal neuronal activity. We then demonstrate that the frequency of hippocampal theta driven by stimulation of the reticular formation also varies with a circadian period. Because this effect can be observed without having to feed the animal to encourage movement we were able to identify what stimulus entrains the circadian oscillation. We show that with reticular-activated recordings started at various times of the day the frequency of theta varies quasi-sinusoidally with a 25 hour period and phase-aligned when referenced to the animal’s regular feeding time, but not the recording start time. Furthermore, we show that theta frequency consistently varied with a circadian period when the data obtained from repeated recordings started at various times of the day were referenced to the start of food availability in the recording chamber. This pattern did not occur when data were referenced to the start of the recording session or

  11. The role of chronobiology and circadian rhythms in type 2 diabetes mellitus: implications for management of diabetes

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    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 diabetes. Keywords: diabetes, clock gene, shift work, eating behavior, sleep loss

  12. Circadian Rhythm and Cartilage Extracellular Matrix Genes in Osseointegration: A Genome-Wide Screening of Implant Failure by Vitamin D Deficiency

    Science.gov (United States)

    Mengatto, Cristiane Machado; Mussano, Federico; Honda, Yoshitomo; Colwell, Christopher S.; Nishimura, Ichiro

    2011-01-01

    Background Successful dental and orthopedic implants require the establishment of an intimate association with bone tissue; however, the mechanistic explanation of how biological systems accomplish osseointegration is still incomplete. We sought to identify critical gene networks involved in osseointegration by exploring the implant failure model under vitamin D deficiency. Methodology Adult male Sprague-Dawley rats were exposed to control or vitamin D-deficient diet prior to the osteotomy surgery in the femur bone and the placement of T-shaped Ti4Al6V implant. Two weeks after the osteotomy and implant placement, tissue formed at the osteotomy site or in the hollow chamber of T-shaped implant was harvested and total RNA was evaluated by whole genome microarray analyses. Principal Findings Two-way ANOVA of microarray data identified 103 genes that were significantly (>2 fold) modulated by the implant placement and vitamin D deficiency. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses assigned the highest z-score to the circadian rhythm pathway including neuronal PAS domain 2 (NPAS2), and period homolog 2 (Per2). NPAS2 and Aryl hydrocarbon receptor nuclear translocator-like (ARNTL/Bmal 1) were upregulated around implant and diminished by vitamin D deficiency, whereas the expression pattern of Per2 was complementary. Hierarchical cluster analysis further revealed that NPAS2 was in a group predominantly composed of cartilage extracellular matrix (ECM) genes. Whereas the expression of bone ECM genes around implant was not significantly affected by vitamin D deficiency, cartilage ECM genes were modulated by the presence of the implant and vitamin D status. In a proof-of-concept in vitro study, the expression of cartilage type II and X collagens was found upregulated when mouse mesenchymal stem cells were cultured on implant disk with 1,25D supplementation. Conclusions This study suggests that the circadian rhythm system and cartilage extracellular matrix may be

  13. The heme-regulatory motif of nuclear receptor Rev-erbβ is a key mediator of heme and redox signaling in circadian rhythm maintenance and metabolism.

    Science.gov (United States)

    Carter, Eric L; Ramirez, Yanil; Ragsdale, Stephen W

    2017-07-07

    Rev-erbβ is a heme-responsive transcription factor that regulates genes involved in circadian rhythm maintenance and metabolism, effectively bridging these critical cellular processes. Heme binding to Rev-erbβ indirectly facilitates its interaction with the nuclear receptor co-repressor (NCoR1), resulting in repression of Rev-erbβ target genes. Fe 3+ -heme binds in a 6-coordinate complex with axial His and Cys ligands, the latter provided by a heme-regulatory motif (HRM). Rev-erbβ was thought to be a heme sensor based on a weak K d value for the Rev-erbβ·heme complex of 2 μm determined with isothermal titration calorimetry. However, our group demonstrated with UV-visible difference titrations that the K d value is in the low nanomolar range, and the Fe 3+ -heme off-rate is on the order of 10 -6 s -1 making Rev-erbβ ineffective as a sensor of Fe 3+ -heme. In this study, we dissected the kinetics of heme binding to Rev-erbβ and provided a K d for Fe 3+ -heme of ∼0.1 nm Loss of the HRM axial thiolate via redox processes, including oxidation to a disulfide with a neighboring cysteine or dissociation upon reduction of Fe 3+ - to Fe 2+ -heme, decreased binding affinity by >20-fold. Furthermore, as measured in a co-immunoprecipitation assay, substitution of the His or Cys heme ligands in Rev-erbβ was accompanied by a significant loss of NCoR1 binding. These results demonstrate the importance of the Rev-erbβ HRM in regulating interactions with heme and NCoR1 and advance our understanding of how signaling through HRMs affects the major cellular processes of circadian rhythm maintenance and metabolism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Shifting the circadian rhythm of feeding in mice induces gastrointestinal, metabolic and immune alterations which are influenced by ghrelin and the core clock gene Bmal1.

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    Jorien Laermans

    Full Text Available BACKGROUND: In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF, a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. METHODS: Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD. Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test. Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. RESULTS: The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1α expression and promoted gastric contractility changes. CONCLUSIONS: This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and

  15. The validity, reliability, and utility of the iButton® for measurement of body temperature circadian rhythms in sleep/wake research.

    Science.gov (United States)

    Hasselberg, Michael J; McMahon, James; Parker, Kathy

    2013-01-01

    Changes in core body temperature due to heat transfer through the skin have a major influence on sleep regulation. Traditional measures of skin temperature are often complicated by extensive wiring and are not practical for use in normal living conditions. This review describes studies examining the reliability, validity and utility of the iButton®, a wireless peripheral thermometry device, in sleep/wake research. A review was conducted of English language literature on the iButton as a measure of circadian body temperature rhythms associated with the sleep/wake cycle. Seven studies of the iButtton as a measure of human body temperature were included. The iButton was found to be a reliable and valid measure of body temperature. Its application to human skin was shown to be comfortable and tolerable with no significant adverse reactions. Distal skin temperatures were negatively correlated with sleep/wake activity, and the temperature gradient between the distal and proximal skin (DPG) was identified as an accurate physiological correlate of sleep propensity. Methodological issues included site of data logger placement, temperature masking factors, and temperature data analysis. The iButton is an inexpensive, wireless data logger that can be used to obtain a valid measurement of human skin temperature. It is a practical alternative to traditional measures of circadian rhythms in sleep/wake research. Further research is needed to determine the utility of the iButton in vulnerable populations, including those with neurodegenerative disorders and memory impairment and pediatric populations. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Epicardial adipose tissue volume a diagnostic study for independent predicting disorder of circadian rhythm of blood pressure in patients with essential hypertension.

    Science.gov (United States)

    Zhou, L; Deng, Y; Gong, J; Chen, X; Zhang, Q; Wang, J

    2016-05-30

    The aim of the study was to determine whether epicardial adipose tissue volume (EATV), a new cardiometabolic risk factor, is associated with circadian changes of blood pressure (BP) in patients with newly diagnosed essential hypertension. Ninety patients with newly diagnosed essential hypertension underwent ambulatory blood pressure monitoring for 24 h. EATV was measured using cardiac computed tomography. These patients were categorized into three groups according to their BP patterns (group 1, n=46, dipper hypertension, also called normal pattern; group 2, n=24, non-dipper hypertension; group 3, n=20, anti-dipper hypertension; group 2 and 3 are also called abnormal pattern). Data were collected retrospectively and compared between hypertensive patients with normal pattern and abnormal pattern. The normal pattern hypertensive patient had significant lower mean EATV and BP ((EATV, 91.3±29.4 cm3) than those of abnormal pattern patients including group 2 (EATV, 116.2±31.06cm3, blood pressure mode was 0.500 (phypertension and anti-dipper hypertension. EATV measured by cardiac computed tomography can be used to indicate the increased risk of circadian rhythm of blood pressure.

  17. Redundant function of REV-ERBalpha and beta and non-essential role for Bmal1 cycling in transcriptional regulation of intracellular circadian rhythms.

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    Andrew C Liu

    2008-02-01

    Full Text Available The mammalian circadian clockwork is composed of a core PER/CRY feedback loop and additional interlocking loops. In particular, the ROR/REV/Bmal1 loop, consisting of ROR activators and REV-ERB repressors that regulate Bmal1 expression, is thought to "stabilize" core clock function. However, due to functional redundancy and pleiotropic effects of gene deletions, the role of the ROR/REV/Bmal1 loop has not been accurately defined. In this study, we examined cell-autonomous circadian oscillations using combined gene knockout and RNA interference and demonstrated that REV-ERBalpha and beta are functionally redundant and are required for rhythmic Bmal1 expression. In contrast, the RORs contribute to Bmal1 amplitude but are dispensable for Bmal1 rhythm. We provide direct in vivo genetic evidence that the REV-ERBs also participate in combinatorial regulation of Cry1 and Rorc expression, leading to their phase-delay relative to Rev-erbalpha. Thus, the REV-ERBs play a more prominent role than the RORs in the basic clock mechanism. The cellular genetic approach permitted testing of the robustness of the intracellular core clock function. We showed that cells deficient in both REV-ERBalpha and beta function, or those expressing constitutive BMAL1, were still able to generate and maintain normal Per2 rhythmicity. Our findings thus underscore the resilience of the intracellular clock mechanism and provide important insights into the transcriptional topologies underlying the circadian clock. Since REV-ERB function and Bmal1 mRNA/protein cycling are not necessary for basic clock function, we propose that the major role of the ROR/REV/Bmal1 loop and its constituents is to control rhythmic transcription of clock output genes.

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

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    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

  19. Neurobiology of circadian systems.

    Science.gov (United States)

    Schulz, Pierre; Steimer, Thierry

    2009-01-01

    Time is a dimension tightly associated with the biology of living species. There are cycles of varied lengths in biological activities, from very short (ultradian) rhythms to rhythms with a period of approximately one day (circadian) and rhythms with longer cycles, of a week, a month, a season, or even longer. These rhythms are generated by endogenous biological clocks, i.e. time-keeping structures, rather than being passive reactions to external fluctuations. In mammals, the suprachiasmatic nucleus (SCN) is the major pacemaker. The pineal gland, which secretes melatonin, is the major pacemaker in other phyla. There also exist biological clocks generating circadian rhythms in peripheral tissues, for example the liver. A series of clock genes generates the rhythm through positive and negative feedback effect of proteins on their own synthesis, and this system oscillates with a circadian period. External factors serve as indicators of the astronomical (solar) time and are called zeitgebers, literally time-givers. Light is the major zeitgeber, which resets daily the SCN circadian clock. In the absence of zeitgebers, the circadian rhythm is said to be free running; it has a period that differs from 24 hours. The SCN, together with peripheral clocks, enables a time-related homeostasis, which can become disorganized in its regulation by external factors (light, social activities, food intake), in the coordination and relative phase position of rhythms, or in other ways. Disturbances of rhythms are found in everyday life (jet lag, shift work), in sleep disorders, and in several psychiatric disorders including affective disorders. As almost all physiological and behavioural functions in humans occur on a rhythmic basis, the possibility that advances, delays or desynchronization of circadian rhythms might participate in neurological and psychiatric disorders has been a theme of research. In affective disorders, a decreased circadian amplitude of several rhythms as well as a

  20. Relations between depressed mood and vocal parameters before, during and after sleep deprivation : a circadian rhythm study

    NARCIS (Netherlands)

    BOUHUYS, AL; SCHUTTE, HK; BEERSMA, DGM; NIEBOER, GLJ

    The mechanism underlying improvement after total sleep deprivation (TSD) was studied in 14 major depressed patients. The suggestions that (1) circadian processes and/or (2) dimensions of arousal may play a role in the response to TSD were investigated. Diurnal variation of depressed mood and of

  1. The reproducibility of the circadian BP rhythm in treated hypertensive patients with polycystic kidney disease and mild chronic renal impairment--a prospective ABPM study.

    Science.gov (United States)

    Covic, Adrian; Mititiuc, Irina; Gusbeth-Tatomir, Paul; Goldsmith, David J

    2002-01-01

    Diurnal BP rhythm is known to be abnormal (reduced BP fall with sleep) in chronic renal failure, dialysis and renal transplantation patients. In subjects with primary hypertension and with reduced diurnal BP fall with sleep there is consistent evidence of increased target-organ damage. However, the few studies that have addressed the reproducibility of diurnal rhythm in normal or hypertensive subjects have concluded that the BP fall with sleep is poorly reproducible. It is not known whether the same is true for patients with renal disease. In 30 subjects with autosomal polycystic kidney disease (ADPKD), mild chronic renal failure and normal office BP levels on standardised anti-hypertensive treatment, ambulatory blood pressure monitoring (ABPM) was done three times over a twelve month period to assess the reproducibility of blood pressure fall with sleep. When comparing ABPM 2 with the ABPM 1 recording (3 months difference between measurements) only 43.3% of the patients maintained the initial dipping category (defined by quartiles of the ABPM 1 diurnal BP distribution). The same proportion of subjects had a similar dipping category, when ABPM 3 was compared to ABPM 1 (9 months difference between measurements), but a large (24%) subset of patients had dramatic shifts in their amplitude in nocturnal BP fall, significantly greater than those recorded after a shorter inter-measurement interval. Equally important, our study reveals the fact that, with time, there is no tendency to decrease circadian variation: a similar proportion (a quarter to one third) of patients increased or decreased their amplitude in nocturnal BP fall, at 3 and 9 months. When several ABPM measurements are repeated for the same patients, the repeatability is even worse, since only 36.6% of our study population maintained the initial dipping category across all three ABPM determinations (ABPM 1 and ABPM 2 and ABPM 3). There is a widespread abnormality in diurnal BP rhythm in ADPKD patients with

  2. Postoperative circadian disturbances

    DEFF Research Database (Denmark)

    Gögenur, Ismail

    2010-01-01

    parameters, and if pharmacological administration of chronobiotics could improve postoperative recovery. Circadian rhythm disturbances were found in all the examined endogenous rhythms. A delay was found in the endogenous rhythm of plasma melatonin and excretion of the metabolite of melatonin (AMT6s...... 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...

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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.

    2015-01-01

    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 ...

  5. An Endogenous Circadian Rhythm in Sleep Inertia Results in Greatest Cognitive Impairment upon Awakening during the Biological Night

    OpenAIRE

    Scheer, Frank A. J. L.; Shea, Thomas J.; Hilton, Michael F.; Shea, Steven A.

    2008-01-01

    Sleep inertia is the impaired cognitive performance immediately upon awakening, which decays over tens of minutes. This phenomenon has relevance to people who need to make important decisions soon after awakening, such as on-call emergency workers. Such awakenings can occur at varied times of day or night, so the objective of the study was to determine whether or not the magnitude of sleep inertia varies according to the phase of the endogenous circadian cycle. Twelve adults (mean, 24 years; ...

  6. Effect of walking on circadian rhythms and sleep quality of patients with lung cancer: a randomised controlled trial.

    Science.gov (United States)

    Chen, Hui-Mei; Tsai, Chun-Ming; Wu, Yu-Chung; Lin, Kuan-Chia; Lin, Chia-Chin

    2016-11-22

    Sleep disturbances and poor rest-activity rhythms, which can reduce the quality of life, are highly prevalent among patients with lung cancer. This trial investigated the effects of a 12-week exercise intervention including home-based walking exercise training and weekly exercise counseling on 111 lung cancer patients. Participants were randomly allocated to receive the intervention or usual-care. Outcomes included objective sleep (total sleep time, TST; sleep efficiency, SE; sleep onset latency, SOL; and wake after sleep onset, WASO), subjective sleep (Pittsburgh Sleep Quality Index, PSQI), and rest-activity rhythms (r24 and Iexercise group significantly improved 3 and 6 months after intervention. The moderating effect of Isleep quality of lung cancer patients and can be considered an optional component of lung cancer rehabilitation.

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

    Science.gov (United States)

    1992-12-29

    Hydroxyindole -acetic acid In vivo brain microdialysis was used to characterize the daily pattern of 5 -hy- Suprachiasmatic nucleus droxyindole-acetic acid...principal serotonin metabolite, 5 - hydroxyindole - SCN is comprised of cells that exhibit a self-generating acetic acid ( 5 -HIAA), in the SCN. The...significance of pacemaker activity [3, 4] and is richly innervated by amino the 5 -HIAA rhythm is not certain, however, because acid, peptidergic and

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

    Science.gov (United States)

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

    2010-02-08

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

  9. Effects of music composed by Mozart and Ligeti on blood pressure and heart rate circadian rhythms in normotensive and hypertensive rats.

    Science.gov (United States)

    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

  10. Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

    Science.gov (United States)

    Queiroz, O; Morel, C

    1974-04-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

  11. Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor

    Science.gov (United States)

    2014-01-01

    Glucocorticoids are pleiotropic hormones, which are involved in almost every cellular, molecular and physiologic network of the organism, and regulate a broad spectrum of physiologic functions essential for life. The cellular response to glucocorticoids displays profound variability both in magnitude and in specificity of action. Tissue sensitivity to glucocorticoids differs among individuals, within tissues of the same individual and within the same cell. The actions of glucocorticoids are mediated by the glucocorticoid receptor, a ubiquitously expressed intracellular, ligand-dependent transcription factor. Multiple mechanisms, such as pre-receptor ligand metabolism, receptor isoform expression, and receptor-, tissue-, and cell type-specific factors, exist to generate diversity as well as specificity in the response to glucocorticoids. Alterations in the molecular mechanisms of glucocorticoid receptor action impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. This review summarizes the recent advances in our understanding of the molecular mechanisms determining tissue sensitivity to glucocorticoids with particular emphasis on novel mutations and new information on the circadian rhythm and ligand-induced repression of the glucocorticoid receptor. PMID:25155432

  12. Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor.

    Science.gov (United States)

    Nicolaides, Nicolas C; Charmandari, Evangelia; Chrousos, George P; Kino, Tomoshige

    2014-08-25

    Glucocorticoids are pleiotropic hormones, which are involved in almost every cellular, molecular and physiologic network of the organism, and regulate a broad spectrum of physiologic functions essential for life. The cellular response to glucocorticoids displays profound variability both in magnitude and in specificity of action. Tissue sensitivity to glucocorticoids differs among individuals, within tissues of the same individual and within the same cell. The actions of glucocorticoids are mediated by the glucocorticoid receptor, a ubiquitously expressed intracellular, ligand-dependent transcription factor. Multiple mechanisms, such as pre-receptor ligand metabolism, receptor isoform expression, and receptor-, tissue-, and cell type-specific factors, exist to generate diversity as well as specificity in the response to glucocorticoids. Alterations in the molecular mechanisms of glucocorticoid receptor action impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. This review summarizes the recent advances in our understanding of the molecular mechanisms determining tissue sensitivity to glucocorticoids with particular emphasis on novel mutations and new information on the circadian rhythm and ligand-induced repression of the glucocorticoid receptor.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. The stability of the circadian rhythm of green finches (Carduelis chloris) under the influence of a weak electrical field.

    Science.gov (United States)

    Lintzen, T; Boese, G; Müller, M; Eichmeier, J; Ruhenstroth-Bauer, G

    1989-01-01

    Free-running activity rhythms of nine green finches (Carduelis chloris) were studied under the influence of a 10-Hz square-wave electrical field. With a field strength of magnitude of E = 2.5 V/m in the empty cage, the population had a mean period of 23.64 +/- 0.77 hr. In the same experiment, but without the electrical field, the period was 23.66 +/- 0.80 hr. These results are in contradiction to Wever's description of a field-induced shortening of the period. A series of experiments with 10-Hz pulses of the same square-wave form, yet with various field strengths (8.7 and 65.2 V/m), also gave no effects.

  15. The photoperiodic response in Syrian hamster depends upon a melatonin-driven circadian rhythm of sensitivity to melatonin.

    Science.gov (United States)

    Pitrosky, B; Kirsch, R; Vivien-Roels, B; Georg-Bentz, I; Canguilhem, B; Pevet, P

    1995-11-01

    The pineal gland, via the daily pattern of melatonin (MEL) secretion, is directly involved in the conduction of photoperiodic information. The duration of MEL secretion is proportional to the duration of the dark period and, whatever the photoperiod is, MEL synthesis occurs 3 or 4 h after the dark onset in Syrian hamsters. In order to determine the relative importance of the duration or the coincidence hypothesis, a daily infusion protocol was used in sexually active pinealectomized hamsters. Long duration of MEL infusion (10 h) completely inhibit testes whereas short duration infusion (5 h) had no effect. When the animals were infused twice within 2 h 30 min separated by 3 h, they presented a complete gonadal atrophy, similar to the one observed with the 10 h infusion. Measurement of plasma MEL during the infusion and separation periods revealed that MEL reached physiological nighttime values during the infusion period and fell to daytime values 1 h after the end of an infusion period. Thus, the results could not be due to a time additive action of the two MEL pulses. An intermediate response was observed when the 2 signals were applied across the light/dark transition. Gonadal regression did not occur when the 2 periods of infusion were separated by 5 h 30 min. The efficiency of this type of infusion was not dependent on the ambiant photoperiod since similar results were obtained in long and short photoperiods. The infusion was also as effective during the day as well as during the night. These results suggest that there is a rhythm of sensitivity to MEL, based on the coincidence hypotheses, that are important for transmission of photoperiodic information. This rhythm of sensitivity to MEL seems to be entrained by MEL itself, since the efficiency of the two pulses of MEL is not dependent of time of application and/or of photoperiod.

  16. Mathematical Modeling of Circadian/Performance Countermeasures

    Data.gov (United States)

    National Aeronautics and Space Administration — We developed and refined our current mathematical model of circadian rhythms to incorporate melatonin as a marker rhythm. We used an existing physiologically based...

  17. Mitochondrial H2O2 signaling is controlled by the concerted action of peroxiredoxin III and sulfiredoxin: Linking mitochondrial function to circadian rhythm.

    Science.gov (United States)

    Rhee, Sue Goo; Kil, In Sup

    2016-11-01

    Mitochondria produce hydrogen peroxide (H 2 O 2 ) during energy metabolism in most mammalian cells as well as during the oxidation of cholesterol associated with the synthesis of steroid hormones in steroidogenic cells. Some of the H 2 O 2 produced in mitochondria is released into the cytosol, where it serves as a key regulator of various signaling pathways. Given that mitochondria are equipped with several H 2 O 2 -eliminating enzymes, however, it had not been clear how mitochondrial H 2 O 2 can escape destruction by these enzymes for such release. Peroxiredoxin III (PrxIII) is the most abundant and efficient H 2 O 2 -eliminating enzyme in mitochondria of most cell types. We found that PrxIII undergoes reversible inactivation through hyperoxidation of its catalytic cysteine residue to cysteine sulfinic acid, and that release of mitochondrial H 2 O 2 likely occurs as a result of such PrxIII inactivation. The hyperoxidized form of PrxIII (PrxIII-SO 2 H) is reduced and reactivated by sulfiredoxin (Srx). We also found that the amounts of PrxIII-SO 2 H and Srx undergo antiphasic circadian oscillation in mitochondria of the adrenal gland, heart, and brown adipose tissue of mice maintained under normal conditions. Cytosolic Srx was found to be imported into mitochondria via a mechanism that requires formation of a disulfide-linked complex with heat shock protein 90, which is likely promoted by H 2 O 2 released from mitochondria. The imported Srx was found to be degraded by Lon protease in a manner dependent on PrxIII hyperoxidation state. The coordinated import and degradation of Srx underlie Srx oscillation and consequent PrxIII-SO 2 H oscillation in mitochondria. The rhythmic change in the amount of PrxIII-SO 2 H suggests that mitochondrial release of H 2 O 2 is also likely a circadian event that conveys temporal information on steroidogenesis in the adrenal gland and on energy metabolism in heart and brown adipose tissue to cytosolic signaling pathways. Copyright

  18. [Affective disorders and biological rhythms].

    Science.gov (United States)

    Le Strat, Y; Ramoz, N; Gorwood, P

    2008-06-01

    Disruptions of circadian rhythms are described in affective disorders, including unipolar and bipolar disorder, but also seasonal affective disorder. Sleep-wake and hormone circadian rhythms are among the most quoted examples. Depression could be conceptualized as a desynchronization between the endogenous circadian pacemaker and the exogenous stimuli, such as sunlight and social rhythms. Accordingly, Clock genes have been studied and the literature suggests that variants in these genes confer a higher risk of relapse, more sleep disturbances associated with depression, as well as incomplete treatment response. Most of therapeutic interventions in depression have an impact on biological rhythms. Some of them exclusively act via a biological pathway, such as sleep deprivation or light therapy. Some psychosocial interventions are specifically focusing on social rhythms, particularly in bipolar disorder, in which the promotion of stabilization is emphasized. Finally, all antidepressant medications could improve biological rhythms, but some new agents are now totally focusing this novel approach for the treatment of depression.

  19. Ambient Light Intensity, Actigraphy, Sleep and Respiration, Circadian Temperature and Melatonin Rhythms and Daytime Performance of Crew Members During Space Flight on STS-90 and STS-95 Missions

    Science.gov (United States)

    Czeisler, Charles A.; Dijk, D.-J.; Neri, D. F.; Hughes, R. J.; Ronda, J. M.; Wyatt, J. K.; West, J. B.; Prisk, G. K.; Elliott, A. R.; Young, L. R.

    1999-01-01

    Sleep disruption and associated waking sleepiness and fatigue are common during space flight. A survey of 58 crew members from nine space shuttle missions revealed that most suffered from sleep disruption, and reportedly slept an average of only 6.1 hours per day of flight as compared to an average of 7.9 hours per day on the ground. Nineteen percent of crewmembers on single shift missions and 50 percent of the crewmembers in dual shift operations reported sleeping pill usage (benzodiazepines) during their missions. Benzodiazepines are effective as hypnotics, however, not without adverse side effects including carryover sedation and performance impairment, anterograde amnesia, and alterations in sleep EEG. Our preliminary ground-based data suggest that pre-sleep administration of 0.3 mg of the pineal hormone melatonin may have the acute hypnotic properties needed for treating the sleep disruption of space flight without producing the adverse side effects associated with benzodiazepines. We hypothesize that pre-sleep administration of melatonin will result in decreased sleep latency, reduced nocturnal sleep disruption, improved sleep efficiency, and enhanced next-day alertness and cognitive performance both in ground-based simulations and during the space shuttle missions. Specifically, we have carried out experiments in which: (1) ambient light intensity aboard the space shuttle is assessed during flight; (2) the impact of space flight on sleep (assessed polysomnographically and actigraphically), respiration during sleep, circadian temperature and melatonin rhythms, waking neurobehavioral alertness and performance is assessed in crew members of the Neurolab and STS-95 missions; (3) the effectiveness of melatonin as a hypnotic is assessed independently of its effects on the phase of the endogenous circadian pacemaker in ground-based studies, using a powerful experimental model of the dyssomnia of space flight; (4) the effectiveness of melatonin as a hypnotic is

  20. Temporal organization of activity in the brown bear (Ursus arctos): roles of circadian rhythms, light, and food entrainment.

    Science.gov (United States)

    Ware, Jasmine V; Nelson, O Lynne; Robbins, Charles T; Jansen, Heiko T

    2012-11-01

    Seasonal cycles of reproduction, migration, and hibernation are often synchronized to changes in daylength (photoperiod). Ecological and evolutionary pressures have resulted in physiological specializations enabling animals to occupy a particular temporal niche within the diel cycle leading to characteristic activity patterns. In this study, we characterized the annual locomotor activity of captive brown bears (Ursus arctos). Locomotor activity was observed in 18 bears of varying ages and sexes during the active (Mar-Oct) and hibernating (Nov-Feb) seasons. All bears exhibited either crepuscular or diurnal activity patterns. Estimates of activity duration (α) and synchronization to the daily light:dark cycle (phase angles) indirectly measured photoresponsiveness. α increased as daylength increased but diverged near the autumnal equinox. Phase angles varied widely between active and hibernating seasons and exhibited a clear annual rhythm. To directly test the role of photoperiod, bears were exposed to controlled photoperiod alterations. Bears failed to alter their daily activity patterns (entrain) to experimental photoperiods during the active season. In contrast, photic entrainment was evident during hibernation when the daily photocycle was shifted and when bears were exposed to a skeleton (11:1:11:1) photoperiod. To test whether entrainment to nonphotic cues superseded photic entrainment during the active season, bears were exposed to a reversed feeding regimen (dark-fed) under a natural photocycle. Activity shifted entirely to a nocturnal pattern. Thus daily activity in brown bears is highly modifiable by photoperiod and food availability in a stereotypic seasonal fashion.

  1. Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline.

    Science.gov (United States)

    Auger, R Robert; Burgess, Helen J; Emens, Jonathan S; Deriy, Ludmila V; Thomas, Sherene M; Sharkey, Katherine M

    2015-10-15

    A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed. © 2015 American Academy of Sleep Medicine.

  2. Circadian rhythms in sleep and wakefulness and in salivary melatonin and cortisol concentrations in mothers of term and preterm infants.

    Science.gov (United States)

    McMillen, I C; Mulvogue, H M; Kok, J S; Deayton, J M; Nowak, R; Adamson, T M

    1993-10-01

    We compared the effects of the demands of term and preterm infants on the daily rhythms of sleep and wakefulness and salivary melatonin and cortisol concentrations in mothers for up to 5 months after either birth (term group) or arrival of the infant home (preterm group). Although there were relatively small differences between the term and preterm groups in the daily patterns of infant sleep-wake behavior, there were more marked differences in the maternal sleep-wake parameters. During the first 8 weeks after the arrival of the infant home, the mothers of preterm infants had significantly less time asleep and fewer sleep bouts per 24 hours than did the mothers of term infants. The mothers of preterm infants spent a significantly longer proportion of each night awake (30-40%) for the first 8 weeks than did the mothers of the term infants (20-30%). There was also a significant difference between the term and preterm groups in the effect of time of day on maternal salivary melatonin concentrations. In the term group, maternal melatonin concentrations were higher at night (10 p.m.-6 a.m.) than at any other time of day. In contrast, in the preterm group maternal melatonin concentrations between 10 p.m. and 6 a.m. were only higher than those measured between 6 a.m. and 2 p.m. Salivary cortisol concentrations were significantly higher in the mothers of preterm infants than in the mothers of term infants throughout the 10-week study period, but the peak in salivary cortisol concentrations occurred between 2 a.m. and 10 a.m. in both the term and preterm groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Circadian timekeeping : from basic clock function to implications for health

    NARCIS (Netherlands)

    Lucassen, Eliane Alinda

    2016-01-01

    In modern society, circadian rhythms and sleep are often disturbed, which may negatively affect health. This thesis examines these associations and focuses on the basic functioning of sleep and the circadian system in mice and in humans. Circadian rhythms are orchestrated by ~20,000 neurons in the

  4. Circadian Biology: Uncoupling Human Body Clocks by Food Timing.

    Science.gov (United States)

    Vetter, Celine; Scheer, Frank A J L

    2017-07-10

    Synchrony of circadian rhythms between tissues/organs appears critical for health. A new study reports that meal timing, a modifiable temporal cue for the circadian system, can selectively uncouple circadian rhythms in metabolic physiology from the central circadian clock in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The effect of CA1 α2 adrenergic receptors on memory retention deficit induced by total sleep deprivation and the reversal of circadian rhythm in a rat model.

    Science.gov (United States)

    Norozpour, Yaser; Nasehi, Mohammad; Sabouri-Khanghah, Vahid; Torabi-Nami, Mohammad; Zarrindast, Mohammad-Reza

    2016-09-01

    The α2 adrenergic receptors which abundantly express in the CA1 region of the hippocampus play an important role in the regulation of sleep and memory retention processes. Based on the available evidence, the aim of our study was to investigate consequences of the activation and deactivation of CA1 α2 adrenergic receptors (by clonidine and yohimbine, respectively) on the impairment of memory retention induced by total sleep deprivation (TSD) and the reversal of circadian rhythm (RCR) in a rat model. To this end, the water box apparatus and passive avoidance task were in turn used to induce sleep deprivation and assess memory retention. Our findings suggested that TSD (for 24 and 36, but not 12h) and RCR (12h/day for 3 consecutive days) impair memory function. The post-training intra-CA1 administration of yohimbine (α2 adrenergic receptor antagonist) on its own, at the dose of 0.1μg/rat, decreased the step-through latency and locomotor activity in the TSD- sham treated but not undisturbed sleep rats. Unlike yohimbine, clonidine (α2 adrenergic receptor agonist), in all applied doses (0.001, 0.01 and 0.1μg/rat), failed to induce such an effect. While the subthreshold dose of yohimbine (0.001μg/rat) abrogated the impairment of memory retention induced by the 24-h TSD, it could potentiate the impairment of memory retention induced by 36-h TSD, suggesting the modulatory effect of yohimbine. Moreover, the subthreshold dose of clonidine (0.1μg/rat) restored the memory retention deficit in TSD rats (24 and 36h). On the other hand, the subthreshold dose of clonidine (0.1μg/rat), but not yohimbine (0.001μg/rat) restored the memory retention deficit in RCR rats. Such interventions however did not alter the locomotor activity. The above observations proposed that CA1 α2 adrenergic receptors play a potential role in memory retention deficits induced by TSD and RCR. Copyright © 2016. Published by Elsevier Inc.

  6. [Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus].

    Science.gov (United States)

    Cugini, P; Amato, S; Tarquini, G; Mercuri, S; Turinese, I; Tego, A; Rossetti, M; Panetti, D; Filardi, T; Curione, M; Morano, S

    2010-01-01

    Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p less than 0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p less than 0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p less than 0.001). The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk

  7. Outline of changes in cortisol and melatonin circadian rhythms in the security guards of Shiraz University of Medical Sciences, Shiraz, Iran

    Directory of Open Access Journals (Sweden)

    2012-09-01

    Full Text Available Introduction: According to the literature, a large number of people working in industries and service providing personnel, such as firefighters, physicians, and nurses, are shift workers. The spread of shift working in industrial societies and the incidence of the problems resulting from shift working have caused the researchers to conduct studies on this issue. The present study also aimed to investigate melatonin and cortisol circadian rhythms in the security guards of Shiraz University of Medical Sciences, Shiraz, Iran. . Material and Method: The present study was conducted among 20 security guards of Shiraz University of Medical Sciences. In order to collect the required data, blood samples were taken from the participants in different times of the day (1, 4, 7, 10, 13, 16, 19, and 22 and cortisol and melatonin levels were determined using radioimmunoassay and enzyme immunoassay techniques, respectively. Then, the data were entered into the SPSS statistical software (v. 16.0 and analyzed using One-Way ANOVA. . Result: The results showed that as the intensity of light increased during night time, the level of plasma cortisol increased, as well. Besides, no statistically significant difference was found between the plasma cortisol levels in natural light and 4500-lux light. On the other hand, a significant difference was observed between the level of plasma cortisol in natural light and 9000-lux light as well as 4500- and 9000-lux lights. The study findings also showed that as the intensity of light increased at night, the level of plasma melatonin decreased. In addition, a statistically significant difference was found between the plasma melatonin levels in natural light and 4500-lux light. Nevertheless, no significant difference was observed between the plasma melatonin levels in natural light and 9000-lux light as well as 4500- and 9000-lux lights. .Conclusion: The present study aimed to investigate the subsequences of shift working in the

  8. Circadian clock and vascular disease.

    OpenAIRE

    Takeda, Norihiko; Maemura, Koji

    2010-01-01

    Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprac...

  9. Sleep, Wakefulness and Circadian Rhythm

    Science.gov (United States)

    1979-09-01

    servent i Laracteriser un rythme biologique Var. 0, A. M). Pour de nombreuses espaces vegttables et animales . I’alternance pt~riodique de la lumiere et...inconnue. 11 a 6ti muntr6, par des expiriences animales que. (a) les rythme3 circannuels persistent pendant l’isolenient et (b que Ies variations...ont one composante endog~ne. Un tensemble cohdrent de connaissances peut etre obtenu d’autres exp~riences animales . Les rythmes eircannuels endog~nes

  10. Glycogen synthase kinase-3β haploinsufficiency lengthens the circadian locomotor activity period in mice.

    Science.gov (United States)

    Lavoie, Joëlle; Hébert, Marc; Beaulieu, Jean-Martin

    2013-09-15

    The mood stabiliser drug lithium has been reported to impact circadian rhythms in v