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Sample records for circadian rhythms animal

  1. Circadian Rhythms

    Science.gov (United States)

    ... body function and health? Circadian rhythms can influence sleep-wake cycles, hormone release, body temperature and other important bodily functions. They have been linked to various sleep disorders, such as insomnia. Abnormal circadian rhythms have also ...

  2. Circadian Rhythm Abnormalities

    OpenAIRE

    Zee, Phyllis C.; Attarian, Hrayr; Videnovic, Aleksandar

    2013-01-01

    Purpose: This article reviews the recent advances in understanding of the fundamental properties of circadian rhythms and discusses the clinical features, diagnosis, and treatment of circadian rhythm sleep disorders (CRSDs).

  3. Circadian Rhythm Sleep Disorders

    Science.gov (United States)

    ... psychiatric and other sleep disorders such as sleep apnea and individuals with a strong need for stable ... and circadian rhythm sleep disorder, free-running type. Prevalence • The prevalence of circadian rhythm sleep disorders in ...

  4. The Scorpion An ideal animal model to study long-term microgravity effects on circadian rhythms

    Science.gov (United States)

    Riewe, Pascal C.; Horn, Eberhard R.

    2000-01-01

    The temporal pattern of light and darkness is basic for the coordination of circadian rhythms and establishment of homoeostasis. The 24th frequency of zeitgebers is probably a function of the Earth's rotation. The only way to eliminate its influence on organisms is to study their behavior in space because the reduced day length during orbiting the Earth might disrupt synchronizing mechanisms based on the 24th rhythm. The stability of microgravity induced disturbances of synchronization as well as the extent of adaptation of different physiological processes to this novel environment can only be studied during long-term exposures to microgravity, i.e., on the International Space Station. Biological studies within the long-term domain on ISS demand the use of experimental models which can be exposed to automatic handling of measurements and which need less or no nutritional care. Scorpions offer these features. We describe a fully automatic recording device for the simultaneous collection of data regarding the sensorimotor system and homoeostatic mechanisms. In particular, we record sensitivity changes of the eyes, motor activity and heart beat and/or respiratory activity. The advantage of the scorpion model is supported by the fact that data can be recorded preflight, inflight and postflight from the same animal. With this animal model, basic insights will be obtained about the de-coupling of circadian rhythms of multiple oscillators and their adaptation to the entraining zeitgeber periodicity during exposure to microgravity for at least three biological parameters recorded simultaneously. .

  5. Circadian rhythm sleep disorders

    Directory of Open Access Journals (Sweden)

    Morgenthaler TI

    2012-05-01

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

  6. Sleep and circadian rhythms

    Science.gov (United States)

    Monk, Timothy H.

    1991-01-01

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

  7. 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…

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

    OpenAIRE

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

    2014-01-01

    Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for...

  9. 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...

  10. Effect of melatonin on endogenous circadian rhythm

    Institute of Scientific and Technical Information of China (English)

    XU Feng; WANG Min; ZANG Ling-he

    2008-01-01

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

  11. Circadian rhythms and addiction: mechanistic insights and future directions.

    Science.gov (United States)

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

    2014-06-01

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

  12. Potent social synchronization can override photic entrainment of circadian rhythms.

    Science.gov (United States)

    Fuchikawa, Taro; Eban-Rothschild, Ada; Nagari, Moshe; Shemesh, Yair; Bloch, Guy

    2016-01-01

    Circadian rhythms in behaviour and physiology are important for animal health and survival. Studies with individually isolated animals in the laboratory have consistently emphasized the dominant role of light for the entrainment of circadian rhythms to relevant environmental cycles. Although in nature interactions with conspecifics are functionally significant, social signals are typically not considered important time-givers for the animal circadian clock. Our results challenge this view. By studying honeybees in an ecologically relevant context and using a massive data set, we demonstrate that social entrainment can be potent, may act without direct contact with other individuals and does not rely on gating the exposure to light. We show for the first time that social time cues stably entrain the clock, even in animals experiencing conflicting photic and social environmental cycles. These findings add to the growing appreciation for the importance of studying circadian rhythms in ecologically relevant contexts. PMID:27210069

  13. Visual impairment and circadian rhythm disorders.

    OpenAIRE

    Lockley, SW; Arendt, J; Skene, DJ

    2007-01-01

    Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal "pacemaker" in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment. Sighted individua...

  14. Neuroanatomy of the Extended Circadian Rhythm System

    OpenAIRE

    Morin, Lawrence P

    2012-01-01

    The suprachiasmatic nucleus (SCN), site of the primary clock in the circadian rhythm system, has three major afferent connections. The most important consists of a retinohypothalamic projection through which photic information, received by classical rod/cone photoreceptors and intrinsically photoreceptive retinal ganglion cells, gains access to the clock. This information influences phase and period of circadian rhythms. The two other robust afferent projections are the median raphe serotoner...

  15. 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.

  16. Circadian rhythm of alpha-amylase in rat parotid gland.

    Science.gov (United States)

    Bellavía, S L; Sanz, E G; Chiarenza, A P; Sereno, R; Vermouth, N T

    1990-01-01

    The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. (alpha-1,4-glucan-4-glucanohydrolase) in parotid gland of 25 day old rats was studied under different experimental conditions (fast, reversed photoperiod, constant light or darkness and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of rats fasted or exposed for 7 days to constant darkness did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod and it disappeared in animals submitted to constant light or darkness for 15 days or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm persisted, with minor changes in the acrophase, in parotids of rats kept during their gestation and post-natal life in constant light or darkness. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, under autonomous nervous system control and maternal coordination. This model appears to be useful in the study of sympathetic nervous system control of target organs and circadian rhythms in general. PMID:2076161

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

    Science.gov (United States)

    Fuller, Charles

    1997-01-01

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

  18. Circadian rhythm of lactate dehydrogenase in rat testis.

    Science.gov (United States)

    Vermouth, N T; Ponce, R H; Carriazo, C S; Blanco, A

    1984-01-01

    Activity of total lactate dehydrogenase (LDH) and of the isozyme X (LDH X or C4) have been determined at 2 hr intervals during 24 hr cycles in testis of adult rats maintained since birth in a photoperiod of 14 hr light: 10 hr dark. LDH X activity of epididymal sections (caput, corpus and cauda) from the same animals was also determined. Total LDH and LDH X activities in testis exhibited circadian rhythms with different timing. LDH X in the three portions of epididymis showed diurnal variations similar to those in testis. Rats subjected to constant light or constant dark presented marked modifications of LDH X profiles, indicating that the photoperiod plays a synchronizer role. While total soluble proteins did not show variations in testis of rats exposed to the photoperiod, a circadian rhythm was demonstrated in animals maintained in constant light or dark. PMID:6467917

  19. Circadian rhythm and cell population growth

    CERN Document Server

    Clairambault, Jean; Lepoutre, Thomas

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    L. C. Roden

    2010-02-01

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

  1. Temperature compensation and entrainment in circadian rhythms

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2011-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock me...

  3. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.

    Science.gov (United States)

    Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta

    2010-05-15

    Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis. PMID:19998493

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

    OpenAIRE

    Vaughn, Bradley

    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...

  5. The role of circadian rhythm in breast cancer

    Science.gov (United States)

    Li, Shujing; Ao, Xiang

    2013-01-01

    The circadian rhythm is an endogenous time keeping system shared by most organisms. The circadian clock is comprised of both peripheral oscillators in most organ tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the central nervous system. The circadian rhythm is crucial in maintaining the normal physiology of the organism including, but not limited to, cell proliferation, cell cycle progression, and cellular metabolism; whereas disruption of the circadian rhythm is closely related to multi-tumorigenesis. In the past several years, studies from different fields have revealed that the genetic or functional disruption of the molecular circadian rhythm has been found in various cancers, such as breast, prostate, and ovarian. In this review, we will investigate and present an overview of the current research on the influence of circadian rhythm regulating proteins on breast cancer. PMID:23997531

  6. A Clinical Approach to Circadian Rhythm Sleep Disorders

    OpenAIRE

    Barion, Ana; Zee, Phyllis C.

    2007-01-01

    Circadian rhythm sleep disorders are characterized by complaints of insomnia and excessive sleepiness that are primarily due to alterations in the internal circadian timing system or a misalignment between the timing of sleep and the 24-hour social and physical environment. In addition to physiological and environmental factors, maladaptive behaviors often play an important role in the development of many of the circadian rhythm sleep disorders. This review will focus on the clinical approach...

  7. Pathophysiology and pathogenesis of circadian rhythm sleep disorders

    Directory of Open Access Journals (Sweden)

    Hida Akiko

    2012-03-01

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

  8. Systemic PPARγ deletion impairs circadian rhythms of behavior and metabolism.

    Science.gov (United States)

    Yang, Guangrui; Jia, Zhanjun; Aoyagi, Toshinori; McClain, Donald; Mortensen, Richard M; Yang, Tianxin

    2012-01-01

    Compelling evidence from both human and animal studies suggests a physiological link between the circadian rhythm and metabolism but the underlying mechanism is still incompletely understood. We examined the role of PPARγ, a key regulator of energy metabolism, in the control of physiological and behavioral rhythms by analyzing two strains of whole-body PPARγ null mouse models. Systemic inactivation of PPARγ was generated constitutively by using Mox2-Cre mice (MoxCre/flox) or inducibly by using the tamoxifen system (EsrCre/flox/TM). Circadian variations in oxygen consumption, CO(2) production, food and water intake, locomotor activity, and cardiovascular parameters were all remarkably suppressed in MoxCre/flox mice. A similar phenotype was observed in EsrCre/flox/TM mice, accompanied by impaired rhythmicity of the canonical clock genes in adipose tissues and liver but not skeletal muscles or the kidney. PPARγ inactivation in isolated preadipocytes following exposure to tamoxifen led to a similar blockade of the rhythmicity of the clock gene expression. Together, these results support an essential role of PPARγ in the coordinated control of circadian clocks and metabolic pathways. PMID:22899986

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

    Science.gov (United States)

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

    2015-01-01

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

  10. Circadian Rhythms: Hijacking the Cyanobacterial Clock

    Science.gov (United States)

    Hoyle, Nathaniel P.; O’Neill, John S

    2016-01-01

    The production of limitless carbon-free energy is a long-sought dream of scientists and politicians alike. One strategy for achieving this aim is the production of hydrogen by photosynthetic microorganisms – harnessing the effectively limitless power of the sun to power our cars, toasters and PCR machines. It may be tempting to think of host expression systems as miniature factories given over entirely to the production our molecule of interest. However, the biological nature of the host must be taken into account if we are to maximize productivity. The circadian rhythm, an organism’s entrainable oscillation of biological processes with a period of around 24 hours, is one such aspect that has received scant attention but is likely to be of particular importance to photosynthetic host systems. In this issue of current biology Xu et al. describe how our knowledge of the Synechococcus elongatus circadian clock can be leveraged to improve the production of exogeneous proteins, including those involved in the production of hydrogen [1]. PMID:24309283

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Xinle Li

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

  13. Circadian hormonal rhythms in two new cases of fatal familial insomnia.

    Science.gov (United States)

    Avoni, P; Cortelli, P; Montagna, P; Tinuper, P; Sforza, E; Contin, M; Parchi, P; Pierangeli, G; Maltoni, P; Pavani, A

    1991-12-01

    We used a chronobiological inferential statistical method to investigate circadian rhythms of hypophyseal hormones, cortisol, melatonin and catecholamines in two females of the same family affected by fatal familial insomnia. Case 1 (confirmed at autopsy) presented an absent or progressive loss of circadian rhythms of all hormones. In case 2 there was a loss of GH circadian rhythm and a less significant rhythm for melatonin, catecholamines and gonadotropins. These results confirm the role of the thalamus in regulating hormonal circadian rhythm. PMID:1805556

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

    Science.gov (United States)

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

    1978-05-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    Pellman, Blake A; Kim, Earnest; Reilly, Melissa; Kashima, James; Motch, Oleksiy; de la Iglesia, Horacio O; Kim, Jeansok J

    2015-01-01

    Virtually all animals have endogenous clock mechanisms that "entrain" to the light-dark (LD) cycle and synchronize psychophysiological functions to optimal times for exploring resources and avoiding dangers in the environment. Such circadian rhythms are vital to human mental health, but it is unknown whether circadian rhythms "entrained" to the LD cycle can be overridden by entrainment to daily recurring threats. We show that unsignaled nocturnal footshock caused rats living in an "ethological" apparatus to switch their natural foraging behavior from the dark to the light phase and that this switch was maintained as a free-running circadian rhythm upon removal of light cues and footshocks. Furthermore, this fear-entrained circadian behavior was dependent on an intact amygdala and suprachiasmatic nucleus. Thus, time-specific fear can act as a non-photic entraining stimulus for the circadian system, and limbic centers encoding aversive information are likely part of the circadian oscillator network that temporally organizes behavior. PMID:26468624

  17. Heterogeneity induces rhythms of weakly coupled circadian neurons.

    Science.gov (United States)

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

    2016-01-01

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

  18. 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…

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

    OpenAIRE

    Pellman, Blake A.; Earnest Kim; Melissa Reilly; James Kashima; Oleksiy Motch; de la Iglesia, Horacio O.; Kim, Jeansok J.

    2015-01-01

    Virtually all animals have endogenous clock mechanisms that “entrain” to the light-dark (LD) cycle and synchronize psychophysiological functions to optimal times for exploring resources and avoiding dangers in the environment. Such circadian rhythms are vital to human mental health, but it is unknown whether circadian rhythms “entrained” to the LD cycle can be overridden by entrainment to daily recurring threats. We show that unsignaled nocturnal footshock caused rats living in an “ethologica...

  20. 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.

  1. 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

  2. Alpha-amylase circadian rhythm of young rat parotid gland: an endogenous rhythm with maternal coordination.

    Science.gov (United States)

    Bellavía, S L; Sanz, E G; Sereno, R; Vermouth, N T

    1992-01-01

    The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. alpha-1,4-glucan-4-glucanohydrolase) in the parotid glands of 25-day-old rats were studied under different experimental designs (fasting, reversed photoperiod, constant lighting conditions and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of fasted rats did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm was present, with changes in the acrophase, in parotids of rats kept during their gestation and postnatal life in constant light or dark. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, and with maternal coordination. PMID:1610312

  3. Studies on circadian rhythm disturbances and melatonin in delirium

    NARCIS (Netherlands)

    A.-M. de Jonghe

    2014-01-01

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

  4. My Path from Chemistry to Phytochrome and Circadian Rhythms

    OpenAIRE

    Tobin, EM

    2016-01-01

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

  5. My Path from Chemistry to Phytochrome and Circadian Rhythms

    Science.gov (United States)

    Tobin, Elaine M.

    2016-01-01

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

  6. Neuroimaging, cognition, light and circadian rhythms

    OpenAIRE

    Gaggioni, Giulia; Maquet, Pierre; Schmidt, Christina, 1984-; Dijk, Derk-Jan; Vandewalle, Gilles

    2014-01-01

    In humans, sleep and wakefulness and the associated cognitive processes are regulated through interactions between sleep homeostasis and the circadian system. Chronic disruption of sleep and circadian rhythmicity is common in our society and there is a need for a better understanding of the brain mechanisms regulating sleep, wakefulness and associated cognitive processes. This review summarizes recent investigations which provide first neural correlates of the combined influence of sleep home...

  7. Sleep and circadian rhythm disruption in schizophrenia†

    OpenAIRE

    Wulff, Katharina; Dijk, Derk-Jan; Middleton, Benita; Foster, Russell G.; Joyce, Eileen M.

    2012-01-01

    Background Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions. Aims A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption. Method We examined the relationship between sleep-wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadia...

  8. Circadian Rhythms and Obesity in Mammals

    OpenAIRE

    Oren Froy

    2012-01-01

    Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabol...

  9. Neuroimaging, cognition, light and circadian rhythms

    Directory of Open Access Journals (Sweden)

    Giulia eGaggioni

    2014-07-01

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

  10. Circadian and ultradian influences on dreaming: a dual rhythm model.

    Science.gov (United States)

    Wamsley, Erin J; Hirota, Yasutaka; Tucker, Matthew A; Smith, Mark R; Antrobus, John S

    2007-01-01

    The dual rhythm model of dreaming states that, under high sensory thresholds, heightened general cortical activation common to both REM/NREM and circadian-driven activation cycles sums to produce the main characteristics of dreaming. In addition, the unique pattern of regional brain activation characteristic of REM sleep amplifies the emotional intensity of the dream. Subjects were awakened from REM and NREM sleep once near the nadir of the core body temperature rhythm, where circadian-driven cortical activation was assumed to be low, and again in the late morning, where this activation was presumed to be high. As predicted, changes in the central characteristics of dream reports mirrored REM/NREM and circadian-driven fluctuations in general activation, while at the same time, the regional activation pattern unique to REM sleep amplified dream emotionality selectively in REM reports. PMID:17208651

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Circadian rhythms and fractal fluctuations in forearm motion

    Science.gov (United States)

    Hu, Kun; Hilton, Michael F.

    2005-03-01

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

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

    OpenAIRE

    Bechtel, William

    2015-01-01

    This paper reviews some of the compelling evidence of disrupted circadian rhythms in individuals with mood disorders (major depressive disorder, seasonal affective disorder, and bipolar disorder) and that treatments such as bright light, designed to alter circadian rhythms, are effective in treating these disorders. Neurotransmitters in brain regions implicated in mood regulation exhibit circadian rhythms. A mouse model originally employed to identify a circadian gene has proven a potent mode...

  14. Circadian Rhythms and Mood Disorders: Are The Phenomena and Mechanisms Causally Related?

    OpenAIRE

    William eBechtel

    2015-01-01

    This paper reviews some of the compelling evidence of disrupted circadian rhythms in individuals with mood disorders (major depressive disorder, seasonal affective disorder, and bipolar disorder) and that treatments such as bright light, designed to alter circadian rhythms, are effective in treating these disorders. Neurotransmitters in brain regions implicated in mood regulation exhibit circadian rhythms. A mouse model originally employed to identify a circadian gene has proven a potent mode...

  15. Quantification of circadian rhythms in single cells.

    Directory of Open Access Journals (Sweden)

    Pål O Westermark

    2009-11-01

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

  16. Stochastic Simulation of Delay-Induced Circadian Rhythms in Drosophila

    Directory of Open Access Journals (Sweden)

    Xu Zhouyi

    2009-01-01

    Full Text Available Circadian rhythms are ubiquitous in all eukaryotes and some prokaryotes. Several computational models with or without time delays have been developed for circadian rhythms. Exact stochastic simulations have been carried out for several models without time delays, but no exact stochastic simulation has been done for models with delays. In this paper, we proposed a detailed and a reduced stochastic model with delays for circadian rhythms in Drosophila based on two deterministic models of Smolen et al. and employed exact stochastic simulation to simulate circadian oscillations. Our simulations showed that both models can produce sustained oscillations and that the oscillation is robust to noise in the sense that there is very little variability in oscillation period although there are significant random fluctuations in oscillation peeks. Moreover, although average time delays are essential to simulation of oscillation, random changes in time delays within certain range around fixed average time delay cause little variability in the oscillation period. Our simulation results also showed that both models are robust to parameter variations and that oscillation can be entrained by light/dark circles. Our simulations further demonstrated that within a reasonable range around the experimental result, the rates that dclock and per promoters switch back and forth between activated and repressed sites have little impact on oscillation period.

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

    Directory of Open Access Journals (Sweden)

    William eBechtel

    2015-08-01

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

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

    Science.gov (United States)

    Bechtel, William

    2015-01-01

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

  19. Dysregulation of circadian rhythms following prolactin-secreting pituitary microadenoma.

    Science.gov (United States)

    Borodkin, Katy; Ayalon, Liat; Kanety, Hanna; Dagan, Yaron

    2005-01-01

    A patient who developed an irregular sleep-wake pattern following prolactin-secreting pituitary microadenoma is described. The patient reported difficulties in sleep onset and awakening at the desired time, which caused major dysfunction in his daily life activities. Despite these difficulties, the sleep-related complaints of the patient remained unrecognized for as long as three yrs. Statistical analyses of the patient's rest-activity patterns revealed that the disruption of the sleep-wake circadian rhythm originated from a disharmony between ultradian (semicircadian) and circadian components. The circadian component displayed shorter than 24 h periodicity most of the time, but the semicircadian component fluctuated between longer and shorter than 12 h periods. Additionally, desynchrony in terms of period length was found in the tentative analyses of the rest-activity pattern, salivary melatonin, and oral temperature. While the salivary melatonin time series data could be characterized by a best-fit cosine curve of 24 h, the time series data of oral temperature was more compatible with 28 h best-fit curve. The rest-activity cycle during the simultaneous measurements, however, was best approximated by a best-fit curve of 21 h. The dysregulation of circadian rhythms occurred concomitantly, but not beforehand, with the onset of pituitary disease, thus suggesting an association between the two phenomena. This association may have interesting implications to the modeling of the circadian time-keeping system. This case also highlights the need to raise the awareness to circadian rhythm sleep disorders and to consider disruptions of sleep-wake cycle in patients with pituitary adenoma. PMID:15865328

  20. Circadian rhythm of TSH secretion during TSH-suppression therapy

    OpenAIRE

    M A Sviridonova; A V Ilyin; V V Fadeyev

    2011-01-01

    Тo investigate circadian rhythm of TSH secretion during TSH-suppression therapy. 17 patients taking TSH-suppression therapy, at the age of 18–60 years have been included. Measurements of serum TSH were performed at8.00–9.00h and 14.00–16.00 during the day. The median of TSH concentrations in the morning was 0,016mU/l, at the daytime – 0.015mU/l. The amplitude of TSH circadian variability reached 200% (Me – 19%). At boundary TSH value stability of TSH-suppression can be broken. As specifying a...

  1. Alteration of daily and circadian rhythms following dopamine depletion in MPTP treated non-human primates.

    Directory of Open Access Journals (Sweden)

    Karim Fifel

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

  2. Monitoring circadian rhythms of individual honey bees in a social environment reveals social influences on postembryonic ontogeny of activity rhythms.

    Science.gov (United States)

    Meshi, A; Bloch, G

    2007-08-01

    Social factors constitute an important component of the environment of many animals and have a profound influence on their physiology and behavior. Studies of social influences on circadian rhythms have been hampered by a methodological trade-off: automatic data acquisition systems obtain high-quality data but are effective only for individually isolated animals and therefore compromise by requiring a context that may not be sociobiologically relevant. Human observers can monitor animal activity in complex social environments but are limited in the resolution and quality of data that can be gathered. The authors developed and validated a method for prolonged, automatic, high-quality monitoring of focal honey bees in a relatively complex social environment and with minimal illumination. The method can be adapted for studies on other animals. The authors show that the system provides a reliable estimation of the actual path of a focal bee, only rarely misses its location for > 1 min, and removes most nonspecific signals from the background. Using this system, the authors provide the first evidence of social influence on the ontogeny of activity rhythms. Young bees that were housed with old foragers show ~24-h rhythms in locomotor activity at a younger age and with stronger rhythms than bees housed with a similar number of young bees. By contrast, the maturation of the hypopharyngeal glands was slower in bees housed with foragers, similar to findings in previous studies. The morphology and function of the hypopharyngeal glands vary along with age-based division of labor. Therefore, these findings indicate that social inhibition of task-related maturation was effective in the experimental setup. This study suggests that although the ontogeny of circadian rhythms is typically correlated with the age-based division of labor, their social regulation is different. PMID:17660451

  3. 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.

  4. 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.

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

    OpenAIRE

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

    2013-01-01

    Introduction: Aging is typically associated with impairing behavioral patterns that are frequently and inappropriately seen as normal. Circadian rhythm changes and depressive disorders have been increasingly proposed as the two main overlapping and interpenetrating changes that take place in older age. This study aims to review the state of the art on the subject concerning epidemiology, pathophysiological mechanism, clinical findings and relevance, as well as available treatment options. Mat...

  6. Delayed Sleep Phase Disorder. Prevalence, sleep, circadian rhythm and treatment

    OpenAIRE

    Saxvig, Ingvild West

    2013-01-01

    Adolescence is often characterized by delayed and irregular sleep patterns, with potential negative consequences in terms of school performance and daytime functioning. At the most extreme, a stably delayed sleep phase may reflect a circadian rhythm sleep disorder of the delayed sleep phase type (delayed sleep phase disorder, DSPD). DSPD is assumed to be common amongst adolescents and young adults, but little is known about its prevalence and aetiology, and no guidelines exist ...

  7. 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...

  8. Implications of circadian rhythm and stress in addiction vulnerability.

    Science.gov (United States)

    Becker-Krail, Darius; McClung, Colleen

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

    Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodeg

  10. 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

    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 whe...... 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....

  11. Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

    Science.gov (United States)

    Truong, Kimberly K; Lam, Michael T; Grandner, Michael A; Sassoon, Catherine S; Malhotra, Atul

    2016-07-01

    Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption. PMID:27104378

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

    OpenAIRE

    Chen, Li; Zhang, Bin; Yang, Lu; Xie, Man-Jiang

    2016-01-01

    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 a...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Damian Moran

    Full Text Available The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea.

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

    Directory of Open Access Journals (Sweden)

    ElizabethMHarrison

    2012-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Akhmedov T. R.

    2014-01-01

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

  17. The effects of the noradrenaline reuptake inhibitor atomoxetine on circadian rhythms in mice.

    OpenAIRE

    O'Keeffe, Saileog

    2010-01-01

    Circadian rhythms are patterns in behavioural, physiological and many others parameters that recur approximately every twenty four hours. Dysfunction of the circadian system is being linked to a number of common illnesses. The psychiatric condition Attention Deficit/Hyperactivity Disorder (ADHD) can be characterised by an early onset of sleep problems and breakdown of stable circadian rhythms which recent studies have shown. The drug atomoxetine used in this research project is used in the...

  18. Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats

    OpenAIRE

    Wollnik, Franziska

    1992-01-01

    Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro...

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

    OpenAIRE

    Newcomb, James M; Kirouac, Lauren E.; NAIMIE, AMANDA A.; BIXBY, KIMBERLY A.; Lee, Colin; MALANGA, STEPHANIE; RAUBACH, MAUREEN; Watson, Winsor H.

    2014-01-01

    Daily rhythms of activity driven by circadian clocks are expressed by many organisms, including molluscs. We initiated this study, with the nudibranch Melibe leonina, with four goals in mind: (1) determine which behaviors are expressed with a daily rhythm; (2) investigate which of these rhythmic behaviors are controlled by a circadian clock; (3) determine if a circadian clock is associated with the eyes or optic ganglia of Melibe, as it is in several other gastropods; and (4) test the hypothe...

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

    Directory of Open Access Journals (Sweden)

    Jee-Hyun Um

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

  1. The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms.

    Science.gov (United States)

    Landgraf, Dominic; Joiner, William J; McCarthy, Michael J; Kiessling, Silke; Barandas, Rita; Young, Jared W; Cermakian, Nicolas; Welsh, David K

    2016-08-01

    Endogenous circadian (∼24 h) clocks regulate key physiological and cognitive processes via rhythmic expression of clock genes. The main circadian pacemaker is the hypothalamic suprachiasmatic nucleus (SCN). Mood disorders, including bipolar disorder (BD), are commonly associated with disturbed circadian rhythms. Dopamine (DA) contributes to mania in BD and has direct impact on clock gene expression. Therefore, we hypothesized that high levels of DA during episodes of mania contribute to disturbed circadian rhythms in BD. The mood stabilizer valproic acid (VPA) also affects circadian rhythms. Thus, we further hypothesized that VPA normalizes circadian disturbances caused by elevated levels of DA. To test these hypotheses, we examined locomotor rhythms and circadian gene cycling in mice with reduced expression of the dopamine transporter (DAT-KD mice), which results in elevated DA levels and mania-like behavior. We found that elevated DA signaling lengthened the circadian period of behavioral rhythms in DAT-KD mice and clock gene expression rhythms in SCN explants. In contrast, we found that VPA shortened circadian period of behavioral rhythms in DAT-KD mice and clock gene expression rhythms in SCN explants, hippocampal cell lines, and human fibroblasts from BD patients. Thus, DA and VPA have opposing effects on circadian period. To test whether the impact of VPA on circadian rhythms contributes to its behavioral effects, we fed VPA to DAT-deficient Drosophila with and without functioning circadian clocks. Consistent with our hypothesis, we found that VPA had potent activity-suppressing effects in hyperactive DAT-deficient flies with intact circadian clocks. However, these effects were attenuated in DAT-deficient flies in which circadian clocks were disrupted, suggesting that VPA functions partly through the circadian clock to suppress activity. Here, we provide in vivo and in vitro evidence across species that elevated DA signaling lengthens the circadian

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    Directory of Open Access Journals (Sweden)

    Maria Angeles Bonmati-Carrion

    2014-12-01

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

  4. The effect of lens aging and cataract surgery on circadian rhythm.

    Science.gov (United States)

    Yan, Shen-Shen; Wang, Wei

    2016-01-01

    Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm. PMID:27500118

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

    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

  7. What time is it? Deep learning approaches for circadian rhythms

    Science.gov (United States)

    Agostinelli, Forest; Ceglia, Nicholas; Shahbaba, Babak; Sassone-Corsi, Paolo; Baldi, Pierre

    2016-01-01

    Motivation: Circadian rhythms date back to the origins of life, are found in virtually every species and every cell, and play fundamental roles in functions ranging from metabolism to cognition. Modern high-throughput technologies allow the measurement of concentrations of transcripts, metabolites and other species along the circadian cycle creating novel computational challenges and opportunities, including the problems of inferring whether a given species oscillate in circadian fashion or not, and inferring the time at which a set of measurements was taken. Results: We first curate several large synthetic and biological time series datasets containing labels for both periodic and aperiodic signals. We then use deep learning methods to develop and train BIO_CYCLE, a system to robustly estimate which signals are periodic in high-throughput circadian experiments, producing estimates of amplitudes, periods, phases, as well as several statistical significance measures. Using the curated data, BIO_CYCLE is compared to other approaches and shown to achieve state-of-the-art performance across multiple metrics. We then use deep learning methods to develop and train BIO_CLOCK to robustly estimate the time at which a particular single-time-point transcriptomic experiment was carried. In most cases, BIO_CLOCK can reliably predict time, within approximately 1 h, using the expression levels of only a small number of core clock genes. BIO_CLOCK is shown to work reasonably well across tissue types, and often with only small degradation across conditions. BIO_CLOCK is used to annotate most mouse experiments found in the GEO database with an inferred time stamp. Availability and Implementation: All data and software are publicly available on the CircadiOmics web portal: circadiomics.igb.uci.edu/. Contacts: fagostin@uci.edu or pfbaldi@uci.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307647

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Hippocampal activity mediates the relationship between circadian activity rhythms and memory in older adults.

    Science.gov (United States)

    Sherman, Stephanie M; Mumford, Jeanette A; Schnyer, David M

    2015-08-01

    Older adults experience parallel changes in sleep, circadian rhythms, and episodic memory. These processes appear to be linked such that disruptions in sleep contribute to deficits in memory. Although more variability in circadian patterns is a common feature of aging and predicts pathology, little is known about how alterations in circadian activity rhythms within older adults influence new episodic learning. Following 10 days of recording sleep-wake patterns using actigraphy, healthy older adults underwent fMRI while performing an associative memory task. The results revealed better associative memory was related to more consistent circadian activity rhythms, independent of total sleep time, sleep efficiency, and level of physical activity. Moreover, hippocampal activity during successful memory retrieval events was positively correlated with associative memory accuracy and circadian activity rhythm (CAR) consistency. We demonstrated that the link between consistent rhythms and associative memory performance was mediated by hippocampal activity. These findings provide novel insight into how the circadian rhythm of sleep-wake cycles are associated with memory in older adults and encourage further examination of circadian activity rhythms as a biomarker of cognitive functioning. PMID:26205911

  10. Alterations in circadian rhythms are associated with increased lipid peroxidation in females with bipolar disorder.

    Science.gov (United States)

    Cudney, Lauren E; Sassi, Roberto B; Behr, Guilherme A; Streiner, David L; Minuzzi, Luciano; Moreira, Jose C F; Frey, Benicio N

    2014-05-01

    Disturbances in both circadian rhythms and oxidative stress systems have been implicated in the pathophysiology of bipolar disorder (BD), yet no studies have investigated the relationship between these systems in BD. We studied the impact of circadian rhythm disruption on lipid damage in 52 depressed or euthymic BD females, while controlling for age, severity of depressive symptoms and number of psychotropic medications, compared to 30 healthy controls. Circadian rhythm disruption was determined by a self-report measure (Biological Rhythm Interview of Assessment in Neuropsychiatry; BRIAN), which measures behaviours such as sleep, eating patterns, social rhythms and general activity. Malondialdehyde (MDA) levels were measured as a proxy of lipid peroxidation. We also measured the activity of total and extracellular superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). Multiple linear regressions showed that circadian rhythm disturbance was independently associated with increased lipid peroxidation in females with BD (p GST activity between bipolar females and controls. Circadian rhythms were not associated with lipid peroxidation in healthy controls, where aging was the only significant predictor. These results suggest an interaction between the circadian system and redox metabolism, in that greater disruption in daily rhythms was associated with increased lipid peroxidation in BD only. Antioxidant enzymes have been shown to follow a circadian pattern of expression, and it is possible that disturbance of sleep and daily rhythms experienced in BD may result in decreased antioxidant defence and therefore increased lipid peroxidation. This study provides a basis for further investigation of the links between oxidative stress and circadian rhythms in the neurobiology of BD. PMID:24438530

  11. Pup circadian rhythm entrainment--effect of maternal ganglionectomy or pinealectomy.

    Science.gov (United States)

    Bellavía, S L; Carpentieri, A R; Vaqué, A M; Macchione, A F; Vermouth, N T

    2006-10-30

    In rodents, during late embryonic and early neonatal development, circadian rhythms develop in synchrony with those of their mothers, which in turn are synchronized with the environmental photoperiod. This paper examines the effect of maternal ganglionectomy (pineal gland sympathetic denervation) or extirpation of the pineal gland on pups' drinking rhythms, a behavior that is continuously monitored in individual animals starting after weaning and studied up to 3 weeks later. Maternal ganglionectomy or pinealectomy performed on the 7th day of gestation significantly disrupts rat pups' drinking behavior, within and among litters. In both treatments, circadian rhythm characteristics of the free-running period (tau), phase, amplitude and alpha were significantly altered compared to those of the control pups born from sham-operated mothers. With the exception of the alpha component, both maternal treatments have similar effects. When melatonin was given to the mothers instead of the endogenous pineal secretory activity for 5 days during the late period of gestation, this treatment reversed the effects of maternal ganglionectomy and pinealectomy. These observations, together with previous studies of our group, indicate that the maternal superior cervical ganglia and pineal gland are necessary components of the mechanism for maternal synchronization, and that maternal melatonin may, directly or indirectly, affect the performance of the pups' central oscillator during early pup rat development. PMID:16899263

  12. Effect of cataract surgery on regulation of circadian rhythms

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 was...... Trials web site. Trials that reported the effect of cataract surgery on circadian rhythms were included. Outcomes were the Pittsburgh Sleep Quality Index (PSQI) global score, number of poor sleepers, Epworth Sleepiness Score, sleep efficiency, and mean concentration of melatonin. Cataract surgery...

  13. Effects of L-Dopa on circadian rhythms of 6-OHDA striatal lesioned rats: a radiotelemetric study.

    Science.gov (United States)

    Boulamery, Audrey; Simon, Nicolas; Vidal, Johanna; Bruguerolle, Bernard

    2010-01-01

    Temporal variation in the motor function of Parkinson's disease (PD) patients suggests the potential importance of a chronobiological and chronopharmacological approach in its clinical management. We previously documented the effects of striatal injection of 6-OHDA (as an animal model of PD) on the circadian rhythms of temperature (T), heart rate (HR), and locomotor activity (A). The present work assessed the possible influence of L-Dopa on these same rhythms in the 6-OHDA animal model of PD. The study began after a four-week recovery period following surgical implantation of telemetric devices to monitor the study variables and/or anaesthesia. The study was divided into an initial one-week control period (W1) for baseline measurement of T, HR, and A rhythms. Thereafter, stereotaxic 6-OHDA lesioning was done. and a second monitoring for two weeks followed (W2, W3). Rats were then randomly divided into two groups: eight control rats received, via a mini-osmotic pump implanted subcutaneously, the excipient saline; the other eight rats received L-Dopa (100 mg/kg SC/day). After a seven-day period (W4), the pumps were removed and the T, HR, and A rhythms were monitored for two weeks (W5 and W6). To control for 6-OHDA striatal dopamine-induced depletion, 12 other rats were injected by identical methods (eight rats with 6-OHDA and four controls with saline) and sacrificed at W1, W3, and W5 for dopamine striatal content determination. To verify the delivery of levodopa from the osmotic pumps, plasma levels of levodopa and its main metabolites 3-OMD, DOPAC, and HVA were determined on separate group of rats receiving the drug under the same experimental conditions (osmotic pumps delivering continuously 10 microl/h for seven days, 100 mg/kg/subcutaneously). Our results agree with previously reported rhythmic changes induced by 6-OHDA--loss of circadian rhythmicity or changes in the main parameters of the registered rhythms. When circadian rhythmicity was abolished, L

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

    Directory of Open Access Journals (Sweden)

    Ron Weiss

    2014-04-01

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

  15. Neurospora circadian rhythms in space: a reexamination of the endogenous-exogenous question.

    Science.gov (United States)

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

    1984-07-13

    To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of our results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected. PMID:11540800

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

    OpenAIRE

    McClung, Colleen A.

    2011-01-01

    Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes that associate w...

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

    OpenAIRE

    Skene, DJ; Deacon, S; Arendt, J

    1996-01-01

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

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

    OpenAIRE

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

    2014-01-01

    The impact of pregnancy and lactation on ultradian rhythms (URs) and circadian rhythms (CRs) of locomotor activity was assessed in circadian rhythmic and arrhythmic Siberian hamsters maintained in a long-day photoperiod (16 h light/day). Progressive decrements in CR robustness and amplitude over the course of gestation were accompanied by enhanced URs. Dark-phase UR period and amplitude increased during early gestation and complexity and robustness increased during late gestation. The persist...

  19. 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, and the…

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

    OpenAIRE

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

    2011-01-01

    Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationsh...

  1. Ambulatory Blood Pressure Monitoring and Circadian Rhythm of Blood Pressure in Diabetes Mellitus

    OpenAIRE

    Elena Matteucci; Ottavio Giampietro

    2013-01-01

    Systolic and diastolic blood pressures display a circadian rhythmicity that can be assessed by 24-hour ambulatory blood pressure monitoring and analysed using the cosinor procedure. Altered characteristics to the circadian rhythm of blood pressure, which may result in adverse health outcomes, have been observed in both prediabetes and diabetes. We have investigated the circadian variability of blood pressure in patients with type 1 and type 2 diabetes. Chronobiologically interpreted ambulator...

  2. The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms.

    OpenAIRE

    Landgraf, D; Joiner, WJ; McCarthy, MJ; Kiessling, S.; Barandas, R; Young, JW; Cermakian, N; Welsh, DK

    2016-01-01

    Endogenous circadian (∼24 h) clocks regulate key physiological and cognitive processes via rhythmic expression of clock genes. The main circadian pacemaker is the hypothalamic suprachiasmatic nucleus (SCN). Mood disorders, including bipolar disorder (BD), are commonly associated with disturbed circadian rhythms. Dopamine (DA) contributes to mania in BD and has direct impact on clock gene expression. Therefore, we hypothesized that high levels of DA during episodes of mania contribute to distu...

  3. Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats.

    Science.gov (United States)

    Wollnik, F

    1992-10-01

    Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro 19-6327, a selective MAO type B inhibitor; c) desipramine, a preferential norepinephrine reuptake inhibitor; d) clomipramine and e) fluoxetine, both serotonin reuptake inhibitors; and f) levoprotiline, an atypical antidepressant whose biochemical mechanism is still unknown. Wheel-running activity rhythms were studied in three inbred strains of laboratory rats (ACI, BH, LEW) under constant darkness (DD). Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Chronic treatment with moclobemide and desipramine consistently increased the overall level, as well as the circadian amplitude, of the activity rhythm. Furthermore, the abnormal activity pattern of the LEW strain was changed into a unimodal activity pattern like that of other laboratory rats. The free-running period tau was slightly shortened by moclobemide and dramatically shortened by desipramine. Effects of moclobemide and desipramine treatment on overall activity level and duration were reversed shortly after termination of treatment, whereas long aftereffects were observed for the free-running period. All other substances tested had no systematic effects on the activity rhythms of any of the strains. The fact that moclobemide and desipramine altered the period, amplitude, and pattern of circadian activity rhythms is consistent with the hypothesis that monoaminergic transmitters

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

    Science.gov (United States)

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

    2016-03-01

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

  5. Circadian activity rhythm in pre-pubertal and pubertal marmosets (Callithrix jacchus) living in family groups.

    Science.gov (United States)

    Melo, Paula R; Gonçalves, Bruno S B; Menezes, Alexandre A L; Azevedo, Carolina V M

    2016-03-01

    In marmosets, a phase advance was observed in activity onset in pubertal animals living in captivity under semi-natural conditions which had stronger correlation with the times of sunrise over the course of the year than the age of the animal. In order to evaluate the effect of puberty on the circadian activity rhythm in male and female marmosets living in family groups in controlled lighting conditions, the activity of 5 dyads of twins (4 ♀/♂ and 1 ♂/♂) and their respective parents was continuously monitored by actiwatches between the 4th and 12th months of age. The families were kept under LD 12:12 h with constant humidity and temperature. The onset of puberty was identified by monitoring fecal steroids. Juveniles showed higher totals of daily activity and differences in the daily distribution of activity in relation to parents, in which the bimodal profile was characterized by higher levels in evening activity in relation to morning activity. Regarding the phase, the activity onset and offset, occurred later in relation to parents. After entering puberty, the activity onset and offset occurred later and there was an increase in total daily activity. On the other hand, when assessing the effect of sex, only females showed a delay in the activity offset and an increase in total daily activity. Therefore, the circadian activity rhythm in marmosets has peculiar characteristics in the juvenile stage in relation to the total of daily activity, the onset and offset of the active phase, and the distribution of activity during this phase. Besides, the entering puberty was associated with a phase delay and increase on total daily activity, with differences between sexes, possibly due to hormonal influences and/or social modulation on rhythm. PMID:26724713

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

    Science.gov (United States)

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

    1971-01-01

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

  7. Impaired release of corticosterone from adrenals contributes to impairment of circadian rhythms of activity in hyperammonemic rats.

    Science.gov (United States)

    Llansola, Marta; Ahabrach, Hanan; Errami, Mohammed; Cabrera-Pastor, Andrea; Addaoudi, Kaoutar; Felipo, Vicente

    2013-08-15

    Patients with liver cirrhosis may present impaired sleep-wake and circadian rhythms, relative adrenal insufficiency and altered hypothalamus-pituitary-adrenal gland (HPA) axis. The underlying mechanisms remain unclear. Circadian rhythms are modulated by corticosteroids which secretion is regulated by HPA axis. Hyperammonemia alters circadian rhythms of activity and corticosterone in rats. The aims were: (1) assessing whether corticosterone alterations are responsible for altered circadian rhythm in hyperammonemia: (2) to shed light on the mechanism by which corticosterone circadian rhythm is altered in hyperammonemia. The effects of daily corticosterone injection at ZT10 on circadian rhythms of activity, plasma corticosterone, adreno-corticotropic hormone (ACTH) and hypothalamic corticotropic releasing hormone (CRH) were assessed in control and hyperammonemic rats. ACTH-induced corticosterone release was analyzed in cultured adrenal cells. Corticosterone injection restores the corticosterone peak in hyperammonemic rats and their activity and circadian rhythm. Plasma ACTH and CRH in hypothalamus are increased in hyperammonemic rats. Corticosterone injection normalizes ACTH. Chronic hyperammonemia impairs adrenal function, reduces corticosterone content and ACTH-induced corticosterone release in adrenals, leading to reduced feedback modulation of HPA axis by corticosterone which contributes to impair circadian rhythms of activity. Impaired circadian rhythms and motor activity may be corrected in hyperammonemia and hepatic encephalopathy by corticosterone treatment. PMID:23376587

  8. A Long Noncoding RNA Perturbs the Circadian Rhythm of Hepatoma Cells to Facilitate Hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Ming Cui

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

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

    Science.gov (United States)

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

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly. PMID:27030628

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

    OpenAIRE

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

    2015-01-01

    Endogenous circadian clocks are poorly understood within early-diverging animal lineages. We have characterized circadian behavioral patterns and identified potential components of the circadian clock in the starlet sea anemone, Nematostella vectensis: a model cnidarian which lacks algal symbionts. Using automatic video tracking we showed that Nematostella exhibits rhythmic circadian locomotor activity, which is persistent in constant dark, shifted or disrupted by external dark/light cues and...

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

    Science.gov (United States)

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

    1995-01-01

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

  16. [Impact of age-related cataract on regulation of circadian rhythm in elderly].

    Science.gov (United States)

    Wang, M S; Liu, M Y; Dong, X R; Wang, W

    2016-04-11

    This review presented an introduction of the visual pathway related circadian rhythm regulation system: the intrinsically photosensitive retinal ganglion cells-suprachiasmatic nucleus-pineal gland-melatonin axis, and discussed the impact of light with different wave length and irradiation received by retina on circadian rhythm and sleep habit. A hypothesis was proposed consequently that the high morbidity of sleep disorder in elderly might be partially attributable to the long-term blue light blocking status induced by age-related cataract. A number of relative literatures were reviewed and a novel research direction was advanced on improving circadian rhythm and sleep condition in elderly based on the current knowledge. (Chin J Ophthalmol, 2016, 52: 309-314). PMID:27094070

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

    Science.gov (United States)

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

    1991-01-01

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

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

    Science.gov (United States)

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

    1987-01-01

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

  19. 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 dement

  20. Circadian rhythms of cyanobacteria: monitoring the biological clocks of individual colonies by bioluminescence.

    OpenAIRE

    Kondo, T.; Ishiura, M

    1994-01-01

    Reproducible circadian rhythms of bioluminescence from individual colonies of cyanobacteria (Synechococcus sp. strain PCC 7942) has been observed. Phenotypic monitoring of colonies on agar plates will enable us to genetically analyze the molecular mechanism of the circadian clock of cyanobacteria by screening for clock mutants. By the introduction of a bacterial luciferase gene, we previously developed a transformed cyanobacterial strain (AMC149) that expresses luciferase as a bioluminescent ...

  1. Short-term influence of cataract surgery on circadian biological rhythm and related health outcomes (CLOCK-IOL trial): study protocol for a randomized controlled trial

    OpenAIRE

    Saeki, Keigo; Obayashi, Kenji; Nishi, Tomo; Miyata, Kimie; Maruoka, Shinji; Ueda, Tetsuo; OKAMOTO, Masahiro; Hasegawa, Taiji; Matsuura, Toyoaki; Tone, Nobuhiro; Ogata, Nahoko; Kurumatani, Norio

    2014-01-01

    Background Light information is the most important cue of circadian rhythm which synchronizes biological rhythm with external environment. Circadian misalignment of biological rhythm and external environment is associated with increased risk of depression, insomnia, obesity, diabetes, cardiovascular disease, and cancer. Increased light transmission by cataract surgery may improve circadian misalignment and related health outcomes. Although some observational studies have shown improvement of ...

  2. Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation.

    Science.gov (United States)

    Xie, Zhongwen; Su, Wen; Liu, Shu; Zhao, Guogang; Esser, Karyn; Schroder, Elizabeth A; Lefta, Mellani; Stauss, Harald M; Guo, Zhenheng; Gong, Ming Cui

    2015-01-01

    As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption. PMID:25485682

  3. 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.

  4. 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

  5. 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.

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    Ramkisoensing, Ashna; Meijer, Johanna H.

    2015-01-01

    In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude...

  8. 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.

  9. Evidence for Time-of-Day Dependent Effect of Neurotoxic Dorsomedial Hypothalamic Lesions on Food Anticipatory Circadian Rhythms in Rats

    OpenAIRE

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

    2011-01-01

    The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiof...

  10. Circadian Rhythm Disorders and Melatonin Production in 127 Blind Women with and without Light Perception.

    Science.gov (United States)

    Flynn-Evans, Erin E; Tabandeh, Homayoun; Skene, Debra J; Lockley, Steven W

    2014-06-10

    Light is the major environmental time cue that synchronizes the endogenous central circadian pacemaker, located in the suprachiasmatic nuclei of the hypothalamus, and is detected exclusively by the eyes primarily via specialized non-rod, non-cone ganglion cell photoreceptors. Consequently, most blind people with no perception of light (NPL) have either nonentrained or abnormally phased circadian rhythms due to this inability to detect light. Conversely, most visually impaired participants with some degree of light perception (LP) exhibit normal entrainment, emphasizing the functional separation of visual and "nonvisual" photoreception. The aims of the study were to identify the prevalence of circadian disorders in blind women, with the further aim of examining how eye disease may relate to the type of circadian disorder. Participants (n = 127, age 50.8 ± 13.4 years) completed an 8-week field study including daily sleep diaries and sequential 4 to 8 hourly urine collections over 48 h on 2 to 3 occasions separated by at least 2 weeks. Circadian type was determined from the timing and time course of the melatonin rhythm measured by cosinor-derived urinary 6-sulfatoxymelatonin rhythm peak. Of the participants with NPL (n = 41), the majority were abnormally phased (24%) or nonentrained (39%), with 37% classified as normally entrained. Of the participants with LP (n = 86), the majority were normally entrained (69%). Eighteen LP participants (21%) were abnormally phased (8 advanced, 10 delayed). Nine LP participants (10%) were nonentrained. The eye conditions most associated with abnormal phase and/or nonentrained circadian rhythms were bilateral enucleation (67%) and retinopathy of prematurity (57%). By contrast, 84% of participants with retinitis pigmentosa and 83% of those with age-related macular degeneration were normally entrained. These findings suggest that the etiology of blindness in addition to LP status is related to an individual's ability to process the

  11. Circadian rhythms of photosynthesis in marine diatom Thalassiosira weissflogii under nitrogen replete and deplete conditions

    Czech Academy of Sciences Publication Activity Database

    Kasalický, Vojtěch; Rottnerová, K.; Sciandra, A.; Babin, M.; Prášil, Ondřej

    Nové Hrady : Springer, 2007, s. 52-52. [Aquafluo - Chlorophyll Fluorescence in Aquatic Sciences Meeting. Nové Hrady (CZ), 28.05.2007-01.06.2007] Institutional research plan: CEZ:AV0Z50200510 Keywords : circadian rhythms Subject RIV: EE - Microbiology, Virology

  12. 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...

  13. Circadian rhythms and sleep—the metabolic connection

    OpenAIRE

    Albrecht, Urs

    2011-01-01

    The circadian system coordinates mammalian physiology and behavior with the environmental light–dark cycle. It allocates sleep to the inactivity phase using various mechanisms involving neurotransmitters, nuclear receptors, and protein kinases. These pathways are related to metabolism, indicating that the circadian system and sleep are connected via metabolic parameters. This suggests that organs other than the brain may “sleep.” A hypothetic view on this aspect is presented providing a diffe...

  14. Circadian Rhythms in Anesthesia and Critical Care Medicine: Potential importance of circadian disruptions

    OpenAIRE

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

    2014-01-01

    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 last 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 deat...

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

    International Nuclear Information System (INIS)

    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 (60Co 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 B12 (VB12), 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 VB12, our patient's organic brain damage was more evident radiologically and endoclinologically. Following the hypothesis that VB12 has a potential to reinforce the entrainment of circadian rhythm, our patient's organic brain damage may include entrainment system. (author)

  16. 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 gradual

  17. 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

  18. Development of circadian rhythms in rat pups exposed to microgravity during gestation.

    Science.gov (United States)

    Hoban-Higgins, T M; Murakami, D M; Tang, I H; Fuller, P M; Fuller, C A

    1999-10-01

    Ten pregnant Sprague Dawley rat dams were exposed to spaceflight aboard the Space Shuttle (STS-70) for gestational days 11-20 (G 11-20; FLT group). Control dams were maintained in either a flight-like (FDS group) or vivarium cage environment (VIV group) on earth. All dams had ad lib access to food and water and were exposed to a light-dark cycle consisting of 12 hours of light (approximately 30 lux) followed by 12 hours of darkness. The dams were closely monitored from G 22 until parturition. All pups were cross-fostered at birth; each foster dam had a litter of 10 pups. Pups remained with their foster dam until post natal day 21 (PN 21). Pup body mass was measured twice weekly. At PN 14 FLT pups had a smaller body mass than did the VIV pups (p < 0.01). Circadian rhythms of body temperature and activity of pups from two FLT dams (n = 8), two FDS dams (n = 9) and two VIV dams (n = 7) were studied starting from age PN 21. All pups had circadian rhythms of temperature and activity at this age. There were no significant differences in rhythms between groups that could be attributed to microgravity exposure. These results indicate that exposure to the microgravity environment of spaceflight during this embryonic development period does not affect the development of the circadian rhythms of body temperature and activity. PMID:11543088

  19. Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1

    Science.gov (United States)

    Bellet, Marina M.; Nakahata, Yasukazu; Boudjelal, Mohamed; Watts, Emma; Mossakowska, Danuta E.; Edwards, Kenneth A.; Cervantes, Marlene; Astarita, Giuseppe; Loh, Christine; Ellis, James L.; Vlasuk, George P.; Sassone-Corsi, Paolo

    2013-01-01

    Circadian rhythms govern a wide variety of physiological and metabolic functions in many organisms, from prokaryotes to humans. We previously reported that silent information regulator 1 (SIRT1), a NAD+-dependent deacetylase, contributes to circadian control. In addition, SIRT1 activity is regulated in a cyclic manner in virtue of the circadian oscillation of the coenzyme NAD+. Here we used specific SIRT1 activator compounds both in vitro and in vivo. We tested a variety of compounds to show that the activation of SIRT1 alters CLOCK:BMAL1-driven transcription in different systems. Activation of SIRT1 induces repression of circadian gene expression and decreases H3 K9/K14 acetylation at corresponding promoters in a time-specific manner. Specific activation of SIRT1 was demonstrated in vivo using liver-specific SIRT1-deficient mice, where the effect of SIRT1 activator compounds was shown to be dependent on SIRT1. Our findings demonstrate that SIRT1 can fine-tune circadian rhythm and pave the way to the development of pharmacological strategies to address a broad range of therapeutic indications. PMID:23341587

  20. 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.

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

    International Nuclear Information System (INIS)

    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-(125I)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, p0.00956x). 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)

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

    Directory of Open Access Journals (Sweden)

    Augustin Luna

    2015-05-01

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

  3. 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....

  4. 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.

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

    OpenAIRE

    ZHANG, XIPING; Dube, Thomas J.; Esser, Karyn A.

    2009-01-01

    The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to ...

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

    OpenAIRE

    Valdez, Pablo

    2012-01-01

    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 d...

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

    Science.gov (United States)

    Ramkisoensing, Ashna; Meijer, Johanna H

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Effects of the circadian rhythm gene period 1 (per1) on psychosocial stress-induced alcohol drinking

    OpenAIRE

    Soyka, Michael; Henriksson, Richard; Albrecht, Urs; Spanagel, Rainer; Michael N Smolka; Rietschel, Marcella; Bilbao, Ainhoa; Treutlein, Jens; Schumann, Gunter; Ridinger, Monika; Wodarz, Norbert; Blomeyer, Dorothea; Witt, Stephanie,; Lathrop, Mark; Dong, Li

    2011-01-01

    Objective: Circadian and stress-response systems mediate environmental changes that affect alcohol drinking. Psychosocial stress is an environmental risk factor for alcohol abuse. Circadian rhythm gene period 1 (Per1) is targeted by stress hormones and is transcriptionally activated in corticotropin releasing factor-expressing cells. The authors hypothesized that Per1 is involved in integrating stress response and circadian rhythmicity and explored its relevance to alcohol drinking.Method: In...

  10. ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila.

    Science.gov (United States)

    Lim, Chunghun; Allada, Ravi

    2013-05-17

    Evidence for transcriptional feedback in circadian timekeeping is abundant, yet little is known about the mechanisms underlying translational control. We found that ATAXIN-2 (ATX2), an RNA-associated protein involved in neurodegenerative disease, is a translational activator of the rate-limiting clock component PERIOD (PER) in Drosophila. ATX2 specifically interacted with TWENTY-FOUR (TYF), an activator of PER translation. RNA interference-mediated depletion of Atx2 or the expression of a mutant ATX2 protein that does not associate with polyadenylate-binding protein (PABP) suppressed behavioral rhythms and decreased abundance of PER. Although ATX2 can repress translation, depletion of Atx2 from Drosophila S2 cells inhibited translational activation by RNA-tethered TYF and disrupted the association between TYF and PABP. Thus, ATX2 coordinates an active translation complex important for PER expression and circadian rhythms. PMID:23687047

  11. Circadian Rhythms, Sleep and Cognitive Skills: Evidence from an Unsleeping Giant

    OpenAIRE

    Giuntella, Osea; Han, Wei; Mazzonna, Fabrizio

    2016-01-01

    This paper analyzes the effects of sleep duration on cognitive skills and depression symptoms of older workers in China. Cognitive skills and mental health have been associated with sleep duration and are known to be strongly related to economic behavior and performance. However, causal evidence is lacking and little is known about sleep deprivation in developing countries. We exploit the relationship between circadian rhythms and bedtime to identify the effects of sleep using sunset time as ...

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

    Science.gov (United States)

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

    1996-01-01

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

  13. Circadian rhythms of hydraulic conductance and growth are enhanced by drought and improve plant performance

    OpenAIRE

    Caldeira, Cecilio Frois; Jeanguenin, Linda; Chaumont, François; Tardieu, Francois

    2014-01-01

    Supplementary information available for this article at http://www.nature.com/ncomms/2014/141105/ncomms6365/suppinfo/ncomms6365_S1.html Circadian rhythms enable plants to anticipate daily environmental variations, resulting in growth oscillations under continuous light. Because plants daily transpire up to 200% of their water content, their water status oscillates from favourable during the night to unfavourable during the day. We show that rhythmic leaf growth under continuous light is ob...

  14. Circadian activity rhythm of the house fly continues after optic tract severance and lobectomy

    OpenAIRE

    Helfrich, Charlotte; Cymborowski, Bronislaw; Engelmann, Wolfgang

    1985-01-01

    Under constant conditions, locomotor activity in about 50% of 63 adult Musca domestica continued to be rhythmic after bilateral severance of optic tracts or bilateral lobectomy. Apparently, the optic lobes of Musca do not contain the oscillator for rhythmic control of locomotor activity as has been proposed for other insects. In 20% of the individuals, several circadian components of activity rhythms were found after operation indicating a role of the optic lobes in the coupling of oscillator...

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

    Science.gov (United States)

    Gu, Changgui; Yang, Huijie

    2016-05-01

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

  16. Eyeless Mexican Cavefish Save Energy by Eliminating the Circadian Rhythm in Metabolism

    OpenAIRE

    Moran, Damian; Softley, Rowan; Warrant, Eric J.

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during t...

  17. Multiscale modelling of tumour growth induced by circadian rhythm disruption in epithelial tissue

    OpenAIRE

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

    2015-01-01

    We propose a multiscale chemo-mechanical model of cancer tumour development in an epithelial tissue. The model is based on transformation of normal cells into the cancerous state triggered by a local failure of spatial synchronisation of the circadian rhythm. The model includes mechanical interactions and chemical signal exchange between neighbouring cells, as well as division of cells and intercalation, and allows for modification of the respective parameters following transformation into th...

  18. Circadian rhythms in the neuorbiology of bipolar of bipolar disorder

    OpenAIRE

    Timothy, Joseph

    2015-01-01

    Daily rhythms of physiology and behaviour in mammals are orchestrated by a hierarchical network of cellular oscillators. The master pacemaker that defines local and systemic timing across the brain and body are the suprachiasmatic nuclei of the hypothalamus (SCN). Disruption to the timing of sleep and daily behavioural activity can manifest in a range of pathologies including neuropsychiatric disorders. Bipolar disorder (BPD) is once such neurological condition that exhibits profound associat...

  19. 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.

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

    Science.gov (United States)

    Zhao, Yanbin; Fent, Karl

    2016-02-01

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

  1. [Effects of ramelteon on a patient with circadian rhythm sleep disorder and mood disorder].

    Science.gov (United States)

    Yoshihara, Shinsuke; Yoshizawa, Mondo; Shirata, Ayaka; Matsuda, Mika; Tamashiro, Motoyuki; Saito, Ichiro; Sakamoto, Kazutaka; Fujimura, Yota; Tamura, Yoshiyuki; Chiba, Shigeru

    2014-01-01

    Ramelteon is a novel hypnotic characterized by its action as a melatonin receptor (MT1/MT2) agonist. It has been reported that ramelteon can alter the phase of the sleep period. We report a patient with circadian rhythm sleep disorder and mood disorder who improved with ramelteon. A 25-year-old man had a 5-year history of emotional instability, excessive daytime sleepiness, and difficulty awakening. He had been diagnosed with mood disorder and narcolepsy by a psychiatrist. Sertraline, milnacipran, valproate, and methylphenidate were ineffective, and so he presented to our hospital. Interview data and a sleep log demonstrated a delayed sleep phase. As other examinations such as actigraphy and video-polysomnography indicated no other diseases, the patient was diagnosed with circadian rhythm sleep disorder, delayed sleep phase type (ICSD-2). In addition, his mental symptoms were consistent with the criteria for cyclothymia (ICD-10). After the administration of ramelteon, the phase of his sleep period gradually advanced and his emotional instability improved. Because of the high rate of comorbidity between these two diseases, we should be aware of circadian rhythm sleep disorders that are masked by mood disorders. PMID:25711117

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

    Science.gov (United States)

    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.

  3. Differential contribution of rod and cone circadian clocks in driving retinal melatonin rhythms in Xenopus.

    Directory of Open Access Journals (Sweden)

    Naoto Hayasaka

    Full Text Available BACKGROUND: Although an endogenous circadian clock located in the retinal photoreceptor layer governs various physiological events including melatonin rhythms in Xenopus laevis, it remains unknown which of the photoreceptors, rod and/or cone, is responsible for the circadian regulation of melatonin release. METHODOLOGY/PRINCIPAL FINDINGS: We selectively disrupted circadian clock function in either the rod or cone photoreceptor cells by generating transgenic Xenopus tadpoles expressing a dominant-negative CLOCK (XCLΔQ under the control of a rod or cone-specific promoter. Eyecup culture and continuous melatonin measurement revealed that circadian rhythms of melatonin release were abolished in a majority of the rod-specific XCLΔQ transgenic tadpoles, although the percentage of arrhythmia was lower than that of transgenic tadpole eyes expressing XCLΔQ in both rods and cones. In contrast, whereas a higher percentage of arrhythmia was observed in the eyes of the cone-specific XCLΔQ transgenic tadpoles compare to wild-type counterparts, the rate was significantly lower than in rod-specific transgenics. The levels of the transgene expression were comparable between these two different types of transgenics. In addition, the average overall melatonin levels were not changed in the arrhythmic eyes, suggesting that CLOCK does not affect absolute levels of melatonin, only its temporal expression pattern. CONCLUSIONS/SIGNIFICANCE: These results suggest that although the Xenopus retina is made up of approximately equal numbers of rods and cones, the circadian clocks in the rod cells play a dominant role in driving circadian melatonin rhythmicity in the Xenopus retina, although some contribution of the clock in cone cells cannot be excluded.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  5. Circadian rhythms and post-transcriptional regulation in higher plants

    Directory of Open Access Journals (Sweden)

    Andres eRomanowski

    2015-06-01

    Full Text Available The circadian clock of plants allows them to cope with daily changes in their environment. This is accomplished by the rhythmic regulation of gene expression, in a process that involves many regulatory steps. One of the key steps involved at the RNA level is post-transcriptional regulation, which ensures a correct control on the different amounts and types of mRNA that will ultimately define the current physiological state of the plant cell. Recent advances in the study of the processes of regulation of pre-mRNA processing, RNA turn-over and surveillance, regulation of translation, function of lncRNAs, biogenesis and function of small RNAs and the development of bioinformatics tools have helped to vastly expand our understanding of how this regulatory step performs its role. In this work we review the current progress in circadian regulation at the post-transcriptional level research in plants. It is the continuous interaction of all the information flow control post-transcriptional processes that allow a plant to precisely time and predict daily environmental changes.

  6. Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine

    OpenAIRE

    Duncan, Marilyn J.; Bruce-Keller, Annadora J.; Conner, Clayton; Knapp, Pamela E.; Xu, Ruquiang; Nath, Avindra; Hauser, Kurt F.

    2008-01-01

    Patients with human immunodeficiency virus (HIV) infection exhibit changes in sleep patterns, motor disorders, and cognitive dysfunction; these symptoms may be secondary to circadian rhythm abnormalities. Studies in mice have shown that intracerebral injection of an HIV protein, transactivator of transcription (Tat), alters the timing of circadian rhythms in a manner similar to light. Therefore, we tested the hypothesis that chronic Tat expression alters circadian rhythms, especially their en...

  7. Pharmacologic modulation of reduced glutathione circadian rhythms with buthionine sulfoximine: relationship with cisplatin toxicity in mice.

    Science.gov (United States)

    Li, X M; Metzger, G; Filipski, E; Boughattas, N; Lemaigre, G; Hecquet, B; Filipski, J; Levi, F

    1997-04-01

    The relationship between the rhythm in reduced glutathione (GSH) and that in cisplatin (CDDP) toxicity was investigated in a total of 560 male B6D2F1 mice, using buthionine sulfoximine (BSO). GSH was measured by high-performance liquid chromatography (HPLC) in four tissues, at each of six sampling times, 4 hr apart. A significant 24-hr rhythm was statistically validated in liver, jejunum, and colon, but not in bone marrow. Relative to liver, glutathione content was 56% in colon, 38% in bone marrow, 25% in jejunum, and negligible in kidney, where cysteine, a final product of GSH catabolism, displayed a 12-hr rhythmic variation. This rhythm may reflect that in the activity of GSH-degrading enzymes. BSO (450 mg/kg ip, 4 hr before sampling) reduced liver GSH threefold and kidney cysteine content was halved, but this pretreatment had no significant effect upon GSH content in the other organs. Furthermore, the period of the physiologic liver GSH rhythm changed from 24 hr to a composite (24 + 12 hr) period. This change in the period may result from an unmasking of the 12-hr rhythm in GSH-degrading enzyme activity by GSH synthesis blockade. Maximal values occurred in the mid-rest span and in the mid-active span after BSO administration. In the other tissues, the 24-hr period remained unchanged. BSO injection largely enhanced CDDP toxicity (as assessed by survival, leukopenia, and histologic lesions in kidney and bone marrow) and kidney mean platinum concentration. Furthermore, BSO pretreatment modified the period of CDDP toxicity rhythm: survival followed a significant 12-hr-rhythm, instead of a 24-hr rhythm. The cycling of GSH concentration results from a balance between synthesis and catabolism and likely constitutes one of the main components of the circadian rhythm in CDDP toxicity in mice. PMID:9144445

  8. The circadian rest-activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy.

    Science.gov (United States)

    Ortiz-Tudela, Elisabet; Iurisci, Ida; Beau, Jacques; Karaboue, Abdoulaye; Moreau, Thierry; Rol, Maria Angeles; Madrid, Juan Antonio; Lévi, Francis; Innominato, Pasquale F

    2014-06-01

    The robustness of the circadian timing system (CTS) was correlated to quality of life and predicted for improved survival in cancer patients. However, chemotherapy disrupted the CTS according to dose and circadian timing in mice. A continuous and repeated measures longitudinal design was implemented here to characterize CTS dynamics in patients receiving a fixed circadian-based chemotherapy protocol. The rest-activity rhythm of 49 patients with advanced cancer was monitored using a wrist actigraph for 13 days split into four consecutive spans of 3-4 days each, i.e., before, during, right after and late after a fixed chronotherapy course. The relative amount of activity in bed vs. out of bed (Ihr amplitude (Amp), interdaily stability (IS) and intradaily variability (IV) were compared according to study span. Circadian disruption (Iimprovement (14.3%); alteration and complete recovery (31%) or sustained deterioration (45%), possibly due to inadequate chronotherapy dosing and/or timing. Improved clinical tolerability could result from the minimization of circadian disruption through the personalization of chronotherapy delivery. PMID:24510611

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  10. 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

  11. BRN 3.1 Knockouts Affect the Vestibular, Autonomic, and Circadian Rhythm Responses to 2G Exposure

    Science.gov (United States)

    Murakami, D. M.; Erkman, L.; Rosenfeld, M. G.; Fuller, C. A.

    1999-01-01

    Our previous studies have demonstrated that 2G exposure via centrifugation significantly attenuated the daily mean and circadian rhythm amplitude of rat body temperature (Tb), heart rate, and activity (Act). In addition, 2G exposure activates neural responses in several vestibular, autonomic, and circadian nuclei. Although we have characterized the effect of 2G on an animal's physiological, neuronal, and behavioral responses, it will be important to understand the underlying neural and physiological mechanisms that mediate those responses. For example, the vestibular responses, proprioceptive feedback, or fluid shifts may be the critical factors that mediate the responses to 2G. As a first step to understand the relative importance of these different response pathways to altered gravitational fields, this study examined the contribution of the vestibular system by utilizing an animal model from molecular biology. Brain 3.1 (Bm 3.1) is a POU domain homeobox gene involved in the normal development of the vestibular and auditory system. Brn 3.1 deletion results in a loss of hair cells in the otoliths, semicircular canals, and cochlea. As a result mice with a Brn 3.1 deletion do not have a functioning vestibular or auditory system. The BRN 3.1 knockout mouse could be a very useful animal model for isolating the role of the vestibular system in mediating the physiological responses to 2G exposure. Therefore, this study compared the effect of 2G exposure via centrifugation between Brn 3.1 knockout (KO) versus Wildtype (W) mice.

  12. Time Matters in Ecotoxicological Sampling Due to Circadian Rhythm.

    Science.gov (United States)

    Zhao, Yanbin; Fent, Karl

    2016-04-01

    As in general, technological inventions also drive the development in the field of toxicology and ecotoxicology. In the past decade, gene expression analysis has become a universally applied technology allowing many insights into toxicological pathways of environmental contaminants. Due to the novel technologies, including quantitative determination of mRNA by quantitative reverse transcription analysis (qRT-PCR), and semiquantitative methods, such as microarrays and RNA-sequencing technologies, toxicological profiles of contaminants could be identified. For instance, gene expression analysis of genes associated with the hypothalamic-pituitary-gonadal axis (HPG axis) in fish had become a conventional end point for endocrine disrupting chemicals. While these gene expression data provide novel insights into identifying potential toxicological end points and molecular mechanisms, often not enough attention is given to the question of mRNA stabilities and reliabilities of transcriptional data, in particular when links to physiological effects are difficult to make. A crucial factor in this issue is the endogenous circadian oscillations of genes during sampling. PMID:27010328

  13. Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens and periaqueductal grey.

    Science.gov (United States)

    Landgraf, Dominic; Long, Jaimie E; Welsh, David K

    2016-05-01

    An association between circadian rhythms and mood regulation is well established, and disturbed circadian clocks are believed to contribute to the development of mood disorders, including major depressive disorder. The circadian system is coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the hypothalamus that receives light input from the retina and synchronizes circadian oscillators in other brain regions and peripheral tissues. Lacking the tight neuronal network that couples single-cell oscillators in the SCN, circadian clocks outside the SCN may be less stable and more susceptible to disturbances, for example by clock gene mutations or uncontrollable stress. However, non-SCN circadian clocks have not been studied extensively in rodent models of mood disorders. In the present study, it was hypothesized that disturbances of local circadian clocks in mood-regulating brain areas are associated with depression-like behaviour in mice. Using the learned helplessness procedure, depression-like behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then circadian rhythms of PER2 expression were examined in brain slices from these mice using luminometry and bioluminescence imaging. It was found that helplessness is associated with absence of circadian rhythms in the nucleus accumbens and the periaqueductal grey, two of the most critical brain regions within the reward circuit. The current study provides evidence that susceptibility of mice to depression-like behaviour is associated with disturbed local circadian clocks in a subset of mood-regulating brain areas, but the direction of causality remains to be determined. PMID:26414405

  14. Mistimed wheel running interferes with re-entrainment of circadian Per1 rhythms in the mouse skeletal muscle and lung.

    Science.gov (United States)

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

    2016-03-01

    Previously, we showed the acceleration of re-entrainment to 8-h phase-advanced light/dark cycles (LD) in the circadian Per1 expression rhythms of the mouse lung and skeletal muscle by 3-h wheel running (WR) at the beginning of shifted dark phase. In the present study, the effects of WR at the end of shifted dark phase were examined on the re-entrainment in mice. LD was advanced by shortening and was delayed by lengthening the first light period in the phase-advance and phase-delay protocol, respectively. Shifted LD was continued for 4 days, which was followed by constant darkness (DD). Per1 expression was measured in the cultured tissues obtained on the first day of DD from mice carrying a bioluminescence reporter of Per1 expression. In the phase-advance protocol, re-entrainment was not influenced by WR in any circadian rhythm examined. In the phase-delay protocol, re-entrainment of the circadian locomotor rhythm was not affected by WR. However, re-entrainment of circadian Per1 rhythm was significantly decelerated in the skeletal muscle and lung. These findings indicate that the effects of WR on re-entrainment depend on the time of day and the peripheral tissues. Mistimed WR interferes with re-entrainment of circadian rhythms in the lung and skeletal muscle. PMID:26818910

  15. Corkscrews and singularities in fruitflies - Resetting behavior of the circadian eclosion rhythm.

    Science.gov (United States)

    Winfree, A. T.

    1971-01-01

    Description of experiments undertaken to define the phase-resetting behavior of the circadian rhythm of pupal eclosion in populations of fruitflies. An attempt is made to determine how and why the resetting response depends on the duration of a standard perturbation as well as on the time at which it is given. Plotting a three-dimensional graph of the measured emergence centroids vs the stimulus variables, the data are found to spiral up around a vertical rotation axis. Using a computer, a smooth surface, called the resetting surface, which approximately fits the helicoidal cloud of data points, is obtained and is shown to be best described as a vertical corkscrew linking together tilted planes. This corkscrew feature of the resetting surface is taken to indicate that there is an isolated perturbation following which there is either no circadian rhythm of emergence in the steady state, or one of unpredictable phase. A hypothesis concerning the clock dynamics underlying the eclosion rhythm is briefly sketched which encompasses the main features of known resetting data using single discrete pulses of any perturbing agent.

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

    International Nuclear Information System (INIS)

    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

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

    CERN Document Server

    Selvam, A M; Mody, S M S

    1998-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Kimihiko [Yokohama City Univ. (Japan). School of Medicine

    2000-03-01

    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)

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

    Science.gov (United States)

    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. PMID:26774754

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

    Directory of Open Access Journals (Sweden)

    Thorpy MJ

    2013-12-01

    Full Text Available Michael J Thorpy,1 Thomas Roth2,31Sleep-Wake Disorders Center, Montefiore Medical Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, NY, USA; 2University of Michigan School of Medicine, Ann Arbor, 3Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Michigan, USAAbstract: While some systems classify medications according to therapeutic class, others are based on the mechanism of action of the drugs. The two main classifications of medications used to treat patients in the United States are those of the United States Pharmacopeia and US Food and Drug Administration, and they vary in their organization of the medication categories. Here we propose a taxonomy for medications used to treat sleep and circadian rhythm disorders based on symptoms and disorders.Keywords: circadian, sleep, taxonomy, classification, diagnosis

  1. Circadian rhythm of blood and urinary copper in presumably healthy subjects of vegetarian food habit

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, R.D.

    Circadian rhythm of blood and urinary copper has been studied in presumably healthy subjects of a particular ethnic group in India who are vegetarians. A definite 24-hr variation has been observed for both blood and urinary copper. The peak for blood copper was 1500 hr and the lowest value was 0600 hr, with values of 0.185 mg/100 ml and 0.160 mg/100 ml respectively. The urinary peak and trough occurred at 0600 and 0300 hr, respectively. Remarkably higher 24-hr copper excretion values were noted (64.49 ..mu..g/day) with a range of 15-100 ..mu..g/day. The blood level of copper (0.134 mg/100 ml) remained within the range reported. One subject out of 25 deviated from the group with respect to circadian phasing and amplitude to urinary copper excretion. 20 references.

  2. Interaction of circadian rhythm and opiate-induced thermic and kinetic responses: a biotelemetric investigation.

    Science.gov (United States)

    Dafters, R I; Taggart, P

    1990-01-01

    The thermic and kinetic effects of a low dose of morphine sulphate (5mg/kg) were monitored using a remote biotelemetric procedure. Drug and control (saline) injections were administered at two times of day, during the high and low phases of the circadian temperature/activity cycle respectively. Standard measures of the responses revealed that the effect of a dose of morphine differs significantly according to the phase of the circadian rhythm in which it is administered. In contrast to previous studies employing standard stress-inducing rectal probing techniques of temperature measurement, the direction and time-course of thermic and kinetic responses were uncorrelated. The implications for research on physiological and behavioral drug effects and for theories of drug tolerance/dependence are considered. PMID:2266784

  3. Sleep, Hormones, and Circadian Rhythms throughout the Menstrual Cycle in Healthy Women and Women with Premenstrual Dysphoric Disorder

    Directory of Open Access Journals (Sweden)

    Ari Shechter

    2010-01-01

    Full Text Available A relationship exists between the sleep-wake cycle and hormone secretion, which, in women, is further modulated by the menstrual cycle. This interaction can influence sleep across the menstrual cycle in healthy women and in women with premenstrual dysphoric disorder (PMDD, who experience specific alterations of circadian rhythms during their symptomatic luteal phase along with sleep disturbances during this time. This review will address the variation of sleep at different menstrual phases in healthy and PMDD women, as well as changes in circadian rhythms, with an emphasis on their relationship with female sex hormones. It will conclude with a brief discussion on nonpharmacological treatments of PMDD which use chronotherapeutic methods to realign circadian rhythms as a means of improving sleep and mood in these women.

  4. Circadian rhythm-dependent alterations of gene expression in Drosophila brain lacking fragile X mental retardation protein.

    Directory of Open Access Journals (Sweden)

    Shunliang Xu

    Full Text Available Fragile X syndrome is caused by the loss of the FMR1 gene product, fragile X mental retardation protein (FMRP. The loss of FMRP leads to altered circadian rhythm behaviors in both mouse and Drosophila; however, the molecular mechanism behind this phenomenon remains elusive. Here we performed a series of gene expression analyses, including of both mRNAs and microRNAs (miRNAs, and identified a number of mRNAs and miRNAs (miRNA-1 and miRNA-281 with circadian rhythm-dependent altered expression in dfmr1 mutant flies. Identification of these RNAs lays the foundation for future investigations of the molecular pathway(s underlying the altered circadian rhythms associated with loss of dFmr1.

  5. Properties of VIP+ synapses in the suprachiasmatic nucleus highlight their role in circadian rhythm.

    Science.gov (United States)

    Achilly, Nathan P

    2016-06-01

    Circadian rhythms coordinate cyclical behavioral and physiological changes in most organisms. In humans, this biological clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus and consists of a heterogeneous neuron population characterized by their enriched expression of various neuropeptides. As highlighted here, Fan et al. (J Neurosci 35: 1905-1029, 2015) developed an elegant experimental system to investigate the synaptic properties of vasoactive intestinal peptide (VIP)-expressing neurons between day and night, and further delineate their broader architecture and function within the SCN. PMID:26581865

  6. Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity.

    OpenAIRE

    Hamm, H E; Menaker, M

    1980-01-01

    There is a large-amplitude circadian rhythm of indoleamine metabolism in the retina-pigment epithelium of the chicken. N-Acetyltransferase activity (arylamine acetyltransferase; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) and melatonin content are 15-fold higher at night than during the day in a cycle of a 4-fold increase during the subjective night. Light at midnight inactivates N-acetyltransferase and lowers melatonin. N-Acetyltransferase activity is found predominantly in the ret...

  7. 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 reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These

  8. Retinoic Acid-Related Orphan Receptors (RORs: Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Directory of Open Access Journals (Sweden)

    Donald N. Cook

    2015-12-01

    Full Text Available In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs. We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

    OpenAIRE

    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–...

  11. Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

    OpenAIRE

    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–...

  12. 近日节律对麻醉药物作用的影响%Effect of circadian rhythms on the action of anaesthetic agents

    Institute of Scientific and Technical Information of China (English)

    曾海波; 尚游; 袁世荧

    2010-01-01

    多数麻醉医生认为,人体是一个非常稳定的有机体.事实上,机体的许多方面因为受到生物节律的影响而会表现出周期性的变化.近日节律是一种重要的生物节律,对动植物乃至人都有诸多重要的影响,这其中也包括对麻醉药物作用的影响.因此,在从事科学研究和临床工作时,近日节律对麻醉药物作用的这种影响不容忽视.%Many anaesthetists assume that humans are homeostatic organisms but in reality we show periodic variations in nearly all facets of our physiology and behaviour, influenced by biologic rhythms. Circadian rhythms is an important biologic rhythm which can affect animals, plants and human beings. Also it make effects on anesthetics, The effects of circadian rhythms should be considered in scientific research of anaesthetic drugs and works of clinical practice of anaesthesia.

  13. Circadian Rhythm Sleep Disorder, Free-Running Type in a Sighted Male with Severe Depression, Anxiety, and Agoraphobia

    OpenAIRE

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

    2011-01-01

    Circadian rhythm sleep disorder, free-running type (CRSD, FRT) is a disorder in which the intrinsic circadian rhythm is no longer entrained to the 24-hour schedule. A unique case of CRSD, FRT in a 67-year-old sighted male is presented. The patient had a progressively delayed time in bed (TIB) each night, so that he would cycle around the 24-h clock approximately every 30 days. This was meticulously documented each night by the patient over the course of 22 years. The patient's CRSD, FRT was a...

  14. Circadian rhythms of psychomotor vigilance, mood, and sleepiness in the ultra-short sleep/wake protocol

    OpenAIRE

    KLINE, Christopher E; Durstine, J. Larry; Davis, J. Mark; Moore, Teresa A.; DEVLIN, Tina M; Youngstedt, Shawn D.

    2010-01-01

    Despite its advantages as a chronobiological technique, the ultra-short sleep/wake protocol remains underutilized in circadian rhythm research. The purpose of this study was to examine circadian rhythms of psychomotor vigilance (PVT), mood, and sleepiness in a sample (n = 25) of healthy young adults while they adhered to a 3-h ultra-short sleep/wake protocol. The protocol involved 1-h sleep intervals in darkness followed by 2-h wake intervals in dim light, repeated for 50–55 h. A 5-min PVT te...

  15. Circadian rhythms of sense and antisense transcription in sugarcane, a highly polyploid crop.

    Directory of Open Access Journals (Sweden)

    Carlos Takeshi Hotta

    Full Text Available Commercial sugarcane (Saccharum hybrid is a highly polyploid and aneuploid grass that stores large amounts of sucrose in its stem. We have measured circadian rhythms of sense and antisense transcription in a commercial cultivar (RB855453 using a custom oligoarray with 14,521 probes that hybridize to sense transcripts (SS and 7,380 probes that hybridize to antisense transcripts (AS.We estimated that 32% of SS probes and 22% AS probes were rhythmic. This is a higher proportion of rhythmic probes than the usually found in similar experiments in other plant species. Orthologs and inparalogs of Arabidopsis thaliana, sugarcane, rice, maize and sorghum were grouped in ortholog clusters. When ortholog clusters were used to compare probes among different datasets, sugarcane also showed a higher proportion of rhythmic elements than the other species. Thus, it is possible that a higher proportion of transcripts are regulated by the sugarcane circadian clock. Thirty-six percent of the identified AS/SS pairs had significant correlated time courses and 64% had uncorrelated expression patterns. The clustering of transcripts with similar function, the anticipation of daily environmental changes and the temporal compartmentation of metabolic processes were some properties identified in the circadian sugarcane transcriptome. During the day, there was a dominance of transcripts associated with photosynthesis and carbohydrate metabolism, including sucrose and starch synthesis. During the night, there was dominance of transcripts associated with genetic processing, such as histone regulation and RNA polymerase, ribosome and protein synthesis. Finally, the circadian clock also regulated hormone signalling pathways: a large proportion of auxin and ABA signalling components were regulated by the circadian clock in an unusual biphasic distribution.

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

    Directory of Open Access Journals (Sweden)

    Daisuke Ono

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

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

    Directory of Open Access Journals (Sweden)

    Rie Miyata

    2016-01-01

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

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

    Science.gov (United States)

    Miyata, Rie; Tanuma, Naoyuki; Sakuma, Hiroshi; Hayashi, Masaharu

    2016-01-01

    Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2'-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm. PMID:27213030

  19. Ontogeny of alpha-amylase circadian rhythms in rat parotid gland.

    Science.gov (United States)

    Sanz, E G; Vermouth, N T; Bellavia, S L

    1986-01-01

    The content of alpha-amylase (alpha-1,4-glucan-4-glucanohydrolase, EC 3.2.1.1.) and total soluble proteins of parotid glands (from rats exposed to a photoperiod of 14 hr light: 10 hr dark), have been determined every 2 or 3 hr over 24 hr periods in 15, 25 and 90-day-old rats. In 35-, 45- and 72-day-old rats, determinations were performed only at 0100 and 1400 hr. The alpha-amylase and total soluble protein contents from 90-day-old rats show a circadian variation, with a maximum value at 2200 hr and a minimum at 1400 hr. Parotids from 15- and 25-day-old rats also show a circadian rhythm. The minimum value is recorded at 0100 hr and the maximum at 1400 hr. At day 35 and after, there is an inversion of the amylase rhythm. In immature rats, it appears that alpha-amylase and soluble protein are under the influence of another synchronizer, whose timing is independent of that imposed by mastication of solid food. PMID:2878787

  20. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Indian Academy of Sciences (India)

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

    2008-12-01

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

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

    Directory of Open Access Journals (Sweden)

    I. Rajagopal

    2011-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Teruya Tamaru

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

  7. Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans.

    Science.gov (United States)

    Cuesta, Marc; Boudreau, Philippe; Dubeau-Laramée, Geneviève; Cermakian, Nicolas; Boivin, Diane B

    2016-03-15

    Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers. PMID:26873990

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

    Directory of Open Access Journals (Sweden)

    Rajagopal I

    2012-08-01

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

  9. 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.

  10. 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

  11. Disrupted Circadian Rhythm as a Common Player in Developmental Models of Neuropsychiatric Disorders.

    Science.gov (United States)

    Marco, Eva M; Velarde, Elena; Llorente, Ricardo; Laviola, Giovanni

    2016-01-01

    The environment in which individuals develop and mature is critical for their physiological and psychological outcome; in particular, the intrauterine environment has reached far more clinical relevance given its potential influence on shaping brain function and thus mental health. Gestational stress and/or maternal infection during pregnancy has been related with an increased incidence of neuropsychiatric disorders, including depression and schizophrenia. In this framework, the use of animal models has allowed a formal and deep investigation of causal determinants. Despite disruption of circadian clocks often represents a hallmark of several neuropsychiatric disorders, the relationship between disruption of brain development and the circadian system has been scarcely investigated. Nowadays, there is an increasing amount of studies suggesting a link between circadian system malfunction, early-life insults and the appearance of neuropsychiatric diseases at adulthood. Here, we briefly review evidence from clinical literature and animal models suggesting that the exposure to prenatal insults, i.e. severe gestational stress or maternal immune activation, changes the foetal hormonal milieu increasing the circulating levels of both glucocorticoids and pro-inflammatory cytokines. These two biological events have been reported to affect genes expression in experimental models and critically interfere with brain development triggering and/or exacerbating behavioural anomalies in the offspring. Herein, we highlight the importance to unravel the individual components of the body circadian system that might also be altered by prenatal insults and that may be causally associated with the disruption of neural and endocrine developmental programming. PMID:26728169

  12. Interactions between Cognition and Circadian Rhythms: Attentional Demands Modify Circadian Entrainment

    OpenAIRE

    Gritton, Howard J.; Sutton, Blair C.; Martinez, Vicente; Sarter, Martin; Lee, Theresa M.

    2009-01-01

    Animals and humans are able to predict and synchronize their daily activity to signals present in their environments. Environmental cues are most often associated with signaling the beginning or the end of a daily activity cycle but they can also be used to time the presentation or availability of scarce resources. If the signal occurs consistently, animals can begin to anticipate its arrival and ultimately become entrained to its presence. While many stimuli can produce anticipation for a da...

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

    Science.gov (United States)

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

    2015-03-01

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

  14. 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. PMID:24797245

  15. 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.

  16. 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.

  17. 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. PMID:15822013

  18. Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics.

    Science.gov (United States)

    Hoffman, D A; Wallace, S M; Verbeeck, R K

    1990-01-01

    The circadian variation of serum inorganic sulfate levels was studied in healthy volunteers. The effect of subchronic acetaminophen administration (650 mg q.i.d. for 4 days) on serum inorganic sulfate levels was investigated and the possible role of fluctuating serum inorganic sulfate levels on the pharmacokinetics of acetaminophen was evaluated. During a 24 h cycle, serum inorganic sulfate levels were lowest in the morning (11.00 h) and typically increased in the afternoon to reach a maximum in the early evening (19.00 h). Average 24 h serum concentrations were 360 microM and the difference between minimum and maximum levels was on average 25.8%. Subchronic administration of acetaminophen (650 mg q.i.d. for 4 days) significantly reduced serum inorganic sulfate levels to a 24 h average of 253 microM. The circadian rhythm, however, was not affected and the difference between minimum (12.00 h) and maximum (18.50 h) serum concentrations was 31.3%. Subchronic acetaminophen administration lead to a significant decrease in the renal excretion (-51%) and renal clearance (-33%) of inorganic sulfate. No significant differences were found in the disposition kinetics of acetaminophen and its glucuronide and sulfate conjugates during two consecutive dosing intervals (08.00-14.00 h, 14.00-20.00 h) on Day 4 of the acetaminophen regimen. PMID:2253663

  19. 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. PMID:26203935

  20. 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.

  1. 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.

  2. 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.

  3. Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans.

    Science.gov (United States)

    Hashimoto, S; Kohsaka, M; Morita, N; Fukuda, N; Honma, S; Honma, K

    1996-12-13

    Eight young males were subjected to a single blind cross-over test to see the effects of vitamin B12 (methylcobalamin; VB12) on the phase-response of the circadian melatonin rhythm to a single bright light exposure. VB12 (0.5 mg/day) or vehicle was injected intravenously at 1230 h for 11 days, which was followed by oral administration (2 mg x 3/day) for 7 days. A serial blood sampling was performed under dim light condition (less than 200 lx) and plasma melatonin rhythm was determined before and after a single bright light exposure (2500 lx for 3 h) at 0700 h. The melatonin rhythm before the light exposure showed a smaller amplitude in the VB12 trial than in the placebo. The light exposure phase-advanced the melatonin rhythm significantly in the VB12 trail, but not in the placebo. These findings indicate that VB12 enhances the light-induced phase-shift in the human circadian rhythm. PMID:8981490

  4. 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 ostatní: 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

  5. 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.

  6. The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

    Science.gov (United States)

    DeRoshia, Charles W.; Colletti, Laura C.; Mallis, Melissa M.

    2008-01-01

    This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

  7. The effects on human sleep and circadian rhythms of 17 days of continuous bedrest in the absence of daylight

    Science.gov (United States)

    Monk, T. H.; Buysse, D. J.; Billy, B. D.; Kennedy, K. S.; Kupfer, D. J.

    1997-01-01

    As part of a larger bedrest study involving various life science experiments, a study was conducted on the effects of 17 days of continuous bedrest and elimination of daylight on circadian rectal temperature rhythms, mood, alertness, and sleep (objective and diary) in eight healthy middle-aged men. Sleep was timed from 2300 to 0700 hours throughout. Three 72-hour measurement blocks were compared: ambulatory prebedrest, early bedrest (days 5-7), and late bedrest (days 15-17). Temperature rhythms showed reduced amplitude and later phases resulting from the bedrest conditions. This was associated with longer nocturnal sleep onset latencies and poorer subjectively rated sleep but with no reliable changes in any of the other sleep parameters. Daily changes in posture and/or exposure to daylight appear to be important determinants of a properly entrained circadian system.

  8. 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; Iaconelli, A; Leccesi, L; Guidone, C; Nanni, G; Holst, Jens Juul

    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 ...... diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.......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...... (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic...

  9. Validation of a cortisol enzyme immunoassay and characterization of salivary cortisol circadian rhythm in chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Heintz, Matthew R; Santymire, Rachel M; Parr, Lisa A; Lonsdorf, Elizabeth V

    2011-09-01

    Monitoring concentrations of stress hormones is an important tool for behavioral research and conservation for animals both in the wild and captivity. Glucocorticoids can be measured in mammals as an indicator of stress by analyzing blood, feces, urine, hair, feathers, or saliva. The advantages of using saliva for measuring cortisol concentrations are three-fold: it is minimally invasive, multiple samples can be collected from the same individual in a short timeframe, and cortisol has a relatively short response time in saliva as compared with other materials. The purpose of this study was to: (1) conduct an adrenocorticotropic hormone (ACTH) challenge as a physiological validation for an enzyme immunoassay to measure salivary cortisol in chimpanzees and (2) characterize the circadian rhythm of salivary cortisol in chimpanzees. We determined that salivary cortisol concentrations peaked 45 min following the ACTH challenge, which is similar to humans. Also, salivary cortisol concentrations peaked early in the morning and decreased throughout the day. We recommend that saliva collection may be the most effective method of measuring stress reactivity and has the potential to complement behavioral, cognitive, physiological, and welfare studies. PMID:21538448

  10. Circadian rhythms of psychomotor vigilance, mood, and sleepiness in the ultra-short sleep/wake protocol

    Science.gov (United States)

    Kline, Christopher E.; Durstine, J. Larry; Davis, J. Mark; Moore, Teresa A.; Devlin, Tina M.; Youngstedt, Shawn D.

    2011-01-01

    Despite its advantages as a chronobiological technique, the ultra-short sleep/wake protocol remains underutilized in circadian rhythm research. The purpose of this study was to examine circadian rhythms of psychomotor vigilance (PVT), mood, and sleepiness in a sample (n = 25) of healthy young adults while they adhered to a 3-h ultra-short sleep/wake protocol. The protocol involved 1-h sleep intervals in darkness followed by 2-h wake intervals in dim light, repeated for 50–55 h. A 5-min PVT test was conducted every 9 h with the standard metrics of mean reaction time (RT; RTmean), median RT (RTmed), fastest 10% of responses (RT10fast), and the reciprocal of the 10% slowest responses (1/RT10slow). Subjective measures of mood and sleepiness were assessed every 3 h. A cosine fit of intra-aural temperature, assessed three times per wake period, established the time of the body temperature minimum (Tmin). Mood, sleepiness, and PVT performances were expressed relative to individual means and compared across eight times of day and across twelve 2-h intervals relative to Tmin. Significant time-of-day and circadian patterns were demonstrated for each of the PVT metrics, as well as for mood and sleepiness. Most mood subscales exhibited significant deterioration in day 2 of the protocol without an alteration of circadian pattern. However, neither sleepiness nor performance was worse on the second day of observation compared to the first day. These data provide further support for the use of the ultra-short sleep/wake protocol for measurement of circadian rhythms. PMID:20205564

  11. Morningness-Eveningness and Flextime Possibilities: Connections Between Circadian Rhythm, Work Day Schedule, Well-Being and Productivity

    OpenAIRE

    Stenvold, Linda Catrine

    2012-01-01

    The current study aimed to investigate earlier reported connections to the morningness- eveningness dimension or flextime, and to offer an explanatory model linking these variables to well-being and productivity. Earlier findings gave the impression that it could be beneficial for both organizations and employees to have work schedules allowing employees to take their own circadian rhythm into account when planning their work day, since well-rested employees have been shown to be happier an...

  12. Sleep, Hormones, and Circadian Rhythms throughout the Menstrual Cycle in Healthy Women and Women with Premenstrual Dysphoric Disorder

    OpenAIRE

    Ari Shechter; Boivin, Diane B.

    2010-01-01

    A relationship exists between the sleep-wake cycle and hormone secretion, which, in women, is further modulated by the menstrual cycle. This interaction can influence sleep across the menstrual cycle in healthy women and in women with premenstrual dysphoric disorder (PMDD), who experience specific alterations of circadian rhythms during their symptomatic luteal phase along with sleep disturbances during this time. This review will address the variation of sleep at different menstrual phases i...

  13. Circadian Rhythm Characteristics in Mood Disorders: Comparison among Bipolar I Disorder, Bipolar II Disorder and Recurrent Major Depressive Disorder

    OpenAIRE

    Chung, Jae Kyung; Lee, Kyu Young; KIM, SE HYUN; Kim, Eui-Joong; Jeong, Seong Hoon; Jung, Hee Yeon; Choi, Jung-Eun; Ahn, Yong Min; Kim, Yong Sik; Joo, Eun-Jeong

    2012-01-01

    Objective Morningness/eveningness (M/E) is a stable characteristic of individuals. Circadian rhythms are altered in episodes of mood disorder. Mood disorder patients were more evening-type than normal population. In this study, we compared the characteristics of M/E among the 257 patients with bipolar I disorder (BPD1), bipolar II disorder (BPD2) and major depressive disorder, recurrent (MDDR). Methods M/E was evaluated using the Korean version of the composite scale of morningness (CS). Fact...

  14. Non-invasive estimation of the circadian rhythm in serum cortisol in patients with ovarian or colorectal cancer.

    Science.gov (United States)

    Mormont, M C; Hecquet, B; Bogdan, A; Benavides, M; Touitou, Y; Levi, F

    1998-11-01

    The variability in toxicity or efficacy of cancer chronotherapy among patients may be due to differences in circadian rhythm. Adequate assessment of circadian rhythm often requires repeated blood sampling over at least a 24-hr period; this cannot be a routine procedure. We attempted to assess the reliability of a 2-timepoint estimate of the 24-hr rhythm of serum cortisol in 19 healthy subjects, 19 women with ovarian cancer and 18 patients with metastatic colorectal cancer. The difference between daily maximum and minimum values (MAX-MIN) was compared with that observed between values at 08.00 and at 16.00 (H8-H16). As significant correlations were found between both variables in all groups, we conclude that the magnitude of circadian changes in serum cortisol may be estimated from blood samples collected at 08.00 and at 16.00. The clinical relevance and the prognostic value of this method of assessment are currently under evaluation in a larger-scale clinical trial. PMID:9797128

  15. Cocaine sensitization and reward are under the influence of circadian genes and rhythm

    OpenAIRE

    Abarca, Carolina; Albrecht, Urs; Spanagel, Rainer

    2002-01-01

    Investigations using the fruit fly Drosophila melanogaster have shown that the circadian clock gene period (Per) can influence behavioral responses to cocaine. Here we show that the mouse homologues of the Drosophila Per gene, mPer1 and mPer2, modulate cocaine sensitization and reward, two phenomena extensively studied in humans and animals because of their importance for drug abuse. In response to an acute cocaine injection mPer1 and mPer2 mutant mice as well as wild-type mice exhibited an a...

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

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    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.

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

    Science.gov (United States)

    Shultzaberger, Ryan K; Paddock, Mark L; Katsuki, Takeo; Greenspan, Ralph J; Golden, Susan S

    2015-01-01

    The temporal measurement of a bioluminescent reporter has proven to be one of the most powerful tools for characterizing circadian rhythms in the cyanobacterium Synechococcus elongatus. Primarily, two approaches have been used to automate this process: (1) detection of cell culture bioluminescence in 96-well plates by a photomultiplier tube-based plate-cycling luminometer (TopCount Microplate Scintillation and Luminescence Counter, Perkin Elmer) and (2) detection of individual colony bioluminescence by iteratively rotating a Petri dish under a cooled CCD camera using a computer-controlled turntable. Each approach has distinct advantages. The TopCount provides a more quantitative measurement of bioluminescence, enabling the direct comparison of clock output levels among strains. The computer-controlled turntable approach has a shorter set-up time and greater throughput, making it a more powerful phenotypic screening tool. While the latter approach is extremely useful, only a few labs have been able to build such an apparatus because of technical hurdles involved in coordinating and controlling both the camera and the turntable, and in processing the resulting images. This protocol provides instructions on how to construct, use, and process data from a computer-controlled turntable to measure the temporal changes in bioluminescence of individual cyanobacterial colonies. Furthermore, we describe how to prepare samples for use with the TopCount to minimize experimental noise and generate meaningful quantitative measurements of clock output levels for advanced analysis. PMID:25662451

  18. 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

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

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    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

  20. Effects of afternoon "siesta" naps on sleep, alertness, performance, and circadian rhythms in the elderly

    Science.gov (United States)

    Monk, T. H.; Buysse, D. J.; Carrier, J.; Billy, B. D.; Rose, L. R.

    2001-01-01

    STUDY OBJECTIVES: To determine the effects of a 90-minute afternoon nap regimen on nocturnal sleep, circadian rhythms, and evening alertness and performance levels in the healthy elderly. DESIGN AND SETTING: Nine healthy elderly subjects (4m, 5f, age range 74y-87y) each experienced both nap and no-nap conditions in two studies each lasting 17 days (14 at home, 3 in the laboratory). In the nap condition a 90-minute nap was enforced between 13:30 and 15:00 every day, in the no-nap condition daytime napping was prohibited, and activity encouraged in the 13:30-15:00 interval. The order of the two conditions was counterbalanced. PARTICIPANTS: N/A INTERVENTIONS: N/A MEASUREMENTS: Diary measures, pencil and paper alertness tests, and wrist actigraphy were used at home. In the 72 hour laboratory studies, these measures were augmented by polysomnographic sleep recording, continuous rectal temperature measurement, a daily evening single trial of a Multiple Sleep Latency Test (MSLT), and computerized tests of mood, activation and performance efficiency. RESULTS: By the second week in the "at home" study, an average of 58 minutes of sleep was reported per siesta nap; in the laboratory, polysomnography confirmed an average of 57 minutes of sleep per nap. When nap and no-nap conditions were compared, mixed effects on nocturnal sleep were observed. Diary measures indicated no significant difference in nocturnal sleep duration, but a significant increase (of 38 mins.) in 24-hour Total Sleep Time (TST) when nocturnal sleeps and naps were added together (psleep efficiency in the nap condition (pSleep Time (TST) by 48 mins. in the nap condition (peffects on Wake After Sleep Onset (WASO), delta sleep measures, or percent stages 1 & 2. Unlike the diary study, the laboratory study yielded no overall increase in 24-hour TST consequent upon the siesta nap regimen. The only measure of evening alertness or performance to show an improvement was sleep latency in a single-trial evening MSLT

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Circadian Rest/Activity Rhythms in Knee Osteoarthritis with Insomnia: A Study of Osteoarthritis Patients and Pain-Free Controls with Insomnia or Normal Sleep

    OpenAIRE

    Spira, Adam P.; Runko, Virginia T.; Finan, Patrick H.; Kaufmann, Christopher N.; Bounds, Sara C; Liu, Lianqi; Buenaver, Luis F.; McCauley, Lea M.; Ancoli-Israel, Sonia; Smith, Michael T

    2014-01-01

    Aberrant circadian rest/activity rhythms (RARs) may promote poor aging-related health outcomes. Osteoarthritis and chronic insomnia are common age-related conditions, but the circadian RARs of each group have not been well characterized or compared. We evaluated actigraphic RARs in individuals with: (1) knee osteoarthritis (KOA) only; (2) chronic insomnia only; (3) KOA + insomnia; and (4) pain-free good sleepers. Compared to participants with KOA only, those with KOA + insomnia had less robus...

  3. Effects of 9-hour time zone changes on fatigue and circadian rhythms of sleep/wake and core temperature

    Science.gov (United States)

    Gander, P. H.; Myhre, G.; Graeber, R. C.; Andersen, H. T.; Lauber, J. K.

    1985-01-01

    Physiological and psychological disruptions caused by transmeridian flights may affect the ability of flight crews to meet operational demands. To study these effects, 9 Royal Norwegian Airforces P3-Orion crewmembers flew from Norway to California (-9 hr), and back (+9 hr). Rectal temperature, heart rate and wrist activity were recorded every 2 min, fatigue and mood were rated every 2 hr during the waking day, and logs were kept of sleep times and ratings. Subjects also completed 4 personality inventories. The time-zone shifts produced negative changes in mood which persisted longer after westward flights. Sleep quality (subjective and objective) and duration were slightly disrupted (more after eastward flights). The circadian rhythms of sleep/wake and temperature both completed the 9-hr delay by day 5 in California, although temperature adjusted more slowly. The size of the delay shift was significantly correlated with scores on extraversion and achievement need personality scales. Response to the 9-hr advance were more variable. One subject exhibited a 15-hr delay in his temperature rhythm, and an atypical sleep/nap pattern. On average, the sleep/wake cycle (but not the temperature rhythm), completed the 9-hr advance by the end of the study. Both rhythms adapted more slowly after the eastward flight.

  4. Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

    Science.gov (United States)

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

    2016-01-01

    The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period.

  5. Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN.

    Science.gov (United States)

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

    2016-09-01

    The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2 (-/-) ). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2 (-/-) SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

  6. 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

  7. A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats.

    Science.gov (United States)

    Takeshige, Yui; Fujisawa, Yoshihide; Rahman, Asadur; Kittikulsuth, Wararat; Nakano, Daisuke; Mori, Hirohito; Masaki, Tsutomu; Ohmori, Koji; Kohno, Masakazu; Ogata, Hiroaki; Nishiyama, Akira

    2016-06-01

    Studies were performed to examine the effects of the selective sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on urinary sodium excretion and circadian blood pressure in salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. Fifteen-week-old obese OLETF rats were treated with 1% NaCl (in drinking water), and vehicle (0.5% carboxymethylcellulose, n=10) or empagliflozin (10 mg kg(-1)per day, p.o., n=11) for 5 weeks. Blood pressure was continuously measured by telemetry system. Glucose metabolism and urinary sodium excretion were evaluated by oral glucose tolerance test and high salt challenge test, respectively. Vehicle-treated OLETF rats developed non-dipper type blood pressure elevation with glucose intolerance and insulin resistance. Compared with vehicle-treated animals, empagliflozin-treated OLETF rats showed an approximately 1000-fold increase in urinary glucose excretion and improved glucose metabolism and insulin resistance. Furthermore, empagliflozin prevented the development of blood pressure elevation with normalization of its circadian rhythm to a dipper profile, which was associated with increased urinary sodium excretion. These data suggest that empagliflozin elicits beneficial effects on both glucose homeostasis and hypertension in salt-replete obese states. PMID:26818652

  8. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  11. The role of chronobiology and circadian rhythms in type 2 diabetes mellitus: implications for management of diabetes

    Directory of Open Access Journals (Sweden)

    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 changes in toxicity of the insecticide dieldrin on larvae of the migratory locust Locusta migratoria migratorioides.

    Science.gov (United States)

    Onyeocha, F A; Fuzeau-Braesch, S

    1991-01-01

    Circadian changes in toxicity of the insecticide dieldrin were documented in the larvae (fifth stage) of the migratory locust, Locusta migratoria migratorioides. Insects were housed under light (L): dark (D) = 12:12, with L from 0800 to 2000 h. Topical applications of dieldrin at fixed clock hours, with doses ranging from 0.1 to 8 micrograms/gm body weight, were carried out in a series of experiments on male and female larvae. Twenty-four h after dosing, mortality was recorded to quantify the median lethal dose (LD50) values with reference to time of treatment. Experiments were performed during February, early and late June, and August. Larvae were more susceptible to dieldrin when dosed during the night rather than during the day [analysis of variance (ANOVA); p less than 0.05]. Moreover, female larvae were less susceptible to dieldrin than were male larvae (ANOVA; p less than 0.05). Cosinor analysis revealed circadian rhythms in susceptibility-resistance to the insecticide in all experiments except no. 2. Toxicity was found to be greatest during the nighttime. Cosinor analysis of pooled data of the four experiments documented circadian rhythmicity to toxicity of dieldrin in female but not in male larvae. Regardless of sex, the timing of least susceptibility (greatest resistance and highest LD50 value) to the insecticide, dieldrin, was around 1500. PMID:1797408

  13. Differential entrainment of a social rhythm in adolescent mice

    OpenAIRE

    Panksepp, Jules B.; Wong, Jenny C.; Kennedy, Bruce C.; Lahvis, Garet P.

    2008-01-01

    Daily routines in animal activities range from sleep-wake cycles, to foraging bouts, to social interactions. Among animals living within groups, it is unclear whether the motivations that underlie social interactions respond to daily light-dark (LD) cycles or endogenous circadian rhythms. Employing two mouse strains (BALB/cJ [BALB] & C57BL/6J [B6]) with genetically based differences in social affect and circadian rhythms, we examined how social investigation (SI) is modulated by social depriv...

  14. 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.

  15. Daily Rhythms in the Cyanobacterium Synechococcus elongatus Probed by High-resolution Mass Spectrometry-based Proteomics Reveals a Small Defined Set of Cyclic Proteins

    OpenAIRE

    Guerreiro, A. C. L.; Benevento, M.; Lehmann, R.; van Breukelen, B.; Post, H.; Giansanti, P.; Maarten Altelaar, A. F.; Axmann, I. M.; Heck, A.J.R.

    2014-01-01

    Circadian rhythms are self-sustained and adjustable cycles, typically entrained with light/dark and/or temperature cycles. These rhythms are present in animals, plants, fungi, and several bacteria. The central mechanism behind these “pacemakers” and the connection to the circadian regulated pathways are still poorly understood. The circadian rhythm of the cyanobacterium Synechococcus elongatus PCC 7942 (S. elongatus) is highly robust and controlled by only three proteins, KaiA, KaiB, and KaiC...

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

    OpenAIRE

    Merrow, M; Spoelstra, K; T. Roenneberg

    2005-01-01

    The daily recurrence of activity and rest are so common as to seem trivial. However, they reflect a ubiquitous temporal programme called the circadian clock. In the absence of either anatomical clock structures or clock genes, the timing of sleep and wakefulness is disrupted. The complex nature of circadian behaviour is evident in the fact that phasing of the cycle during the day varies widely for individuals, resulting in extremes colloquially called 'larks' and 'owls'. These behavioural osc...

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

    NARCIS (Netherlands)

    P.K. Jha

    2016-01-01

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

  18. Circadian abnormalities in a mouse model of high trait anxiety and depression

    OpenAIRE

    Griesauer, Irene; Diao, Weifei; Ronovsky, Marianne; Elbau, Immanuel; Sartori, Simone; Singewald, Nicolas; Pollak, Daniela D.

    2014-01-01

    Introduction Dysregulation of circadian rhythms is a key symptom of mood disorders, including anxiety disorders and depression. Whether the circadian abnormalities observed in depressed patients are cause or consequence of the disease remains elusive. Here we aimed to explore potential disturbances of circadian rhythms in a validated genetic animal model of high trait anxiety and co-morbid depression and examine its molecular correlates. Materials and methods Mice selectively bred for high (H...

  19. Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner*

    Science.gov (United States)

    Kawai, Masanobu; Kinoshita, Saori; Shimba, Shigeki; Ozono, Keiichi; Michigami, Toshimi

    2014-01-01

    The circadian clock network is well known to link food intake and metabolic outputs. Phosphorus is a pivotal nutritional factor involved in energy and skeletal metabolisms and possesses a circadian profile in the circulation; however, the precise mechanisms whereby phosphate metabolism is regulated by the circadian clock network remain largely unknown. Because sympathetic tone, which displays a circadian profile, is activated by food intake, we tested the hypothesis that phosphate metabolism was regulated by the circadian clock network through the modification of food intake-associated sympathetic activation. Skeletal Fgf23 expression showed higher expression during the dark phase (DP) associated with elevated circulating FGF23 levels and enhanced phosphate excretion in the urine. The peaks in skeletal Fgf23 expression and urine epinephrine levels, a marker for sympathetic tone, shifted from DP to the light phase (LP) when mice were fed during LP. Interestingly, β-adrenergic agonist, isoproterenol (ISO), induced skeletal Fgf23 expression when administered at ZT12, but this was not observed in Bmal1-deficient mice. In vitro reporter assays revealed that ISO trans-activated Fgf23 promoter through a cAMP responsive element in osteoblastic UMR-106 cells. The mechanism of circadian regulation of Fgf23 induction by ISO in vivo was partly explained by the suppressive effect of Cryptochrome1 (Cry1) on ISO signaling. These results indicate that the regulation of skeletal Fgf23 expression by sympathetic activity is dependent on the circadian clock system and may shed light on new regulatory networks of FGF23 that could be important for understanding the physiology of phosphate metabolism. PMID:24302726

  20. 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.

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

    Science.gov (United States)

    Chang, Yung-Sen; Chiang, Bor-Luen

    2016-01-01

    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. PMID:27043528

  2. The role of chronobiology and circadian rhythms in type 2 diabetes mellitus: implications for management of diabetes

    OpenAIRE

    Kurose, Takeshi

    2014-01-01

    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 d...

  3. 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

  4. Circadian rhythm in plasma concentrations of gamma-hydroxybutyric acid in alcoholics.

    Science.gov (United States)

    Hoes, M J; Vree, T B; Guelen, P J

    1981-08-01

    Gamma-hydroxybutyric acid (GHB) was orally administered to six alcoholics at 09.00 and 23.00 h. The plasma concentrations of GHB show a clear circadian pattern, the area under the curve in the daytime experiments being 61% of that in the night experiments. The significance of alcohol dehydrogenase, the catabolic enzyme of GHB, for the difference is discussed. It is concluded that, although the activity of alcohol dehydrogenase in alcoholics is quantitatively disturbed, it remains subject to physiologic circadian activation. PMID:7341501

  5. Circadian rhythms of body temperature and locomotor activity in aging BALB/c mice: early and late life span predictors.

    Science.gov (United States)

    Basso, Andrea; Del Bello, Giovanna; Piacenza, Francesco; Giacconi, Robertina; Costarelli, Laura; Malavolta, Marco

    2016-08-01

    Impairment of one or more parameters of circadian rhythms (CR) of body temperature (BT) and locomotor activity (LMA) are considered among the hallmarks of mammalian aging. These alterations are frequently used as markers for imminent death in laboratory mice. However, there are still contradictory data for particular strains and it is also uncertain which changes might predict senescence changes later in life, including the force of mortality. In the present paper we use telemetry to study LMA and CR of BT during aging of BALB/c mice. At our knowledge this is the first time that CR of BT and LMA are investigated in this strain in a range of age covering the whole lifespan, from young adult up to very old age. CR of BT was analyzed with a cosine model using a cross sectional approach and follow-up measurements. The results show that BT, LMA, amplitude, goodness-of-fit (GoF) to circadian cycle of temperature decrease with different shapes during chronological age. Moreover, we found that the % change of amplitude and BT in early life (5-19 months) can predict the remaining lifespan of the mice. Later in life (22-32 months), best predictors are single measurements of LMA and GoF. The results of this study also offer potential measures to rapidly identifying freely unrestrained mice with the worst longitudinal outcome and against which existing or novel biomarkers and treatments may be assessed. PMID:26820297

  6. 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. PMID:25179226

  7. 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. PMID:25179226

  8. 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

  9. 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…

  10. Effect of photic stimuli disturbing overt circadian rhythms on the dorsomedial and ventrolateral SCN rhythmicity

    Czech Academy of Sciences Publication Activity Database

    Sumová, Alena; Illnerová, Helena

    2005-01-01

    Roč. 1048, č. 1-2 (2005), s. 161-169. ISSN 0006-8993 R&D Projects: GA AV ČR(CZ) IAA5011304 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian clock * suprachiasmatic nucleus * photic entrainment Subject RIV: ED - Physiology Impact factor: 2.296, year: 2005

  11. Circadian control of the daily plasma glucose rhythm: an interplay of GABA and glutamate.

    Directory of Open Access Journals (Sweden)

    Andries Kalsbeek

    Full Text Available The mammalian biological clock, located in the hypothalamic suprachiasmatic nuclei (SCN, imposes its temporal structure on the organism via neural and endocrine outputs. To further investigate SCN control of the autonomic nervous system we focused in the present study on the daily rhythm in plasma glucose concentrations. The hypothalamic paraventricular nucleus (PVN is an important target area of biological clock output and harbors the pre-autonomic neurons that control peripheral sympathetic and parasympathetic activity. Using local administration of GABA and glutamate receptor (antagonists in the PVN at different times of the light/dark-cycle we investigated whether daily changes in the activity of autonomic nervous system contribute to the control of plasma glucose and plasma insulin concentrations. Activation of neuronal activity in the PVN of non-feeding animals, either by administering a glutamatergic agonist or a GABAergic antagonist, induced hyperglycemia. The effect of the GABA-antagonist was time dependent, causing increased plasma glucose concentrations only when administered during the light period. The absence of a hyperglycemic effect of the GABA-antagonist in SCN-ablated animals provided further evidence for a daily change in GABAergic input from the SCN to the PVN. On the other hand, feeding-induced plasma glucose and insulin responses were suppressed by inhibition of PVN neuronal activity only during the dark period. These results indicate that the pre-autonomic neurons in the PVN are controlled by an interplay of inhibitory and excitatory inputs. Liver-dedicated sympathetic pre-autonomic neurons (responsible for hepatic glucose production and pancreas-dedicated pre-autonomic parasympathetic neurons (responsible for insulin release are controlled by inhibitory GABAergic contacts that are mainly active during the light period. Both sympathetic and parasympathetic pre-autonomic PVN neurons also receive excitatory inputs, either

  12. 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

  13. Consequences of manganese intoxication on the circadian rest-activity rhythms in the rat.

    Science.gov (United States)

    Bouabid, Safa; Fifel, Karim; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

    2016-09-01

    Manganese (Mn) intoxication is associated with neurological dysfunctions collectively known as Parkinsonism or Manganism. Like in Parkinson's disease, Manganism is associated with motor disturbances, together with non-motor symptoms including cognitive and neuropsychiatric deficits. Although sleep dysfunctions are commonly reported among workers exposed to Mn, their underlying pathophysiology remains unknown. In this study, we investigated the rest-activity rhythms in rats treated daily with MnCl2 (10mg/kg, i.p) for 5weeks. Locomotor activity was assessed under a light-dark (LD) cycle, constant darkness (DD) and during adjustment to 6h shifts of the LD cycle. In LD conditions, Mn-treated rats exhibited a more fragmented and less stable rest-activity rhythm in addition to a reduction in the total 24-h amount of locomotor activity as well as in the activity confined to the active dark phase of the LD. Consequently, a significant decrease in the amplitude of the rest-activity rhythm was observed. These disturbances were displayed during and after Mn treatment. Furthermore, after the 6-h phase advance of the LD cycle, Mn-treated rats failed to re-adjust accurately their behavioral activity to the new shifted LD cycle. Upon release from LD into DD, Mn-treated rats expressed a normal and stable free-running period of their rest-activity rhythm (23.92±0.07h in Mn group vs. 24.01±0.04h in control rats). However, their rest-activity rhythm remained highly fragmented and less stable. Our results provide the first evidence that chronic Mn intoxication leads to impairment of rest-activity rhythms in addition to the motor and non-motor disturbances reported in Manganism. PMID:27316552

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

    Directory of Open Access Journals (Sweden)

    Braun Donald P

    2011-05-01

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

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

    DEFF Research Database (Denmark)

    Luuk, Hendrik; Fahrenkrug, Jan; Hannibal, Jens

    2012-01-01

    The dorsomedial hypothalamic nucleus (DMH) has been proposed as a candidate for the neural substrate of a food-entrainable oscillator. The existence of a food-entrainable oscillator in the mammalian nervous system was inferred previously from restricted feeding-induced behavioral rhythmicity in...... rodents with suprachiasmatic nucleus lesions. In the present study, we have characterized the circadian rhythmicity of behavior in Wfs1-deficient mice during ad libitum and restricted feeding. Based on the expression of Wfs1 protein in the DMH it was hypothesized that Wfs1-deficient mice will display...... significantly lower body weight and reduced wheel-running activity. Circadian rhythmicity of behavior was normal in Wfs1-deficient mice under ad libitum feeding apart from elongated free-running period in constant light. The amount of food anticipatory activity induced by restricted feeding was not...

  16. Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders

    OpenAIRE

    Boivin, DB

    2000-01-01

    Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion...

  17. Non-Alcoholic Fatty Pancreas Disease Pathogenesis: A Role for Developmental Programming and Altered Circadian Rhythms

    OpenAIRE

    Carter, R; Mouralidarane, A.; Soeda, J.; S Ray; Pombo, J.; Saraswati, R.; Novelli, M; Fusai, G.; Rappa, F.; Saracino, C; Pazienza, V; L. Poston; Taylor, PD; Vinciguerra, M Oben JA.

    2014-01-01

    Objectives Emerging evidence suggests that maternal obesity (MO) predisposes offspring to obesity and the recently described non-alcoholic fatty pancreas disease (NAFPD) but involved mechanisms remain unclear. Using a pathophysiologically relevant murine model, we here investigated a role for the biological clock - molecular core circadian genes (CCG) in the generation of NAFPD. Design Female C57BL6 mice were fed an obesogenic diet (OD) or standard chow (SC) for 6 weeks, prior to pregnancy an...

  18. Variation in circadian rhythms is maintained among and within populations in Boechera stricta.

    Science.gov (United States)

    Salmela, Matti J; Greenham, Kathleen; Lou, Ping; McClung, C Robertson; Ewers, Brent E; Weinig, Cynthia

    2016-06-01

    Circadian clocks have evolved independently in all three domains of life, and fitness benefits of a functional clock have been demonstrated in experimental genotypes in controlled conditions. Still, little is known about genetic variation in the clock and its fitness consequences in natural populations from heterogeneous environments. Using Wyoming populations of the Arabidopsis relative Boechera stricta as our study system, we demonstrate that genetic variation in the clock can occur at multiple levels: means of circadian period among populations sampled at different elevations differed by less than 1 h, but means among families sampled within populations varied by as much as 3.5 h. Growth traits also varied among and within populations. Within the population with the most circadian variation, we observed evidence for a positive correlation between period and growth and a negative correlation between period and root-to-shoot ratio. We then tested whether performance tradeoffs existed among families of this population across simulated seasonal settings. Growth rankings of families were similar across seasonal environments, but for root-to-shoot ratio, genotype × environment interactions contributed significantly to total variation. Therefore, further experiments are needed to identify evolutionary mechanisms that preserve substantial quantitative genetic diversity in the clock in this and other species. PMID:26514754

  19. Circadian Control of the Daily Plasma Glucose Rhythm: An Interplay of GABA and Glutamate

    OpenAIRE

    Andries Kalsbeek; Ewout Foppen; Ingrid Schalij; Caroline Van Heijningen; Jan van der Vliet; Eric Fliers; Ruud M. Buijs

    2008-01-01

    The mammalian biological clock, located in the hypothalamic suprachiasmatic nuclei (SCN), imposes its temporal structure on the organism via neural and endocrine outputs. To further investigate SCN control of the autonomic nervous system we focused in the present study on the daily rhythm in plasma glucose concentrations. The hypothalamic paraventricular nucleus (PVN) is an important target area of biological clock output and harbors the pre-autonomic neurons that control peripheral sympathet...

  20. Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks.

    Science.gov (United States)

    Wolff, Gretchen; Duncan, Marilyn J; Esser, Karyn A

    2013-08-01

    Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study. PMID:23703115

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Effect of circadian rhythm disturbance on morphine preference and addiction in male rats: Involvement of period genes and dopamine D1 receptor.

    Science.gov (United States)

    Garmabi, B; Vousooghi, N; Vosough, M; Yoonessi, A; Bakhtazad, A; Zarrindast, M R

    2016-05-13

    It is claimed that a correlation exists between disturbance of circadian rhythms by factors such as alteration of normal light-dark cycle and the development of addiction. However, the exact mechanisms involved in this relationship are not much understood. Here we have studied the effect of constant light on morphine voluntary consumption and withdrawal symptoms and also investigated the involvement of Per1, Per2 and dopamine D1 receptor in these processes. Male wistar rats were kept under standard (LD) or constant light (LL) conditions for one month. The plasma concentration of melatonin was evaluated by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to determine the mRNA expression of Per1, Per2 and dopamine D1 receptor in the striatum and prefrontal cortex. Morphine preference (50mg/L) was evaluated in a two-bottle-choice paradigm for 10weeks and withdrawal symptoms were recorded after administration of naloxone (3mg/kg). One month exposure to constant light resulted in a significant decrease of melatonin concentration in the LL group. In addition, mRNA levels of Per2 and dopamine D1 receptor were up-regulated in both the striatum and prefrontal cortex of the LL group. However, expression of Per1 gene was only up-regulated in the striatum of LL rats in comparison to LD animals. Furthermore, after one month exposure to constant light, morphine consumption and preference ratio and also severity of naloxone-induced withdrawal syndrome were significantly greater in LL animals. It is concluded that exposure to constant light by up-regulation of Per2 and dopamine D1 receptor in the striatum and prefrontal cortex and up-regulation of Per1 in the striatum and the possible involvement of melatonin makes animals vulnerable to morphine preference and addiction. PMID:26892296

  3. The Influence of Light Quality, Circadian Rhythm, and Photoperiod on the CBF-Mediated Freezing Tolerance

    Directory of Open Access Journals (Sweden)

    Chang Ho Kang

    2013-05-01

    Full Text Available Low temperature adversely affects crop yields by restraining plant growth and productivity. Most temperate plants have the potential to increase their freezing tolerance upon exposure to low but nonfreezing temperatures, a process known as cold acclimation. Various physiological, molecular, and metabolic changes occur during cold acclimation, which suggests that the plant cold stress response is a complex, vital phenomenon that involves more than one pathway. The C-Repeat Binding Factor (CBF pathway is the most important and well-studied cold regulatory pathway that imparts freezing tolerance to plants. The regulation of freezing tolerance involves the action of phytochromes, which play an important role in light-mediated signalling to activate cold-induced gene expression through the CBF pathway. Under normal temperature conditions, CBF expression is regulated by the circadian clock through the action of a central oscillator and also day length (photoperiod. The phytochrome and phytochrome interacting factor are involved in the repression of the CBF expression under long day (LD conditions. Apart from the CBF regulon, a novel pathway involving the Z-box element also mediates the cold acclimation response in a light-dependent manner. This review provides insights into the progress of cold acclimation in relation to light quality, circadian regulation, and photoperiodic regulation and also explains the underlying molecular mechanisms of cold acclimation for introducing the engineering of economically important, cold-tolerant plants.

  4. Winter Depression: Integrating mood, circadian rhythms, and the sleep/wake and light/dark cycles into a bio-psycho-social-environmental model

    Science.gov (United States)

    Emens, Jonathan S.; Songer, Jeannie B.; Sims, Neelam; Laurie, Amber L.; Fiala, Steven C.; Buti, Allie L.

    2009-01-01

    Synopsis The phase shift hypothesis (PSH) states that most patients with SAD become depressed in the winter because of a delay in circadian rhythms with respect to the sleep/wake cycle: According to the PSH, these patients should preferentially respond to the antidepressant effects of bright light exposure when it is scheduled in the morning so as to provide a corrective phase advance and restore optimum alignment between the circadian rhythms tightly coupled to the endogenous circadian pacemaker and those rhythms that are related to the sleep/wake cycle. Recent support for the PSH has come from studies in which symptom severity was shown to correlate with the degree of circadian misalignment: it appears that a subgroup of patients are phase advanced, not phase delayed; however, the phase-delayed type is predominant in SAD and perhaps in other disorders as well, such as non-seasonal unipolar depression. It is expected that during the next few years the PSH will be tested in these and other conditions, particularly since healthy subjects appear to have more severe symptoms of sub-clinical dysphoria correlating with phase-delayed circadian misalignment; critically important will be the undertaking of treatment trials to investigate the therapeutic efficacy of morning bright light or afternoon/evening low-dose melatonin in these disorders in which symptoms are more severe as the dim light melatonin onset (DLMO) is delayed with respect to the sleep/wake cycle (non-restorative sleep should also be evaluated, as well as bipolar disorder). The possibility that some individuals (and disorders) will be of the phase-advanced type should be considered, taking into account that the correct timing of phase-resetting agents for them will be bright light scheduled in the evening and/or low-dose melatonin taken in the morning. While sleep researchers and clinicians are accustomed to phase-typing patients with circadian-rhythm sleep disorders according to the timing of sleep, phase

  5. 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. PMID:24998020

  6. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    Science.gov (United States)

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  7. The electroretinogram as a method for studying circadian rhythms in the mammalian retina

    Indian Academy of Sciences (India)

    Morven A. Cameron; Alun R. Barnard; Robert J. Lucas

    2008-12-01

    Circadian clocks are thought to regulate retinal physiology in anticipation of the large variation in environmental irradiance associated with the earth’s rotation upon its axis. In this review we discuss some of the rhythmic events that occur in the mammalian retina, and their consequences for retinal physiology. We also review methods of tracing retinal rhythmicity in vivo and highlight the electroretinogram (ERG) as a useful technique in this field. Principally, we discuss how this technique can be used as a quick and noninvasive way of assessing physiological changes that occur in the retina over the course of the day. We highlight some important recent findings facilitated by this approach and discuss its strengths and limitations.

  8. Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex

    International Nuclear Information System (INIS)

    In order to investigate diurnal variation in adenosine A1 receptors binding parameters, Bmax and Kd values of specifically bound N6-cyclohexyl-[3H]adenosine were determined in the cerebral cortex of mice that had been housed under controlled light-dark cycles for 4 weeks. Significant differences were found for Bmax values measured at 3-hr intervals across a 24-h period, with low Bmax values during the light period and high Bmax values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%. No substantial rhythm was found in the Kd values. It is suggested that the changes in the density of A1 receptors could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system

  9. 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.

  10. 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.

  11. Effect of Circadian Rhythm on Peak of Maximal Fat Oxidation on Non-Athletic Men

    Directory of Open Access Journals (Sweden)

    Hassan Darvakh

    2014-06-01

    Full Text Available 4TBackground: The aim of this4T7T 4T7Tstudy is to investigate4T7T 4T7Tthe effect of4T7T 4T7Tcircadian rhythm4T7T 4T7Ton the4T7T 4T7Tmaximal4T7T 4T7Tfat oxidation (4T7TMFO4T7T and4T7T 4T7TFATMAX4T7T in4T7T students4T7T 4T7Twithout practice. 4TMaterials and Methods: The subjects of this study4T 4Twere4T ten 4Tnon4T9T-athletes9T male students (N=10, with 4Tthe4T9T 4T9Tbody mass index4T 4Tand4T 4Tmaximal oxygen consumption4T 4Tbelow 504T%, who were 4Tselected randomly. Run test was performed4T 4Twith4T 4Tthree-minute stages and4T 4Tincreased4T 4Tspeed and slope to4T 4Texhaustion4T 4Tat4T 4T6-84T 4Tam4T , 4T5-74T 4Tpm4T ,4Tand4T 4T9.5-11 pm4T. P4Tost hoc4T7T 4T7TLSD4T7T 4T7Ttest was used for describing the4T7T 4T7Tanalytical4T7T 4T7Tfindings4T and 4Trepeated measures4T7T 4T7Tto compare4T7T 4T7Tdata4T in three times of 4Tmorning, afternoon, and night. 4TResults: The results4T7T 4T7Tgenerally showed that average4T7T of 4T7Tmaximal4T7T 4T7Tfat oxidation4T at night is more than evening and morning .4TThere4T7T 4T7Tis a4T7T 4T7Tslight4T7T 4T7Tdifference4T7T 4T7Tbetween the4T7T 4T7Tafternoon and4T morning (p=0.006, but MFO and FATMAX mean in evening is more than morning and night. 4TThere4T7T 4T7Tis a4T7T 4T7Tslight4T7T 4T7Tdifference4T7T 4T7Tbetween the4T7T 4T7Tmorning and4T7T 4T7Tnight 4T(p=0.002 4TConclusion: So it can be conclude4T7Td 4T7Tthat4T7T 4T7Tcircadian rhythm4T7T 4T7Tinfluences4T7T 4T7Tthe maximal4T7T 4T7Tfat4T7T 4T7Toxidation4T7T 4T7Tand4T7T 4T7Tfat4T7T 4T7Toxidation4T7T 4T7Tis significantly4T7T 4T7Thigher4T7T 4T7Tin the4T7T 4T7Tevening4T7T 4T7Tthan4T7T 4T7Tin the morning4T7T 4T7Tand4T7T 4T7Tit is good for fats.

  12. Cold-induced cysts of the photosynthetic dinoflagellate Lingulodinium polyedrum have an arrested circadian bioluminescence rhythm and lower levels of protein phosphorylation.

    Science.gov (United States)

    Roy, Sougata; Letourneau, Louis; Morse, David

    2014-02-01

    Dinoflagellates are microscopic, eukaryotic, and primarily marine plankton. Temporary cyst formation is a well-known physiological response of dinoflagellate cells to environmental stresses. However, the molecular underpinnings of cold-induced cyst physiology have never been described. Cultures of the photosynthetic dinoflagellate Lingulodinium polyedrum readily form temporary cysts when placed at low (8°C±1°C) temperature and excyst to form normal motile cells following a return to normal temperature (18°C±1°C). The normal circadian bioluminescence rhythm and the expected changes in Luciferin Binding Protein abundance were arrested in L. polyedrum cysts. Furthermore, after excystment, the bioluminescence rhythm initiates at a time corresponding to zeitgeber 12, independent of the time when the cells encysted. Phosphoprotein staining after two-dimensional polyacrylamide gel electrophoresis, as well as column-based phosphoprotein enrichment followed by liquid chromatography tandem mass spectrometry, showed cyst proteins are hypophosphorylated when compared with those from motile cells, with the most marked decreases found for predicted Casein Kinase2 target sites. In contrast to the phosphoproteome, the cyst proteome is not markedly different from motile cells, as assessed by two-dimensional polyacrylamide gel electrophoresis. In addition to changes in the phosphoproteome, RNA sequencing revealed that cysts show a significant decrease in the levels of 132 RNAs. Of the 42 RNAs that were identified by sequence analysis, 21 correspond to plastid-encoded gene products and 11 to nuclear-encoded cell wall/plasma membrane components. Our data are consistent with a model in which the highly reduced metabolism in cysts is achieved primarily by alterations in the phosphoproteome. The stalling of the circadian rhythm suggests temporary cysts may provide an interesting model to address the circadian system of dinoflagellates. PMID:24335505

  13. Feeding Period Restriction Alters the Expression of Peripheral Circadian Rhythm Genes without Changing Body Weight in Mice

    OpenAIRE

    Jang, Hagoon; Lee, Gung; Kong, Jinuk; Choi, Goun; Park, Yoon Jeong; Kim, Jae Bum

    2012-01-01

    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 ex...

  14. 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 disorders. PMID:27312974

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

    Directory of Open Access Journals (Sweden)

    Bridget C Lear

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

  16. Chronic Ethanol Intake Modulates Photic and Non-Photic Circadian Phase Responses in the Syrian Hamster

    OpenAIRE

    Seggio, Joseph A.; Logan, Ryan W.; Rosenwasser, Alan M.

    2007-01-01

    Chronic alcohol intake disrupts sleep and other circadian biological rhythms in both human alcoholics and in experimental animals. Recent studies from our laboratory indicate that these effects may be due, in part, to ethanol-induced alterations in fundamental properties of the circadian pacemaker. The present study explored the effects of chronic voluntary ethanol intake (25% v/v) on circadian phase responses to both photic and non-photic stimuli in Syrian hamsters. Hamsters were used in the...

  17. Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan.

    Science.gov (United States)

    Longo, Valter D; Panda, Satchidananda

    2016-06-14

    Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Upon >24 hr of fasting, humans, rodents, and other mammals enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, allows the daily fasting period to last >12 hr, thus imparting pleiotropic benefits. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting-mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both basic science and translational research are warranted to develop fasting-associated interventions into feasible, effective, and inexpensive treatments with the potential to improve healthspan. PMID:27304506

  18. COMPARATIVE STUDY OF CIRCADIAN RHYTHM OF PEAK EXPIRATORY FLOW RATE IN SOUTH INDIAN HEALTHY FEMALES AND ASTHMATIC FEMALES

    Directory of Open Access Journals (Sweden)

    Sindhura

    2016-02-01

    Full Text Available AIM AND OBJECTIVES Cross-sectional study to compare the peak expiratory flow rate with the help of “Mini-Wright” peak flow meter among females, normal healthy subjects and subjects who are asthmatics of age group 20–40 years. METHOD 60 adult females of age group 20-40 years (30-Healthy and 30-Asthmatics for whom baseline pulmonary function testing was done to differentiate normal and asthmatic. All cases were clinically examined to rule-out any obvious cardiopulmonary diseases. Subjects were provided one mini Wright’s peak expiratory flow meter, were individually trained for measuring their own PEFR in L/min and were instructed to record the readings with Wright’s portable peak flow meter at 5:00 am, 8:00 am, 11:00 am, 14:00 pm, 17:00 pm, 20:00 pm and 23:00 pm on two consecutive days. They were instructed to obtain at least three recordings at a time. RESULTS In healthy subjects it is observed that mean PEFR values at morning 5:00 hours was 276.966, which is the lowest value of day and 440.653 at evening 17:00 hour, which is the highest value of the day for this shows there is a progressive rise of about 59.1% in mean PEFR value from early morning till evening and at night 11:00 hours we got a mean value of 340.143, a decline of 22.809% when compared to peak value of the day (17:00 hours. In Asthmatic, early morning mean PEFR value at 5:00 hours was 157.888, which is lowest value of the day and 369.774 at evening at 17:00 hours, which is the highest mean PEFR value of the day. There is a significant rise of about 134.2002% in the mean PEFR value from early morning till evening and at night 11:00 hours we got a mean value of 197.666, a decline of 46.5441% when compared to peak value of the day (17:00 hours. CONCLUSION It is seen that though the circadian rhythm in asthmatics follows a similar pattern, i.e. PEFR dip in morning and PEFR peak in late afternoon, but the swing of PEFR from the mean value is more than in normal subjects. A

  19. 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

    OpenAIRE

    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 neurolog...

  20. Circadian Misalignment and Health

    OpenAIRE

    Baron, Kelly Glazer; Reid, Kathryn J.

    2014-01-01

    Circadian rhythms are near 24-hour patterns of physiology and behavior that are present independent of external cues including hormones, body temperature, mood, and sleep propensity. The term “circadian misalignment” describes a variety of circumstances, such as inappropriately timed sleep and wake, misalignment of sleep/wake with feeding rhythms, or misaligned central and peripheral rhythms. The predominance of early research focused on misalignment of sleep to the biological night. However,...

  1. Circadian genes differentially affect tolerance to ethanol in Drosophila

    Science.gov (United States)

    Pohl, Jascha B.; Ghezzi, Alfredo; Lew, Linda K.; Robles, Roseanna B.; Cormack, Lawrence; Atkinson, Nigel S.

    2016-01-01

    Background There is a strong relationship between circadian rhythms and ethanol responses. Ethanol consumption has been shown to disrupt physiological and behavioral circadian rhythms in mammals (Spanagel et al., 2005b). The Drosophila central circadian pacemaker is composed of proteins encoded by the per, tim, cyc, and Clk genes. Using Drosophila mutant analysis we asked whether these central components of the circadian clock make the equivalent contribution towards ethanol tolerance and whether rhythmicity itself is necessary for tolerance. Methods We tested flies carrying mutations in core clock genes for the capacity to acquire ethanol tolerance. Tolerance was assayed by comparing the sedation curves of populations during their first and second sedation. Animals that had acquired tolerance sedated more slowly. Movement was also monitored as the flies breathe the ethanol vapor to determine if other facets of the ethanol response were affected by the mutations. Gas chromatography was used to measure internal ethanol concentration. Constant light was used to non-genetically destabilize the PER and TIM proteins. Results A group of circadian mutations, all of which eliminate circadian rhythms, do not disrupt tolerance identically. Mutations in per, tim, and cyc completely block tolerance. However, a mutation in Clk does not interfere with tolerance. Constant light also disrupts the capacity to acquire tolerance. These lines did not differ in ethanol absorption. Conclusions Mutations affecting different parts of the intracellular circadian clock can block the capacity to acquire rapid ethanol tolerance. However, the role of circadian genes in ethanol tolerance is independent of their role in producing circadian rhythmicity. The interference in the capacity to acquire ethanol tolerance by some circadian mutations is not merely a downstream effect of a nonfunctional circadian clock, instead these circadian genes play an independent role in ethanol tolerance. PMID

  2. Cardiac atrial circadian rhythms in PERIOD2::LUCIFERASE and per1:luc mice: amplitude and phase responses to glucocorticoid signaling and medium treatment.

    Directory of Open Access Journals (Sweden)

    Daan R van der Veen

    Full Text Available Circadian rhythms in cardiac function are apparent in e.g., blood pressure, heart rate, and acute adverse cardiac events. A circadian clock in heart tissue has been identified, but entrainment pathways of this clock are still unclear. We cultured tissues of mice carrying bioluminescence reporters of the core clock genes, period 1 or 2 (per1(luc or PER2(LUC and compared in vitro responses of atrium to treatment with medium and a synthetic glucocorticoid (dexamethasone [DEX] to that of the suprachiasmatic nucleus (SCN and liver. We observed that PER2(LUC, but not per1(luc is rhythmic in atrial tissue, while both per1(luc and PER2(LUC exhibit rhythmicity in other cultured tissues. In contrast to the SCN and liver, both per1(luc and PER2(LUC bioluminescence amplitudes were increased in response to DEX treatment, and the PER2(LUC amplitude response was dependent on the time of treatment. Large phase-shift responses to both medium and DEX treatments were observed in the atrium, and phase responses to medium treatment were not attributed to serum content but the treatment procedure itself. The phase-response curves of atrium to both DEX and medium treatments were found to be different to the liver. Moreover, the time of day of the culturing procedure itself influenced the phase of the circadian clock in each of the cultured tissues, but the magnitude of this response was uniquely large in atrial tissue. The current data describe novel entrainment signals for the atrial circadian clock and specifically highlight entrainment by mechanical treatment, an intriguing observation considering the mechanical nature of cardiac tissue.

  3. Cardiac Atrial Circadian Rhythms in PERIOD2::LUCIFERASE and per1:luc Mice: Amplitude and Phase Responses to Glucocorticoid Signaling and Medium Treatment

    Science.gov (United States)

    Xi, Yang; Li, Lei; Duffield, Giles E.

    2012-01-01

    Circadian rhythms in cardiac function are apparent in e.g., blood pressure, heart rate, and acute adverse cardiac events. A circadian clock in heart tissue has been identified, but entrainment pathways of this clock are still unclear. We cultured tissues of mice carrying bioluminescence reporters of the core clock genes, period 1 or 2 (per1luc or PER2LUC) and compared in vitro responses of atrium to treatment with medium and a synthetic glucocorticoid (dexamethasone [DEX]) to that of the suprachiasmatic nucleus (SCN) and liver. We observed that PER2LUC, but not per1luc is rhythmic in atrial tissue, while both per1luc and PER2LUC exhibit rhythmicity in other cultured tissues. In contrast to the SCN and liver, both per1luc and PER2LUC bioluminescence amplitudes were increased in response to DEX treatment, and the PER2LUC amplitude response was dependent on the time of treatment. Large phase-shift responses to both medium and DEX treatments were observed in the atrium, and phase responses to medium treatment were not attributed to serum content but the treatment procedure itself. The phase-response curves of atrium to both DEX and medium treatments were found to be different to the liver. Moreover, the time of day of the culturing procedure itself influenced the phase of the circadian clock in each of the cultured tissues, but the magnitude of this response was uniquely large in atrial tissue. The current data describe novel entrainment signals for the atrial circadian clock and specifically highlight entrainment by mechanical treatment, an intriguing observation considering the mechanical nature of cardiac tissue. PMID:23110090

  4. Circadian rhythms of myocardial ischemia and chronotherapy%心肌缺血的昼夜节律性与时辰疗法

    Institute of Scientific and Technical Information of China (English)

    张恩晖; 王海峰; 陈莉; 刘佃花; 于剑光; 蔡国君

    2016-01-01

    The occurrence of the clinical manifestations of myocardial ischemia shows clear circadian rhythmicity ,and they are unevenly distributed during the 24 h with higher morbidity during the initial hours of the daily activity span and in the late afternoon or early evening .Such temporal patterns result from circadian rhythms in pathophysiological mechanisms plus cyclic environmental stressors that trigger these clinical events .β‐receptor antagonist medications ,oral nitrate ,and calcium channel blocker have been shown to be influenced by the circadian time of their administration .Here we briefly review the char‐acteristics of circadian rhythmicity in MI ,the pathophysiological mechanisms as well as the current chronotherapy ,and then discuss the future treatment strategies .%临床上心肌缺血(M I )的发作频率伴有昼夜变化,在清晨和傍晚是发病高峰期。产生这一现象主要是受到机体病理生理机制的昼夜节律性以及外界的环境因素影响。目前β‐受体阻断剂、硝酸酯类以及钙通道阻滞剂等药物的治疗作用已经被证明受到机体昼夜节律的影响。因此,笔者对MI发作的昼夜节律特点、病理生理机制以及目前临床上的时辰疗法进行综述,并对未来的治疗策略进行探讨。

  5. Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior

    OpenAIRE

    Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B.; Singewald, Nicolas; Pollak, Daniela D.

    2015-01-01

    ABSTRACT Introduction Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs – also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. Materials and methods The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular leve...

  6. Animal clocks: when science meets nature

    OpenAIRE

    Kronfeld-Schor, Noga; Bloch, Guy; Schwartz, William J.

    2013-01-01

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian ‘clock’), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day–night cycle. Our knowledge of the circadian system of animals at the molecular, cellular, tissue and organismal levels is remarkable, and we are beginning to understand how each of these levels contributes to the emergent properties and increased complexity of th...

  7. 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. PMID:19110891

  8. Effect of sympathetic denervation of the pineal gland on maternal co-ordination of the circadian rhythm of alpha-amylase in parotid gland from young rats.

    Science.gov (United States)

    Bellavía, S L; Sanz, E G; Gallará, R V; Carpentieri, A; Vermouth, N T

    1993-12-01

    Twenty-five-day-old rats maintained in constant darkness since birth and born from mothers kept in the dark since the 14th day of pregnancy showed a circadian rhythm of alpha-amylase content in parotid glands, which may be explained by a mechanism of maternal co-ordination. Rats in the same conditions, except that their mothers had been submitted to bilateral excision of the superior cervical ganglia 30 days before mating, did not show diurnal variations of alpha-amylase activity in the parotid glands. When ganglionectomized mothers were treated with a daily dose of melatonin (1 mg/kg) from the 14th day of gestation up to the 10th day of lactation, their litters showed significant diurnal variations of amylase in the parotid glands, suggesting a role of the maternal pineal gland in the maternal-fetal and/or maternal-neonatal transfer of photoperiodic information. PMID:8141675

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

    Science.gov (United States)

    Nishino, H.

    1977-01-01

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

  10. Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant rate.

    Science.gov (United States)

    Caussanel, J P; Lévi, F; Brienza, S; Misset, J L; Itzhaki, M; Adam, R; Milano, G; Hecquet, B; Mathé, G

    1990-06-20

    The toxic effects and tissue uptake of both cisplatin and oxaliplatin--[(1R, 2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O']platinum--were previously shown to vary similarly according to dosing time in mice. A 4-hour infusion of cisplatin resulted in fewer side effects and allowed administration of higher doses at 16 hours than at 4 hours in patients with cancer. We hypothesized that the continuous venous infusion of oxaliplatin for 5 days would be less toxic and would deliver a higher dose to the patient if the drug were infused at a circadian rhythm-modulated rate (peak at 16 hr; schedule B) rather than at a constant rate (schedule A). We tested this hypothesis in a randomized phase I trial. We escalated the dose of oxaliplatin to the patient by 25 mg/m2 per course. Courses were repeated every 3 weeks. An external, multichannel, programmable-in-time pump was used for the infusions. Toxicity was assessable for 94 courses in 23 patients (12 patients with breast carcinoma, nine with hepatocellular carcinoma, and two with cholangiocarcinoma). The incidence of neutropenia of World Health Organization grades II-IV and the incidence of distal paresthesias were 10 or more times higher (P less than .05) with schedule A than with schedule B. In addition, vomiting was 55% higher (P = .15) with schedule A than with schedule B. Furthermore, with schedule B, the mean dose of oxaliplatin (P less than .001) and its maximum tolerated dose (P = .06) could be increased by 15% over those doses with schedule A. An objective response was achieved in two of the 12 patients with previously treated breast cancer. We recommend that the dose of oxaliplatin for phase II trials be 175 mg/m2, delivered according to the circadian rhythm-modulated rate. PMID:2348469

  11. 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.

    Directory of Open Access Journals (Sweden)

    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

  12. 口腔鳞状细胞癌体内生长的昼夜生物节律特征%Circadian rhythm of oral squamous cell carcinoma in vivo

    Institute of Scientific and Technical Information of China (English)

    杨凯; 赵宁波; 陈丹; 赵丹; 唐洪; 赵春蓉

    2013-01-01

    目的:探讨口腔鳞状细胞癌体内生长的昼夜生物节律改变特征.方法:32只裸鼠置于12h光照、12h黑暗交替的环境中,将人颊鳞状细胞癌BcaCD885细胞接种于裸鼠颊部,建立颊鳞状细胞癌模型,3周后在24h内,按灯亮后4、10、16、22h4个时间点分别处死8只裸鼠时间以开灯后的小时数为参考(hours after light onset,HALO),即4HALO、10HALO、16HALO、22HALO.取出肿瘤测量体积,用流式细胞仪测定肿瘤细胞的增殖指数(proliferation index,PI)和凋亡指数(apoptosis index,AI).用余弦分析法检验肿瘤体积、肿瘤细胞PI和AI是否具有昼夜节律性,用方差分析各指标在4个时间点差异的显著性.结果:肿瘤体积和肿瘤细胞PI具有明显的昼夜节律变化特征,肿瘤体积在不同时间点的差异具有统计学意义,肿瘤体积的峰值和谷值分别出现在3.23HALO、15.23HALO,肿瘤细胞PI的峰值和谷值分别出现在6.60HALO、18.1 6HALO.肿瘤细胞的AI无昼夜节律性,但在不同时间点差异具有统计学意义.结论:体内生长的口腔鳞状细胞癌的细胞增殖活性和肿瘤体积具有昼夜节律变化特点,肿瘤体积和细胞AI在昼夜不同时间点差异变化较大.%Objective:To investigate the change of circadian rhythm in oral squamous cell carcinoma(OSCC)in vivo.Methods:Totally 32 nude mice were maintained in 12 h light alternating with 12 h dark.Human oral squamous cell carcinoma cell line BcaCD885 was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model.Mice were sacrificed at 4 different time points 4,10,16,22 h(4 hours after light onset(HALO),10HALO,16HALO,22HALO) of 24 h 3 weeks after transplantation,with 8 mice of each group.Tumors were dissected away and tumor sizes were measured.Tumor cell proliferation index(PI) and apoptosis index(AI) were determined by flow cytometry.Cosine analysis was used to detect circadian rhythm of tumor size,tumor cell PI and AI.Variance of

  13. Period gene expression in relation to seasonality and circadian rhythms in the linden bug,Pyrrhocoris apterus (Heteroptera)

    Czech Academy of Sciences Publication Activity Database

    Hodková, Magdalena; Syrová, Zdeňka; Doležel, David; Šauman, Ivo

    2003-01-01

    Roč. 100, - (2003), s. 267-273. ISSN 1210-5759 R&D Projects: GA ČR GA206/02/0900; GA ČR GA204/01/0404 Institutional research plan: CEZ:AV0Z5007907 Keywords : circadian clock * per mRNA * photoperiod Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.741, year: 2003

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

    OpenAIRE

    Banks, G.; Heise, I; Starbuck, B; Osborne, T.; Wisby, L; De Potter, P; Jackson, IJ; Foster, RG; Peirson, SN; Nolan, PM

    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 ...

  15. 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; ...

  16. Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila.

    Science.gov (United States)

    De Nobrega, Aliza K; Lyons, Lisa C

    2016-04-01

    Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes makes Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibited rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the loss-of-righting reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrated circadian rhythms in the loss-of-righting reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol

  17. Development of a Configurable Growth Chamber with a Computer Vision System to Study Circadian Rhythm in Plants

    Directory of Open Access Journals (Sweden)

    Marcos Egea-Cortines

    2012-11-01

    Full Text Available Plant development is the result of an endogenous morphogenetic program that integrates environmental signals. The so-called circadian clock is a set of genes that integrates environmental inputs into an internal pacing system that gates growth and other outputs. Study of circadian growth responses requires high sampling rates to detect changes in growth and avoid aliasing. We have developed a flexible configurable growth chamber comprising a computer vision system that allows sampling rates ranging between one image per 30 s to hours/days. The vision system has a controlled illumination system, which allows the user to set up different configurations. The illumination system used emits a combination of wavelengths ensuring the optimal growth of species under analysis. In order to obtain high contrast of captured images, the capture system is composed of two CCD cameras, for day and night periods. Depending on the sample type, a flexible image processing software calculates different parameters based on geometric calculations. As a proof of concept we tested the system in three different plant tissues, growth of petunia- and snapdragon (Antirrhinum majus flowers and of cladodes from the cactus Opuntia ficus-indica. We found that petunia flowers grow at a steady pace and display a strong growth increase in the early morning, whereas Opuntia cladode growth turned out not to follow a circadian growth pattern under the growth conditions imposed. Furthermore we were able to identify a decoupling of increase in area and length indicating that two independent growth processes are responsible for the final size and shape of the cladode.

  18. Deletion of the secretory vesicle proteins IA-2 and IA-2β disrupts circadian rhythms of cardiovascular and physical activity

    OpenAIRE

    Kim, Soo Mi; Power, Andrea; Brown, Timothy M.; Constance, Cara M.; Coon, Steven L.; Nishimura, Takuya; Hirai, Hiroki; Cai, Tao; Eisner, Christoph; David R Weaver; Piggins, Hugh D.; Klein, David C.; Schnermann, Jürgen; Notkins, Abner L.

    2009-01-01

    Targeted deletion of IA-2 and IA-2β, major autoantigens in type 1 diabetes and transmembrane secretory vesicle proteins, results in impaired secretion of hormones and neurotransmitters. In the present study, we evaluated the effect of these deletions on daily rhythms in blood pressure, heart rate, core body temperature, and spontaneous physical and neuronal activity. We found that deletion of both IA-2 and IA-2β profoundly disrupts the usual diurnal variation of each of these parameters, wher...

  19. Postoperative circadian disturbances

    DEFF Research Database (Denmark)

    Gögenur, Ismail

    2010-01-01

    postoperative recovery 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...... after major surgery was increased on the fourth day after surgery and the total excretion of AMT6s in urine was correlated to sleep efficiency and wake time after sleep onset, but was not correlated to the occurrence of postoperative cognitive dysfunction. We could only prove an effect of melatonin...... rhythm, autonomic nervous system tone, myocardial ischaemia and activity rhythm after surgery. Correlation exists between circadian rhythm parameters and measures of postoperative sleep quality and recovery. However, oral melatonin treatment in the first three nights after surgery, cannot yet be...

  20. Egg-laying rhythm in Drosophila melanogaster

    Indian Academy of Sciences (India)

    T. Manjunatha; Shantala Hari Dass; Vijay Kumar Sharma

    2008-12-01

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

  1. Effects of Exposure to Extremely Low Frequency Electro-magnetic Fields on Circadian Rhythms and Distribution of Some Leukocyte Differentiation Antigens in Dairy Cows

    Institute of Scientific and Technical Information of China (English)

    CALOGERO STELLETTA; PAOLA DE NARDO; FRANCESCO SANTIN; GIUSEPPE BASSO; BARBARA MICHIELOTTO; GIUSEPPE PICCIONE; MASSIMO MORGANTE

    2007-01-01

    Objective To investigate the effects of extremely low frequency magnetic and electric fields (ELFEMFs) emitted from 380 kV transmission lines on some leukocyte differentiation antigens in dairy cows. Methods The study was carried out in 5 cows exposed to 1.98-3.28 μT of ELFEMFs and in 5 control cows exposed to 0.2-0.7 μT of ELFEMFs. Following haematological and immunologic parameters were measured in both groups: WBC, CD45R, CD6, CI4, CD8, CD21, and CD1 1B leukocyte antigen expression. Results Some of the haematological and immunologic parameters under investigation were similar in both groups. However, CD8 (T lymphocyte surface antigen) was higher in the exposed group (1.35 ± 0.120 vs 0.50 ± 0.14 × 103/mL). Furthermore, the CD4/CD8 ratio (0.84 ± 0.05 and 2.19 ± 0.16 for exposed and not exposed cows respectively) and circadian rhythm were different between the two groups. Conclusion Exposure to ELFEMFs is responsible of the abnormal temporal variations and distribution of some haematological and immunological parameters in dairy cows.

  2. Sex difference in the near-24-hour intrinsic period of the human circadian timing system

    OpenAIRE

    Duffy, Jeanne F.; Cain, Sean W.; Chang, Anne-Marie; Phillips, Andrew J. K.; Münch, Mirjam Y.; Gronfier, Claude; Wyatt, James K.; Dijk, Derk-Jan; Wright, Kenneth P.; Czeisler, Charles A.

    2011-01-01

    The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in cir...

  3. Ritmo circadiano y variaciones temporales en el paro cardiaco súbito extrahospitalario Circadian rhythm and time variations in out-hospital sudden cardiac arrest

    Directory of Open Access Journals (Sweden)

    J.B. López-Messa

    2012-09-01

    transform and Cosinor testing. Results: We studied 1286 cases reported between January 2007 and June 2008. Statistically significant differences were observed in terms of younger age, higher incidence in the victim's home, and greater frequency of family-cohabiting persons as witnesses in the period between 0 and 8hours. Chronobiological analysis found daily rhythm (circadian with acrophase at 11.16h (p<0.001 and weekly rhythm (circaseptan with acrophase on Wednesday (p<0.05. The median alert time-care time interval and emergency team activation time-care time were 11.7min and 8.0min, respectively, without differences between periods. Conclusions: We have demonstrated the presence of a daily rhythm of emergence of OHCA with a morning peak and a weekly rhythm with a peak on Wednesdays. These results can guide the planning of resources and improvements in response in certain time periods.

  4. The sublethal effects of endosulfan on the circadian rhythms and locomotor activity of two sympatric parasitoid species.

    Science.gov (United States)

    Delpuech, Jean-Marie; Bussod, Sophie; Amar, Aurelien

    2015-08-01

    The organochlorine insecticide endosulfan is dispersed worldwide and significantly contributes to environmental pollution. It is an antagonist of the neurotransmitter gamma-aminobutyric acid (GABA), which is also indirectly involved in photoperiodic time measurement. In this study, we show that endosulfan at a dose as low as LC 0.1 modified the rhythm of locomotor activity of two sympatric parasitoid species, Leptopilina boulardi and Leptopilina heterotoma. The insecticide strongly increased the nocturnal activity of both species and synchronized their diurnal activity; these activities were not synchronized under control conditions. Parasitoids are important species in ecosystems because they control the populations of other insects. In this paper, we discuss the possible consequences of these sublethal effects and highlight the importance of such effects in evaluating the consequences of environmental pollution due to insecticides. PMID:25898969

  5. 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.

  6. Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in [3H]-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

    International Nuclear Information System (INIS)

    Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [3H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude

  7. 脑卒中病人睡眠-觉醒昼夜节律紊乱的影像学研究%Imaging study of sleep-wake circadian rhythm disorder in stroke patients

    Institute of Scientific and Technical Information of China (English)

    世全; 段劲峰; 冯由军

    2016-01-01

    目的:探讨睡眠-觉醒昼夜节律紊乱脑卒中患者的脑结构改变,了解生物钟系统与其他脑组织之间可能的联系。方法收集存在睡眠-觉醒昼夜节律紊乱脑卒中患者(观察组)21例和无睡眠-觉醒昼夜节律紊乱脑卒中病人(对照组)92例影像学资料,比较两者之间的差别,寻找最可能引起睡眠-觉醒昼夜节律紊乱的脑区损害。结果通过比较发现,位于侧脑室枕角前部、丘脑外侧、岛叶后方、颞叶内侧的脑区脑组织损害可能与睡眠-觉醒昼夜节律紊乱有关。结论脑卒中病人中睡眠-觉醒昼夜节律紊乱的出现可能与特定的脑区损害有关。%Objective To analysis the brain structural changes of sleep-wake circadian rhythm disorders in the stroke pa-tients,in order to understand the possible links between the circadian clock system and other brain tissue.Methods Retrospec-tive analysis of imaging data of stroke patients was performed,who were divided into study group composed of 21 cases with sleep-wake circadian rhythm disorders and the control group made up of 92 cases without this disorder,comparing the data be-tween two groups and finding the possible damaged brain areas causing this disorder.Result We found that the affected brain regions located in front of the lateral ventricle occipital horn,the lateral of the hypothalamus,the rear of the insular cortex,the medial of the temporal lobe may have some relationship with sleep-wake circadian rhythm disorders in the stroke patients.Con-clusion The sleep-wake circadian rhythm disorders in the stroke patients may be related to the specific damaged brain regions.

  8. 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

  9. Circadian Clocks, Stress, and Immunity

    Science.gov (United States)

    Dumbell, Rebecca; Matveeva, Olga; Oster, Henrik

    2016-01-01

    In mammals, molecular circadian clocks are present in most cells of the body, and this circadian network plays an important role in synchronizing physiological processes and behaviors to the appropriate time of day. The hypothalamic–pituitary–adrenal endocrine axis regulates the response to acute and chronic stress, acting through its final effectors – glucocorticoids – released from the adrenal cortex. Glucocorticoid secretion, characterized by its circadian rhythm, has an important role in synchronizing peripheral clocks and rhythms downstream of the master circadian pacemaker in the suprachiasmatic nucleus. Finally, glucocorticoids are powerfully anti-inflammatory, and recent work has implicated the circadian clock in various aspects and cells of the immune system, suggesting a tight interplay of stress and circadian systems in the regulation of immunity. This mini-review summarizes our current understanding of the role of the circadian clock network in both the HPA axis and the immune system, and discusses their interactions. PMID:27199894

  10. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Science.gov (United States)

    Udoh, Uduak S.; Valcin, Jennifer A.; Gamble, Karen L.; Bailey, Shannon M.

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases. PMID:26473939

  11. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  12. The relationship between circadian disruption and the development of metabolic syndrome and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Karatsoreos IN

    2014-12-01

    Full Text Available Ilia N Karatsoreos Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA Abstract: Circadian (daily rhythms are pervasive in nature, and expressed in nearly every behavioral and physiological process. In mammals, circadian rhythms are regulated by the master brain clock in the suprachiasmatic nucleus of the hypothalamus that coordinates the activity of “peripheral” oscillators throughout the brain and body. While much progress has been made in understanding the basic functioning of the circadian clock at the level of genes, molecules, and cells, our understanding of how these clocks interact with complex systems is still in its infancy. Much recent work has focused on the role of circadian clocks in the etiology of disorders as diverse as cancer, diabetes, and obesity. Given the rapid rise in obesity, and the economic costs involved in treating its associated cardiometabolic disorders such as heart disease and diabetes mellitus, understanding the development of obesity and metabolic dysregulation is crucial. Significant epidemiological data indicate a role for circadian rhythms in metabolic disorders. Shift workers have a higher incidence of obesity and diabetes, and laboratory studies in humans show misaligning sleep and the circadian clock leads to hyperinsulinemia. In animal models, body-wide “clock gene” knockout mice are prone to obesity. Further, disrupting the circadian clock by manipulating the light–dark cycle can result in metabolic dysregulation and development of obesity. At the molecular level, elegant studies have shown that targeted disruption of the genetic circadian clock in the pancreas leads to diabetes, highlighting the fact that the circadian clock is directly coupled to metabolism at the cellular level. Keywords: glucose, metabolism, sleep, rhythms, obesity

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

    Institute of Scientific and Technical Information of China (English)

    党荣理; 董言德; 郑重; 郭晓霞; 张映梅; 张桂林; 赵彤言

    2011-01-01

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

  14. 年龄相关性白内障对老年人生物节律的影响%Impact of age-related cataract on regulation of circadian rhythm in elderly

    Institute of Scientific and Technical Information of China (English)

    王旻舒; 刘梦媛; 董栩然; 王薇

    2016-01-01

    This review presented an introduction of the visual pathway related circadian rhythm regulation system: the intrinsically photosensitive retinal ganglion cells-suprachiasmatic nucleus-pineal gland-melatonin axis, and discussed the impact of light with different wave length and irradiation received by retina on circadian rhythm and sleep habit.A hypothesis was proposed consequently that the high morbidity of sleep disorder in elderly might be partially attributable to the long-term blue light blocking status induced by age-related cataract.A number of relative literatures were reviewed and a novel research direction was advanced on improving circadian rhythm and sleep condition in elderly based on the current knowledge.%通过介绍视觉通路相关的生物节律调节系统,即内在光敏视网膜神经节细胞-下丘脑视交叉上核-松果体-褪黑素调节轴,探讨不同波长和强度的光线作用于视网膜,继而对生物节律和睡眠情况的影响,由此提出老年人睡眠障碍的发生率较高的原因之一可能与年龄相关性白内障造成的长期蓝光屏蔽有关.通过回顾相关文献,为改善老年人生物节律和睡眠状况提供新的研究方向.

  15. Cardiovascular tissues contain independent circadian clocks

    Science.gov (United States)

    Davidson, A. J.; London, B.; Block, G. D.; Menaker, M.

    2005-01-01

    Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

  16. Die circadiane Uhr im Immunsystem

    OpenAIRE

    Keller, Maren

    2010-01-01

    Daily rhythms of a variety of immunological phenomena and functions are well known, but so far they have largely been neglected. Examples of daily rhythms in the immune system are: circadian differences in susceptibility to bacterial infection and daily variations in the symptoms of diseases such as rheumatoid arthritis or asthma. Therefore, it is very important for clinical diagnosis and pharmacological therapies to elucidate the connections between the circadian clock and the immune system....

  17. Biological Rhythms and Preeclampsia

    OpenAIRE

    Ditisheim, Agnès J.; Dibner, Charna; Philippe, Jacques; Pechère-Bertschi, Antoinette

    2013-01-01

    The impact of impaired circadian rhythm on health has been widely studied in shift workers and trans-meridian travelers. A part from its correlation with sleep and mood disorders, biological rhythm impairment is a recognized risk factor for cardiovascular diseases and breast cancer. Preeclampsia is a major public health issue, associated with a significant maternal and fetal morbidity and mortality worldwide. While the risks factors for this condition such as obesity, diabetes, pre-existing h...

  18. Effects of plasma ghrelin, obestatin, and ghrelin/obestatin ratio on blood pressure circadian rhythms in patients with obstructive sleep apnea syndrome

    Institute of Scientific and Technical Information of China (English)

    Liu Weiying; Yue Hongmei; Zhang Jiabin; Pu Jiayuan; Yu Qin

    2014-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease.Ghrelin and obestatin are two peptides from the same source but have opposite roles.Both of them can affect feeding and regulate vascular tune.The aim of this study was to investigate the relationship between plasma ghrelin,obestatin,the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.Methods This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group),30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group).Polysomnography (PSG) was performed in the OSAS group and over-weight group.Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring.The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).Results Plasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P <0.05).Plasma obestatin levels were lower in the over-weight group and OSAS group,but there was no significant difference among the three groups.The blood pressure in OSAS patients was higher,and there was a significant difference in all blood pressure parameters compared to the control group,and in the daytime average diastolic blood pressure (DBP),nocturnal average systolic blood pressure (SBP) and DBP,DBP variability values as compared to over-weight subjects.Furthermore,there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P <0.01).Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters.In contrast,the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P <0.05),as well as a

  19. Effects of Gravity on Insect Circadian Rhythmicity

    Science.gov (United States)

    Hoban-Higgins, Tana M.

    2000-01-01

    Circadian rhythms - endogenous daily rhythmic fluctuations in virtually all characteristics of life - are generated and coordinated by the circadian timing system (CTS). The CTS is synchronized to the external 24-hour day by time cues such as the light/dark cycle. In an environment without time cues, the length of an animal's day is determined by the period of its internal pacemaker (tau) and the animal is said to be free-running. All life on earth evolved under the solar day; the CTS exists as an adaptation that allows organisms to anticipate and to prepare for rhythmic environmental fluctuations. All life on earth also evolved under the force of earth's gravitational environment. While it is therefore not surprising that changes in the lighting environment affect the CTS, it is surprising that changes in the gravitational environment would do so. However, recent data from one of our laboratories using the brn-3.1 knockout mouse revealed that this model, which lacks the sensory receptor hair cells within the neurovestibular system, does not respond to exposure to a hyperdynamic environment in the same fashion as normal mice. The brn-3.1 mice did not show the expected suppression of circadian rhythmicity shown by control mice exposed to 2G. Exposure to altered ambient force environments affects the amplitude, mean and timing of circadian rhythms in species from unicellular organisms to man. In addition, there is a circadian influence on the homeostatic response to acute 2G acceleration and pulses of 2G can act as a time cue, synchronizing the CTS. This is of significance because maintenance of internal and external temporal coordination is critical for normal physiological and psychological function. Typically, during adaptation to an increased gravitational environment (+G), an initial acute reaction is followed by adaptation and, eventually, a new steady state (14-16), which can take weeks to months to establish. Until the development of space stations, exposure

  20. Chromatin Dynamics of Circadian Transcription

    OpenAIRE

    Aguilar-Arnal, Lorena; Sassone-Corsi, Paolo

    2015-01-01

    The molecular circadian clock orchestrates the daily cyclical expression of thousands of genes. Disruption of this transcriptional program leads to a variety of pathologies, including insomnia, depression and metabolic disorders. Circadian rhythms in gene expression rely on specific chromatin transitions which are ultimately coordinated by the molecular clock. As a consequence, a highly plastic and dynamic circadian epigenome can be delineated across different tissues and cell types. Intrigui...

  1. Visual impairment and circadiam rhythm disorders

    OpenAIRE

    Lockley, Steven W.; Arendt, Josephine; Skene, Debra J.

    2007-01-01

    Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal “pacemaker” in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment Sighted individual...

  2. Endocrine Effects of Circadian Disruption.

    Science.gov (United States)

    Bedrosian, Tracy A; Fonken, Laura K; Nelson, Randy J

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems. PMID:26208951

  3. The transcription factor Runx2 is under circadian control in the suprachiasmatic nucleus and functions in the control of rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    Meghan E Reale

    Full Text Available Runx2, a member of the family of runt-related transcription factors, is rhythmically expressed in bone and may be involved in circadian rhythms in bone homeostasis and osteogenesis. Runx2 is also expressed in the brain, but its function is unknown. We tested the hypothesis that in the brain, Runx2 may interact with clock-controlled genes to regulate circadian rhythms in behavior. First, we demonstrated diurnal and circadian rhythms in the expression of Runx2 in the mouse brain. Expression of Runx2 mRNA and protein mirrored that of the core clock genes, Period1 and Period2, in the suprachiasmatic nucleus (SCN, the paraventricular nucleus and the olfactory bulb. The rhythm of Runx2 expression was eliminated in the SCN of Bmal1(-/- mice. Moreover, by crossbreeding mPer2(Luc mice with Runx2(+/- mice and recording bioluminescence rhythms, a significant lengthening of the period of rhythms was detected in cultured SCN of Runx2(-/- animals compared to either Runx2(+/- or Runx2(+/+ mice. Behavioral analyses of Runx2 mutant mice revealed that Runx2(+/- animals displayed a significantly lengthened free-running period of running wheel activity compared to Runx2(+/+ littermates. Taken together, these findings provide evidence for clock gene-mediated rhythmic expression of Runx2, and its functional role in regulating circadian period at the level of the SCN and behavior.

  4. Shift work and circadian dysregulation of reproduction

    Directory of Open Access Journals (Sweden)

    Karen L. Gamble

    2013-08-01

    Full Text Available Health impairments, including reproductive issues, are associated with working nights or rotating shifts. For example, shift work has been associated with an increased risk of irregular menstrual cycles, endometriosis, infertility, miscarriage, low birth weight or pre-term delivery, and reduced incidence of breastfeeding. Based on what is known about circadian regulation of endocrine rhythms in rodents (and much less in humans, the circadian clock is an integral regulatory part of the reproductive system. When this 24-h program is disordered by environmental perturbation (such as shift work or genetic alterations, the endocrine system can be impaired. The purpose of this review is to explore the hypothesis that misalignment of reproductive hormones with the environmental light-dark cycle and/or sleep wake rhythms can disrupt menstrual cycles, pregnancy, and parturition. We highlight the role of the circadian clock in regulating human reproductive physiology and shift work-induced pathology within each step of the reproductive axis while exploring potential mechanisms from the animal model literature. In addition to documenting the reproductive hazards of shift work, we also point out important gaps in our knowledge as critical areas for future investigation. For example, future studies should examine whether forced desynchronization disrupts gonadotropin secretion rhythms and whether there are sleep/wake schedules that are better or worse for the adaptation of the reproductive system to shift work. These studies are necessary in order to define not only whether or not shift-work induced circadian misalignment impairs reproductive capacity, but also to identify strategies for the future that can minimize this desynchronization.

  5. Shift work and circadian dysregulation of reproduction.

    Science.gov (United States)

    Gamble, Karen L; Resuehr, David; Johnson, Carl Hirschie

    2013-01-01

    Health impairments, including reproductive issues, are associated with working nights or rotating shifts. For example, shift work has been associated with an increased risk of irregular menstrual cycles, endometriosis, infertility, miscarriage, low birth weight or pre-term delivery, and reduced incidence of breastfeeding. Based on what is known about circadian regulation of endocrine rhythms in rodents (and much less in humans), the circadian clock is an integral regulatory part of the reproductive system. When this 24-h program is disordered by environmental perturbation (such as shift work) or genetic alterations, the endocrine system can be impaired. The purpose of this review is to explore the hypothesis that misalignment of reproductive hormones with the environmental light-dark cycle and/or sleep-wake rhythms can disrupt menstrual cycles, pregnancy, and parturition. We highlight the role of the circadian clock in regulating human reproductive physiology and shift work-induced pathology within each step of the reproductive axis while exploring potential mechanisms from the animal model literature. In addition to documenting the reproductive hazards of shift work, we also point out important gaps in our knowledge as critical areas for future investigation. For example, future studies should examine whether forced desynchronization disrupts gonadotropin secretion rhythms and whether there are sleep/wake schedules that are better or worse for the adaptation of the reproductive system to shift work. These studies are necessary in order to define not only whether or not shift work-induced circadian misalignment impairs reproductive capacity, but also to identify strategies for the future that can minimize this desynchronization. PMID:23966978

  6. Development of circadian oscillators in neurosphere cultures during adult neurogenesis.

    Directory of Open Access Journals (Sweden)

    Astha Malik

    Full Text Available Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ, a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in individual spheres, and cell types were characterized by confocal immunofluorescence microscopy at early and late developmental stages in vitro. Circadian rhythms were observed in neurospheres induced to differentiate into neurons or glia, and rhythms emerged within 3-4 days as differentiation proceeded, suggesting that the neural stem cell state suppresses the functioning of the circadian clock. Evidence was also provided that neural stem progenitor cells derived from the SVZ of adult mice are self-sufficient clock cells capable of producing a circadian rhythm without input from known circadian pacemakers of the organism. Expression of mPer1 occurred in high frequency oscillations before circadian rhythms were detected, which may represent a role for this circadian clock gene in the fast cycling of gene expression responsible for early cell differentiation.

  7. Change of rat heart circadian autophagy rhythm due to aging%大鼠心脏自噬昼夜节律的老年化改变研究

    Institute of Scientific and Technical Information of China (English)

    晏浩; 李文林; 徐建军; 朱书强; 龙翔; 车建鹏

    2012-01-01

    目的 探讨大鼠心脏自噬昼夜节律的老年化改变及可能机制.方法 随机选取健康雄性SD大鼠48只,其中6月龄大鼠24只(青年组)和26月龄大鼠24只(老年组).观察大鼠昼夜活动习性,分别在03:00,06:00,09:00,12:00,15:00,18:00,21:00,24:00各时间点收集心脏样本,运用冷冻切片免疫荧光染色结合激光扫描共聚焦成像技术、亚细胞结构细胞核-细胞质分离技术和免疫印迹技术检测心脏自噬规律及可能调控机制.结果 青年组大鼠昼伏夜出,自噬昼夜节律曲线明显,其中18:00 LC3-Ⅰ转化LC3-Ⅱ明显高于12:00,而在15:00细胞核C/EBPβ表达明显高于18:00(P<0.05);而老年组大鼠夜间及昼间均嗜睡,LC3-Ⅰ转化LC3-Ⅱ和细胞核C/EBPβ昼夜无节律性变化.结论 衰老改变心脏自噬的昼夜节律,核转录因子C/EBPβ参与其调控.%Objective To study the change of rat heart circadian autophagy rhythm due to aging and its possible mechanism. Methods Forty-eight SD rats were randomly divided into 6-month old group(young group,w = 24) and 26-month old group(aged group,? = 24). Their circadian activity was observed. Heart tissue samples were collected at 03,06,09,12,15,18,21,24 h,respectively, frozen and cut into sections. Heart circadian autophagy rhythm and its possible regulation mechanism were detected by laser scanning,confocal imaging technique,nucleus and cytilipin separation technique and Western blot,respectively,with immunofluorescence staining. Results The rats in young group hid by day and came out by night with a significant circadian autophagy rhythm curve. The LC3- I was converted to LC3- H at 18 h and reached its peak at 12 h. The expression level of nucleus-C/EBP-(3 was significantly higher at 15 h than at 18 h(P0. 05). Conclusion Aging can change the heart circadian autophagy rhythm with involvement of nucleus-C/EBP-(3 in its regulation.

  8. Biological Rhythms and Preeclampsia

    Science.gov (United States)

    Ditisheim, Agnès J.; Dibner, Charna; Philippe, Jacques; Pechère-Bertschi, Antoinette

    2013-01-01

    The impact of impaired circadian rhythm on health has been widely studied in shift workers and trans-meridian travelers. A part from its correlation with sleep and mood disorders, biological rhythm impairment is a recognized risk factor for cardiovascular diseases and breast cancer. Preeclampsia is a major public health issue, associated with a significant maternal and fetal morbidity and mortality worldwide. While the risks factors for this condition such as obesity, diabetes, pre-existing hypertension have been identified, the underlying mechanism of this multi-factorial disease is yet not fully understood. The disruption of the light/dark cycle in pregnancy has been associated with adverse outcomes. Slightly increased risk for “small for gestational age” babies, “low birth weight” babies, and preterm deliveries has been reported in shift working women. Whether altered circadian cycle represents a risk factor for preeclampsia or preeclampsia is itself linked with an abnormal circadian cycle is less clear. There are only few reports available, showing conflicting results. In this review, we will discuss recent observations concerning circadian pattern of blood pressure in normotensive and hypertensive pregnancies. We explore the hypothesis that circadian misalignments may represent a risk factor for preeclampsia. Unraveling potential link between circadian clock gene and preeclampsia could offer a novel approach to our understanding of this multi-system disease specific to pregnancy. PMID:23579266

  9. Biological rhythms and preeclampsia

    Directory of Open Access Journals (Sweden)

    Agnès eDitisheim

    2013-04-01

    Full Text Available The impact of impaired circadian rhythm on health has been widely studied in shift workers and trans-meridian travelers. A part from its correlation with sleep and mood disorders, biological rhythm impairment is a recognized risk factor for cardiovascular diseases and breast cancer.Preeclampsia is a major public health issue, associated with a significant maternal and fetal morbidity and mortality worldwide. While the risks factors for this condition such as obesity, diabetes, pre-existing hypertension have been identified, the underlying mechanism of this multi-factorial disease is yet not fully understood.The disruption of the light/dark cycle in pregnancy has been associated with adverse outcomes. Slightly increased risk for small for gestational age babies, low birth weight babies and preterm deliveries has been reported in shift working women. Whether altered circadian cycle represents a risk factor for preeclampsia or preeclampsia is itself linked with an abnormal circadian cycle is less clear. There are only few reports available, showing conflicting results. In this review, we will discuss recent observations concerning circadian pattern of blood pressure in normotensive and hypertensive pregnancies. We explore the hypothesis that circadian misalignments may represent a risk factor for preeclampsia. Unraveling potential link between circadian clock gene and preeclampsia could offer a novel approach to our understanding of this multi-system disease specific to pregnancy.

  10. The calcineurin-NFAT pathway controls activity-dependent circadian gene expression in slow skeletal muscle

    OpenAIRE

    Dyar, Kenneth A.; Stefano Ciciliot; Guidantonio Malagoli Tagliazucchi; Giorgia Pallafacchina; Jana Tothova; Carla Argentini; Lisa Agatea; Reimar Abraham; Miika Ahdesmäki; Mattia Forcato; Silvio Bicciato; Stefano Schiaffino; Bert Blaauw

    2015-01-01

    Objective: Physical activity and circadian rhythms are well-established determinants of human health and disease, but the relationship between muscle activity and the circadian regulation of muscle genes is a relatively new area of research. It is unknown whether muscle activity and muscle clock rhythms are coupled together, nor whether activity rhythms can drive circadian gene expression in skeletal muscle. Methods: We compared the circadian transcriptomes of two mouse hindlimb muscles wi...

  11. Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury.

    Science.gov (United States)

    Li, Dongpeng; Ma, Shanshan; Guo, Dewei; Cheng, Tian; Li, Hongwei; Tian, Yi; Li, Jianbin; Guan, Fangxia; Yang, Bo; Wang, Jian

    2016-10-01

    Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague-Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID:26886755

  12. [Vector systems and rhythms in movements and orientation of elk (Alces alces L.) and other wild animals (Mammalia)].

    Science.gov (United States)

    Zaĭtsev, V A

    2002-01-01

    The orientation of elk and other mammals studied in fields with visual and instrumental tracing has obviously hierarchical organization. Animals usually choose general direction headed for distant markers and then select short-distance landmarks. Movements of animals to distant and close landmarks is characterized by almost constant or regularly changing angles between main direction and movement vector. Fragments of trajectories represent left-side or right-side spirals with decreasing or increasing curvature according to the main direction. Three types of spirals differed by average values of initial angles are considered. Orientation to distant landmarks or along direction of movement possesses discrete reaction on the given landmarks and has some characters of iteration process. Special rhythms of activity (rhythms of orientation changing) participate in regulation of changing of movement directions and orientation reactions. They take part in formation of sinusoid, spiral and other trajectories. Rhythmic regulation involves great statistical variability of parameters (lengths, angles, time periods between consecutive orientations) that can be adaptive meaning. Lengths of orientation vectors and trajectory fragments are similar to some linear elements of landscape. Angular parameters of orientation are more variable. The main ones are similar to the angular parameters of Earth rotation. It looks, that orientation parameters evolved under the influence of Sun-Earth compass in inertial field of Earth rotation. PMID:12298181

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

    Directory of Open Access Journals (Sweden)

    Jonathan eShelton

    2015-01-01

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

  14. The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity

    OpenAIRE

    Franken, Paulus; Lopez Molina, Luis; Marcacci, Lysiane; Schibler, Ulrich; Tafti, Mehdi

    2000-01-01

    Albumin D-binding protein (DBP) is a PAR leucine zipper transcription factor that is expressed according to a robust circadian rhythm in the suprachiasmatic nuclei, harboring the circadian master clock, and in most peripheral tissues. Mice lacking DBP display a shorter circadian period in locomotor activity and are less active. Thus, although DBP is not essential for circadian rhythm generation, it does modulate important clock outputs. We studied the role of DBP in the circadian and homeosta...

  15. Reduced anxiety and depression-like behaviours in the circadian period mutant mouse afterhours.

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    Robert Keers

    Full Text Available BACKGROUND: Disruption of the circadian rhythm is a key feature of bipolar disorder. Variation in genes encoding components of the molecular circadian clock has been associated with increased risk of the disorder in clinical populations. Similarly in animal models, disruption of the circadian clock can result in altered mood and anxiety which resemble features of human mania; including hyperactivity, reduced anxiety and reduced depression-like behaviour. One such mutant, after hours (Afh, an ENU-derived mutant with a mutation in a recently identified circadian clock gene Fbxl3, results in a disturbed (long circadian rhythm of approximately 27 hours. METHODOLOGY: Anxiety, exploratory and depression-like behaviours were evaluated in Afh mice using the open-field, elevated plus maze, light-dark box, holeboard and forced swim test. To further validate findings for human mania, polymorphisms in the human homologue of FBXL3, genotyped by three genome wide case control studies, were tested for association with bipolar disorder. PRINCIPAL FINDINGS: Afh mice showed reduced anxiety- and depression-like behaviour in all of the behavioural tests employed, and some evidence of increased locomotor activity in some tests. An analysis of three separate human data sets revealed a gene wide association between variation in FBXL3 and bipolar disorder (P = 0.009. CONCLUSIONS: Our results are consistent with previous studies of mutants with extended circadian periods and suggest that disruption of FBXL3 is associated with mania-like behaviours in both mice and humans.

  16. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Brianne Alyssia Kent

    2014-09-01

    Full Text Available Alzheimer’s disease (AD is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behaviour and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.

  17. Circadian rhythm and photic induction of the C-terminal splice variant of NMDAR1 subunit in the rat suprachiasmatic nucleus

    Czech Academy of Sciences Publication Activity Database

    Bendová, Zdeňka; Janoušková, Hana; Svobodová, Irena

    2014-01-01

    Roč. 68, č. 2 (2014), s. 85-88. ISSN 0887-4476 R&D Projects: GA ČR(CZ) GAP303/10/1227 Institutional support: RVO:67985823 Keywords : circadian clock * NMDA receptor * NR1 subunit * rat * suprachiasmatic nucleus Subject RIV: FH - Neurology Impact factor: 2.127, year: 2014

  18. Effect of dietary phosphate intake on the circadian rhythm of serum phosphate concentrations in chronic kidney disease: a crossover study1234

    OpenAIRE

    Ix, Joachim H.; Anderson, Cheryl AM; Smits, Gerard; Persky, Martha S.; Block, Geoffrey A.

    2014-01-01

    Background: Previous trials of binders in chronic kidney disease (CKD) stages 3–5 have shown only modest changes in serum phosphate but evaluated morning phosphate. It is unknown whether a circadian pattern of phosphate concentrations exists in CKD and is modifiable by dietary manipulation.

  19. Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Reppert, S.M.; Perlow, M.J.; Ungerleider, L.G.; Mishkin, M.; Tamarkin, L.; Orloff, D.G.; Hoffman, H.J.; Klein, D.C.

    1981-12-01

    The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

  20. Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

    International Nuclear Information System (INIS)

    The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN

  1. A influência dos ritmos circadianos no metabolismo da serpente Bothrops jararaca (Serpentes, Viperidae - DOI: 10.4025/actascibiolsci.v30i3.5030 The influence of circadian rhythms on the metabolism of the snake Bothrops jararaca (Serpentes, Viperidae - DOI: 10.4025/actascibiolsci.v30i3.5030

    Directory of Open Access Journals (Sweden)

    José Geraldo Pereira da Cruz

    2008-10-01

    circadian phase as the increase in body temperature in the 30ºC. The increase of body temperature and oxygen consumption of B. jararaca occurs in the scotophase of the photoperiod, consistent with that of nocturnal species. However, prior to a scotophase period the snakes under 20ºC maintain body temperature and oxygen consumption at higher levels during the day. These results demonstrate for the first time that ectothermic animals may display physiologically generated circadian rhythms of body temperature similar to those recorded in endotherms. Circadian rhythms allow animals to anticipate environmental changes: physiological parameters such as body temperature and mobilization of energy reserves have to be adjusted before the expected environmental changes actually take place.

  2. Circadian rhythms of clock gene expression in Nile tilapia (Oreochromis niloticus) central and peripheral tissues: influence of different lighting and feeding conditions.

    Science.gov (United States)

    Costa, Leandro S; Serrano, Ignacio; Sánchez-Vázquez, Francisco J; López-Olmeda, Jose F

    2016-08-01

    The present research aimed to investigate the existence of clock gene expression rhythms in tilapia, their endogenous origin, and how light and feeding cycles synchronize these rhythms. In the first experiment, two groups of fish were kept under an LD cycle and fed at two different time points: in the middle of the light (ML) or in the middle of the dark (MD) phase. In the second experiment, fish fed at ML was fasted and kept under constant lighting (LL) conditions for 1 day. In both experiments, the samples from central (optic tectum and hypothalamus) and peripheral (liver) tissues were collected every 3 h throughout a 24 h cycle. The expression levels of clock genes bmal1a, clock1, per1b, cry2a, and cry5 were analyzed by quantitative PCR. All the clock genes analyzed in brain regions showed daily rhythms: clock1, bmal1a, and cry2a showed the acrophase approximately at the end of the light phase (ZT 8:43-11:22 h), whereas per1b and cry5 did so between the end of the dark phase and the beginning of the light phase, respectively (ZT 21:16-4:00 h). These rhythms persisted under constant conditions. No effect of the feeding time was observed in the brain. In the liver, however, the rhythms of clock1 and cry5 were influenced by feeding, and a shift was observed in the MD fish group (ZT 3:58 h for clock1 and 11:20 h for cry5). This study provides the first insights into the molecular clock of tilapia, a very important fish species for aquaculture. It also reveals the endogenous origin of clock gene rhythms and the ability of feeding time to shift the phase in some clock genes in the peripheral, but not the central, oscillator. PMID:27085855

  3. Bidirectional Interactions between Circadian Entrainment and Cognitive Performance

    Science.gov (United States)

    Gritton, Howard J.; Kantorowski, Ana; Sarter, Martin; Lee, Theresa M.

    2012-01-01

    Circadian rhythms influence a variety of physiological and behavioral processes; however, little is known about how circadian rhythms interact with the organisms' ability to acquire and retain information about their environment. These experiments tested whether rats trained outside their endogenous active period demonstrate the same rate of…

  4. Distinct, Time-Dependent Effects of Voluntary Exercise on Circadian and Ultradian Rhythms and Stress Responses of Free Corticosterone in the Rat Hippocampus

    OpenAIRE

    Droste, Susanne K; Collins, Andrew; Lightman, Stafford L.; Linthorst, Astrid C E; Reul, Johannes M. H. M.

    2009-01-01

    Previous work has shown that allowing rats to voluntarily exercise in a running wheel for 4 wk modifies the hypothalamic-pituitary-adrenal axis and behavioral coping responses to stress. To investigate whether long-term voluntary exercise would also affect the free, biologically active fraction of corticosterone in the brain, we conducted an in vivo microdialysis study in the hippocampus of rats. We monitored both the baseline circadian and ultradian patterns of corticosterone in hippocampus ...

  5. Circadian Gene Networks In Bone Regeneration

    OpenAIRE

    Hassan, Nathaniel

    2012-01-01

    BACKGROUND: Previous studies suggested that vitamin D played a significant role in bone regeneration, facilitating the establishment of implant osseointegration. A whole genome microarray study further suggested that the vitamin D axis might involve circadian rhythm gene expression in the bone peripheral tissue.OBJECTIVES: To identify key gene networks involved with vitamin D receptor in the bone regeneration process and to explore any correlation with circadian rhythm gene expression in bone...

  6. The circadian clock in mammals

    OpenAIRE

    Zordan, Mauro; Kyriacou, Charalambos P

    2000-01-01

    The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship be...

  7. The circadian clock in mammals

    OpenAIRE

    Zordan, M. A.; Kyriacou, C P

    2005-01-01

    The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship be...

  8. Animal Care Practices in Experiments on Biological Rhythms and Sleep: Report of the Joint Task Force of the Society for Research on Biological Rhythms and the Sleep Research Society

    OpenAIRE

    Bittman, Eric L; Kilduff, Thomas S.; Kriegsfeld, Lance J.; Szymusiak, Ronald; Toth, Linda A; Turek, Fred W.

    2013-01-01

    Many physiological and molecular processes are strongly rhythmic and profoundly influenced by sleep. The continuing effort of biological, medical, and veterinary science to understand the temporal organization of cellular, physiological, behavioral and cognitive function holds great promise for the improvement of the welfare of animals and human beings. As a result, attending veterinarians and IACUC are often charged with the responsibility of evaluating experiments on such rhythms or the eff...

  9. Natural selection against a circadian clock gene mutation in mice

    NARCIS (Netherlands)

    Spoelstra, K.; Wikelski, Martin; Daan, Serge; Loudon, Andrew; Hau, Michaela

    2015-01-01

    Circadian rhythms with an endogenous period close or equal to the natural light-dark cycle are considered evolutionarily adaptive (‘circadian resonance hypothesis’). Despite remarkable insight into the molecular mechanisms driving circadian cycles, this hypothesis has not been tested under natural c

  10. The circadian clock in cancer development and therapy

    Science.gov (United States)

    Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The...

  11. Phase resetting of the mammalian circadian clock by DNA damage

    NARCIS (Netherlands)

    Oklejewicz, Malgorzata; Destici, Eugin; Tamanini, Filippo; Hut, Roelof A.; Janssens, Roel; van der Horst, Gijsbertus T. J.

    2008-01-01

    To anticipate the momentum of the day, most organisms have developed an internal clock that drives circadian rhythms in metabolism, physiology, and behavior [1]. Recent studies indicate that cell-cycle progression and DNA-damage-response pathways are under circadian control [2-4]. Because circadian

  12. [Directional hearing in relation to individual circadian biorhythm].

    Science.gov (United States)

    Karnicki, C

    1990-01-01

    Acuity angle of the directional hearing was investigated in connection with the individual circadian rhythm. Two groups of 15 persons represented the morning and evening form of the circadian rhythm. Body temperature fixed the rhythm character. The evaluations of the angle acuity of the directional hearing were performed in the highest and the lowest point of body temperature as well as in the neutral point, which was determined in the morning group in the middle between the two extremes. The possibility of the sound localization in individual and linked with the body temperature circadian rhythm. PMID:2234972

  13. Metabolic consequences of sleep and circadian disorders

    OpenAIRE

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

    2014-01-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight g...

  14. Circadian regulators of intestinal lipid absorption

    OpenAIRE

    Hussain, M. Mahmood; Pan, Xiaoyue

    2015-01-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circa...

  15. Disruption of circadian clocks has ramifications for metabolism, brain, and behavior

    OpenAIRE

    Karatsoreos, Ilia N.; Bhagat, Sarah; Bloss, Erik B.; Morrison, John H.; McEwen, Bruce S.

    2011-01-01

    Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken....

  16. Comparison of effects of bright light therapy alone or combined with fluoxetine on severity of depression, circadian rhythms, mood disturbance, and sleep quality, in patients with non-seasonal depression

    Directory of Open Access Journals (Sweden)

    Ağargün MY

    2013-06-01

    Full Text Available Mehmet Yücel Agargün,1 Gokben Hizli Sayar,2 Hüseyin Bulut,3 Oguz Tan21Medipol University, Department of Psychiatry, Istanbul, Turkey; 2Uskudar University, Neuropsychiatry Istanbul Hospital, Istanbul, Turkey; 3Büyükçekmece Government Hospital, Department of Psychiatry, Istanbul, TurkeyPurpose: To compare effects of bright light therapy (BLT alone or combined with the selective serotonin reuptake inhibitor (SSRI fluoxetine, on severity of depression, circadian rhythms, mood disturbance, and sleep quality, in patients with non-seasonal depression.Patients and methods: Drug-free patients who were administered 10,000 lux of BLT for 30 minutes for 7 days comprised the BLT group (n = 7, while patients who started fluoxetine as an add-on treatment day comprised the SSRI + BLT group (n = 8. The primary outcomes were severity of depression, measured using the Hamilton Depression Rating Scale (HAM-D and the Beck Depression Inventory (BDI; chronotype, measured using the Morningness Eveningness Questionnaire (MEQ; mood disturbance, measured using the Profile of Mood States (POMS survey; and sleep quality, measured using the Pittsburgh Sleep Quality Index (PSQI, before and after treatment in both groups.Results: All patients completed the study, and none reported obvious side effects. The mean onset age of depression was 26.1 years ± 5.3 years in the BLT group and 27 years ± 9.5 years in the SSRI + BLT group (P = 0.425. The number of past depressive episodes was 1.29 ± 0.76 in the BLT group, and 1.5 ± 0.8 in the SSRI + BLT group (P = 0.427. The difference between pre- and posttreatment scores revealed no significant difference between groups for the HAM-D scale, BDI, MEQ, POMS survey, and the PSQI.Conclusion: This study suggests that BLT is effective with respect to the severity of depression, circadian rhythms, mood disturbance, and sleep quality, in non-seasonal depression. However, there was no evidence in favor of adjunctive fluoxetine with BLT

  17. Calculating the Social Rhythm Metric (SRM) and Examining Its Use in Interpersonal Social Rhythm Therapy (IPSRT) in a Healthy Population Study

    OpenAIRE

    Theun Pieter van Tienoven; Joeri Minnen; Sarah Daniels; Djiwo Weenas; Anke Raaijmakers; Ignace Glorieux

    2014-01-01

    In psychiatry, the social zeitgeber theory argues that social life provides important social cues that entrain circadian rhythms. Disturbance of these social cues might lead do dis-entrainment of circadian rhythms and evoke somatic symptoms that increase the risk of mood disorders. In preventing and treating patients with bipolar disorders, the Interpersonal and Social Rhythm Therapy (IPSRT) relies on the Social Rhythm Metric (SRM) to (re)establish patients’ social cues and an re-entrain circ...

  18. circadian rhythm of calling behavior in the emei music frog (babina daunchina)is associated with habitat temperature and relative humidity

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    generally,the function of vocalizations made by male anurans are to attract females or defend resources.typically,males vocalize in choruses during one or more periods in a twenty-four-hour cycle,which varies,however,among species.nevertheless,the causal factors influencing circadian variations of calling patterns in anuran species are not clear.in this study,male chorus vocalizations were monitored in the emei music frog (babina daunchina)for 17 consecutive days during the breeding season,while its habitat air temperature and relative humidity in the course of experiments were measured as well.the results revealed that the circadian calling patterns were characterized by two periods of peak vocalization,which were observed from 0500 h to 0700 h and from 1300 h to 2000 h,while the lowest activity period was found from 2100 h to 2200 h.both calls/h and notes/h were positively correlated with air temperature and negatively with relative humidity.overall,our data indicate that the emei music frogs (b.daunchina)could regulate their vocal activities based on the changes of physical micro-environment (e.g.,temperature or humidity)to maximize reproductive success.

  19. How Temperature Changes Reset a Circadian Oscillator

    NARCIS (Netherlands)

    Merrow, Martha; Loros, Jennifer J.; Dunlap, Jay C.

    1998-01-01

    Circadian rhythms control many physiological activities. The environmental entrainment of rhythms involves the immediate responses of clock components. Levels of the clock protein FRQ were measured in Neurospora at various temperatures; at higher temperatures, the amount of FRQ oscillated around hig

  20. Daily rhythms in mobile telephone communication

    CERN Document Server

    Aledavood, Talayeh; Roberts, Sam G B; Reed-Tsochas, Felix; Moro, Esteban; Dunbar, Robin I M; Saramäki, Jari

    2015-01-01

    Circadian rhythms are known to be important drivers of human activity and the recent availability of electronic records of human behaviour has provided fine-grained data of temporal patterns of activity on a large scale. Further, questionnaire studies have identified important individual differences in circadian rhythms, with people broadly categorised into morning-like or evening-like individuals. However, little is known about the social aspects of these circadian rhythms, or how they vary across individuals. In this study we use a unique 18-month dataset that combines mobile phone calls and questionnaire data to examine individual differences in the daily rhythms of mobile phone activity. We demonstrate clear individual differences in daily patterns of phone calls, and show that these individual differences are persistent despite a high degree of turnover in the individuals' social networks. Further, women's calls were longer than men's calls, especially during the evening and at night, and these calls wer...

  1. 大鼠视交叉上核与松果体中Clock基因转录的昼夜节律性及不同光反应性%Circadian rhythms and different photoresponses of Clock gene transcription in the rat suprachiasmatic nucleus and pineal gland

    Institute of Scientific and Technical Information of China (English)

    王国卿; 傅春玲; 李建祥; 杜玉珍; 童建

    2006-01-01

    The aim of this study was to observe and compare the endogenous circadian rhythm and photoresponse of Clock gene transcription in the suprachiasmatic nucleus (SCN) and pineal gland (PG) of rats. With free access to food and water in special darkrooms, Sprague-Dawley rats were housed under the light regime of constant darkness (DD) for 8 weeks (n=36) or 12 hour-light:12 hour-dark cycle (LD) for 4 weeks (n=36), respectively. Then, their SCN and PG were dissected out every 4 h in a circadian day, 6rats at each time (n=6). All animal treatments and sampling during the dark phases were conducted under red dim light (<0.1 lux). The total RNA was extracted from each sample and the semi-quantitative RT-PCR was used to determine the temporal mRNA changes of Clock gene in the SCN and PG at different circadian times (CT) or zeitgeber times (ZT). The grayness ratio of Clock/H3.3 bands was served as the relative estimation of Clock gene expression. The experimental data were analyzed by the Cosine method and the Clock Lab software to fit original results measured at 6 time points and to simulate a circadian rhythmic curve which was then examined for statistical difference by the amplitude F test. The main results are as follows: (1) The mRNA levels of Clock gene in the SCN under DD regime displayed the circadian oscillation (P<0.05). The endogenous rhythmic profiles of Clock gene transcription in the PG were similar to those in the SCN (P>0.05) throughout the day with the peak at the subjective night (CT15 in the SCN or CT18 in the PG)and the trough during the subjective day (CT3 in the SCN or CT6 in the PG). (2) Clock gene transcription in the SCN under LD cycle also showed the circadian oscillation (P<0.05), and the rhythmic profile was anti-phasic to that under DD condition (P<0.05). The amplitude and the mRNA level at the peak of Clock gene transcription in the SCN under LD were significantly increased compared with that under DD (P<0.05), while the value of

  2. Circadian adaptations to meal timing: Neuroendocrine mechanisms

    Directory of Open Access Journals (Sweden)

    Danica F Patton

    2013-10-01

    Full Text Available Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus is directly entrained by daily light-dark cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this

  3. The Effects of Gravity on the Circadian Timing System

    Science.gov (United States)

    Fuller, Charles A.

    1999-01-01

    All vertebrates have a physiological control system that regulates the timing of the rhythms of their daily life. Dysfunction of this system, the circadian timing system (CTS), adversely affects an organism's ability to respond to environmental challenges and has been linked to physiological and psychological disorders. Exposure to altered gravitational environments (the microgravity of space and hyperdynamic environments produced via centrifugation) produces changes in both the functioning of the CTS and the rhythmic variables it controls. The earliest record of primate rhythms in a spaceflight environment come from Biosatellite III. The subject, a pig-tailed macaque, showed a loss of synchronization of the body temperature rhythm and a fragmented sleep-wake cycle. Alterations in the rhythm of body temperature were also seen in rhesus macaques flown on COSMOS 1514. Squirrel monkeys exposed to chronic centrifugation showed an initial decrease in the amplitude and mean of their body temperature and activity rhythms. In a microgravity environment, Squirrel monkeys on Spacelab-3 showed a reduction in the mean and amplitude of their feeding rhythms. Since 1992 we have had the opportunity to participate on three US/Russian sponsored biosatellite missions on which a total of six juvenile male rhesus macaques were flown. These animals uniformly exhibited delays in the phasing of their temperature rhythms, but not their heart rate or activity rhythms during spaceflight. There was also a tendency for changes in waveform mean and amplitude. These data suggest that the spaceflight environment may have a differential effect on the different oscillators controlling different rhythmic variables. Ongoing studies are examining the effects of +G on the CTS. The long-term presence of humans in space highlights the need for effective countermeasures to gravitational effects on the CTS.

  4. Effect of pinealectomy and prolonged melatonin administration on circadian testicular function in food restricted rats

    Energy Technology Data Exchange (ETDEWEB)

    Ostrowska, Z.; Zwirska-Korczala, K.; Kajdaniuk, D.; Gorski, J.; Buntner, B. [Slaska Akademia Medyczna, Katowice (Poland)

    1995-12-31

    The effect of pinealectomy and exogenous melatonin on the circadian testosterone variations was investigated (using the radioimmunoassay method) after 3 weeks of 50% food restriction in sexually mature male Wistar rats at 3-h intervals under 12:12 light-dark cycle. The circadian periodicity of testosterone secretion was maintained after caloric deprivation, however its mean 24-h concentration was lower and rhythm disturbances appeared in the form of acrophase shifts from 18.00 to 0.50 h. In pinealectomized animals the mean 24-h testosterone level and amplitude values were significantly increased without the rhythm disturbances. As compared to the control animals, underfed pinealectomized rats had a partial recovery of reduced testosterone levels during the 24-h cycle and showed a normalization of the rhythm acrophase. Melatonin administration was found to inhibit the testosterone mesor value in pinealectomized rats with acrophase shifts from 16.58 to 14.51 h. In comparison with the pinealectomized ones the underfed pinealectomized rats had a greater reduction of the mesor and amplitude values after the melatonin administration. These findings indicate that long-term food restriction sensitizes the circadian testicular axis to antigonadotropic action of the pineal gland. (author). 42 refs, 3 figs, 1 tab.

  5. Acute myocardial infarction and infarct size: do circadian variations play a role?

    Directory of Open Access Journals (Sweden)

    Ibáñez B

    2012-08-01

    Full Text Available Aída Suárez-Barrientos,1 Borja Ibáñez1,21Cardiovascular Institute, Hospital Clínico San Carlos, 2Centro Nacional de Investigaciones Cardiovasculares, Madrid, SpainAbstract: The circadian rhythm influences cardiovascular system physiology, inducing diurnal variations in blood pressure, heart rate, cardiac output, endothelial functions, platelet aggregation, and coronary arterial flow, among other physiological parameters. Indeed, an internal circadian network modulates cardiovascular physiology by regulating heart rate, metabolism, and even myocyte growth and repair ability. Consequently, cardiovascular pathology is also controlled by circadian oscillations, with increased morning incidence of cardiovascular events. The potential circadian influence on the human tolerance to ischemia/reperfusion has not been systematically scrutinized until recently. It has since been proven, in both animals and humans, that infarct size varies during the day depending on the symptom onset time, while circadian fluctuations in spontaneous cardioprotection in humans with ST-segment elevation myocardial infarction (STEMI have also been demonstrated. Furthermore, several studies have proposed that the time of day at which revascularization occurs in patients with STEMI may also influence infarct size and reperfusion outcomes. The potential association of the circadian clock with infarct size advocates the acknowledgment of time of day as a new prognostic factor in patients suffering acute myocardial infarction, which would open up a new field for chronotherapeutic targets and lead to the inclusion of time of day as a variable in clinical trials that test novel cardioprotective strategies.Keywords: cardioprotection, circadian rhythm, reperfusion injury, ST-segment elevation myocardial infarction

  6. Molecular Mechanisms of Circadian Regulation During Spaceflight

    Science.gov (United States)

    Zanello, S. B.; Boyle, R.

    2012-01-01

    The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ip

  7. Circadian Control of Global Transcription

    Science.gov (United States)

    Li, Shujing; Zhang, Luoying

    2015-01-01

    Circadian rhythms exist in most if not all organisms on the Earth and manifest in various aspects of physiology and behavior. These rhythmic processes are believed to be driven by endogenous molecular clocks that regulate rhythmic expression of clock-controlled genes (CCGs). CCGs consist of a significant portion of the genome and are involved in diverse biological pathways. The transcription of CCGs is tuned by rhythmic actions of transcription factors and circadian alterations in chromatin. Here, we review the circadian control of CCG transcription in five model organisms that are widely used, including cyanobacterium, fungus, plant, fruit fly, and mouse. Comparing the similarity and differences in the five organisms could help us better understand the function of the circadian clock, as well as its output mechanisms adapted to meet the demands of diverse environmental conditions. PMID:26682214

  8. Circadian Control of Global Transcription

    Directory of Open Access Journals (Sweden)

    Shujing Li

    2015-01-01

    Full Text Available Circadian rhythms exist in most if not all organisms on the Earth and manifest in various aspects of physiology and behavior. These rhythmic processes are believed to be driven by endogenous molecular clocks that regulate rhythmic expression of clock-controlled genes (CCGs. CCGs consist of a significant portion of the genome and are involved in diverse biological pathways. The transcription of CCGs is tuned by rhythmic actions of transcription factors and circadian alterations in chromatin. Here, we review the circadian control of CCG transcription in five model organisms that are widely used, including cyanobacterium, fungus, plant, fruit fly, and mouse. Comparing the similarity and differences in the five organisms could help us better understand the function of the circadian clock, as well as its output mechanisms adapted to meet the demands of diverse environmental conditions.

  9. Endocrine regulation of circadian physiology.

    Science.gov (United States)

    Tsang, Anthony H; Astiz, Mariana; Friedrichs, Maureen; Oster, Henrik

    2016-07-01

    Endogenous circadian clocks regulate 24-h rhythms of behavior and physiology to align with external time. The endocrine system serves as a major clock output to regulate various biological processes. Recent findings suggest that some of the rhythmic hormones can also provide feedback to the circadian system at various levels, thus contributing to maintaining the robustness of endogenous rhythmicity. This delicate balance of clock-hormone interaction is vulnerable to modern lifestyle factors such as shiftwork or high-calorie diets, altering physiological set points. In this review, we summarize the current knowledge on the communication between the circadian timing and endocrine systems, with a focus on adrenal glucocorticoids and metabolic peptide hormones. We explore the potential role of hormones as systemic feedback signals to adjust clock function and their relevance for the maintenance of physiological and metabolic circadian homeostasis. PMID:27106109

  10. Circatidal rhythms of locomotion in the American horseshoe crab Limulus polyphemus: Underlying mechanisms and cues that influence them

    Directory of Open Access Journals (Sweden)

    Christopher C. CHABOT, Winsor H. WATSON III

    2010-10-01

    Full Text Available While eye sensitivity in the American horseshoe crab Limulus polyphemus has long been known to be under the control of an endogenous circadian clock, only recently has horseshoe crab locomotion been shown to be controlled by a separate clock system. In the laboratory, this system drives clear activity rhythms throughout much of the year, not just during the mating season when horseshoe crabs express clear tidal rhythms in the field. Water temperature is a key factor influencing the expression of these rhythms: at 17oC tidal rhythms are expressed by most animals, while at 11oC expression of circatidal rhythms is rarely seen, and at 4oC rhythms are suppressed. Neither long (16:8 Light:Dark nor short (8:16 photoperiods modify this behavior at any of these temperatures. Synchronization of these circatidal rhythms can be most readily effected by water pressure cycles both in situ and in the lab, while temperature and current cycles play lesser, but possibly contributory, roles. Interestingly, Light:Dark cycles appear to have synchronizing as well as “masking” effects in some individuals. Evidence that each of two daily bouts of activity are independent suggests that the Limulus circatidal rhythm of locomotion is driven by two (circalunidian clocks, each with a period of 24.8h. While the anatomical locations of either the circadian clock, that drives fluctuations in visual sensitivity, or the circatidal clock, that controls tidal rhythms of locomotion, are currently unknown, preliminary molecular analyses have shown that a 71 kD protein that reacts with antibodies directed against the Drosophila PERIOD (PER protein is found in both the protocerebrum and the subesophageal ganglion [Current Zoology 56 (5: 499–517, 2010].

  11. Rhythm and Randomness in Human Contact

    CERN Document Server

    Freeman, Mervyn P; Yoneki, Eiko; Crowcroft, Jon

    2010-01-01

    There is substantial interest in the effect of human mobility patterns on opportunistic communications. Inspired by recent work revisiting some of the early evidence for a L\\'evy flight foraging strategy in animals, we analyse datasets on human contact from real world traces. By analysing the distribution of inter-contact times on different time scales and using different graphical forms, we find not only the highly skewed distributions of waiting times highlighted in previous studies but also clear circadian rhythm. The relative visibility of these two components depends strongly on which graphical form is adopted and the range of time scales. We use a simple model to reconstruct the observed behaviour and discuss the implications of this for forwarding efficiency.

  12. Integration of human sleep-wake regulation and circadian rhythmicity

    Science.gov (United States)

    Dijk, Derk-Jan; Lockley, Steven W.

    2002-01-01

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

  13. DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

    Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent with...... validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted...

  14. Circadian Clock Regulates Bone Resorption in Mice.

    Science.gov (United States)

    Xu, Cheng; Ochi, Hiroki; Fukuda, Toru; Sato, Shingo; Sunamura, Satoko; Takarada, Takeshi; Hinoi, Eiichi; Okawa, Atsushi; Takeda, Shu

    2016-07-01

    The circadian clock controls many behavioral and physiological processes beyond daily rhythms. Circadian dysfunction increases the risk of cancer, obesity, and cardiovascular and metabolic diseases. Although clinical studies have shown that bone resorption is controlled by circadian rhythm, as indicated by diurnal variations in bone resorption, the molecular mechanism of circadian clock-dependent bone resorption remains unknown. To clarify the role of circadian rhythm in bone resorption, aryl hydrocarbon receptor nuclear translocator-like (Bmal1), a prototype circadian gene, was knocked out specifically in osteoclasts. Osteoclast-specific Bmal1-knockout mice showed a high bone mass phenotype due to reduced osteoclast differentiation. A cell-based assay revealed that BMAL1 upregulated nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (Nfatc1) transcription through its binding to an E-box element located on the Nfatc1 promoter in cooperation with circadian locomotor output cycles kaput (CLOCK), a heterodimer partner of BMAL1. Moreover, steroid receptor coactivator (SRC) family members were shown to interact with and upregulate BMAL1:CLOCK transcriptional activity. Collectively, these data suggest that bone resorption is controlled by osteoclastic BMAL1 through interactions with the SRC family and binding to the Nfatc1 promoter. © 2016 American Society for Bone and Mineral Research. PMID:26841172

  15. Nonphotic entrainment of the human circadian pacemaker

    Science.gov (United States)

    Klerman, E. B.; Rimmer, D. W.; Dijk, D. J.; Kronauer, R. E.; Rizzo, J. F. 3rd; Czeisler, C. A.

    1998-01-01

    In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals "free run" even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.

  16. Rhythms and synchronization patterns in gene expression in the Aedes aegypti mosquito

    Directory of Open Access Journals (Sweden)

    Carlson Jonathan O

    2011-03-01

    Full Text Available Abstract Background Aedes aegypti is arguably the most studied of all mosquito species in the laboratory and is the primary vector of both Dengue and Yellow Fever flaviviruses in the field. A large number of transcriptional studies have been made in the species and these usually report transcript quantities observed at a certain age or stage of development. However, circadian oscillation is an important characteristic of gene expression in many animals and plants, modulating both their physiology and behavior. Circadian gene expression in mosquito species has been previously reported but for only a few genes directly involved in the function of the molecular clock. Results Herein we analyze the transcription profiles of 21,494 messenger RNAs using an Ae. aegypti Agilent® microarray. Transcripts were quantified in adult female heads at 24 hours and then again at 72 hours and eight subsequent time points spaced four hours apart. We document circadian rhythms in multiple molecular pathways essential for growth, development, immune response, detoxification/pesticide resistance. Circadian rhythms were also noted in ribosomal protein genes used for normalization in reverse transcribed PCR (RT-PCR to determine transcript abundance. We report pervasive oscillations and intricate synchronization patterns relevant to all known biological pathways. Conclusion These results argue strongly that transcriptional analyses either need to be made over time periods rather than confining analyses to a single time point or development stage or exceptional care needs to be made to synchronize all mosquitoes to be analyzed and compared among treatment groups.

  17. Chronic unpredictable stress induces a reversible change of PER2 rhythm in the suprachiasmatic nucleus.

    Science.gov (United States)

    Jiang, Wen-Gao; Li, Su-Xia; Zhou, Shuang-Jiang; Sun, Yan; Shi, Jie; Lu, Lin

    2011-07-01

    Many clinical studies have shown that circadian rhythm abnormalities are strongly associated with major depression. The master clock of the circadian system in mammals is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus, where Per1 and Per2 are essential core components of circadian rhythm oscillation. Chronic unpredictable stress (CUS) is a reliable animal model of depression with good face, predictive, and constructive validity. In the present study, we investigated the effects of CUS on the circadian expression of PER1 and PER2 in the SCN. We found that CUS led to depressive-like behavior and reduced the amplitude of PER2 oscillation in the SCN, which were blocked by 3 weeks of desipramine (DMI) treatment. 2 weeks after termination of CUS, the decreased peak of PER2 expression returned to control levels, whereas depressive-like behavior remained unchanged. Our findings suggest that the dampened amplitude of PER2 expression in the SCN may participate in the development of depressive-like behavior induced by CUS but is unlikely involved in the long-lasting effects of CUS on depressive-like behavior. PMID:21621196

  18. Circadian clocks, epigenetics, and cancer

    KAUST Repository

    Masri, Selma

    2015-01-01

    The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work and cancer incidence are linked. Accumulating evidence implicates the circadian clock in cancer survival and proliferation pathways. At the molecular level, multiple control mechanisms have been proposed to link circadian transcription and cell-cycle control to tumorigenesis.The circadian gating of the cell cycle and subsequent control of cell proliferation is an area of active investigation. Moreover, the circadian clock is a transcriptional system that is intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape at the level of histone modifications, DNA methylation, and small regulatory RNAs are differentially controlled in cancer cells. This concept raises the possibility that epigenetic control is a common thread linking the clock with cancer, though little scientific evidence is known to date.This review focuses on the link between circadian clock and cancer, and speculates on the possible connections at the epigenetic level that could further link the circadian clock to tumor initiation or progression.

  19. Circadian influences on myocardial infarction.

    Science.gov (United States)

    Virag, Jitka A I; Lust, Robert M

    2014-01-01

    Components of circadian rhythm maintenance, or "clock genes," are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. While it is known that the central master clock in the SCN synchronizes peripheral physiologic rhythms, the mechanisms by which the information is transmitted are complex and may include hormonal, metabolic, and neuronal inputs. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on myocardial infarct incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and myocardial infarction may provide insights into possible preventative and therapeutic strategies for susceptible populations. PMID:25400588

  20. Circadian and wakefulness-sleep modulation of cognition in humans.

    Science.gov (United States)

    Wright, Kenneth P; Lowry, Christopher A; Lebourgeois, Monique K

    2012-01-01

    Cognitive and affective processes vary over the course of the 24 h day. Time of day dependent changes in human cognition are modulated by an internal circadian timekeeping system with a near-24 h period. The human circadian timekeeping system interacts with sleep-wakefulness regulatory processes to modulate brain arousal, neurocognitive and affective function. Brain arousal is regulated by ascending brain stem, basal forebrain (BF) and hypothalamic arousal systems and inhibition or disruption of these systems reduces brain arousal, impairs cognition, and promotes sleep. The internal circadian timekeeping system modulates cognition and affective function by projections from the master circadian clock, located in the hypothalamic suprachiasmatic nuclei (SCN), to arousal and sleep systems and via clock gene oscillations in brain tissues. Understanding the basic principles of circadian and wakefulness-sleep physiology can help to recognize how the circadian system modulates human cognition and influences learning, memory and emotion. Developmental changes in sleep and circadian processes and circadian misalignment in circadian rhythm sleep disorders have important implications for learning, memory and emotion. Overall, when wakefulness occurs at appropriate internal biological times, circadian clockwork benefits human cognitive and emotion function throughout the lifespan. Yet, when wakefulness occurs at inappropriate biological times because of environmental pressures (e.g., early school start times, long work hours that include work at night, shift work, jet lag) or because of circadian rhythm sleep disorders, the resulting misalignment between circadian and wakefulness-sleep physiology leads to impaired cognitive performance, learning, emotion, and safety. PMID:22529774

  1. Circadian and Wakefulness-Sleep Modulation of Cognition in Humans

    Directory of Open Access Journals (Sweden)

    Kenneth P Wright

    2012-04-01

    Full Text Available Cognitive and affective processes vary over the course of the 24 hour day. Time of day dependent changes in human cognition are modulated by an internal circadian timekeeping system with a near-24-hour period. The human circadian timekeeping system interacts with sleep-wakefulness regulatory processes to modulate brain arousal, neurocognitive and affective function. Brain arousal is regulated by ascending brain stem, basal forebrain and hypothalamic arousal systems and inhibition or disruption of these systems reduces brain arousal, impairs cognition, and promotes sleep. The internal circadian timekeeping system modulates cognition and affective function by projections from the master circadian clock, located in the hypothalamic suprachiasmatic nuclei, to arousal and sleep systems and via clock gene oscillations in brain tissues. Understanding the basic principles of circadian and wakefulness-sleep physiology can help to recognize how the circadian system modulates human cognition and influences learning, memory and emotion. Developmental changes in sleep and circadian processes and circadian misalignment in circadian rhythm sleep disorders have important implications for learning, memory and emotion. Overall, when wakefulness occurs at appropriate internal biological times, circadian clockwork benefits human cognitive and emotion function throughout the lifespan. Yet, when wakefulness occurs at inappropriate biological times because of environmental pressures (e.g., early school start times, long work hours that include work at night, shift work, jet lag or because of circadian rhythm sleep disorders, the resulting misalignment between circadian and wakefulness-sleep physiology leads to impaired cognitive performance, learning, emotion, and safety.

  2. Modelling of intercellular synchronization in the Drosophila circadian clock

    Institute of Scientific and Technical Information of China (English)

    Wang Jun-Wei; Chen Ai-Min; Zhang Jia-Jun; Yuan Zhan-Jiang; Zhou Tian-Shou

    2009-01-01

    In circadian rhythm generation, intercellular signaling factors are shown to play a crucial role in both sustaining intrinsic cellular rhythmicity and acquiring collective behaviours across a population of circadian neurons. However, the physical mechanism behind their role remains to be fully understood. In this paper, we propose an indirectly coupled multicellular model for the synchronization of Drosophila circadian oscillators combining both intracellular and intercellular dynamics. By simulating different experimental conditions, we find that such an indirect coupling way can synchronize both heterogeneous self-sustained circadian neurons and heterogeneous mutational damped circadian neurons. Moreover, they can also be entrained to ambient light-dark (LD) cycles depending on intercellular signaling.

  3. Daily Rhythms in Mobile Telephone Communication.

    Science.gov (United States)

    Aledavood, Talayeh; López, Eduardo; Roberts, Sam G B; Reed-Tsochas, Felix; Moro, Esteban; Dunbar, Robin I M; Saramäki, Jari

    2015-01-01

    Circadian rhythms are known to be important drivers of human activity and the recent availability of electronic records of human behaviour has provided fine-grained data of temporal patterns of activity on a large scale. Further, questionnaire studies have identified important individual differences in circadian rhythms, with people broadly categorised into morning-like or evening-like individuals. However, little is known about the social aspects of these circadian rhythms, or how they vary across individuals. In this study we use a unique 18-month dataset that combines mobile phone calls and questionnaire data to examine individual differences in the daily rhythms of mobile phone activity. We demonstrate clear individual differences in daily patterns of phone calls, and show that these individual differences are persistent despite a high degree of turnover in the individuals' social networks. Further, women's calls were longer than men's calls, especially during the evening and at night, and these calls were typically focused on a small number of emotionally intense relationships. These results demonstrate that individual differences in circadian rhythms are not just related to broad patterns of morningness and eveningness, but have a strong social component, in directing phone calls to specific individuals at specific times of day. PMID:26390215

  4. Proteomics of the photoneuroendocrine circadian system of the brain

    DEFF Research Database (Denmark)

    Møller, Morten; Lund-Andersen, Casper; Rovsing, Louise;

    2010-01-01

    The photoneuroendocrine circadian system of the brain consists of (a) specialized photoreceptors in the retina, (b) a circadian generator located in the forebrain that contains "clock genes," (c) specialized nuclei in the forebrain involved in neuroendocrine secretion, and (d) the pineal gland. The...... circadian generator is a nucleus, called the suprachiasmatic nucleus (SCN). The neurons of this nucleus contain "clock genes," the transcription of which exhibits a circadian rhythm. Most circadian rhythms are generated by the neurons of this nucleus and, via neuronal and humoral connections, the SCN......-generating system in mammals is described, and recent proteomic studies that investigate day/night changes in the retina, SCN, and pineal gland are reviewed. Further circadian changes controlled by the SCN in gene and protein expression in the liver are discussed....

  5. Timing of temporal and frontal seizures in relation to the circadian phase : A prospective pilot study

    NARCIS (Netherlands)

    Hofstra, Wytske A.; Gordijn, Marijke C. M.; van der Palen, Job; van Regteren, Renate; Grootemarsink, Bertine E.; de Weerd, Al W.

    2011-01-01

    There is strong evidence that epileptic seizures occur in diurnal or 24-h patterns. A study in rat models of partial epilepsy showed circadian seizure patterns, and in humans circadian rhythmicity in interictal discharges has been found, suggesting that circadian rhythm may play a role in epilepsy.

  6. A role for the circadian genes in drug addiction

    OpenAIRE

    Falcón, Edgardo; McClung, Colleen A.

    2008-01-01

    Diurnal and circadian rhythms are prominent in nearly all bodily functions. Chronic disruptions in normal sleep wake and social schedules can lead to serious health problems such as those seen in shift worker’s syndrome. Moreover, genetic disruptions in normal circadian gene functions have recently been linked to a variety of psychiatric conditions including depression, bipolar disorder, seasonal affective disorder and alcoholism. Recent studies are beginning to determine how these circadian ...

  7. Circadian Clock Genes: Effects on Dopamine, Reward and Addiction

    OpenAIRE

    Parekh, Puja K.; Ozburn, Angela R; McClung, Colleen A.

    2015-01-01

    Addiction is a widespread public health issue with social and economic ramifications. Substance abuse disorders are often accompanied by disruptions in circadian rhythms including sleep/wake cycles, which can exacerbate symptoms of addiction and dependence. Additionally, genetic disturbance of circadian molecular mechanisms can predispose some individuals to substance abuse disorders. In this review, we will discuss how circadian genes can regulate midbrain dopaminergic activity and subsequen...

  8. Recent Advances of Study on Molecular Circadian Rhythms and Correlated Disease%近日节律调控机制与相关疾病研究进展

    Institute of Scientific and Technical Information of China (English)

    陈图南; 蔡云; 王晖; 胡志安

    2012-01-01

    In mammals, an endogenous timing system synchronizes physiology and behavior to the rhythmic succession of day and night. On the cellular level which is the core mechanism of this system, a number of so-called clock genes were discovered, and these genes and their protein products were shown to organize into a transcriptional/translational feedback loops to give a near 24h rhythm. Recent years, several new clock components have been identified, there is now evidence that transcription may not play an only central role in determining the functioning of the clock: the identification of post-translational modifications of the clock proteins and the chrom-atin remodeling has revealed new levels of control. Disruption of the genes necessary for the circadian clock to function has diverse effects, including metabolism disorder disease and tumors. This review describes the recent advances in our knowledge of the molecular clockwork and correlated disease with human.%近日节律是生命体生理及行为变量遵循内源性的以接近1个太阳日的周期进行循环的生物过程,人体近日节律调控机制及其相关疾病研究已成为当前生物医学新兴领域和研究热点.过去二十年间,以生物钟基因及其相互作用环路为核心的一系列机制研究不断取得新的进展,初步形成了近日节律的分子模型,近年来,生物钟基因在染色体重塑、转录翻译调控、转录后修饰等多个层次的调控模式得到深入的研究.同时,近日节律失控与肿瘤、代谢紊乱等临床疾病的相关性及其影响机的转化研究日益增多,形成了新兴的时间医学.本文谨就近年来近日节律分子机制及其疾病相关研究的概况和最新进展做一总结.

  9. Circadian influences on myocardial infarction

    OpenAIRE

    Virag, Jitka A. I.; Lust, Robert M.

    2014-01-01

    Components of circadian rhythm maintenance, or “clock genes,” are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial...

  10. The circadian clock coordinates ribosome biogenesis.

    Directory of Open Access Journals (Sweden)

    Céline Jouffe

    Full Text Available Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis.

  11. Chronotype and stability of spontaneous locomotor activity rhythm in BMAL1-deficient mice.

    Science.gov (United States)

    Pfeffer, Martina; Korf, Horst-Werner; von Gall, Charlotte

    2015-02-01

    Behavior, physiological functions and cognitive performance change over the time of the day. These daily rhythms are either externally driven by rhythmic environmental cues such as the light/dark cycle (masking) or controlled by an internal circadian clock, the suprachiasmatic nucleus (SCN), which can be entrained to the light/dark cycle. Within a given species, there is genetically determined variability in the temporal preference for the onset of the active phase, the chronotype. The chronotype is the phase of entrainment between external and internal time and is largely regulated by the circadian clock. Genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population. However, little is known about the determination of the chronotype, the stability of the locomotor rhythm and the re-synchronization capacity to jet lag in an animal without a functional endogenous clock. Therefore, we analyzed the chronotype of BMAL1-deficient mice (BMAL1-/-) as well as the effects of repeated experimental jet lag on locomotor activity rhythms. Moreover, light-induced period expression in the retina was analyzed to assess the responsiveness of the circadian light input system. In contrast to wild-type mice, BMAL1-/- showed a significantly later chronotype, adapted more rapidly to both phase advance and delay but showed reduced robustness of rhythmic locomotor activity after repeated phase shifts. However, photic induction of Period in the retina was not different between the two genotypes. Our findings suggest that a disturbed clockwork is associated with a late chronotype, reduced rhythm stability and higher vulnerability to repeated external desynchronization. PMID:25216070

  12. NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators

    OpenAIRE

    Landgraf, Dominic; Wang, Lexie L.; Diemer, Tanja; Welsh, David K.

    2016-01-01

    Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, CLOCK-deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and periph...

  13. Dissociation of Ultradian and Circadian Phenotypes in Female and Male Siberian Hamsters

    OpenAIRE

    Prendergast, Brian J.; Cisse, Yasmine M.; Cable, Erin J.; Zucker, Irving

    2012-01-01

    Three experiments addressed whether pronounced alterations in the circadian system yielded concomitant changes in ultradian timing. Female Siberian hamsters were housed in a 16L:8D photoperiod after being subjected to a disruptive phase-shifting protocol that produced 3 distinct permanent circadian phenotypes: some hamsters entrained their circadian rhythms (CRs) with predominantly nocturnal locomotor activity (ENTR), others displayed free-running CRs (FR), and a third cohort was circadian ar...

  14. Social Rhythm Therapies for Mood Disorders: an Update.

    Science.gov (United States)

    Haynes, Patricia L; Gengler, Devan; Kelly, Monica

    2016-08-01

    Social rhythms are patterns of habitual daily behaviors that may impact the timing of the circadian system directly or indirectly through light exposure. According to the social rhythm hypothesis of depression, depressed individuals possess a vulnerability in the circadian timing system that inhibits natural recovery after disrupting life events. Social rhythm therapies (SRTs) support the implementation of regular, daily patterns of activity in order to facilitate recovery of circadian biological processes and also to improve mood. The majority of SRT research has examined interpersonal and social rhythm therapy (IPSRT) for bipolar disorder. Recent studies have examined IPSRT in inpatient settings, using alternative modes of delivery (group, combined individual and group, internet-based applications) and with brief timeframes. New forms of SRTs are developing that target mood in individuals who have experienced specific types of stressful life events. This manuscript reviews the theoretical and biological bases of SRTs and current literature on SRT outcomes. PMID:27338753

  15. Interpersonal and social rhythm therapy: an intervention addressing rhythm dysregulation in bipolar disorder

    OpenAIRE

    FRANK, ELLEN; Swartz, Holly A.; Boland, Elaine

    2007-01-01

    Bipolar disorder is characterized by frequent recurrences, often related to noncompliance with drug treatment, stressful life events, and disruptions in social rhythms. Interpersonal and social rhythm therapy (IPSRT) was designed to directly address these problem areas. This article discusses the circadian basis of IPSRT and the importance of stable daily routines in the maintenance of the euthymic state, as well as the two large controlled trials which empirically support this intervention. ...

  16. Sleep, mood, and circadian responses to bright green light during sleep

    OpenAIRE

    Grandner, Michael Andrew

    2007-01-01

    Based on human and animal research, it appears that light administered in the last two hours of sleep might be particularly effective as an antidepressant and in advancing circadian rhythms. Green light might be more effective than white light. An obvious advantage of light treatment during sleep is that disturbance and time cost during waking hours might be avoided. For these reasons, we decided to explore effects of a light treatment with a green light mask used for in the last hours of sle...

  17. Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders.

    Science.gov (United States)

    Barandas, Rita; Landgraf, Dominic; McCarthy, Michael J; Welsh, David K

    2015-12-01

    Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms. PMID:26483181

  18. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    International Nuclear Information System (INIS)

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks

  19. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory, E-mail: Tory.Hagen@oregonstate.edu [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  20. The Effects of Daily Rhythms on Sports Functions and Physiological Variables of Immune Elite Swimmers

    OpenAIRE

    Gholamreza Sharifi; Alireza Babai Mazreno; Marjan Mirjalili; Mohammad Hassan Ehrampoush

    2014-01-01

    Introduction Daily rhythm as one of the biological rhythms with a period of about 24 hours on various body systems and physiological responses affect on them. Body temperature is a fundamental variable as one of the specifications used daily rhythms The main purpose of this study was evaluating the effect of circadian rhythms on exercise performing and physiological variants of security system in swimmers. Materials and Methods In one study, before and after the 12 men swimmers in the league,...

  1. Sleep, Rhythms, and the Endocrine Brain: Influence of Sex and Gonadal Hormones

    OpenAIRE

    Mong, Jessica A.; Baker, Fiona C.; Mahoney, Megan M.; Paul, Ketema N.; Schwartz, Michael D.; Semba, Kazue; Silver, Rae

    2011-01-01

    While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids...

  2. Postoperative circadian disturbances

    DEFF Research Database (Denmark)

    Gögenur, Ismail

    2010-01-01

    reduced the first night after minimally invasive surgery. The core body temperature rhythm was disturbed after both major and minor surgery. There was a change in the sleep wake cycle with a significantly increased duration of REM-sleep in the day and evening time after major surgery compared with...... after major surgery was increased on the fourth day after surgery and the total excretion of AMT6s in urine was correlated to sleep efficiency and wake time after sleep onset, but was not correlated to the occurrence of postoperative cognitive dysfunction. We could only prove an effect of melatonin...... substitution 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...

  3. Differential effect of lithium on the circadian oscillator in young and old hamsters

    International Nuclear Information System (INIS)

    Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. It is also known to lengthen circadian period in several organisms. Previously, we reported that there was the association between lengthening circadian period by lithium and GSK-3 protein and its enzyme activity in the mouse suprachiasmatic nucleus (SCN). In this study, we show that lithium affects the circadian oscillator in young and old hamster SCN, in an age-dependent manner. We found that basal levels of phosphorylated GSK-3 (pGSK-3) protein expression in old hamsters are much lower than that in young hamsters. Furthermore, in the old hamsters, lithium did not affect the period of the locomotor activity rhythm or pGSK-3 expression, while changing period and pGSK-3 in the younger animals. These results indicate that the content of pGSK-3 in the SCN has an important role in age-dependent effects of lithium on the circadian oscillator

  4. Coordination of the maize transcriptome by a conserved circadian clock

    Directory of Open Access Journals (Sweden)

    Harmon Frank G

    2010-06-01

    Full Text Available Abstract Background The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system. Results Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways. Conclusions Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species.

  5. Circadian Organization of Behavior and Physiology in Drosophila

    Science.gov (United States)

    Allada, Ravi; Chung, Brian Y.

    2010-01-01

    Circadian clocks organize behavior and physiology to adapt to daily environmental cycles. Genetic approaches in the fruit fly, Drosophila melanogaster, have revealed widely conserved molecular gears of these 24-h timers. Yet much less is known about how these cell-autonomous clocks confer temporal information to modulate cellular functions. Here we discuss our current knowledge of circadian clock function in Drosophila, providing an overview of the molecular underpinnings of circadian clocks. We then describe the neural network important for circadian rhythms of locomotor activity, including how these molecular clocks might influence neuronal function. Finally, we address a range of behaviors and physiological systems regulated by circadian clocks, including discussion of specific peripheral oscillators and key molecular effectors where they have been described. These studies reveal a remarkable complexity to circadian pathways in this “simple” model organism. PMID:20148690

  6. Keeping the right time in space: importance of circadian clock and sleep for physiology and performance of astronauts

    OpenAIRE

    Guo, Jin-Hu; Qu, Wei-Min; Chen, Shan-Guang; CHEN, XIAO-PING; Lv, Ke; Huang, Zhi-Li; Wu, Yi-Lan

    2014-01-01

    The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth’s environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we su...

  7. Analysis of the effects of resistance training on circadan rhythm of endocrine hormones

    Directory of Open Access Journals (Sweden)

    Ardalan Shariat

    2015-07-01

    Full Text Available In the past decade, the number of the studies conducted on the effects of resistance training on circadian rhythm of endocrine hormones is increasing exponentially. The aim of this report is to explore the current and prevailing studies in an attempt to elucidate the findings of resistance training on circadian rhythm of endocrine hormones. Analysis of the available research from 2001 until 2015 demonstrated a wide variety of methodologies and sampled populations. However, all sampled studies made use of a pre-test, post-test experimental design taking place during the day. In addition, the primary hormones assessed were testosterone and cortisol, sampled via saliva. Collectively the sampled studies demonstrated that resistance training is capable of affecting the circadian rhythm of endocrine hormone secretion. However, it must be noted that these alterations were primary following training and the alterations transient in nature, with endocrine responses returning to normal circadian rhythm ranges via natural feedback mechanisms.

  8. Circadian clocks are designed optimally

    CERN Document Server

    Hasegawa, Yoshihiko

    2014-01-01

    Circadian rhythms are acquired through evolution to increase the chances for survival by synchronizing to the daylight cycle. Reliable synchronization is realized through two trade-off properties: regularity to keep time precisely, and entrainability to synchronize the internal time with daylight. Since both properties have been tuned through natural selection, their adaptation can be formalized in the framework of mathematical optimization. By using a succinct model, we found that simultaneous optimization of regularity and entrainability entails inherent features of the circadian mechanism irrespective of model details. At the behavioral level we discovered the existence of a dead zone, a time during which light pulses neither advance nor delay the clock. At the molecular level we demonstrate the role-sharing of two light inputs, phase advance and delay, as is well observed in mammals. We also reproduce the results of phase-controlling experiments and predict molecular elements responsible for the clockwork...

  9. Circadian organization of the mammalian retina: from gene regulation to physiology and diseases.

    Science.gov (United States)

    McMahon, Douglas G; Iuvone, P Michael; Tosini, Gianluca

    2014-03-01

    The retinal circadian system represents a unique structure. It contains a complete circadian system and thus the retina represents an ideal model to study fundamental questions of how neural circadian systems are organized and what signaling pathways are used to maintain synchrony of the different structures in the system. In addition, several studies have shown that multiple sites within the retina are capable of generating circadian oscillations. The strength of circadian clock gene expression and the emphasis of rhythmic expression are divergent across vertebrate retinas, with photoreceptors as the primary locus of rhythm generation in amphibians, while in mammals clock activity is most robust in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules to entrain circadian rhythms in the retina and also in other ocular structures. Recent studies have also suggested GABA as an important component of the system that regulates retinal circadian rhythms. These transmitter-driven influences on clock molecules apparently reinforce the autonomous transcription-translation cycling of clock genes. The molecular organization of the retinal clock is similar to what has been reported for the SCN although inter-neural communication among retinal neurons that form the circadian network is apparently weaker than those present in the SCN, and it is more sensitive to genetic disruption than the central brain clock. The melatonin-dopamine system is the signaling pathway that allows the retinal circadian clock to reconfigure retinal circuits to enhance light-adapted cone-mediated visual function during the day and dark-adapted rod-mediated visual signaling at night. Additionally, the retinal circadian clock also controls circadian rhythms in disk shedding and phagocytosis, and possibly intraocular pressure. Emerging experimental data also indicate that circadian clock is also implicated in the pathogenesis of eye disease and compelling experimental data

  10. Circadian and pharmacological regulation of casein kinase I in the hamster suprachiasmatic nucleus

    Indian Academy of Sciences (India)

    Patricia V. Agostino; Santiago A. Plano; Diego A. Golombek

    2008-12-01

    In mammals, the mechanism for the generation of circadian rhythms and entrainment by light–dark (LD) cycles resides in the hypothalamic suprachiasmatic nuclei (SCN), and the principal signal that adjusts this biological clock with environmental timing is the light:dark cycle. Within the SCN, rhythms are generated by a complex of molecular feedback loops that regulate the transcription of clock genes, including per and cry. Posttranslational modification plays an essential role in the regulation of biological rhythms; in particular, clock gene phosphorylation by casein kinase I, both epsilon (CKI) and delta (CKI), regulates key molecular mechanisms in the circadian clock. In this paper, we report for the first time that CKI activity undergoes a significant circadian rhythm in the SCN (peaking at circadian time 12, the start of the subjective night), and its pharmacological inhibition alters photic entrainment of the clock, indicating that CKI may be a key element in this pathway.

  11. Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder.

    Science.gov (United States)

    Bunney, B G; Li, J Z; Walsh, D M; Stein, R; Vawter, M P; Cartagena, P; Barchas, J D; Schatzberg, A F; Myers, R M; Watson, S J; Akil, H; Bunney, W E

    2015-02-01

    Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small

  12. Circadian Dysrhythmias, Physiological Aberrations, and the Link to Skin Cancer

    Directory of Open Access Journals (Sweden)

    Daniel Gutierrez

    2016-04-01

    Full Text Available Circadian rhythms are core regulators of a variety of mammalian physiologic processes and oscillate in a 24-h pattern. Many peripheral organs possess endogenous rhythmicity that is then modulated by a master clock; the skin is one of these peripheral organs. The dysregulation of rhythms is associated with decreased ability to ameliorate cellular stressors at a local and global level, which then increases the propensity for the development of neoplastic growths. In this article, we review the implications of altered circadian rhythms on DNA repair as well as modified gene expression of core clock proteins with particular focus on skin models. These findings are then correlated with epidemiologic data regarding skin cancer to showcase the effects of circadian disruption on this phenomenon.

  13. Circadian control of mouse heart rate and blood pressure by the suprachiasmatic nuclei: behavioral effects are more significant than direct outputs.

    Directory of Open Access Journals (Sweden)

    W John Sheward

    Full Text Available BACKGROUND: Diurnal variations in the incidence of events such as heart attack and stroke suggest a role for circadian rhythms in the etiology of cardiovascular disease. The aim of this study was to assess the influence of the suprachiasmatic nucleus (SCN circadian clock on cardiovascular function. METHODOLOGY/PRINCIPAL FINDINGS: Heart rate (HR, blood pressure (BP and locomotor activity (LA were measured in circadian mutant (Vipr2(-/- mice and wild type littermates, using implanted radio-telemetry devices. Sleep and wakefulness were studied in similar mice implanted with electroencephalograph (EEG electrodes. There was less diurnal variation in the frequency and duration of bouts of rest/activity and sleep/wake in Vipr2(-/- mice than in wild type (WT and short "ultradian" episodes of arousal were more prominent, especially in constant conditions (DD. Activity was an important determinant of circadian variation in BP and HR in animals of both genotypes; altered timing of episodes of activity and rest (as well as sleep and wakefulness across the day accounted for most of the difference between Vipr2(-/- mice and WT. However, there was also a modest circadian rhythm of resting HR and BP that was independent of LA. CONCLUSIONS/SIGNIFICANCE: If appropriate methods of analysis are used that take into account sleep and locomotor activity level, mice are a good model for understanding the contribution of circadian timing to cardiovascular function. Future studies of the influence of sleep and wakefulness on cardiovascular physiology may help to explain accumulating evidence linking disrupted sleep with cardiovascular disease in man.

  14. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Susie Lee

    Full Text Available BACKGROUND: Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Period1 and 2 (Per or Cryptochrome1 and 2 (Cry are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone. However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: Mice lacking Per1 and 2, Cry1 and 2, or one copy of Bmal1, all show increased spontaneous and radiation-induced tumor development. The neoplastic growth of Per-mutant somatic cells is not controlled cell-autonomously but is dependent upon extracellular mitogenic signals. Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation. Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. CONCLUSIONS/SIGNIFICANCE: Tumor suppression in vivo is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor.

  15. Interactions between the circadian clock and metabolism: there are good times and bad times

    Institute of Scientific and Technical Information of China (English)

    Mi Shi; Xiangzhong Zheng

    2013-01-01

    An endogenous circadian (~24 h) clock regulates rhythmic processes of physiology,metabolism and behavior in most living organisms.While able to free-run under constant conditions,the circadian clock is coupled to day:night cycles to increase its amplitude and align the phase of circadian rhythms to the right time of the day.Disruptions of the circadian clock are correlated with brain dysfunctions,cardiovascular diseases and metabolic disorders.In this review,we focus on the interactions between the circadian clock and metabolism.We discuss recent findings on circadian clock regulation of feeding behavior and rhythmic expression of metabolic genes,and present evidence of metabolic input to the circadian clock.We emphasize how misalignment of circadian clocks within the body and with environmental cycles or daily schedules leads to the increasing prevalence of metabolic syndromes in modern society.

  16. Effects of Ovarian Hormones on Internal Circadian Organization in Rats1

    OpenAIRE

    Murphy, Zachary C.; Pezuk, Pinar; Menaker, Michael; Sellix, Michael T

    2013-01-01

    The circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is the central pacemaker driving rhythms in endocrine physiology. Gonadal steroid hormones affect behavioral rhythms and clock gene expression. However, the impact of fluctuating ovarian steroid levels during the estrous cycle on internal circadian organization remains to be determined. Further, it is not known if steroid hormone depletion, as in menopause, affects the timing system. To determine the influence of est...

  17. Prospective evaluation of the Circadian Efficacy of (Day)Light in Rooms

    OpenAIRE

    Pechacek, C.; Andersen, Marilyne; Lockley, S. W.

    2008-01-01

    Recent studies have attempted to link environmental cues, such as lighting, with human performance and health, and initial findings seem to indicate a positive correlation between the two. Light is the major environmental time cue that resets the human circadian pacemaker, an endogenous clock in the hypothalamus that controls the timing of many 24-hour rhythms in physiology and behavior. Insufficient or inappropriate light exposure can disrupt normal circadian rhythms which may result in adve...

  18. Different circadian oscillators control Ca2+ fluxes and Lhcb gene expression

    OpenAIRE

    Sai, Jiqing; Johnson, Carl Hirschie

    1999-01-01

    Circadian biological clocks control many biological events, but the pathways by which these events are controlled are largely unknown. Based on a model suggesting that cytosolic-free calcium levels control the expression of the Lhcb gene in plants, we tested whether the circadian oscillation of free calcium is responsible for driving the rhythm of Lhcb expression. We found that these rhythms free-run with different periods in tobacco seedlings in constant conditions. Moreover, robust oscillat...

  19. Comparison of effects of bright light therapy alone or combined with fluoxetine on severity of depression, circadian rhythms, mood disturbance, and sleep quality, in patients with non-seasonal depression

    OpenAIRE

    Ağargün MY; Hızlı Sayar G; Bulut H; Tan O

    2013-01-01

    Mehmet Yücel Agargün,1 Gokben Hizli Sayar,2 Hüseyin Bulut,3 Oguz Tan21Medipol University, Department of Psychiatry, Istanbul, Turkey; 2Uskudar University, Neuropsychiatry Istanbul Hospital, Istanbul, Turkey; 3Büyükçekmece Government Hospital, Department of Psychiatry, Istanbul, TurkeyPurpose: To compare effects of bright light therapy (BLT) alone or combined with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, on severity of depression, circadian ...

  20. Comprehensive analysis of circadian periodic pattern in plant transcriptome

    OpenAIRE

    Ptitsyn Andrey

    2008-01-01

    Abstract Background Circadian rhythm is a crucial factor in orchestration of plant physiology, keeping it in synchrony with the daylight cycle. Previous studies have reported that up to 16% of plant transcriptome are circadially expressed. Results Our studies of mammalian gene expression revealed circadian baseline oscillation in nearly 100% of genes. Here we present a comprehensive analysis of periodicity in two independent data sets. Application of the advanced algorithms and analytic appro...

  1. Temperature as a universal resetting cue for mammalian circadian oscillators

    OpenAIRE

    Buhr, Ethan D.; Yoo, Seung-Hee; Takahashi, Joseph S.

    2010-01-01

    Environmental temperature cycles are a universal entraining cue for all circadian systems at the organismal level with the exception of homeothermic vertebrates. We report here that resistance to temperature entrainment is a property of the suprachiasmatic nucleus (SCN) network and is not a cell autonomous property of mammalian clocks. This differential sensitivity to temperature allows the SCN to drive circadian rhythms in body temperature which can then act as a universal cue for the entrai...

  2. Mistimed sleep disrupts circadian regulation of the human transcriptome.

    OpenAIRE

    Archer, SN; Laing, EE; Möller-Levet, CS; Van der Veen, DR; Bucca, G; Lazar, AS; Santhi, N.; Slak, A; Kabiljo, R.; von Schantz, M.; Smith, CP; DIJK, DJ

    2014-01-01

    Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature i...

  3. Ultradian rhythm unmasked in the Pdf clock mutant of Drosophila

    Indian Academy of Sciences (India)

    Yuuichi Seki; Teiichi Tanimura

    2014-09-01

    A diverse range of organisms shows physiological and behavioural rhythms with various periods. Extensive studies have been performed to elucidate the molecular mechanisms of circadian rhythms with an approximately 24 h period in both Drosophila and mammals, while less attention has been paid to ultradian rhythms with shorter periods. We used a video-tracking method to monitor the movement of single flies, and clear ultradian rhythms were detected in the locomotor behaviour of wild type and clock mutant flies kept under constant dark conditions. In particular, the Pigment-dispersing factor mutant (Pdf01) demonstrated a precise and robust ultradian rhythmicity, which was not temperature compensated. Our results suggest that Drosophila has an endogenous ultradian oscillator that is masked by circadian rhythmic behaviours.

  4. Working night shifts affects surgeons' biological rhythm

    DEFF Research Database (Denmark)

    Amirian, Ilda; Andersen, Lærke T; Rosenberg, Jacob;

    2015-01-01

    BACKGROUND: Chronic sleep deprivation combined with work during the night is known to affect performance and compromise residents' own safety. The aim of this study was to examine markers of circadian rhythm and the sleep-wake cycle in surgeons working night shifts. METHODS: Surgeons were monitored...... prospectively for 4 days: pre call, on call, post call day 1 (PC1), and post call day 2 (PC2). The urinary metabolite of melatonin and cortisol in saliva were measured to assess the circadian rhythm. Sleep and activity were measured by actigraphy. Subjective measures were assessed by the Karolinska Sleepiness...... Scale and Visual Analog Scale of fatigue, general well-being, and sleep quality. RESULTS: For both metabolite of melatonin and cortisol, a significant difference (P < .05) was found in the measurement period between on call and pre call values. There was increased sleep time during the day on call and...

  5. Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

    Science.gov (United States)

    Dijk, D. J.; Duffy, J. F.

    1999-01-01

    The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

  6. Gravitational biology and the mammalian circadian timing system

    Science.gov (United States)

    Fuller, Charles A.; Murakami, Dean M.; Sulzman, Frank M.

    1989-01-01

    Using published reports, this paper compares and contrasts results on the effects of altered gravitational fields on the regulation in mammals of several physiological and behavioral variables with the circadian regulation of the same variables. The variables considered include the temperature regulation, heart rate, activity, food intake, and calcium balance. It is shown that, in rats, the homeostatic regulation of the body temperature, heart rate, and activity becomes depressed following exposure to a 2 G hyperdynamic field, and recovers within 6 days of 1 G condition. In addition, the circadian rhythms of these variables exhibit a depression of the rhythm amplitude; a recovery of this condition requires a minimum of 7 days.

  7. Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa

    NARCIS (Netherlands)

    Diernfellner, ACR; Schafmeier, T; Merrow, MW; Brunner, M; Diernfellner, Axel C.R.

    2005-01-01

    Expression levels and ratios of the long (1) and short (s) isoforms of the Neurospora circadian clock protein FREQUENCY (FRQ) are crucial for temperature compensation of circadian rhythms. We show that the ratio of 1-FRQ versus s-FRQ is regulated by thermosensitive splicing of intron 6 of frq, a pro

  8. Synchronization of circadian bioluminescence as a group-foraging strategy in cave glowworms.

    Science.gov (United States)

    Maynard, Andrew J; Merritt, David J

    2013-07-01

    Flies of the genus Arachnocampa are sit-and-lure predators that use bioluminescence to attract flying prey to their silk webs. Some species are most common in rainforest habitat and others inhabit both caves and rainforest. We have studied the circadian regulation of bioluminescence in two species: one found in subtropical rainforest with no known cave populations and the other found in temperate rainforest with large populations in limestone caves. The rainforest species is typical of most nocturnal animals in that individuals are entrained by the light:dark (LD) cycle to be active at night; in this case, their propensity to bioluminesce is greatest at night. The dual-habitat species shows an opposite phase response to the same entrainment; its bioluminescence propensity rhythm is entrained by LD exposure to peak during the day. Nevertheless, in LD environments, individuals do not bioluminesce during the day because ambient light inhibits their bioluminescence (negative masking), pushing bioluminescence into the dark period. This unusual and unexpected phenomenon could be related to their association with caves and has been suggested to be an adaptation of the circadian system that promotes synchronization of a colony's output of bioluminescence. Here, we use controlled laboratory experiments to show that individuals do synchronize their bioluminescence rhythms when in visual contact with each other. Entrainment of the bioluminescence rhythm to the biological photophase causes colony-wide synchronization, creating a daily sinusoidal rhythm of the intensity of bioluminescence in the many thousands of individuals making up a colony. This synchronization could provide a group-foraging advantage, allowing the colony to glow most brightly when the prey are most likely to be active. PMID:23575257

  9. Endocannabinoid signalling: has it got rhythm?

    OpenAIRE

    Vaughn, Linda K.; Denning, Gerene; Stuhr, Kara L.; de Wit, Harriet; Hill, Matthew N.; Hillard, Cecilia J.

    2010-01-01

    Endogenous cannabinoid signalling is widespread throughout the body, and considerable evidence supports its modulatory role in many fundamental physiological processes. The daily and seasonal cycles of the relationship of the earth and sun profoundly affect the terrestrial environment. Terrestrial species have adapted to these cycles in many ways, most well studied are circadian rhythms and hibernation. The purpose of this review was to examine literature support for three hypotheses: (i) end...

  10. Examining the Acute and Chronic Effects of Sepsis on the Circadian Clock in the Mouse

    OpenAIRE

    O'Callaghan, Emma

    2013-01-01

    Circadian rhythms are recurring patterns (~24hrs) in behaviour and physiology that are driven primarily by an endogenous biological timekeeping system, with the master pacemaker located in the suprachiasmatic nucleus. Studies have indicated bidirectional relationships between the circadian and the immune systems, however while there is much evidence regarding the regulation of immune function by the circadian system, information regarding the impact of immune processes on the timekeeping syst...

  11. Immunity’s fourth dimension: approaching the circadian-immune connection

    OpenAIRE

    Arjona, Alvaro; Adam C Silver; Walker, Wendy E; Fikrig, Erol

    2012-01-01

    The circadian system ensures the generation and maintenance of self-sustained ~24 h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related di...

  12. Nutrition and the circadian system.

    Science.gov (United States)

    Potter, Gregory D M; Cade, Janet E; Grant, Peter J; Hardie, Laura J

    2016-08-01

    The human circadian system anticipates and adapts to daily environmental changes to optimise behaviour according to time of day and temporally partitions incompatible physiological processes. At the helm of this system is a master clock in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN are primarily synchronised to the 24-h day by the light/dark cycle; however, feeding/fasting cycles are the primary time cues for clocks in peripheral tissues. Aligning feeding/fasting cycles with clock-regulated metabolic changes optimises metabolism, and studies of other animals suggest that feeding at inappropriate times disrupts circadian system organisation, and thereby contributes to adverse metabolic consequences and chronic disease development. 'High-fat diets' (HFD) produce particularly deleterious effects on circadian system organisation in rodents by blunting feeding/fasting cycles. Time-of-day-restricted feeding, where food availability is restricted to a period of several hours, offsets many adverse consequences of HFD in these animals; however, further evidence is required to assess whether the same is true in humans. Several nutritional compounds have robust effects on the circadian system. Caffeine, for example, can speed synchronisation to new time zones after jetlag. An appreciation of the circadian system has many implications for nutritional science and may ultimately help reduce the burden of chronic diseases. PMID:27221157

  13. Sleep Deprivation and Circadian Disruption: Stress, Allostasis, and Allostatic Load.

    Science.gov (United States)

    McEwen, Bruce S; Karatsoreos, Ilia N

    2015-03-01

    Sleep has important homeostatic functions, and circadian rhythms organize physiology and behavior on a daily basis to insure optimal function. Sleep deprivation and circadian disruption can be stressors, enhancers of other stressors that have consequences for the brain and many body systems. Whether the origins of circadian disruption and sleep disruption and deprivation are from anxiety, depression, shift work, long-distance air travel, or a hectic lifestyle, there are consequences that impair brain functions and contribute to the cumulative wear and tear on body systems caused by too much stress and/or inefficient management of the systems that promote adaptation. PMID:26055668

  14. Dissociation of ultradian and circadian phenotypes in female and male Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Cisse, Yasmine M; Cable, Erin J; Zucker, Irving

    2012-08-01

    Three experiments addressed whether pronounced alterations in the circadian system yielded concomitant changes in ultradian timing. Female Siberian hamsters were housed in a 16L:8D photoperiod after being subjected to a disruptive phase-shifting protocol that produced 3 distinct permanent circadian phenotypes: some hamsters entrained their circadian rhythms (CRs) with predominantly nocturnal locomotor activity (ENTR), others displayed free-running CRs (FR), and a third cohort was circadian arrhythmic (ARR). The period of the ultradian locomotor rhythm (UR) did not differ among the 3 circadian phenotypes; neuroendocrine generation of URs remains viable in the absence of coherent circadian organization and appears to be mediated by substrates functionally and anatomically distinct from those that generate CRs. Pronounced light-dark differences in several UR characteristics in ENTR hamsters were completely absent in circadian arrhythmic hamsters. The disruptive phase-shifting protocol may compromise direct visual input to ultradian oscillators but more likely indirectly affects URs by interrupting visual afference to the circadian system. Additional experiments documented that deuterium oxide and constant light, each of which substantially lengthened the period of free-running CRs, failed to change the period of concurrently monitored URs. The resistance of URs to deuteration contrasts with the slowing of virtually all other biological timing processes, including CRs. Considered together, the present results point to the existence of separable control mechanisms for generation of circadian and ultradian rhythms. PMID:22855573

  15. Circadian Metabolism in the Light of Evolution

    DEFF Research Database (Denmark)

    Gerhart-Hines, Zachary; Lazar, Mitchell A.

    2015-01-01

    A review. Circadian rhythm, or daily oscillation, of behaviors and biol. processes is a fundamental feature of mammalian physiol. that has developed over hundreds of thousands of years under the continuous evolutionary pressure of energy conservation and efficiency. Evolution has fine-tuned the...... energetic balance and adaptability, and it discusses potential therapeutic strategies to reset clock metabolic control to modern time for the benefit of human health. [on SciFinder(R)]...

  16. Circadian clock, cell cycle and cancer

    OpenAIRE

    Cansu Özbayer; İrfan Değirmenci

    2011-01-01

    There are a few rhythms of our daily lives that we are under the influence. One of them is characterized by predictable changes over a 24-hour timescale called circadian clock. This cellular clock is coordinated by the suprachiasmatic nucleus in the anterior hypothalamus. The clock consist of an autoregulatory transcription-translation feedback loop compose of four genes/proteins; BMAL1, Clock, Cyrptochrome, and Period. BMAL 1 and Clock are transcriptional factors and Period and Cyrptochrome ...

  17. Preliminary study of the effect circadian rhythm and food on the concentration of endogenous reduced glutathione in plasma of healthy Chinese by HPLC-MS/MS%液-质联用法初步研究健康人血浆内源性还原型谷胱甘肽的昼夜差异及饮食影响

    Institute of Scientific and Technical Information of China (English)

    张全英; 华雯妍; 朱艺芳; 黄明; 王蒙; 施爱明; 周文佳

    2011-01-01

    目的:初步研究时辰及饮食对健康中国人血浆中内源性还原型谷胱甘肽(GSH)的影响.方法:16名男性健康受试者分别在不同时辰、餐前及餐后采集静脉血2 mL,以已建立的HPLC-MS/MS快速测定法测定血浆中内源性GSH的浓度,数据使用SPSS软件统计分析,比较不同时辰以及餐前餐后血浆中内源性GSH浓度差异有无显著性.结果:全部测定在一批内完成,16名男性健康受试者早晨空腹、早晨餐后和晚上空腹的血浆GSH浓度分别为(0.18±0.06),(0.23±0.11),(0.12±0.04)mg·L-1. 3组数据两两配时t检验结果P值均小于0.05,具有显著性差异.结论:初步研究显示时辰和饮食对血浆中内源性GSH浓度影响均有显著性.%OBJECTIVE To study the effect of circadian rhythm and food on the concentration of endogenous GSH in plasma of healthy Chinese volunteers. METHODS The plasma samples of sixteen healthy male volunteers were collected fasting in the morning, after meal in the morning and fasting in the evening. All the samples were determined by HPLC-MS/MS method which has been validated. All of the concentration data were statistic by the SPSS statistical soft to analysis if the concentrations were significant deviation. RESULTS All of the determinations were finished in one batch , the concentration fasting in the morning, after meal in the morning and fasting in the evening of sixteen healthy male volunteers were (0. 18 ± 0. 06), (0. 23 ± 0. 12) and (0. 12 ± 0. 04) mg·L- 1, respectively. Paired t-test between two of three data showed that P<0. 05, which means there was significant difference between each others. CONCLUSION The results showed that both circadian rhythm and food effect have significant influence on the concentration of endogenous GSH in plasma.

  18. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA.

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    2008-10-01

    Full Text Available The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER

  19. Optimal implementations for reliable circadian clocks.

    Science.gov (United States)

    Hasegawa, Yoshihiko; Arita, Masanori

    2014-09-01

    Circadian rhythms are acquired through evolution to increase the chances for survival through synchronizing with the daylight cycle. Reliable synchronization is realized through two trade-off properties: regularity to keep time precisely, and entrainability to synchronize the internal time with daylight. We find by using a phase model with multiple inputs that achieving the maximal limit of regularity and entrainability entails many inherent features of the circadian mechanism. At the molecular level, we demonstrate the role sharing of two light inputs, phase advance and delay, as is well observed in mammals. At the behavioral level, the optimal phase-response curve inevitably contains a dead zone, a time during which light pulses neither advance nor delay the clock. We reproduce the results of phase-controlling experiments entrained by two types of periodic light pulses. Our results indicate that circadian clocks are designed optimally for reliable clockwork through evolution. PMID:25238386

  20. Circadian oscillators in the mouse brain

    DEFF Research Database (Denmark)

    Rath, Martin F; Rovsing, Louise; Møller, Morten

    2014-01-01

    The circadian timekeeper of the mammalian brain resides in the suprachiasmatic nucleus of the hypothalamus (SCN), and is characterized by rhythmic expression of a set of clock genes with specific 24-h daily profiles. An increasing amount of data suggests that additional circadian oscillators...... residing outside the SCN have the capacity to generate peripheral circadian rhythms. We have recently shown the presence of SCN-controlled oscillators in the neocortex and cerebellum of the rat. The function of these peripheral brain clocks is unknown, and elucidating this could involve mice with...... conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje and...

  1. Evolution of circadian organization in vertebrates

    Directory of Open Access Journals (Sweden)

    M. Menaker

    1997-03-01

    Full Text Available Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations: i in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN, ii in many non-mammalian vertebrates of all classes (but not in any mammals the pineal gland is both a photoreceptor and a circadian oscillator, and iii in all non-mammalian vertebrates (but not in any mammals there are extraretinal (and extrapineal circadian photoreceptors. An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates

  2. Circadian rhythmicity of synapses in mouse somatosensory cortex.

    Science.gov (United States)

    Jasinska, Malgorzata; Grzegorczyk, Anna; Woznicka, Olga; Jasek, Ewa; Kossut, Malgorzata; Barbacka-Surowiak, Grazyna; Litwin, Jan A; Pyza, Elzbieta

    2015-10-01

    The circadian rhythmicity displayed by motor behavior of mice: activity at night and rest during the day; and the associated changes in the sensory input are reflected by cyclic synaptic plasticity in the whisker representations located in the somatosensory (barrel) cortex. It was not clear whether diurnal rhythmic changes in synapse density previously observed in the barrel cortex resulted from changes in the activity of the animals, from daily light/dark (LD) rhythm or are driven by an endogenous clock. These changes were investigated in the barrel cortex of C57BL/6 mouse strain kept under LD 12 : 12 h conditions and in constant darkness (DD). Stereological analysis of serial electron microscopic sections was used to assess numerical density of synapses. In mice kept under LD conditions, the total density of synapses and the density of excitatory synapses located on dendritic spines was higher during the light period (rest phase). In contrast, the density of inhibitory synapses located on dendritic spines increased during the dark period (activity phase). Under DD conditions, the upregulation of the inhibitory synapses during the activity phase was retained, but the cyclic changes in the density of excitatory synapses were not observed. The results show that the circadian plasticity concerns only synapses located on spines (and not those on dendritic shafts), and that excitatory and inhibitory synapses are differently regulated during the 24 h cycle: the excitatory synapses are influenced by light, whilst the inhibitory synapses are driven by the endogenous circadian clock. PMID:26274013

  3. Dissociation of Circadian and Circatidal Timekeeping in the Marine Crustacean Eurydice pulchra

    Czech Academy of Sciences Publication Activity Database

    Zhang, L.; Hastings, M. H.; Green, E. W.; Tauber, E.; Sládek, Martin; Webster, S. G.; Kyriacou, C. P.; Wilcockson, D. C.

    2013-01-01

    Roč. 23, č. 19 (2013), s. 1863-1873. ISSN 0960-9822 Institutional support: RVO:67985823 Keywords : tidal rhythms * circadian rhythms * circatidal oscillator * Eurydice pulchra * casein kinase 1 * clock genes, chromatophore Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.916, year: 2013

  4. Protocolo de actuación preventiva para riesgo debido a alteraciones del ritmo circadiano en médicos de urgencias que trabajan en turnos de 24 horas Preventive action protocol for risk due to circadian rhythm disturbances in emergency physicians working in 24 hours shifts

    Directory of Open Access Journals (Sweden)

    Loreto Fillat de Acosta

    2009-12-01

    Full Text Available La autora analiza la situación patológica de los médicos de urgencias con turnos de 24 horas que alteran el ritmo circadiano, el estudio describe las condiciones de trabajo que afectan el ritmo biológico sueño-vigilia y las tareas intelectuales y de habilidades mecánicas desempeñadas por este personal, los daños a prevenir (accidentes in itinere, accidentes por manipulación de material biológico, enfermedades somáticas y psíquicas y el riesgo para los pacientes. Se propone un protocolo de actuación preventiva que abarca la mayor parte del trabajo, cuándo actuar, revisión de recursos, actuaciones a realizar en una unidad de salud laboral y sistema de comunicación al resto del hospital, Servicio de Prevención de Riesgos Laborales y Sistema Nacional de Salud.The author analyzes the pathological situation concerning to emergency physicians with 24-hour shifts which disturb their circadian rhythms, the study describes the working conditions that affect the biological sleep-wake rhythm and intellectual tasks and mechanical skills performed by these staff, damage to be prevented (commuting accidents, accidents caused by handling of biological material, somatic and psychic diseases and the risk to patients. After that, it's developed a proposal of preventive action protocol covering most of the work and finally when to act, available resources and actions to be taken in an occupational health unit, in addition to the communication system to the rest of the hospital, Occupational and Hazard Preventive Service and the National Health System.

  5. Basic Principles of Interpersonal Social Rhythm Therapy in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Gokben Hizli Sayar

    2014-08-01

    Full Text Available Interpersonal Social Rhythm Therapy is a psychotherapy modality that helps the patient recognize the relationship between disruptions in social rhythms and the onset of previous episodes of psychiatric disorders. It uses psychoeducation and behavioral techniques to maintain social rhythm and sleep/wake regularity. It is closely related to and ldquo;social zeitgeber theory and rdquo; that emphasizes the importance that social rhythm regularity may play in synchronization of circadian rhythms in individuals with or at risk for bipolar spectrum disorders. Interpersonal and social rhythm therapy have been shown to stabilize social rhythms and enhance course and outcome in bipolar disorder. This review focuses on the theoretical principles and the basic steps of interpersonal and social rhythm therapy as a psychotherapy approach in bipolar disorder. PubMed, Scopus, Google Scholar databases were searched without temporal restriction. Search terms included interpersonal social rhythm therapy, bipolar, mood disorders. Abstracts were reviewed for relevance, and randomized controlled trials of interpersonal and social rhythm therapy in bipolar disorder selected. These researches also summarized on the final part of this review. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 438-446

  6. An automated tracking system for Caenorhabditis elegans locomotor behavior and circadian studies application.

    Science.gov (United States)

    Simonetta, Sergio H; Golombek, Diego A

    2007-04-15

    Automation of simple behavioral patterns, such as locomotor activity, is fundamental for pharmacological and genetic screening studies. Recently, circadian behaviors in locomotor activity and stress responses were reported in the nematode Caenorhabditis elegans, a well-known model in genetics and developmental studies. Here we present a new method for long-term recordings of C. elegans (as well as other similar-sized animals) locomotor activity based on an infrared microbeam scattering. Individual nematodes were cultured in a 96-well microtiter plate; we tested L15, CeMM and E. coli liquid cultures in long-term activity tracking experiments, and found CeMM to be the optimal medium. Treatment with 0.2% azide caused an immediate decrease in locomotor activity as recorded with our system. In addition to the validation of the method (including hardware and software details), we report its application in chronobiological studies. Circadian rhythms in animals entrained to light-dark and constant dark conditions (n=48 and 96 worms, respectively) at 16 degrees C, were analyzed by LS periodograms. We obtained a 24.2+/-0.44 h period (52% of significantly rhythmic animals) in LD, and a 23.1+/-0.40 h period (37.5% of significantly rhythmic animals) under DD. The system is automateable using microcontrollers, of low-cost construction and highly reproducible. PMID:17207862

  7. [Circadian organization of the indices of external respiration in bronchial asthma patients].

    Science.gov (United States)

    Fedoseev, G B; Degtiareva, Z Ia; Savich, A A; Alekseev, M Iu; Bolodon, S A

    1985-01-01

    Circadian rhythms of external respiration function (ERF) and body function (BF) were studied in 20 patients with mild bronchial asthma, 20 patients with bronchial asthma of medium gravity and in 14 healthy subjects. Circadian rhythms of the medium-group parameters of ERF were shown to be statistically insignificant, whereas individual circadian chronograms demonstrated circadian rhythms for all the patients with BA and healthy subjects. Essential differences were found in the organization of the temporary structure of circadian rhythms of ERF in BA patients and healthy subjects. It was discovered that in BA patients, the maximal pathological alterations develop within the period from the midnight to 8 a. m., whereas the minimal disorders of ERF are recorded within the period from the noon to 8 p. m. It is suggested that deterioration of bronchial patency which brings about the development of obstruction in BA patients is the result of hypersynchronization and increased amplitude of the circadian rhythms of those parameters of ERF which determine the bronchial patency. PMID:4002163

  8. Extensive circadian and light regulation of the transcriptome in the malaria mosquito Anopheles gambiae

    OpenAIRE

    Rund, Samuel SC; James E. Gentile; Duffield, Giles E.

    2013-01-01

    Background Mosquitoes exhibit 24 hr rhythms in flight activity, feeding, reproduction and development. To better understand the molecular basis for these rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized microarray analysis on time-of-day specific collections of mosquitoes over 48 hr to explore the coregulation of gene expression rhythms by the circadian clock and light, and compare these with the 24 hr rhythmic gene expression in the diurnal Aedes aegypti dengue vec...

  9. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

    Science.gov (United States)

    Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

    2016-01-01

    Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

  10. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

    Directory of Open Access Journals (Sweden)

    Erika Navarrete

    Full Text Available Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB. We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1, pups were randomly assigned to one of the following conditions: intact pups (INT, intact pups fed by enteral gavage (INT+ENT, sham operated pups (SHAM, pups with unilateral lesions of the olfactory bulb (OBx-UNI, and pups with bilateral lesions of the olfactory bulb (OBx-BI. At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00, and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

  11. Circadian rhythm variations of clock gene PER1 expression in oral squamous cell carcinoma and their relations with tumor growth in vivo%生物钟PER1基因在口腔鳞癌中的昼夜节律变化及与体内肿瘤生长的关系

    Institute of Scientific and Technical Information of China (English)

    赵宁波; 杨凯; 陈丹; 唐洪; 赵丹; 赵春蓉

    2013-01-01

    目的 探讨生物钟PER1基因在口腔鳞癌中的昼夜节律变化情况和与肿瘤体内生长的关系.方法 60只裸鼠置于12 h光照和12 h黑暗交替环境中饲养3周后,将人颊鳞癌BcaCD885细胞接种于裸鼠颊部,建立口腔颊鳞癌模型.3周成瘤后,在24 h内按灯亮后4、10、16、22 h(4 HALO、10 HALO、16 HALO、22 HALO)的4个时间点分别处死15只裸鼠,取出肿瘤,称量,常规切片在HE染色下计算各时间点肿瘤的有丝分裂指数(MI);分别用S-P免疫组化、Western blot和Real-time RT-PCR检测各时间点癌细胞中PER1蛋白和mRNA的表达;分别用方差分析和余弦分析检验各指标在4个时间点的差异性和是否具有昼夜节律性.结果 颊鳞癌细胞PER1蛋白、PER1 mRNA、肿瘤MI和肿瘤质量在昼夜不同时间点具有显著性差异(P<0.01),其变化波动具有昼夜节律性特征(P<0.05);肿瘤MI和肿瘤质量与PER1的表达水平呈反比关系,PER1 mRNA表达的峰值与肿瘤MI和质量的谷值均位于活动相的中期,而PER1 mRNA表达的谷值与肿瘤MI和质量的峰值均位于休息相中期.结论 口腔鳞癌中PER1的表达、肿瘤MI和质量在昼夜不同时间点的波动具有24 h昼夜节律性规律,PER1在口腔鳞癌中为抑癌基因.%Objective To determine the circadian rhythm variations of the expression of clock gene PER1 in oral squamous cell carcinoma (OSCC) and their relations with tumor growth in vivo.Methods Sixty nude mice were raised under 12 h light/12 h dark cycles for 3 weeks.Human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice to establish a nude mice model of OSCC.In 3 weeks after the implantation,15 mice were sacrificed at 4 time points,including 4 h after light onset (HALO),10 HALO,16 HALO and 22 HALO,respectively,during a period of 24 h.Tumor tissues were excised and weighed.HE stained sections were prepared and mitotic index (MI) was calculated.The protein and mRNA expression of PER1 in the tumor

  12. From animal cage to aircraft cabin: an overview of evidence translation in jet lag research.

    Science.gov (United States)

    Atkinson, Greg; Batterham, Alan M; Dowdall, Nigel; Thompson, Andrew; van Drongelen, Alwin

    2014-12-01

    Recent laboratory experiments on rodents have increased our understanding of circadian rhythm mechanisms. Typically, circadian biologists attempt to translate their laboratory-based findings to treatment of jet lag symptoms in humans. We aimed to scrutinise the strength of the various links in the translational pathway from animal model to human traveller. First, we argue that the translation of findings from pre-clinical studies to effective jet lag treatments and knowledge regarding longer-term population health is not robust, e.g. the association between circadian disruption and cancer found in animal models does not translate well to cabin crew and pilots, who have a lower risk of most cancers. Jet lag symptoms are heterogeneous, making the true prevalence and the effects of any intervention difficult to quantify precisely. The mechanistic chain between in vitro and in vivo treatment effects has weak links, especially between circadian rhythm disruption in animals and the improvement of jet lag symptoms in humans. While the number of animal studies has increased exponentially between 1990 and 2014, only 1-2 randomised controlled trials on jet lag treatments are published every year. There is one relevant Cochrane review, in which only 2-4 studies on melatonin, without baseline measures, were meta-analysed. Study effect sizes reduced substantially between 1987, when the first paper on melatonin was published, and 2000. We suggest that knowledge derived from a greater number of human randomised controlled trials would provide a firmer platform for circadian biologists to cite jet lag treatment as an important application of their findings. PMID:25342081

  13. Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin: identification of cardiac clock-controlled genes using open access bioinformatics data.

    Directory of Open Access Journals (Sweden)

    Peter S Podobed

    Full Text Available Circadian rhythms are important for healthy cardiovascular physiology and are regulated at the molecular level by a circadian clock mechanism. We and others previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over 24 h daily cycles; the heart is genetically a different organ day versus night. However, which rhythmic mRNAs are regulated by the circadian mechanism is not known. Here, we used open access bioinformatics databases to identify 94 transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart-enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E-boxes, as determined by UCSC table browser, circadian mammalian promoter/enhancer database PEDB, and the European Bioinformatics Institute alignment tool (EMBOSS. Lastly, we validated findings by demonstrating that Titin cap (Tcap, telethonin was targeted by transcriptional activators CLOCK and BMAL1 by showing 1 Tcap mRNA and TCAP protein had a diurnal rhythm in murine heart; 2 cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3 Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in Clock(Δ19/Δ19 hearts; 4 BMAL1 bound to the Tcap promoter by ChIP assay; 5 BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay; and 6 CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus this study identifies circadian regulated genes in silico, with validation of Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function.

  14. Suprachiasmatic Nucleus and Subparaventricular Zone Lesions Disrupt Circadian Rhythmicity but Not Light-Induced Masking Behavior in Nile Grass Rats.

    Science.gov (United States)

    Gall, Andrew J; Shuboni, Dorela D; Yan, Lily; Nunez, Antonio A; Smale, Laura

    2016-04-01

    The ventral subparaventricular zone (vSPVZ) receives direct retinal input and influences the daily patterning of activity in rodents, making it a likely candidate for the mediation of acute behavioral responses to light (i.e., masking). We performed chemical lesions aimed at the vSPVZ of diurnal grass rats (Arvicanthis niloticus) using N-methyl-D,L-aspartic acid (NMA), a glutamate agonist. Following NMA lesions, we placed grass rats in various lighting conditions (e.g., 12:12 light-dark, constant dark, constant light); presented a series of light pulses at circadian times (CT) 6, 14, 18, and 22; and placed them in a 7-h ultradian cycle to assess behavioral masking. Extensive bilateral lesions of the vSPVZ disrupted the expression of circadian rhythms of activity and abolished the circadian modulation of masking responses to light, without affecting light-induced masking behavior per se. We also found that in diurnal grass rats, NMA was capable of destroying not only neurons of the vSPVZ but also those of the suprachiasmatic nucleus (SCN), even though excitotoxins have been ineffective at destroying cells within the SCN of nocturnal rodents. The vulnerability of the grass rat's SCN to NMA toxicity raises the possibility of a difference in density of receptors for glutamate between nocturnal and diurnal species. In cases in which damage extended to the SCN, masking responses to light were present and similar to those displayed by animals with damage restricted to the vSPVZ. Thus, extensive bilateral lesions of the SCN and vSPVZ disrupted the expression of circadian rhythms without affecting acute responses to light in a diurnal species. Our present and previous results suggest that retinorecipient brain areas other than the SCN or vSPVZ, such as the intergeniculate leaflet or olivary pretectal nucleus, may be responsible for the mediation of masking responses to light in the diurnal grass rat. PMID:26801650

  15. Temperature regulates transcription in the zebrafish circadian clock.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available It has been well-documented that temperature influences key aspects of the circadian clock. Temperature cycles entrain the clock, while the period length of the circadian cycle is adjusted so that it remains relatively constant over a wide range of temperatures (temperature compensation. In vertebrates, the molecular basis of these properties is poorly understood. Here, using the zebrafish as an ectothermic model, we demonstrate first that in the absence of light, exposure of embryos and primary cell lines to temperature cycles entrains circadian rhythms of clock gene expression. Temperature steps drive changes in the basal expression of certain clock genes in a gene-specific manner, a mechanism potentially contributing to entrainment. In the case of the per4 gene, while E-box promoter elements mediate circadian clock regulation, they do not direct the temperature-driven changes in transcription. Second, by studying E-box-regulated transcription as a reporter of the core clock mechanism, we reveal that the zebrafish clock is temperature-compensated. In addition, temperature strongly influences the amplitude of circadian transcriptional rhythms during and following entrainment by light-dark cycles, a property that could confer temperature compensation. Finally, we show temperature-dependent changes in the expression levels, phosphorylation, and function of the clock protein, CLK. This suggests a mechanism that could account for changes in the amplitude of the E-box-directed rhythm. Together, our results imply that several key transcriptional regulatory elements at the core of the zebrafish clock respond to temperature.

  16. Circadian regulation of epithelial functions in the intestine

    Czech Academy of Sciences Publication Activity Database

    Pácha, Jiří; Sumová, Alena

    2013-01-01

    Roč. 208, č. 1 (2013), s. 11-24. ISSN 1748-1708 R&D Projects: GA ČR(CZ) GAP303/10/0969; GA ČR(CZ) GAP303/11/0668 Institutional support: RVO:67985823 Keywords : circadian rhythms * intestine * colon * proliferation * digestion * intestinal transport Subject RIV: ED - Physiology Impact factor: 4.251, year: 2013

  17. Keeping the right time in space:importance of circadian clock and sleep for physiology and performance of astronauts

    Institute of Scientific and Technical Information of China (English)

    Jin-Hu Guo; Wei-Min Qu; Shan-Guang Chen; Xiao-Ping Chen; Ke Lv; Zhi-Li Huang; Yi-Lan Wu

    2014-01-01

    The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth’s environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.

  18. Daily Rhythms in Mosquitoes and Their Consequences for Malaria Transmission.

    Science.gov (United States)

    Rund, Samuel S C; O'Donnell, Aidan J; Gentile, James E; Reece, Sarah E

    2016-01-01

    The 24-h day involves cycles in environmental factors that impact organismal fitness. This is thought to select for organisms to regulate their temporal biology accordingly, through circadian and diel rhythms. In addition to rhythms in abiotic factors (such as light and temperature), biotic factors, including ecological interactions, also follow daily cycles. How daily rhythms shape, and are shaped by, interactions between organisms is poorly understood. Here, we review an emerging area, namely the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the parasites they transmit. We focus on mosquitoes, malaria parasites and vertebrate hosts, because this system offers the opportunity to integrate from genetic and molecular mechanisms to population dynamics and because disrupting rhythms offers a novel avenue for disease control. PMID:27089370

  19. Seasonal variations in daily rhythms of activity in athletic horses.

    Science.gov (United States)

    Bertolucci, C; Giannetto, C; Fazio, F; Piccione, G

    2008-07-01

    Circadian rhythms reflect extensive programming of biological activity that meets and exploits the challenges and opportunities offered by the periodic nature of the environment. In the present investigation, we recorded the total activity of athletic horses kept at four different times of the year (vernal equinox, summer solstice, autumn equinox and winter solstice), to evaluate the presence of seasonal variations of daily activity rhythms. Athletic Thoroughbred horses were kept in individual boxes with paddock. Digitally integrated measure of total activity of each mare was continuously recorded by actigraphy-based data loggers. Horse total activities were not evenly distributed over the day, but they were mainly diurnal during the year. Daily activity rhythms showed clear seasonal variations, with the highest daily amount of activity during the vernal equinox and the lowest during the winter solstice. Interestingly, the amount of activity during either photophase or scotophase changed significantly throughout the year. Circadian analysis of horse activities showed that the acrophase, the estimated time at which the peak of the rhythm occurs, did not change during the year, it always occurred in the middle of the photoperiod. Analysing the time structure of long-term and continuously measured activity and feeding could be a useful method to critically evaluate athletic horse management systems in which spontaneous locomotor activity and feeding are severely limited. Circadian rhythms are present in several elements of sensory motor and psychomotor functions and these would be taken into consideration to plan the training schedules and competitions in athletic horses. PMID:22443706

  20. Estimation methods for human circadian phase by use of peripheral tissues.

    Science.gov (United States)

    Matsumura, Ritsuko; Node, Koichi; Akashi, Makoto

    2016-09-01

    Almost all living organisms, including humans, exhibit diurnal rhythms of physiology and behavior, which are driven by the circadian clock. Many studies have found that chronic misalignment between circadian and environmental/social rhythms carries a significant risk of various disorders, including sleep disorders, metabolic syndrome, cardiovascular diseases and cancer. However, irregular sleep-wake cycles and circadian maladjustment often cause 'social jet lag', which is minor but chronic jet-lag in our daily lives. Establishment of objective and convenient circadian-phase estimation methods in the clinical setting would therefore greatly contribute not only to resolving this global health problem but also to developing chronomedicine, a clinical approach for optimizing the time of day of treatments. Traditional melatonin-based methods have limitations with respect to circadian-phase evaluation; however, estimation methods based on clock gene expression may be able to compensate for these limitations. As a representative application of circadian-phase estimation based on clock gene expression, our method of using hair follicle cells may aid in the rapid clinical detection of circadian-related sleep problems, especially circadian rhythm sleep disorders that are masked because of forced adaptation to social time schedules. PMID:27334057

  1. Light-Emitting Diodes (LED) for Primary Animal Habitat Lighting in Highly Controlled Environments

    Science.gov (United States)

    Winget, C. M.; Syrkin, N.; Heeke, D.; Mele, G.; Holley, D. C.; Dalton, Bonnie P. (Technical Monitor)

    1996-01-01

    Significant alterations in Biological Clock responses have been reported following sidereal time changes (e.g., Jet-lag), and exposure to microgravity (e.g., daytime sleepiness). Additionally, light reduces circulating melatonin (spectral specificity greatest between 450-500 nm). It was hypothesized that LEDs can replace the current light sources used in zero gravity and terrestrial research laboratories because of their small size, low mass, low energy consumption and long functional life. This report evaluates the capacity of LEDs to entrain the circadian system of rats as judged by measurement of overt behavioral circadian rhythms (activity, feeding, drinking). These data were collected in highly controlled environments similar to the shuttle Animal Enclosure Modules. Two groups were compared: control - animals exposed to standard cool-white fluorescent lights, and test - animals exposed to LEDs with a spectral power distribution matching the fluorescent lights. Gross locomotor activity, feeding and drinking frequencies were continuously monitored and stored at 10 minute intervals. Animals were exposed to the following photoperiods: 28 days of 12L:12D, 19 days of 24L:0D and 16 days of 12L:12D. Light intensities tested varied between 0.1 to 100 lux. Rats received food and water ad libitum, and temperature and humidity were controlled throughout the study. The general health status of all rats was acceptable for each day of this study. No incidents of aggressive behavior were observed. Growth, locomotor activity, food and water consumption were comparable for all groups of animals, i.e, the circadian characteristics of the animals under these conditions were comparable. These results indicate that LED arrays are as effective in maintaining circadian rhythm stability as the commonly used cool-white fluorescent light sources. LEDs with their flexible spectrum, low energy requirements and minimal heat production have advantages for some chronopharmacology studies and

  2. Relationships between circadian rhythm of ambulatory blood pressure and vascular endothelial function and carotid intima-media thickness in prehypertensives%正常高值血压者动脉血压昼夜节律与血管内皮功能及颈动脉内膜中层厚度的关系

    Institute of Scientific and Technical Information of China (English)

    梁薇芬; 张赛丹

    2012-01-01

    Objective To investigate the relationships between circadian rhythm of ambulatory blood pressure and carotid arterial intima-media thickness (IMT), vascular endothelial function assessed by flow mediated dilation (FMD) in prehypertensives. Methods One hundred and four prehypertensives collected continually from the physical examination center of Xiangya hospital between August 2010 and December 2010 were divided into two groups according to the circadian rhythm of ambulatory blood pressure monitoring (ABPM): the dipper group (55 cases) and the non-dipper group (49 cases). Forty normotensives were enrolled as control group. FMD and IMT were detected by high resolution ultrasonography. Results Dipper pattern and non-dipper pattern of prehypertension accounted for 52. 9% and 47. 1% respectively. Compared to the control group, IMT values of two prehypertensive groups were higher [(0. 74±0. 06), (0. 75±0. 06) vs (0. 47±0. 05)mm, while the FMD values were lower (8. 07 + 1.18)%, (5.89 + 0.93)% vs (13. 78±1. 98)%, all P<0. 05]. The FMD value of dipper group was higher than that of non-dipper group. FMD value was negatively correlated with IMT (r= -0. 843, P<0. 01). Conclusion Prehypertensives demonstrated abnormal ABPM rhythm, increased IMT value and decreased FMD. Compared to dipper prehypertensives, non-dipper individuals showed a more severe impairment of endothelial function as manifested by a reduced ability of FMD.%目的 了解正常高值血压动态血压昼夜节律及血管内皮功能(FMD)、颈动脉内膜中层厚度(IMT),探讨三者之间的关系.方法 连续收集2010-08-12湘雅医院体检中心正常高值血压者104例,根据动态血压昼夜变化规律分为杓型组(55例)和非杓型组(49例),健康体检者40例为对照组.高分辨超声检测肱动脉FMD及颈动脉IMT.结果 正常高值血压动态血压呈杓型及非杓型各占52.9%及47.1%,杓型组与非杓型组的IMT大于对照组[(0.74±0.06)、(0.75±0.06)比(0.47±0

  3. Animal clocks: when science meets nature.

    Science.gov (United States)

    Kronfeld-Schor, Noga; Bloch, Guy; Schwartz, William J

    2013-08-22

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian 'clock'), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day-night cycle. Our knowledge of the circadian system of animals at the molecular, cellular, tissue and organismal levels is remarkable, and we are beginning to understand how each of these levels contributes to the emergent properties and increased complexity of the system as a whole. For the most part, these analyses have been carried out using model organisms in standard laboratory housing, but to begin to understand the adaptive significance of the clock, we must expand our scope to study diverse animal species from different taxonomic groups, showing diverse activity patterns, in their natural environments. The seven papers in this Special Feature of Proceedings of the Royal Society B take on this challenge, reviewing the influences of moonlight, latitudinal clines, evolutionary history, social interactions, specialized temporal niches, annual variation and recently appreciated post-transcriptional molecular mechanisms. The papers emphasize that the complexity and diversity of the natural world represent a powerful experimental resource. PMID:23825215

  4. Diurnal oscillations of soybean circadian clock and drought responsive genes.

    Directory of Open Access Journals (Sweden)

    Juliana Marcolino-Gomes

    Full Text Available Rhythms produced by the endogenous circadian clock play a critical role in allowing plants to respond and adapt to the environment. While there is a well-established regulatory link between the circadian clock and responses to abiotic stress in model plants, little is known of the circadian system in crop species like soybean. This study examines how drought impacts diurnal oscillation of both drought responsive and circadian clock genes in soybean. Drought stress induced marked changes in gene expression of several circadian clock-like components, such as LCL1-, GmELF4- and PRR-like genes, which had reduced expression in stressed plants. The same conditions produced a phase advance of expression for the GmTOC1-like, GmLUX-like and GmPRR7-like genes. Similarly, the rhythmic expression pattern of the soybean drought-responsive genes DREB-, bZIP-, GOLS-, RAB18- and Remorin-like changed significantly after plant exposure to drought. In silico analysis of promoter regions of these genes revealed the presence of cis-elements associated both with stress and circadian clock regulation. Furthermore, some soybean genes with upstream ABRE elements were responsive to abscisic acid treatment. Our results indicate that some connection between the drought response and the circadian clock may exist in soybean since (i drought stress affects gene expression of circadian clock components and (ii several stress responsive genes display diurnal oscillation in soybeans.

  5. Interaction of MAGED1 with nuclear receptors affects circadian clock function

    OpenAIRE

    Wang, Xiaohan; Tang, Jing; Xing, Lijuan; Shi, Guangsen; Ruan, Haibin; Gu, Xiwen; Liu, Zhiwei; Wu, Xi; Gao, Xiang; Xu, Ying

    2010-01-01

    The circadian clock has a central role in physiological adaption and anticipation of day/night changes. In a genetic screen for novel regulators of circadian rhythms, we found that mice lacking MAGED1 (Melanoma Antigen Family D1) exhibit a shortened period and altered rest–activity bouts. These circadian phenotypes are proposed to be caused by a direct effect on the core molecular clock network that reduces the robustness of the circadian clock. We provide in vitro and in vivo evidence indica...

  6. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.

    Science.gov (United States)

    Leone, Vanessa; Gibbons, Sean M; Martinez, Kristina; Hutchison, Alan L; Huang, Edmond Y; Cham, Candace M; Pierre, Joseph F; Heneghan, Aaron F; Nadimpalli, Anuradha; Hubert, Nathaniel; Zale, Elizabeth; Wang, Yunwei; Huang, Yong; Theriault, Betty; Dinner, Aaron R; Musch, Mark W; Kudsk, Kenneth A; Prendergast, Brian J; Gilbert, Jack A; Chang, Eugene B

    2015-05-13

    Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet. PMID:25891358

  7. Methylphenidate modifies the motion of the circadian clock.

    Science.gov (United States)

    Antle, Michael C; van Diepen, Hester C; Deboer, Tom; Pedram, Pardis; Pereira, Rob Rodrigues; Meijer, Johanna H

    2012-10-01

    People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia. PMID:22763623

  8. Influence of gravity on the circadian timing system.

    Science.gov (United States)

    Fuller, C A; Hoban-Higgins, T M; Griffin, D W; Murakami, D M

    1994-01-01

    The circadian timing system (CTS) is responsible for daily temporal coordination of physiological and behavioral functions both internally and with the external environment. Experiments in altered gravitational environments have revealed changes in circadian rhythms of species ranging from fungi to primates. The altered gravitational environments examined included both the microgravity environment of spaceflight and hyperdynamic environments produced by centrifugation. Acute exposure to altered gravitational environments changed homeostatic parameters such as body temperature. These changes were time of day dependent. Exposure to gravitational alterations of relatively short duration produced changes in both the homeostatic level and the amplitude of circadian rhythms. Chronic exposure to a non-earth level of gravity resulted in changes in the period of the expressed rhythms as well as in the phase relationships between the rhythms and between the rhythms and the external environment. In addition, alterations in gravity appeared to act as a time cue for the CTS. Altered gravity also affected the sensitivity of the pacemaker to other aspects of the environment (i.e., light) and to shifts of time cues. Taken together, these studies lead to the conclusion that the CTS is indeed sensitive to gravity and its alterations. This finding has implications for both basic biology and space medicine. PMID:11537948

  9. Integration of light and temperature in the regulation of circadian gene expression in Drosophila.

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    Catharine E Boothroyd

    2007-04-01

    Full Text Available Circadian clocks are aligned to the environment via synchronizing signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we found that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcript levels appear to be modified broadly by changes in temperature, there is a specific set of temperature-entrained circadian mRNA profiles that continue to oscillate in constant conditions. There are marked differences in the biological functions represented by temperature-driven or circadian regulation. The set of temperature-entrained circadian transcripts overlaps significantly with a previously defined set of transcripts oscillating in response to a photocycle. In follow-up studies, all thermocycle-entrained circadian transcript rhythms also responded to light/dark entrainment, whereas some photocycle-entrained rhythms did not respond to temperature entrainment. Transcripts encoding the clock components Period, Timeless, Clock, Vrille, PAR-domain protein 1, and Cryptochrome were all confirmed to be rhythmic after entrainment to a daily thermocycle, although the presence of a thermocycle resulted in an unexpected phase difference between period and timeless expression rhythms at the transcript but not the protein level. Generally, transcripts that exhibit circadian rhythms both in response to thermocycles and photocycles maintained the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases of these transcripts indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. This interpretation is further supported by comparative analysis of the circadian phases observed for temperature-entrained and light-entrained circadian locomotor behavior. Taken

  10. Influence of weeks of circadian misalignment on leptin levels

    Directory of Open Access Journals (Sweden)

    June Nguyen

    2009-12-01

    Full Text Available June Nguyen, Kenneth P Wright JrDepartment of Integrative Physiology, Sleep and Chronobiology Laboratory, University of Colorado, Boulder, CO, USAAbstract: The neurobiology of circadian, wakefulness–sleep, and feeding systems interact to influence energy homeostasis. Sleep and circadian disruptions are reported to be associated with increased risk of diabetes and obesity, yet the roles of energy balance hormones in these associations are largely unknown. Therefore, in the current study we aimed to assess the influence of several weeks of circadian misalignment (sleep and wakefulness occurring at an inappropriate biological time on the anorexigenic adipocyte hormone leptin. We utilized data from a previous study designed to assess physiological and cognitive consequences of changes in day length and light exposure as may occur during space flight, including exploration class space missions and exposure to the Martian Sol (day length. We hypothesized that circadian misalignment during an exploration class spaceflight simulation would reduce leptin levels. Following a three-week ~8 hours per night home sleep schedule, 14 healthy participants lived in the laboratory for more than one month. After baseline data collection, participants were scheduled to either 24.0 or 24.6 hours of wakefulness–sleep schedules for 25 days. Changes in the phase of the circadian melatonin rhythm, sleep, and leptin levels were assessed. Half of participants analyzed exhibited circadian misalignment with an average change in phase angle from baseline of ~4 hours and these participants showed reduced leptin levels, sleep latency, stage 2 and total sleep time (7.3 to 6.6 hours and increased wakefulness after sleep onset (all P < 0.05. The control group remained synchronized and showed significant increases in sleep latency and leptin levels. Our findings indicate that weeks of circadian misalignment, such as that which occurs in circadian sleep disorders, alters leptin

  11. Voiced Reading and Rhythm

    Institute of Scientific and Technical Information of China (English)

    詹艳萍

    2007-01-01

    Since voiced reading is an important way in learning English,rhythm is the most critical factor that enables to read beautifully.This article illustrates the relationship between rhythm and voiced reading,the importance of rhythm,and the methods to develop the sense of rhythm.

  12. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    Science.gov (United States)

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system. PMID:26915078

  13. Genetic adaptation of the human circadian clock to day-length latitudinal variations and relevance for affective disorders

    OpenAIRE

    De Forni, D; Pozzoli, U; R. Cagliani; C. Tresoldi; G. Menozzi; Riva, S; F. Guerini; Comi, G; Bolognesi, E; Bresolin, N.; Clerici, M.; Sironi, M.

    2014-01-01

    Background The temporal coordination of biological processes into daily cycles is a common feature of most living organisms. In humans, disruption of circadian rhythms is commonly observed in psychiatric diseases, including schizophrenia, bipolar disorder, depression and autism. Light therapy is the most effective treatment for seasonal affective disorder and circadian-related treatments sustain antidepressant response in bipolar disorder patients. Day/night cycles represent a major circadian...

  14. Plasticity of the intrinsic period of the human circadian timing system.

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    Frank A J L Scheer

    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.

  15. Novel putative mechanisms to link circadian clocks to healthy aging.

    Science.gov (United States)

    Popa-Wagner, Aurel; Catalin, Bogdan; Buga, Ana-Maria

    2015-08-01

    The circadian clock coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Multiple-oscillator circadian mechanisms are likely to play a role in regulating human health and may contribute to the aging process. Our aim is to give an overview of how the central clock in the hypothalamus and peripheral clocks relate to aging and metabolic disorders, including hyperlipidemia and hyperglycemia. In particular, we unravel novel putative mechanisms to link circadian clocks to healthy aging. This review may lead to the design of large-scale interventions to help people stay healthy as they age by adjusting daily activities, such as feeding behavior, and or adaptation to age-related changes in individual circadian rhythms. PMID:24297467

  16. Effects of different per translational kinetics on the dynamics of a core circadian clock model.

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    Paula S Nieto

    Full Text Available Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.

  17. Endogenous rhythms influence interpersonal synchrony.

    Science.gov (United States)

    Zamm, Anna; Wellman, Chelsea; Palmer, Caroline

    2016-05-01

    Interpersonal synchrony, the temporal coordination of actions between individuals, is fundamental to social behaviors from conversational speech to dance and music-making. Animal models indicate constraints on synchrony that arise from endogenous rhythms: Intrinsic periodic behaviors or processes that continue in the absence of change in external stimulus conditions. We report evidence for a direct causal link between endogenous rhythms and interpersonal synchrony in a music performance task, which places high demands on temporal coordination. We first establish that endogenous rhythms, measured by spontaneous rates of individual performance, are stable within individuals across stimulus materials, limb movements, and time points. We then test a causal link between endogenous rhythms and interpersonal synchrony by pairing each musician with a partner who is either matched or mismatched in spontaneous rate and by measuring their joint behavior up to 1 year later. Partners performed melodies together, using either the same or different hands. Partners who were matched for spontaneous rate showed greater interpersonal synchrony in joint performance than mismatched partners, regardless of hand used. Endogenous rhythms offer potential to predict optimal group membership in joint behaviors that require temporal coordination. (PsycINFO Database Record PMID:26820249

  18. Lithium impacts on the amplitude and period of the molecular circadian clockwork.

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    Jian Li

    Full Text Available Lithium salt has been widely used in treatment of Bipolar Disorder, a mental disturbance associated with circadian rhythm disruptions. Lithium mildly but consistently lengthens circadian period of behavioural rhythms in multiple organisms. To systematically address the impacts of lithium on circadian pacemaking and the underlying mechanisms, we measured locomotor activity in mice in vivo following chronic lithium treatment, and also tracked clock protein dynamics (PER2::Luciferase in vitro in lithium-treated tissue slices/cells. Lithium lengthens period of both the locomotor activity rhythms, as well as the molecular oscillations in the suprachiasmatic nucleus, lung tissues and fibroblast cells. In addition, we also identified significantly elevated PER2::LUC expression and oscillation amplitude in both central and peripheral pacemakers. Elevation of PER2::LUC by lithium was not associated with changes in protein stabilities of PER2, but instead with increased transcription of Per2 gene. Although lithium and GSK3 inhibition showed opposing effects on clock period, they acted in a similar fashion to up-regulate PER2 expression and oscillation amplitude. Collectively, our data have identified a novel amplitude-enhancing effect of lithium on the PER2 protein rhythms in the central and peripheral circadian clockwork, which may involve a GSK3-mediated signalling pathway. These findings may advance our understanding of the therapeutic actions of lithium in Bipolar Disorder or other psychiatric diseases that involve circadian rhythm disruptions.

  19. A role for Drosophila ATX2 in activation of PER translation and circadian behavior.

    Science.gov (United States)

    Zhang, Yong; Ling, Jinli; Yuan, Chunyan; Dubruille, Raphaëlle; Emery, Patrick

    2013-05-17

    A negative transcriptional feedback loop generates circadian rhythms in Drosophila. PERIOD (PER) is a critical state-variable in this mechanism, and its abundance is tightly regulated. We found that the Drosophila homolog of ATAXIN-2 (ATX2)--an RNA-binding protein implicated in human neurodegenerative diseases--was required for circadian locomotor behavior. ATX2 was necessary for PER accumulation in circadian pacemaker neurons and thus determined period length of circadian behavior. ATX2 was required for the function of TWENTY-FOUR (TYF), a crucial activator of PER translation. ATX2 formed a complex with TYF and promoted its interaction with polyadenylate-binding protein (PABP). Our work uncovers a role for ATX2 in circadian timing and reveals that this protein functions as an activator of PER translation in circadian neurons. PMID:23687048

  20. Photoperiodic plasticity in circadian clock neurons in insects

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    Sakiko eShiga

    2013-08-01

    Full Text Available Since Bünning’s observation of circadian rhythms and photoperiodism in the runner bean Phaseolus multiflorus in 1936, many studies have shown that photoperiodism is based on the circadian clock system. In insects, involvement of circadian clock genes or neurons has been recently shown in the photoperiodic control of developmental arrests, diapause. Based on molecular and neuronal studies in Drosophila melanogaster, photoperiodic changes have been reported for expression patterns of the circadian clock genes, subcellular distribution of clock proteins, fiber distribution, or the number of plausible clock neurons in different species. Photoperiod sets peaks of per or tim mRNA abundance at lights-off in Sarcophaga crassipalpis, Chymomyza costata and Protophormia terraenovae. Abundance of per and Clock mRNA changes by photoperiod in Pyrrhocoris apterus. Subcellular Per distribution in circadian clock neurons changes with photoperiod in P. terraenovae. Although photoperiodism is not known in Leucophaea maderae, under longer day length, more stomata and longer commissural fibers of circadian clock neurons have been found. These plastic changes in the circadian clock neurons could be an important constituent for photoperiodic clock mechanisms to integrate repetitive photoperiodic information and produce different outputs based on day length.