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Sample records for generating circadian rhythms

  1. Circadian Rhythms

    MedlinePlus

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

  2. Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons

    PubMed Central

    Webb, Alexis B.; Angelo, Nikhil; Huettner, James E.; Herzog, Erik D.

    2009-01-01

    Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate or Period2 gene expression in single neurons. We found that fully isolated SCN neurons can sustain circadian cycling for at least 1 week. Plating SCN neurons at <100 cells/mm2 eliminated synaptic inputs and revealed circadian neurons that contained arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) or neither. Surprisingly, arrhythmic neurons (nearly 80% of recorded neurons) also expressed these neuropeptides. Furthermore, neurons were observed to lose or gain circadian rhythmicity in these dispersed cell cultures, both spontaneously and in response to forskolin stimulation. In SCN explants treated with tetrodotoxin to block spike-dependent signaling, neurons gained or lost circadian cycling over many days. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontaneous onset of arrhythmicity. We conclude that individual SCN neurons can generate circadian oscillations; however, there is no evidence for a specialized or anatomically localized class of cell-autonomous pacemakers. Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling. PMID:19805326

  3. Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons.

    PubMed

    Webb, Alexis B; Angelo, Nikhil; Huettner, James E; Herzog, Erik D

    2009-09-22

    Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate or Period2 gene expression in single neurons. We found that fully isolated SCN neurons can sustain circadian cycling for at least 1 week. Plating SCN neurons at <100 cells/mm(2) eliminated synaptic inputs and revealed circadian neurons that contained arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) or neither. Surprisingly, arrhythmic neurons (nearly 80% of recorded neurons) also expressed these neuropeptides. Furthermore, neurons were observed to lose or gain circadian rhythmicity in these dispersed cell cultures, both spontaneously and in response to forskolin stimulation. In SCN explants treated with tetrodotoxin to block spike-dependent signaling, neurons gained or lost circadian cycling over many days. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontaneous onset of arrhythmicity. We conclude that individual SCN neurons can generate circadian oscillations; however, there is no evidence for a specialized or anatomically localized class of cell-autonomous pacemakers. Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling. PMID:19805326

  4. Sleep and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.

    1991-01-01

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

  5. Biological Clocks & Circadian Rhythms

    ERIC Educational Resources Information Center

    Robertson, Laura; Jones, M. Gail

    2009-01-01

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

  6. Circadian Rhythms in Cyanobacteria.

    PubMed

    Cohen, Susan E; Golden, Susan S

    2015-12-01

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

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

    PubMed

    Miura, Shigehiro; Shimokawa, Tetsuya; Nomura, Taishin

    2008-01-01

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

  8. Circadian Rhythm Sleep Disorders

    PubMed Central

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

    2014-01-01

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

  9. Circadian rhythms: basic neurobiology and clinical applications.

    PubMed

    Moore, R Y

    1997-01-01

    Circadian rhythms are major features of adaptation to our environment. In mammals, circadian rhythms are generated and regulated by a circadian timing system. This system consists of entertainment pathways, pacemakers, and pace-maker output to effector systems that are under circadian control. The primary entertainment pathway is the retinohypothalamic tract, which terminates in the circadian pacemakers, the suprachiasmatic nuclei of the hypothalamus. The output of the suprachiasmatic nuclei is principally to the hypothalamus, the midline thalamus, and the basal forebrain. This provides a temporal organization to the sleep-wake cycle, to many physiological and endocrine functions, and to psychomotor performance functions. Disorders of circadian timing primarily affect entertainment and pacemaker functions. The pineal hormone, melatonin, appears to be promising agent for therapy of some circadian timing disorders. PMID:9046960

  10. In vitro circadian rhythms: imaging and electrophysiology.

    PubMed

    Beaulé, Christian; Granados-Fuentes, Daniel; Marpegan, Luciano; Herzog, Erik D

    2011-06-30

    In vitro assays have localized circadian pacemakers to individual cells, revealed genetic determinants of rhythm generation, identified molecular players in cell-cell synchronization and determined physiological events regulated by circadian clocks. Although they allow strict control of experimental conditions and reduce the number of variables compared with in vivo studies, they also lack many of the conditions in which cellular circadian oscillators normally function. The present review highlights methods to study circadian timing in cultured mammalian cells and how they have shaped the hypothesis that all cells are capable of circadian rhythmicity. PMID:21819387

  11. In vitro circadian rhythms: imaging and electrophysiology

    PubMed Central

    Beaulé, Christian; Granados-Fuentes, Daniel; Marpegan, Luciano; Herzog, Erik D.

    2013-01-01

    In vitro assays have localized circadian pacemakers to individual cells, revealed genetic determinants of rhythm generation, identified molecular players in cell-cell synchronization and determined physiological events regulated by circadian clocks. Although they allow strict control of experimental conditions and reduce the number of variables compared with in vivo studies, they also lack many of the conditions in which cellular circadian oscillators normally function. The present review highlights methods to study circadian timing in cultured mammalian cells and how they have shaped the hypothesis that all cells are capable of circadian rhythmicity. PMID:21819387

  12. Circadian rhythm and its role in malignancy

    PubMed Central

    2010-01-01

    Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs) including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer. PMID:20353609

  13. Phenotyping Circadian Rhythms in Mice.

    PubMed

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

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

  14. Yes, circadian rhythms actually do affect almost everything.

    PubMed

    Dunlap, Jay C; Loros, Jennifer J

    2016-07-01

    Circadian rhythms in the level of intracellular Mg appear to be widely conserved phylogenetically, and have the potential to impact nearly all aspects of metabolism. Moreover, the clock regulates the ion channels that generate the rhythm, demonstrating that the whole cell operates as a circadian system. PMID:27241553

  15. [Molecular oscillatory machinery of circadian rhythms].

    PubMed

    Yamaguchi, Yoshiaki; Okamura, Hitoshi

    2012-07-01

    Many metabolic and physiological processes display daily rhythms oscillated by the internal circadian clock system. This rhythm is generated by interlocked transcription-(post) translation feedback loops of clock genes: the core oscillatory loop, being composed of CLOCK/BMAL1 heterodimer activating the expressions of PER and CRY that directly repress CLOCK/BMAL1, is accompanied by accessory loops consisted with REV-ERB nuclear receptor repressing Bmal1 or with DBP competing with E4BP4 on D-box site. These clock proteins are regulated by phosphorylation and ubiquitination (PER/CRY), and acetylation (CLOCK/BMAL1). Recently, a deacetylating protein SIRT1 mediated metabolic pathway is discovered to be interlocked with core oscillatory loop via Nampt expression, a late-limiting enzyme in NAD+ salvage pathway. Since many key-step enzymes of metabolisms are regulated by the circadian clock, circadian clock system may intimately link to cellular metabolism. PMID:22844791

  16. Phenotyping Circadian Rhythms in Mice

    PubMed Central

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

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

  17. Circadian Rhythm Control: Neurophysiological Investigations

    NASA Technical Reports Server (NTRS)

    Glotzbach, S. F.

    1985-01-01

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

  18. Circadian Rhythm Disruption Promotes Lung Tumorigenesis.

    PubMed

    Papagiannakopoulos, Thales; Bauer, Matthew R; Davidson, Shawn M; Heimann, Megan; Subbaraj, Lakshmipriya; Bhutkar, Arjun; Bartlebaugh, Jordan; Vander Heiden, Matthew G; Jacks, Tyler

    2016-08-01

    Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression. PMID:27476975

  19. Neurobiology of Circadian Rhythm Regulation.

    PubMed

    Rosenwasser, Alan M; Turek, Fred W

    2015-12-01

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

  20. Circadian rhythms: glucocorticoids and arthritis.

    PubMed

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

    2006-06-01

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

  1. Circadian rhythms in myocardial metabolism and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. CIRCADIAN RHYTHM REPROGRAMMING DURING LUNG INFLAMMATION

    PubMed Central

    Haspel, Jeffrey A.; Chettimada, Sukrutha; Shaik, Rahamthulla S.; Chu, Jen-Hwa; Raby, Benjamin A.; Cernadas, Manuela; Carey, Vincent; Process, Vanessa; Hunninghake, G. Matthew; Ifedigbo, Emeka; Lederer, James A.; Englert, Joshua; Pelton, Ashley; Coronata, Anna; Fredenburgh, Laura E.; Choi, Augustine M. K.

    2014-01-01

    Circadian rhythms are known to regulate immune responses in healthy animals, but it is unclear whether they persist during acute illnesses where clock gene expression is disrupted by systemic inflammation. Here, we use a genome-wide approach to investigate circadian gene and metabolite expression in the lungs of endotoxemic mice and find that novel cellular and molecular circadian rhythms are elicited in this setting. The endotoxin-specific circadian program exhibits unique features, including a divergent group of rhythmic genes and metabolites compared to the basal state and a distinct periodicity and phase distribution. At the cellular level endotoxin treatment also alters circadian rhythms of leukocyte counts within the lung in a bmal1-dependent manner, such that granulocytes rather than lymphocytes become the dominant oscillating cell type. Our results show that inflammation produces a complex reorganization of cellular and molecular circadian rhythms that are relevant to early events in lung injury. PMID:25208554

  3. Circadian rhythms and cancer chemotherapy.

    PubMed

    Wood, P A; Hrushesky, W J

    1996-01-01

    Temporal coordination of biologic processes with an approximately 24-h cycle (circadian) is common throughout the animal and plant kingdom and even in some prokaryotic organisms. In all organisms studied, the capability to keep biologic time is an inherited characteristic located intracellularly. These biological clocks anticipate and get the organism ready for regular environmental changes. This indicates both the ubiquity and the weight of the selective environmental pressure to keep time accurately. Several molecular strategies for biologic time keeping have apparently arisen independently several times throughout evolution. The anatomic, biochemical, and molecular mechanisms of the clock are in the process of being defined. This temporal organization at the cellular, organ, and organismic levels results in predictable differences in the capacity of plants, animals, and human beings to respond to therapeutic interventions administered at different times throughout important biologic cycles (e.g., circadian timed therapy). In the treatment of the cancer bearing host, circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, enhanced tumor control, and improved host survival. The routine clinical application of such principles is facilitated by the availability of programmable drug delivery devices. Rhythm frequency ranges other than 24-h (e.g., low frequency: menstrual; high frequency: 10 to 120 min) may also be important to understanding health and disease and to designing successful therapy in diseases as diverse as cancer, infertility, and diabetes. PMID:8959371

  4. Circadian rhythms from multiple oscillators: lessons from diverse organisms.

    PubMed

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

    2005-07-01

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

  5. Genetic Basis of Human Circadian Rhythm Disorders

    PubMed Central

    Jones, Christopher R.; Huang, Angela L.; Ptáček, Louis J.; Fu, Ying-Hui

    2012-01-01

    Circadian rhythm disorders constitute a group of phenotypes that usually present as altered sleep-wake schedules. Until a human genetics approach was applied to investigate these traits, the genetic components regulating human circadian rhythm and sleep behaviors remained mysterious. Steady advances in the last decade have dramatically improved our understanding of the genes involved in circadian rhythmicity and sleep regulation. Finding these genes presents new opportunities to use a wide range of approaches, including in vitro molecular studies and in vivo animal modeling, to elevate our understanding of how sleep and circadian rhythms are regulated and maintained. Ultimately, this knowledge will reveal how circadian and sleep disruption contribute to various ailments and shed light on how best to maintain and recover good health. PMID:22849821

  6. [Circadian rhythm sleep disorders in psychiatric diseases].

    PubMed

    Bromundt, Vivien

    2014-11-01

    Circadian rhythm sleep disorders are prevalent among psychiatric patients. This is most probable due to a close relationship between functional disturbances of the internal clock, sleep regulation and mental health. Mechanisms on molecular level of the circadian clock and neurotransmitter signalling are involved in the development of both disorders. Moreover, circadian disorders and psychiatric diseases favour each other by accessory symptoms such as stress or social isolation. Actimetry to objectively quantify the rest-activity cycle and salivary melatonin profiles as marker for the circadian phase help to diagnose circadian rhythm sleep disorders in psychiatric patients. Chronotherapeutics such as bright light therapy, dark therapy, melatonin administration, and wake therapy are used to synchronise and consolidate circadian rhythms and help in the treatment of depression and other psychiatric disorders, but are still neglected in medicine. More molecular to behavioural research is needed for the understanding of the development of circadian disorders and their relationship to psychiatric illnesses. This will help to boost the awareness and treatment of circadian rhythm sleep disorders in psychiatry. PMID:25377290

  7. Glucocorticoids Play a Key Role in Circadian Cell Cycle Rhythms

    PubMed Central

    Dickmeis, Thomas; Lahiri, Kajori; Nica, Gabriela; Vallone, Daniela; Santoriello, Cristina; Neumann, Carl J; Hammerschmidt, Matthias; Foulkes, Nicholas S

    2007-01-01

    Clock output pathways play a pivotal role by relaying timing information from the circadian clock to a diversity of physiological systems. Both cell-autonomous and systemic mechanisms have been implicated as clock outputs; however, the relative importance and interplay between these mechanisms are poorly understood. The cell cycle represents a highly conserved regulatory target of the circadian timing system. Previously, we have demonstrated that in zebrafish, the circadian clock has the capacity to generate daily rhythms of S phase by a cell-autonomous mechanism in vitro. Here, by studying a panel of zebrafish mutants, we reveal that the pituitary–adrenal axis also plays an essential role in establishing these rhythms in the whole animal. Mutants with a reduction or a complete absence of corticotrope pituitary cells show attenuated cell-proliferation rhythms, whereas expression of circadian clock genes is not affected. We show that the corticotrope deficiency is associated with reduced cortisol levels, implicating glucocorticoids as a component of a systemic signaling pathway required for circadian cell cycle rhythmicity. Strikingly, high-amplitude rhythms can be rescued by exposing mutant larvae to a tonic concentration of a glucocorticoid agonist. Our work suggests that cell-autonomous clock mechanisms are not sufficient to establish circadian cell cycle rhythms at the whole-animal level. Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part. PMID:17373855

  8. Characterisation of circadian rhythms of various duckweeds.

    PubMed

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

    2015-01-01

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

  9. Heterogeneity induces rhythms of weakly coupled circadian neurons.

    PubMed

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

    2016-01-01

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

  10. Heterogeneity induces rhythms of weakly coupled circadian neurons

    PubMed Central

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

    2016-01-01

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

  11. Role of Circadian Rhythms in Potassium Homeostasis

    PubMed Central

    Gumz, Michelle L.; Rabinowitz, Lawrence

    2013-01-01

    It has been known for decades that urinary potassium excretion varies with a circadian pattern. In this review, we consider the historical evidence for this phenomenon and present an overview of recent developments in the field. Extensive evidence from the latter part of the last century clearly demonstrates that circadian potassium excretion does not depend on endogenous aldosterone. Of note is the recent discovery that the expression of several renal potassium transporters varies with a circadian pattern that appears to be consistent with substantial clinical data regarding daily fluctuations in urinary potassium levels. We propose the circadian clock mechanism as a key regulator of renal potassium transporters, and consequently renal potassium excretion. Further investigation into the mechanism of regulation of renal potassium transport by the circadian clock is warranted in order to increase our understanding of the clinical relevance of circadian rhythms to potassium homeostasis. PMID:23953800

  12. Circadian rhythms of women with fibromyalgia

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  13. Neuroanatomy of the Extended Circadian Rhythm System

    PubMed Central

    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 serotonergic pathway and the geniculohypothalamic (GHT), NPY-containing pathway from the thalamic intergeniculate leaflet (IGL). Beyond this simple framework, the number of anatomical routes that could theoretically be involved in rhythm regulation is enormous, with the SCN projecting to 15 regions and being directly innervated by about 35. If multisynaptic afferents to the SCN are included, the number expands to approximately brain 85 areas providing input to the SCN. The IGL, a known contributor to circadian rhythm regulation, has a still greater level of complexity. This nucleus connects abundantly throughout the brain (to approximately 100 regions) by pathways that are largely bilateral and reciprocal. Few of these sites have been evaluated for their contributions to circadian rhythm regulation, although most have a theoretical possibility of doing so via the GHT. The anatomy of IGL connections suggests that one of its functions may be regulation of eye movements during sleep. Together, neural circuits of the SCN and IGL are complex and interconnected. As yet, few have been tested with respect to their involvement in rhythm regulation. PMID:22766204

  14. Circadian rhythms of performance: new trends

    NASA Technical Reports Server (NTRS)

    Carrier, J.; Monk, T. H.

    2000-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  16. Circadian Rhythms, Sleep Deprivation, and Human Performance

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. Procedures for numerical analysis of circadian rhythms

    PubMed Central

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

    2010-01-01

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

  19. Circadian rhythm of gravitaxis in Euglena gracilis.

    PubMed

    Lebert, M; Porst, M; Hader, D P

    1999-09-01

    Euglena gracilis, a unicellular, photosynthetic flagellate is a model system for environmentally controlled behavioral reactions. One pronounced reaction is the orientation with respect to gravity. In synchronized cultures with no cell growth a distinct circadian rhythm of negative gravitactic orientation could be observed. The main maximum of sensitivity was detected 5 h after the beginning of the subjective day, the main minimum 5 h before the beginning of the subjective day. Transferring synchronized cultures to continuous light resulted in an almost instantaneous loss of rhythmicity. In contrast, after transfer to permanent darkness cells exhibited a circadian rhythm with a progressive shortening of the period for more than 5 days. These findings are in contrast to the circadian rhythm of phototaxis in Euglena, where a free-running period of 24 h was observed. Parallel measurements of negative gravitactic orientation, velocity, cell shape as well as cAMP concentration in synchronized cultures revealed a circadian rhythm of all reactions. The results are discussed with regard to the possible role of cell shape and cAMP in gravitactic orientation. PMID:11542916

  20. Circadian rhythms, alcohol and gut interactions

    PubMed Central

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

    2015-01-01

    The circadian clock establishes rhythms throughout the body with an approximately 24 hour period that affect expression of hundreds of genes. Epidemiological data reveal chronic circadian misalignment, common in our society, significantly increases the risk for a myriad of diseases, including cardiovascular disease, diabetes, cancer, infertility and gastrointestinal disease. Disruption of intestinal barrier function, also known as gut leakiness, is especially important in alcoholic liver disease (ALD). Several studies have shown that alcohol causes ALD in only a 20–30% subset of alcoholics. Thus, a better understanding is needed of why only a subset of alcoholics develops ALD. Compelling evidence shows that increased gut leakiness to microbial products and especially LPS play a critical role in the pathogenesis of ALD. Clock and other circadian clock genes have been shown to regulate lipid transport, motility and other gut functions. We hypothesized that one possible mechanism for alcohol-induced intestinal hyper-permeability is through disruption of central or peripheral (intestinal) circadian regulation. In support of this hypothesis, our recent data shows that disruption of circadian rhythms makes the gut more susceptible to injury. Our in vitro data show that alcohol stimulates increased Clock and Per2 circadian clock proteins and that siRNA knockdown of these proteins prevents alcohol-induced permeability. We also show that intestinal Cyp2e1-mediated oxidative stress is required for alcohol-induced upregulation of Clock and Per2 and intestinal hyperpermeability. Our mouse model of chronic alcohol feeding shows that circadian disruption through genetics (in ClockΔ19 mice) or environmental disruption by weekly 12h phase shifting results in gut leakiness alone and exacerbates alcohol-induced gut leakiness and liver pathology. Our data in human alcoholics show they exhibit abnormal melatonin profiles characteristic of circadian disruption. Taken together our

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

    PubMed

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

    2015-09-15

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

  2. Metabolic circadian rhythms in embryonic turtles.

    PubMed

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

    2013-07-01

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

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

    NASA Technical Reports Server (NTRS)

    Miyoshi, Yashuhiro

    1993-01-01

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

  4. Circadian Rhythms in Photosynthesis 1

    PubMed Central

    Hennessey, Timothy L.; Field, Christopher B.

    1991-01-01

    Net carbon assimilation and stomatal conductance to water vapor oscillated repeatedly in red kidney bean, Phaseolus vulgaris L., plants transferred from a natural photoperiod to constant light. In a gas exchange system with automatic regulation of selected environmental and physiological variables, assimilation and conductance oscillated with a free-running period of approximately 24.5 hours. The rhythms in carbon assimilation and stomatal conductance were closely coupled and persisted for more than a week under constant conditions. A rhythm in assimilation occurred when either ambient or intercellular CO2 partial pressure was held constant, demonstrating that the rhythm in assimilation was not entirely the result of stomatal effects on CO2 diffusion. Rhythms in assimilation and conductance were not expressed in plants grown under constant light at a constant temperature, demonstrating that the rhythms did not occur spontaneously but were induced by an external stimulus. In plants grown under constant light with a temperature cycle, a rhythm was entrained in stomatal conductance but not in carbon assimilation, indicating that the oscillators driving the rhythms differed in their sensitivity to environmental stimuli. PMID:16668261

  5. Environmental synchronizers of squirrel monkey circadian rhythms

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

    Silver, Rae; Kriegsfeld, Lance J.

    2015-01-01

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

  8. Circadian rhythm asynchrony in man during hypokinesis.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  9. Sleep, Circadian Rhythms, and Anxious Traits.

    PubMed

    Coles, Meredith E; Schubert, Jessica R; Nota, Jacob A

    2015-09-01

    Anxiety is adaptive and plays an important role in keeping us safe. However, when anxiety becomes too extreme, it can cause significant disruptions and distress. Understanding the mechanisms underlying excessive anxiety and how to best treat it is a priority for researchers and clinicians. There is increasing recognition that disruptions in the amount and timing of sleep are associated with anxiety symptoms and characteristics. In the current paper, we explore the intersections between sleep, circadian rhythms, and anxiety. First, we review accumulating evidence that anxiety is associated with disruptions in sleep and circadian rhythms in both clinical and nonclinical samples and across ages. Next, we discuss the data linking sleep disruptions with anxiety-related traits (anxiety sensitivity, neuroticism, and perfectionism) and patterns of cognition and emotion. Finally, potential treatment implications are highlighted. Overall, these data suggest that delineating the role of disruptions in the amount and timing of sleep holds promise for improving the lives of individuals with heightened anxiety. PMID:26216591

  10. INTRINSIC CIRCADIAN RHYTHMS IN THE CARDIOMYOCYTE

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Temperature compensation and entrainment in circadian rhythms

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  12. Circadian rhythms, sleep, and performance in space

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

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

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

    PubMed

    Mallis, M M; DeRoshia, C W

    2005-06-01

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

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

    PubMed

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

    2015-07-17

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

  15. The role of circadian rhythm in breast cancer

    PubMed Central

    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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  17. [The kidney and circadian rhythms: a whole new world?].

    PubMed

    Manfredini, Roberto; Sasso, Ferdinando Carlo; Pala, Marco; De Giorgi, Alfredo; Fabbian, Fabio

    2013-01-01

    Chronobiology is a branch of biomedical sciences devoted to the study of biological rhythms. Biological rhythms exist at any level of living organisms and, according to their cycle length, may be divided into three main types: circadian, ultradian, and infradian rhythms. Circadian rhythms are the most commonly and widely studied. The principal circadian clock is located in the suprachiasmatic nucleus of the hypothalamus, and is supposed to regulate peripheral clocks via neurohumoral modulation. Circadian clocks have been identified within almost all mammalian cell types, and circadian clock genes seem to be essential for cardiovascular health. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids regulated by rest/activity and feeding/fasting cycles. However, most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock, comprising a system of autoregulatory transcriptional/translational feedback loops, which have also been found in the kidney. PMID:24403200

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

    ERIC Educational Resources Information Center

    Watts, Barbara L.

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

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

    PubMed

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

    2014-04-23

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system. PMID:24760863

  20. Vasoactive Intestinal Polypeptide Mediates Circadian Rhythms in Mammalian Olfactory Bulb and Olfaction

    PubMed Central

    Miller, Jae-eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E.

    2014-01-01

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system. PMID:24760863

  1. Circadian rhythms and the suprachiasmatic nucleus in perinatal development, aging and Alzheimer's disease.

    PubMed

    Mirmiran, M; Swaab, D F; Kok, J H; Hofman, M A; Witting, W; Van Gool, W A

    1992-01-01

    Circadian rhythms are already present in the fetus. At a certain stage of pre-natal hypothalamic development (around 30 weeks of gestation) the fetus becomes responsive to maternal circadian signals. Moreover, recent studies showed that the fetal biological clock is able to generate circadian rhythms, as exemplified by the rhythms of body temperature and heart rate of pre-term babies in the absence of maternal or environmental entrainment factors. Pre-term babies that are deprived of maternal entrainment and kept under constant environmental conditions (e.g., continuous light) in the neonatal intensive care unit run the risk of developing a biological clock dysfunctioning. However, the fact should be acknowledged that at least in mice the development of the circadian pacemaker (i.e., SCN) does not depend on environmental influences (Davis and Menaker, 1981), although other data suggest that severe disruption of the maternal circadian rhythm indeed abolishes the circadian rhythm of the fetal SCN (Shibata and Moore, 1988). During aging and in particular in AD circadian rhythms are disturbed. These disturbances include phase advance and reduced period and amplitude, as well as an increased intradaily variability and a decreased interdaily stability of the rhythm. Among the factors underlying these changes the loss of SCN neurons seems to play a central role. Other contributory factors may be reduced amount of light, degenerative changes in the visual system and the level of activity and decreased melatonin. PMID:1480747

  2. Characterization of neurospora circadian rhythms in space

    NASA Technical Reports Server (NTRS)

    Ferraro, James S.

    1987-01-01

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

  3. Circadian temperature rhythms of older people

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  4. Methods to Record Circadian Rhythm Wheel Running Activity in Mice

    PubMed Central

    Siepka, Sandra M.; Takahashi, Joseph S.

    2013-01-01

    Forward genetic approaches (phenotype to gene) are powerful methods to identify mouse circadian clock components. The success of these approaches, however, is highly dependent on the quality of the phenotype— specifically, the ability to measure circadian rhythms in individual mice. This article outlines the factors necessary to measure mouse circadian rhythms, including choice of mouse strain, facilities and equipment design and construction, experimental design, high-throughput methods, and finally methods for data analysis. PMID:15817291

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

    PubMed

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

    2011-04-01

    Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Sulzman, F. W.

    1981-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

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

  10. Circadian Rhythms: Hijacking the Cyanobacterial Clock

    PubMed Central

    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 Floral Scent Emission.

    PubMed

    Fenske, Myles P; Imaizumi, Takato

    2016-01-01

    To successfully recruit pollinators, plants often release attractive floral scents at specific times of day to coincide with pollinator foraging. This timing of scent emission is thought to be evolutionarily beneficial to maximize resource efficiency while attracting only useful pollinators. Temporal regulation of scent emission is tied to the activity of the specific metabolic pathways responsible for scent production. Although floral volatile profiling in various plants indicated a contribution by the circadian clock, the mechanisms by which the circadian clock regulates timing of floral scent emission remained elusive. Recent studies using two species in the Solanaceae family provided initial insight into molecular clock regulation of scent emission timing. In Petunia hybrida, the floral volatile benzenoid/phenylpropanoid (FVBP) pathway is the major metabolic pathway that produces floral volatiles. Three MYB-type transcription factors, ODORANT 1 (ODO1), EMISSION OF BENZENOIDS I (EOBI), and EOBII, all of which show diurnal rhythms in mRNA expression, act as positive regulators for several enzyme genes in the FVBP pathway. Recently, in P. hybrida and Nicotiana attenuata, homologs of the Arabidopsis clock gene LATE ELONGATED HYPOCOTYL (LHY) have been shown to have a similar role in the circadian clock in these plants, and to also determine the timing of scent emission. In addition, in P. hybrida, PhLHY directly represses ODO1 and several enzyme genes in the FVBP pathway during the morning as an important negative regulator of scent emission. These findings facilitate our understanding of the relationship between a molecular timekeeper and the timing of scent emission, which may influence reproductive success. PMID:27148293

  12. Circadian Rhythms in Floral Scent Emission

    PubMed Central

    Fenske, Myles P.; Imaizumi, Takato

    2016-01-01

    To successfully recruit pollinators, plants often release attractive floral scents at specific times of day to coincide with pollinator foraging. This timing of scent emission is thought to be evolutionarily beneficial to maximize resource efficiency while attracting only useful pollinators. Temporal regulation of scent emission is tied to the activity of the specific metabolic pathways responsible for scent production. Although floral volatile profiling in various plants indicated a contribution by the circadian clock, the mechanisms by which the circadian clock regulates timing of floral scent emission remained elusive. Recent studies using two species in the Solanaceae family provided initial insight into molecular clock regulation of scent emission timing. In Petunia hybrida, the floral volatile benzenoid/phenylpropanoid (FVBP) pathway is the major metabolic pathway that produces floral volatiles. Three MYB-type transcription factors, ODORANT 1 (ODO1), EMISSION OF BENZENOIDS I (EOBI), and EOBII, all of which show diurnal rhythms in mRNA expression, act as positive regulators for several enzyme genes in the FVBP pathway. Recently, in P. hybrida and Nicotiana attenuata, homologs of the Arabidopsis clock gene LATE ELONGATED HYPOCOTYL (LHY) have been shown to have a similar role in the circadian clock in these plants, and to also determine the timing of scent emission. In addition, in P. hybrida, PhLHY directly represses ODO1 and several enzyme genes in the FVBP pathway during the morning as an important negative regulator of scent emission. These findings facilitate our understanding of the relationship between a molecular timekeeper and the timing of scent emission, which may influence reproductive success. PMID:27148293

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

    PubMed

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

    2013-11-01

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

  14. The effect of stress on circadian rhythms.

    PubMed

    Brodan, V; Kuhn, E; Veselková, A; Kaucká, J

    1982-01-01

    The authors chose four types of intensive stress in man and show their effect on the circadian rhythms of selected parameters. Sleep deprivation reduces mean sideraemia and oscilation amplitudes. The morning rhythm maximum shifts to early morning hours. Acute fasting does not change the biorhythm of serum iron despite that mean sideraemia increases. On the other hand, realimentation is associated with a marked drop of iron level and a shift of the morning maximum to early afternoon hours. Stress induced by isolation in humid warm environment initiates a decrease of systolic blood pressure. While biorhythm amplitude remains unchanged peak systolic pressure moves from the usual 18 to 20 hours up to 23 to 24 hours. Stress caused by diagnostic cardiac catheterization results in biorhythm inversion of the urinary excretion of catecholamines and 17-OH-corticoids. On the day of catheterization, performed in all cases in the morning hours, the usual morning peak values of adrenaline shifted to afternoon hours and those of noradrenaline and 17-OH-corticoids even to late night hours. For practical purposes, biorhythm changes can be used as indicators of the effect and intensity of stress. PMID:7075389

  15. Preliminary characterization of persisting circadian rhythms during space flight

    NASA Technical Reports Server (NTRS)

    Sultzman, F. M.

    1984-01-01

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

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

    PubMed Central

    Fergus, Daniel J.; Shaw, Kerry L.

    2013-01-01

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

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

    PubMed

    Fergus, Daniel J; Shaw, Kerry L

    2013-05-01

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

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

    PubMed Central

    Wang, Yusi; Pati, Paramita; Xu, Yiming; Chen, Feng; Stepp, David W.; Huo, Yuqing; Rudic, R. Daniel; Fulton, David J. R.

    2016-01-01

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

  19. p38 MAP kinase regulates circadian rhythms in Drosophila.

    PubMed

    Vrailas-Mortimer, Alysia D; Ryan, Sarah M; Avey, Matthew J; Mortimer, Nathan T; Dowse, Harold; Sanyal, Subhabrata

    2014-12-01

    The large repertoire of circadian rhythms in diverse organisms depends on oscillating central clock genes, input pathways for entrainment, and output pathways for controlling rhythmic behaviors. Stress-activated p38 MAP Kinases (p38K), although sparsely investigated in this context, show circadian rhythmicity in mammalian brains and are considered part of the circadian output machinery in Neurospora. We find that Drosophila p38Kb is expressed in clock neurons, and mutants in p38Kb either are arrhythmic or have a longer free-running periodicity, especially as they age. Paradoxically, similar phenotypes are observed through either transgenic inhibition or activation of p38Kb in clock neurons, suggesting a requirement for optimal p38Kb function for normal free-running circadian rhythms. We also find that p38Kb genetically interacts with multiple downstream targets to regulate circadian locomotor rhythms. More specifically, p38Kb interacts with the period gene to regulate period length and the strength of rhythmicity. In addition, we show that p38Kb suppresses the arrhythmic behavior associated with inhibition of a second p38Kb target, the transcription factor Mef2. Finally, we find that manipulating p38K signaling in free-running conditions alters the expression of another downstream target, MNK/Lk6, which has been shown to cycle with the clock and to play a role in regulating circadian rhythms. These data suggest that p38Kb may affect circadian locomotor rhythms through the regulation of multiple downstream pathways. PMID:25403440

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

    PubMed

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

    2008-11-28

    We have established human retinal pigment epithelial cell lines stably expressing the luciferase gene, driven by the human Bmal1 promoter, to obtain human-derived cells that show circadian rhythms of bioluminescence after dexamethasone treatment. The average circadian period of bioluminescence for the obtained clones was 24.07+/-0.48 h. Lithium (10 mM) in the medium significantly lengthened the circadian period of bioluminescence, which is consistent with previous reports, while 2 mM or 5 mM lithium had no effect. This is the first report on the establishment of human-derived cell lines that proliferate infinitely and show circadian rhythms of bioluminescence, and also the first to investigate the effects of low-dose lithium on the circadian rhythms of human-derived cells in vitro. The established cells will be useful for various in vitro studies of human circadian rhythms and for the development of new therapies for human disorders related to circadian rhythm disturbances. PMID:18809466

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

    NASA Astrophysics Data System (ADS)

    Li, Ying; Liu, Zengrong

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

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

    PubMed Central

    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

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

    PubMed

    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

  4. Modeling and Validating Chronic Pharmacological Manipulation of Circadian Rhythms

    PubMed Central

    Kim, J K; Forger, D B; Marconi, M; Wood, D; Doran, A; Wager, T; Chang, C; Walton, K M

    2013-01-01

    Circadian rhythms can be entrained by a light-dark (LD) cycle and can also be reset pharmacologically, for example, by the CK1δ/ε inhibitor PF-670462. Here, we determine how these two independent signals affect circadian timekeeping from the molecular to the behavioral level. By developing a systems pharmacology model, we predict and experimentally validate that chronic CK1δ/ε inhibition during the earlier hours of a LD cycle can produce a constant stable delay of rhythm. However, chronic dosing later during the day, or in the presence of longer light intervals, is not predicted to yield an entrained rhythm. We also propose a simple method based on phase response curves (PRCs) that predicts the effects of a LD cycle and chronic dosing of a circadian drug. This work indicates that dosing timing and environmental signals must be carefully considered for accurate pharmacological manipulation of circadian phase. PMID:23863866

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

    PubMed

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

    1978-05-01

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

  6. Regulation of circadian rhythms in mammals by behavioral arousal.

    PubMed

    Webb, Ian C; Antle, Michael C; Mistlberger, Ralph E

    2014-06-01

    Circadian rhythms in most mammals are synchronized to local time by phase and period resetting actions of daily light-dark cycles on a retino-recipient, light-entrainable circadian pacemaker, the suprachiasmatic nucleus (SCN). The SCN receives input from other brain regions, some of which mediate the phase and period resetting actions of behavioral arousal on circadian rhythms. We review historical milestones in the discovery of so-called "nonphotic" circadian clock resetting induced by environmentally stimulated arousal, or by feedback from clock-controlled rest-activity cycles. Topics include species generality, interactions between concurrent or successive photic and nonphotic inputs to the circadian clock, neural pathways, neurotransmitters, and clock cell responses that mediate resetting by behavioral arousal. The role of behavioral inputs to the circadian clock in determining the phase of entrainment to local time in natural environments is not well understood. Nonetheless, nonphotic effects are of sufficient magnitude to raise issues for the design of experiments in behavioral neuroscience (any procedure that is sufficiently arousing may alter the timing of circadian clocks that regulate dependent variables of primary interest). Nonphotic inputs to the clock may be exploited in strategies to reset or strengthen circadian rhythms in humans. PMID:24773430

  7. Circadian rhythms in the short-tailed shrew, Blarina brevicauda.

    PubMed

    Antipas, A J; Madison, D M; Ferraro, J S

    1990-08-01

    Circadian rhythms of wheel running and feeding were measured in the short-tailed shrew. Shrews were strongly nocturnal, and their activity rhythms entrained to both long-day (LD 16:8) and short-day (LD 6:18) photocycles. Under conditions of continuous light (LL) or darkness (DD), the activity rhythms free-ran with average periodicities of 25.1 hours and 24.1 hours, respectively. In LL the level of activity was depressed, and in some cases wheel running was completely inhibited. No significant sex differences were observed in the period or amplitude of the monitored circadian rhythms. All shrews fed throughout the day and night; however, unlike in previous reports, ultradian periods of feeding behavior were not found. The results are related to Aschoff's four observations for the effect of light on activity rhythms in nocturnal rodents. PMID:2255728

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    1993-01-01

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

  11. Inositols affect the mating circadian rhythm of Drosophila melanogaster

    PubMed Central

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

    2015-01-01

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

  12. Vasoactive intestinal polypeptide entrains circadian rhythms in astrocytes.

    PubMed

    Marpegan, Luciano; Krall, Thomas J; Herzog, Erik D

    2009-04-01

    Many mammalian cell types show daily rhythms in gene expression driven by a circadian pacemaker. For example, cultured astrocytes display circadian rhythms in Period1 and Period2 expression. It is not known, however, how or which intercellular factors synchronize and sustain rhythmicity in astrocytes. Because astrocytes are highly sensitive to vasoactive intestinal polypeptide (VIP), a neuropeptide released by neurons and important for the coordination of daily cycling, the authors hypothesized that VIP entrains circadian rhythms in astrocytes. They used astrocyte cultures derived from knock-in mice containing a bioluminescent reporter of PERIOD2 (PER2) protein, to assess the effects of VIP on the rhythmic properties of astrocytes. VIP induced a dose-dependent increase in the peak-to-trough amplitude of the ensemble rhythms of PER2 expression with maximal effects near 100 nM VIP and threshold values between 0.1 and 1 nM. VIP also induced dose- and phase-dependent shifts in PER2 rhythms and daily VIP administration entrained bioluminescence rhythms of astrocytes to a predicted phase angle. This is the first demonstration that a neuropeptide can entrain glial cells to a phase predicted by a phase-response curve. The authors conclude that VIP potently entrains astrocytes in vitro and is a candidate for coordinating daily rhythms among glia in the brain. PMID:19346450

  13. Vasoactive intestinal polypeptide entrains circadian rhythms in astrocytes

    PubMed Central

    Marpegan, Luciano; Krall, Thomas J.; Herzog, Erik D.

    2009-01-01

    Many mammalian cell types show daily rhythms in gene expression driven by a circadian pacemaker. For example, cultured astrocytes display circadian rhythms in Period1 and Period2 expression. It is not known, however, how or which intercellular factors synchronize and sustain rhythmicity in astrocytes. Because astrocytes are highly sensitive to vasoactive intestinal polypeptide (VIP), a neuropeptide released by neurons and important for the coordination of daily cycling, we hypothesized that VIP entrains circadian rhythms in astrocytes. We used astrocyte cultures derived from knock-in mice containing a bioluminescent reporter of PERIOD2 (PER2) protein, to assess the effects of VIP on the rhythmic properties of astrocytes. VIP induced a dose-dependent increase in the peak-to-trough amplitude of the ensemble rhythms of PER2 expression with maximal effects near 100nM VIP and threshold values between 0.1 and 1 nM. VIP also induced dose- and phase-dependent shifts in PER2 rhythms and daily VIP administration entrained bioluminescence rhythms of astrocytes to a predicted phase angle. This is the first demonstration that a neuropeptide can entrain glial cells to a phase predicted by a phase response curve. We conclude that VIP potently entrains astrocytes in vitro and is a candidate for coordinating daily rhythms among glia in the brain. PMID:19346450

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

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

    PubMed

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

    2015-03-01

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

  17. Energy intake and the circadian rhythm of core body temperature in sheep

    PubMed Central

    Maloney, Shane K; Meyer, Leith C R; Blache, D; Fuller, A

    2013-01-01

    We tested the hypothesis that different levels of energy intake would alter the circadian rhythm of core body temperature (Tc) in ovariectomized sheep. We measured arterial blood temperature every 5 min while ten sheep were offered a maintenance diet, 70% of maintenance requirements, or 150% of maintenance requirements, for 12 days, and later fasted for 2 days. The rhythmicity of Tc was analyzed for its dominant period and then a least-squares cosine wave was fitted to the data that generated a mesor, amplitude, and acrophase for the rhythm. When energy intake was less than maintenance requirements we observed a significant decrease in the mesor and minimum, and a significant increase in the amplitude and goodness of fit, of the body temperature rhythm. Fasting also resulted in a decrease in the maximum of the body temperature rhythm. Feeding the sheep to excess did not affect the mesor or maximum of the rhythm, but did result in a decrease in the goodness of fit of the rhythm in those sheep that consumed more energy than when they were on the maintenance diet, indicating that circadian rhythmicity was decreased when energy intake increased. Our data indicate that modulation of the circadian rhythm of body temperature, characterized by inactive-phase hypothermia, occurs when energy intake is reduced. The response may be an adaptation to energy imbalance in large mammals. PMID:24303185

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

    PubMed

    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

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

    PubMed

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

    2015-04-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

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

    PubMed

    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

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

    SciTech Connect

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

    2007-06-08

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

  3. An antennal circadian clock and circadian rhythms in peripheral pheromone reception in the moth Spodoptera littoralis.

    PubMed

    Merlin, Christine; Lucas, Philippe; Rochat, Didier; François, Marie-Christine; Maïbèche-Coisne, Martine; Jacquin-Joly, Emmanuelle

    2007-12-01

    Circadian rhythms are observed in mating behaviors in moths: females emit sex pheromones and males are attracted by these pheromones in rhythmic fashions. In the moth Spodoptera littoralis, we demonstrated the occurrence of a circadian oscillator in the antenna, the peripheral olfactory organ. We identified different clock genes, period (per), cryptochrome1 (cry1) and cryptochrome2 (cry2), in this organ. Using quantitative real-time PCR (qPCR), we found that their corresponding transcripts cycled circadianly in the antenna as well as in the brain. Electroantennogram (EAG) recordings over 24 h demonstrated for the first time a circadian rhythm in antennal responses of a moth to sex pheromone. qPCR showed that out of one pheromone-binding protein (PBP), one olfactory receptor (OR), and one odorant-degrading enzyme (ODE), all putatively involved in the pheromone reception, only the ODE transcript presented a circadian rhythm that may be related to rhythms in olfactory signal resolution. Peripheral or central circadian clock control of olfaction is then discussed in light of recent data. PMID:18057325

  4. Cryptochrome restores dampened circadian rhythms and promotes healthspan in aging Drosophila

    PubMed Central

    Rakshit, Kuntol; Giebultowicz, Jadwiga M.

    2013-01-01

    Summary Circadian clocks generate daily rhythms in molecular, cellular, and physiological functions providing temporal dimension to organismal homeostasis. Recent evidence suggests two-way relationship between circadian clocks and aging. While disruption of the circadian clock leads to premature aging in animals, there is also age-related dampening of output rhythms such as sleep/wake cycles and hormonal fluctuations. Decay in the oscillations of several clock genes was recently reported in aged fruit flies, but mechanisms underlying these age-related changes are not understood. We report that the circadian light-sensitive protein CRYPTOCHROME (CRY), is significantly reduced at both mRNA and protein levels in heads of old Drosophila melanogaster. Restoration of CRY using the binary GAL4/UAS system in old flies significantly enhanced the mRNA oscillatory amplitude of several genes involved in the clock mechanism. Flies with CRY overexpressed in all clock cells maintained strong rest/activity rhythms in constant darkness late in life when rhythms were disrupted in most control flies. WE also observed a remarkable extension of healthspan in flies with elevated CRY. Conversely, CRY deficient mutants showed accelerated functional decline and accumulated greater oxidative damage. Interestingly, overexpression of CRY in central clock neurons alone was not sufficient to restore rest/activity rhythms or extend healthspan. Together, these data suggest novel anti-aging functions of CRY and indicate that peripheral clocks play an active role in delaying behavioral and physiological aging. PMID:23692507

  5. My Path from Chemistry to Phytochrome and Circadian Rhythms

    PubMed Central

    Tobin, Elaine M.

    2016-01-01

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

  6. Neuroimaging, cognition, light and circadian rhythms.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Circadian rhythms in liver physiology and liver diseases.

    PubMed

    Tong, Xin; Yin, Lei

    2013-04-01

    In mammals, circadian rhythms function to coordinate a diverse panel of physiological processes with environmental conditions such as food and light. As the driving force for circadian rhythmicity, the molecular clock is a self-sustained transcription-translational feedback loop system consisting of transcription factors, epigenetic modulators, kinases/phosphatases, and ubiquitin E3 ligases. The molecular clock exists not only in the suprachiasmatic nuclei of the hypothalamus but also in the peripheral tissues to regulate cellular and physiological function in a tissue-specific manner. The circadian clock system in the liver plays important roles in regulating metabolism and energy homeostasis. Clock gene mutant animals display impaired glucose and lipid metabolism and are susceptible to diet-induced obesity and metabolic dysfunction, providing strong evidence for the connection between the circadian clock and metabolic homeostasis. Circadian-controlled hepatic metabolism is partially achieved by controlling the expression and/or activity of key metabolic enzymes, transcription factors, signaling molecules, and transporters. Reciprocally, intracellular metabolites modulate the molecular clock activity in response to the energy status. Although still at the early stage, circadian clock dysfunction has been implicated in common chronic liver diseases. Circadian dysregulation of lipid metabolism, detoxification, reactive oxygen species (ROS) production, and cell-cycle control might contribute to the onset and progression of liver steatosis, fibrosis, and even carcinogenesis. In summary, these findings call for a comprehensive study of the function and mechanisms of hepatic circadian clock to gain better understanding of liver physiology and diseases. PMID:23720334

  9. Circadian rhythms and fractal fluctuations in forearm motion

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Hilton, Michael F.

    2005-03-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Fuller, Charles

    1997-01-01

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

  12. Nuclear receptors linking circadian rhythms and cardiometabolic control

    PubMed Central

    Duez, Hélène; Staels, Bart

    2010-01-01

    Many behavioral and physiological processes, including locomotor activity, blood pressure, body temperature, sleep(fasting)/wake(feeding) cycles as well as metabolic regulation display diurnal rhythms. The biological clock ensures proper metabolic alignment of energy substrate availability and processing. Studies in animals and humans highlight a strong link between circadian disorders and altered metabolic responses and cardiovascular events. Shiftwork, for instance, increases the risk to develop metabolic abnormalities resembling the Metabolic Syndrome. Nuclear receptors have long been known as metabolic regulators. Several of them (ie. Rev-erbα, RORα, PPARs) are subjected to circadian variations and are integral components of the molecular clock machinery. In turn, these nuclear receptors regulate downstream target genes in a circadian manner, acting to properly gate metabolic events to the appropriate circadian time window. PMID:20631353

  13. Rhythms of Life: The Plant Circadian Clock - (By Katherine Hubbard and Antony Dodd).

    PubMed

    2016-04-01

    Summaryplantcell;28/4/tpc.116.tt0416/FIG1F1fig1This teaching tool explores circadian rhythms in plants. The topic is presented as a series of concepts illustrated by examples, including the architecture of circadian clocks and the connections between the oscillator and circadian-regulated processes such as metabolism and flowering. The Teaching Tool introduces some of the techniques used to investigate circadian biology and explores how understanding circadian rhythms could lead to crop improvement. PMID:27169989

  14. Quantification of Circadian Rhythms in Single Cells

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  16. Circadian rhythms in liver metabolism and disease

    PubMed Central

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

    2015-01-01

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

  17. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

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

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

    PubMed

    Bechtel, William

    2015-01-01

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

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

    PubMed Central

    Martin, Tristan; Moussay, Sébastien; Bulla, Ingo; Bulla, Jan; Toupet, Michel; Etard, Olivier; Denise, Pierre; Davenne, Damien; Coquerel, Antoine; Quarck, Gaëlle

    2016-01-01

    Background New insights have expanded the influence of the vestibular system to the regulation of circadian rhythmicity. Indeed, hypergravity or bilateral vestibular loss (BVL) in rodents causes a disruption in their daily rhythmicity for several days. The vestibular system thus influences hypothalamic regulation of circadian rhythms on Earth, which raises the question of whether daily rhythms might be altered due to vestibular pathology in humans. The aim of this study was to evaluate human circadian rhythmicity in people presenting a total bilateral vestibular loss (BVL) in comparison with control participants. Methodology and Principal Findings Nine patients presenting a total idiopathic BVL and 8 healthy participants were compared. Their rest-activity cycle was recorded by actigraphy at home over 2 weeks. The daily rhythm of temperature was continuously recorded using a telemetric device and salivary cortisol was recorded every 3 hours from 6:00AM to 9:00PM over 24 hours. BVL patients displayed a similar rest activity cycle during the day to control participants but had higher nocturnal actigraphy, mainly during weekdays. Sleep efficiency was reduced in patients compared to control participants. Patients had a marked temperature rhythm but with a significant phase advance (73 min) and a higher variability of the acrophase (from 2:24 PM to 9:25 PM) with no correlation to rest-activity cycle, contrary to healthy participants. Salivary cortisol levels were higher in patients compared to healthy people at any time of day. Conclusion We observed a marked circadian rhythmicity of temperature in patients with BVL, probably due to the influence of the light dark cycle. However, the lack of synchronization between the temperature and rest-activity cycle supports the hypothesis that the vestibular inputs are salient input to the circadian clock that enhance the stabilization and precision of both external and internal entrainment. PMID:27341473

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

    PubMed Central

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

    2015-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1−/− and ClockΔ19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

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

    PubMed Central

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

    2015-01-01

    The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (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. PMID:26394143

  2. Calculating activation energies for temperature compensation in circadian rhythms

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  3. Sleep and Circadian Rhythms in Four Orbiting Astronauts

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-20

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  10. Links between Circadian Rhythms and Psychiatric Disease

    PubMed Central

    Karatsoreos, Ilia N.

    2014-01-01

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

  11. Design and Analysis of Temperature Preference Behavior and its Circadian Rhythm in Drosophila

    PubMed Central

    Goda, Tadahiro; Leslie, Jennifer R.; Hamada, Fumika N.

    2014-01-01

    The circadian clock regulates many aspects of life, including sleep, locomotor activity, and body temperature (BTR) rhythms1,2. We recently identified a novel Drosophila circadian output, called the temperature preference rhythm (TPR), in which the preferred temperature in flies rises during the day and falls during the night 3. Surprisingly, the TPR and locomotor activity are controlled through distinct circadian neurons3. Drosophila locomotor activity is a well known circadian behavioral output and has provided strong contributions to the discovery of many conserved mammalian circadian clock genes and mechanisms4. Therefore, understanding TPR will lead to the identification of hitherto unknown molecular and cellular circadian mechanisms. Here, we describe how to perform and analyze the TPR assay. This technique not only allows for dissecting the molecular and neural mechanisms of TPR, but also provides new insights into the fundamental mechanisms of the brain functions that integrate different environmental signals and regulate animal behaviors. Furthermore, our recently published data suggest that the fly TPR shares features with the mammalian BTR3. Drosophila are ectotherms, in which the body temperature is typically behaviorally regulated. Therefore, TPR is a strategy used to generate a rhythmic body temperature in these flies5-8. We believe that further exploration of Drosophila TPR will facilitate the characterization of the mechanisms underlying body temperature control in animals. PMID:24457268

  12. Burn trauma disrupts circadian rhythms in rat liver

    PubMed Central

    Rao, Rohit; Yang, Qian; Orman, Mehmet A; Berthiaume, Francois; Ierapetritou, Marianthi G; Androulakis, Ioannis P

    2016-01-01

    Circadian rhythms play an important role in maintaining homeostasis and solid organ function. The purpose of this study is to assess the implications of burn injury in rats on the underlying circadian patterns of gene expression in liver. Circadian-regulated genes and burn-induced genes were identified by applying consensus clustering methodology to temporally differentially expressed probe sets obtained from burn and sham-burn data sets. Of the liver specific genes which we hypothesize that exhibit circadian rhythmicity, 88% are not differentially expressed following the burn injury. Specifically, the vast majority of the circadian regulated-genes representing central carbon and nitrogen metabolism are “up-regulated” after the burn injury, indicating the onset of hypermetabolism. In addition, cell-cell junction and membrane structure related genes showing rhythmic behavior in the control group were not differentially expressed across time in the burn group, which could be an indication of hepatic damage due to the burn. Finally, the suppression of the immune function related genes is observed in the postburn phase, implying the severe “immunosuppression”. Our results demonstrated that the short term response (24-h post injury) manifests a loss of circadian variability possibly compromising the host in terms of subsequent challenges. PMID:27335693

  13. Circadian rhythm of lactate dehydrogenase in rat testis.

    PubMed

    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

  14. Circadian rhythms of gastrointestinal function are regulated by both central and peripheral oscillators

    PubMed Central

    Malloy, Jaclyn N.; Paulose, Jiffin K.; Li, Ye

    2012-01-01

    Circadian clocks are responsible for daily rhythms in a wide array of processes, including gastrointestinal (GI) function. These are vital for normal digestive rhythms and overall health. Previous studies demonstrated circadian clocks within the cells of GI tissue. The present study examines the roles played by the suprachiasmatic nuclei (SCN), master circadian pacemaker for overt circadian rhythms, and the sympathetic nervous system in regulation of circadian GI rhythms in the mouse Mus musculus. Surgical ablation of the SCN abolishes circadian locomotor, feeding, and stool output rhythms when animals are presented with food ad libitum, while restricted feeding reestablishes these rhythms temporarily. In intact mice, chemical sympathectomy with 6-hydroxydopamine has no effect on feeding and locomotor rhythmicity in light-dark cycles or constant darkness but attenuates stool weight and stool number rhythms. Again, however, restricted feeding reestablishes rhythms in locomotor activity, feeding, and stool output rhythms. Ex vivo, intestinal tissue from PER2::LUC transgenic mice expresses circadian rhythms of luciferase bioluminescence. Chemical sympathectomy has little effect on these rhythms, but timed administration of the β-adrenergic agonist isoproterenol causes a phase-dependent shift in PERIOD2 expression rhythms. Collectively, the data suggest that the SCN are required to maintain feeding, locomotor, and stool output rhythms during ad libitum conditions, acting at least in part through daily activation of sympathetic activity. Even so, this input is not necessary for entrainment to timed feeding, which may be the province of oscillators within the intestines themselves or other components of the GI system. PMID:22723262

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

    PubMed

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

    2016-03-01

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

  16. Implications of circadian rhythm and stress in addiction vulnerability

    PubMed Central

    Becker-Krail, Darius; McClung, Colleen

    2016-01-01

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

  17. Evolving roles of circadian rhythms in liver homeostasis and pathology

    PubMed Central

    Chen, Lu; Jia, Leijuan; Yuan, Jie; Sun, Mei; Zhang, Wen; Wang, Peipei; Zuo, Jian; Xu, Zhenyu; Luan, Jiajie

    2016-01-01

    Circadian clock in mammals is determined by a core oscillator in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronized peripheral clocks in other tissues. The coherent timing systems could sustain robust output of circadian rhythms in response to the entrainment controlled environmentally. Disparate approaches have discovered that clock genes and clock-controlled genes (CCGs) exist in nearly all mammalian cell types and are essential for establishing the mechanisms and complexity of internal time-keeping systems. Accumulating evidence demonstrates that the control of homeostasis and pathology in the liver involves intricate loops of transcriptional and post-translational regulation of clock genes expression. This review will focus on the recent advances with great importance concerning clock rhythms linking liver homeostasis and diseases. We particularly highlight what is currently known of the evolving insights into the mechanisms underlying circadian clock. Eventually, findings during recent years in the field might prompt new circadian-related chronotherapeutic strategies for the diagnosis and treatment of liver diseases by coupling these processes PMID:26843619

  18. Evolving roles of circadian rhythms in liver homeostasis and pathology.

    PubMed

    Zhou, Dexi; Wang, Yaqin; Chen, Lu; Jia, Leijuan; Yuan, Jie; Sun, Mei; Zhang, Wen; Wang, Peipei; Zuo, Jian; Xu, Zhenyu; Luan, Jiajie

    2016-02-23

    Circadian clock in mammals is determined by a core oscillator in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronized peripheral clocks in other tissues. The coherent timing systems could sustain robust output of circadian rhythms in response to the entrainment controlled environmentally. Disparate approaches have discovered that clock genes and clock-controlled genes (CCGs) exist in nearly all mammalian cell types and are essential for establishing the mechanisms and complexity of internal time-keeping systems. Accumulating evidence demonstrates that the control of homeostasis and pathology in the liver involves intricate loops of transcriptional and post-translational regulation of clock genes expression. This review will focus on the recent advances with great importance concerning clock rhythms linking liver homeostasis and diseases. We particularly highlight what is currently known of the evolving insights into the mechanisms underlying circadian clock . Eventually , findings during recent years in the field might prompt new circadian-related chronotherapeutic strategies for the diagnosis and treatment of liver diseases by coupling these processes. PMID:26843619

  19. Implicit Associations Have a Circadian Rhythm

    PubMed Central

    Zadra, Jonathan R.; Proffitt, Dennis R.

    2014-01-01

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

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

    PubMed

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

    2014-11-01

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

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

    SciTech Connect

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

    1982-09-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

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

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

    PubMed

    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

  4. Circadian activity rhythms and mortality: the Study of Osteoporotic Fractures

    PubMed Central

    Tranah, Gregory J.; Blackwell, Terri; Ancoli-Israel, Sonia; Paudel, Misti L.; Ensrud, Kristine E.; Cauley, Jane A.; Redline, Susan; Hillier, Teresa A.; Cummings, Steven R; Stone, Katie L.

    2010-01-01

    OBJECTIVES To determine whether circadian activity rhythms are associated with mortality in community-dwelling older women. DESIGN Prospective study of mortality. SETTING A cohort study of health and aging. PARTICIPANTS 3,027 community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84 years). MEASUREMENTS Activity data were collected with wrist actigraphy for a minimum of three 24-hour periods and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), mean activity level (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained. RESULTS Over an average of 4.1 years of follow-up there were 444 (15%) deaths. There was an inverse association between peak activity height and all-cause mortality rates with higher mortality rates observed in the lowest activity quartile (Hazard ratio [HR]=2.18, 95% CI, 1.63–2.92) compared with the highest quartile after adjusting for age, clinic site, race, BMI, cognitive function, exercise, IADL impairments, depression, medications, alcohol, smoking, self-reported health status, married status, and co-morbidities. Increased risk of all-cause mortality was observed between lower mean activity level (HR=1.71, 95% CI, 1.29–2.27) and rhythm robustness (HR=1.97, 95% CI, 1.50–2.60). Increased mortality from cancer (HR=2.09, 95% CI, 1.04–4.22) and stroke (HR=2.64, 95% CI, 1.11–6.30) was observed for a delayed timing of peak activity (after 4:33PM; >1.5 SD from mean) when compared to the mean peak range (2:50PM–4:33PM). CONCLUSION Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g. physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in the elderly

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. Circadian rhythms in a long-term duration space flight

    NASA Astrophysics Data System (ADS)

    Alpatov, Alexey M.

    In order to maintain cosmonaut health and performance, it is important for the work-rest schedule to follow human circadian rhythms (CR). What happens with CR in space flight? Investigations of CR in mammals revealed, that the circadian phase in flight is less stable, probably due to a displacement of the range of entrainment, resulting from internal period change (the latter was confirmed on insects). The circadian period may be a gravity-dependent parameter. If so, the basic biological requirement for the day length might be different in weightlessness. On this basis, a higher risk of desynchronosis is expected in a long-duration space flight. As a countermeasure, a non-24-hr day length could be suggested, being close to the internal circadian period (in humans about 25 hr). Taking into account a possible displacement of period in weightlessness, it seems reasonable to establish a flexible work-rest schedule, capable to follow the body temperature CR by means of biofeedback.

  9. Circadian rhythms in cardiac arrhythmias and opportunities for their chronotherapy.

    PubMed

    Portaluppi, Francesco; Hermida, Ramón C

    2007-08-31

    It is now well established that nearly all functions of the body, including those that influence the pharmacokinetics and pharmacodynamics of medications, exhibit significant 24-hour variation. The electrical properties of the heart as well as cardiac arrhythmias also vary as circadian rhythms, even though the suboptimal methods initially used for their investigation slowed their identification and thorough characterization. The application of continuous Holter monitoring of the electrical properties of the heart has revealed 24-hour variation in the occurrence of ventricular premature beats with the peak in events, in diurnally active persons, between 6 a.m. and noon. After the introduction of implantable cardioverter-defibrillators, ventricular tachycardia or fibrillation were also found to peak in the same period of the day. Even defibrillator energy requirements show circadian variation, thus supporting the need for a temporal awareness in the therapeutic approach to arrhythmias. Imbalanced autonomic tone, circulating levels of catecholamines, increased heart rate and blood pressure, all established determinants of cardiac arrhythmias, show circadian variations and underlie the genesis of the circadian pattern of cardiac arrhythmias. Arrhythmogenesis appears to be suppressed during nighttime sleep, and this can influence the evaluation of the efficacy of antiarrhythmic medications in relation to their administration time. Unfortunately, very few studies have been undertaken to assess the proper timing (chronotherapy) of antiarrhythmic medications as means to maximize efficacy and possibly reduce side effects. Further research in this field is warranted and could bring new insight and clinical advantage. PMID:17659808

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

    PubMed

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

    2016-02-01

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

  11. Microcomputerized measurement of the circadian locomotor rhythm in microorganisms.

    PubMed

    Tanakadate, A; Ishikawa, H; Hasegawa, K

    1985-02-01

    A computerized close-up video/photoamplifier system was implemented for the study of circadian locomotor rhythm in a population of a ciliate protozoan, Paramecium. This fully microcomputerized system facilitated automatic long-term measurement of three parameters in parallel: (1) numbers of specimens per 10 min traversing beneath a fixed point in an experimental vessel, (2) times taken by specimens to traverse the point, and (3) interval times between subsequent specimens traversing the point. Stochastic analyses using these parameters can derive the circadian fluctuation of physiological variables, such as swimming speed and the frequency of avoiding reaction (abrupt change in swimming direction). The computerized system simultaneously accomplished the acquisition of these three sets of data, their transient storage, and their graphic display according to given format. The system software was constituted so that an experimenter with little computer knowledge, could easily operate the system by answering questions displayed on the computer monitor. PMID:3839082

  12. Comparison of circadian rhythms in male and female humans

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    NASA Technical Reports Server (NTRS)

    Lafferty, J. F.

    1972-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.

    2005-01-01

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

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

    PubMed Central

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

    2014-01-01

    The disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification resulted in cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Collected at baseline, during and after therapy longitudinal data sets were processed using Fast Fourier Transform Cosinor and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p<0.05) for 49/61 temperature time series (80.3%), and 15/16 rest-activity patterns (93.7%) at baseline. However, individual circadian amplitudes varied from 0.04 °C to 2.86 °C for skin surface temperature (median, 0.72 °C), and from 16.6 to 146.1 acc/min for rest-activity (median, 88.9 acc/min). Thirty-nine pairs of baseline temperature and rest-activity time series (75%) were correlated (r>|0.7|; p<0.05). Individual circadian acrophases at baseline were scattered from 15:18 to 6:05 for skin surface temperature, and from 12:19 to 15:18 for rest-activity, with respective median values of 01:10 (25–75% quartiles, 22:35–3:07) and 14:12 (13:14–14:31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. In contrast, transient or sustained disruption

  18. Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease

    PubMed Central

    Verwey, Michael; Dhir, Sabine; Amir, Shimon

    2016-01-01

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

  19. Circadian rhythms of female mating activity governed by clock genes in Drosophila

    PubMed Central

    Sakai, Takaomi; Ishida, Norio

    2001-01-01

    The physiological and behavioral activities of many animals are restricted to specific times of the day. The daily fluctuation in the mating activity of some insects is controlled by an endogenous clock, but the genetic mechanism that controls it remains unknown. Here we demonstrate that wild-type Drosophila melanogaster display a robust circadian rhythm in the mating activity, and that these rhythms are abolished in period- or timeless-null mutant flies (per01 and tim01). Circadian rhythms were lost when rhythm mutant females were paired with wild-type males, demonstrating that female mating activity is governed by clock genes. Furthermore, we detected an antiphasic relationship in the circadian rhythms of mating activity between D. melanogaster and its sibling species Drosophila simulans. Female- and species-specific circadian rhythms in the mating activity of Drosophila seem to cause reproductive isolation. PMID:11470898

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

    PubMed

    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

  1. Absence of Circadian Rhythms of Preterm Premature Rupture of Membranes and Preterm Placental Abruption

    PubMed Central

    Luque-Fernandez, Miguel Angel; Ananth, Cande V.; Sanchez, Sixto E.; Qiu, Chun-fang; Hernandez-Diaz, Sonia; Valdimarsdottir, Unnur; Gelaye, Bizu; Williams, Michelle A.

    2014-01-01

    Purpose Data regarding circadian rhythm in the onset of spontaneous preterm premature rupture of membranes (PROM) and placental abruption (PA) cases are conflicting. We modeled the time of onset of preterm PROM and PA cases and examined if the circadian profiles varied based on the gestational age at delivery. Methods We used parametric and nonparametric methods, including trigonometric regression in the framework of generalized linear models, to test the presence of circadian rhythms in the time of onset of preterm PROM and PA cases, among 395 women who delivered a singleton between 2009 and 2010 in Lima, Peru. Results We found a diurnal circadian pattern, with a morning peak at 07h:32’ (95%CI:05h:46’ – 09h:18’) among moderate preterm PROM cases (P-value<0.001), and some evidence of a diurnal circadian periodicity among PA cases in term infants (P-value=0.067). However, we did not find evidence of circadian rhythms in the time of onset of extremely or very preterm PROM (P-value=0.259) and preterm PA (P-value=0.224). Conclusions The circadian rhythms of the time of onset of preterm PROM and PA cases varied based on gestational weeks at delivery. While circadian rhythms were presented among moderate preterm PROM and term PA cases, there was no evidence of circadian rhythms among preterm PA and very or extremely preterm PROM cases, underlying other mechanisms associated with the time of onset. PMID:25453346

  2. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    PubMed Central

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

    2014-01-01

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

  3. Wavelet-based analysis of circadian behavioral rhythms.

    PubMed

    Leise, Tanya L

    2015-01-01

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

  4. Effect of circadian rhythm on CNS oxygen toxicity.

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    PubMed Central

    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

  12. Circadian rhythm of breath hydrogen in young women.

    PubMed

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

    1998-08-01

    Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of alpha-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21-23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, alpha-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 +/- 3.9 ppm (mean +/- SE), which did not differ from the value for the previous night. Alpha-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 +/- 2.4 ppm (P < 0.05). There was a clear circadian pattern of breath hydrogen, high in the morning and decreasing to the nadir by 16:00. After dinner, the level increased again and stayed high during the night. Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day. PMID:9719227

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

    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 < 0.05). We found decreased extracellular SOD (p < 0.05), but no differences in total SOD, CAT or 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

  16. Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation

    PubMed Central

    Sahar, Saurabh; Nin, Veronica; Barbosa, Maria Thereza; Chini, Eduardo Nunes; Sassone-Corsi, Paolo

    2011-01-01

    The Intracellular levels of nicotinamide adenine dinucleotide (NAD+) are rhythmic and controlled by the circadian clock. However, whether NAD+ oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD+ hydrolase CD38. We found that rhythmicity of NAD+ was altered in the CD38-deficient mice. The high, chronic levels of NAD+ results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD+ levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD+ levels influence the circadian clock. PMID:21937766

  17. Circadian rhythms, oxidative stress, and antioxidative defense mechanisms.

    PubMed

    Hardeland, Rüdiger; Coto-Montes, Ana; Poeggeler, Burkhard

    2003-11-01

    Endogenous circadian and exogenously driven daily rhythms of antioxidative enzyme activities and of low molecular weight antioxidants (LMWAs) are described in various phylogenetically distant organisms. Substantial amplitudes are detected in several cases, suggesting the significance of rhythmicity in avoiding excessive oxidative stress. Mammalian and/or avian glutathione peroxidase and, as a consequence, glutathione reductase activities follow the rhythm of melatonin. Another hint for an involvement of melatonin in the control of redox processes is seen in its high-affinity binding to cytosolic quinone reductase 2, previously believed to be a melatonin receptor. Although antioxidative protection by pharmacological doses of melatonin is repeatedly reported, explanations of these findings are still insufficient and their physiological and chronobiological relevance is not yet settled. Recent data indicate a role of melatonin in the avoidance of mitochondrial radical formation, a function which may prevail over direct scavenging. Rhythmic changes in oxidative damage of protein and lipid molecules are also reported. Enhanced oxidative protein modification accompanied by a marked increase in the circadian amplitude of this parameter is detected in the Drosophila mutant rosy, which is deficient in the LMWA urate. Preliminary evidence for the significance of circadian rhythmicity in diminishing oxidative stress comes from clock mutants. In Drosophila, moderately enhanced protein damage is described for the arrhythmic and melatonin null mutant per0, but even more elevated, periodic damage is found in the short-period mutant per(s), synchronized to LD 12:12. Remarkably large increases in oxidative protein damage, along with impairment of tissue integrity and--obviously insufficient--compensatory elevations in protective enzymes are observed in a particularly vulnerable organ, the Harderian gland, of another short-period mutant tau, in the Syrian hamster. Mice deficient in

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

    PubMed Central

    Weldemichael, Dawit A.; Grossberg, George T.

    2010-01-01

    Circadian Rhythm Disturbances (CRDs) affect as many as a quarter of Alzheimer's disease (AD) patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients. PMID:20862344

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

    PubMed

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

    2015-12-01

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

  20. Do Urgent Caesarean Sections Have a Circadian Rhythm?

    PubMed Central

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

    2016-01-01

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

  1. Clock Genes Show Circadian Rhythms in Salivary Glands

    PubMed Central

    Zheng, L.; Seon, Y.J.; McHugh, J.; Papagerakis, S.; Papagerakis, P.

    2012-01-01

    Circadian rhythms are endogenous self-sustained oscillations with 24-hour periods that regulate diverse physiological and metabolic processes through complex gene regulation by “clock” transcription factors. The oral cavity is bathed by saliva, and its amount and content are modified within regular daily intervals. The clock mechanisms that control salivary production remain unclear. Our objective was to evaluate the expression and periodicity of clock genes in salivary glands. Real-time quantitative RT-PCR, in situ hybridization, and immunohistochemistry were performed to show circadian mRNA and protein expression and localization of key clock genes (Bmal1, Clock, Per1, and Per2), ion and aqua channel genes (Ae2a, Car2, and Aqp5), and salivary gland markers. Clock gene mRNAs and clock proteins were found differentially expressed in the serous acini and duct cells of all major salivary glands. The expression levels of clock genes and Aqp5 showed regular oscillatory patterns under both light/dark and complete-dark conditions. Bmla1 overexpression resulted in increased Aqp5 expression levels. Analysis of our data suggests that salivary glands have a peripheral clock mechanism that functions both in normal light/dark conditions and in the absence of light. This finding may increase our understanding of the control mechanisms of salivary content and flow. PMID:22699207

  2. Gravity and thermoregulation: metabolic changes and circadian rhythms

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

    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

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

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Altered circadian rhythm of the clock genes in fibrotic livers induced by carbon tetrachloride.

    PubMed

    Chen, Peng; Kakan, Xiamusiya; Zhang, Jianfa

    2010-04-16

    Disruption in circadian rhythms either by mutation in mice or by shiftwork in people, is associated with an increased risk for the development of multiple organ diseases. In turn, organ disease may influence the function of clock genes and peripheral circadian systems. Here we showed that hepatic fibrosis induced by carbon tetrachloride in mice leads to alterations in the circadian rhythms of hepatic clock genes. Especially, we found an impaired daily Cry2 rhythm in the fibrotic livers, with markedly decreased levels during the day time while compared with control livers. Associatively, the expressions of two important clock-regulated genes peroxisome proliferator-activated receptor alpha and cytochrome P450 oxidoreductase lost circadian rhythm with significantly decreased levels during the light-dark (12/12h) cycle in fibrotic livers. PMID:20233594

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

    ERIC Educational Resources Information Center

    Mindell, J. A.; And Others

    1996-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Zera, Anthony J

    2016-08-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

    This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression. PMID:27545669

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

    PubMed

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

    2016-01-01

    This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression. PMID:27545669

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

    ERIC Educational Resources Information Center

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

    1998-01-01

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

  16. Genetics and Epigenetics of Circadian Rhythms and Their Potential Roles in Neuropsychiatric Disorders

    PubMed Central

    Liu, Chunyu; Chung, Michael

    2015-01-01

    Circadian rhythms alterations have been implicated in multiple neuropsychiatric disorders, particularly sleep-wake disorders, addiction, and anxiety and mood disorders. Circadian rhythms are known to be maintained by a set of classic clock genes that form complex mutual and self regulatory loops. While many other genes showing rhythmic expression have been identified through genome-wide studies, their roles in the circadian regulation remain largely unknown. In attempts to directly connect circadian rhythms and neuropsychiatric disorders, genetic studies have identified genes with mutations associated with several rare forms of sleep disorders or sleep-related traits. Other than that, genetic studies of circadian genes in psychiatric disorders have yielded limited success. As important mediator of environmental factors and regulators of circadian rhythms, the epigenetic system may hold the key to the etiology or pathology of psychiatric disorders, their subtypes or endophenotypes. Epigenomic regulations of the circadian system and its related changes have not been thoroughly explored in the context of neuropsychiatric disorders. We argue for systematic investigation of the circadian system, particularly epigenetic regulation, and its involvement in neuropsychiatric disorders, to improve our understanding of human behavior and disease etiology. PMID:25652815

  17. Improved automated monitoring and new analysis algorithm for circadian phototaxis rhythms in Chlamydomonas

    PubMed Central

    Gaskill, Christa; Forbes-Stovall, Jennifer; Kessler, Bruce; Young, Mike; Rinehart, Claire A.; Jacobshagen, Sigrid

    2010-01-01

    Automated monitoring of circadian rhythms is an efficient way of gaining insight into oscillation parameters like period and phase for the underlying pacemaker of the circadian clock. Measurement of the circadian rhythm of phototaxis (swimming towards light) exhibited by the green alga Chlamydomonas reinhardtii has been automated by directing a narrow and dim light beam through a culture at regular intervals and determining the decrease in light transmittance due to the accumulation of cells in the beam. In this study, the monitoring process was optimized by constructing a new computer-controlled measuring machine that limits the test beam to wavelengths reported to be specific for phototaxis and by choosing an algal strain, which does not need background illumination between test light cycles for proper expression of the rhythm. As a result, period and phase of the rhythm are now unaffected by the time a culture is placed into the machine. Analysis of the rhythm data was also optimized through a new algorithm, whose robustness was demonstrated using virtual rhythms with various noises. The algorithm differs in particular from other reported algorithms by maximizing the fit of the data to a sinusoidal curve that dampens exponentially. The algorithm was also used to confirm the reproducibility of rhythm monitoring by the machine. Machine and algorithm can now be used for a multitude of circadian clock studies that require unambiguous period and phase determinations such as light pulse experiments to identify the photoreceptor(s) that reset the circadian clock in C. reinhardtii. PMID:20116270

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

    PubMed Central

    2011-01-01

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

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

    PubMed

    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

  20. Photocontrol of Dark Circadian Rhythms in Stomata of Phaseolus vulgaris L

    PubMed Central

    Holmes, M. Geoffrey; Klein, William H.

    1986-01-01

    Stomatal diffusion resistance in primary leaves of Phaseolus vulgaris L. which had been grown in light:dark cycles followed a marked circadian rhythm when the plants were transferred to continuous darkness. Reentrainment of the rhythm required more than one inductive change in photoperiod. The phasing of the rhythm of dark stomatal opening was contolled primarily by the light-on (dawn) signal, whereas the rhythm of dark closure was related to the light-off (dusk) signal. The evidence points to a dual control of the circadian clock in which a product of photosynthesis plays a major role. No evidence for phytochrome involvement in the phasing of the rhythm was found. An influence of phytochrome on the amplitude of the stomatal rhythm was observed in which removal of phytochrome-far-red absorbing form caused rapid damping. PMID:16665006

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

    PubMed

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

    2015-09-01

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

  2. Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer

    PubMed Central

    Altman, Brian J.

    2016-01-01

    Circadian rhythms are 24-h oscillations present in most eukaryotes and many prokaryotes that synchronize activity to the day-night cycle. They are an essential feature of organismal and cell physiology that coordinate many of the metabolic, biosynthetic, and signal transduction pathways studied in biology. The molecular mechanism of circadian rhythm is controlled both by signal transduction and gene transcription as well as by metabolic feedback. The role of circadian rhythm in cancer cell development and survival is still not well understood, but as will be discussed in this Review, accumulated research suggests that circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations. Thus, a complete understanding of the genetic and metabolic alterations in cancer must take potential circadian rhythm perturbations into account, as this disruption itself will influence how gene expression and metabolism are altered in the cancer cell compared to its non-transformed neighbor. It will be important to better understand these circadian changes in both normal and cancer cell physiology to potentially design treatment modalities to exploit this insight. PMID:27500134

  3. Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

    PubMed

    Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

    2011-04-01

    Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels. PMID:21682138

  4. Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer.

    PubMed

    Altman, Brian J

    2016-01-01

    Circadian rhythms are 24-h oscillations present in most eukaryotes and many prokaryotes that synchronize activity to the day-night cycle. They are an essential feature of organismal and cell physiology that coordinate many of the metabolic, biosynthetic, and signal transduction pathways studied in biology. The molecular mechanism of circadian rhythm is controlled both by signal transduction and gene transcription as well as by metabolic feedback. The role of circadian rhythm in cancer cell development and survival is still not well understood, but as will be discussed in this Review, accumulated research suggests that circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations. Thus, a complete understanding of the genetic and metabolic alterations in cancer must take potential circadian rhythm perturbations into account, as this disruption itself will influence how gene expression and metabolism are altered in the cancer cell compared to its non-transformed neighbor. It will be important to better understand these circadian changes in both normal and cancer cell physiology to potentially design treatment modalities to exploit this insight. PMID:27500134

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

    PubMed Central

    Xu, Kanyan

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Melatonin shifts human circadian rhythms according to a phase-response curve.

    PubMed

    Lewy, A J; Ahmed, S; Jackson, J M; Sack, R L

    1992-10-01

    A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle. PMID:1394610

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

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

  9. The circadian rhythm in adult attention-deficit/hyperactivity disorder: current state of affairs.

    PubMed

    Kooij, J J Sandra; Bijlenga, Denise

    2013-10-01

    Adults with ADHD often have sleep problems that are caused by a delay of their internal circadian rhythm system. Such individuals are often typified as 'evening' or 'night' persons. This review focuses on the link between ADHD symptoms and the evening typology through multiple pathways. Etiology of the internal circadian rhythm system, the genetic basis for evening typology, overlap between ADHD symptoms and evening preference and risk factors for various chronic health conditions, including metabolic syndrome and cancer, are discussed. The treatment perspectives to reset the delayed rhythm in adults with ADHD involve psychoeducation on sleep hygiene, melatonin in the afternoon or evening and bright light therapy in the morning. PMID:24117273

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

    PubMed

    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

  11. Actigraphic estimates of circadian rhythms and sleep/wake in older schizophrenia patients

    PubMed Central

    Martin, Jennifer; Jeste, Dilip V.; Caliguiri, Michael P.; Patterson, Thomas; Heaton, Robert; Ancoli-Israel, Sonia

    2009-01-01

    Twenty-four hour circadian activity rhythms and light-exposure levels of 28 older schizophrenia patients (mean age=58 years) were examined using an Actillume recorder. Sleep and wake were scored using the algorithm of the ACTION3 software which revealed that the patients slept for 67% of the night and napped for 9% of the day. Patients with more disturbed sleep and less robust circadian rhythms performed more poorly on neuropsychological tests. Patients with higher cognitive functioning and fewer extrapyramidal symptoms were more alert during the day. Few patients were exposed to high levels of illumination during the day, and older age was associated with lower levels of light exposure. Duration of antipsychotic use and higher antipsychotic doses were associated with decreased daytime alertness and less robust circadian activity rhythms. Patients taking antipsychotics were more sleepy both during the day and night than patients not taking antipsychotics. The circadian rhythm disturbances found in these patients did not seem to be due solely to low levels of illumination exposure. Life-style factors, behavioral factors, psychiatric symptoms and medications were likely contributors to the disturbed rhythms. The effects of the sleep disturbances did not seem to be benign. There were strong relationships between sleep and circadian rhythms and functioning. PMID:11163547

  12. Circadian rhythms in the mating behavior of the cockroach, Leucophaea maderae.

    PubMed

    Rymer, Jennifer; Bauernfeind, Amy L; Brown, Scott; Page, Terry L

    2007-02-01

    Mating behavior of small populations of virgin males and females of the cockroach Leucophaea maderae were continuously monitored via time-lapse video recording in controlled laboratory conditions. The time of onset of copulation was found to be rhythmic in a light cycle of 12 h light alternated with 12 h of darkness, with the peak of mating behavior occurring near the light to dark transition. This rhythm persisted in constant dim red illumination and constant temperature. In constant conditions, the period of the rhythm was slightly less than 24 h, with a peak of copulation during the late subjective day. These data demonstrated that mating behavior is gated by a circadian clock. When males and females were taken from light cycles that were 12 h out of phase, a bimodal rhythm was observed with one peak in the males' late subjective day and a second peak of equal amplitude in the late subjective day of females. The results indicated that circadian systems in both males and females contribute to the circadian rhythm in copulation. Bilateral section of the optic tracts (OTX) of both males and females abolished the rhythm, but the rhythm persisted when OTX females were paired with intact males or when OTX males were paired with intact females. Furthermore, when OTX males or OTX females were paired with intact animals that were 12 h out of phase, a bimodal rhythm was still observed. These results suggested that the circadian pacemaker in the optic lobes of both male and female cockroaches participates in the control of mating, but that a pacemaker outside the optic lobes is also likely involved. Finally, it was shown that the female's olfactory response (measured by electroantennogram) to components of the male sex pheromone exhibited a circadian rhythm, but the data suggested the peripheral olfactory rhythm is not likely to be involved in the rhythm of mating behavior. PMID:17229924

  13. How the circadian rhythm affects sleep, wakefulness, and overall health: background for understanding shift work disorder.

    PubMed

    Krystal, Andrew D

    2012-02-01

    It is estimated that 15 to 25% of the U.S. labor force works night, evening, or rotating shifts. These non-traditional schedules can affect the circadian rhythm, a self-sustained rhythm of biological processes that plays an important role in modulating sleep/wake function, resulting in circadian rhythm sleep disorder, shift work type, usually referred to as shift work disorder. The disorder consists of a constant or recurrent pattern of sleep interruption that results in insomnia when sleep is needed and excessive sleepiness during waking hours. Clinicians need more information about the role of the circadian rhythm in human functioning as well as the pathophysiology, prevalence, and consequences of shift work disorder, so that they can recognize and diagnose this problem in clinical practice. PMID:22401482

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

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

  15. Circadian rhythm in olfactory response in the antennae controlled by the optic lobe in the cockroach.

    PubMed

    Page, Terry L; Koelling, Erin

    2003-07-01

    The olfactory response in antennae of the cockroach, Leucophaea maderae, was investigated by measuring electroantennograms (EAGs) in restrained animals. The amplitude of the EAG response to pulses of ethyl acetate, octanol, or fenchone, exhibited a robust, light entrained, circadian rhythm that persisted at least 14 days in constant darkness. Dilution-response curves measured at the peak and trough of the rhythm indicated there was a 10-fold change in sensitivity. The EAG rhythm was abolished by severing the optic tracts, while entrainment was abolished by ablation of the compound eyes. The results indicate that the circadian system modulates olfactory sensitivity in the antennae and that the rhythm is driven by a circadian pacemaker in the optic lobes that is entrained by photoreceptors in the compound eyes. PMID:12837322

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

    PubMed Central

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

    2015-01-01

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

  17. A long noncoding RNA perturbs the circadian rhythm of hepatoma cells to facilitate hepatocarcinogenesis.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Yang, Yaoming; Duguay, David; Bédard, Nathalie; Rachalski, Adeline; Baquiran, Gerardo; Na, Chan Hyun; Fahrenkrug, Jan; Storch, Kai-Florian; Peng, Junmin; Wing, Simon S.; Cermakian, Nicolas

    2012-01-01

    Summary 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. PMID:23213472

  19. Metazoan circadian rhythm: toward an understanding of a light-based zeitgeber in sponges.

    PubMed

    Müller, Werner E G; Schröder, Heinz C; Pisignano, Dario; Markl, Julia S; Wang, Xiaohong

    2013-07-01

    In all eukaryotes, the 24-h periodicity in the environment contributed to the evolution of the molecular circadian clock. We studied some elements of a postulated circadian clock circuit in the lowest metazoans, the siliceous sponges. First, we identified in the demosponge Suberites domuncula the enzyme luciferase that generates photons. Then (most likely), the photons generated by luciferase are transmitted via the biosilica glass skeleton of the sponges and are finally harvested by cryptochrome in the same individual; hence, cryptochrome is acting as a photosensor. This information-transduction system, generation of light (luciferase), photon transmission (through the siliceous spicules), and photon reception (cryptochrome), all occur in the same individual. Therefore, we propose that this photoreception/phototransduction process might function as a nerve-cell-like signal transmitting system. This was corroborated by the fact that S. domuncula reacts to different wavelengths of light, originating from the sponge environment, with a differential gene expression of the transcription factor SOX. Recently, we succeeded in demonstrating that in sponges a light/dark controlled gene is expressed, which encodes for nocturnin, a protein showing poly(A)-specific 3'-exoribonuclease activity. Quantitative real-time polymerase chain reaction analyses revealed that primmorphs, 3D cell aggregates of sponge cells, after transfer from light to dark, show a 10-fold increased expression of the nocturnin gene. In contrast, the expression level of the gene encoding glycogenin decreases in the dark by three- to four-fold. It is concluded that sponges are provided with the molecular circadian clock protein nocturnin which is highly expressed in the dark. This finding together with the proposed light-transduction and spicule-based signaling system strongly supports the view that already the lowest metazoans, the sponges, have elements of a circadian rhythm, characteristic of higher

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

    PubMed

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

    2016-01-01

    Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species. PMID:27577611

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

    PubMed Central

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

    2016-01-01

    Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species. PMID:27577611

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

    PubMed

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

    2015-12-01

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

  3. Quantitative characterization of circadian rhythm of pulmonary function in asthmatic patients treated with inhaled corticosteroids.

    PubMed

    Zhou, Di; Li, Hongshan; Wang, Yaning; Hochhaus, Guenther; Sinha, Vikram; Zhao, Liang

    2015-08-01

    The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV1) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV1 measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV1 measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV1, and sex. Age and height were found to have significant effects on the mean FEV1 level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV1 occurred in the early morning and maximum FEV1 occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV1 circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development. PMID:26099861

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  5. [Estimation of death time by measurement of circadian melatonin rhythm].

    PubMed

    Mikami, H

    1993-05-01

    In order to establish a method for the estimation of death time (DT) from measuring melatonin (MT) contents in pineal bodies (PBs) and biological fluids, 85 cadavers were investigated--44 dead in Sapporo (N 43 degrees 4', E 141 degrees 21') and 41 in Tokyo (N 35 degrees 39', E 139 degrees 44'). MT contents were measured by radioimmunoassay in 76 PBs, 27 sera and 14 urines. Exponential differences were recognized between peaks in nighttime and nadirs in daytime of pineal MT contents, i. e., ranging 0.099-63.158 ng per PB and 1.2-609.6 pg/mg. Circadian rhythms were also observed on the concentrations of MT in serum (11-205 pg/ml), and in urine (7.5-137.5 pg/ml). Consequently, criteria of the DT estimation were proposed as follows. 1) Pineal MT contents--(1) 0-0.2 ng/PB:DT 11:00-17:00, (2) 0.2-0.3 ng/PB:DT 7:00-20:00, (3) 0.3-1 ng/PB: incapable of DT estimation, (4) 1-4 ng/PB:DT 16:00-10:00, (5) 4-8 ng/PB:DT 20:00-8:00, (6) 8 ng/PB over: DT 20:00-5:00, 2) Serum MT concentration--(1) 0-100 pg/ml: incapable of DT estimation, (2) 100pg/ml over: DT 22:00-1:00, and 3) Urinary MT concentration--(1) 0-35pg/ml: incapable of DT estimation, (2) 35 g/ml over: DT 18:00-6:00. Furthermore, width of the estimation is able to be narrowed by the combination of these three criteria. The present method is very useful in narrowing the width of DT estimation which has been usually carried out by observing the progress of cadaveric phenomena on and in dead bodies. PMID:8319934

  6. Circadian rhythm in the biting behaviour of a mosquito Armigeres subalbatus (Coquillett).

    PubMed

    Pandian, R S

    1994-04-01

    The crepuscular biting rhythm of A. subalbatus has been found to be a genuine circadian rhythm. When the entrained biting rhythm is allowed to freerun in constant darkness (DD) and continuous illumination (LL), it persists in DD (tau = 24.36 hr) and also in LL of ca. 0.1 1x (tau-23.82 hr) thus deviating from the strict 24 hr periodicity of the geophysical day. The biting rhythm becomes arrhythmic in LL of 1.0, 10, 0.4, 4, 40 lx even the first cycle damping away. PMID:7916332

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

    NASA Astrophysics Data System (ADS)

    Yokoi, Sayoko

    2013-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Traeger, Stefanie; Nowrousian, Minou

    2015-01-01

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

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

    PubMed

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

    2015-07-17

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  13. Reduction of translation rate stabilizes circadian rhythm and reduces the magnitude of phase shift.

    PubMed

    Nakajima, Masato; Koinuma, Satoshi; Shigeyoshi, Yasufumi

    2015-08-14

    In the intracellular environment, the circadian oscillator is exposed to molecular noise. Nevertheless, cellular rhythms are robust and show almost constant period length for several weeks. To find which molecular processes modulate the stability, we examined the effects of a sublethal dose of inhibitors for processes in the molecular clock. Inhibition of PER1/2 phosphorylation by CKIε/δ led to reduced amplitude and enhancement of damping, suggesting that inhibition of this process destabilized oscillation. In contrast, moderate inhibition of translation led to stabilization of the circadian oscillation. Moreover, inhibition of translation also reduced magnitude of phase shift. These results suggest that some specific molecular processes are crucial for stabilizing the circadian rhythm, and that the molecular clock may be stabilized by optimizing parameters of some crucial processes in the primary negative feedback loop. Moreover, our findings also suggested that rhythm stability is closely associated with phase stability against stimuli. PMID:26141234

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

    PubMed

    Klimovitskuĭ, 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. PMID:3695331

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

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Jacklet, J. W.

    1971-01-01

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

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

    PubMed

    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

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    PubMed

    Kohyama, Jun

    2014-07-01

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

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

    PubMed Central

    Li, Jun Z

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Fukuda, Hirokazu; Ukai, Kazuya; Oyama, Tokitaka

    2012-10-01

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

  5. Circadian Rhythm Hypotheses of Mixed Features, Antidepressant Treatment Resistance, and Manic Switching in Bipolar Disorder

    PubMed Central

    Son, Gi-Hoon; Geum, Dongho

    2013-01-01

    Numerous hypotheses have been put forth over the years to explain the development of bipolar disorder. Of these, circadian rhythm hypotheses have gained much importance of late. While the hypothalamus-pituitary-adrenal (HPA) axis hyperactivation hypothesis and the monoamine hypothesis somewhat explain the pathogenic mechanism of depression, they do not provide an explanation for the development of mania/hypomania. Interestingly, all patients with bipolar disorder display significant disruption of circadian rhythms and sleep/wake cycles throughout their mood cycles. Indeed, mice carrying the Clock gene mutation exhibit an overall behavioral profile that is similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, and lower anxiety. It was recently reported that monoamine signaling is in fact regulated by the circadian system. Thus, circadian rhythm instability, imposed on the dysregulation of HPA axis and monoamine system, may in turn increase individual susceptibility for switching from depression to mania/hypomania. In addition to addressing the pathophysiologic mechanism underlying the manic switch, circadian rhythm hypotheses can explain other bipolar disorder-related phenomena such as treatment resistant depression and mixed features. PMID:24302944

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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

  10. Vitamin B12 affects non-photic entrainment of circadian locomotor activity rhythms in mice.

    PubMed

    Ebihara, S; Mano, N; Kurono, N; Komuro, G; Yoshimura, T

    1996-07-15

    Administration of vitamin B12 (VB12) has been reported to normalize human sleep-wake rhythm disorders such as non-24-h sleep-wake syndrome (HNS), delayed sleep phase syndrome (DSPS) or insomnia. However, the mechanisms of the action of VB12 on the rhythm disorders are unknown. In the present study, therefore, effects of VB12 on circadian rhythms of locomotor activity were examined in mice. In the first experiment, CBA/J mice were maintained under continuous light condition (LL) or blinded, and after free-running rhythms became stable, the mice were intraperitoneally injected with either VB12 or saline at a fixed time every day. In all the mice with tau > 24 h, saline injections resulted in entrainment of circadian rhythms, whereas not all the mice with tau < 24 h entrained to the injection. In contrast to saline injections, VB12 injections did not always induce entrainment and about half of the mice with tau > 24 h free-ran during the injection. In the second experiment, the amount of phase advances of circadian rhythms induced by a single injection of saline at circadian time (CT) 11 under LL was compared between the mice with and without VB12 silastic tubes. The results showed that the amplitude of phase advances was smaller in the mice with VB12 than those without VB12. In the third experiment, daily injections of saline were given to the mice with VB12 silastic tubes maintained under LL. In this chronic treatment of VB12 as well, attenuating effects of VB12 on saline-induced entrainment were observed. These results suggest that VB12 affects the mechanisms implicated in non-photic entrainment of circadian rhythms in mice. PMID:8842380

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

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

    SciTech Connect

    Rubin, N.H.

    1982-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

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

  15. Circadian Rhythm Disruption Was Observed in Hand, Foot, and Mouth Disease Patients

    PubMed Central

    Zhu, Yu; Jiang, Zhou; Xiao, Guoguang; Cheng, Suting; Wen, Yang; Wan, Chaomin

    2015-01-01

    Abstract Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications. Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method. Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P < 0.01) of temperature and respiratory rate were significantly different among 3 groups. But no statistical difference of amplitude in temperature and respiratory rate was observed among the 3 groups (P = 0.14). MESOR value of HR (P < 0.001) was significantly different in 3 groups. However, amplitude and acrophase revealed no statistical difference in circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory

  16. Circadian rhythm disruption was observed in hand, foot, and mouth disease patients.

    PubMed

    Zhu, Yu; Jiang, Zhou; Xiao, Guoguang; Cheng, Suting; Wen, Yang; Wan, Chaomin

    2015-03-01

    Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications. Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method. Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P < 0.01) of temperature and respiratory rate were significantly different among 3 groups. But no statistical difference of amplitude in temperature and respiratory rate was observed among the 3 groups (P = 0.14). MESOR value of HR (P < 0.001) was significantly different in 3 groups. However, amplitude and acrophase revealed no statistical difference in circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory rate for

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

    PubMed Central

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

    2015-01-01

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

  18. Dysregulation of neuroendocrine crossroads: depression, circadian rhythms and the retina--a hypothesis.

    PubMed

    Steiner, M; Werstiuk, E S; Seggie, J

    1987-01-01

    The pathophysiology of depression and the mechanism of action of lithium and other antidepressant drugs involve alterations in circadian rhythms. These include changes in both the intrinsic rhythm of circadian oscillators and in the sensitivity of the retina to LIGHT. The retina in humans is the only photoreceptor for circadian entrainment. The retinal-hypothalamic-pineal axis is the essential pathway for neuronal entrainment of rhythms which use light as a phase cue. A common substance throughout this axis in many species is MELATONIN. Retinal melatonin has been implicated in regulation of the sensitivity of the retina to light. The hypothalamus, at THE NEUROENDOCRINE CROSSROADS, has a central role in the integration of neurotransmitters and hormones in circadian rhythms. DYSREGULATION of the hypothalamic-pituitary-adrenal, as well as -gonadal, axes has been documented in depressed patients. Abnormalities in circulating melatonin have also been found in patients with affective disorders. It is speculated that the availability of melatonin along the retinal-hypothalamic-pineal axis may have important implications in the genesis of affective disorders. More specifically--is there a latent biochemical defect which causes a phase shift and change in circadian rhythms of melatonin and/or other neurotransmitters in the retina which then alters the sensitivity of the retina to light (for the visible spectrum) which in turn desynchronizes all other biological rhythms thus disrupting mental well-being? We suggest that variations of retinal photosensitivity in humans can be measured by using a visual testing system, and that depressed patients might show changes in photosensitivity which could be corrected when treated with lithium and/or antidepressants. It is our working hypothesis that the primary defect in depression may be a change in retinal function, and that behavioural and neuroendocrine concomitants of this disorder are secondary events. PMID:2888161

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

    PubMed Central

    Merrow, Martha; Spoelstra, Kamiel; Roenneberg, Till

    2005-01-01

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

  20. Circadian rhythm in larval release by the crab Rhithropanopeus harrisii: entrainment model.

    PubMed

    Forward, Richard B; Moeller, Bianca P; Cohen, Jonathan H

    2014-04-01

    The subtidal crab Rhithropanopeus harrisii has a circadian rhythm in larval release; under constant conditions eggs hatch in the 2-3-h interval after the time of sunset in nontidal estuaries. Eggs that are removed from the female hatch rhythmically, indicating that the circadian rhythm resides in the embryos. The model for entrainment is that mature embryos have functional sensory systems that detect and entrain to environmental cycles. This model was reexamined by confirming that the visual system of advanced embryos responds to light and thus could mediate entrainment to the light/dark cycle. We then determined whether the hatching rhythm of mature embryos that are removed from the female can be entrained to new light/dark cycles. Contrary to expectations, these embryos did not entrain to new cycles. Instead, they remained entrained to the light/dark cycle to which they were exposed when still attached to the female, suggesting that the female entrains the rhythm. Indeed, hatching by embryos collected from the field when they had not yet developed eye pigments, kept in constant conditions attached to their mother, exhibited the circadian hatching rhythm. They could also be entrained to a new photoperiod in the laboratory. The role of the female is further supported by experiments showing that the hatching rhythm in embryos carried by females lacking one but not both eyes can be entrained to a new cycle in the laboratory. Thus, the revised model is that the female perceives the light/dark cycle and entrains the circadian rhythm in the embryos. PMID:24797091

  1. Alignment of R-R interval signals using the circadian heart rate rhythm.

    PubMed

    Gayraud, Nathalie T H; Manis, George

    2015-01-01

    R-R interval signals that come from different subjects are regularly aligned and averaged according to the horological starting time of the recordings. We argue that the horological time is a faulty alignment criterion and provide evidence in the form of a new alignment method. Our main motivation is that the human heart rate (HR) rhythm follows a circadian cycle, whose pattern can vary among different classes of people. We propose two novel alignment algorithms that consider the HR circadian rhythm, the Puzzle Piece Alignment Algorithm (PPA) and the Event Based Alignment Algorithm (EBA). First, we convert the R-R interval signal into a series of time windows and compute the mean HR per window. Then our algorithms search for matching circadian patterns to align the signals. We conduct experiments using R-R interval signals extracted from two databases in the Physionet Data Bank. Both algorithms are able to align the signals with respect to the circadian rhythmicity of HR. Furthermore, our findings confirm the presence of more than one pattern in the circadian HR rhythm. We suggest an automatic classification of signals according to the three most prominent patterns. PMID:26737009

  2. Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar

    PubMed Central

    Tao, Jiang; Zhai, Yue; Park, Hyun; Han, Junli; Dong, Jianhui; Xie, Ming; Gu, Ting; Lewi, Keidren; Ji, Fang; Jia, William

    2016-01-01

    Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation. PMID:27494172

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

    ERIC Educational Resources Information Center

    Richdale, Amanda L.; Prior, Margot R.

    1992-01-01

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

  4. Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar.

    PubMed

    Tao, Jiang; Zhai, Yue; Park, Hyun; Han, Junli; Dong, Jianhui; Xie, Ming; Gu, Ting; Lewi, Keidren; Ji, Fang; Jia, William

    2016-01-01

    Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation. PMID:27494172

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  6. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed

    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

  9. Effect of Circadian Rhythm on Clinical and Pathophysiological Conditions and Inflammation.

    PubMed

    Kizaki, Takako; Sato, Shogo; Shirato, Ken; Sakurai, Takuya; Ogasawara, Junetsu; Izawa, Tetsuya; Ohira, Yoshinobu; Suzuki, Kenji; Ohno, Hideki

    2015-01-01

    Circadian rhythms have long been known to regulate numerous physiological processes that vary across the diurnal cycle. The circadian clock system also controls various parameters of the immune system and its biological defense functions, allowing an organism to anticipate daily changes in activity and feeding and the associated risk of infection. Inflammation is an immune response triggered in living organisms in response to external stimuli. The risk of sepsis, an excessive inflammatory response, has been shown to have a diurnal variation. On the other hand, inflammatory responses are emerging to be induced by endogenous factors. Recent studies have suggested that chronic inflammation causes chronic diseases including rheumatoid arthritis, allergies, and aging-related diseases and that proteins encoded by clock genes affect the development of such chronic inflammatory diseases or increase the severity of their symptoms. Therefore, detailed understanding of circadian rhythm effects on inflammatory responses is expected to lead to new strategies for prevention or treatment of inflammatory diseases. PMID:26757391

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

    PubMed Central

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

    2007-01-01

    The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses “exogenous” circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the “endogenous” circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non–24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from “Option” to “Guideline,” depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm

  11. Circadian Activity Rhythms and Sleep in Nurses Working Fixed 8-hr Shifts.

    PubMed

    Kang, Jiunn-Horng; Miao, Nae-Fang; Tseng, Ing-Jy; Sithole, Trevor; Chung, Min-Huey

    2015-05-01

    Shift work is associated with adverse health outcomes. The aim of this study was to explore the effects of shift work on circadian activity rhythms (CARs) and objective and subjective sleep quality in nurses. Female day-shift (n = 16), evening-shift (n = 6), and night-shift (n = 13) nurses wore a wrist actigraph to monitor the activity. We used cosinor analysis and time-frequency analysis to study CARs. Night-shift nurses exhibited the lowest values of circadian rhythm amplitude, acrophase, autocorrelation, and mean of the circadian relative power (CRP), whereas evening-shift workers exhibited the greatest standard deviation of the CRP among the three shift groups. That is, night-shift nurses had less robust CARs and evening-shift nurses had greater variations in CARs compared with nurses who worked other shifts. Our results highlight the importance of assessing CARs to prevent the adverse effects of shift work on nurses' health. PMID:25332463

  12. Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm

    PubMed Central

    Cheon, Solmi; Park, Noheon; Cho, Sehyung; Kim, Kyungjin

    2013-01-01

    Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2 induction by GC signaling and its relevance to the regulation of circadian timing. We found that GC prominently induced Per2 expression and delayed the circadian phase. The overlapping GRE and E-box (GE2) region in the proximal Per2 promoter was responsible for GC-mediated Per2 induction. The GRE in the Per2 promoter was unique in that brain and muscle ARNT-like protein-1 (BMAL1) was essential for GC-induced Per2 expression, whereas other GRE-containing promoters, such as Per1 and mouse mammary tumor virus, responded to dexamethasone in the absence of BMAL1. This specialized regulatory mechanism was mediated by BMAL1-dependent binding of the GC receptor to GRE in Per2 promoter. When Per2 induction was abrogated by the mutation of the GRE or E-box, the circadian oscillation phase failed to be delayed compared with that of the wild-type. Therefore, the current study demonstrates that the rapid Per2 induction mediated by GC is crucial for delaying the circadian rhythm. PMID:23620290

  13. Drosophila TRPA1 functions in temperature control of circadian rhythm in pacemaker neurons.

    PubMed

    Lee, Youngseok; Montell, Craig

    2013-04-17

    Most animals from flies to humans count on circadian clocks to synchronize their physiology and behaviors. Daily light cycles are well known environmental cues for setting circadian rhythms. Warmer and cooler temperatures that mimic day and night are also effective in entraining circadian activity in most animals. Even vertebrate organisms can be induced to show circadian responses through exposure to temperature cycles. In poikilothermic animals such as Drosophila, temperature differences of only 2-3°C are sufficient to synchronize locomotor rhythms. However, the molecular sensors that participate in temperature regulation of circadian activity in fruit flies or other animals are enigmatic. It is also unclear whether such detectors are limited to the periphery or may be in the central brain. Here, we showed that Drosophila TRPA1 (transient receptor potential cation channel A1) was necessary for normal activity patterns during temperature cycles. The trpA1 gene was expressed in a subset of pacemaker neurons in the central brain. In response to temperature entrainment, loss of trpA1 impaired activity, and altered expression of the circadian clock protein period (Per) in a subset of pacemaker neurons. These findings underscore a role for a thermoTRP in temperature regulation that extends beyond avoidance of noxious or suboptimal temperatures. PMID:23595730

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

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

    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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-08-22

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

  20. Circadian Rhythms of Isoprene Biosynthesis in Grey Poplar Leaves1

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Circadian activity rhythms and risk of incident dementia and MCI in older women

    PubMed Central

    Tranah, Gregory J.; Blackwell, Terri; Stone, Katie L.; Ancoli-Israel, Sonia; Paudel, Misti L.; Ensrud, Kristine E.; Cauley, Jane A.; Redline, Susan; Hillier, Teresa A.; Cummings, Steven R; Yaffe, Kristine

    2011-01-01

    Objective Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI). Method Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, BMI, functional status, depression, medications, alcohol, caffeine, smoking, health status, and co-morbidities. Results After 4.9 years of follow-up, 195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older women with decreased activity rhythms had a higher likelihood of developing dementia or MCI when comparing those in the lowest quartiles of amplitude (Odds ratio[OR]=1.57,95% CI,1.09–2.25) or rhythm robustness (OR=1.57,95%CI,1.10–2.26) to women in the highest quartiles. An increased risk of dementia or MCI (OR=1.83,95% CI,1.29–2.61) was found for women whose timing of peak activity occurred later in the day (after 3:51PM) when compared to those with average timing (1:34PM–3:51PM). Interpretation Older, healthy women with decreased circadian activity rhythm amplitude and robustness, and delayed rhythms have increased odds of developing dementia and MCI. If confirmed, future studies should examine whether interventions (physical activity, bright light exposure) that influence activity rhythms will reduce the risk of cognitive deterioration in the elderly. PMID:22162057

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

    PubMed Central

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

    2015-01-01

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

  11. Effects of microgravity on circadian rhythms in insects

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    PubMed Central

    Ramkisoensing, Ashna; Meijer, Johanna H.

    2015-01-01

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

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

    PubMed

    Ramkisoensing, Ashna; Meijer, Johanna H

    2015-01-01

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

  14. Circadian rhythms and depression: effects of exercise in an animal model.

    PubMed

    Solberg, L C; Horton, T H; Turek, F W

    1999-01-01

    There is a clear link between altered circadian rhythms and depressive disorders, although the nature of this relationship is unknown. In addition, exercise affects both mood and alters clock function. To investigate the relationship between circadian rhythms, depression, and exercise, 3-wk-old mice housed on a 12:12-h light-dark cycle were exposed to chronic stress (CS) for 6 wk before being placed into constant darkness (DD). One-half of both the control and stressed mice were given access to a running wheel. Stressed mice consumed significantly less of a 2% sucrose solution during CS and exhibited a significant increase in immobility in the forced swim test 3 wk after the termination of stress relative to control mice. These effects were more pronounced in mice without running wheels. Stressed mice also exhibited altered percent distribution of total activity and increased fragmentation of daily activity rhythms during CS relative to control mice. Alterations in percent distribution were more pronounced in animals without running wheels. No activity rhythm changes were seen in DD, and there were no differences in light-induced phase shifts between stressed and control mice. These results suggest that CS causes long-term depressive-like symptoms but does not have long-lasting effects on activity rhythms. These changes were more pronounced in mice without running wheels, suggesting that exercise may protect against the harmful effects of stress. PMID:9887189

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-15

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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Loh, Dawn Hsiao-Wei; Kuljis, Dika Ana; Azuma, Lauren; Wu, Yingfei; Truong, Danny; Wang, Huei-Bin; Colwell, Christopher Scott

    2015-01-01

    The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP) expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produced about half the offspring of their wild type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle i.e. ovulation occurs less frequently and results in the release of fewer oocytes compared to controls. Circadian rhythms of wheel running activity are disrupted in the female mutant mice as are the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibit lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success. PMID:25252712

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

    PubMed

    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

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

    PubMed

    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

  2. Influence of circadian rhythms on rat muscle glycogen metabolism during and after exercise.

    PubMed

    Garetto, L P; Armstrong, R B

    1983-01-01

    Marked circadian fluctuations in skeletal muscle glycogen concentrations have previously been reported. The purpose of the present study was to estimate the influence of these rhythms on muscle glycogen metabolism during and after high-intensity treadmill exercise. Male Sprague-Dawley rats ran five 1-min sprints at 75 m min-1 interspersed by 1-3 min rest intervals either at 08.00 h (morning) or at 20.00 h (night). All muscles sampled lost significant amounts of glycogen during exercise at both time periods. There were no differences in rates of loss between morning and night, even though glycogen levels in several muscles (high-oxidative muscles) were significantly higher before exercise in the morning. Following exercise, glycogen restoration in muscle samples primarily composed of fast-twitch fibres was more rapid in the morning than at night. There was no difference in glycogen restoration rates between the two time periods in the muscle primarily composed of slow-twitch fibres. Although liver glycogen was lower after exercise at night than in the morning, there were no differences in post-exercise blood glucose levels between the two time periods. In conclusion, circadian rhythms do not appear to influence rates of glycogen loss during high-speed running. However, since glycogen loss is the same at all times of day, one would predict that circadian changes in pre-exercise muscle glycogen concentrations would affect muscular endurance. Muscle glycogen restoration after exercise does appear to be affected by circadian rhythms, although interpretation of these data is complicated by possible changes in patterns of muscle fibre contraction at different times of the day. These circadian influences should be considered in the design of exercise studies using laboratory rodents. PMID:6833943

  3. Involvement of 5-HT₇ receptors in vortioxetine's modulation of circadian rhythms and episodic memory in rodents.

    PubMed

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

    2015-02-01

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

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

    PubMed

    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. PMID:27249952

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

    PubMed

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

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

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

    PubMed

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

    1977-08-01

    Studies on daily and circadian rhythms in wheel running and electrographically defined wakefulness, NREM sleep, and REM sleep in M. musculus were done to gather data on the temporal distribution of activity and sleep. Generally, peaks in NREM and sleep tended to coincide and to alternate with the coincident peaks of wakefulness and wheel running. However, during the active phase of the circadian wheel running cycle some NREM and REM sleep did occur; conversely, during its rest phase, wakefulness was often present. The most striking finding was that in mice with clearly entrained or free-running activity onsets, the circadian peak-through patterns in wakefulness, NREM, and REM sleep were not always distinct--they could be damped and/or polyphasic. Several explanations of these phenomena are considered. PMID:195675

  9. Circadian rhythms in Mexican blind cavefish Astyanax mexicanus in the lab and in the field.

    PubMed

    Beale, Andrew; Guibal, Christophe; Tamai, T Katherine; Klotz, Linda; Cowen, Sophie; Peyric, Elodie; Reynoso, Víctor H; Yamamoto, Yoshiyuki; Whitmore, David

    2013-01-01

    Biological clocks have evolved as an adaptation to life on a rhythmic planet, synchronising physiological processes to the environmental light-dark cycle. Here we examine circadian clock function in Mexican blind cavefish Astyanax mexicanus and its surface counterpart. In the lab, adult surface fish show robust circadian rhythms in per1, which are retained in cave populations, but with substantial alterations. These changes may be due to increased levels of light-inducible genes in cavefish, including clock repressor per2. From a molecular standpoint, cavefish appear as if they experience 'constant light' rather than perpetual darkness. Micos River samples show similar per1 oscillations to those in the lab. However, data from Chica Cave shows complete repression of clock function, while expression of several light-responsive genes is raised, including DNA repair genes. We propose that altered expression of light-inducible genes provides a selective advantage to cavefish at the expense of a damped circadian oscillator. PMID:24225650

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

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.

    1992-01-01

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

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

    PubMed

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

    2012-07-01

    We previously reported that early night peripheral bacterial lipopolysaccharide (LPS) injection produces phase delays in the circadian rhythm of locomotor activity in mice. We now assess the effects of proinflammatory cytokines on circadian physiology, including their role in LPS-induced phase shifts. First, we investigated whether differential systemic induction of classic proinflammatory cytokines could explain the time-specific behavioral effects of peripheral LPS. Induction levels for plasma interleukin (IL)-1α, IL-1β, IL-6, or tumor necrosis factor (TNF)-α did not differ between animals receiving a LPS challenge in the early day or early night. We next tested the in vivo effects of central proinflammatory cytokines on circadian physiology. We found that intracerebroventricular (i.c.v.) delivery of TNF-α or interleukin IL-1β induced phase delays on wheel-running activity rhythms. Furthermore, we analyzed if these cytokines mediate the LPS-induced phase shifts and found that i.c.v. administration of soluble TNF-α receptor (but not an IL-1β antagonistic) prior to LPS stimulation inhibited the phase delays. Our work suggests that the suprachiasmatic nucleus (SCN) responds to central proinflammatory cytokines in vivo, producing phase shifts in locomotor activity rhythms. Moreover, we show that the LPS-induced phase delays are mediated through the action of TNF-α at the central level, and that systemic induction of proinflammatory cytokines might be necessary, but not sufficient, for this behavioral outcome. PMID:22734572

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

    NASA Astrophysics Data System (ADS)

    Zhao, Yanbin; Fent, Karl

    2016-02-01

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

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

    PubMed

    Zhao, Yanbin; Fent, Karl

    2016-01-01

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

  14. The Development and Course of Bipolar Spectrum Disorders: An Integrated Reward and Circadian Rhythm Dysregulation Model

    PubMed Central

    Alloy, Lauren B.; Nusslock, Robin; Boland, Elaine M.

    2014-01-01

    In this article, we present and review the evidence for two major biopsychosocial theories of the onset and course of bipolar spectrum disorders (BSDs) that integrate behavioral, environmental, and neurobiological mechanisms: the reward hypersensitivity and the social and circadian rhythm disruption models. We describe the clinical features, spectrum, age of onset, and course of BSDs. We then discuss research designs relevant to demonstrating whether a hypothesized mechanism represents a correlate, vulnerability, or predictor of the course of BSDs, as well as important methodological issues. We next present the reward hypersensitivity model of BSD, followed by the social/circadian rhythm disruption model of BSD. For each model, we review evidence regarding whether the proposed underlying mechanism is associated with BSDs, provides vulnerability to the onset of BSDs, and predicts the course of BSDs. We then present a new integrated reward/circadian rhythm (RCR) dysregulation model of BSD and discuss how the RCR model explains the symptoms, onset, and course of BSDs. We end with recommendations for future research directions. PMID:25581235

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

    PubMed

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

    2016-08-01

    Crohn's disease (CD) and ulcerative colitis (UC) are the main representatives of inflammatory bowel diseases (IBD), a group of chronic, immune system-mediated inflammatory diseases of the gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions in IBD is not entirely identified and understood: excessive activation of the immune system may come as a result of the interaction of various environmental and infectious factors, genetic predisposition, and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the risk factors for the development of IBD. Currently, there is very little knowledge about circadian rhythm and IBD and there are only a few studies on the relationship between sleep disturbances and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. Furthermore, the relationship between the expression of circadian rhythm genes and severe course of IBD is still unknown. The aim of this review is to show the current state of knowledge about the relationship between circadian rhythm disorders, sleep disturbance and inflammation in the GI tract and to analyze the possibility of employing this knowledge in diagnosis and treatment of IBD. PMID:27166084

  16. An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm

    PubMed Central

    Freeman, Amanda A.H.; Mandilaras, Konstantinos; Missirlis, Fanis; Sanyal, Subhabrata

    2013-01-01

    Although the neurophysiological correlates of sleep have been thoroughly described, genetic mechanisms that control sleep architecture, long surmised from ethological studies, family histories and clinical observations, have only been investigated during the past decade. Key contributions to the molecular understanding of sleep have come from studies in Drosophila, benefitting from a strong history of circadian rhythm research. For instance, a number of recent papers have highlighted the role of the E3 ubiquitin ligase Cullin-3 in the regulation of circadian rhythm and sleep. We propose that different Cullin-3 substrate adaptors may affect specific molecular pathways and diverse aspects of circadian rhythm and sleep. We have previously shown that mutations in BTBD9, a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor, lead to reduced dopamine, increased locomotion and sleep fragmentation. Here, we propose that Cullin-3 acts together with BTBD9 to limit the accumulation of iron regulatory proteins in conditions of iron deficiency. Our model is consistent with clinical observations implicating iron homeostasis in the pathophysiology of RLS and predicts that lack of BTBD9 leads to misregulation of cellular iron storage, inactivating the critical biosynthetic enzyme Tyrosine Hydroxylase in dopaminergic neurons, with consequent phenotypic effects on sleep. PMID:23455037

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

    PubMed

    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

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

    PubMed

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

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea. PMID:25251018

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

    PubMed Central

    Zhao, Yanbin; Fent, Karl

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea. PMID:25251018

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  2. Changing the Waveform of Circadian Rhythms: Considerations for Shift-Work

    PubMed Central

    Harrison, Elizabeth M.; Gorman, Michael R.

    2012-01-01

    Circadian disruption in shift-work is common and has deleterious effects on health and performance. Current efforts to mitigate these harms reasonably focus on the phase of the circadian pacemaker, which unfortunately in humans, shifts slowly and often incompletely. Temporal reorganization of rhythmic waveform (i.e., the shape of its 24 h oscillation), rather than phase, however, may better match performance demands of shift-workers and can be quickly and feasibly implemented in animals. In fact, a bifurcated pacemaker waveform may permit stable entrainment of a bimodal sleep/wake rhythm promoting alertness in both night and daylight hours. Although bifurcation has yet to be formally assessed in humans, evidence of conserved properties of circadian organization and plasticity predict its occurrence: humans respond to conventional manipulations of waveform (e.g., photoperiodism); behaviorally, the sleep/wake rhythm is adaptable; and finally, the human circadian system likely derives from the same multiple cellular oscillators that permit waveform flexibility in the rodent pacemaker. In short, investigation into untried manipulations of waveform in humans to facilitate adjustment to challenging schedules is justified. PMID:22557994

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

    PubMed Central

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

    2015-01-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

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

    PubMed

    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 (ICircadian disruption (Irhythm parameters being worsened in the whole group of patients (p < 0.05). Mean parameter values subsequently recovered to near baseline values. The occurrence of circadian disruption on chemotherapy was associated with a higher risk of clinically relevant fatigue (p = 0.028) or body weight loss (p = 0.05). Four CTS dynamic patterns characterized treatment response including no change (9.5% of the patients); improvement (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

  5. Scheduled Daily Mating Induces Circadian Anticipatory Activity Rhythms in the Male Rat

    PubMed Central

    Landry, Glenn J.; Opiol, Hanna; Marchant, Elliott G.; Pavlovski, Ilya; Mear, Rhiannon J.; Hamson, Dwayne K.; Mistlberger, Ralph E.

    2012-01-01

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

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

    PubMed

    Landry, Glenn J; Opiol, Hanna; Marchant, Elliott G; Pavlovski, Ilya; Mear, Rhiannon J; Hamson, Dwayne K; Mistlberger, Ralph E

    2012-01-01

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

  7. Convergent Rhythm Generation from Divergent Cellular Mechanisms

    PubMed Central

    Rodriguez, Jason C.; Blitz, Dawn M.

    2013-01-01

    Different modulatory inputs commonly elicit distinct rhythmic motor patterns from a central pattern generator (CPG), but they can instead elicit the same pattern. We are determining the rhythm-generating mechanisms in this latter situation, using the gastric mill (chewing) CPG in the crab (Cancer borealis) stomatogastric ganglion, where stimulating the projection neuron MCN1 (modulatory commissural neuron 1) or bath applying CabPK (C. borealis pyrokinin) peptide elicits the same gastric mill motor pattern, despite configuring different gastric mill circuits. In both cases, the core rhythm generator includes the same reciprocally inhibitory neurons LG (lateral gastric) and Int1 (interneuron 1), but the pyloric (food-filtering) circuit pacemaker neuron AB (anterior burster) is additionally necessary only for CabPK rhythm generation. MCN1 drives this rhythm generator by activating in the LG neuron the modulator-activated inward current (IMI), which waxes and wanes periodically due to phasic feedback inhibition of MCN1 transmitter release. Each buildup of IMI enables the LG neuron to generate a self-terminating burst and thereby alternate with Int1 activity. Here we establish that CabPK drives gastric mill rhythm generation by activating in the LG neuron IMI plus a slowly activating transient, low-threshold inward current (ITrans-LTS) that is voltage, time, and Ca2+ dependent. Unlike MCN1, CabPK maintains a steady IMI activation, causing a subthreshold depolarization in LG that facilitates a periodic postinhibitory rebound burst caused by the regular buildup and decay of the availability of ITrans-LTS. Thus, different modulatory inputs can use different rhythm-generating mechanisms to drive the same neuronal rhythm. Additionally, the same ionic current (IMI) can play different roles under these different conditions, while different currents (IMI, ITrans-LTS) can play the same role. PMID:24227716

  8. Microglia modulate respiratory rhythm generation and autoresuscitation.

    PubMed

    Lorea-Hernández, Jonathan-Julio; Morales, Teresa; Rivera-Angulo, Ana-Julia; Alcantara-Gonzalez, David; Peña-Ortega, Fernando

    2016-04-01

    Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBötzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation. PMID:26678570

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

    PubMed

    Kumar, Vinod; Gwinner, Eberhard

    2005-09-01

    In many birds periodic melatonin secretion by the pineal organ is essential for the high-amplitude self-sustained output of the circadian pacemaker, and thus for the persistence of rhythmicity in 24 h oscillations controlled by it. The elimination of the pineal melatonin rhythm, or a reduction of its amplitude, renders the circadian pacemaker a less self-sustained, often highly damped, oscillatory system. A reduction in the degree of self-sustainment of a rhythm should not only increase its range of entrainment but also shorten the resynchronization times following phase-shifts of the zeitgeber. This hypothesis has not yet been directly tested. We therefore carried out the present study in which house sparrows (Passer domesticus) were subjected to both 6-h advance and 6-h delay phase-shifts of the light-dark cycle before and after the pinealectomy, and the rhythms in locomotion and feeding were recorded. The results indicate that following the delay, but not the advance, phase shift, resynchronization times were significantly shorter after pinealectomy. The dependence of resynchronization times on the presence or absence of the pineal organ is not only of theoretical interest but might also be of functional significance in the natural life of birds. A reduction or elimination of the amplitude of the melatonin secretion rhythm by the pineal organ might be responsible for faster adjustment to changes in zeitgeber conditions in nature. PMID:16151793

  10. Aberrant Development of the Suprachiasmatic Nucleus and Circadian Rhythms in Mice Lacking the Homeodomain Protein Six6

    PubMed Central

    Clark, Daniel D.; Gorman, Michael R.; Hatori, Megumi; Meadows, Jason D.; Panda, Satchidananda; Mellon, Pamela L.

    2013-01-01

    The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus is the central pacemaker for peripheral and organismal circadian rhythms. The development of this hypothalamic structure depends on genetic programs throughout embryogenesis. We have investigated the role of the homeodomain transcription factor Six6 in the development of the SCN. We first showed that Six6 mRNA has circadian regulation in the mouse SCN. We then characterized the behavioral activity patterns of Six6-null mice under various photoperiod manipulations and stained their hypothalami using SCN-specific markers. Six6-null mice display abnormal patterns of circadian behavior indicative of SCN abnormalities. The ability of light exposure to reset rhythms correlates with the presence or absence of optic nerves, but all Six6-null mice show irregular rhythms. In contrast, wild-type mice with crushed optic nerves maintain regular rhythms regardless of light exposure. Using immunohistochemistry for arginine vasopressin (AVP), vasoactive intestinal polypeptide (VIP), and β-galactosidase, we demonstrated the lack of these SCN markers in all Six6- null mice regardless of the presence of optic nerve or partial circadian rhythms. Therefore, Six6 is required for the normal development of the SCN, and the Six6-null mouse can mount independent, although irregular, circadian rhythms despite the apparent absence of a histochemically defined SCN. PMID:23382588

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Circadian rhythm of mechanically mediated differentiation of osteoblasts

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Klingler, E.

    1984-01-01

    The differential of osteoblasts in response to orthodontic pressure in the periodontal ligament of the maxillary-first-molar periodontal ligaments of 12-h-light/dark-entrained 7-wk-old male Simonsen outbred rats is measured by (H-3)-Thymidine nuclear-volume morphometry (Roberts et al., 1983) at hourly intervals throughout the circadian cycle. The results are presented in graphs and discussed. Preosteoblast large nuclei (D-cells) are found to synthesize DNA mainly in light and to divide in the following dark period, while small-nucleus osteoprogenitors (A-cells) synthesize in darkness and divide in light. These findings are seen as consistent with a model in which the sequence of proliferation and differentiation requires at least 60 h (five 12-h periods) and the shift from A to D cells lasts about 19 h.

  14. Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

    PubMed Central

    2013-01-01

    Background Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. PMID:23521808

  15. Aggressive and sexual social stimuli do not phase shift the circadian temperature rhythm in rats.

    PubMed

    Meerlo, P; Daan, S

    1998-05-01

    The objective of the present study was to determine whether the rat circadian system is sensitive to social stimuli. Male rats were subjected to a sociosexual interaction with an estrous female or to an aggressive interaction with a dominant male conspecific. The interactions lasted for 1 h and took place in the middle of the circadian resting phase. Control animals were picked up and handled for a few minutes, but were otherwise left undisturbed. Animals were housed under constant dim red light during the whole period of the experiment. To assess the effects of the interactions on free-running circadian rhythmicity, body temperature was measured by means of radio telemetry. neither the sociosexual interaction with a female nor the aggressive interaction with another male induced phase shifts or changes in the free-running period. The rat circadian system does not seem to be sensitive to social stimuli directly. Moreover, the finding that aggressive interactions do not phase shift circadian rhythms indicates that the endogenous pacemaker in rats is not sensitive to stressors. PMID:9653577

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

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Connell, Linda J.; Graeber, R. Curtis

    1986-01-01

    Experiments were conducted to estimate the magnitude of the masking effect produced in humans by alternate periods of physical activity and rest or sleep on the circadian rhythms of heart rate and core temperature. The heart rate, rectal temperature, and nondominant wrist activity were monitored in 12 male subjects during 6 days of normal routine at home and during 6 days of controlled bed-rest regimen. The comparisons of averaged waveforms for the activity, heart rate, and temperature indicated that about 45 percent of the range of the circadian heart rate rhythm during normal routine and about 14 percent of the range of the circadian temperature rhythm were attributable to the effects of activity. The smaller effect of activity on the temperature rhythm may be partially attributable to the fact that core temperature is being more rigorously conserved than heart rate, at least during moderate exercise.

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

    SciTech Connect

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

    1988-09-01

    In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from (26-14C)cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man.

  18. Contribution of C3 carboxylation to the circadian rhythm of carbon dioxide uptake in a Crassulacean acid metabolism plant Kalanchoë daigremontiana.

    PubMed

    Wyka, Tomasz P; Lüttge, Ulrich E

    2003-05-01

    During the endogenous circadian rhythm of carbon dioxide uptake in continuous light by a Crassula cean acid metabolism plant, Kalanchoë daigremontiana, the two carboxylating enzymes, phosphoenolpyruvate carboxylase (PEPC) and ribulose 1,5 bisphosphate carboxylase/oxygenase (Rubisco), are active simultaneously, although, until now, only the role of PEPC in generating the rhythm has been acknowledged. According to the established model, the rhythm is primarily regulated at the PEPC activity level, modulated by periodic compartmentation of its inhibitor, malate, in the vacuole and controlled by tension/relaxation of the tonoplast. However, the circadian accumulation of malic acid (the main indicator of PEPC activity) dampened significantly within the first few periods without affecting the rhythm's amplitude. Moreover, the amount of malate accumulated during a free-running oscillation was several-fold lower than the amount expected if PEPC were the key carboxylating enzyme, based on a 1:1 stoichiometry of CO(2) and malate. Together with the observation that rates of CO(2) uptake under continuous light were higher than in darkness, the evidence shows that C(3) carboxylation greatly contributes to the generation of rhythmic CO(2) uptake in continuous light in this 'obligate' CAM plant. Because the shift from predominantly CAM to predominantly C(3) carboxylation is smooth and does not distort the trajectory of the rhythm, its control probably arises from a robust network of oscillators, perhaps also involving stomata. PMID:12709493

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

    PubMed

    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

  20. Circadian rhythm of mechanically mediated differentiation of osteoblasts.

    PubMed

    Roberts, W E; Klingler, E; Mozsary, P G

    1984-01-01

    Rats entrained to alternating 12 h light/dark periods were sacrificed at hourly intervals over one complete circadian cycle. Each animal was injected with 3H-Thymidine 1 h before death. Autoradiographs of serial sections of maxillary first molar periodontal ligament (PDL) were prepared. Nuclear volume was determined for labeled fibroblastlike PDL cells along a physiological bone forming surface. Preosteoblasts (large nuclei), the immediate proliferating precursors of osteoblasts, were found to synthesize DNA primarily during the environmental light period and divide during the subsequent dark cycle. Less differentiated precursor cells (small nuclei), the proliferating predecessors of preosteoblasts, were in S phase primarily during the dark period and divided in the following light cycle. Since previous studies have indicated, the stress/strain-mediated increase in nuclear size to form preosteoblasts also requires about 8-12 h, the least complex osteoblast differentiation model, which is consistent with the present data, is a 60 h sequence involving at least four cell types and five alternating dark/light cycles. The principal rate-limiting step in osteoblast differentiation is the mechanically related shift in nuclear size (change in genomic expression) associated with formation of preosteoblasts. PMID:6430524

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

    PubMed

    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

  2. Improvement of Circadian Rhythm of Heart Rate Variability by Eurythmy Therapy Training

    PubMed Central

    Seifert, Georg; Kanitz, Jenny-Lena; Pretzer, Kim; Henze, Günter; Witt, Katharina; Reulecke, Sina; Voss, Andreas

    2013-01-01

    Background. Impairment of circadian rhythm is associated with various clinical problems. It not only has a negative impact on quality of life but can also be associated with a significantly poorer prognosis. Eurythmy therapy (EYT) is an anthroposophic movement therapy aimed at reducing fatigue symptoms and stress levels. Objective. This analysis of healthy subjects was conducted to examine whether the improvement in fatigue symptoms was accompanied by improvements in the circadian rhythm of heart rate variability (HRV). Design. Twenty-three women performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs) were recorded before and after the EYT trial. HRV was quantified by parameters of the frequency and time domains and the nonlinear parameters of symbolic dynamics. Results. The day-night contrast with predominance of vagal activity at night becomes more pronounced after the EYT training, and with decreased Ultralow and very low frequencies, the HRV shows evidence of calmer sleep. During the night, the complexity of the HRV is significantly increased indicated by nonlinear parameters. Conclusion. The analysis of the circadian patterns of cardiophysiological parameters before and after EYT shows significant improvements in HRV in terms of greater day-night contrast caused by an increase of vagal activity and calmer and more complex HRV patterns during sleep. PMID:23533496

  3. Altered Circadian Rhythm and Metabolic Gene Profile in Rats Subjected to Advanced Light Phase Shifts

    PubMed Central

    Herrero, Laura; Valcarcel, Lorea; da Silva, Crhistiane Andressa; Albert, Nerea; Diez-Noguera, Antoni; Cambras, Trinitat; Serra, Dolors

    2015-01-01

    The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level. PMID:25837425

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

    NASA Technical Reports Server (NTRS)

    Tang, I. H.; Murakami, D. M.; Fuller, C. A.

    1999-01-01

    Circadian rhythms of activity (Act) and body temperature (Tb) were recorded from male Syrian hamsters under square-wave (LDSq) and simulated natural (LDSN, with dawn and dusk transitions) light-dark cycles. Light intensity and data sampling were under the synchronized control of a laboratory computer. Changes in reactive and predictive onsets and offsets for the circadian rhythms of Act and Tb were examined in both lighting conditions. The reactive Act onset occurred 1.1 h earlier (P < 0.01) in LDSN than in LDSq and had a longer alpha-period (1.7 h; P < 0.05). The reactive Tb onset was 0.7 h earlier (P < 0.01) in LDSN. In LDSN, the predictive Act onset advanced by 0.3 h (P < 0.05), whereas the Tb predictive onset remained the same as in LDSq. The phase angle difference between Act and Tb predictive onsets decreased by 0.9 h (P < 0.05) in LDSN, but the offsets of both measures remained unchanged. In this study, animals exhibited different circadian entrainment characteristics under LDSq and LDSN, suggesting that gradual and abrupt transitions between light and dark may provide different temporal cues.

  5. Ecdysis behaviors and circadian rhythm of ecdysis in the stick insect, Carausius morosus

    PubMed Central

    Wadsworth, Tracy; Carriman, Andrew; Gutierrez, Alba A.; Moffatt, Christopher; Fuse, Megumi

    2014-01-01

    Successful ecdysis in insects depends on proper timing and sequential activation of an elaborate series of motor programs driven by a relatively conserved network of neuropeptides. The behaviors must be activated at the appropriate times to ensure successful loosening and shedding of the old cuticle, and can be influenced by environmental cues in the form of immediate sensory feedback and by circadian rhythms. We assessed the behaviors, components of the neural network and the circadian basis of ecdysis in the stick insect, Carausius morosus. C. morosus showed many of the characteristic pre-ecdysis and ecdysis behaviors previously described in crickets and locusts. Ecdysis was described in three phases, namely the (i) preparatory or pre-ecdysis phase, (ii) the ecdysial phase, and (iii) the post-ecdysis or exuvial phase. The frequencies of pushups and sways during the preparatory phase were quantified as well as durations of all the phases. The regulation of ecdysis appeared to act via elevation of cGMP, as described in many other insects, although eclosion hormone-like immunoreactivity was not noted using a lepidopteran antiserum. Finally, C. morosus showed a circadian rhythm to the onset of ecdysis, with ecdysis occurring just prior or at lights on. Ecdysis could be induced precociously with mechanical stimulation. PMID:25450561

  6. Ecdysis behaviors and circadian rhythm of ecdysis in the stick insect, Carausius morosus.

    PubMed

    Wadsworth, Tracy; Carriman, Andrew; Gutierrez, Alba A; Moffatt, Christopher; Fuse, Megumi

    2014-12-01

    Successful ecdysis in insects depends on proper timing and sequential activation of an elaborate series of motor programs driven by a relatively conserved network of neuropeptides. The behaviors must be activated at the appropriate times to ensure successful loosening and shedding of the old cuticle, and can be influenced by environmental cues in the form of immediate sensory feedback and by circadian rhythms. We assessed the behaviors, components of the neural network and the circadian basis of ecdysis in the stick insect, Carausius morosus. C. morosus showed many of the characteristic pre-ecdysis and ecdysis behaviors previously described in crickets and locusts. Ecdysis was described in three phases, namely the (i) preparatory or pre-ecdysis phase, (ii) the ecdysial phase, and (iii) the post-ecdysis or exuvial phase. The frequencies of push-ups and sways during the preparatory phase were quantified as well as durations of all the phases. The regulation of ecdysis appeared to act via elevation of cGMP, as described in many other insects, although eclosion hormone-like immunoreactivity was not noted using a lepidopteran antiserum. Finally, C. morosus showed a circadian rhythm to the onset of ecdysis, with ecdysis occurring just prior to or at lights on. Ecdysis could be induced precociously with mechanical stimulation. PMID:25450561

  7. Organizational influence of the postnatal testosterone surge on the circadian rhythm of core body temperature of adult male rats.

    PubMed

    Zuloaga, Damian G; McGivern, Robert F; Handa, Robert J

    2009-05-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus coordinates physiological and behavioral circadian rhythms such as activity, body temperature, and hormone secretion. Circadian rhythms coordinated by the SCN often show sex differences arising from both organizational and activational effects of gonadal hormones. In males, little is known about the organizational role of testosterone on the circadian regulation of core body temperature (CBT) in adulthood. To explore this, we castrated or sham-operated male rats on the day of birth, and at 4 months of age, implanted them with transmitters that measured CBT rhythms under a 12:12 light/dark cycle. This study revealed a significantly earlier rise in CBT during the light phase in neonatally castrated males. Subsequently, we found that treating neonatally castrated males with testosterone propionate (TP) in adulthood did not reverse the effect of neonatal castration, thus indicating an organizational role for testosterone. In contrast, a single injection of TP at the time of neonatal surgery, to mimic the postnatal surge of testosterone, coupled with TP treatment in adulthood, normalized the circadian rise in CBT. In a final study we examined CBT circadian rhythms in intact adult male and female rats and detected no differences in the rise of CBT during the light phase, although there was a greater overall elevation in female CBT. Together, results of these studies reveal an early organizational role of testosterone in males on the timing of the circadian rise of CBT, a difference that does not appear to reflect "defeminization". PMID:19272357

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

    PubMed

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

    2016-03-01

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

  9. Time-of-day effects in implicit racial in-group preferences are likely selection effects, not circadian rhythms

    PubMed Central

    2016-01-01

    Time-of-day effects in human psychological functioning have been known of since the 1800s. However, outside of research specifically focused on the quantification of circadian rhythms, their study has largely been neglected. Moves toward online data collection now mean that psychological investigations take place around the clock, which affords researchers the ability to easily study time-of-day effects. Recent analyses have shown, for instance, that implicit attitudes have time-of-day effects. The plausibility that these effects indicate circadian rhythms rather than selection effects is considered in the current study. There was little evidence that the time-of-day effects in implicit attitudes shifted appropriately with factors known to influence the time of circadian rhythms. Moreover, even variables that cannot logically show circadian rhythms demonstrated stronger time-of-day effects than did implicit attitudes. Taken together, these results suggest that time-of-day effects in implicit attitudes are more likely to represent processes of selection rather than circadian rhythms, but do not rule out the latter possibility. PMID:27114886

  10. Time-of-day effects in implicit racial in-group preferences are likely selection effects, not circadian rhythms.

    PubMed

    Schofield, Timothy P

    2016-01-01

    Time-of-day effects in human psychological functioning have been known of since the 1800s. However, outside of research specifically focused on the quantification of circadian rhythms, their study has largely been neglected. Moves toward online data collection now mean that psychological investigations take place around the clock, which affords researchers the ability to easily study time-of-day effects. Recent analyses have shown, for instance, that implicit attitudes have time-of-day effects. The plausibility that these effects indicate circadian rhythms rather than selection effects is considered in the current study. There was little evidence that the time-of-day effects in implicit attitudes shifted appropriately with factors known to influence the time of circadian rhythms. Moreover, even variables that cannot logically show circadian rhythms demonstrated stronger time-of-day effects than did implicit attitudes. Taken together, these results suggest that time-of-day effects in implicit attitudes are more likely to represent processes of selection rather than circadian rhythms, but do not rule out the latter possibility. PMID:27114886

  11. Suprachiasmatic Nucleus as the Site of Androgen Action on Circadian Rhythms

    PubMed Central

    Model, Zina; Butler, Matthew P.; LeSauter, Joseph; Silver, Rae

    2015-01-01

    Androgens act widely in the body in both central and peripheral sites. Prior studies indicate that in the mouse, suprachiasmatic nucleus (SCN) cells bear androgen receptors (ARs). The SCN of the hypothalamus in mammals is the locus of a brain clock that regulates circadian rhythms in physiology and behavior. Gonadectomy results in reduced AR expression in the SCN and in marked lengthening of the period of free-running activity rhythms. Both responses are restored by systemic administration of androgens, but the site of action remains unknown. Our goal was to determine whether intracranial androgen implants targeted to the SCN are sufficient to restore the characteristic free-running period in gonadectomized male mice. The results indicate that hypothalamic implants of testosterone propionate in or very near the SCN produce both anatomical and behavioral effects, namely increased AR expression in the SCN and restored period of free-running locomotor activity. The effect of the implant on the period of the free-running locomotor rhythm is positively correlated with the amount of AR expression in the SCN. There is no such correlation of period change with amount of AR expression in other brain regions examined, namely the preoptic area, bed nucleus of the stria terminalis and premammillary nucleus. We conclude that the SCN is the site of action of androgen effects on the period of circadian activity rhythmicity. PMID:26012711

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

    NASA Technical Reports Server (NTRS)

    Winfree, A. T.

    1971-01-01

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

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

    PubMed

    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

  14. Circadian Rhythmicity of Active GSK3 Isoforms Modulates Molecular Clock Gene Rhythms in the Suprachiasmatic Nucleus

    PubMed Central

    Besing, R.C.; Paul, J.R.; Hablitz, L.M.; Rogers, C.O.; Johnson, R.L.; Young, M.E.; Gamble, K.L.

    2015-01-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprised of clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least five core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3β isoform. Whether phosphorylation of the other primary isoform (GSK3α) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (α and β) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN from wild-type mice housed in constant darkness for two weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 μM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. PMID:25724980

  15. Vasopressin deficiency and circadian rhythms during food-restriction stress.

    PubMed

    Murphy, H M; Wideman, C H; Nadzam, G R

    1993-01-01

    Vasopressin-containing, Long-Evans (LE) rats and vasopressin-deficient, Brattleboro (DI) rats were monitored for activity and core body temperature via telemetry. Rats were exposed to a 12-12 light-dark cycle and allowed to habituate with ad lib access to food and water. The habituation period was followed by an experimental period of 23 h of food-restriction stress in which a 1-h feeding period was provided during the light cycle. Although both strains of animals showed nocturnal activity and temperature rhythms during the habituation period, DI rats were more active than LE rats. The DI rats also had a lower body temperature in the dark. During the experimental period, both strains exhibited a phase shift of activity and body temperature correlating with the presentation of food. The DI rats developed a diurnal shift more rapidly than LE rats. The DI animals showed a dramatic increase in activity during the light phase and a marked decrease in body temperature during the dark phase. The LE animals showed a significant attenuation of activity, but maintained both nocturnal and diurnal temperature peaks throughout the food-restricted condition. PMID:8134303

  16. The parathyroid hormone circadian rhythm is truly endogenous--a general clinical research center study

    NASA Technical Reports Server (NTRS)

    el-Hajj Fuleihan, G.; Klerman, E. B.; Brown, E. N.; Choe, Y.; Brown, E. M.; Czeisler, C. A.

    1997-01-01

    While circulating levels of PTH follow a diurnal pattern, it has been unclear whether these changes are truly endogenous or are dictated by external factors that themselves follow a diurnal pattern, such as sleep-wake cycles, light-dark cycles, meals, or posture. We evaluated the diurnal rhythm of PTH in 11 normal healthy male volunteers in our Intensive Physiologic Monitoring Unit. The first 36 h spent under baseline conditions were followed by 28-40 h of constant routine conditions (CR; enforced wakefulness in the strict semirecumbent position, with the consumption of hourly snacks). During baseline conditions, PTH levels followed a bimodal diurnal rhythm with an average amplitude of 4.2 pg/mL. A primary peak (t1max) occurred at 0314 h, and the secondary peak (t2max) occurred at 1726 h, whereas the primary and secondary nadirs (t1min and t2min) took place, on the average, at 1041 and 2103 h, respectively. This rhythm was preserved under CR conditions, albeit with different characteristics, thus confirming its endogenous nature. The serum ionized calcium (Cai) demonstrated a rhythm in 3 of the 5 subjects studied that varied widely between individuals and did not have any apparent relation to PTH. Urinary calcium/creatinine (UCa/Cr), phosphate/Cr (UPO4/Cr), and sodium/Cr (UNa/Cr) ratios all followed a diurnal rhythm during the baseline day. These rhythms persisted during the CR, although with different characteristics for the first two parameters, whereas that of UNa/Cr was unchanged. In general, the temporal pattern for the UCa/Cr curve was a mirror image of the PTH curve, whereas the UPO4/Cr pattern moved in parallel with the PTH curve. In conclusion, PTH levels exhibit a diurnal rhythm that persists during a CR, thereby confirming that a large component of this rhythm is an endogenous circadian rhythm. The clinical relevance of this rhythm is reflected in the associated rhythms of biological markers of PTH effect at the kidney, namely UCa/Cr and UPO4/Cr.

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

    PubMed

    Lubinski, Alexander J; Page, Terry L

    2016-04-01

    The cockroach, Leucophaea maderae, can be trained in an associative olfactory memory task by either classical or operant conditioning. When trained by classical conditioning, memory formation is regulated by a circadian clock, but once the memory is formed, it can be recalled at any circadian time. In contrast, when trained via operant conditioning, animals can learn the task at any circadian phase, but the ability to recall the long-term memory is tied to the phase of training. The optic lobes of the cockroach contain a circadian clock that drives circadian rhythms of locomotor activity, mating behavior, sensitivity of the compound eye to light, and the sensitivity of olfactory receptors in the antennae. To evaluate the role of the optic lobes in regulating learning and memory processes, the authors examined the effects of surgical ablation of the optic lobes on memory formation in classical conditioning and memory recall following operant conditioning. The effect of optic lobe ablation was to "rescue" the deficit in memory acquisition at a time the animals normally cannot learn and "rescue" the animal's ability to recall a memory formed by operant conditioning at a phase where memory was not normally expressed. The results suggested that the optic lobe pacemaker regulates these processes through inhibition at "inappropriate" times of day. As a pharmacological test of this hypothesis, the authors showed that injections of fipronil, an antagonist of GABA and glutamate-activated chloride channels, had the same effects as optic lobe ablation on memory formation and recall. The data suggest that the optic lobes contain the circadian clock(s) that regulate learning and memory processes via inhibition of neural processes in the brain. PMID:26714872

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

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

    NASA Technical Reports Server (NTRS)

    Ede, M. C. M.

    1975-01-01

    The mechanisms that underlie the circadian variations in electrolyte content in body fluid compartments were investigated, and the mechanisms that control the oscillations were studied in order to investigate what effects internal desynchronization in such a system would have during manned space flight. The studies were performed using volunteer human subjects and squirrel monkeys. The intercompartmental distribution of potassium was examined when dietary intake, activity, and posture are held constant throughout each 24-hour day. A net flux of potassium was observed out of the body cell mass during the day and a reverse flux from the extracellular fluid into the body cell mass during the night, counterbalanced by changes in urinary potassium excretion. Experiments with monkeys provided evidence for the synchronization of renal potassium excretion by the rhythm of cortisol secretion with the light-dark cycle. Three models of the circadian timing system were formalized.

  1. Hopf Bifurcations in a Model for Circadian Rhythms in Arabidopsis Thaliana

    NASA Astrophysics Data System (ADS)

    Shindell, Orrin; Tagg, Randall

    2011-03-01

    Arabidopsis thaliana is a plant used for many fundamental studies, including circadian rhythms. Numerically integrating the 7-equation kinetic model of Locke et al. [J. Theor. Bio. 234 (2005) 383], we have mapped regions of parameter space where circadian expression of key mRNA and proteins undergoes limit cycle oscillation. We seek to relate this to the work of Fukuda et al. [Phys. Rev. Lett. 99 (2007) 098102], where a coupled system of cells individually described by Stuart-Landau equations is used phenomenologically to describe experimentally observed spatio-temporal patterns in the plant leaves. To that end we have done a weakly nonlinear analysis of the system of kinetic equations. We also comment on possible experimental directions to further connect the kinetic models to dynamics in this multi-cellular system.

  2. Influences of horizontal hypokinesia on performance and circadian physiological rhythms in female humans

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Deroshia, C. W.; Sandler, H.

    1982-01-01

    Eight females from 35-45 yr of age were subjected to seven days of ambulatory control, seven days of bed rest, and a five day recovery period, with 30 min of centrifugation on day seven of bedrest to determine the effects of weightlessness on the circadian rhythms of females in that age group. Heart rate and rectal temperature (RT) were monitored and each subject was tested in a flight simulator twice a day in conditions of varying levels of turbulence. The flight simulations were run during the morning and acrophase of the circadian RT and performance errors wery monitored for 6 min. No significant differences were detected in the group performance data pre-, during, and post-bedrest, although better performance in the simulator was observed after the centrifuge exposure. An RT phase shift was statistically significant between pre- and during bedrest stages.

  3. Dynamics of three coupled van der Pol oscillators with application to circadian rhythms

    NASA Astrophysics Data System (ADS)

    Rompala, Kevin; Rand, Richard; Howland, Howard

    2007-08-01

    In this work we study a system of three van der Pol oscillators. Two of the oscillators are identical, and are not directly coupled to each other, but rather are coupled via the third oscillator. We investigate the existence of the in-phase mode in which the two identical oscillators have the same behavior. To this end we use the two variable expansion perturbation method (also known as multiple scales) to obtain a slow flow, which we then analyze using the computer algebra system MACSYMA and the numerical bifurcation software AUTO. Our motivation for studying this system comes from the presence of circadian rhythms in the chemistry of the eyes. We model the circadian oscillator in each eye as a van der Pol oscillator. Although there is no direct connection between the two eyes, they are both connected to the brain, especially to the pineal gland, which is here represented by a third van der Pol oscillator.

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

    PubMed

    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

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

    PubMed

    Caldeira, Cecilio F; Jeanguenin, Linda; Chaumont, François; Tardieu, François

    2014-01-01

    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 observed in plants that experience large alternations of water status during an entrainment period, but is considerably buffered otherwise. Measurements and computer simulations show that this is due to oscillations of plant hydraulic conductance and plasma membrane aquaporin messenger RNA abundance in roots during continuous light. A simulation model suggests that circadian oscillations of root hydraulic conductance contribute to acclimation to water stress by increasing root water uptake, thereby favouring growth and photosynthesis. They have a negative effect in favourable hydraulic conditions. Climate-driven control of root hydraulic conductance therefore improves plant performances in both stressed and non-stressed conditions. PMID:25370944

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

    PubMed Central

    Caldeira, Cecilio F.; Jeanguenin, Linda; Chaumont, François; Tardieu, François

    2014-01-01

    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 observed in plants that experience large alternations of water status during an entrainment period, but is considerably buffered otherwise. Measurements and computer simulations show that this is due to oscillations of plant hydraulic conductance and plasma membrane aquaporin messenger RNA abundance in roots during continuous light. A simulation model suggests that circadian oscillations of root hydraulic conductance contribute to acclimation to water stress by increasing root water uptake, thereby favouring growth and photosynthesis. They have a negative effect in favourable hydraulic conditions. Climate-driven control of root hydraulic conductance therefore improves plant performances in both stressed and non-stressed conditions. PMID:25370944

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

    PubMed Central

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

    2009-01-01

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioural and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics. PMID:20167942

  8. Involvement of Wee1 in the circadian rhythm-dependent intestinal damage induced by docetaxel.

    PubMed

    Obi-Ioka, Yuri; Ushijima, Kentaro; Kusama, Mikio; Ishikawa-Kobayashi, Eiko; Fujimura, Akio

    2013-10-01

    Docetaxel, a semisynthetic taxane, is effective for the treatment of some solid cancers; however, docetaxel-induced intestinal damage leads to poor prognosis in some patients. Although such adverse effects have been reported to depend on the dosing-time of docetaxel, the mechanisms involved remain unclear. Wee1 expression is controlled by the clock gene complex, clock/bmal1, and contributes to cell-cycle progression. The present study was undertaken to evaluate the potential role of Wee1 in the circadian rhythm-dependent profile of docetaxel. Male mice were maintained under a 12-hour light/dark cycle. Intestinal damage after repeated dosing of docetaxel (20 mg/kg) for 3 weeks was more severe at 14 hours after light on (HALO) than at 2 HALO. The intestinal protein expressions of Wee1, phosphorylated CDK1, and cleaved Caspase-3 were higher in the 14-HALO group than in the 2-HALO group, whereas that of survivin was lower in the 14-HALO group. Thus, it is speculated that elevated Wee1 expression inhibited CDK1 activity more by phosphorylation, which in turn caused the lower expression of survivin and consequently more activated Caspase-3 in the 14-HALO group. There were no significant differences in plasma docetaxel concentrations between the 2- and 14-HALO groups. Bindings of CLOCK and BMAL1 to the E-box regions at the wee1 gene promoter were not altered by docetaxel treatment at 2 and 14 HALO. These findings suggest that Wee1 is directly or indirectly involved in the mechanism of the circadian rhythm-dependent changes in docetaxel-induced intestinal damage. However, the mechanism for a circadian rhythm-dependent change in intestinal Wee1 expression by docetaxel remains to be determined. PMID:23892568

  9. Effect of feeding and temperature on the circadian rhythms of cortisol, thyroxine and triiodothyronine in pigs

    SciTech Connect

    Becker, B.A.; Nienaber, J.A.; Ford, J.J.; Hahn, G.L.

    1986-03-05

    An experiment was conducted to evaluate the circadian rhythms of cortisol, thyroxine (T/sub 4/) and triiodothyronine (T/sub 3/) in pigs under two temperature and feeding regimes. Twenty-eight barrows were randomly assigned to one of the following: 1) ad-libitum fed at 5/sup 0/C(AL-5); 2) ad-libitum fed at 20/sup 0/C(AL-20); 3) meal fed at 5/sup 0/C(M-5); and 4) meal fed at 20/sup 0/C(M-20). M-5 and M-20 animals were fed at 0730 and 1400 hrs. Lights were on from 0600 to 2000 hrs. After 5 wks, blood samples were collected for 27 hrs. Serum cortisol, T/sub 4/ and T/sub 3/ concentrations were determined by RIA. No significant differences were found in the mesors, amplitudes or acrophases for cortisol. The mesors for T/sub 4/ (p<.01) were 60.6 +/- 5.6, 40.2 +/- 5.6, 61.2 +/- 5.6 and 49.1 +/- 5.0 ng/ml for AL-5, AL-20, M-5, and M-20, respectively. The mesors for T/sub 3/ (p<.01) were .85 +/- .06, .69 +/- .06, .92 +/- .06 and .66 +/- .05 ng/ml for AL-5, AL-20, M-5, and M-20 respectively. No differences in the amplitudes or acrophases for T/sub 3/ or T/sub 4/ were found. These data show that temperature and feeding regimes do not entrain the circadian rhythm of cortisol in pigs. The circadian rhythms of T/sub 4/ and T/sub 3/ are also not altered by feeding regimes but are affected by temperature.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    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

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

    PubMed Central

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  13. Advancing Circadian Rhythms Before Eastward Flight: A Strategy to Prevent or Reduce Jet Lag

    PubMed Central

    Eastman, Charmane I.; Gazda, Clifford J; Burgess, Helen J.; Crowley, Stephanie J.; Fogg, Louis F.

    2005-01-01

    Study Objectives To develop a practical pre-eastward flight treatment to advance circadian rhythms as much as possible but not misalign them with sleep. Design One group had their sleep schedule advanced by 1 hour per day and another by 2 hours per day. Setting Baseline at home, treatment in lab. Participants Young healthy adults (11 men, 15 women) between the ages of 22 and 36 years. Interventions Three days of a gradually advancing sleep schedule (1 or 2 hours per day) plus intermittent morning bright light (one-half hour ~5000 lux, one-half hour of < 60 lux) for 3.5 hours. Measurements and Results The dim light melatonin onset was assessed before and after the 3-day treatment. Subjects completed daily sleep logs and symptom questionnaires and wore wrist activity monitors. The dim light melatonin onset advanced more in the 2-hours-per-day group than in the 1-hour-per-day group (median phase advances of 1.9 and 1.4 hours), but the difference between the means (1.8 and 1.5 hours) was not statistically significant. By the third treatment day, circadian rhythms were misaligned relative to the sleep schedule, and subjects had difficulty falling asleep in the 2-hours-per-day group, but this was not the case in the 1-hour-per-day group. Nevertheless, the 2-hours-per-day group did slightly better on the symptom questionnaires. In general, sleep disturbance and other side effects were small. Conclusions A gradually advancing sleep schedule with intermittent morning bright light can be used to advance circadian rhythms before eastward flight and, thus, theoretically, prevent or reduce subsequent jet lag. Given the morning light treatment used here, advancing the sleep schedule 2 hours per day is not better than advancing it 1 hour per day because it was too fast for the advance in circadian rhythms. A diagram is provided to help the traveler plan a preflight schedule. PMID:15700719

  14. Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²⁺ rhythms in vivo.

    PubMed

    Liang, Xitong; Holy, Timothy E; Taghert, Paul H

    2016-02-26

    In Drosophila, molecular clocks control circadian rhythmic behavior through a network of ~150 pacemaker neurons. To explain how the network's neuronal properties encode time, we performed brainwide calcium imaging of groups of pacemaker neurons in vivo for 24 hours. Pacemakers exhibited daily rhythmic changes in intracellular Ca(2+) that were entrained by environmental cues and timed by molecular clocks. However, these rhythms were not synchronous, as each group exhibited its own phase of activation. Ca(2+) rhythms displayed by pacemaker groups that were associated with the morning or evening locomotor activities occurred ~4 hours before their respective behaviors. Loss of the receptor for the neuropeptide PDF promoted synchrony of Ca(2+) waves. Thus, neuropeptide modulation is required to sequentially time outputs from a network of synchronous molecular pacemakers. PMID:26917772

  15. Circadian Rhythms of Chloroplast Orientation and Photosynthetic Capacity in Ulva123

    PubMed Central

    Britz, Steven J.; Briggs, Winslow R.

    1976-01-01

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

  16. Synchronous Drosophila circadian pacemakers display non-synchronous Ca2+ rhythms in vivo

    PubMed Central

    Liang, Xitong; Holy, Timothy E.; Taghert, Paul H.

    2016-01-01

    In Drosophila, molecular clocks control circadian rhythmic behavior through a network of ~150 pacemaker neurons. To explain how the network’s neuronal properties encode time, we performed brain-wide calcium imaging of groups of pacemaker neurons in vivo for 24 hours. Pacemakers exhibited daily rhythmic changes in intracellular Ca2+ that were entrained by environmental cues and timed by molecular clocks. However, these rhythms were not synchronous, as each group exhibited its own phase of activation. Ca2+ rhythms displayed by pacemaker groups that were associated with the morning or evening locomotor activities occurred ~4 hours before their respective behaviors. Loss of receptor for neuropeptide PDF promoted synchrony of Ca2+ waves. Thus neuropeptide modulation is required to sequentially time outputs from a network of synchronous molecular pacemakers. PMID:26917772

  17. A Novel Quantitative Trait Locus on Mouse Chromosome 18, “era1,” Modifies the Entrainment of Circadian Rhythms

    PubMed Central

    Wisor, Jonathan P.; Striz, Martin; DeVoss, Jason; Murphy, Greer M.; Edgar, Dale M.; O'Hara, Bruce F.

    2007-01-01

    Study Objectives: The mammalian circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus conveys 24-h rhythmicity to sleep-wake cycles, locomotor activity, and other behavioral and physiological processes. The timing of rhythms relative to the light/dark (LD12:12) cycle is influenced in part by the endogenous circadian period and the time of day specific sensitivity of the clock to light. We now describe a novel circadian rhythm phenotype, and a locus influencing that phenotype, in a segregating population of mice. Methods: By crossbreeding 2 genetically distinct nocturnal strains of mice (Cast/Ei and C57BL/6J) and backcrossing the resulting progeny to Cast/Ei, we have produced a novel circadian phenotype, called early runner mice. Results: Early runner mice entrain to a light/dark cycle at an advanced phase, up to 9 hours before dark onset. This phenotype is not significantly correlated with circadian period in constant darkness and is not associated with disruption of molecular circadian rhythms in the SCN, as assessed by analysis of period gene expression. We have identified a genomic region that regulates this phenotype—a major quantitative trait locus on chromosome 18 (near D18Mit184) that we have named era1 for Early Runner Activity locus one. Phase delays caused by light exposure early in the subjective night were of smaller magnitude in backcross offspring that were homozygous Cast/Ei at D18Mit184 than in those that were heterozygous at this locus. Conclusion: Genetic variability in the circadian response to light may, in part, explain the variance in phase angle of entrainment in this segregating mouse population. Citation: Wisor JP; Striz M; DeVoss J; Murphy GM; Edgar DM; O'Hara BF. A novel quantitative trait locus on mouse chromosome 18, “era1,” modifies the entrainment of circadian rhythms. SLEEP 2007;30(10):1255-1263. PMID:17969459

  18. The core clock gene Per1 phases molecular and electrical circadian rhythms in SCN neurons.

    PubMed

    Jones, Jeff R; McMahon, Douglas G

    2016-01-01

    The brain's biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used a Per1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAA receptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock gene Per1, but persists in the absence of the core clock gene Per2. These results suggest that Per1 plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping. PMID:27602274

  19. The core clock gene Per1 phases molecular and electrical circadian rhythms in SCN neurons

    PubMed Central

    Jones, Jeff R.

    2016-01-01

    The brain’s biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used a Per1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAA receptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock gene Per1, but persists in the absence of the core clock gene Per2. These results suggest that Per1 plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping. PMID:27602274

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

    PubMed Central

    Sakuma, Hiroshi

    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

  1. Circadian rhythms in diving behavior and ventilatory response to asphyxia in canvasback ducks.

    PubMed

    Woodin, M; Stephenson, R

    1998-03-01

    Underwater feeding behavior was measured in 10 captive canvasback ducks (Aythya valisineria) for 12 days under a 12:12-h light-dark photoperiod. Feeding activity exhibited a daily rhythm, with 76% of dives occurring at night. In separate experiments on six of these ducks, a circadian rhythm was observed in the duration of voluntary dives. Dives at night (14.7 +/- 0.7 s) were significantly longer than those during the day (10.7 +/- 0.7 s). These day-night differences in diving behavior were accompanied by day-night differences in respiratory responses to progressive asphyxia. In the same six ducks, ventilation increased exponentially as a function of inspired CO2 concentration during rebreathing in a closed-circuit barometric plethysmograph. The exponential rate constant for inspired ventilation was significantly smaller at night (0.23 +/- 0.02) than during the day (0.26 +/- 0.01). We suggest that intermittent apneic exercise is facilitated by reduced respiratory chemosensitivity and that the respiratory and behavioral control systems are synchronized by the circadian timing system in diving ducks. PMID:9530234

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

    PubMed

    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. PMID:27078397

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    Whole body heat production (HP) and heat loss (HL) were examined to determine their relative contributions to light masking of the circadian rhythm in body temperature (Tb). Squirrel monkey metabolism (n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of body temperature and activity. Feeding was also measured. Responses to an entraining light-dark (LD) cycle (LD 12:12) and a masking LD cycle (LD 2:2) were compared. HP and HL contributed to both the daily rhythm and the masking changes in Tb. All variables showed phase-dependent masking responses. Masking transients at L or D transitions were generally greater during subjective day; however, L masking resulted in sustained elevation of Tb, HP, and HL during subjective night. Parallel, apparently compensatory, changes of HL and HP suggest action by both the circadian timing system and light masking on Tb set point. Furthermore, transient HL increases during subjective night suggest that gain change may supplement set point regulation of Tb.

  5. Circadian rhythms (temperature, heart rate, vigilance, mood) of short and long sleepers: effects of sleep deprivation.

    PubMed

    Benoit, O; Foret, J; Merle, B; Reinberg, A

    1981-01-01

    Seven long sleepers (LS) (sleep greater than or equal to 9 h) and seven short sleepers (SS) (sleep less than or equal to 7 h), aged 20 to 23 years, were selected among medical students. They measured their axillary temperature (T), heart rate (HR) and self-estimated their vigilance (V) and mood (M) every 4 h from awakening to bed time during a ten-day control span and during the two sleep deprived nights. Polygraphic sleep recordings were performed on 3 control days and recovery from 24 h (day sleep) or 36 h (night sleep) sleep deprivations. For the 4 variables (T, HR, V and M), group circadian patterns were analyzed by means of the cosinor method for the control span and after both types of sleep deprivation. The acrophases of the 4 variables clustered more in LS than in SS. The acrophases of V and M were found to be more closely related to the sleep/wake rhythm than those of T and HR. Sleep deprivation resulted in a large change of the circadian rhythms in LS but had little effect in SS as indicated by the non detection of most acrophases in LS and the persistence of such acrophases in SS. This difference might be explained by the large interindividual variability of changes induced by the sleep deprivation in LS. Moreover, day sleep recovery was more disturbed in LS than in SS. PMID:7327054

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

    PubMed

    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

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

    PubMed

    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

  8. Circadian Rhythm Genes CLOCK and PER3 Polymorphisms and Morning Gastric Motility in Humans

    PubMed Central

    Yamaguchi, Mitsue; Kotani, Kazuhiko; Tsuzaki, Kokoro; Takagi, Ayaka; Motokubota, Naoko; Komai, Naho; Sakane, Naoki; Moritani, Toshio; Nagai, Narumi

    2015-01-01

    Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut. PMID:25775462

  9. Selective serotonin reuptake inhibitors and raft inhibitors shorten the period of Period1-driven circadian bioluminescence rhythms in rat-1 fibroblasts.

    PubMed

    Nomura, Kazumi; Castanon-Cervantes, Oscar; Davidson, Alec; Fukuhara, Chiaki

    2008-06-01

    Alterations in circadian rhythm generation may be related to the development of mood disorders. Although it has been reported that the most popular antidepressant, selective serotonin reuptake inhibitors (SSRIs) affect circadian phase, no data are available that describe the effects of SSRIs on other circadian parameters (period, amplitude and damping rate) in dissociated cells. In the present study we used real-time monitoring of bioluminescence in rat-1 fibroblasts expressing the Period1-luciferase transgene, and that in Period1-luciferase transgenic mouse suprachiasmatic nucleus (SCN) explants, in order to characterize the effects of SSRI on circadian oscillator function in vitro. We found that mRNA of the serotonin transporter (SERT), a target of SSRIs, was expressed in rat-1 fibroblasts. Sertraline, fluoxetine, fluvoxamine, citalopram and paroxetine all significantly shortened the period of Period1-bioluminescence rhythms in rat-1 fibroblasts. The amplitude was reduced by sertraline, and the damping rate was decreased by sertraline, fluoxetine, flvoxamine and paroxetine. The effect of sertraline was dose-dependent, and it also shortened the circadian period in the SCN. SERT is associated with lipid microdomains, which are required for efficient SERT activity. Indeed, cholesterol chelating reagent methyl-beta-cyclodextrin significantly reduced the period and the amplitude in rat-1 fibroblasts. Furthermore, lipid binding reagent xylazine significantly reduced the period. In summary our data present evidence that SSRIs affect circadian rhythmicity. The action of SSRIs is likely mediated by suppression of SERT activity. A better understanding of the relationship between mental illness and biological timing may yield new insight into disease etiology and avenues for treatment. PMID:18482738

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

    PubMed

    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 < 0.05). Though the MESOR and amplitude of the activity levels were not different among the three chronotypes, the acrophases compared by the ANOVA post-hoc test were significantly

  11. Light-sampling behavior in photoentrainment of a rodent circadian rhythm.

    PubMed

    DeCoursey, P J

    1986-08-01

    Behavioral aspects of photoentrainment of circadian locomotor activity rhythms were recorded for a nocturnal den-dwelling rodent, the flying squirrel, Glaucomys volans. Methods included both telemetric monitoring and infrared observations of animals under constant dark (DD) or light-dark (LD) schedules in either standard wheel cages or in newly developed simulated den cages. By means of the den cages, several aspects of a circadian activity cycle could be simultaneously measured emphasizing the arousal from rest, the light-sampling behavior by which a squirrel assessed the environmental photoregimen, and the phase-shifting by which photoentrainment was achieved. Each animal in a den cage remained for 12 or more hours of its rest period almost exclusively in the darkened nest box, then at an abrupt arousal time moved to the light-sampling porthole. In darkness each animal initiated wheel activity immediately after arousal; light at arousal time, however, induced a return to the nest box for a nap and a delay phase-shift in onset of activity of approximately 40 min. On subsequent days, each animal appeared to be free-running (tau FR less than 24 h) until onset again advanced into the light period. A squirrel usually viewed only a few minutes light per day, and on free-running days occasionally saw none of the 12-h light period. The significance of these data for theories of circadian photoentrainment is discussed. PMID:3761222

  12. Coordinated regulation of circadian rhythms and homeostasis by the suprachiasmatic nucleus.

    PubMed

    Nakagawa, Hachiro; Okumura, Nobuaki

    2010-01-01

    We have demonstrated that in rats activities of various enzymes related to gluconeogenesis and amino acid metabolism show circadian rhythms. Based on these results, we have explored the molecular mechanisms underlying circadian oscillation and phase response to light of the master clock located in the dorsomedial subdivision of the suprachiasmatic nucleus (SCN) and found various proteins closely related to phase response such as BIT/SHPS-1 and those of circadian oscillation, some of which are involved in protein-tyrosine phosphorylation.On the other hand, we have presented several lines of evidence that the ventrolateral subdivision of the SCN includes not only the control center of energy supply to the brain, but also that of homeostasis such as blood glucose, blood pressure, water balance, and body temperature. We have also shown that besides these functions, the latter subdivision is involved in the regulations of hormone secretions such as insulin, glucagon, corticosterone and vasopressin. It has been also shown by electrophysiological means that light exposure to rat eye enhances sympathetic nerve activity, whereas it depresses parasympathetic nerve activity. Thus, environmental light is implicated not only in the phase-shift through the retinohypthalamic tract (RHT), but also control of autonomic nerve activities through the RHT, It is also discussed in this review how the two divisions are interconnected and how environmental light is involved in this interconnection. PMID:20431263

  13. Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability.

    PubMed

    Yamamoto, Naomune; Otsuka, Kuniaki; Kubo, Yutaka; Hayashi, Mitsutoshi; Mizuno, Koh; Ohshima, Hiroshi; Mukai, Chiaki

    2015-04-01

    We evaluated their circadian rhythms using data from electrocardiographic records and examined the change in circadian period related to normal RR intervals for astronauts who completed a long-term (≥6-month) mission in space. The examinees were seven astronauts, five men and two women, from 2009 to 2010. Their mean ± SD age was 52.0 ± 4.2 years (47-59 yr). Each stayed in space for more than 160 days; their average length of stay was 172.6 ± 14.6 days (163-199 days). We conducted a 24-h Holter electrocardiography before launch (Pre), at one month after launch (DF1), at two months after launch (DF2), at two weeks before return (DF3), and at three months after landing (Post), comparing each index of frequency-domain analysis and 24-h biological rhythms of the NN intervals (normal RR intervals). Results show that the mean period of Normal Sinus (NN) intervals was within 24 ± 4 h at each examination. Inter-individual variability differed among the stages, being significantly smaller at DF3 (Pre versus DF1 versus DF3 versus Post = 22.36 ± 2.50 versus 25.46 ± 4.37 versus 22.46 ± 1.75 versus 26.16 ± 7.18 h, p < 0.0001). The HF component increased in 2 of 7 astronauts, whereas it decreased in 3 of 7 astronauts and 1 was remained almost unchanged at DF1. During DF3, about 6 months after their stay in space, the HF component of 5 of 7 astronauts recovered from the decrease after launch, with prominent improvement to over 20% in 3 astronauts. Although autonomic nervous functions and circadian rhythms were disturbed until one month had passed in space, well-scheduled sleep and wake rhythms and meal times served as synchronizers. PMID:25392280

  14. Single-cell resolution fluorescence imaging of circadian rhythms detected with a Nipkow spinning disk confocal system.

    PubMed

    Enoki, Ryosuke; Ono, Daisuke; Hasan, Mazahir T; Honma, Sato; Honma, Ken-Ichi

    2012-05-30

    Single-point laser scanning confocal imaging produces signals with high spatial resolution in living organisms. However, photo-induced toxicity, bleaching, and focus drift remain challenges, especially when recording over several days for monitoring circadian rhythms. Bioluminescence imaging is a tool widely used for this purpose, and does not cause photo-induced difficulties. However, bioluminescence signals are dimmer than fluorescence signals, and are potentially affected by levels of cofactors, including ATP, O(2), and the substrate, luciferin. Here we describe a novel time-lapse confocal imaging technique to monitor circadian rhythms in living tissues. The imaging system comprises a multipoint scanning Nipkow spinning disk confocal unit and a high-sensitivity EM-CCD camera mounted on an inverted microscope with auto-focusing function. Brain slices of the suprachiasmatic nucleus (SCN), the central circadian clock, were prepared from transgenic mice expressing a clock gene, Period 1 (Per1), and fluorescence reporter protein (Per1::d2EGFP). The SCN slices were cut out together with membrane, flipped over, and transferred to the collagen-coated glass dishes to obtain signals with a high signal-to-noise ratio and to minimize focus drift. The imaging technique and improved culture method enabled us to monitor the circadian rhythm of Per1::d2EGFP from optically confirmed single SCN neurons without noticeable photo-induced effects or focus drift. Using recombinant adeno-associated virus carrying a genetically encoded calcium indicator, we also monitored calcium circadian rhythms at a single-cell level in a large population of SCN neurons. Thus, the Nipkow spinning disk confocal imaging system developed here facilitates long-term visualization of circadian rhythms in living cells. PMID:22480987

  15. Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy.

    PubMed

    De Rui, M; Middleton, B; Sticca, A; Gatta, A; Amodio, P; Skene, D J; Montagnese, S

    2015-02-01

    Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized

  16. Thermotaxis, circadian rhythms, and TRP channels in Drosophila.

    PubMed

    Bellemer, Andrew

    2015-01-01

    The fruit fly Drosophila melanogaster is a poikilothermic organism that must detect and respond to both fine and coarse changes in environmental temperature in order maintain optimal body temperature, synchronize behavior to daily temperature fluctuations, and to avoid potentially injurious environmental hazards. Members of the Transient Receptor Potential (TRP) family of cation channels are well known for their activation by changes in temperature and their essential roles in sensory transduction in both invertebrates and vertebrates. The Drosophila genome encodes 13 TRP channels, and several of these have key sensory transduction and modulatory functions in allowing larval and adult flies to make fine temperature discriminations to attain optimal body temperature, detect and avoid large environmental temperature fluctuations, and make rapid escape responses to acutely noxious stimuli. Drosophila use multiple, redundant signaling pathways and neural circuits to execute these behaviors in response to both increases and decreases in temperature of varying magnitudes and time scales. A plethora of powerful molecular and genetic tools and the fly's simple, well-characterized nervous system have given Drosophila neurobiologists a powerful platform to study the cellular and molecular mechanisms of TRP channel function and how these mechanisms are conserved in vertebrates, as well as how these channels function within sensorimotor circuits to generate both simple and complex thermosensory behaviors. PMID:27227026

  17. Thermotaxis, circadian rhythms, and TRP channels in Drosophila

    PubMed Central

    Bellemer, Andrew

    2015-01-01

    The fruit fly Drosophila melanogaster is a poikilothermic organism that must detect and respond to both fine and coarse changes in environmental temperature in order maintain optimal body temperature, synchronize behavior to daily temperature fluctuations, and to avoid potentially injurious environmental hazards. Members of the Transient Receptor Potential (TRP) family of cation channels are well known for their activation by changes in temperature and their essential roles in sensory transduction in both invertebrates and vertebrates. The Drosophila genome encodes 13 TRP channels, and several of these have key sensory transduction and modulatory functions in allowing larval and adult flies to make fine temperature discriminations to attain optimal body temperature, detect and avoid large environmental temperature fluctuations, and make rapid escape responses to acutely noxious stimuli. Drosophila use multiple, redundant signaling pathways and neural circuits to execute these behaviors in response to both increases and decreases in temperature of varying magnitudes and time scales. A plethora of powerful molecular and genetic tools and the fly's simple, well-characterized nervous system have given Drosophila neurobiologists a powerful platform to study the cellular and molecular mechanisms of TRP channel function and how these mechanisms are conserved in vertebrates, as well as how these channels function within sensorimotor circuits to generate both simple and complex thermosensory behaviors. PMID:27227026

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

    PubMed

    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

  19. PDP1ε functions downstream of the circadian oscillator to mediate behavioral rhythms Abbreviated title: PDP1ε function in the circadian clock

    PubMed Central

    Benito, Juliana; Zheng, Hao; Hardin, Paul E.

    2007-01-01

    The Drosophila circadian oscillator is comprised of autoregulatory period/timeless (per/tim) and Clock (Clk) feedback loops that control rhythmic transcription. In the Clk loop, CLOCK-CYCLE (CLK-CYC) heterodimers activate vrille (vri) and PAR domain protein 1ε (Pdp1ε) transcription, then sequential repression by VRI and activation by PDP1ε mediate rhythms in Clk transcription. Since VRI and PDP1ε bind the same regulatory element, the VRI/PDP1ε ratio is thought to control the level of Clk transcription. Thus, constant high or low PDP1ε levels in clock cells should eliminate Clk mRNA cycling and disrupt circadian oscillator function. Here we show that reducing PDP1ε levels in clock cells by ~70% via RNA interference or increasing PDP1ε levels by ~10-fold in clock cells does not alter Clk mRNA cycling or circadian oscillator function. However, constant low or high PDP1ε levels in clock cells disrupt locomotor activity rhythms despite persistent circadian oscillator function in brain pacemaker neurons that extend morphologically normal projections into the dorsal brain. These results demonstrate that the VRI/PDP1ε ratio neither controls Clk mRNA cycling nor circadian oscillator function, and argue that PDP1ε is not essential for Clk activation. PDP1ε is nevertheless required for behavioral rhythmicity, which suggests that it functions to regulate oscillator output. PMID:17344391

  20. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

    PubMed Central

    Sletten, Tracey L.; Segal, Ahuva Y.; Flynn-Evans, Erin E.; Lockley, Steven W.; Rajaratnam, Shantha M. W.

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID

  1. Advancing Human Circadian Rhythms with Afternoon Melatonin and Morning Intermittent Bright Light

    PubMed Central

    Revell, Victoria L.; Burgess, Helen J.; Gazda, Clifford J.; Smith, Mark R.; Fogg, Louis F.; Eastman, Charmane I.

    2013-01-01

    Context Both light and melatonin can be used to phase shift the human circadian clock, but the phase advancing effect of the combination has not been extensively investigated. Objective The objective of the study was to determine whether phase advances induced by morning intermittent bright light and a gradually advancing sleep schedule could be increased with afternoon melatonin. Participants Healthy adults (25 males, 19 females, between the ages of 19 and 45 yr) participated in the study. Design There were 3 d of a gradually advancing sleep/dark period (wake time 1 h earlier each morning), bright light on awakening [ four 30-min bright-light pulses (∼5000 lux) alternating with 30 min room light < 60 lux] and afternoon melatonin, either 0.5 or 3.0 mg melatonin timed to induce maximal phase advances, or matching placebo. The dim light melatonin onset was measured before and after the treatment to determine the phase advance. Results There were significantly larger phase advances with 0.5 mg (2.5 h, n = 16) and 3.0 mg melatonin (2.6 h, n = 13), compared with placebo (1.7 h, n = 15), but there was no difference between the two melatonin doses. Subjects did not experience jet lag-type symptoms during the 3-d treatment Conclusions Afternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome. PMID:16263827

  2. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase.

    PubMed

    Sletten, Tracey L; Segal, Ahuva Y; Flynn-Evans, Erin E; Lockley, Steven W; Rajaratnam, Shantha M W

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual's circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID

  3. mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression.

    PubMed

    Chen, Xiao; Rosbash, Michael

    2016-05-24

    Circadian rhythms in metazoan eukaryotes are controlled by an endogenous molecular clock. It functions in many locations, including subsets of brain neurons (clock neurons) within the central nervous system. Although the molecular clock relies on transcription/translation feedback loops, posttranscriptional regulation also plays an important role. Here, we show that the abundant Drosophila melanogaster microRNA mir-276a regulates molecular and behavioral rhythms by inhibiting expression of the important clock gene timeless (tim). Misregulation of mir-276a in clock neurons alters tim expression and increases arrhythmicity under standard constant darkness (DD) conditions. mir-276a expression itself appears to be light-regulated because its levels oscillate under 24-h light-dark (LD) cycles but not in DD. mir-276a is regulated by the transcription activator Chorion factor 2 in flies and in tissue-culture cells. Evidence from flies mutated using the clustered, regularly interspaced, short palindromic repeats (CRISPR) tool shows that mir-276a inhibits tim expression: Deleting the mir-276a-binding site in the tim 3' UTR causes elevated levels of TIM and ∼50% arrhythmicity. We suggest that this pathway contributes to the more robust rhythms observed under light/dark LD conditions than under DD conditions. PMID:27162360

  4. Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila.

    PubMed

    Taghert, P H; Hewes, R S; Park, J H; O'Brien, M A; Han, M; Peck, M E

    2001-09-01

    In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is expressed by the ventral subset of lateral pacemaker neurons and is required for circadian locomotor rhythms. Residual rhythmicity in pdf mutants likely reflects the activity of other neurotransmitters. We asked whether other neuropeptides contribute to such auxiliary mechanisms. We used the gal4/UAS system to create mosaics for the neuropeptide amidating enzyme PHM; amidation is a highly specific and widespread modification of secretory peptides in Drosophila. Three different gal4 drivers restricted PHM expression to different numbers of peptidergic neurons. These mosaics displayed aberrant locomotor rhythms to degrees that paralleled the apparent complexity of the spatial patterns. Certain PHM mosaics were less rhythmic than pdf mutants and as severe as per mutants. Additional gal4 elements were added to the weakly rhythmic PHM mosaics. Although adding pdf-gal4 provided only partial improvement, adding the widely expressed tim-gal4 largely restored rhythmicity. These results indicate that, in Drosophila, peptide amidation is required for neuropeptide regulation of behavior. They also support the hypothesis that multiple amidated neuropeptides, acting upstream, downstream, or in parallel to PDF, help organize daily locomotor rhythms. PMID:11517257

  5. Adjustment of sleep and the circadian temperature rhythm after flights across nine time zones

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Myhre, Grete; Graeber, R. Curtis; Lauber, John K.; Andersen, Harald T.

    1989-01-01

    The adjustment of sleep-wake patterns and the circadian temperature rhythm was monitored in nine Royal Norwegian Airforce volunteers operating P-3 aircraft during a westward training deployment across nine time zones. Subjects recorded all sleep and nap times, rated nightly sleep quality, and completed personality inventories. Rectal temperature, heart rate, and wrist activity were continuously monitored. Adjustment was slower after the return eastward flight than after the outbound westward flight. The eastward flight produced slower readjustment of sleep timing to local time and greater interindividual variability in the patterns of adjustment of sleep and temperature. One subject apparently exhibited resynchronization by partition, with the temperature rhythm undergoing the reciprocal 15-h delay. In contrast, average heart rates during sleep were significantly elevated only after westward flight. Interindividual differences in adjustment of the temperature rhythm were correlated with some of the personality measures. Larger phase delays in the overall temperature waveform (as measured on the 5th day after westward flight) were exhibited by extraverts, and less consistently by evening types.

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

    PubMed

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

    2014-01-01

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

  7. A Failure to Detect an Influence of Magnetic Fields on the Growth Rate and Circadian Rhythm of Neurospora crassa1

    PubMed Central

    Bitz, D. Michael; Sargent, Malcolm L.

    1974-01-01

    Low strength magnetic fields, 6.36 and 32.25 gauss, were found to have no effect, with one questionable exception, on the circadian rhythm and growth rate of Neurospora crassa. This was true whether the fields were continuous, pulsed 20 minutes daily, or on a 12: 12, on-off cycle. PMID:16658667

  8. Circadian Rhythms in Executive Function during the Transition to Adolescence: The Effect of Synchrony between Chronotype and Time of Day

    ERIC Educational Resources Information Center

    Hahn, Constanze; Cowell, Jason M.; Wiprzycka, Ursula J.; Goldstein, David; Ralph, Martin; Hasher, Lynn; Zelazo, Philip David

    2012-01-01

    To explore the influence of circadian rhythms on executive function during early adolescence, we administered a battery of executive function measures (including a Go-Nogo task, the Iowa Gambling Task, a Self-ordered Pointing task, and an Intra/Extradimensional Shift task) to Morning-preference and Evening-preference participants (N = 80) between…

  9. Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase

    PubMed Central

    An, Sungwon; Irwin, Robert P.; Allen, Charles N.; Tsai, Connie

    2011-01-01

    Circadian oscillations in the suprachiasmatic nucleus (SCN) depend on transcriptional repression by Period (PER)1 and PER2 proteins within single cells and on vasoactive intestinal polypeptide (VIP) signaling between cells. Because VIP is released by SCN neurons in a circadian pattern, and, after photic stimulation, it has been suggested to play a role in the synchronization to environmental light cycles. It is not known, however, if or how VIP entrains circadian gene expression or behavior. Here, we tested candidate signaling pathways required for VIP-mediated entrainment of SCN rhythms. We found that single applications of VIP reset PER2 rhythms in a time- and dose-dependent manner that differed from light. Unlike VIP-mediated signaling in other cell types, simultaneous antagonism of adenylate cyclase and phospholipase C activities was required to block the VIP-induced phase shifts of SCN rhythms. Consistent with this, VIP rapidly increased intracellular cAMP in most SCN neurons. Critically, daily VIP treatment entrained PER2 rhythms to a predicted phase angle within several days, depending on the concentration of VIP and the interval between VIP applications. We conclude that VIP entrains circadian timing among SCN neurons through rapid and parallel changes in adenylate cyclase and phospholipase C activities. PMID:21389307

  10. Lithium and genetic inhibition of GSK3beta enhance the effect of methamphetamine on circadian rhythms in the mouse.

    PubMed

    Mohawk, Jennifer A; Miranda-Anaya, Manuel; Tataroglu, Ozgur; Menaker, Michael

    2009-03-01

    Lithium, a drug commonly used to treat mood disorders, and the psychostimulant methamphetamine are both capable of altering circadian rhythmicity. Although the actions of lithium on the circadian system are thought to occur through inhibition of glycogen synthase kinase-3beta (GSK3beta), the mechanism by which methamphetamine alters circadian rhythms is unknown. We tested the effects of concurrent methamphetamine and lithium treatment on the circadian wheel-running behavior of mice. Methamphetamine alone lengthened both the active duration and the free-running period of locomotor activity in animals housed in constant conditions. Administering lithium enhanced the period-lengthening effects of methamphetamine in animals housed in constant darkness. This effect was even more pronounced when animals were housed in constant light. Lithium increased both methamphetamine intake and serum levels of methamphetamine, possibly contributing to the effects on circadian behavior. We also tested the effect of methamphetamine in mutant mice possessing only one allele for Gsk3beta. These animals, when treated with methamphetamine, responded like wild-type mice treated with a combination of methamphetamine and lithium, displaying long, free-running rhythms. These data, together with many others in the literature, point to a complicated interaction between the circadian system and the development and possible treatment of psychopathologies such as bipolar disorder and drug addiction. PMID:19339873

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

    PubMed

    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

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

    PubMed

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

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

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

    PubMed Central

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

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm−2 s−1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  14. Hierarchy of models: From qualitative to quantitative analysis of circadian rhythms in cyanobacteria

    NASA Astrophysics Data System (ADS)

    Chaves, M.; Preto, M.

    2013-06-01

    A hierarchy of models, ranging from high to lower levels of abstraction, is proposed to construct "minimal" but predictive and explanatory models of biological systems. Three hierarchical levels will be considered: Boolean networks, piecewise affine differential (PWA) equations, and a class of continuous, ordinary, differential equations' models derived from the PWA model. This hierarchy provides different levels of approximation of the biological system and, crucially, allows the use of theoretical tools to more exactly analyze and understand the mechanisms of the system. The Kai ABC oscillator, which is at the core of the cyanobacterial circadian rhythm, is analyzed as a case study, showing how several fundamental properties—order of oscillations, synchronization when mixing oscillating samples, structural robustness, and entrainment by external cues—can be obtained from basic mechanisms.

  15. Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol

    NASA Technical Reports Server (NTRS)

    Chavarri, M.; Ganguly, A.; Luetscher, J. A.; Zager, P. G.

    1977-01-01

    Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  17. Circadian rhythm of onset of stroke - in 50 cases of ischemic stroke.

    PubMed

    Uddin, M S; Hoque, M I; Uddin, M K; Kamol, S A; Chowdhury, R H

    2015-01-01

    Stroke is a leading cause of death and disability worldwide. While the immediate consequence of stroke include permanent cognitive deficits, paralysis, visual impairment and sensory disturbances; stroke also results in long term dysregulation of sleep and mood, which may be equally disabling. The influence of ischemic stroke on circadian rhythm regulation, which is strongly linked to sleep and mood, may thus potentially influence long term recovery in stroke patients. Stroke induces immediate changes in the timing of pineal melatonin secretion, indicating that cortical and basal ganglia infarction impacts the timing of melatonin rhythms. This study was done to find out the time of onset of most of the ischemic stroke attack and to determine the outcome of ischemic stroke during hospital stay. All ischemic stroke patients admitted in Medicine wards in Comilla Medical College Hospital during the period of 1st November 2010 to 30th April 2011 included in this study. After admission, a careful history and a thorough clinical examination was carried out. Data collection was done on a preset questionnaire which involved to identify the risk factors, the time of onset of ischemic stroke, and outcome during hospital stay. All the cases were investigated. Among the 50 ischemic stroke patients, 68% were male and 32% female. Maximum age groups were 61-70 years (50%). By occupational category, maximum were retired persons (46%); 68% were hypertensive, 38% smoker and 16% had diabetes. Dyslipidemia was present in 44% patients. Most of the ischemic stroke (44%) occurred in the morning to late morning (6:01AM-12:00PM) and majority (80%) of the patients was discharged with residual neurological dysfunction. This study supports the presence of a circadian pattern in the onset of ischemic stroke, with higher risk in the morning to late morning. Most of the patients were discharged with residual neurological dysfunction. PMID:25725678

  18. No endogenous circadian rhythm in resting plasma Hsp72 concentration in humans

    PubMed Central

    Fortes, Matthew B.

    2008-01-01

    Extra-cellular (e) heat shock protein (Hsp)72 has been shown to be elevated in a number of clinical conditions and has been proposed as a potential diagnostic marker. From a methodological and diagnostic perspective, it is important to investigate if concentrations of eHsp72 fluctuate throughout the day; hence, the purpose of the study was to measure resting concentrations of plasma eHsp72 throughout a 24-h period. Blood samples were taken every hour from 1200–2100 hours and from 0700–1200 hours the following day from seven healthy recreationally active males. Participants remained in the laboratory throughout the trial, performed light sedentary activities and were provided with standardised meals and fluids. Physical activity was quantified throughout by the use of an accelerometer. Ethylenediaminetetraacetic acid blood samples were analysed for eHsp72 concentration using a commercially available high-sensitivity enzyme-linked immunosorbent assay (intra-assay coefficient of variation = 1.4%). One-way repeated measures analysis of variance revealed that measures of physiological stress such as heart rate, systolic and diastolic blood pressure remained stable throughout the trial and subjects remained sedentary throughout (mean activity energy expenditure above resting metabolic rate—35.7 ± 10.0 kcal∙h−1). Plasma Hsp72 concentration did not fluctuate significantly throughout the day and showed no apparent endogenous circadian rhythm in absolute (P = 0.367) or plasma volume change corrected data (P = 0.380). Individual coefficients of variation ranged from 3.8–7.7% (mean 5.4%). Mean Hsp72 concentration across all subjects and time points was 1.49 ± 0.08 ng∙ml−1. These data show that in a rested state, plasma eHsp72 concentration shows no apparent endogenous circadian rhythm. PMID:18839337

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

    PubMed

    Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

    2011-01-01

    Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9-12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9-12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle. PMID:22022521

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

    PubMed

    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

  1. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet

    PubMed Central

    Kc, Ranjan; Li, Xin; Forsyth, Christopher B.; Voigt, Robin M.; Summa, Keith C.; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W.; Meng, Qing-Jun; Im, Hee-Jeong

    2015-01-01

    A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications. PMID:26584570

  2. Phase Shift of the Circadian Rhythm of Lemna Caused by Pulses of a Leucine Analog, Trifluoroleucine

    PubMed Central

    Kondo, Takao

    1988-01-01

    Pulses of a fluorinated analog of leucine, 5′,5′,5′-trifluoroleucine, reset the phase of the circadian rhythm of K+ uptake in Lemna gibba G3 under continuous light conditions. The trifluoroleucine pulse caused the largest delay phase-shifts during the early subjective phase but it caused only small phase advances. The action of trifluoroleucine was investigated and the following results were obtained. (a) The uptake of trifluoroleucine was essentially the same at all circadian phases, even though phase shifting was dramatically different at different phases. At effective phases, the magnitude of phase shifting was well correlated with the amount of trifluoroleucine taken up by the duckweed. (b) The trifluoroleucine pulse lowered the endogenous content of valine and leucine but these decreases did not correlate with phase shifting. (c) Protein synthesis was not affected by trifluoroleucine pulses which caused large phase shifts. (d) Pulses of 4-azaleucine, a different structural analog of leucine, also caused phase shifting. However, neither the direction nor the effective times of phase shifting were similar to those of trifluoroleucine. Taken together, these results negate the proposition that trifluoroleucine and azaleucine caused phase shift by disturbing amino acid metabolism and/or inhibiting protein synthesis, but they suggest instead that these analogs are incorporated into some protein(s) which are necessary for normal clock operation. PMID:16666410

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

    NASA Astrophysics Data System (ADS)

    Qin, Chuanjie; Shao, Ting

    2015-05-01

    The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene ( Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%-88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.

  4. Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats

    NASA Technical Reports Server (NTRS)

    McDonald, R. B.; Hoban-Higgins, T. M.; Ruhe, R. C.; Fuller, C. A.; Horwitz, B. A.

    1999-01-01

    We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

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

    PubMed

    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

  6. The expression of locomotor circadian rhythm in female German cockroach, Blattella germanica (L.).

    PubMed

    Lin, T M; Lee, H J

    1996-07-01

    Fifteen percent of intact female German cockroaches (n = 13), Blattella germanica (L.) (Dictyoptera: Blattellidae), had weak free-running locomotor rhythmicity under 28 degrees C and constant darkness conditions. However, 86% of ovariectomized females (n = 14) showed a strong free-running rhythm under the same conditions with a circadian period of 23.60 +/- 0.15 h, similar to the male's period of 23.45 +/- 0.03 h. In addition, the locomotory activities occurred mainly during the subjective night under DD conditions as was the case in males. These results indicated that female locomotion was under the control of a circadian oscillator, which was masked by the existence of ovaries. This internal masking effect could be removed by the existence of males, but females had no effect on the locomotor pattern of another female. Since the male failed to entrain female locomotion, its role as a zeitgeber was excluded. That the locomotory pattern of the females still coincided with their reproductive cycle when exposed to male odor suggests that exposure to a male only partially removed the internal masking effects. PMID:8877117

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

    NASA Technical Reports Server (NTRS)

    Ferraro, J. S.; Sulzman, F. M.

    1988-01-01

    Feedback lighting provides illumination primarily during the subjective night (i.e., the photosensitive portion of the circadian cycle) in response to a given behavior. This technique has previously been used to test the nonparametric model of entrainment in nocturnal rodents. In three species (Rattus norvegicus, Mesocricetus auratus, and Mus musculus), the free-running period of the locomotor activity rhythm was similar whether the animals were exposed to continuous light or discrete light pulses occurring essentially only during the subjective night (i.e., feedback lighting). In the current experiments, feedback lighting was presented to squirrel monkeys so that light fell predominantly during the subjective night. Feedback lighting was linked to the drinking behavior in this diurnal primate so that when the animal drank, the lights went out. Despite the seemingly adverse predicament, the monkeys maintained regular circadian drinking rhythms. Furthermore, just as the period of the free-running activity rhythms of nocturnal rodents exposed to continuous light or feedback lighting were similar, the period of the drinking rhythms of the squirrel monkeys in continuous light and feedback lighting were comparable (25.6 +/- 0.1 and 25.9 +/- 0.1 hours, respectively), despite a substantial decrease in the total amount of light exposure associated with feedback lighting. The free-running period of monkeys exposed to continuous dark (24.5 +/- 0.1 hours) was significantly shorter than either of the two lighting conditions (P < 0.001). The results presented for the drinking rhythm were confirmed by examination of the temperature and activity rhythms. Therefore, discrete light pulses given predominately during the subjective night are capable of simulating the effects of continuous light on the free-running period of the circadian rhythms of a diurnal primate. The response of squirrel monkeys to feedback lighting thus lends further support for the model and suggests that the

  8. Biochemical genetics of the circadian rhythm in Neurospora crassa: studies on the cel strain

    SciTech Connect

    Lakin-Thomas, P.L.

    1985-01-01

    In Neurospora crassa, the cel mutation lengthens the period of the circadian rhythm when the medium is supplemented with linoleic acid (18:2). Double mutant strains were constructed between cel and the clock mutants prd-1 and four alleles at the frq locus. It was found that: (1) the effect of 18:2 on cel was blocked by prd-1, i.e., prd-1 is epistatic to cel. (2) cel and frq interact such that the percent increase in the period produced by 18:2 was inversely proportional to the period of the frq parent. (3) Data from the literature on period effects in double mutant strains support a multiplicative rather than an additive model. A biochemical interpretation of these interactions is discussed, based on the control of flux through metabolic pathways. Because the cel strain is known to be deficient in the pantothenate derivative normally attached to the fatty acid synthetase (FAS) complex, the possibility that cel may affect other pantothenate-modified proteins was investigated. It was found that in the cel/sup +/ strain, five proteins of molecular weights (M/sub r/) 9000, 19,000, 22,000, 140,000, and 200,000 were labelled with (/sup 14/C)pantothenate. In the cel strain, only the 200 k (FAS) label was reduced in amount. Therefore, there is no evidence that cel affects circadian rhythmicity through any deficiency other than FAS. A biochemical model for circadian rhythmicity in Neurospora is presented. Oscillations in cytoplasmic and mitochondrial Ca/sup 2 +/ are proposed; clock mutations are postulated to affect Ca/sup 2 +/ transporters and the mitochondrial membrane; and phase-shifting effects are accounted for by changes in Ca/sup 2 +/ or ATP levels.

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

    PubMed

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

    2015-01-01

    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

  10. Dipper and non-dipper blood pressure 24-hour patterns: circadian rhythm-dependent physiologic and pathophysiologic mechanisms.

    PubMed

    Fabbian, Fabio; Smolensky, Michael H; Tiseo, Ruana; Pala, Marco; Manfredini, Roberto; Portaluppi, Francesco

    2013-03-01

    Neuroendocrine mechanisms are major determinants of the normal 24-h blood pressure (BP) pattern. At the central level, integration of the major driving factors of this temporal variability is mediated by circadian rhythms of monoaminergic systems in conjunction with those of the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, opioid, renin-angiotensin-aldosterone, plus endothelial systems and specific vasoactive peptides. Humoral secretions are typically episodic, coupled either to sleep and/or the circadian endogenous (suprachiasmatic nucleus) central pacemaker clock, but exhibiting also weekly, monthly, seasonal, and annual periodicities. Sleep induction and arousal are influenced also by many hormones and chemical substances that exhibit 24-h variation, e.g., arginine vasopressin, vasoactive intestinal peptide, melatonin, somatotropin, insulin, steroids, serotonin, corticotropin-releasing factor, adrenocorticotropic hormone, thyrotropin-releasing hormone, endogenous opioids, and prostaglandin E2, all with established effects on the cardiovascular system. As a consequence, physical, mental, and pathologic stimuli that activate or inhibit neuroendocrine effectors of biological rhythmicity may also interfere with, or modify, the temporal BP structure. Moreover, immediate adjustment to exogenous components/environment demands by BP rhythms is modulated by the circadian-time-dependent responsiveness of biological oscillators and their neuroendocrine effectors. This knowledge contributes to a better understanding of the pathophysiology of abnormalities of the 24-h BP pattern and level and their correction through circadian rhythm-based chronotherapeutic strategies. PMID:23002916

  11. Axillary and thoracic skin temperatures poorly comparable to core body temperature circadian rhythm: results from 2 adult populations.

    PubMed

    Thomas, Karen A; Burr, Robert; Wang, Shu-Yuann; Lentz, Martha J; Shaver, Joan

    2004-01-01

    Data from 2 separate studies were used to examine the relationships of axillary or thoracic skin temperature to rectal temperature and to determine the phase relationships of the circadian rhythms of these temperatures. In study 1, axillary skin and rectal temperatures were recorded in 19 healthy women, 21 to 36 years of age. In study 2, thoracic skin and rectal temperatures were recorded in 74 healthy women, 39 to 59 years of age. In both studies, temperatures were recorded continuously for 24 h while subjects carried out normal activities. Axillary and thoracic probes were insulated purposely to prevent ambient effects. Cosinor analysis was employed to estimate circadian rhythm mesor, amplitude, and acrophase. In addition, correlations between temperatures at various measurement sites were calculated and agreement determined. The circadian timing of axillary and skin temperature did not closely approximate that of rectal temperature: the mean acrophase (clock time) for study 1 was 18:57 h for axillary temperature and 16:12 h for rectal; for study 2, it was 03:05 h for thoracic and 15:05 h for rectal. Across individual subjects, the correlations of axillary or thoracic temperatures with rectal temperatures were variable. Results do not support the use of either axillary or skin temperature as a substitute for rectal temperature in circadian rhythm research related to adult women. PMID:14737919

  12. Maximum entropy spectral analysis for circadian rhythms: theory, history and practice

    PubMed Central

    2013-01-01

    There is an array of numerical techniques available to estimate the period of circadian and other biological rhythms. Criteria for choosing a method include accuracy of period measurement, resolution of signal embedded in noise or of multiple periodicities, and sensitivity to the presence of weak rhythms and robustness in the presence of stochastic noise. Maximum Entropy Spectral Analysis (MESA) has proven itself excellent in all regards. The MESA algorithm fits an autoregressive model to the data and extracts the spectrum from its coefficients. Entropy in this context refers to “ignorance” of the data and since this is formally maximized, no unwarranted assumptions are made. Computationally, the coefficients are calculated efficiently by solution of the Yule-Walker equations in an iterative algorithm. MESA is compared here to other common techniques. It is normal to remove high frequency noise from time series using digital filters before analysis. The Butterworth filter is demonstrated here and a danger inherent in multiple filtering passes is discussed. PMID:23844660

  13. Sensitivity to Stimulation, a Component of the Circadian Rhythm in Luminescence in Gonyaulax1

    PubMed Central

    Christianson, Roger; Sweeney, Beatrice M.

    1972-01-01

    A new method for the stimulation of bioluminescence in the dinoflagellate Gonyaulax polyedra is described. With this technique, in which cells flow through a capillary coil, it is possible to graduate the intensity of the stimulus by varying the flow rate. In continuous darkness, the threshold stimulus for cells in the middle of the day phase is greater than that for cells in the middle of the night phase. Some evidence suggests heterogeneity of sensitivity to stimulation among either cells or individual luminescent sources within a cell. At stimulus intensities much above threshold, the luminescence of both day- and night-phase cells is proportional to the number of cells within the capillary coil. Night-phase cells emit about 14 times as much light as do day-phase cells in continuous darkness. Single bioluminescent flashes from cells were recorded with a high speed camera. No significant difference in flash kinetics was found between cells in the day and the night phase in continuous darkness. Cells in the night phase emit a flash three to five times brighter than that from day-phase cells. About twice as many flashes are recorded in a given time from a population of night-phase cells. The activity of both luciferin and luciferase have been shown to vary rhythmically. The differences in threshold and number of flahses are evidence for a second component of the circadian rhythm in luminescence, a rhythm in sensitivity to stimulation. PMID:16658099

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

    NASA Technical Reports Server (NTRS)

    Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)

    1999-01-01

    The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

  15. Voluntary exercise enhances activity rhythms and ameliorates anxiety- and depression-like behaviors in the sand rat model of circadian rhythm-related mood changes.

    PubMed

    Tal-Krivisky, Katy; Kronfeld-Schor, Noga; Einat, Haim

    2015-11-01

    Physical exercise is a non-pharmacological treatment for affective disorders. The mechanisms of its effects are unknown although some suggest a relationship to synchronization of circadian rhythms. One way to explore mechanisms is to utilize animal models. We previously demonstrated that the diurnal fat sand rat is an advantageous model for studying the interactions between photoperiods and mood. The current study was designed to evaluate the effects of voluntary exercise on activity rhythms and anxiety and depression-like behaviors in sand rats as a step towards better understanding of the underlying mechanisms. Male sand rats were housed in short photoperiod (SP; 5h light/19 h dark) or neutral light (NP; 12h light/12h dark) regimens for 3 weeks and divided into subgroups with or without running wheels. Activity was monitored for 3 additional weeks and then animals were tested in the elevated plus-maze, the forced swim test and the social interaction test. Activity rhythms were enhanced by the running wheels. As hypothesized, voluntary exercise had significant effects on SP animals' anxiety- and depression-like behaviors but not on NP animals. Results are discussed in the context of interactions between physical exercise, circadian rhythms and mood. We suggest that the sand rat model can be used to explore the underlying mechanism of the effects of physical exercise for mood disorders. PMID:26253214

  16. A tunable artificial circadian clock in clock-defective mice

    PubMed Central

    D'Alessandro, Matthew; Beesley, Stephen; Kim, Jae Kyoung; Chen, Rongmin; Abich, Estela; Cheng, Wayne; Yi, Paul; Takahashi, Joseph S.; Lee, Choogon

    2015-01-01

    Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators. PMID:26617050

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

    PubMed Central

    St. Hilaire, Melissa A.; Lockley, Steven W.

    2015-01-01

    Objective/Background Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep–wake disorder. Patients/Methods Three totally blind males (63.0 ± 7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48 h every 1–2 weeks. Participants completed daily sleep–wake logs, and rated their alertness and mood using nine-point scales every ~2–4 h while awake on urine sampling days. Caffeine capsules (150 mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period τ and compared to placebo (n = 2) or no treatment (n = 1) in a single-masked manner. Results Non-24-h aMT6s rhythms were confirmed in all three participants (τ range = 24.32–24.57 h). Daily administration of 150 mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p < 0.0001) but did not decrease the occurrence of daytime naps compared with placebo. Conclusions Although caffeine was able to improve daytime alertness acutely and may therefore provide temporary symptomatic relief, the inability of caffeine to correct the underlying circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep–Wake Disorder in the blind appropriately. PMID:25891543

  18. Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation

    NASA Technical Reports Server (NTRS)

    Millet, C.; Custaud, M. A.; Allevard, A. M.; Zaouali-Ajina, M.; Monk, T. H.; Arnaud, S. B.; Claustrat, B.; Gharib, C.; Gauquelin-Koch, G.

    2001-01-01

    We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450 (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of the aldosterone rhythm.

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

    PubMed

    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

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

    PubMed Central

    Grimaldi, Benedetto

    2015-01-01

    The discovery that inhibition of a circadian regulator enhances autophagy-dependent cancer cell death reveals potential avenues for the development of new multifunctional anticancer agents. Further studies may elucidate novel crosstalk between circadian rhythm, metabolism, and autophagy that determines cancer cell viability. PMID:27308413

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2008-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  4. The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis

    PubMed Central

    Solt, Laura A; Kojetin, Douglas J; Burris, Thomas P

    2011-01-01

    Research efforts spanning the past two decades have established a clear link between nuclear receptor function, regulation of the circadian clock and lipid homeostasis. As such, this family of receptors represents an important area of research. Recent advances in the field have identified two nuclear receptor subfamilies, the REV-ERBs and the ‘retinoic acid receptor-related orphan receptors’ (RORs), as critical regulators of the circadian clock with significant roles in lipid homeostasis. In this review, the latest information garnered from cutting-edge research on these two nuclear receptor subfamilies will be discussed. Through direct targeting of the REV-ERBs and RORs with synthetic ligands, generation of novel tools aimed at characterizing their function in vivo have been developed, which may lead to novel therapeutics for the treatment of metabolic disorders. PMID:21526899

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

    PubMed Central

    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

  6. Health Impact of Fasting in Saudi Arabia during Ramadan: Association with Disturbed Circadian Rhythm and Metabolic and Sleeping Patterns

    PubMed Central

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

    2014-01-01

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

  7. Elucidation of the Role of Clp Protease Components in Circadian Rhythm by Genetic Deletion and Overexpression in Cyanobacteria

    PubMed Central

    Kitayama, Yohko; Kondo, Takao

    2013-01-01

    In the cyanobacterium Synechococcus elongatus PCC7942, KaiA, KaiB, and KaiC are essential elements of the circadian clock, and Kai-based oscillation is thought to be the basic circadian timing mechanism. The Kai-based oscillator coupled with transcription/translation feedback and other intercellular factors maintains the stability of the 24-hour period in vivo. In this study, we showed that disruption of the Clp protease family genes clpP1, clpP2, and clpX and the overexpression of clpP3 cause long-period phenotypes. There were no significant changes in the levels of the clock proteins in these mutants. The overexpression of clpX led to a decrease in kaiBC promoter activity, the disruption of the circadian rhythm, and eventually cell death. However, after the transient overexpression of clpX, the kaiBC gene expression rhythm recovered after a few days. The rhythm phase after recovery was almost the same as the phase before clpX overexpression. These results suggest that the core Kai-based oscillation was not affected by clpX overexpression. Moreover, we showed that the overexpression of clpX sequentially upregulated ribosomal protein subunit mRNA levels, followed by upregulation of other genes, including the clock genes. Additionally, we found that the disruption of clpX decreased the expression of the ribosomal protein subunits. Finally, we showed that the circadian period was prolonged following the addition of a translation inhibitor at a low concentration. These results suggest that translational efficiency affects the circadian period and that clpX participates in the control of translation efficiency by regulating the transcription of ribosomal protein genes. PMID:23913328

  8. Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Cederholm, Tommy; Sjögren, Per; Lindholm, Bengt; Ärnlöv, Johan; Carrero, Juan Jesús

    2015-01-01

    Background Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. Methods This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). Results UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m2) in its association with the changes of both night-time systolic BP (SBP) and night–day SBP ratio. After stratification, UAER strongly predicted night–day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER. Conclusions UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations. PMID:26413281

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

    PubMed Central

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

    2016-01-01

    The impact of sleep restriction on the endogenous circadian rhythms of hunger and satiety were examined in 28 healthy young men. Participants were scheduled to 2 × 24-h days of baseline followed by 8 × 28-h days of forced desynchrony during which sleep was either moderately restricted (equivalent to 6 h in bed/24 h; n = 14) or severely restricted (equivalent to 4 h in bed/24 h; n = 14). Self-reported hunger and satisfaction were assessed every 2.5 h during wake periods using visual analogue scales. Participants were served standardised meals and snacks at regular intervals and were not permitted to eat ad libitum. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. Both hunger and satiety exhibited a marked endogenous circadian rhythm. Hunger was highest, and satiety was lowest, in the biological evening (i.e., ~17:00–21:00 h) whereas hunger was lowest, and satiety was highest in the biological night (i.e., 01:00–05:00 h). The results are consistent with expectations based on previous reports and may explain in some part the decrease in appetite that is commonly reported by individuals who are required to work at night. Interestingly, the endogenous rhythms of hunger and satiety do not appear to be altered by severe—as compared to moderate—sleep restriction. PMID:26840322

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

    PubMed

    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

  11. Constant light induces alterations in melatonin levels, food intake, feed efficiency, visceral adiposity, and circadian rhythms in rats.

    PubMed

    Wideman, Cyrilla H; Murphy, Helen M

    2009-10-01

    Melatonin levels, metabolic parameters, circadian rhythm activity patterns, and behavior were observed in rats subjected to a 12-h/12-h light/dark cycle (LD) compared to animals exposed to continuous dark (DD) or continuous light (LL). LD and DD animals were similar in melatonin levels, food intake, relative food intake, feed efficiency, water intake, circadian activity levels, and behavior. LL animals had lower melatonin levels in the subjective dark compared to LD and DD animals. Food intake, relative food intake, and water intake values were lower and feed efficiency was more positive in LL animals compared to LD and DD animals. In addition, LL animals exhibited greater visceral adiposity than the other two groups. The circadian rhythmicity of activity became free-running in LL animals and there was a decrease in overall activity. Notable behavioral changes in LL animals were an increase in irritability and excitability. Results indicate that a decrease in melatonin levels and concomitant changes in metabolism, circadian rhythms, and behavior are consequences of exposure to constant light. PMID:19761654

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

    PubMed Central

    Crowley, Stephanie J.; Eastman, Charmane I.

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Kujanik, Stefan; Mikulecky, Miroslav

    2010-09-01

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

  14. Disruption of behavioral circadian rhythms induced by psychophysiological stress affects plasma free amino acid profiles without affecting peripheral clock gene expression in mice.

    PubMed

    Oishi, Katsutaka; Yamamoto, Saori; Itoh, Nanako; Miyazaki, Koyomi; Nemoto, Tadashi; Nakakita, Yasukazu; Kaneda, Hirotaka

    2014-07-18

    Disordered circadian rhythms are associated with various psychiatric conditions and metabolic diseases. We recently established a mouse model of a psychophysiological stress-induced chronic sleep disorder (CSD) characterized by reduced amplitude of circadian wheel-running activity and sleep-wake cycles, sleep fragmentation and hyperphagia. Here, we evaluate day-night fluctuations in plasma concentrations of free amino acids (FAA), appetite hormones and prolactin as well as the hepatic expression of circadian clock-related genes in mice with CSD (CSD mice). Nocturnal increases in wheel-running activity and circadian rhythms of plasma prolactin concentrations were significantly disrupted in CSD mice. Hyperphagia with a decreased leptin/ghrelin ratio was found in CSD mice. Day-night fluctuations in plasma FAA contents were severely disrupted without affecting total FAA levels in CSD mice. Nocturnal increases in branched-chain amino acids such as Ile, Leu, and Val were further augmented in CSD mice, while daytime increases in Gly, Ala, Ser, Thr, Lys, Arg, His, Tyr, Met, Cys, Glu, and Asn were significantly attenuated. Importantly, the circadian expression of hepatic clock genes was completely unaffected in CSD mice. These findings suggest that circadian clock gene expression does not always reflect disordered behavior and sleep rhythms and that plasma FFA profiles could serve as a potential biomarker of circadian rhythm disorders. PMID:24971530

  15. [Effect of modafinil on electroretinograms of Lycosa tarentula in relation visual circadian rhythm (Araneae, Lycosidae)].

    PubMed

    Carricaburu, P; Muñoz-Cuevas, A

    1998-01-01

    Injections of modafinil, a drug able to induce in vertebrates an awakening effect via an effective central alpha 1-adrenergic tone, induce modifications of the amplitude and latency of electroretinograms (ERGs) in the spider Lycosa tarentula, during dark adaptation. Results of experiments are different from one eye type to another as circadian activity rhythms of the retinae also differ. Modafinil induces a decrease of diurnal amplitudes and has no effect on nocturnal amplitudes of ERGs of anterior-lateral eyes; in the case of posterior-median eyes, the amplitudes are increased in daytime as well as at night. Prazosin, antagonist of alpha 1-adrenergic receptors, injected after modafinil, induces a decrease of the amplitudes of ERGs in the same eyes. These results are discussed in relation to the visual activity of this species, both diurnal and nocturnal. The concepts of waking state versus sleep are not precisely characterized in arachnids, so that the effects of modafinil on L. tarentula may not be considered like those described in vertebrates. PMID:10101611

  16. Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

    PubMed Central

    Urbanski, Henryk F.

    2011-01-01

    Hormones play a major role in regulating behavior and physiology, and their efficacy is often dependent on the temporal pattern in which they are secreted. Significant insights into the mechanisms underlying rhythmic hormone secretion have been gained from transgenic rodent models, suggesting that many of the body's rhythmic functions are regulated by a coordinated network of central and peripheral circadian pacemakers. Some neuroendocrine rhythms are driven by transcriptional-posttranslational feedback circuits comprising ‘core clock genes’, while others represent a cyclic cascade of neuroendocrine events. This review focuses on recent data from the rhesus macaque, a non-human primate model with high clinical translation potential. With primary emphasis on adrenal and gonadal steroids, it illustrates the rhythmic nature of hormone secretion, and discusses the impact that fluctuating hormone levels have on the accuracy of clinical diagnoses and on the design of effective hormone replacement therapies in the elderly. In addition, this minireview raises awareness of the rhythmic expression patterns shown by many genes, and discusses how this could impact interpretation of data obtained from gene profiling studies, especially from nocturnal rodents. PMID:21508622

  17. Frequency spectra and cosinor for evaluating circadian rhythms in rodent data and in man during Gemini and Vostok flights.

    PubMed

    Halberg, F

    1970-01-01

    With the advent of a capability for extraterrestrial existence of lifeforms, chronobiology--the study of biological rhythms--has reached a position analogous to that of classical endocrinology. Just as an endocrine gland can be removed from an experimental animal, the effects of removal examined and the gland (or an extract) then replaced to determine whether the removal effects are reversible, lifeforms should be rigorously evaluated by rhythmometry before and during their (attempted) removal from Earth effects, as well as following their return to Earth. Methods lending themselves to such studies before, during and after travel in extraterrestrial space are illustrated herein, and their applications may be of value to preventive medicine as well as to basic science. Analyses of terrestrial control data and of restricted time series from extraterrestrial missions indicate that substantial scientific returns on Earth can be anticipated if in the routine of all mammalian space travelers provisions are made for: (1) monitoring body core temperature so as to evaluate its stable circadian rhythm--a phenomenon of interest in itself and also a reference rhythm for other variables; (2) saving aliquots from all urine samples, whereby a spectrum of diverse rhythms can be examined; (3) repeating simple performance tests, e.g., of grip strength or eye-hand coordination. Plans also should be implemented in unmanned space vehicles for explicit chronobiologic studies so designed that daily cosinor analysis can determine, e.g., whether circadian phase control or the desynchronized period length be altered as we move away from the Earth. Thus, some of the mechanisms underlying rhythms are now amenable to study on experimental mammals in unmanned space vehicles. In view of the high degree of generality of mammalian rhythms--many related to human well-being and optimal performance--and of dramatic consequences from some rhythmic variations in man, such studies deserve time and

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

    NASA Technical Reports Server (NTRS)

    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 (p<0.025). The laboratory study revealed a decrease of 2.4% in nocturnal sleep efficiency in the nap condition (p<0.025), a reduction of nocturnal Total Sleep Time (TST) by 48 mins. in the nap condition (p<0.001) which resulted primarily from significantly earlier waketimes (p<0.005), but no reliable effects on Wake After Sleep Onset (WASO), delta sleep measures, or percent stages 1 & 2. Unlike the diary study, the laboratory study

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

    NASA Astrophysics Data System (ADS)

    Basu, Priyoneel; Singaravel, Muniyandi; Haldar, Chandana

    2012-03-01

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

  20. Circadian rhythms in circulating T lymphocyte subtypes and plasma testosterone, total and free cortisol in five healthy men

    PubMed Central

    Lévi, F. A.; Canon, Chantal; Touitou, Y.; Sulon, J.; Mechkouri, M.; Ponsart, Emilie Demey; Touboul, J. P.; Vannetzel, J. M.; Mowzowicz, Irène; Reinberg, A.; Mathe, G.

    1988-01-01

    Circadian variations of circulating T lymphocyte subtypes and their possible relations with those of endogenous cortisol or testosterone were investigated in five healthy young men. Venous blood (40 ml) was obtained every 4 h for 24 h from each subject in January, March, June, August and November. Leucocyte and differential counts were measured. Mononuclear cells were isolated on Ficoll-Paque gradient, and samples were incubated with OKT3, OKT4 or OKT8 monoclonal antibodies for characterizing all T, T helper and T suppressor-cytotoxic lymphocytes respectively. The proportion of labelled lymphocytes was determined under an epifluorescence microscope and the counts of circulating lymphocyte subsets (cells/mm3) computed. Total and free cortisol and testosterone were also determined in the corresponding plasma samples. Results from analysis of variance and cosinor indicated statistically significant differences (P<0·001) as a function of both individual subject and circadian sampling time for all variables. Circadian rhythms (with a period, τ≡24 h) were validated for total, T and T helper lymphocytes and for the T helper: T suppressor-cytotoxic ratio (P<0·001), with double amplitudes (2A, total extent of variation accounted for by the fitted cosine function) ranging from 25% up to 50% of the 24 h mean (M), and acrophases (Φ, time of maximum) localized near 0100 h. A rhythm with τ≡12 h characterized circulating T suppressor-cytotoxic lymphocytes (P<0·001; 2A=36% of M; Φ=0830 and 2030 h). Circadian rhythms were also found for plasma cortisol (either total or free) and testosterone (P<0·001). No correlation was found however between time-qualified data of these hormones and the immunological variables herein investigated (162 pairs of data) whether or not a 4 h or an 8 h lag time was considered to allow for hormonal actions to operate. This suggests that neither the circadian organization of the adrenal cortex nor that of the testis play a prominent role in

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

    PubMed

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

    2016-01-01

    Salivary samples were collected over a 24-hr period from one group of six juvenile (7-12 years) and one group of three adult (24-25 years) African elephant females, Loxodonta africana, and the cortisol concentration was measured in unextracted samples by EIA. Samples were collected during May, June, and November 2012 (n = 147) using cotton swabs at 4-hr intervals from 20:00 to 20:00 of the next day (seven samples per animal in each trial). The animals are kept under standard zoo management: the herd is maintained in their indoor enclosures until 10:00 and then released into the outdoor enclosures until 21:00-21:30 (May/June) and 18:30-19:00 (November). No adult elephant bull was present at the zoo during this time. The results demonstrate a clear diurnal pattern of cortisol secretion with the lowest concentration observed at 20:00 (2.03 ± 0.08 ng/ml saliva) and the peak concentrations at 08:00 (5.26 ± 0.35 ng/ml saliva). Although the cortisol values were higher in the adult cows compared to the juvenile cows in the May-June period, the differences were not significant. However, the values obtained in November from the juvenile group were significantly higher (P < 0.05) than the concentrations measured in this group in June. In conclusion, salivary cortisol in zoo elephants follows a circadian rhythm (sleep-wake cycle) adapted to daily zoo husbandry routines. PMID:26748465

  2. The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors

    PubMed Central

    Duncan, Marilyn J.; Hester, James M.; Hopper, Jason A.; Franklin, Kathleen M.

    2010-01-01

    Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment. PMID:20525077

  3. Effects of circadian rhythm phase alteration on physiological and psychological variables: Implications to pilot performance (including a partially annotated bibliography)

    NASA Technical Reports Server (NTRS)

    Holley, D. C.; Winger, C. M.; Deroshia, C. W.; Heinold, M. P.; Edgar, D. M.; Kinney, N. E.; Langston, S. E.; Markley, C. L.; Anthony, J. A.

    1981-01-01

    The effects of environmental synchronizers upon circadian rhythmic stability in man and the deleterious alterations in performance and which result from changes in this stability are points of interest in a review of selected literature published between 1972 and 1980. A total of 2,084 references relevant to pilot performance and circadian phase alteration are cited and arranged in the following categories: (1) human performance, with focus on the effects of sleep loss or disturbance and fatigue; (2) phase shift in which ground based light/dark alteration an