Sample records for generating circadian rhythms

  1. 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

  2. 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.

  3. Role of Neuronal Membrane Events in Circadian Rhythm Generation

    Microsoft Academic Search

    Gabriella B. Lundkvist; Gene D. Block

    2005-01-01

    Circadian clock systems are composed of an input or “entrainment” pathway by which synchronization to the external environment occurs, a pacemaker responsible for generating rhythmicity, and an output or “expression” pathway through which rhythmic signals act to modulate physiology and behavior. The circadian pacemaker contains molecular feedback loops of rhythmically expressed genes and their protein products, which, through interactions, generate

  4. Biological Clocks and Circadian Rhythms

    NSDL National Science Digital Library

    Laura Robertson

    2009-02-01

    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 rhythms, they are provided with opportunities to connect learning to experiences and observations from their own lives. This article describes how to reset the biological clock of a shamrock plant while shedding light on its circadian rhythms.

  5. Circadian Rhythm Abnormalities

    PubMed Central

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

    2013-01-01

    Purpose: This article reviews the recent advances in understanding of the fundamental properties of circadian rhythms and discusses the clinical features, diagnosis, and treatment of circadian rhythm sleep disorders (CRSDs). Recent Findings: Recent evidence strongly points to the ubiquitous influence of circadian timing in nearly all physiologic functions. Thus, in addition to the prominent sleep and wake disturbances, circadian rhythm disorders are associated with cognitive impairment, mood disturbances, and increased risk of cardiometabolic disorders. The recent availability of biomarkers of circadian timing in clinical practice has improved our ability to identify and treat these CRSDs. Summary: Circadian rhythms are endogenous rhythms with a periodicity of approximately 24 hours. These rhythms are synchronized to the physical environment by social and work schedules by various photic and nonphotic stimuli. CRSDs result from a misalignment between the timing of the circadian rhythm and the external environment (eg, jet lag and shift work) or a dysfunction of the circadian clock or its afferent and efferent pathways (eg, delayed sleep-phase, advanced sleep-phase, non–24-hour, and irregular sleep-wake rhythm disorders). The most common symptoms of these disorders are difficulties with sleep onset and/or sleep maintenance and excessive sleepiness that are associated with impaired social and occupational functioning. Effective treatment for most of the CRSDs requires a multimodal approach to accelerate circadian realignment with timed exposure to light, avoidance of bright light at inappropriate times, and adherence to scheduled sleep and wake times. In addition, pharmacologic agents are recommended for some of the CRSDs. For delayed sleep-phase, non–24-hour, and shift work disorders, timed low-dose melatonin can help advance or entrain circadian rhythms; and for shift work disorder, wake-enhancing agents such as caffeine, modafinil, and armodafinil are options for the management of excessive sleepiness. PMID:23385698

  6. Neurobiology of circadian rhythm sleep disorders

    Microsoft Academic Search

    Prasanth Manthena; Phyllis C. Zee

    2006-01-01

    To adapt to a 24-hour environment, nearly all organisms, from mammals to single-celled organisms, have developed endogenous\\u000a mechanisms that generate nearly 24-hour (circadian) rhythms in physiology and behavior, the most notable being that of the\\u000a daily cycles of sleep and wake. Disruption of these circadian rhythms is often accompanied by disorders of sleep and wakefulness.\\u000a With the recent advances in

  7. [Circadian rhythms and systems biology].

    PubMed

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

    2010-01-01

    Cellular rhythms represent a field of choice for studies in system biology. The examples of circadian rhythms and of the cell cycle show how the experimental and modeling approaches contribute to clarify the conditions in which periodic behavior spontaneously arises in regulatory networks at the cellular level. Circadian rhythms originate from intertwined positive and negative feedback loops controlling the expression of several clock genes. Models can be used to address the dynamical bases of physiological disorders related to dysfunctions of the mammalian circadian clock. The cell cycle is driven by a network of cyclin-dependent kinases (Cdks). Modeled in the form of four modules coupled through multiple regulatory interactions, the Cdk network operates in an oscillatory manner in the presence of sufficient amounts of growth factor. For circadian rhythms and the cell cycle, as for other recently observed cellular rhythms, periodic behavior represents an emergent property of biological systems related to their regulatory structure. PMID:20132775

  8. Running for time: circadian rhythms and melanoma.

    PubMed

    Markova-Car, Elitza P; Juriši?, Davor; Ili?, Nataša; Kraljevi? Paveli?, Sandra

    2014-09-01

    Circadian timing system includes an input pathway transmitting environmental signals to a core oscillator that generates circadian signals responsible for the peripheral physiological or behavioural events. Circadian 24-h rhythms regulate diverse physiologic processes. Deregulation of these rhythms is associated with a number of pathogenic conditions including depression, diabetes, metabolic syndrome and cancer. Melanoma is a less common type of skin cancer yet more aggressive often with a lethal ending. However, little is known about circadian control in melanoma and exact functional associations between core clock genes and development of melanoma skin cancer. This paper, therefore, comprehensively analyses current literature data on the involvement of circadian clock components in melanoma development. In particular, the role of circadian rhythm deregulation is discussed in the context of DNA repair mechanisms and influence of UV radiation and artificial light exposure on cancer development. The role of arylalkylamine N-acetyltransferase (AANAT) enzyme and impact of melatonin, as a major output factor of circadian rhythm, and its protective role in melanoma are discussed in details. We hypothesise that further understanding of clock genes' involvement and circadian regulation might foster discoveries in the field of melanoma diagnostics and treatment. PMID:24729125

  9. 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

  10. Studying circadian rhythms in Drosophila melanogaster

    PubMed Central

    Tataroglu, Ozgur; Emery, Patrick

    2014-01-01

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

  11. CHAPTER SEVEN Circadian Rhythms, Sleep

    E-print Network

    Pennsylvania, University of

    ­wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing process that neurobiologically modulates both the homeostatic drive for sleep and waking alertnessCHAPTER SEVEN Circadian Rhythms, Sleep Deprivation, and Human Performance Namni Goel*, Mathias

  12. Circadian rhythms in the green sunfish retina.

    PubMed

    Dearry, A; Barlow, R B

    1987-05-01

    We investigated the occurrence of circadian rhythms in retinomotor movements and retinal sensitivity in the green sunfish, Lepomis cyanellus. When green sunfish were kept in constant darkness, cone photoreceptors exhibited circadian retinomotor movements; rod photoreceptors and retinal pigment epithelium (RPE) pigment granules did not. Cones elongated during subjective night and contracted during subjective day. These results corroborate those of Burnside and Ackland (1984. Investigative Ophthalmology and Visual Science. 25:539-545). Electroretinograms (ERGs) recorded in constant darkness in response to dim flashes (lambda = 640 nm) exhibited a greater amplitude during subjective night than during subjective day. The nighttime increase in the ERG amplitude corresponded to a 3-10-fold increase in retinal sensitivity. The rhythmic changes in the ERG amplitude continued in constant darkness with a period of approximately 24 h, which indicates that the rhythm is generated by a circadian oscillator. The spectral sensitivity of the ERG recorded in constant darkness suggests that cones contribute to retinal responses during both day and night. Thus, the elongation of cone myoids during the night does not abolish the response of the cones. To examine the role of retinal efferents in generating retinal circadian rhythms, we cut the optic nerve. This procedure did not abolish the rhythms of retinomotor movement or of the ERG amplitude, but it did reduce the magnitude of the nighttime phases of both rhythms. Our results suggest that more than one endogenous oscillator regulates the retinal circadian rhythms in green sunfish. Circadian signals controlling the rhythms may be either generated within the eye or transferred to the eye via a humoral pathway. PMID:3598559

  13. Circadian rhythms in the green sunfish retina

    PubMed Central

    1987-01-01

    We investigated the occurrence of circadian rhythms in retinomotor movements and retinal sensitivity in the green sunfish, Lepomis cyanellus. When green sunfish were kept in constant darkness, cone photoreceptors exhibited circadian retinomotor movements; rod photoreceptors and retinal pigment epithelium (RPE) pigment granules did not. Cones elongated during subjective night and contracted during subjective day. These results corroborate those of Burnside and Ackland (1984. Investigative Ophthalmology and Visual Science. 25:539-545). Electroretinograms (ERGs) recorded in constant darkness in response to dim flashes (lambda = 640 nm) exhibited a greater amplitude during subjective night than during subjective day. The nighttime increase in the ERG amplitude corresponded to a 3-10-fold increase in retinal sensitivity. The rhythmic changes in the ERG amplitude continued in constant darkness with a period of approximately 24 h, which indicates that the rhythm is generated by a circadian oscillator. The spectral sensitivity of the ERG recorded in constant darkness suggests that cones contribute to retinal responses during both day and night. Thus, the elongation of cone myoids during the night does not abolish the response of the cones. To examine the role of retinal efferents in generating retinal circadian rhythms, we cut the optic nerve. This procedure did not abolish the rhythms of retinomotor movement or of the ERG amplitude, but it did reduce the magnitude of the nighttime phases of both rhythms. Our results suggest that more than one endogenous oscillator regulates the retinal circadian rhythms in green sunfish. Circadian signals controlling the rhythms may be either generated within the eye or transferred to the eye via a humoral pathway. PMID:3598559

  14. [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

  15. Circadian rhythm of photosynthesis in

    Microsoft Academic Search

    H Schubert; S Gerbersdorf; E Titlyanov; T Titlyanova; M Granbom; C Pape; K Lüning

    2004-01-01

    Various processes in the output pathway of the circadian clock are thought to act as important clock targets resulting in the circadian rhythms of photosynthesis observed in various algae. Examples of such processes are synchronization of the cell cycle, pigmentation, and light or dark reaction of photosynthesis. The newly detected, robust photosynthetic circadian rhythm in the red macroalga Kappaphycus alvarezii

  16. [Circadian rhythms in body temperature and sleep].

    PubMed

    Honma, Ken-ichi

    2013-12-01

    A 24 hour variation of core body temperature in humans is primarily regulated by the endogenous circadian pacemaker located in the suprachiasmatic nucleus. And the expression of circadian rhythm is modified by the thermoregulatory mechanism controlling heat production and heat loss, which also show circadian rhythms. On the other hand, circadian rhythms in sleep-wakefulness are expressed by two independent but mutually coupled oscillators, the circadian pacemaker and the oscillator specific to sleep-wakefulness. However, neither the mechanism nor the site of oscillation of the latter is known. The time cues for these two oscillators are different. They are usually but frequently uncoupled under free-running conditions. Body temperature and sleep-wakefulness influence the counterpart in various extents, exerting masking effects on either circadian rhythm. PMID:24437258

  17. 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

  18. A proposal for robust temperature compensation of circadian rhythms.

    PubMed

    Hong, Christian I; Conrad, Emery D; Tyson, John J

    2007-01-23

    The internal circadian rhythms of cells and organisms coordinate their physiological properties to the prevailing 24-h cycle of light and dark on earth. The mechanisms generating circadian rhythms have four defining characteristics: they oscillate endogenously with period close to 24 h, entrain to external signals, suffer phase shifts by aberrant pulses of light or temperature, and compensate for changes in temperature over a range of 10 degrees C or more. Most theoretical descriptions of circadian rhythms propose that the underlying mechanism generates a stable limit cycle oscillation (in constant darkness or dim light), because limit cycles quite naturally possess the first three defining properties of circadian rhythms. On the other hand, the period of a limit cycle oscillator is typically very sensitive to kinetic rate constants, which increase markedly with temperature. Temperature compensation is therefore not a general property of limit cycle oscillations but must be imposed by some delicate balance of temperature dependent effects. However, "delicate balances" are unlikely to be robust to mutations. On the other hand, if circadian rhythms arise from a mechanism that concentrates sensitivity into a few rate constants, then the "balancing act" is likely to be more robust and evolvable. We propose a switch-like mechanism for circadian rhythms that concentrates period sensitivity in just two parameters, by forcing the system to alternate between a stable steady state and a stable limit cycle. PMID:17229851

  19. Circadian rhythms, diet, and neuronal excitability.

    PubMed

    Allen, Charles N

    2008-11-01

    Many aspects of normal biological function are governed by circadian rhythms, including metabolism, ingestive behaviors, and sleep-wake cycles. Certain pathological processes as well are also affected by the circadian rhythms. For example, it is well known that seizure occurrence can be influenced by the sleep-wake cycle. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with proven efficacy in the treatment of intractable epilepsies. While the mechanisms underlying the clinical effects of the KD remain unclear, there are emerging links between circadian rhythms and KD action. Such factors should be considered when planning and administering the KD to patients. PMID:19049609

  20. Circadian Rhythms: A Circadian Loop asSIRTs Itself

    NSDL National Science Digital Library

    Herman Wijnen (University of Virginia; Department of Biology)

    2009-05-01

    Access to the article is free, however registration and sign-in are required: Daily time keeping in many organisms depends on internal circadian clocks that temporally organize biological functions relative to each other as well as the environment. These clocks generate rhythms in physiology and behavior by using circuits of gene expression that are organized in negative-feedback loops. Two studies in this issue, by Nakahata et al. and Ramsey et al., propose the addition of a new negative-feedback loop to this circuitry that involves the metabolite nicotinamide adenine dinucleotide (NAD+) and the protein SIRTUIN1 (SIRT1). The new loop suggests connections between the circadian clock and SIRT1-dependent functions associated with cell survival, development, inflammation, and metabolism.

  1. Circadian Metabolic Rhythms in Obese Children

    Microsoft Academic Search

    Jehan-François Desjeux; Catherine Gernez-Lestradet; Ingeborg Deschamps; Sylvine Machinot; Frédérique Rolland; Henri Lestradet

    1982-01-01

    Obese children display constant hyperinsulinism and, frequently, hyperphagia. In animals, lesions of the hypothalamic system affect simultaneously the circadian rhythm of insulin secretion and of food intake. In this study, circadian metabolic rhythm was examined in obese and non-obese children, by two different protocols. (1) Oral glucose tolerance tests (OGTT) were carried out at 9 a.m. and 3 p.m. on

  2. Circadian rhythms of locomotor activity in Drosophila

    Microsoft Academic Search

    André Klarsfeld; Jean-Christophe Leloup; François Rouyer

    2003-01-01

    Drosophila is by far the most advanced model to understand the complex biochemical interactions upon which circadian clocks rely. Most of the genes that have been characterized so far were isolated through genetic screens using the locomotor activity rhythms of the adults as a circadian output. In addition, new techniques are available to deregulate gene expression in specific cells, allowing

  3. 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

  4. Analysis of circadian rhythms in embryonic stem cells.

    PubMed

    Paulose, Jiffin K; Rucker, Edmund B; Cassone, Vincent M

    2015-01-01

    Recent attention on the early development of circadian rhythms has yielded several avenues of potential study regarding molecular and physiological rhythms in embryonic stem cells (ESCs) and their derivatives. While general guidelines of experimental design are-as always-applicable, there are certain idiosyncrasies with respect to experiments involving circadian rhythms that will be addressed. ESCs provide a number of challenges to the circadian biologist: growth rates are normally much higher than in established cell culture systems, the cells' innate drive towards differentiation and the lack of known synchronizing input pathways are a few examples. Some of these challenges can be addressed post hoc, such as normalization to total RNA or protein for transcript abundance studies. Most others, as outlined here, require special handling of the samples before and during experimentation in order to preserve any potential circadian oscillation that is present. Failure to do so may result in a disruption of endogenous oscillation(s) or, potentially worse, generation of an artificial oscillation that has no biological basis. This chapter begins with cultured ESCs, derived from primary blastocysts or in the form of cell lines, and outlines two methods of measuring circadian rhythms: the 2DG method of measuring glucose uptake (Sokoloff et al. J Neurochem 28:897-916, 1977) and real-time measurement of molecular rhythms using transgenic bioluminescence (Yoo et al. Proc Natl Acad Sci U S A 101:5339-5346, 2004). PMID:25388387

  5. Cannabinoids and hamster circadian activity rhythms.

    PubMed

    Sanford, Anna E; Castillo, Elizabeth; Gannon, Robert L

    2008-07-30

    Circadian activity rhythms in hamsters are entrained to the daily light:dark cycle by photic information arriving from the retina to the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals. The effects of light on adjusting the timing of the circadian pacemaker is modified, both positively and negatively, by a variety of transmitter systems, but the effects of endocannabinoids have not been reported. Therefore, in this study we evaluated cannabinoids specific for the cannabinoid type 1 receptor (CB(1)) for their ability to modulate light-induced phase advances in hamster circadian activity rhythms. All compounds were administered intraperitoneally. The CB(1) agonist CP55940 potently inhibited light-induced phase shifts with near 90% inhibition achieved with a dose of 0.125 mg/kg. The inhibitory effect of CP55940 was partially reversed by the CB(1) antagonist LY320135 and completely reversed with 1 mg/kg of the CB(1) antagonist AM 251. Neither LY320135 nor AM 251 had any effect on light-induced phase shifts when administered alone. Further evidence for CB(1) involvement in hamster circadian rhythms was provided by immunohistochemical detection of CB(1) receptors in four separate nuclei comprising the principal components of the hamster circadian system: the suprachiasmatic nucleus, intergeniculate leaflet of the thalamus, and dorsal and median raphe nuclei. Altogether these data indicate that the endocannabinoid system has the capability to modulate circadian rhythms in the hamster and cannabis use should be evaluated for adverse effects on circadian rhythms in humans. PMID:18582849

  6. Neuroanatomy of the extended circadian rhythm system.

    PubMed

    Morin, Lawrence P

    2013-05-01

    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

  7. 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

  8. Addressing circadian rhythm disturbances in depressed patients

    Microsoft Academic Search

    RW Lam

    2008-01-01

    AbstractDesynchronisation of normal circadian rhythms, including the sleep–wake rhythm, is common in major depressive disorder (MDD). The association between sleep disturbances and depression has long been recognised. Disturbed sleep is a diagnostic criterion for MDD, and insomnia commonly precedes the onset of symptomatic mood disorders. Disruptions of the sleep–wake cycle (sleep architecture and timing) are residual symptoms that may prevent

  9. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease

    Microsoft Academic Search

    Katharina Wulff; Silvia Gatti; Joseph G. Wettstein; Russell G. Foster

    2010-01-01

    Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory

  10. The use of fluorescent proteins to analyze circadian rhythms.

    PubMed

    Shor, Ekaterina; Hassidim, Miriam; Green, Rachel M

    2014-01-01

    Compared with luciferase which is widely used as a reporter for circadian rhythms in Arabidopsis thaliana, available fluorescent markers are generally too stable to allow circadian oscillations to be measured. However, we have developed a technique to use the nuclear localization of circadian-controlled transcription factors fused to a fluorescent reporter as a means of measuring circadian rhythms. This technique has the advantage of being suitable for analyzing rhythms at the level of individual cells and in living plants. PMID:24792054

  11. 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.

  12. 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

  13. 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...

  14. 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 ~1gcm(-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 10dpa, 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 26dpa, 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

  15. 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

  16. Circadian rhythms synchronize mitosis in Neurospora crassa

    PubMed Central

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

    2014-01-01

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

  17. 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.

  18. 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

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

    PubMed

    Silver, Rae; Kriegsfeld, Lance J

    2014-06-01

    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

  20. 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.

  1. [Dyslipidemia induced disorder of circadian rhythm].

    PubMed

    Shimba, Shigeki

    2013-12-01

    Several epidemiological studies have suggested that the perturbation of circadian rhythm has adverse metabolic consequences (e.g., dyslipidemia) in humans. At the molecular level, circadian rhythms are encoded by an autoregulatory loop composed of a set of transcription activators (BMAL1/CLOCK) that induce expression of repressors (PER/CRY). The mammalian molecular clock is not only expressed within the master suprachiasmatic nucleus pacemaker neurons, but also within nearly all cells. In addition to this core loop, BMAL1/CLOCK also induce expression of the orphan nuclear hormone receptor, which modulates Bmal1 transcription. Disruption of clock genes results in metabolic deregulation in mice. In this article, the roles of clock genes in the regulation of metabolism were summarized based on the phenotypes of the knockout mice. PMID:24437265

  2. Circadian rhythms in lizards: phase response curve for melatonin.

    PubMed

    Underwood, H

    1986-01-01

    Single biweekly injections of melatonin were administered to lizards (Sceloporus occidentalis) free-running (exhibiting their endogenous circadian activity rhythm) in constant dim illumination. The injections caused phase shifts in the activity rhythm whose magnitude and direction were a function of the time of the melatonin injections, relative to activity onsets. Plotting the direction and amount of phase shift versus the time (phase) at which the injection was given generates a phase-response curve (PRC). The PRC shows that injections administered between midsubjective day and early subjective night (6-15 hr after activity onset) elicit phase advances in the activity rhythm, whereas injections given at other phases of the activity cycle induce phase delays. The existence of a PRC for melatonin suggests that the daily endogenous rhythm of melatonin (i.e., of pineal origin) may be involved in phasing, or entraining, the circadian system of lizards. The shape of the PRC also allows predictions as to the effects of continuous exogenous melatonin administration on the period of free-running activity rhythms as well as on the mechanism of entrainment of activity rhythms to daily melatonin injections. PMID:3723331

  3. N-NITROSOMELATONIN ENHANCES PHOTIC SYNCHRONIZATION OF MAMMALIAN CIRCADIAN RHYTHMS

    PubMed Central

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

    2014-01-01

    Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide-donor, N-nitrosomelatonin, to enhance the photic synchronization of circadian rhythms in hamsters. The intraperitoneal administration of this drug before a sub-saturating light pulse at circadian time 18 generated a two-fold increase of locomotor rhythm phase-advances, having no effect over saturating light pulses. This potentiation was also obtained even when inhibiting suprachiasmatic nitric oxide synthase activity. However, N-nitrosomelatonin had no effect on light-induced phase delays at circadian time 14. The photic-enhancing effects were correlated with an increased suprachiasmatic immunoreactivity of cFOS and PER1. Moreover, in vivo nitric oxide release by N-nitrosomelatonin was verified by measuring nitrate and nitrite levels in suprachiasmatic nuclei homogenates. The compound also accelerated resynchronization to an abrupt 6-h advance in the light:dark cycle (but not resynchronization to a 6-hour delay). Here we demonstrate the chronobiotic properties of N-nitrosomelatonin, emphasizing the importance of nitric oxide-mediated transduction for circadian phase advances. PMID:24261470

  4. [Stress, cancer and circadian rhythm of melatonin].

    PubMed

    Kwiatkowski, F; Abrial, C; Gachon, F; Chevrier, R; Curé, H; Chollet, P

    2005-06-01

    Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments. PMID:15939136

  5. Circadian rhythms, sleep, and performance in space

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

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

  6. 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 performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed. PMID:15943202

  7. 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

  8. Neural regulation of the hepatic circadian rhythm.

    PubMed

    Shibata, Shigenobu

    2004-09-01

    A microarray analysis experiment has revealed that there are many genes, including so-called clock genes, expressing a circadian rhythm in the liver. The clock genes mentioned above are expressed not only in the suprachiasmatic nucleus (SCN) of the hypothalamus, where the master clock exists, but also in other brain regions and various peripheral tissues. In the liver, clock genes are abundantly expressed and show a clear circadian rhythm. Thus, clock genes seem to play a critical role in the molecular clockworks of both the SCN and the liver. Although oscillation of clock genes in the liver is controlled under the circadian clock mechanism in the SCN, we do not know the resetting signals on liver clock function. Over the past few years, use of the pseudorabies virus, a transsynaptic tract tracer, has allowed us to map neural connections between the SCN and peripheral tissues in several physiological systems. Communication between the SCN and peripheral tissues occurs through autonomic nervous systems involving the sympathetic and parasympathetic neurons. This review mainly describes both anatomical and physiological experiments to reveal the sympathetic control over liver clock function. Although further study is necessary to produce the precise mechanism underlying neural control of liver clock systems, evolution of this mechanism will help our understanding of liver clock functions such as drug metabolism and energy metabolism. PMID:15382011

  9. Stochastic Simulation of Delay-Induced Circadian Rhythms in

    Microsoft Academic Search

    Zhouyi Xu; Xiaodong Cai

    2009-01-01

    Abstract Circadian rhythms are ubiquitous in all eukaryotes and some prokaryotes. Several compu- tational models with or without time delays have been developed for circadian rhythms. Exact stochastic simulations have been carried out for several models without time delays, but no exact stochastic simulation has been done for models with delays. In this paper, we proposed a detailed and a

  10. Circadian Rhythms, Aging, and Life Span in Mammals

    NSDL National Science Digital Library

    Oren Froy (The Hebrew University of Jerusalem Institute of Biochemistry, Food Science and Nutrition)

    2011-08-01

    Resetting the circadian clock leads to well being and increased life span, whereas clock disruption is associated with aging and morbidity. Increased longevity and improved health can be achieved by different feeding regimens that reset circadian rhythms and may lead to better synchrony in metabolism and physiology. This review focuses on recent findings concerning the relationships between circadian rhythms, aging attenuation, and life-span extension in mammals.

  11. Addressing circadian rhythm disturbances in depressed patients.

    PubMed

    Lam, R W

    2008-09-01

    Desynchronisation of normal circadian rhythms, including the sleep-wake rhythm, is common in major depressive disorder (MDD). The association between sleep disturbances and depression has long been recognised. Disturbed sleep is a diagnostic criterion for MDD, and insomnia commonly precedes the onset of symptomatic mood disorders. Disruptions of the sleep-wake cycle (sleep architecture and timing) are residual symptoms that may prevent the attainment of high-quality remission and delay recovery from MDD. Therefore, early recognition and treatment of sleep disturbances may be important for the treatment and prevention of recurrent depression. Evidence suggests that melatonergic (MT(1) and MT(2)) and the 5-HT(2C) serotonergic receptor subtypes are important modulators of circadian rhythmicity. Agomelatine is the first melatonergic antidepressant; an agonist of melatonin MT(1) and MT(2) receptors, with additional antagonist properties at the 5-HT(2C) receptors. Agomelatine combines antidepressant efficacy including quality and efficiency of sleep, with a more favourable side-effect profile than current antidepressant treatments, including neutral effects on sexual function, bodyweight and the absence of discontinuation symptoms. These positive features provide a novel approach to the treatment of depression and the attainment of high-quality remission in MDD. PMID:18753278

  12. Circadian rhythms in rheumatology - a glucocorticoid perspective

    PubMed Central

    2014-01-01

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

  13. 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

  14. 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

  15. Circadian Rhythms in Prokaryotes: Luciferase as a Reporter of Circadian Gene Expression in Cyanobacteria

    Microsoft Academic Search

    Takao Kondo; Carl A. Strayer; Resham D. Kulkarni; Walter Taylor; Masahiro Ishiura; Susan S. Golden; Carl Hirschie Johnson

    1993-01-01

    We have used a luciferase reporter gene and continuous automated monitoring of bioluminescence to demonstrate unequivocally that cyanobacteria exhibit circadian behaviors that are fundamentally the same as circadian rhythms of eukaryotes. We also show that these rhythms can be studied by molecular methods in Synechococcus sp. PCC7942, a strain for which genetic transformation is well established. A promoterless segment of

  16. 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.

  17. 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

  18. Synergistic Interactions between the Molecular and Neuronal Circadian Networks Drive Robust Behavioral Circadian Rhythms in Drosophila melanogaster

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

  20. 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

  1. Endogenous circadian rhythm in human motor activity uncoupled from circadian influences

    E-print Network

    Stanley, H. Eugene

    -mediated changes in motor activity or whether activ- ity and heart rate dynamics are decoupled across the circadian influences key physiologic functions, such as body temperature and heart rate, and is nor- mally synchronizedEndogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac

  2. Analysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm

    PubMed Central

    Yan, Jun; Wang, Haifang; Liu, Yuting; Shao, Chunxuan

    2008-01-01

    Circadian rhythm is fundamental in regulating a wide range of cellular, metabolic, physiological, and behavioral activities in mammals. Although a small number of key circadian genes have been identified through extensive molecular and genetic studies in the past, the existence of other key circadian genes and how they drive the genomewide circadian oscillation of gene expression in different tissues still remains unknown. Here we try to address these questions by integrating all available circadian microarray data in mammals. We identified 41 common circadian genes that showed circadian oscillation in a wide range of mouse tissues with a remarkable consistency of circadian phases across tissues. Comparisons across mouse, rat, rhesus macaque, and human showed that the circadian phases of known key circadian genes were delayed for 4–5 hours in rat compared to mouse and 8–12 hours in macaque and human compared to mouse. A systematic gene regulatory network for the mouse circadian rhythm was constructed after incorporating promoter analysis and transcription factor knockout or mutant microarray data. We observed the significant association of cis-regulatory elements: EBOX, DBOX, RRE, and HSE with the different phases of circadian oscillating genes. The analysis of the network structure revealed the paths through which light, food, and heat can entrain the circadian clock and identified that NR3C1 and FKBP/HSP90 complexes are central to the control of circadian genes through diverse environmental signals. Our study improves our understanding of the structure, design principle, and evolution of gene regulatory networks involved in the mammalian circadian rhythm. PMID:18846204

  3. Treatment of circadian rhythm disorders--melatonin.

    PubMed

    Arendt, J; Deacon, S

    1997-03-01

    Melatonin has clear acute and delayed effects on sleep and circadian rhythms. Decrements in core temperature and alertness have been found at different times of day following low pharmacological and physiological doses of melatonin. When correctly timed, melatonin induces both phase advances and phase delays of the circadian system in humans. When timed to advance, the decrement in temperature and alertness and the degree of shift are closely related to dose. In both simulation and field studies, correctly timed melatonin can alleviate some of the problems of shiftwork and jet lag, notably enhancing sleep and alertness and hastening adaptation of rhythms to the imposed schedule. Performance effects and changes in sleep architecture need to be fully evaluated. The optimization of dose and formulation is also an area that requires further work. Whether or not recently developed melatonin analogs (72) will prove more or less useful than melatonin in adapting to phase shift remains to be seen. If incorrectly timed, melatonin has the potential to induce deleterious effects. While short-term studies indicate that it has very low toxicity, there are no long-term safety data. All of the studies reported here concern healthy adult volunteers and the use of a preparation licensed for human experimental use and available on a named patient basis on prescription. There are no data on uncontrolled preparations available over the counter in some countries. Its effects in pregnancy, interaction with other medications, and many other considerations remain to be addressed. Thus, while melatonin is useful in well-controlled conditions, the indiscriminate use of unlicensed preparations is not advisable. PMID:9095378

  4. Circadian rhythms in insect disease vectors

    PubMed Central

    Meireles-Filho, Antonio Carlos Alves; Kyriacou, Charalambos Panayiotis

    2013-01-01

    Organisms from bacteria to humans have evolved under predictable daily environmental cycles owing to the Earth’s rotation. This strong selection pressure has generated endogenous circadian clocks that regulate many aspects of behaviour, physiology and metabolism, anticipating and synchronising internal time-keeping to changes in the cyclical environment. In haematophagous insect vectors the circadian clock coordinates feeding activity, which is important for the dynamics of pathogen transmission. We have recently witnessed a substantial advance in molecular studies of circadian clocks in insect vector species that has consolidated behavioural data collected over many years, which provided insights into the regulation of the clock in the wild. Next generation sequencing technologies will facilitate the study of vector genomes/transcriptomes both among and within species and illuminate some of the species-specific patterns of adaptive circadian phenotypes that are observed in the field and in the laboratory. In this review we will explore these recent findings and attempt to identify potential areas for further investigation. PMID:24473802

  5. Circadian rhythms in insect disease vectors.

    PubMed

    Meireles-Filho, Antonio Carlos Alves; Kyriacou, Charalambos Panayiotis

    2013-01-01

    Organisms from bacteria to humans have evolved under predictable daily environmental cycles owing to the Earth's rotation. This strong selection pressure has generated endogenous circadian clocks that regulate many aspects of behaviour, physiology and metabolism, anticipating and synchronising internal time-keeping to changes in the cyclical environment. In haematophagous insect vectors the circadian clock coordinates feeding activity, which is important for the dynamics of pathogen transmission. We have recently witnessed a substantial advance in molecular studies of circadian clocks in insect vector species that has consolidated behavioural data collected over many years, which provided insights into the regulation of the clock in the wild. Next generation sequencing technologies will facilitate the study of vector genomes/transcriptomes both among and within species and illuminate some of the species-specific patterns of adaptive circadian phenotypes that are observed in the field and in the laboratory. In this review we will explore these recent findings and attempt to identify potential areas for further investigation. PMID:24473802

  6. Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts

    Microsoft Academic Search

    Yi Qu; Meng Mao; Xihong Li; Yanyou Liu; Jianmin Ding; Zhou Jiang; Chaomin Wan; Lin Zhang; Zhengrong Wang; Dezhi Mu

    2008-01-01

    The synchronization of the circadian signals to external or suprachiasmatic nucleus stimulation in the peripheral clocks is\\u000a essential for maintaining the usual function of human body. However, aging will disrupt the synchronization of peripheral\\u000a circadian rhythms, thus leading to some age-associated diseases. Up to now, little is known about the modification of the\\u000a oscillatory rhythms in aged cells. A recent

  7. Circadian Rhythm of Cyanothece RF1( Synechococcus RF1)

    Microsoft Academic Search

    Tan-Chi Huang; Rong-Fong Lin

    \\u000a Cyanothece RF-1 (Synechococcus RF-1) is a unicellular N2-fixing cyano-bacterium isolated from a rice field in Taiwan. The activity of nitrogen fixation in RF-1 revealed circadian\\u000a rhythms when the cultures were placed in continuous light after diurnal regimen. RF-1 is the first prokaryotic organism shown\\u000a to exhibit cir-cadian rhythms regulated by a “biological clock.” In addition to nitrogen fixation, the uptake

  8. Circadian Rhythm Profiles in Women with Night Eating Syndrome

    Microsoft Academic Search

    Namni Goel; Albert J. Stunkard; Naomi L. Rogers; Hans P. A. Van Dongen; Kelly C. Allison; John P. OReardon; Rexford S. Ahima; David E. Cummings; Moonseong Heo; David F. Dinges

    2009-01-01

    Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings accompanied by food intake. Patients with NES display a delayed circadian pattern of food intake but retain a normal sleep-wake cycle. These characteristics initiated the current study, in which the phase and amplitude of behavioral and neuroendocrine circadian rhythms in patients with NES were evaluated. Fifteen women with

  9. CLINICAL REVIEW Circadian rhythms, sleep, and substance abuse

    E-print Network

    Schumaker, Mark

    CLINICAL REVIEW Circadian rhythms, sleep, and substance abuse Brant P. Hasler a,*, Leisha J. Smith abuse Substance dependence Addiction Alcohol Opiates Methamphetamine Cocaine s u m m a r y Substance in knowledge persist, particularly regarding whether circadian disturbance leads to substance abuse

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

    PubMed

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

    1991-12-01

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

  11. Inactivation of Cipc alters the expression of Per1 but not circadian rhythms in mice.

    PubMed

    Qu, ZhiPeng; Wang, XiaoHan; Liu, DongChuan; Gao, Xiang; Xu, Ying

    2015-04-01

    Circadian clocks are comprised of self-sustained transcriptional/translational feedback loops, which regulate the rhythms of physiology and behavior in mammals. CLOCK-interacting protein, Circadian (CIPC), has been indicated as an additional negative-feedback regulator of the circadian clock in vitro, although its physiological roles in circadian clock are unknown. Here, we generated Cipc homozygous knockout (Cipc (-/-)) mice and assessed the resultant circadian phenotypes. Surprisingly, the mRNA expression profiles of core clock genes in the liver of Cipc (-/-) mice showed no significant differences from that in wild-type mice except for Per1. Cipc (-/-) mice displayed normal locomotor rhythm and entrained activity pattern in both 12:12 light-dark cycle and constant dark cycle. Furthermore, deletion of Cipc in lungs and adipose tissues did not influence their peripheral clock. The results from this work provided more conclusive data suggesting that CIPC is not critically required for basic clock function. PMID:25862660

  12. JOURNAL OF BIOLOGICAL RHYTHMS / December 2001Gorman et al. / SPLIT CIRCADIAN RHYTHMS IN HAMSTERS Temporal Reorganization of the Suprachiasmatic

    E-print Network

    Lee, Theresa

    JOURNAL OF BIOLOGICAL RHYTHMS / December 2001Gorman et al. / SPLIT CIRCADIAN RHYTHMS IN HAMSTERS Temporal Reorganization of the Suprachiasmatic Nuclei in Hamsters with Split Circadian Rhythms Michael R. The refinement of a procedure for splitting hamster rhythms in a 24-h light- dark:light-dark cycle has enabled

  13. The development of circadian rhythm of human body temperature

    Microsoft Academic Search

    Kazuo Abe; Hideki Sasaki; Kyoko Takebayashi; Seki Fukui; Haruo Nambu

    1978-01-01

    Daily periodic changes of body temperature were examined in 138 subjects ranging in age between 5 days and 44 years. Whereas the circadian rhythm of human body temperature was not discerned in newborn babies, body temperatures were higher during daytime than during nighttime in infants over one month. Temperature rhythm similar to that of adults, with respect to phase, was

  14. Neuronal circadian rhythm: phase shifting by a protein synthesis inhibitor.

    PubMed

    Jacklet, J W

    1977-10-01

    A potent inhibitor of protein synthesis, anisomycin, was applied (10(-6)M) in 6-hour pulses at specific phases in the circadian rhythm of endogenous compound action potential (CAP) activity recorded from the eye of Aplysia in vitro. The phase of the circadian rhythm was systematically advanced or delayed (up to 15 hours) depending on the specific phase at which the pulse was applied. The resultant phase response curve implicates protein synthesis on the eukaryotic ribosome as a fundamental part of the controlling processes that constitutes the circadian clock. PMID:897685

  15. Dopaminergic Regulation of Circadian Food Anticipatory Activity Rhythms in the Rat

    PubMed Central

    Smit, Andrea N.; Patton, Danica F.; Michalik, Mateusz; Opiol, Hanna; Mistlberger, Ralph E.

    2013-01-01

    Circadian activity rhythms are jointly controlled by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) and by food-entrainable circadian oscillators (FEOs) located elsewhere. The SCN mediates synchrony to daily light-dark cycles, whereas FEOs generate activity rhythms synchronized with regular daily mealtimes. The location of FEOs generating food anticipation rhythms, and the pathways that entrain these FEOs, remain to be clarified. To gain insight into entrainment pathways, we developed a protocol for measuring phase shifts of anticipatory activity rhythms in response to pharmacological probes. We used this protocol to examine a role for dopamine signaling in the timing of circadian food anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats then received the D2 agonist quinpirole (1 mg/kg IP) alone or after pretreatment with the dopamine synthesis inhibitor ?-methylparatyrosine (AMPT). By comparison with vehicle injections, quinpirole administered 1-h before lights-off (19h before mealtime) induced a phase delay of activity onset prior to the next meal. Delay shifts were larger in rats pretreated with AMPT, and smaller following quinpirole administered 4-h after lights-on. A significant shift was not observed in response to the D1 agonist SKF81297. These results provide evidence that signaling at D2 receptors is involved in phase control of FEOs responsible for circadian food anticipatory rhythms in rats. PMID:24312417

  16. 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 CK1?/? 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 CK1?/? 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

  17. ‘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

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

    PubMed Central

    Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

    2013-01-01

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

  19. Circadian Rhythms of Ethylene Emission in Arabidopsis1[w

    PubMed Central

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

    2004-01-01

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

  20. Endogenous circadian rhythm in electroretinogram of free-moving lizards.

    PubMed

    Fowlkes, D H; Karwoski, C J; Proenza, L M

    1984-01-01

    An endogenous circadian rhythm in the electroretinogram (ERG) of free-moving lizards, Anolis carolinensis, can be demonstrated in experiments lasting up to eight days. The rhythm does not appear to arise from processes that could modulate the amount of light reaching the photoreceptors. Moreover, since the rhythm is well-developed in the b-wave, but not a-wave, the direct modulation of neural processes proximal to the photoreceptors may be involved. Lastly, this rhythm may have ecological significance for this diurnally active species, since the largest responses occur at projected midday. PMID:6698728

  1. The Impact of HIF1? on the Per2 Circadian Rhythm in Renal Cancer Cell Lines

    PubMed Central

    Okabe, Takashi; Kumagai, Megumi; Nakajima, Yoshihiro; Shirotake, Suguru; Kodaira, Kiichiro; Oyama, Masafumi; Ueno, Munehisa; Ikeda, Masaaki

    2014-01-01

    In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy. In this study, the rhythmic expression of the Per2 gene was not detectable in renal cancer cell lines, with the exception of Caki-2 cells. In Caki-2 cells, HIF1? increased the amplitude of Per2 oscillation by directly binding to the HIF-binding site located on the Per2 promoter. These results indicate that HIF1? may enhance the amplitude of the Per2 circadian rhythm. PMID:25333958

  2. Circadian Rhythm Profiles in Women with Night Eating Syndrome

    PubMed Central

    Goel, Namni; Stunkard, Albert J.; Rogers, Naomi L.; Van Dongen, Hans P.A.; Allison, Kelly C.; O’Reardon, John P.; Ahima, Rexford S.; Cummings, David E.; Heo, Moonseong; Dinges, David F.

    2012-01-01

    Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings accompanied by food intake. Patients with NES display a delayed circadian pattern of food intake but retain a normal sleep-wake cycle. These characteristics initiated the current study, in which the phase and amplitude of behavioral and neuroendocrine circadian rhythms in patients with NES were evaluated. Fifteen women with NES (mean age ± SD, 40.8 ± 8.7 y) and 14 control subjects (38.6 ± 9.5 y) were studied in the laboratory for 3 nights, with food intake measured daily. Blood also was collected for 25 h (every 2 h from 0800 to 2000 h, and then hourly from 2100 to 0900 h) and assayed for glucose and 7 hormones (insulin, ghrelin, leptin, melatonin, cortisol, thyroid-stimulating hormone [TSH] and prolactin). Statistical analyses utilized linear mixed-effects cosinor analysis. Control subjects displayed normal phases and amplitudes for all circadian rhythms. In contrast, patients with NES showed a phase delay in the timing of meals, and delayed circadian rhythms for total caloric, fat, and carbohydrate intake. In addition, phase delays of 1.0 to 2.8 h were found in 2 food-regulatory rhythms—leptin and insulin—and in the circadian melatonin rhythm (with a trend for a delay in the circadian cortisol rhythm). In contrast, circulating levels of ghrelin, the primary hormone that stimulates food intake, were phase advanced by 5.2 h. The glucose rhythm showed an inverted circadian pattern. Patients with NES also showed reduced amplitudes in the circadian rhythms of food intake, cortisol, ghrelin, and insulin, but increased TSH amplitude. Thus, patients with NES demonstrated significant changes in the timing and amplitude of various behavioral and physiological circadian markers involved in appetite and neuroendocrine regulation. As such, NES may result from dissociations between central (suprachiasmatic nucleus) timing mechanisms and putative oscillators elsewhere in the central nervous system or periphery, such as the stomach or liver. Considering these results, chronobiologic treatments for NES such as bright light therapy may be useful. Indeed, bright light therapy has shown efficacy in reducing night eating in case studies and should be evaluated in controlled clinical trials. PMID:19150931

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

    PubMed

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

    2012-12-26

    The circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is a hierarchical multioscillator system in which neuronal networks play crucial roles in expressing coherent rhythms in physiology and behavior. However, our understanding of the neuronal network is still incomplete. Intracellular calcium mediates the input signals, such as phase-resetting stimuli, to the core molecular loop involving clock genes for circadian rhythm generation and the output signals from the loop to various cellular functions, including changes in neurotransmitter release. Using a unique large-scale calcium imaging method with genetically encoded calcium sensors, we visualized intracellular calcium from the entire surface of SCN slice in culture including the regions where autonomous clock gene expression was undetectable. We found circadian calcium rhythms at a single-cell level in the SCN, which were topologically specific with a larger amplitude and more delayed phase in the ventral region than the dorsal. The robustness of the rhythm was reduced but persisted even after blocking the neuronal firing with tetrodotoxin (TTX). Notably, TTX dissociated the circadian calcium rhythms between the dorsal and ventral SCN. In contrast, a blocker of gap junctions, carbenoxolone, had only a minor effect on the calcium rhythms at both the single-cell and network levels. These results reveal the topological specificity of the circadian calcium rhythm in the SCN and the presence of coupled regional pacemakers in the dorsal and ventral regions. Neuronal firings are not necessary for the persistence of the calcium rhythms but indispensable for the hierarchical organization of rhythmicity in the SCN. PMID:23213253

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

    PubMed

    Fifel, Karim; Cooper, Howard M

    2014-11-01

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

  5. 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.

  6. Inositols affect the mating circadian rhythm of Drosophila melanogaster.

    PubMed

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

    2015-01-01

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

  7. Nicotine phase-advances the circadian neuronal activity rhythm in rat suprachiasmatic nuclei explants.

    PubMed

    Trachsel, L; Heller, H C; Miller, J D

    1995-04-01

    In vivo studies reported that cholinergic agents affect mammalian circadian rhythmicity. To study phase resetting properties of cholinergic compounds more directly, we carried out experiments in rat suprachiasmatic nuclei slices. Compounds were added to the perfusate for 1 h at specific phases of the circadian cycle. On the following day, the time of peak neuronal activity, a measure of the phase of the endogenous circadian pacemaker, was assessed by means of extracellular recording in the suprachiasmatic nuclei. The peak of neuronal activity occurred at circadian time 5.8 +/- 0.7 (mean +/- 95% confidence limits) in the control slice (circadian time 0: lights-on). Ten-micromolar carbachol had no effect on the phase of the circadian rhythm when given at circadian times 6 and 15, while at circadian time 21 a phase advance of one hour was observed. By contrast, 10 microM nicotine significantly phase advanced (> 1 h) the neuronal circadian rhythm at all but one experimental circadian phase. The circadian times of maximal nicotinic phase advances were 15 (+2.6 h) and 21 (+2.8 h). A concentration response curve for nicotine was generated and pharmacological blocking experiments were performed at circadian time 15. The estimated maximum response of nicotine was 3.4 h, and the estimated concentration for half maximal response was 5 microM. The Hill coefficient (= 1.08) indicated that the effects of nicotine may be explained by a single receptor occupancy model. Mecamylamine (20 microM) almost completely antagonized the nicotinic phase-advances, whereas tetrodotoxin (1 microM) or high Mg2+ (10 mM) did not significantly attenuate the nicotinic phase-advances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7609878

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

    PubMed Central

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

    2015-01-01

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

  9. Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease.

    PubMed

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

    2015-01-01

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

  10. 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.

  11. 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.

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

    PubMed Central

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

    2015-01-01

    The rotation of the earth and associated alternating cycles of light and dark–the basis of our circadian rhythms–are fundamental to human biology and culture. However, it was not until 1971 that researchers first began to describe the molecular mechanisms for the circadian system. During the last few years, groundbreaking research has revealed a multitude of circadian genes affecting a variety of clinical diseases, including diabetes, obesity, sepsis, cardiac ischemia, and sudden cardiac death. Anesthesiologists, in the operating room and intensive care units, manage these diseases on a daily basis as they significantly impact patient outcomes. Intriguingly, sedatives, anesthetics, and the ICU 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

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

    SciTech Connect

    Shirai, Hidenori [Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566 (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8502 (Japan); Oishi, Katsutaka [Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566 (Japan); Kudo, Takashi [Division of Physiology and Pharmacology, School of Science and Engineering, Waseda University, Nishitokyo, Tokyo 202-0021 (Japan); Shibata, Shigenobu [Division of Physiology and Pharmacology, School of Science and Engineering, Waseda University, Nishitokyo, Tokyo 202-0021 (Japan); Ishida, Norio [Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566 (Japan) and Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8502 (Japan)]. 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.

  14. 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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  17. Circadian Rhythms: In the Loop at Last

    NSDL National Science Digital Library

    Russell N. Van Gelder (Washington University; Department of Ophthalmology and Visual Sciences/Department of Molecular Biology and Pharmacology)

    2003-06-06

    This Viewpoint compares and contrasts the circadian clocks of mammals and of Drosophila, emphasizing how different players are used to create the same basic script. Both the general script and the specific details of the murine and Drosophila circadian pathways are available at Science's Signal Transduction Knowledge Environment Connections Maps.

  18. Disrupted Circadian Rhythms in a Mouse Model of Schizophrenia

    PubMed Central

    Oliver, Peter L.; Sobczyk, Melanie V.; Maywood, Elizabeth S.; Edwards, Benjamin; Lee, Sheena; Livieratos, Achilleas; Oster, Henrik; Butler, Rachel; Godinho, Sofia I.H.; Wulff, Katharina; Peirson, Stuart N.; Fisher, Simon P.; Chesham, Johanna E.; Smith, Janice W.; Hastings, Michael H.; Davies, Kay E.; Foster, Russell G.

    2012-01-01

    Summary Sleep and circadian rhythm disruption has been widely observed in neuropsychiatric disorders including schizophrenia [1] and often precedes related symptoms [2]. However, mechanistic basis for this association remains unknown. Therefore, we investigated the circadian phenotype of blind-drunk (Bdr), a mouse model of synaptosomal-associated protein (Snap)-25 exocytotic disruption that displays schizophrenic endophenotypes modulated by prenatal factors and reversible by antipsychotic treatment [3, 4]. Notably, SNAP-25 has been implicated in schizophrenia from genetic [5–8], pathological [9–13], and functional studies [14–16]. We show here that the rest and activity rhythms of Bdr mice are phase advanced and fragmented under a light/dark cycle, reminiscent of the disturbed sleep patterns observed in schizophrenia. Retinal inputs appear normal in mutants, and clock gene rhythms within the suprachiasmatic nucleus (SCN) are normally phased both in vitro and in vivo. However, the 24 hr rhythms of arginine vasopressin within the SCN and plasma corticosterone are both markedly phase advanced in Bdr mice. We suggest that the Bdr circadian phenotype arises from a disruption of synaptic connectivity within the SCN that alters critical output signals. Collectively, our data provide a link between disruption of circadian activity cycles and synaptic dysfunction in a model of neuropsychiatric disease. PMID:22264613

  19. Disrupted circadian rhythms in a mouse model of schizophrenia.

    PubMed

    Oliver, Peter L; Sobczyk, Melanie V; Maywood, Elizabeth S; Edwards, Benjamin; Lee, Sheena; Livieratos, Achilleas; Oster, Henrik; Butler, Rachel; Godinho, Sofia I H; Wulff, Katharina; Peirson, Stuart N; Fisher, Simon P; Chesham, Johanna E; Smith, Janice W; Hastings, Michael H; Davies, Kay E; Foster, Russell G

    2012-02-21

    Sleep and circadian rhythm disruption has been widely observed in neuropsychiatric disorders including schizophrenia [1] and often precedes related symptoms [2]. However, mechanistic basis for this association remains unknown. Therefore, we investigated the circadian phenotype of blind-drunk (Bdr), a mouse model of synaptosomal-associated protein (Snap)-25 exocytotic disruption that displays schizophrenic endophenotypes modulated by prenatal factors and reversible by antipsychotic treatment [3, 4]. Notably, SNAP-25 has been implicated in schizophrenia from genetic [5-8], pathological [9-13], and functional studies [14-16]. We show here that the rest and activity rhythms of Bdr mice are phase advanced and fragmented under a light/dark cycle, reminiscent of the disturbed sleep patterns observed in schizophrenia. Retinal inputs appear normal in mutants, and clock gene rhythms within the suprachiasmatic nucleus (SCN) are normally phased both in vitro and in vivo. However, the 24 hr rhythms of arginine vasopressin within the SCN and plasma corticosterone are both markedly phase advanced in Bdr mice. We suggest that the Bdr circadian phenotype arises from a disruption of synaptic connectivity within the SCN that alters critical output signals. Collectively, our data provide a link between disruption of circadian activity cycles and synaptic dysfunction in a model of neuropsychiatric disease. PMID:22264613

  20. ANIMAL RESPONSES TO CIRCADIAN RHYTHMS IN FORAGE QUALITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. Thermistor-based Breathing Sensor for Circadian Rhythm Evaluation

    Microsoft Academic Search

    Emil Jovanov; Dejan Raskovic; Rick Hormigo

    2001-01-01

    One of the most frequently used methods to sense breathing pattern is to detect airflow using a nasal thermistor or a thermocouple sensor. Prolonged, minimally intrusive measurement of the breathing pattern is particularly important for polysomnography, sleeping disorders, stress monitoring, biofeedback techniques, and circadian rhythm analysis. Although most applications require only breathing pattern, some applications and diagnostic procedures require monitoring

  2. 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.

  3. Wavelet analysis of circadian and ultradian behavioral rhythms.

    PubMed

    Leise, Tanya L

    2013-01-01

    : We review time-frequency methods that can be useful in quantifying circadian and ultradian patterns in behavioral records. These records typically exhibit details that may not be captured through commonly used measures such as activity onset and so may require alternative approaches. For instance, activity may involve multiple bouts that vary in duration and magnitude within a day, or may exhibit day-to-day changes in period and in ultradian activity patterns. The discrete Fourier transform and other types of periodograms can estimate the period of a circadian rhythm, but we show that they can fail to correctly assess ultradian periods. In addition, such methods cannot detect changes in the period over time. Time-frequency methods that can localize frequency estimates in time are more appropriate for analysis of ultradian periods and of fluctuations in the period. The continuous wavelet transform offers a method for determining instantaneous frequency with good resolution in both time and frequency, capable of detecting changes in circadian period over the course of several days and in ultradian period within a given day. The discrete wavelet transform decomposes a time series into components associated with distinct frequency bands, thereby facilitating the removal of noise and trend or the isolation of a particular frequency band of interest. To demonstrate the wavelet-based analysis, we apply the transforms to a numerically-generated example and also to a variety of hamster behavioral records. When used appropriately, wavelet transforms can reveal patterns that are not easily extracted using other methods of analysis in common use, but they must be applied and interpreted with care. PMID:23816159

  4. Diagnosis and assessment of sleep and circadian rhythm disorders.

    PubMed

    Buysse, Daniel J

    2005-03-01

    Sleep and wakefulness are fundamental behavioral and neurobiological states that characterize all higher animals, including human beings. This article presents an overview of the current state of our knowledge concerning the function of sleep and sleep-wake rhythms, the neurobiology of circadian rhythms, how wakefulness and sleep are studied, and the clinical assessment and diagnosis of sleep and circadian rhythm disorders. Major theories of the function of sleep and sleep-wake rhythms are reviewed, including ecological or environmental advantage, physical restoration, optimizing waking function, learning and integration of experience, and survival. The author then reviews what is known about the neurobiology of endogenous circadian rhythms and how they are affected by environmental time cues. How sleep is studied using polysomnography (PSG) is explained, and the PSG characteristics of the three major neurobehavioral states, wakefulness, rapid eye movement (REM) sleep, and non-rapid eye movement (NREM) sleep, are described. Systems of classifying sleep disorders are reviewed, including those of the DSM-IV-TR, the International Classification of Sleep Disorders, and the ICD-10. Methods of assessing sleep complaints are then described, including taking an accurate history from the patient and bed partner, use of sleep history questionnaires and sleep-wake diaries, use of actigraphy, and use of PSG. PMID:15803045

  5. CIRCADIAN RHYTHMS: Integrating Circadian Timekeeping with Cellular Physiology

    NSDL National Science Digital Library

    Marie C. Harrisingh (Yale School of Medicine; Department of Cellular and Molecular Physiology)

    2008-05-16

    Access to the article is free, however registration and sign-in are required: Models of circadian timekeeping mechanisms in plants, flies, and mammals are expanding to include intracellular small-molecule signals.

  6. CIRCADIAN RHYTHMS Marking Time for a Kingdom

    NSDL National Science Digital Library

    Michael Young (The Rockefeller University; Laboratory of Genetics and National Science Foundation Center for Biological Timing)

    2000-04-21

    The author provides perspective on a study reported on page 483 of this issue. Findings from this study identifying a crucial circadian gene in hamsters represents "a major breakthrough for time-conscious mammals".

  7. Sleep and circadian rhythm disruption in schizophrenia†

    PubMed Central

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

    2012-01-01

    Background Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions. Aims A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption. Method We examined the relationship between sleep-wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadian clock timing, by collecting weekly 48 h profiles of a urinary metabolite of melatonin in 20 out-patients with schizophrenia and 21 healthy control individuals matched for age, gender and being unemployed. Results Significant sleep/circadian disruption occurred in all the participants with schizophrenia. Half these individuals showed severe circadian misalignment ranging from phase-advance/delay to non-24 h periods in sleep-wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production. Conclusions Severe circadian sleep/wake disruptions exist despite stability in mood, mental state and newer antipsychotic treatment. They cannot be explained by the individuals' level of everyday function. PMID:22194182

  8. A Model for the Circadian Rhythm of Cyanobacteria that Maintains Oscillation without Gene Expression

    PubMed Central

    Kurosawa, Gen; Aihara, Kazuyuki; Iwasa, Yoh

    2006-01-01

    An intriguing property of the cyanobacterial circadian clock is that endogenous rhythm persists when protein abundances are kept constant either in the presence of translation and transcription inhibitors or in the constant dark condition. Here we propose a regulatory mechanism of KaiC phosphorylation for the generation of circadian oscillations in cyanobacteria. In the model, clock proteins KaiA and KaiB are assumed to have multiple states, regulating the KaiC phosphorylation process. The model can explain 1), the sustained oscillation of gene expression and protein abundance when the expression of the kaiBC gene is regulated by KaiC protein, and 2), the sustained oscillation of phosphorylated KaiC when transcription and translation processes are inhibited and total protein abundance is fixed. Results of this work suggest that KaiA and KaiB strengthen the nonlinearity of KaiC phosphorylation, thereby promoting the circadian rhythm in cyanobacteria. PMID:16798799

  9. Cellular circadian pacemaking and the role of cytosolic rhythms.

    PubMed

    Hastings, Michael H; Maywood, Elizabeth S; O'Neill, John S

    2008-09-01

    The daily rhythms that adapt organisms to the solar cycle are driven by internal circadian clocks. The hypothesis that the core pacemakers of these clocks consist of auto-regulatory transcriptional/post-translational feedback loops (TTFLs) was first developed in flies and fungi and has now been extended successfully to describe circadian timing mechanisms in mammals and plants. TTFL models revolve around the protein products of 'clock' genes that feedback periodically to regulate their own expression. From this simple beginning, the models have been expanded to encompass multiple, interlinked loops. However, experimental data now highlight the limitations of the TTFL model. Until recently, the focus on transcription caused rhythms in cytosolic signalling pathways to be viewed as outputs of the 'core' transcriptional clockwork, or else as a mechanism for its entrainment by extra-cellular stimuli. Recent work in Arabidopsis thaliana, Drosophila melanogaster and mammals now reveals that cytosolic rhythms in small signalling molecules have a central role within the circadian pacemaker. The logic is consistent across taxa: oscillatory cytoplasmic elements integrate with transcriptional feedback loops to sustain them and determine their rhythmic properties. Thus, clock outputs can constitute inputs to subsequent cycles and so become indistinguishable from a core mechanism. This emphasises the interdependence of nuclear and cytoplasmic processes in circadian pacemaking, such that the pacemakers of some species might encompass the entire cell and its intercellular environment. PMID:18786386

  10. Observation of the circadian photosynthetic rhythm in cyanobacteria with a dissolved-oxygen meter

    Microsoft Academic Search

    Uan-Chen Yen; Tan-Chi Huang; Tsu-Chiang Yen

    2004-01-01

    This research investigated the feasibility of employing a dissolved-oxygen (DO) meter to monitor the circadian photosynthetic rhythm of cyanobacteria. Three cyanobacteria, Synechocystis sp. PCC 6803, Synechococcus sp. PCC 7942, and Cyanothece RF-1, were used to examine the proposed method. Their circadian photosynthetic rhythms were successfully observed; moreover, the different characteristics among these rhythms were clearly exhibited. The advantage of this

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Constitutive Expression of the CIRCADIAN CLOCK ASSOCIATED 1 ( CCA1) Gene Disrupts Circadian Rhythms and Suppresses Its Own Expression

    Microsoft Academic Search

    Zhi-Yong Wang; Elaine M. Tobin

    1998-01-01

    The CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene encodes a MYB-related transcription factor involved in the phytochrome induction of a light-harvesting chlorophyll a\\/b-protein (Lhcb) gene. Expression of the CCA1 gene is transiently induced by phytochrome and oscillates with a circadian rhythm. Constitutive expression of CCA1 protein in transgenic plants abolished the circadian rhythm of several genes with dramatically different phases. These

  16. Sex Differences in Behavioral Circadian Rhythms in Laboratory Rodents

    PubMed Central

    Krizo, Jessica A.; Mintz, Eric M.

    2014-01-01

    There is a strong bias in basic research on circadian rhythms toward the use of only male animals in studies. Furthermore, of the studies that use female subjects, many use only females and do not compare results between males and females. This review focuses on behavioral aspects of circadian rhythms that differ between the sexes. Differences exist in the timing of daily onset of activity, responses to both photic and non-photic stimuli, and in changes across the lifespan. These differences may reflect biologically important traits that are ecologically relevant and impact on a variety of responses to behavioral and physiological challenges. Overall, more work needs to be done to investigate differences between males and females as well as differences that are the result of hormonal changes across the lifespan. PMID:25620955

  17. [Arterial blood pressure circadian rhythm: significance and clinical implications].

    PubMed

    Gonzalez Rodriguez, E; Hernandez, A; Dibner, C; Koehler Ballan, B; Pechère-Bertschi, A

    2012-09-12

    Arterial blood pressure circadian rhythm: significance and clinical implications Arterial blood pressure exhibits a circadian rhythm characterized by a decrease during the sleep period and a steep increase in the early morning hours that can be characterized by 24 h ambulatory blood pressure monitoring (ABPM). The absence of a nocturnal dipping or an excessive morning surge, commonly observed in hypertensive patients, is associated with an increased cardiovascular and renal risk. Numerous studies show that a better control of nocturnal blood pressure can be obtained by the administration of anti-hypertensive medication at the evening time, improving microalbuminuria, left heart hypertrophy, or arterial intima-media thickness, but only one study has so far demonstrated a decrease of major cardiovascular events. In this context, the decision on restoring or not the nocturnal dipping should be left to the judgement of the clinician, and applied in an individual manner to each patient. PMID:23029984

  18. Circadian and ultradian rhythms in period mutants of Drosophila melanogaster

    Microsoft Academic Search

    Harold B. Dowse; Jeffrey C. Hall; John M. Ringo

    1987-01-01

    Using digital techniques for signal analysis—the correlogram and a high-resolution analysis of time series, maximum-entropy spectral analysis (MESA)—we have detected both circadian and ultradian rhythms in the locomotor activity of free-runningper0 males and in females lacking theper locus (per-; heterozygous for two deficiencies, each of which deletes the gene). Over half theper0 individuals and half theper- individuals tested were rhythmically

  19. Circadian rhythms in the green sunfish retina

    Microsoft Academic Search

    ALLEN DEARRY; ROBERT B. BARLOW

    1987-01-01

    We investigatedthe occurrence of circadianrhythms in retino- motor movements and retinalsensitivity in the green sunfish,Lepomis cyanellus. When green sunfish were kept in constant darkness, cone photoreceptors exhibited circadian retinomotor movements ;rod photoreceptors and retinal pigment epithelium (RPE) pigment granules did not.Cones elongated during subjectivenightand contracted during subjectiveday .These resultscorroborate those of Burnside and Ackland (1984 .Investigative Ophthalmology and Visual Science.25

  20. 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

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

    PubMed

    Zhdanova, Irina V; Masuda, Ken; Bozhokin, Sergey V; Rosene, Douglas L; González-Martínez, Janis; Schettler, Steven; Samorodnitsky, Eric

    2012-01-01

    In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment. PMID:22413014

  2. Familial Circadian Rhythm Disorder in the Diurnal Primate, Macaca mulatta

    PubMed Central

    Zhdanova, Irina V.; Masuda, Ken; Bozhokin, Sergey V.; Rosene, Douglas L.; González-Martínez, Janis; Schettler, Steven; Samorodnitsky, Eric

    2012-01-01

    In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment. PMID:22413014

  3. 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

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

    PubMed Central

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

    2013-01-01

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

  5. Circadian Rhythms of Chemotaxis to Ammonium and of Methylammonium Uptake in Chlamydomonas 1

    PubMed Central

    Byrne, Thomas Edward; Wells, Marion Robert; Johnson, Carl Hirschie

    1992-01-01

    Chlamydomonas reinhardtii expresses a well-documented circadian rhythm of phototaxis, which peaks in the subjective daytime. We find that vegetative cells also express circadian rhythms of chemotaxis to ammonium and ammonium uptake (as gauged by uptake of [14C]methylammonium). The chemotaxis rhythm peaks in the subjective night. Methylammonium uptake is light dependent, and its rhythm peaks at subjective dawn. Unlike vegetative cells, gametes are not attracted to ammonium. We believe this to be the first report of a circadian rhythm of chemotaxis. PMID:16668759

  6. Locomotor activity rhythm in Drosophila melanogaster after 600 generations in an aperiodic environment

    NASA Astrophysics Data System (ADS)

    Sheeba, V.; Chandrashekaran, M. K.; Joshi, Amitabh; Sharma, Vijay Kumar

    2002-09-01

    The locomotor activity rhythm of flies from four populations of Drosophila melanogaster, maintained under constant light for more than 600 generations, was recorded in continuous light (LL) and continuous darkness (DD) using four different protocols. The main objective behind these experiments was to estimate the proportion of flies exhibiting circadian rhythm of locomotor activity in LL, and to investigate whether this could be increased by subjecting the flies to various light regimes. About 26% of the flies exhibited a circadian rhythm of locomotor activity in LL, and the proportion increased to about 48% after an exposure to 12 h of darkness. About 77% of the flies exhibited a circadian locomotor activity rhythm in DD. Persistence of circadian locomotor activity rhythm in a considerable proportion of these flies suggests an intrinsic adaptive value to possessing circadian rhythmicity, derived, perhaps, from the need to synchronise various processes within the organism.

  7. 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

  8. Respiratory Rhythm Generation In Vivo

    PubMed Central

    Richter, Diethelm W.; Smith, Jeffrey C.

    2014-01-01

    The cellular and circuit mechanisms generating the rhythm of breathing in mammals have been under intense investigation for decades. Here, we try to integrate the key discoveries into an updated description of the basic neural processes generating respiratory rhythm under in vivo conditions. PMID:24382872

  9. Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms

    Microsoft Academic Search

    David K. Welsh; Diomedes E. Logothetis; Markus Meister; Steven M. Reppert

    1995-01-01

    Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses,

  10. Natural plasticity in circadian rhythms is mediated by reorganization in the molecular clockwork in honeybees

    Microsoft Academic Search

    Yair Shemesh; Mira Cohen; Guy Bloch

    2007-01-01

    Various animals naturally switch to con- siderable periods of around-the-clock activity with no apparent ill effects. Such plasticity in overt circadian rhythms might be observed because the clock is masked by the influence of external factors, is uncoupled from behavioral outputs, or results from genuine plasticity in the clock machinery. We studied honeybees in which plasticity in circadian rhythms is

  11. Genetics of Circadian Rhythms in Mammalian Model Organisms

    PubMed Central

    Lowrey, Phillip L.; Takahashi, Joseph S.

    2013-01-01

    The mammalian circadian system is a complex hierarchical temporal network which is organized around an ensemble of uniquely coupled cells comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. This central pacemaker is entrained each day by the environmental light/dark cycle and transmits synchronizing cues to cell-autonomous oscillators in tissues throughout the body. Within cells of the central pacemaker and the peripheral tissues, the underlying molecular mechanism by which oscillations in gene expression occur involves interconnected feedback loops of transcription and translation. Over the past 10 years we have learned much regarding the genetics of this system, including how it is particularly resilient when challenged by single-gene mutations, how accessory transcriptional loops enhance the robustness of oscillations, how epigenetic mechanisms contribute to the control of circadian gene expression, and how, from coupled neuronal networks, emergent clock properties arise. Here we will explore the genetics of the mammalian circadian system from cell-autonomous molecular oscillations, to interactions among central and peripheral oscillators and ultimately, to the daily rhythms of behavior observed in the animal. PMID:21924978

  12. Genes for iron metabolism influence circadian rhythms in Drosophila melanogaster.

    PubMed

    Mandilaras, Konstantinos; Missirlis, Fanis

    2012-08-01

    Haem has been previously implicated in the function of the circadian clock, but whether iron homeostasis is integrated with circadian rhythms is unknown. Here we describe an RNA interference (RNAi) screen using clock neurons of Drosophila melanogaster. RNAi is targeted to iron metabolism genes, including those involved in haem biosynthesis and degradation. The results indicate that Ferritin 2 Light Chain Homologue (Fer2LCH) is required for the circadian activity of flies kept in constant darkness. Oscillations of the core components in the molecular clock, PER and TIM, were also disrupted following Fer2LCH silencing. Other genes with a putative function in circadian biology include Transferrin-3, CG1358 (which has homology to the FLVCR haem export protein) and five genes implicated in iron-sulfur cluster biosynthesis: the Drosophila homologues of IscS (CG12264), IscU (CG9836), IscA1 (CG8198), Iba57 (CG8043) and Nubp2 (CG4858). Therefore, Drosophila genes involved in iron metabolism are required for a functional biological clock. PMID:22885802

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

    NASA Astrophysics Data System (ADS)

    Yen, Tsu-Chiang; Cheng, Da-Long

    2005-03-01

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

  14. [Circadian rhythms of the sex steroids of female Papio hamadryas in long-term hypokinesia].

    PubMed

    Shekhova, A N; Goncharov, N P; Katsiia, G V

    1984-09-01

    Radioimmunoassay was used to study the effect of restricted motor activity on circadian rhythms of blood plasma sexual steroids and cortisol in female Papio hamadryas during different phases of the menstrual cycle. Instact animals manifested clear-cut circadian rhythms of the testosterone and cortisol content during both the phases and those of estradiol and progesterone during the follicular phase of the cycle. Two-week immobilization did not produce any changes in the general pattern of circadian rhythms of cortisol and testosterone but led to a decrease in their mean daily concentrations, with that decrease being more pronounced for testosterone of females immobilized during the luteal phase. The authors established unbalance of sexual steroids with a dramatic fall of the mean daily concentrations of estradiol and progesterone and desynchronism of their circadian rhythms regardless of the cycle phase at the moment of immobilization. The mechanisms responsible for alterations in circadian rhythms of sexual steroids in hypokinetic females are discussed. PMID:6487794

  15. 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.

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

    PubMed Central

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

    2011-01-01

    Background AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKI? and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo. Methodology/Principal Finding The catalytic subunit of AMPK has two isoforms: ?1 and ?2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPK?1?/? and AMPK?2?/? mice. We found that both ?1?/? and ?2?/? mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but ?1?/? mice have a shorter circadian period whereas ?2?/? mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in ?1?/? mice, but not in ?2?/? mice. The circadian pattern of core clock gene expression was severely disrupted in fat in ?1?/? mice, but it was severely disrupted in the heart and skeletal muscle of ?2?/? mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both ?1?/? and ?2?/? mice. The circadian rhythm of nicotinamide phosphoryl-transferase (NAMPT) activity, which converts nicotinamide (NAM) to NAD+, is an important regulator of the circadian clock. We found that the NAMPT rhythm was absent in AMPK-deficient tissues and cells. Conclusion/Significance This study demonstrates that the catalytic activity of AMPK regulates circadian rhythm of behavior, energy metabolism and gene expression in isoform- and tissue-specific manners. PMID:21483791

  17. A review and applications of monthly circadian rhythms.

    PubMed

    Barber, C F

    2010-04-01

    Much is known and has been written around the concept and application of circadian rhythms to the human body, which has contributed to a greater understanding of how the physiology of the human body works, interacts and changes over a twenty 4-h time period. What is less understood is whether and how the physical body and mental behaviour changes over the much larger time scale of a month and beyond. This paper sets out to explore this relationship between time, physiology and behaviour through investigating both the existing literature on the subject and the connection between the phases of the moon and the occurrence of epileptic seizures and aggression. PMID:20465778

  18. The selective tachykinin neurokinin 1 (NK 1) receptor antagonist, GR 205,171, stereospecifically inhibits light-induced phase advances of hamster circadian activity rhythms

    Microsoft Academic Search

    Robert L. Gannon; Mark J. Millan

    2005-01-01

    Circadian rhythms in mammals are generated by master pacemaker cells located within the suprachiasmatic nucleus of the hypothalamus. In hamsters, the suprachiasmatic nucleus contains a small collection of cells immunoreactive for substance P, the endogenous ligand of tachykinin neurokinin 1 (NK1) receptors. In addition, two other nuclei which form part of the circadian system, the intergeniculate leaflet of the thalamus

  19. Short-term and circadian rhythms in the behaviour of the vole, Microtus agrestis (L.)

    Microsoft Academic Search

    Ulrich Lehmann

    1976-01-01

    The activity behaviour of the vole, Microtus agrestis, has been recorded in order to investigate the relationship between short-term rhythm and circadian rhythm. A simple device was developed, allowing separate monitoring of the time spent in or outside the nest, wheel-running, eating and drinking. Under natural light conditions during summer, a distinct differentiation between a short term rhythm of eating

  20. 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

  1. 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

  2. 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

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

    PubMed

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

    2015-01-01

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

  4. 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

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

    PubMed

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

    2014-10-21

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

  6. Circadian rhythm in pineal N-acetyltransferase activity: phase shifting by light pulses (I).

    PubMed

    Binkley, S; Muller, G; Hernandez, T

    1981-09-01

    N-Acetyltransferase activity (NAT) in the pineal gland has a circadian rhythm which is responsive to environmental light-dark cycles. The rhythm entrains to (synchronizes with or is phased by) light-dark cycles. To assess the means by which phase resetting is accomplished, the phase response of the pineal NAT rhythm to light pulses was examined using chicks (Gallus domesticus). When 4-h light pulses were imposed on chicks at intervals over a 24-h period of darkness and the time of the next rise in NAT was determined in darkness, it was found that: (1) pulses early in the subjective dark time delayed the rise in NAT, (2) pulses late in the subjective dark time advanced the rise in NAT, and (3) pulses in the subjective light time were relatively ineffective. These results are typical of a circadian phase response curve and show that an enzyme with a circadian rhythm is similar to other circadian rhythms studied. PMID:7276958

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. Phase shifting of the circadian rhythm in the eye of Bulla by inhibition of chloride conductance.

    PubMed

    Michel, S; Khalsa, S B; Block, G D

    1992-11-01

    Inhibition of Cl- conductance has been previously found to shorten the free-running period of the circadian eye rhythm of the marine snail Bulla gouldiana. In this study, we describe a phase-response curve for 6-h pulses of Cl(-)-free seawater, consisting only of phase advances with the largest in the late subjective night (1.5 h) and smaller phase shifts in the late subjective day. Intracellular recordings revealed that at both circadian times retinal pacemaker neurons hyperpolarized in response to the removal of extracellular chloride. Since previous studies indicate that membrane potential generates both phase advances and delays it seems unlikely that the action of chloride removal is mediated exclusively by the change in membrane potential. PMID:1283451

  11. Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

    PubMed Central

    Nawarathna, Upekshani; Fisher, Kate; Shneerson, John M.; Reddy, Akhilesh B.; Barker, Roger A.

    2014-01-01

    IMPORTANCE Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erb?). RESULTS Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms. PMID:24687146

  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. Circadian rhythms investigated on the cellular and molecular levels.

    PubMed

    Gebicke-Haerter, P J; Pildaín, L V; Matthäus, F; Schmitt, A; Falkai, P

    2013-05-01

    Investigations on circadian rhythms have markedly advanced our understanding of health and disease with the advent of high-throughput technologies like microarrays and epigenetic profiling. They elucidated the multi-level behaviour of interactive oscillations from molecules to neuronal networks and eventually to processes of learning and memory in an impressive manner. The small-world topology of synchronized firing through neuron-neuron and neuron-glia gap junctions is discussed as a mathematical approach to these intensively studied issues. It has become evident that, apart from some disorders caused by gene mutations, the majority of disorders originating from disturbances of rhythms arise from environmental influences and epigenetic changes. In this context, it was mandatory to think of and devise experiments on temporary scales, which exponentially increased the volumes of data obtained from time-series and rapidly became prohibitive of manual inspection. Therefore, more and more sophisticated mathematical algorithms have been developed to identify rhythmic expression of genes and to find coexpression by their clustering. It is expected that disturbed rhythmic behaviour in mental disorders is reflected in altered oscillatory behaviour of gene expression. PMID:23599242

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Dong, Chaohua; Bai, Suhua; Du, Liqiang

    2015-08-01

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

  16. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists

    E-print Network

    Gillette, Martha U.

    Review Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists Fred W. Tureka,*, Martha U. Gilletteb a Department of Neurobiology and Physiology, Center for Sleep and Circadian Biology, Northwestern University, 2205 Tech Drive, Hogan Hall 2-160, Evanston, IL

  17. A CIRCADIAN RHYTHM IN THE LOCOMOTOR BEHAVIOUR OF THE GIANT GARDEN SLUG LIMAX MAXIMUS

    Microsoft Academic Search

    P. G. SOKOLOVE; C. M. BEISWANGER; D. J. PRIOR

    SUMMARY The locomotor activity of the garden slug Limax maximus was examined for components of circadian rhythmicity. Behavioural (running wheel) studies clearly demonstrated that the activity satisfies the principal criteria of circadian rhythmicity. In constant darkness at a constant temperature, the locomotor activity freeran with a period of about 24 h (range 23-6-24-6 h). The rhythm was also expressed in

  18. Pre and post-nicotine circadian activity rhythms can be differentiated by a paired environmental cue

    Microsoft Academic Search

    Andrea G. Gillman; Ann E. K. Kosobud; William Timberlake

    2008-01-01

    Previous studies have shown that addictive drugs presented daily at fixed times produce circadian (oscillator-driven) anticipatory and evoked activity rhythms in rats. Other studies have shown that environmental cues paired with addictive drugs produce tolerance to drug effects and elicit craving behavior when presented without the drug. The present study tested these circadian entrainment and paired-cue conditioning effects together. This

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

    PubMed

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

    2013-01-01

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

  20. Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei.

    PubMed

    Li, Jia-Da; Burton, Katherine J; Zhang, Chengkang; Hu, Shuang-Bao; Zhou, Qun-Yong

    2009-03-01

    The suprachiasmatic nuclei (SCN) serve as the principal circadian pacemakers that coordinate daily cycles of behavior and physiology for mammals. A network of transcriptional and translational feedback loops underlies the operating molecular mechanism for circadian oscillation within the SCN neurons. It remains unclear how timing information is transmitted from SCN neurons to eventually evoke circadian rhythms. Intercellular communication between the SCN and its target neurons is critical for the generation of coherent circadian rhythms. At the molecular level, neuropeptides encoded by clock-controlled genes have been indicated as important output mediators. Arginine vasopressin (AVP) is the product of one such clock-controlled gene. Previous studies have demonstrated a circadian rhythm of AVP levels in the cerebrospinal fluid and the SCN. The physiological effects of AVP are mediated by three types of AVP receptors, designated as V1a, V1b, and V2. In this study, we report that V1a mRNA levels displayed a circadian rhythm in the SCN, peaking during night hours. The circadian rhythmicity of locomotor activities was significantly reduced in V1a-deficient (V1a(-/-)) mice (50-75% reduction in the power of fast Fourier transformation). However, the light masking and light-induced phase shift effects are intact in V1a(-/-) mice. Whereas the expression of clock core genes was unaltered, the circadian amplitude of prokineticin 2 (PK2) mRNA oscillation was attenuated in the SCN of V1a(-/-) mice ( approximately 50% reduction in the peak levels). In vitro experiments demonstrated that AVP, acting through V1a receptor, was able to enhance the transcriptional activity of the PK2 promoter. These studies thus indicate that AVP-V1a signaling plays an important role in the generation of overt circadian rhythms. PMID:19052319

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. Blind Man Living in Normal Society Has Circadian Rhythms of 24.9 Hours

    Microsoft Academic Search

    L. E. M. Miles; D. M. Raynal; M. A. Wilson

    1977-01-01

    A psychologically normal blind man, living and working in normal society, suffered from a severe cyclic sleep-wake disorder. Investigations showed that he had circadian rhythms of body temperature, alertness, performance, cortisol secretion, and urinary electrolyte excretion which were desynchronized from the 24-hour societal schedule. These rhythms all had periods which were longer than 24 hours and indistinguishable from the period

  4. Entrainment of the circadian activity rhythm of a lizard to melatonin injections.

    PubMed

    Underwood, H; Harless, M

    1985-08-01

    The circadian activity rhythms of lizards (Sceloporus occidentalis) can be entrained (synchronized) to a period of 24 hr by melatonin injections given every other day at the same time of day, but not by saline injections. The activity onsets of the entrained lizards exhibited two preferred phase-relationships (approximately 165 degrees and approximately 30 degrees) with the time of melatonin injections with the 30 degree phase only rarely observed. These results suggest that endogenous rhythms of melatonin secretion (i.e., from the pineal organ) may be involved in synchronizing circadian oscillations within the lizard's multioscillator circadian system. PMID:4070395

  5. Circadian rhythms in Synechococcus elongatus PCC 7942: insights into the regulatory mechanisms of the cyanobacterial clock system 

    E-print Network

    Mackey, Shannon Rose

    2009-06-02

    Circadian rhythms of behavior have been well characterized in organisms including mammals, plants, insects, fungi, and photosynthetic bacteria. Cyanobacteria, such as the unicellular Synechococcus elongatus PCC 7942, display ...

  6. Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster.

    PubMed

    Ma, Lingling; Ma, Jun; 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

  7. Analysis of a gene regulatory cascade mediating circadian rhythm in zebrafish.

    PubMed

    Li, Ying; Li, Guang; Wang, Haifang; Du, Jiulin; Yan, Jun

    2013-01-01

    In the study of circadian rhythms, it has been a puzzle how a limited number of circadian clock genes can control diverse aspects of physiology. Here we investigate circadian gene expression genome-wide using larval zebrafish as a model system. We made use of a spatial gene expression atlas to investigate the expression of circadian genes in various tissues and cell types. Comparison of genome-wide circadian gene expression data between zebrafish and mouse revealed a nearly anti-phase relationship and allowed us to detect novel evolutionarily conserved circadian genes in vertebrates. We identified three groups of zebrafish genes with distinct responses to light entrainment: fast light-induced genes, slow light-induced genes, and dark-induced genes. Our computational analysis of the circadian gene regulatory network revealed several transcription factors (TFs) involved in diverse aspects of circadian physiology through transcriptional cascade. Of these, microphthalmia-associated transcription factor a (mitfa), a dark-induced TF, mediates a circadian rhythm of melanin synthesis, which may be involved in zebrafish's adaptation to daily light cycling. Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms. PMID:23468616

  8. 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.

  9. 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

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

    PubMed

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

    2013-08-01

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

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

    PubMed Central

    van Alphen, Pascal; Hellingwerf, Klaas J.

    2015-01-01

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

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

    PubMed

    van Alphen, Pascal; Hellingwerf, Klaas J

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Circadian rhythm of aldosterone in dairy cattle during the summer

    NASA Astrophysics Data System (ADS)

    Aranas, T. J.; Roussel, J. D.; Seybt, S. H.

    1987-09-01

    Twelve Holstein heifers, pregnant from 120 150 days were used to study the circadian rhythm of aldosterone, cortisol, progesterone, sodium and potassium in dairy cattle during the summer in Louisiana. Cortisol was not significantly influenced by time (time 1 = 06.00 h). Aldosterone, sodium, potassium and progesterone changed significantly (P<.01) with time. Aldosterone peaked (116.5±17.2 pg/ml) at 08.00 h and then generally declined to 16.00 h (26.7±2.0 pg/ml). Sodium generally increased from 06.00 h (320.1±7.3 mg%) to 18.00 h (377.9±6.1 mg%), and then declined. Potassium generally increased from 06.00 h (20.9±0.5 mg%) to 22.00 h (23.0±0.3 mg%). Progesterone generally increased from 07.00 h (2.8±0.4 mg/ml) to 24.00 h (7.5±1.4 mg/ml). Aldosterone was significantly related to temperature associated with the time of the day samples were taken (r = 0.66, P<.02).

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Consumption of high-fat diet acutely alters the daily rhythm of eating behavior and circadian organization (the phase relationship between oscillators in central and peripheral tissues) in mice. Voluntary wheel-running activity counteracts the obesogenic effects of high-fat diet and also modulates circadian rhythms in mice. In this study, we sought to determine whether voluntary wheel-running activity could prevent the proximate effects of high-fat diet consumption on circadian organization and behavioral rhythms in mice. Mice were housed with locked or freely rotating running wheels and fed chow or high-fat diet for 1 week and rhythms of locomotor activity, eating behavior, and molecular timekeeping (PERIOD2::LUCIFERASE luminescence rhythms) in ex vivo tissues were measured. Wheel-running activity delayed the phase of the liver rhythm by 4 h in both chow- and high-fat diet-fed mice. The delayed liver phase was specific to wheel-running activity since an enriched environment without the running wheel did not alter the phase of the liver rhythm. In addition, wheel-running activity modulated the effect of high-fat diet consumption on the daily rhythm of eating behavior. While high-fat diet consumption caused eating events to be more evenly dispersed across the 24 h-day in both locked-wheel and wheel-running mice, the effect of high-fat diet was much less pronounced in wheel-running mice. Together these data demonstrate that wheel-running activity is a salient factor that modulates liver phase and eating behavior rhythms in both chow- and high-fat-diet fed mice. Wheel-running activity in mice is both a source of exercise and a self-motivating, rewarding behavior. Understanding the putative reward-related mechanisms whereby wheel-running activity alters circadian rhythms could have implications for human obesity since palatable food and exercise may modulate similar reward circuits. PMID:24624109

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Gannon, Robert L

    2014-10-17

    The synchronization of circadian rhythms in sleep, endocrine and metabolic functions with the environmental light cycle is essential for health, and dysfunction of this synchrony is thought to play a part in the development of many neurological disorders. There is a demonstrable need to develop new therapeutics for the treatment of neurological disorders such as depression and schizophrenia, and oxytocin is currently being investigated for this purpose. There are no published reports describing activity of oxytocin receptor ligands on mammalian circadian rhythms and that, then, is the purpose of this study. Non-peptide oxytocin receptor ligands that cross the blood brain barrier were systemically injected in hamsters to determine their ability to modulate light-induced phase advances and delays of circadian wheel running rhythms. The oxytocin receptor agonist WAY267464 (10 mg/kg) inhibited light induced phase advances of wheel running rhythms by 55%, but had no effect on light-induced phase delays. In contrast, the oxytocin receptor antagonist WAY162720 (10 mg/kg) inhibited light-induced phase delays by nearly 75%, but had no effect on light-induced phase advances. Additionally, WAY162720 was able to antagonize the inhibitory effects of WAY267464 on light-induced phase advances. These results are consistent for a role of oxytocin in the phase-delaying effects of light on circadian activity rhythms early in the night. Therefore, oxytocin may prove to be useful in developing therapeutics for the treatment of mood disorders with a concomitant dysfunction in circadian rhythms. Investigators should also be cognizant that oxytocin ligands may negatively affect circadian rhythms during clinical trials for other conditions. PMID:25148710

  19. 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.

  20. Biomarkers of aging: changes in circadian rhythms related to the modulation of metabolic output.

    PubMed

    Duffy, P H; Feuers, R J

    1991-06-01

    Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) many variables that are related to the modulation of metabolic output vary dramatically at different times of the day; (2) various experimental variable and treatment groups must be synchronized with environmental cues that control circadian rhythms; and (3) multiple circadian variables may interact together to modulate the rate of aging. The rhythm for physiological factors such as whole animal metabolic output, body temperature, heart rate, urine flow, potassium, etc. were found to be dissociated or altered by the senescence process; behavioral variables such as spontaneous activity, wheel running, feeding and drinking, verbal performance, as well as sleep-wakefulness rhythms, seem to be accurate predictors of biological age. Circadian rhythms for a variety of enzymes of intermediary metabolism which are directly associated with energy metabolism have been well documented. These well-defined rhythms of enzyme activity have also been shown to degenerate with aging. Rhythms tend to lose amplitude as activity falls with age and as a general loss of regulation (especially time of day where maximal activity might be found) of activity across the 24-h span occurs. As with behavioral variables, changes in enzyme rhythms appear to accurately predict aging. Generally speaking, the loss of temporal organization with age, characterized by decreased circadian amplitude, loose internal synchronization, and poor response to external environmental time queues, is associated with poor health states and decreased longevity. Temporal rhythms for whole animal parameters are highly correlated with molecular events, such as regulation of cellular metabolism. DNA repair, and gene expression. Automated data acquisition and process control systems will be required for future chronobiological studies to develop biomarkers of aging. PMID:1910594

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

    PubMed Central

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

    2014-01-01

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

  2. 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.

  3. 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.

  4. 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

  5. A circadian rhythm in the locomotive behaviour of the giant garden slug Limax maximus.

    PubMed

    Sokolove, P G; Beiswanger, C M; Prior, D J; Gelperin, A

    1977-02-01

    The locomotor activity of the garden slug Limax maximus was examined for components of circadian rhythmicity. Behavioural (running wheel) studies clearly demonstrated that the activity satisfies the principal criteria of circadian rhythmicity. In constant darkness at a constant temperature, the locomotor activity freeran with a period of about 24 h (range 23-6-24-6 h). The rhythm was also expressed in constant light with a period for individual slugs that tended to be shorter in LL than in DD. The period of the rhythm was temperature compensated (11-5-21-5 degrees C) with a Q10 approximately equal to 1-00. The locomotor rhythm could be entrained to 24 h LD cycles such that the circadian activity peak occurred during the dark. The phase angle between the onset of activity and lights-off was not fixed, but was a function of the photoperiod of the entraining light cycle. PMID:858993

  6. 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 CKI?/? 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

  7. 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.

  8. Fibroblast Circadian Rhythms of PER2 Expression Depend on Membrane Potential and Intracellular Calcium

    PubMed Central

    Noguchi, Takako; Wang, Connie W.; Pan, Haiyun

    2012-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes circadian rhythms of cells and tissues throughout the body. In SCN neurons, rhythms of clock gene expression are suppressed by manipulations that hyperpolarize the plasma membrane or lower intracellular Ca2+. However, whether clocks in other cells also depend on membrane potential and calcium is unknown. In this study, we investigate the effects of membrane potential and intracellular calcium on circadian rhythms in mouse primary fibroblasts. Rhythms of clock gene expression were monitored using a PER2::LUC knockin reporter. We found that rhythms were lost or delayed at lower (hyperpolarizing) K+ concentrations. Bioluminescence imaging revealed that this loss of rhythmicity in cultures was due to loss of rhythmicity of single cells rather than desynchrony among cells. In lower Ca2+ concentrations, rhythms were advanced or had shorter periods. Buffering intracellular Ca2+ by the calcium chelator 1,2-Bis(2-aminophenoxy) ethane-N,N,N?,N?-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) or manipulation of IP3-sensitive intracellular calcium stores by thapsigargin delayed rhythms. These results suggest that the circadian clock in fibroblasts, as in SCN neurons, is regulated by membrane potential and Ca2+. Changes in intracellular Ca2+ may mediate the effects of membrane potential that we observed. PMID:22734566

  9. The Circadian Rhythm of Salivary Cortisol in Growing Pigs: Effects of Age, Gender, and Stress

    Microsoft Academic Search

    Marko A. W. Ruis; Joop H. A. Te Brake; Bas Engel; E. Dinand Ekkel; Willem G. Buist; Harry J. Blokhuis; Jaap M. Koolhaas

    1997-01-01

    Ruis, M. A. W., J. H. A. Te Brake, B. Engel, E. D. Ekkel, W. G. Buist, H. J. Blokhuis, J. M. Koolhaas. The circadian rhythm of salivary cortisol in growing pigs: effects of age, gender and stress. Physiol Behav 62(3) 623–630, 1997.—This experiment was designed to examine circadian rhythmicity of cortisol in saliva of growing pigs, in relation to

  10. Seasonal effects on the freerunning rhythm of circadian activity of longnose dace ( Rhinichthys cataractae )

    Microsoft Academic Search

    Martin Kavaliers

    1981-01-01

    Synopsis Freerunning circadian rhythms of locomotor activity in individual longnose dace sampled from a population at 41°N latitude were recorded under constant darkness throughout the year. There was an annual cycle in the length of the circadian period, with maximum and minimum lengths of mean period of 23.6 and 21.6 h recorded during summer (June) and winter (December), respectively. These

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

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. 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

  14. Circadian rhythms in Neurospora crassa on a polydimethylsiloxane microfluidic device for real-time gas perturbations

    PubMed Central

    Lee, Kang Kug; Ahn, Chong H.; Hong, Christian I.

    2013-01-01

    Racetubes, a conventional system employing hollow glass tubes, are typically used for monitoring circadian rhythms from the model filamentous fungus, Neurospora crassa. However, a major technical limitation in using a conventional system is that racetubes are not amenable for real-time gas perturbations. In this work, we demonstrate a simple microfluidic device combined with real-time gas perturbations for monitoring circadian rhythms in Neurospora crassa using bioluminescence assays. The developed platform is a useful toolbox for investigating molecular responses under various gas conditions for Neurospora and can also be applied to other microorganisms. PMID:24404062

  15. Behavioral and neurochemical sources of variability of circadian period and phase: studies of circadian rhythms of npy-/- mice.

    PubMed

    Harrington, Mary; Molyneux, Penny; Soscia, Stephanie; Prabakar, Cheruba; McKinley-Brewer, Judy; Lall, Gurprit

    2007-03-01

    The cycle length or period of the free-running rhythm is a key characteristic of circadian rhythms. In this study we verify prior reports that locomotor activity patterns and running wheel access can alter the circadian period, and we report that these treatments also increase variability of the circadian period between animals. We demonstrate that the loss of a neurochemical, neuropeptide Y (NPY), abolishes these influences and reduces the interindividual variability in clock period. These behavioral and environmental influences, from daily distribution of peak locomotor activity and from access to a running wheel, both act to push the mean circadian period to a value < 24 h. Magnitude of light-induced resetting is altered as well. When photoperiod was abruptly changed from a 18:6-h light-dark cycle (LD18:6) to LD6:18, mice deficient in NPY were slower to respond to the change in photoperiod by redistribution of their activity within the prolonged dark and eventually adopted a delayed phase angle of entrainment compared with controls. These results support the hypothesis that nonphotic influences on circadian period serve a useful function when animals must respond to abruptly changing photoperiods and point to the NPYergic pathway from the intergeniculate leaflet innervating the suprachiasmatic nucleus as a circuit mediating these effects. PMID:17082354

  16. 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

  17. Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

    PubMed Central

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

    2014-01-01

    With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

  18. A circadian rhythm in the susceptibility of the boll weevil, Anthonomus grandis Boheman to methyl parathion 

    E-print Network

    Cole, Charles L

    1967-01-01

    2. Naintenance of adults 3. Collection and inoculation of eggs 4. Flaintenance of immature stages Determining if There is a Circadian Rhythm Involved in the Susceptibility of the Boll Weevil to Methyl Parathion . . . . . . . . . . . . . . ~ 18... to Nethyl Parathion l. Effect af time of dsy of treatment on mor talities produced in boll weevils exposed to surfaces treated with methyl parathion 2. Possible mechanism involved in the entrain- ment of the susceptibility rhythm Nortalities Produced...

  19. 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?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 the common group were concentrated between 3 and 9 PM, whereas those for the severe group were more dispersive. And the high values for the critical group were equally distributed in 24 hours of the day. Circadian rhythm of patients' temperature in the common group was the same as the normal rhythm of human body temperature. Circadian rhythm of patients' temperature, HR and respiratory rate in 3 groups were significantly different. PMID:25761178

  20. Circadian Clocks in Antennal Neurons Are Necessary and Sufficient for Olfaction Rhythms in Drosophila

    Microsoft Academic Search

    Shintaro Tanoue; Parthasarathy Krishnan; Balaji Krishnan; Stuart E Dryer; Paul E Hardin

    2004-01-01

    Background: The Drosophila circadian clock is controlled by interlocked transcriptional feedback loops that operate in many neuronal and nonneuronal tissues. These clocks are roughly divided into a central clock, which resides in the brain and is known to control rhythms in locomotor activity, and peripheral clocks, which comprise all other clock tissues and are thought to control other rhythmic outputs.

  1. Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms.

    PubMed

    Takahashi, J S; DeCoursey, P J; Bauman, L; Menaker, M

    Environmental light cycles are the dominant synchronizers of circadian rhythms in the field, and artificial light cycles and pulses are the major tools used in the laboratory to analyse properties of circadian systems. It is therefore surprising that few studies have analysed the physical parameters of light stimuli that affect circadian rhythms. There have previously been no spectral sensitivity measurements for phase shifting the circadian rhythms of mammals and only two preliminary reports on the wavelength dependence of this response exist. Using the magnitude of phase shift caused by a single 15-min pulse of monochromatic light given 6 h after activity onset, we have now characterized the spectral sensitivity of the photoreceptors responsible for phase shifting the locomotor rhythm of the hamster (Mesocricetus auratus). The sensitivity curve for this response has a maximum near 500 nm and is similar to the absorption spectrum for rhodopsin. Although the spectral sensitivity is consistent with a rhodopsin-based photopigment, two features of the photoreceptive system that mediates entrainment are unusual: the threshold of the response is high, especially for a predominantly rod retina like that of the hamster, and the reciprocal relationship between intensity and duration holds for extremely long durations (up to 45 min). These results suggest that the photoreceptive system mediating entrainment is markedly different from that involved in visual image formation. PMID:6700721

  2. Systematic individual differences in sleep homeostatic and circadian rhythm contributions to neurobehavioral impairment

    E-print Network

    Pennsylvania, University of

    Systematic individual differences in sleep homeostatic and circadian rhythm contributions to neurobehavioral impairment during sleep deprivation Hans P.A. Van Dongena,*, Amy M. Bendera, and David F. Dingesb@mail.med.upenn.edu aSleep and Performance Research Center, Washington State University Spokane, PO Box 1495,Spokane, WA

  3. Age of appearance of circadian rhythm in salivary cortisol values in infancy

    Microsoft Academic Search

    D A Price; G C Close; B A Fielding

    1983-01-01

    Samples of saliva (4 in 24 hours), collected at monthly intervals for the first 6 months of life in 8 term infants by their mothers, were analysed for cortisol by radioimmunoassay. Values in the first month were more variable, daily mean values were greater, and amplitudes of variation were greater than in subsequent months. The circadian rhythm appeared by the

  4. CIRCADIAN RHYTHMS IN PLANTS: MA-CHINE LEARNING MODELS AND BIOIN-

    E-print Network

    Chaudhuri, Surajit

    estimation using Kalman filter meth- ods for state space models. Some preliminary results includeTH E U N I V E R S ITY OF E D I N B U R G H CIRCADIAN RHYTHMS IN PLANTS: MA- CHINE LEARNING MODELS[3], a species of unicellular plant; it has been described as the smallest known free

  5. A Mutant Drosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless

    Microsoft Academic Search

    Ravi Allada; Neal E White; W. Venus So; Jeffrey C Hall; Michael Rosbash

    1998-01-01

    We report the identification, characterization, and cloning of a novel Drosophila circadian rhythm gene, dClock. The mutant, initially called Jrk, manifests dominant effects: heterozygous flies have a period alteration and half are arrhythmic, while homozygous flies are uniformly arrhythmic. Furthermore, these flies express low levels of the two clock proteins, PERIOD (PER) and TIMELESS (TIM), due to low per and

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Entrainment of circadian rhythms: retinofugal pathways and unilateral suprachiasmatic nucleus lesions.

    PubMed

    Donaldson, J A; Stephan, F K

    1982-12-01

    The role of retinohypothalamic input to the suprachiasmatic nuclei (SCN) as well as SCN afferents from the ventrolateral geniculate nuclei (LGNV) in the entrainment of circadian drinking rhythms was investigated in the rat. Bilateral lesions of the LGNV and the primary optic tracts had no affect on the entrainment of drinking rhythms to a light-dark cycle, the response to a 12 hr phase shift of the light-dark cycle, or on the period of the free-running circadian rhythm in constant light or constant darkness. Unilateral blinding in rats with or without LGNV lesions retarded the rate of phase shifting by 2 days and decreased the period of the free-running rhythm in constant light. For rats with unilateral SCN lesions, or such lesions combined with either ipsi- or contra-lateral blinding, the rate of re-entrainment was intermediate between intact and unilaterally blinded rats indicating that unilateral SCN lesions partially reversed the effects of unilateral blinding. Unilateral SCN lesions had no effect on the period of the free-running rhythm in constant light or darkness. These results are consistent with the interpretation that the asymmetrical innervation of the two SCN by the RHT in unilaterally blinded rats delays re-entrainment by changing the phase response curve of the circadian system. This change may be mediated by neural connections between the two SCN. PMID:7163396

  9. Circadian rhythm disorganization produces profound cardiovascular and renal disease in hamsters.

    PubMed

    Martino, Tami A; Oudit, Gavin Y; Herzenberg, Andrew M; Tata, Nazneen; Koletar, Margaret M; Kabir, Golam M; Belsham, Denise D; Backx, Peter H; Ralph, Martin R; Sole, Michael J

    2008-05-01

    Sleep deprivation, shift work, and jet lag all disrupt normal biological rhythms and have major impacts on health; however, circadian disorganization has never been shown as a causal risk factor in organ disease. We now demonstrate devastating effects of rhythm disorganization on cardiovascular and renal integrity and that interventions based on circadian principles prevent disease pathology caused by a short-period mutation (tau) of the circadian system in hamsters. The point mutation in the circadian regulatory gene, casein kinase-1epsilon, produces early onset circadian entrainment with fragmented patterns of behavior in +/tau heterozygotes. Animals die at a younger age with cardiomyopathy, extensive fibrosis, and severely impaired contractility; they also have severe renal disease with proteinuria, tubular dilation, and cellular apoptosis. On light cycles appropriate for their genotype (22 h), cyclic behavioral patterns are normalized, cardiorenal phenotype is reversed, and hearts and kidneys show normal structure and function. Moreover, hypertrophy does not develop in animals whose suprachiasmatic nucleus was ablated as young adults. Circadian organization therefore is critical for normal health and longevity, whereas chronic global asynchrony is implicated in the etiology of cardiac and renal disease. PMID:18272659

  10. Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms.

    PubMed

    Dubocovich, M L; Yun, K; Al-Ghoul, W M; Benloucif, S; Masana, M I

    1998-09-01

    This study demonstrates the involvement of the MT2 (Mel1b) melatonin receptor in mediating phase advances of circadian activity rhythms by melatonin. In situ hybridization histochemistry with digoxigenin-labeled oligonucleotide probes revealed for the first time the expression of mt1 and MT2 melatonin receptor mRNA within the suprachiasmatic nucleus of the C3H/HeN mouse. Melatonin (0.9 to 30 microg/mouse, s.c.) administration during 3 days at the end of the subjective day (CT 10) to C3H/HeN mice kept in constant dark phase advanced circadian rhythms of wheel running activity in a dose-dependent manner [EC50=0.72 microg/mouse; 0.98+/-0.08 h (n=15) maximal advance at 9 microg/mouse]. Neither the selective MT2 melatonin receptor antagonists 4P-ADOT and 4P-PDOT (90 microg/mouse, s.c.) nor luzindole (300 microg/mouse, s.c.), which shows 25-fold higher affinity for the MT2 than the mt1 subtype, affected the phase of circadian activity rhythms when given alone at CT 10. All three antagonists, however, shifted to the right the dose-response curve to melatonin, as they significantly reduced the phase shifting effects of 0.9 and 3 microg melatonin. This is the first study to demonstrate that melatonin phase advances circadian rhythms by activation of a membrane-bound melatonin receptor and strongly suggests that this effect is mediated through the MT2 melatonin receptor subtype within the circadian timing system. We conclude that the MT2 melatonin receptor subtype is a novel therapeutic target for the development of subtype-selective analogs for the treatment of circadian sleep and mood-related disorders. PMID:9737724

  11. Long-Term Acute Care Patients Weaning From Prolonged Mechanical Ventilation Maintain Circadian Rhythm

    PubMed Central

    Koldobskiy, Dafna; Diaz-Abad, Montserrat; Scharf, Steven M; Brown, John; Verceles, Avelino C

    2015-01-01

    BACKGROUND Circadian rhythm regulates many physiologic and immunologic processes. Disruption of these processes has been demonstrated in acutely ill, mechanically ventilated patients in the ICU setting. Light has not been studied as an entraining stimulus in the chronically mechanically ventilated patient. The purpose of this study was to determine the association of naturally occurring ambient light levels in a long-term acute care (LTAC) hospital with circadian rhythm in patients recovering from critical illness and requiring prolonged mechanical ventilation (PMV). METHODS We performed a prospective observational study of 15 adult patients who were recovering from critical illness and receiving PMV and who were admitted to the ventilator weaning unit at an LTAC hospital. Demographic data were obtained from chart review. Light stimuli in each patient room were assessed using a photometer device placed at eye level. Circadian rhythm was assessed by wrist actigraphy. Cumulative data were obtained from each device for a 48-h period, averaged into 4-h intervals, and analyzed. RESULTS Patients receiving PMV were obese (mean body mass index of 32.7 ± 10.3 kg/m2) and predominantly female (73%) and had an average age of 63.1 ± 14.3 y. Light exposure to this cohort maintained diurnal variation (P < .001) and was significantly different across time periods. Circadian rhythm, as represented by actigraphy, also maintained diurnal variation (P < .001) and was in phase with light. Linear regression of movement and time demonstrated a moderate relationship between light and actigraphy (R2 = 0.56). CONCLUSIONS Despite requiring continued high-level care and a prolonged stay in a medical facility, patients recovering from critical illness and actively weaning from PMV maintain their circadian rhythm in phase with normal diurnal variations of light. PMID:24026184

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

    NASA Astrophysics Data System (ADS)

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

    2006-08-01

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

  13. Toward the Beginning of Time: Circadian Rhythms in Metabolism Precede Rhythms in Clock Gene Expression in Mouse Embryonic Stem Cells

    PubMed Central

    Paulose, Jiffin K.; Rucker, Edmund B.; Cassone, Vincent M.

    2012-01-01

    The appearance, progression, and potential role for circadian rhythms during early development have previously focused mainly on the suprachiasmatic nucleus (SCN) and peri- and postnatal expression of canonical clock genes. More recently, gene expression studies in embryonic stem cells have shown that some clock genes are expressed in undifferentiated cells; however rhythmicity was only established when cells are directed toward a neural fate. These studies also concluded that a functional clock is not present in ESCs, based solely on their gene expression. The null hypothesis underlying the present study is that embryonic stem cells become rhythmic in both clock gene expression and glucose utilization only when allowed to spontaneously differentiate. Undifferentiated stem cells (ESCs, n?=?6 cultures/timepoint for all experiments) were either maintained in their pluripotent state or released into differentiation (dESCs, n?=?6 cultures/timepoint for all experiments). Glucose utilization was assayed through 2-deoxyglucose uptake measurement, and clock gene and glucose transporter expression was assayed every 4 hours for 2 days in ESCs and dESCs by quantitative PCR (qPCR) in the same cell lysates. Undifferentiated stem cells expressed a self-sustained rhythm in glucose uptake that was not coincident with rhythmic expression of clock genes. This physiological rhythm was paralleled by glucose transporter mRNA expression. Upon differentiation, circadian patterns of some but not all clock genes were expressed, and the amplitude of the glucose utilization rhythm was enhanced in dESCs. These data provide the earliest evidence of a functional circadian clock, in addition to further challenging the idea that rhythmic transcription of clock genes are necessary for rhythmic physiological output and suggest a role for a clock-controlled physiology in the earliest stages of development. PMID:23155474

  14. The Nuclear Receptor Genes HR3 and E75 Are Required for the Circadian Rhythm in a Primitive Insect

    PubMed Central

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

    2014-01-01

    Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim) and period (per). Although the transcriptional regulation of Clock (Clk) has been profoundly studied, little is known about the regulation of cycle (cyc). Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Ror? and Rev-erb?, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes. PMID:25502221

  15. The Paramecium circadian behavioral rhythm: light phase response curves and entrainment.

    PubMed

    Hasegawa, K; Tanakadate, A

    1987-01-01

    The population of a ciliate protozoan, Paramecium multimicronucleatum, exhibits a circadian rhythm as measured by the number of the cells traversing an observation point ("traverse frequency," or TF). The present study examined phase shifting of the TF rhythm by administering 2-hr light pulses at different phases of the circadian cycle to cultures free-running in constant darkness (DD). The results were summarized in a phase response curve (PRC), categorized as Type 1. This PRC indicated a relatively narrow phase zone insensitive to the light pulse ("dead zone"). Entrainment of the rhythm to light pulses repeated at 24-hr intervals was also examined, and it was found that the rhythm gradually reached a steady state, following several transient cycles, with the pulses falling at a phase corresponding to the narrow dead zone. Such a steady-state rhythm, with a minimum at approximately 3 hr after the pulse and a maximum at approximately 12 hr after the pulse, was mathematically simulated by superimposing a response function to the pulse on a sinusoidal function representative of the free-running rhythm in DD. PMID:2979666

  16. 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

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

    PubMed Central

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

    2011-01-01

    Circadian rhythm sleep disorder, free-running type (CRSD, FRT) is a disorder in which the intrinsic circadian rhythm is no longer entrained to the 24-hour schedule. A unique case of CRSD, FRT in a 67-year-old sighted male is presented. The patient had a progressively delayed time in bed (TIB) each night, so that he would cycle around the 24-h clock approximately every 30 days. This was meticulously documented each night by the patient over the course of 22 years. The patient's CRSD, FRT was associated with severe depression, anxiety, and agoraphobia. The agoraphobia may have exacerbated the CRSD, FRT. Entrainment and stabilization of his circadian rhythm was accomplished after treatment that included melatonin, light therapy, and increased sleep structure. Citation: Brown MA; Quan SF; Eichling PS. Circadian rhythm sleep disorder, free-running type in a sighted male with severe depression, anxiety, and agoraphobia. J Clin Sleep Med 2011;7(1):93-94. PMID:21344043

  18. 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.

  19. Optic enucleation eliminates circadian rhythm shifts induced by stimulating the intergeniculate leaflet in Syrian hamsters.

    PubMed

    Kaur, Satvinder; Rusak, Benjamin

    2007-11-01

    The intergeniculate leaflet (IGL) is a region of the lateral geniculate complex that is part of the circadian system. It receives direct innervation by specialized retinal ganglion cells involved in circadian rhythm entrainment and is also reciprocally connected to the suprachiasmatic nucleus (SCN), which is the principal circadian pacemaker. Electrical stimulation in the IGL results in shifts of circadian rhythms with a pattern of phase dependence that resembles that elicited by periods of darkness. IGL stimulation also increases levels of c-Fos in the dorsolateral part of the caudal SCN. A previous study showed that optic enucleation prevents increases in c-Fos in the SCN, suggesting the hypothesis that this increase is related to antidromic activation of retinal ganglion cells which bifurcate and project to both SCN and IGL. We tested whether phase shifts induced by IGL stimulation are also dependent on intact retinal innervation. Electrical stimulation of the IGL for 60 min at circadian time (CT)9 (with CT12 defined as activity onset) induced phase advances in nine hamsters with electrodes in the IGL, while other placements did not evoke shifts. After optic enucleation, six of these hamsters received an identical second stimulation; none showed substantial phase shifts. These results are consistent with the hypothesis that phase shifts induced by IGL stimulation depend on antidromic activation of retinal ganglion cells. PMID:17931778

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

    PubMed Central

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

    2014-01-01

    Biological rhythms, generated by feedback loops containing interacting genes, proteins and/or cells, time physiological processes in many organisms. While many of the components of the systems that generate biological rhythms have been identified, much less is known about the details of their interactions. Using examples from the circadian (daily) clock in three organisms, Neurospora, Drosophila and mouse, we show, with mathematical models of varying complexity, how interactions among (i) promoter sites, (ii) proteins forming complexes, and (iii) cells can have a drastic effect on timekeeping. Inspired by the identification of many transcription factors, for example as involved in the Neurospora circadian clock, that can both activate and repress, we show how these multiple actions can cause complex oscillatory patterns in a transcription–translation feedback loop (TTFL). Inspired by the timekeeping complex formed by the NMO–PER–TIM–SGG complex that regulates the negative TTFL in the Drosophila circadian clock, we show how the mechanism of complex formation can determine the prevalence of oscillations in a TTFL. Finally, we note that most mathematical models of intracellular clocks model a single cell, but compare with experimental data from collections of cells. We find that refitting the most detailed model of the mammalian circadian clock, so that the coupling between cells matches experimental data, yields different dynamics and makes an interesting prediction that also matches experimental data: individual cells are bistable, and network coupling removes this bistability and causes the network to be more robust to external perturbations. Taken together, we propose that the interactions between components in biological timekeeping systems are carefully tuned towards proper function. We also show how timekeeping can be controlled by novel mechanisms at different levels of organization. PMID:24904739

  1. Long-lasting effects of sepsis on circadian rhythms in the mouse.

    PubMed

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

    2012-01-01

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

  2. The selective tachykinin neurokinin 1 (NK1) receptor antagonist, GR 205,171, stereospecifically inhibits light-induced phase advances of hamster circadian activity rhythms.

    PubMed

    Gannon, Robert L; Millan, Mark J

    2005-12-19

    Circadian rhythms in mammals are generated by master pacemaker cells located within the suprachiasmatic nucleus of the hypothalamus. In hamsters, the suprachiasmatic nucleus contains a small collection of cells immunoreactive for substance P, the endogenous ligand of tachykinin neurokinin 1 (NK1) receptors. In addition, two other nuclei which form part of the circadian system, the intergeniculate leaflet of the thalamus and the raphe nuclei, also contain fibers and/or cell bodies immunoreactive for substance P. In light of these observations, we evaluated the influence of the selective tachykinin NK1 receptor antagonist, GR 205,171, upon circadian activity rhythms in the hamster. Systemic injection of GR 205,171 dose-dependently (2.5-40.0 mg/kg, i.p.) inhibited light-induced phase advances in hamster circadian wheel running activity rhythms by approximately 50%. In contrast, GR 226,206, the less active enantiomer of GR 205,171, failed to affect light-induced phase advances. In addition, we examined the potential ability of GR 205,171 to induce non-photic phase shifts in hamster wheel running rhythms when injected at mid-day to late night circadian times. However, GR 205,171 (40 mg/kg) did not elicit non-photic phase shifts at these times indicating that tachykinin NK1 receptor antagonists are only effective when a light stimulus is applied to the pacemaker. Although GR 205,171 may, in theory, activate several sites within the circadian system, we suggest that GR 205,171 acts in the raphe nuclei to increase inhibitory serotonergic input to pacemaker cells in the suprachiasmatic nuclei, thereby suppressing photic modulation of the pacemaker. These findings have important implications for the use of tachykinin NK1 receptor antagonists in the treatment of depression and other central nervous system disorders. PMID:16307740

  3. CRY, a Drosophila Clock and Light-Regulated Cryptochrome, Is a Major Contributor to Circadian Rhythm Resetting and Photosensitivity

    Microsoft Academic Search

    Patrick Emery; W. Venus So; Maki Kaneko; Jeffrey C Hall; Michael Rosbash

    1998-01-01

    Light is a major environmental signal for circadian rhythms. We have identified and analyzed cry, a novel Drosophila cryptochrome gene. All characterized family members are directly photosensitive and include plant blue light photoreceptors. We show that cry transcription is under circadian regulation, influenced by the Drosophila clock genes period, timeless, Clock, and cycle. We also show that cry protein levels

  4. 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

  5. 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

  6. Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms

    PubMed Central

    Gérard, Claude; Goldbeter, Albert

    2012-01-01

    The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERB?, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values. PMID:22693436

  7. 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.

  8. Circadian locomotor activity rhythms of the burbot, Lota lota : Seasonal differences in period length and the effect of pinealectomy

    Microsoft Academic Search

    Martin Kavaliers

    1980-01-01

    The burbot,Lota lota, displayed a freerunning circadian locomotor activity rhythm under constant darkness. There was a seasonal change in the length of the circadian period (t). Fish captured during winter had a meant of 21.2±0.30 h as opposed to at of 23.5±0.25 in summer. Removal of the pineal organ had significant effects on the length and stability of the circadian

  9. 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 1?/? 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

  10. 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 1?/? 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

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

    PubMed

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

    2014-10-01

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

  12. High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light.

    PubMed

    Lockley, Steven W; Brainard, George C; Czeisler, Charles A

    2003-09-01

    The endogenous circadian oscillator in mammals, situated in the suprachiasmatic nuclei, receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells. The human circadian pacemaker is exquisitely sensitive to ocular light exposure, even in some people who are otherwise totally blind. The magnitude of the resetting response to white light depends on the timing, intensity, duration, number and pattern of exposures. We report here that the circadian resetting response in humans, as measured by the pineal melatonin rhythm, is also wavelength dependent. Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density. Similarly, 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light, and is dependent on the duration of exposure in addition to wavelength. These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system, the sensitivity of which peaks at approximately 555 nm. Thus photopic lux, the standard unit of illuminance, is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker. PMID:12970330

  13. A clockwork Bulla: cellular study of a model circadian system

    Microsoft Academic Search

    Gene D. Block; Michael E. Geusz; Sal Bir S. Khalsa; Stephan Michel

    1995-01-01

    The retina of the cloudy bubble snail, Bulla gouldiana, expresses a circadian rhythm in spontaneous optic nerve impulses. The rhythm is generated by a group of approximately 100 electrically coupled neurons at the base of the retina, each of which is competent to generate a circadian periodicity in complete cellular isolation. While the precise processes responsible for rhythm generation remain

  14. The Downs and Ups of Mechanistic Research: Circadian Rhythm Research as an Exemplar

    Microsoft Academic Search

    William Bechtel

    2010-01-01

    In the context of mechanistic explanation, reductionistic research pursues a decomposition of complex systems into their component\\u000a parts and operations. Using research on the mechanisms responsible for circadian rhythms, I consider both the gains that have\\u000a been made by discovering genes and proteins that figure in these intracellular oscillators and also highlight the increasingly\\u000a recognized need to understand higher-level integration,

  15. Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

    Microsoft Academic Search

    Ricardo Mora-Rodríguez; Jesús García Pallarés; Álvaro López-Samanes; Juan Fernando Ortega; Valentín E. Fernández-Elías

    2012-01-01

    PurposeTo investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern.MethodsTwelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg?1; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo

  16. Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy

    Microsoft Academic Search

    Henrik P Hansen; Peter Rossing; Lise Tarnow; Flemming S Nielsen; Berit R Jensen; Hans-Henrik Parving

    1996-01-01

    Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy. The aim of our study was to evaluate the diurnal relationship between arterial blood pressure and albuminuria, and some potential mechanisms responsible for impaired nocturnal blood pressure reduction (non-dippers, groups I and II) in diabetic nephropathy (DN). Twenty-four-hour ambulatory blood pressure, heart rate (HR) variation (autonomic nervous function) and

  17. Circadian Rhythm in the Cardiovascular System: Considerations in Non-Invasive Electrophysiology

    Microsoft Academic Search

    Yi-Fang Guo; Phyllis K. Stein

    2002-01-01

    Most cardiovascular activities show a circadian rhythm, as do electrophysiological phenomenon. Under theinfluence of both external stimuli and endogenous homoeostatic mechanisms, cardiac electrophysiologicalproperties change diurnally and enable the cardiovascular system adapt to rest-exercise cycles. According torecent reports, almost all non-invasive electrophysiological phenomena, such as electrocardiographic indices,cardiac refractoriness and conduction, pacing and defibrillation threshold, heart rate variability indices, andeven Q-T dispersion

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

    PubMed Central

    Thorpy, Michael J; Roth, Thomas

    2013-01-01

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

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

    PubMed

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

    2015-06-01

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

  20. Circadian Rhythm in the Visual System of the Lizard Anolis carolinensis

    Microsoft Academic Search

    Andrew P. Shaw; C. Raul Collazo; Keith Easterling; Cheryl D. Young; Chester J. Karwoski

    1993-01-01

    The electroretinogram (ERG) was recorded from free-moving Anolis lizards once per hour for 5 days. As in our previous work, the b-wave, but not the a-wave, showed a reliable circadian rhythm (CR) in amplitude, with an acrophase near projected noon. Both the a- and b-waves showed a CR in peak time (implicit time, or IT), with the a-wave IT being

  1. 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.

  2. 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.

  3. 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

  4. Circadian Rhythms Differ between Sexes and Closely Related Species of Nasonia Wasps

    PubMed Central

    Bertossa, Rinaldo C.; van Dijk, Jeroen; Diao, Wenwen; Saunders, David; Beukeboom, Leo W.; Beersma, Domien G. M.

    2013-01-01

    Activity rhythms in 24 h light-dark cycles, constant darkness, and constant light conditions were analyzed in four different Nasonia species for each sex separately. Besides similarities, clear differences are evident among and within Nasonia species as well as between sexes. In all species, activity in a light-dark cycle is concentrated in the photophase, typical for diurnal organisms. Contrary to most diurnal insect species so far studied, Nasonia follows Aschoff's rule by displaying long (>24 h) internal rhythms in constant darkness but short (<24 h) in constant light. In constant light, N. vitripennis males display robust circadian activity rhythms, whereas females are usually arrhythmic. In contrast to other Nasonia species, N. longicornis males display anticipatory activity, i.e. activity shortly before light-on in a light-dark cycle. As expected, N. oneida shows activity patterns similar to those of N. giraulti but with important differences in key circadian parameters. Differences in circadian activity patterns and parameters between species may reflect synchronization of specific life-history traits to environmental conditions. Scheduling mating or dispersion to a specific time of the day could be a strategy to avoid interspecific hybridization in Nasonia species that live in sympatry. PMID:23555911

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

    PubMed Central

    Zhang, Xiping; Dube, Thomas J.

    2009-01-01

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

  6. 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

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

    PubMed

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

    2015-01-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R(2), 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

  8. Light as a central modulator of circadian rhythms, sleep and affect

    PubMed Central

    LeGates, T.A.; Fernandez, D.C.; Hattar, S

    2014-01-01

    Light has profoundly influenced the evolution of life on earth. As widely appreciated, light allows us to generate images of our environment. However, light, through the atypical intrinsically photosensitive retinal ganglion cells (ipRGCs; Box 1), also influences behaviors that are essential for our health and quality of life, yet are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes, and regulation of sleep. Irregular light environments lead to problems in circadian rhythms and sleep, which eventually cause mood and learning deficits. Recently, it was found that irregular light can also directly impact mood and learning without producing major disruptions in circadian rhythms and sleep. Here, we will discuss the indirect and direct influence of light on mood and learning and provide a model for how light, the circadian clock, and sleep interact to influence mood and cognitive functions. Box 1Intrinsically photosensitive retinal ganglion cells (ipRGCs)Retinal photoreceptors transduce light energy into electrical signals that initiate vision. The classical photoreceptors, rods and cones, possess modified cilia that consist of stacks of membranes in which photopigments (rhodopsin and cone opsins) are concentrated. Rods are exquisitely sensitive and are able to detect even a few photons. Rods are therefore used for night vision. Cones are less sensitive than rods and are used for day and color vision. Color vision is mediated by cone photoreceptors that express cone-opsins with sensitivity peaks at different wavelengths (colors) of light. Humans have three cone types: short, mid and long wavelength sensitive cones (for simplicity, we will refer to these as blue, green and red cones, respectively). Rods and cones relay photic information through multisynaptic pathways to retinal ganglion cells (RGCs), which innervate different areas in the brain for complex visual processing13.A surprising discovery showed that a subpopulation of RGCs is intrinsically photosensitive and express the photopigment melanopsin. These cells were thus termed ipRGCs17–19. The melanopsin gene (Opn4) was originally cloned from Xenopus laevis dermal melanophores, and was shown to have orthologs in many mammalian species, including humans141. Sequence analysis shows that melanopsin shares more homology with invertebrate opsins than with vertebrate opsins, suggesting that melanopsin may use a different mechanism for light signaling than that used by the photopigments present in the rods and cones of vertebrates142. ipRGCs do not have modified membranes in which the photopigment can be concentrated: thus, melanopsin protein is expressed uniformly throughout the soma, dendrites, and the initial segment of the axon143. The lack of membrane specialization makes ipRGCs less sensitive to light than rods and cones. However, ipRGCs are able to incorporate light signals over extended period of time, resulting in an increase in their sensitivity during prolonged light stimulation. ipRGCs are most sensitive to wavelengths of light that are in the blue region of the light spectrum144, 145. As ganglion cells, ipRGCs also convey light information from rods and cones in addition to their intrinsic melanopsin-dependent pathway and can control a variety of light-mediated behaviors30.Originally, ipRGCs were thought to comprise a uniform population, however, recent discoveries revealed that ipRGCs are highly diverse, comprising at least five distinct subtypes (M1-M5) in rodents based on morphological and electrophysiological analyses22–29. The originally identified population is now known as M1 ipRGCs and project predominantly to brain regions involved in non-image forming visual functions, whereas the non-M1 ipRGCs show widespread projections to areas in the brain important for image formation. ipRGC subtypes express varying levels of the melanopsin protein and have different patterns of dendrite stratification in the inner plexiform layer (IPL)27, 28, 146, 147, indicating

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

    NASA Astrophysics Data System (ADS)

    Kumar, Vinod; Gwinner, Eberhard

    2005-09-01

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

  10. Progressive disruption of the circadian rhythm of melatonin in fatal familial insomnia.

    PubMed

    Portaluppi, F; Cortelli, P; Avoni, P; Vergnani, L; Maltoni, P; Pavani, A; Sforza, E; Degli Uberti, E C; Gambetti, P; Lugaresi, E

    1994-05-01

    Fatal familial insomnia (FFI) is a disease characterized by loss of sleep activity due to selective thalamic degeneration. To assess the secretory pattern of melatonin (MT) in FFI, we studied two cases of overt disease under standardized conditions and polysomnographic control. Each patient underwent repeated 24-h study sessions, and MT was assayed at 30-min intervals. Six healthy volunteers were used as controls. Slow wave sleep was never recorded, whereas occasional episodes of enacted dreaming accompanied by rapid ocular movements and complex muscular activities were documented, with no detectable rhythm. Plasma MT concentrations gradually decreased as the disease progressed. A significant circadian rhythm was detected in the earlier recordings, with decreasing amplitudes with disease progression. Complete rhythm obliteration was achieved in the most advanced stage. Normally placed nocturnal acrophases were detected in the earlier stages, but then a shift toward the daytime hours was observed. Thalamic lesions of FFI appear to determine a progressive disruption of the sleep/wake cycle accompanied by decreased circulating levels of MT, with progressive alterations in the circadian rhythm of this hormone. On the other hand, decreased secretion of MT may contribute to the sleep disturbances of FFI. PMID:8175963

  11. Effects of illumination on the rabbit's EEG during the two phases of its circadian rhythm.

    PubMed

    Bobbert, A C; van Hartevelt, J H

    1987-01-01

    After exposure to a LD 12:12 regimen for several weeks, rabbits exhibit a programmed circadian rhythm in the RMS values of their occipital and frontal EEG's during 54-hr recordings in constant darkness. Illumination at levels of 80, 160 and 230 Lx raises these RMS values in both phases of the rhythm. The induced rise is large in the phase with low RMS values and small in the other, whereas light-induced changes in spectral composition of the EEG's are slight in either phase. Bilateral optic nerve sectioning results in similar changes in properties of the EEG and in the amplitude of its rhythm. The results are discussed with reference to the influence exerted by steady illumination on the overall-level of retinal maintained "dark" discharge. PMID:3508743

  12. Convergent rhythm generation from divergent cellular mechanisms.

    PubMed

    Rodriguez, Jason C; Blitz, Dawn M; Nusbaum, Michael P

    2013-11-13

    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 Ca(2+) 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

  13. The colony environment, but not direct contact with conspecifics, influences the development of circadian rhythms in honey bees.

    PubMed

    Eban-Rothschild, Ada; Shemesh, Yair; Bloch, Guy

    2012-06-01

    Honey bee (Apis mellifera) workers emerge from the pupae with no circadian rhythms in behavior or brain clock gene expression but show strong rhythms later in life. This postembryonic development of circadian rhythms is reminiscent of that of infants of humans and other primates but contrasts with most insects, which typically emerge from the pupae with strong circadian rhythms. Very little is known about the internal and external factors regulating the ontogeny of circadian rhythms in bees or in other animals. We tested the hypothesis that the environment during early life influences the later expression of circadian rhythms in locomotor activity in young honey bees. We reared newly emerged bees in various social environments, transferred them to individual cages in constant laboratory conditions, and monitored their locomotor activity. We found that the percentage of rhythmic individuals among bees that experienced the colony environment for their first 48 h of adult life was similar to that of older sister foragers, but their rhythms were weaker. Sister bees isolated individually in the laboratory for the same period were significantly less likely to show circadian rhythms in locomotor activity. Bees experiencing the colony environment for only 24 h, or staying for 48 h with 30 same-age sister bees in the laboratory, were similar to bees individually isolated in the laboratory. By contrast, bees that were caged individually or in groups in single- or double-mesh enclosures inside a field colony were as likely to exhibit circadian rhythms as their sisters that were freely moving in the same colony. These findings suggest that the development of the circadian system in young adult honey bees is faster in the colony than in isolation. Direct contact with the queen, workers, or the brood, contact pheromones, and trophallaxis, which are all important means of communication in honey bees, cannot account for the influence of the colony environment, since they were all withheld from the bees in the double-mesh enclosures. Our results suggest that volatile pheromones, the colony microenvironment, or both influence the ontogeny of circadian rhythms in honey bees. PMID:22653890

  14. Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome.

    PubMed

    Hamilos, D L; Nutter, D; Gershtenson, J; Ikle, D; Hamilos, S S; Redmond, D P; Di Clementi, J D; Schmaling, K B; Jones, J F

    2001-03-01

    The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms. In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight-matched and were known to have normal basal metabolic rates and thyroid function. CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. CBT time series were analysed by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and sigma2. Average parameters for each group were compared by Student's t-test. By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0.02). The optimal harmonic-regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant. We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT. PMID:11318826

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

    PubMed Central

    Romanowski, Andrés; Yanovsky, Marcelo J.

    2015-01-01

    The circadian clock of plants allows them to cope with daily changes in their environment. This is accomplished by the rhythmic regulation of gene expression, in a process that involves many regulatory steps. One of the key steps involved at the RNA level is post-transcriptional regulation, which ensures a correct control on the different amounts and types of mRNA that will ultimately define the current physiological state of the plant cell. Recent advances in the study of the processes of regulation of pre-mRNA processing, RNA turn-over and surveillance, regulation of translation, function of lncRNAs, biogenesis and function of small RNAs, and the development of bioinformatics tools have helped to vastly expand our understanding of how this regulatory step performs its role. In this work we review the current progress in circadian regulation at the post-transcriptional level research in plants. It is the continuous interaction of all the information flow control post-transcriptional processes that allow a plant to precisely time and predict daily environmental changes. PMID:26124767

  16. Visual responses in teleosts. Electroretinograms, eye movements, and circadian rhythms.

    PubMed

    McMahon, D G; Barlow, R B

    1992-07-01

    We have recorded ocular potentials in response to brief flashes of light from two teleosts, the white perch (Roccus americana) and the green sunfish (Lepomis cyanellus). The animals were respired and maintained in an alert state for up to 2 d. Responses were recorded with corneal and transcleral electrodes. The responses of green sunfish were composed of electroretinogram (ERG) and eye movement potentials, whereas the responses in white perch contained only the ERG. Injection of curare abolished the sunfish eye movement potentials, unmasking the ERG. Observation under infrared illumination established a direct relationship between eye movements and the fast potentials which could be abolished by curare. We found no evidence of circadian changes in the amplitude of the ERG b-wave of either species. However, our results combined with those of a previous study of sunfish ocular potentials (Dearry, A., and B. Barlow, Jr. 1987. J. Gen. Physiol. 89: 745-770) suggest that the sunfish visual system exhibits rhythmic changes in oculomotor responses, which appear to be controlled by a circadian oscillator. PMID:1512556

  17. Visual responses in teleosts. Electroretinograms, eye movements, and circadian rhythms

    PubMed Central

    1992-01-01

    We have recorded ocular potentials in response to brief flashes of light from two teleosts, the white perch (Roccus americana) and the green sunfish (Lepomis cyanellus). The animals were respired and maintained in an alert state for up to 2 d. Responses were recorded with corneal and transcleral electrodes. The responses of green sunfish were composed of electroretinogram (ERG) and eye movement potentials, whereas the responses in white perch contained only the ERG. Injection of curare abolished the sunfish eye movement potentials, unmasking the ERG. Observation under infrared illumination established a direct relationship between eye movements and the fast potentials which could be abolished by curare. We found no evidence of circadian changes in the amplitude of the ERG b-wave of either species. However, our results combined with those of a previous study of sunfish ocular potentials (Dearry, A., and B. Barlow, Jr. 1987. J. Gen. Physiol. 89: 745-770) suggest that the sunfish visual system exhibits rhythmic changes in oculomotor responses, which appear to be controlled by a circadian oscillator. PMID:1512556

  18. Exercise as a synchroniser of human circadian rhythms: an update and discussion of the methodological problems.

    PubMed

    Atkinson, Greg; Edwards, Ben; Reilly, Thomas; Waterhouse, Jim

    2007-03-01

    We review the literature on whether exercise is a synchroniser of human circadian rhythms, and highlight the specific methodological problems that are associated with this topic. In applied research, exercise has been investigated as a treatment for jet lag and shift-work problems. In these studies, there have been difficulties in controlling the characteristics of the exercise bout, the athletic status of research participants and exposure to other confounding synchronisers. Therefore, it is unclear at present whether exercise can help mitigate the problems associated with transmeridian travel and shift-work. In laboratory-based experiments, participants have exercised at various times of the day and the change in phase of various circadian rhythms has been measured. Although it is difficult to control for the considerable masking effects of exercise on these estimates of circadian timing, it is clear that nocturnal exercise can induce phase delays in the onset of melatonin. Reports of exercise-induced phase advances of the melatonin rhythm are rarer, as are any phase-shifting effects at all on the body temperature rhythm. In practical terms, the substantial levels of activity needed to obtain phase shifts may not be attainable by the majority of people. In mechanistic terms, the lack of agreement with the phase-shifting effects of bright light suggests that exercise is not exerting its effects via photic entrainment pathways. An alternative explanation may involve exercise-induced hyperthermia. Moreover, it is perplexing why exercise should have a different phase response curve to light, given that humans are diurnally active. PMID:17165050

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

    PubMed

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

    2014-06-01

    Circadian rhythms are responsive to external and internal cues, light and metabolism being among the most important. In mammals, the light signal is sensed by the retina and transmitted to the suprachiasmatic nucleus (SCN) master clock [1], where it is integrated into the molecular oscillator via regulation of clock gene transcription. The SCN synchronizes peripheral oscillators, an effect that can be overruled by incoming metabolic signals [2]. As a consequence, peripheral oscillators can be uncoupled from the master clock when light and metabolic signals are not in phase. The signaling pathways responsible for coupling metabolic cues to the molecular clock are being rapidly uncovered [3-5]. Here we show that insulin-phosphatidylinositol 3-kinase (PI3K)-Forkhead box class O3 (FOXO3) signaling is required for circadian rhythmicity in the liver via regulation of Clock. Knockdown of FoxO3 dampens circadian amplitude, an effect that is rescued by overexpression of Clock. Subsequently, we show binding of FOXO3 to two Daf-binding elements (DBEs) located in the Clock promoter area, implicating Clock as a transcriptional target of FOXO3. Transcriptional oscillation of both core clock and output genes in the liver of FOXO3-deficient mice is affected, indicating a disrupted hepatic circadian rhythmicity. Finally, we show that insulin, a major regulator of FOXO activity [6-9], regulates Clock levels in a PI3K- and FOXO3-dependent manner. Our data point to a key role of the insulin-FOXO3-Clock signaling pathway in the modulation of circadian rhythms. PMID:24856209

  20. [Peculiarities of circadian rhythms in plants from different geographical latitudes].

    PubMed

    Mayer, W

    1966-09-01

    1 Two species of plants (Taraxacum arcticum and Arnica angustifolia), collected in Spitsbergen (geogr. latitude 76-80 degrees) exhibit endogenous circadian leaf movements but also movements with shorter periods. Astragalus frigidus, A. alpinus and Hedysarum hedysaroides, collected in arctic regions of continental Europe, also show endogenous diurnal leaf movements. 2. In most of the species tested, there was no difference in the length of the free running periods of plants from arctic and Central-European regions. This is also the case when individuals of the same species collected in different regions are compared. However, in Taraxacum arcticum the period is shorter than in T. officinale In general, under constant conditions the circadian oscillations of arctic plants persist for a shorter period than those of other plants. 3. The free running periods of several of the investigated species from tropical regions are much longer than 24 hours, i.e., much longer than those of species from Central-European and arctic regions. 4. The free running periods of several tropical species are temperature-independent (Erythrina senegalensis, Albizzia lophanta, Rhynchosia memmonia, Vigna catjang, Phaseolus multiflorus). In other tropical species, however, the periods decrease rather strongly with increasing temperature (Phaseolus mungo, Canavalia obtusifolia, Clitoria ternatea, Dolichos lablab, Vigna sesquipedalis, Dolichos zebra). The temperature does not influence the amplitudes in Phaseolus mungo and Vigna sesquipedalis, but it strongly influences the amplitudes in Erythrina senegalensis, in LD-cycles as well as in continuous light. 5. The arctic plant Astragalus frigidus still shows free running oscillations at 12°C, whereas several tropical species oscillate only at temperatures above 17°C. 6. The differences in the periods of tropical and non-tropical species (see under [3]) disappear if the plants are compared not at the same temperature but at temperatures which are optimal for them. If tropical plants are tested 27°C and Central-European and arctic species at 17°C, the periods always approach the value of 24 hours. PMID:24557984

  1. Disruption of cardiovascular circadian rhythms in mice post myocardial infarction: relationship with central angiotensin II receptor expression

    PubMed Central

    Mousa, Tarek M.; Schiller, Alicia M.; Zucker, Irving H.

    2014-01-01

    Abstract Angiotensin II (Ang II) is well known to participate in the abnormal autonomic cardiovascular control that occurs during the development of chronic heart failure (CHF). Disrupted cardiovascular circadian rhythm in CHF is also well accepted; however, the mechanisms underlying and the role of central Ang II type 1 receptors (AT1R) and oxidative stress in mediating such changes are not clear. In a post myocardial infarction (MI) CHF mouse model we investigated the circadian rhythm for mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS) following MI. The cardiovascular parameters represent the middle 6?h averages during daytime (6:00–18:00) and nighttime (18:00–6:00). HR increased with the severity of CHF reaching its maximum by 12 weeks post?MI; loss of circadian HR and BRS rhythms were observed as early as 4 weeks post?MI in conjunction with a significant blunting of the BRS and an upregulation in the AT1R and gp91phox proteins in the brainstem. Loss of MAP circadian rhythm was observed 8 weeks post?MI. Circadian AT1R expression was demonstrated in sham animals but was lost 8 weeks following MI. Losartan reduced AT1R expression in daytime (1.18 ± 0.1 vs. 0.85 ± 0.1; P < 0.05) with a trend toward a reduction in the AT1R mRNA expression in the nighttime (1.2 ± 0.1 vs. 1.0 ± 0.1; P > 0.05) but failed to restore circadian variability. The disruption of circadian rhythm for HR, MAP and BRS along with the upregulation of AT1 and gp91phox suggests a possible role for central oxidative stress as a mediator of circadian cardiovascular parameters in the post?MI state. PMID:25413327

  2. 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.

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

    PubMed

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

    2015-04-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3? isoform. Whether phosphorylation of the other primary isoform (GSK3?) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (? and ?) 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 (? and ?) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. PMID:25724980

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

    PubMed

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

    2015-07-01

    The quality of life of hemodialysis (HD) patients is hampered by reduced nocturnal sleep quality and excessive daytime sleepiness. In addition to the sleep/wake cycle, levels of circadian biomarkers (e.g. melatonin) are disturbed in end-stage renal disease (ESRD). This suggests impaired circadian clock performance in HD patients, but the underlying mechanism is unknown. In this observational study, diurnal rhythms of sleep, serum melatonin and cortisol concentrations and clock gene mRNA expression are compared between HD patients (n?=?9) and healthy control subjects (n?=?9). In addition, the presence of circulating factors that might affect circadian rhythmicity is tested in vitro with cell culture experiments. Reduced sleep quality (median sleep onset latency [interquartile range] of 23.9 [17.3]?min for patients versus 5.0 [10] minutes for controls, p?circadian control of cortisol rhythm and circadian expression of the clock gene REV-ERB? were found. HD patient serum had a higher capacity to synchronize cells in vitro, suggesting an accumulated level of clock resetting compounds in HD patients. These compounds were not cleared by hemodialysis treatment or related to frequently used medications. In conclusion, the abovementioned results strongly suggest a disturbance in circadian timekeeping in peripheral tissues of HD patients. Accumulation of clock resetting compounds possibly contributes to this. Future studies are needed for a better mechanistic understanding of the interaction between renal failure and perturbation of the circadian clock. PMID:26101944

  5. Fragile X-Related Proteins Regulate Mammalian Circadian Behavioral Rhythms

    PubMed Central

    Zhang, Jing; Fang, Zhe; Jud, Corinne; Vansteensel, Mariska J.; Kaasik, Krista; Lee, Cheng Chi; Albrecht, Urs; Tamanini, Filippo; Meijer, Johanna H.; Oostra, Ben A.; Nelson, David L.

    2008-01-01

    Fragile X syndrome results from the absence of the fragile X mental retardation 1 (FMR1) gene product (FMRP). FMR1 has two paralogs in vertebrates: fragile X related gene 1 and 2 (FXR1 and FXR2). Here we show that Fmr1/Fxr2 double knockout (KO) and Fmr1 KO/Fxr2 heterozygous animals exhibit a loss of rhythmic activity in a light:dark (LD) cycle, and that Fmr1 or Fxr2 KO mice display a shorter free-running period of locomotor activity in total darkness (DD). Molecular analysis and in vitro electrophysiological studies suggest essentially normal function of cells in the suprachiasmatic nucleus (SCN) in Fmr1/Fxr2 double KO mice. However, the cyclical patterns of abundance of several core clock component messenger (m) RNAs are altered in the livers of double KO mice. Furthermore, FXR2P alone or FMRP and FXR2P together can increase PER1- or PER2-mediated BMAL1-Neuronal PAS2 (NPAS2) transcriptional activity in a dose-dependent manner. These data collectively demonstrate that FMR1 and FXR2 are required for the presence of rhythmic circadian behavior in mammals and suggest that this role may be relevant to sleep and other behavioral alterations observed in fragile X patients. PMID:18589395

  6. Does Disruption of Circadian Rhythms Contribute to Beta-Cell Failure in Type 2 Diabetes?

    PubMed Central

    Rakshit, Kuntol; Thomas, Anthony P.

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by the loss of beta-cell secretory function and mass. The pathophysiology of beta-cell failure in T2DM involves a complex interaction between genetic susceptibilities and environmental risk factors. One environmental condition that is gaining greater appreciation as a risk factor for T2DM is the disruption of circadian rhythms (eg, shift-work and sleep loss). In recent years, circadian disruption has become increasingly prevalent in modern societies and consistently shown to augment T2DM susceptibility (partly mediated through its effects on pancreatic beta-cells). Since beta-cell failure is essential for development of T2DM, we will review current work from epidemiologic, clinical, and animal studies designed to gain insights into the molecular and physiological mechanisms underlying the predisposition to beta-cell failure associated with circadian disruption. Elucidating the role of circadian clocks in regulating beta-cell health will add to our understanding of T2DM pathophysiology and may contribute to the development of novel therapeutic and preventative approaches. PMID:24532160

  7. 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.

  8. 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.

  9. Influences of horizontal hypokinesia on performance and circadian physiological rhythms in female humans

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Deroshia, C. W.; Sandler, H.

    1982-01-01

    Eight females from 35-45 yr of age were subjected to seven days of ambulatory control, seven days of bed rest, and a five day recovery period, with 30 min of centrifugation on day seven of bedrest to determine the effects of weightlessness on the circadian rhythms of females in that age group. Heart rate and rectal temperature (RT) were monitored and each subject was tested in a flight simulator twice a day in conditions of varying levels of turbulence. The flight simulations were run during the morning and acrophase of the circadian RT and performance errors wery monitored for 6 min. No significant differences were detected in the group performance data pre-, during, and post-bedrest, although better performance in the simulator was observed after the centrifuge exposure. An RT phase shift was statistically significant between pre- and during bedrest stages.

  10. 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

  11. 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.

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

    PubMed

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

    2015-06-01

    Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Ppar?, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-?, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood. PMID:25928088

  13. The pineal clock affects behavioral circadian rhythms but not photoperiodic induction in the Indian weaver bird ( Ploceus philippinus )

    Microsoft Academic Search

    Sangeeta Rani; Sudhi Singh; Vinod Kumar

    2005-01-01

    We investigated whether pineal is part of the circadian clock system which regulates circadian rhythms of activity and photosensitivity\\u000a in the Indian weaver bird (Ploceus philippinus). Two experiments were performed. The first experiment examined the induction of testicular growth, and androgen-dependent\\u000a beak pigmentation and luteinizing hormone (LH)-specific plumage coloration in pinealectomised (pinx) and sham-operated (sham)\\u000a birds exposed to short day

  14. Effect of ambient temperature on the circadian activity rhythm in common marmosets, Callithrix j. jacchus (primates).

    PubMed

    Pálková, M; Sigmund, L; Erkert, H G

    1999-03-01

    Whereas the (zeitgeber) effect of ambient temperature Ta and temperature cycles TaC's on circadian rhythmicity has been well documented for heterothermic mammals, inconsistent results have been obtained for strictly homeothermic species. Hence, it might be inferred that the susceptibility of the mammalian circadian timing system (CTS) to Ta and TaC's depends on the range of the animals' core and/or brain temperature rhythm. This hypothesis was tested in the common marmoset (Callithrix j. jacchus, n = 12), a small diurnal primate with an amplitude in body temperature rhythm that is larger than for other homeothermic primates studied so far. Within the range 20-30 degrees C, no systematic effects of constant Ta on most parameters of the marmosets' light-dark (LD)-entrained and free-running circadian activity rhythm (CAR) were found. Significant differences could be established in the average amount of activity per circadian cycle. It was highest at Ta 25 degrees C (LD) and 20 degrees C (light-light, LL) and most probably reflected a temperature-induced masking effect. A 24 h trapezoidal TaC of 20:30 degrees C entrained the free-running CAR in two of six marmosets and produced relative coordination in all others. Accordingly, in all animals tested, it had an effect on the CTS. In marmosets free running in LL at a Ta of 20 degrees C or 30 degrees C, 3 h warm and cold pulses of 30 degrees C and 20 degrees C, respectively, produced neither systematic phase responses nor period responses of the CAR. So, there is no evidence of a phase-response mechanism underlying circadian entrainment. The results show that large-amplitude TaC's function as a weak zeitgeber for the marmosets' CTS. Since this zeitgeber effect is significantly larger than that found in owl monkeys, the results are consistent with the starting hypothesis that the zeitgeber effect of a given TaC on the mammalian CTS may be related to the amplitude of the species' core and/or brain temperature cycle. PMID:10219487

  15. Pharmacology of Myopia and Potential Role for Intrinsic Retinal Circadian Rhythms

    PubMed Central

    Stone, Richard A.; Pardue, Machelle T.; Iuvone, P. Michael; Khurana, Tejvir S.

    2013-01-01

    Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetycholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine’s role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors. PMID:23313151

  16. The influence of L-arginine on circadian rhythm and circadian period genes

    Microsoft Academic Search

    Yuting Yang; Shuting Cheng; Yonghong Li; Zhou Jiang; Yanyou Liu; Yuhui Wang; Jing Xiao; Huiling Guo; Zhengrong Wang

    2012-01-01

    To study the effect of L-arginine on circadian system, ICR mice and AR4-2J cells were treated with L-arginine. The locomotor activity of the mice intraperitoneally injected with a high dose of L-arginine was observed. We also detected effects of arginine on Per1 and Per2 gene expressions in AR4-2J cells. Double-plotted actograms were applied to analyze the locomotor activity of the

  17. Properties of the Aplysia visual system: in vitro entrainment of the circadian rhythm and centrifugal regulation of the eye

    Microsoft Academic Search

    Arnold Eskin

    1971-01-01

    1.Properties of the visual system of Aplysia californica were studied by recording optic nerve impulses extracellularly from isolated eyes in constant darkness.2.In vivo entrainment of the circadian rhythm of afferent optic nerve impulses by LD 12:12 cycles phase advanced 13 hours was essentially complete after only one exposure of the animal to this light cycle.3.The impulse rhythms of eyes exposed

  18. Two-oscillator structure of the pacemaker controlling the circadian rhythm of N-acetyltransferase in the rat pineal gland

    Microsoft Academic Search

    Helena Illnerová; Ji?í Van??ek

    1982-01-01

    1.The organization of the pacemaker driving the circadian rhythm of N-acetyltransferase activity in the rat pineal gland was studied by observing changes of the rhythm caused by 1 min light pulses applied at night. These pulses proved to be effective phase-shifting signals.2.After 1 min light pulses applied in the first half of the night. N-acetyltransferase activity began to increase anew

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

    PubMed

    Hotta, Carlos Takeshi; Nishiyama, Milton Yutaka; Souza, Glaucia Mendes

    2013-01-01

    Commercial sugarcane (Saccharum hybrid) is a highly polyploid and aneuploid grass that stores large amounts of sucrose in its stem. We have measured circadian rhythms of sense and antisense transcription in a commercial cultivar (RB855453) using a custom oligoarray with 14,521 probes that hybridize to sense transcripts (SS) and 7,380 probes that hybridize to antisense transcripts (AS).We estimated that 32% of SS probes and 22% AS probes were rhythmic. This is a higher proportion of rhythmic probes than the usually found in similar experiments in other plant species. Orthologs and inparalogs of Arabidopsis thaliana, sugarcane, rice, maize and sorghum were grouped in ortholog clusters. When ortholog clusters were used to compare probes among different datasets, sugarcane also showed a higher proportion of rhythmic elements than the other species. Thus, it is possible that a higher proportion of transcripts are regulated by the sugarcane circadian clock. Thirty-six percent of the identified AS/SS pairs had significant correlated time courses and 64% had uncorrelated expression patterns. The clustering of transcripts with similar function, the anticipation of daily environmental changes and the temporal compartmentation of metabolic processes were some properties identified in the circadian sugarcane transcriptome. During the day, there was a dominance of transcripts associated with photosynthesis and carbohydrate metabolism, including sucrose and starch synthesis. During the night, there was dominance of transcripts associated with genetic processing, such as histone regulation and RNA polymerase, ribosome and protein synthesis. Finally, the circadian clock also regulated hormone signalling pathways: a large proportion of auxin and ABA signalling components were regulated by the circadian clock in an unusual biphasic distribution. PMID:23936527

  20. Staining in the brain of Pachymorpha sexguttata mediated by an antibody against a Drosophila clock-gene product: labeling of cells with possible importance for the beetle's circadian rhythms

    Microsoft Academic Search

    Brigitte Frisch; Gerta Fleissner; Günther Fleissner; Christian Brandes; Jeffrey C. Hall

    1996-01-01

    Central nervous system ganglia within the head of the beetle Pachymorpha sexguttata were labeled using an antibody that recognizes an evolutionarily conserved region of the period (per) gene product of Drosophila melanogaster. per and the protein it encodes (PER) are believed to play a central role in the generation of endogenous circadian rhythms in flies; therefore anti-PER-mediated immunoreactivity may help

  1. Irradiance responsivity and unequivocal type-1 phase responsivity of rat circadian activity rhythms.

    PubMed

    Bauer, M S

    1992-11-01

    Behavioral, neuropharmacological, and molecular studies of light-induced phase shifting of rodent circadian rhythms evaluate carefully the phase dependence of light responsivity. However, much less information is available regarding the dependence of such effects on the duration and irradiance of the photic stimulus used. In this study, very brief (5-min) white light pulses of 50 microW/cm2 (175 lux) administered to hooded rats elicited unequivocal type-1 phase responsivity, without significant changes in period, and with phase shift variability comparable to that in studies using longer, higher intensity pulses. Irradiance dependence was demonstrated in the phase-delay, phase-advance, and crossover portions of the phase-response curve, with minimal phase shifting seen during the dead zone even at very high irradiance. These results indicate that maximal phase-shifting magnitude may be achieved with shorter, less intense photic stimuli than are often used in studies of the neural mechanisms involved in light responsivity of rat circadian rhythms. PMID:1443229

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

    PubMed

    Liu, Qi; Gong, Yinhua; Shi, Yun; Jiang, Liqun; Zheng, Chunli; Ge, Liang; Liu, Jianping; Zhu, Jiabi

    2013-06-01

    This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit(®) NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease(®) were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases. PMID:23649996

  3. 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 (?(2) with p?=?0.011) and the photoperiod at birth (?(2) with p?circadian rhythm of activity levels was influenced by the chronotype; second, the chronotype had a significant effect on sleep parameters: the E-types had a reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These findings suggest that E-types accumulate a sleep deficit during weekdays due to social and academic commitments and that they recover from this deficit during "free days" on the weekend. PMID:25469597

  4. Coordinated regulation of circadian rhythms and homeostasis by the suprachiasmatic nucleus

    PubMed Central

    Nakagawa, Hachiro; Okumura, Nobuaki

    2010-01-01

    We have demonstrated that in rats activities of various enzymes related to gluconeogenesis and amino acid metabolism show circadian rhythms. Based on these results, we have explored the molecular mechanisms underlying circadian oscillation and phase response to light of the master clock located in the dorsomedial subdivision of the suprachiasmatic nucleus (SCN) and found various proteins closely related to phase response such as BIT/SHPS-1 and those of circadian oscillation, some of which are involved in protein-tyrosine phosphorylation. On the other hand, we have presented several lines of evidence that the ventrolateral subdivision of the SCN includes not only the control center of energy supply to the brain, but also that of homeostasis such as blood glucose, blood pressure, water balance, and body temperature. We have also shown that besides these functions, the latter subdivision is involved in the regulations of hormone secretions such as insulin, glucagon, corticosterone and vasopressin. It has been also shown by electrophysiological means that light exposure to rat eye enhances sympathetic nerve activity, whereas it depresses parasympathetic nerve activity. Thus, environmental light is implicated not only in the phase-shift through the retinohypthalamic tract (RHT), but also control of autonomic nerve activities through the RHT, It is also discussed in this review how the two divisions are interconnected and how environmental light is involved in this interconnection. PMID:20431263

  5. Circadian rhythm of extracellular pH in crayfish at different levels of oxygenation.

    PubMed

    Sakakibara, Y; Burtin, B; Massabuau, J C

    1987-09-01

    The extracellular pH regulation was studied in the crayfish Astacus leptodactylus (a night animal) as a function of circadian rhythm. The venous acid-base balance (ABB) was determined in the morning (10 a.m.-12 a.m.) and in the evening (10 p.m.-12 p.m.) at PO2 ranging from 29 to 6 kPa and constant ABB in the water at 13 degrees C. In the morning the venous pH (pHv) was maintained constant by metabolic means independently of PO2 from 29 to 10 kPa. In the evening pHv again was constant and independent of PO2 but it was more alkaline by 0.1 unit corresponding to a shift along the in vitro buffer line. At that time, the ventilation required for providing a unit quantity of O2 (i.e. the ventilatory requirement) increased more than for simply providing O2. The related circadian changes of sensitivity of the ventilatory control system were assessed by comparing morning and evening ventilatory responses to 1-h periods of hypoxia and then hypercapnia. In the evening, the amplitude of the responses to both O2 and CO2 increased but the increase in CO2 sensitivity was proportionally more important. This is consistent with the increase of ventilatory requirement and the related decrease of hemolymph PCO2 during this period. It is concluded that in this animal there exists a circadian rhythm of extracellular pH that is achieved by controlling the CO2 partial pressure in the hemolymph. Results are discussed in terms of O2 transport processes and metabolic modulation through pH adjustments. PMID:3659603

  6. Circadian Rhythms in Executive Function during the Transition to Adolescence: The Effect of Synchrony between Chronotype and Time of Day

    ERIC Educational Resources Information Center

    Hahn, Constanze; Cowell, Jason M.; Wiprzycka, Ursula J.; Goldstein, David; Ralph, Martin; Hasher, Lynn; Zelazo, Philip David

    2012-01-01

    To explore the influence of circadian rhythms on executive function during early adolescence, we administered a battery of executive function measures (including a Go-Nogo task, the Iowa Gambling Task, a Self-ordered Pointing task, and an Intra/Extradimensional Shift task) to Morning-preference and Evening-preference participants (N = 80) between…

  7. Mating frequency, duration, and circadian mating rhythm of New Zealand wheat bug Nysius huttoni White (Heteroptera: Lygaeidae)

    Microsoft Academic Search

    Q. Wang; G. L. Shi

    2004-01-01

    The mating frequency, duration, and circadian mating rhythm of the New Zealand bug, Nysius huttoni, were investigated in the laboratory (25 ± 1°C, 75 ± 10% RH and a photoperiod of 16: 8h light: dark). Mating occurred throughout the 24h cycle, with a peak taking place between 1 and 8 h into the photophase. Caged pairs mated 67.9 ± 15.3

  8. Circadian rhythm of oviposition in the blood sucking bugs, Triatoma phyllosoma, T. infestans and panstrongylus megistus (hemiptera: Reduviidae)

    Microsoft Academic Search

    C. Constantinou

    1984-01-01

    In Triatoma phyllosoma, T. infestans and Panstrongylus megistus egg laying in LD 12:12 occurs during the dark phase of the light cycle with a marked peak near the light off signal. The timing of maximum oviposition is influenced by the ratio of light to darkness. The rhythm of oviposition is circadian, free?running in DD in P. megistus and in LD

  9. Circadian rhythms of locomotor activity and hippocampal clock genes expression are dampened in vitamin A-deficient rats.

    PubMed

    Navigatore-Fonzo, Lorena S; Delgado, Silvia M; Golini, Rebeca S; Anzulovich, Ana C

    2014-04-01

    The main external time giver is the day-night cycle; however, signals from feeding and the activity/rest cycles can entrain peripheral clocks, such as the hippocampus, in the absence of light. Knowing that vitamin A and its derivatives, the retinoids, may act as regulators of the endogenous clock activity, we hypothesized that the nutritional deficiency of vitamin A may influence the locomotor activity rhythm as well as the endogenous circadian patterns of clock genes in the rat hippocampus. Locomotor activity was recorded during the last week of the treatment period. Circadian rhythms of clock genes expression were analyzed by reverse transcription-polymerase chain reaction in hippocampus samples that were isolated every 4 hours during a 24-hour period. Reduced glutathione (GSH) levels were also determined by a kinetic assay. Regulatory regions of clock PER2, CRY1, and CRY2 genes were scanned for RXRE, RARE, and RORE sites. As expected, the locomotor activity pattern of rats shifted rightward under constant dark conditions. Clock genes expression and GSH levels displayed robust circadian oscillations in the rat hippocampus. We found RXRE and RORE sites on regulatory regions of clock genes. Vitamin A deficiency dampened rhythms of locomotor activity as well as modified endogenous rhythms of clock genes expression and GSH levels. Thus, vitamin A may have a role in endogenous clock functioning and participate in the circadian regulation of the cellular redox state in the hippocampus, a peripheral clock with relevant function in memory and learning. PMID:24774069

  10. Single injections of triazolam, a short-acting benzodiazepine, lengthen the period of the circadian activity rhythm in golden hamsters

    Microsoft Academic Search

    J. E. Joy; S. Losee-Olson; F. W. Turek

    1989-01-01

    Summary Single injections of the benzodiazepine, triazolam, induce phase shifts and cause a lengthening of the circadian activity rhythm in the golden hamster. The effect of triazolam on period depends on the phase of injection, but is not dependent on the direction of the phase shifts. Triazolam injections caused increases in period that were associated with phase advances as well

  11. Circadian rhythm affects the preventive role of pulsed electromagnetic fields on ovariectomy-induced osteoporosis in rats

    Microsoft Academic Search

    Da Jing; Guanghao Shen; Jinghui Huang; Kangning Xie; Jing Cai; Qiaoling Xu; Xiaoming Wu; Erping Luo

    2010-01-01

    Pulsed electromagnetic fields (PEMF) have been proved effective in the prevention of osteoporosis both experimentally and clinically. Chronotherapy studies have shown that circadian rhythm (CR) played an important role in the occurrence, development and treatment of several diseases. CR has also been recognized as an essential feature of bone metabolism. Therefore, it is of therapeutic significance to investigate the impact

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

    PubMed Central

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

    2014-01-01

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

  13. Entrainment of the circadian rhythm from the eye of Aplysia: role of serotonin.

    PubMed

    Corrent, G; Eskin, A; Kay, I

    1982-03-01

    The finding that serotonin (5-HT) treatments as short as 1.5 h in duration produce phase shifts in a circadian rhythm from the isolated eye of Aplysia suggested that release of 5-HT was part of an ocular entrainment pathway. Since light cycles entrain this rhythm, we compared phase shifting by 5-HT and by light. The similarity in the shapes of the phase-response curves for 5-HT and light pulses indicates that 5-HT treatments are capable of entraining the rhythm. Also, "skeleton" 5-HT treatments phase shift as well as continuous 5-HT treatments. However, 5-HT does not appear to mediate the phase shifts produced by light, since 1) treatments that should block transmitter release do not change the phase shifts produced by light pulses; 2) the response curves of 5-HT and light pulses are displaced by 12 h relative to one another on the phase axis of the response curve; and 3) light-induced phase shifts are apparent almost immediately, whereas 5-HT-induced phase shifts become evident only about 24 h after 5-HT treatment. The eye appears to contain two independent entrainment pathways, one for light and one utilizing 5-HT. PMID:6278957

  14. 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.

  15. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

    PubMed Central

    Sletten, Tracey L.; Segal, Ahuva Y.; Flynn-Evans, Erin E.; Lockley, Steven W.; Rajaratnam, Shantha M. W.

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID:26043207

  16. Comparison of light, food, and temperature as environmental synchronizers of the circadian rhythm of activity in mice.

    PubMed

    Refinetti, Roberto

    2015-07-01

    Although entrainment (and masking) of circadian rhythms by light has been extensively studied, much less attention has been given to other environmental cycles that can modulate circadian rhythms in mammals. In this study in mice, the entraining strength of different environmental cycles was compared. Running-wheel activity was monitored before, after, and while the animals were under one of four environmental cycles: a full light-dark cycle with 12 h of light and 12 h of darkness each day, a cycle of 1 h of light per day, a cycle of food availability consisting of 80 % of the baseline free-feeding amount presented once a day, and an ambient temperature cycle consisting of 23 h at 24 °C and 1 h at 12 °C each day. Four measures of zeitgeber strength were used: percentage of animals that entrained, rhythm robustness in the entrained state, stability of activity onsets, and stability of acrophases. The results indicate that, at least in mice, a full light-dark cycle is the most powerful modulator of the circadian rhythm of locomotor activity, as a consequence of both entrainment and masking. When entrainment alone is considered, temperature seems to be as strong a modulator as light, while food restriction is a weaker modulator and affects primarily a food-anticipatory component of the activity rhythm. PMID:25800223

  17. 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

  18. 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

  19. Repeated psychosocial stress at night affects the circadian activity rhythm of male mice.

    PubMed

    Bartlang, Manuela S; Oster, Henrik; Helfrich-Förster, Charlotte

    2015-06-01

    We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2. PMID:25900040

  20. A Circadian Clock in Antarctic Krill: An Endogenous Timing System Governs Metabolic Output Rhythms in the Euphausid Species Euphausia superba

    PubMed Central

    Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

    2011-01-01

    Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (?9–12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ?9–12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle. PMID:22022521

  1. 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

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

    NASA Technical Reports Server (NTRS)

    Ferraro, J. S.; Sulzman, F. M.

    1988-01-01

    Feedback lighting provides illumination primarily during the subjective night (i.e., the photosensitive portion of the circadian cycle) in response to a given behavior. This technique has previously been used to test the nonparametric model of entrainment in nocturnal rodents. In three species (Rattus norvegicus, Mesocricetus auratus, and Mus musculus), the free-running period of the locomotor activity rhythm was similar whether the animals were exposed to continuous light or discrete light pulses occurring essentially only during the subjective night (i.e., feedback lighting). In the current experiments, feedback lighting was presented to squirrel monkeys so that light fell predominantly during the subjective night. Feedback lighting was linked to the drinking behavior in this diurnal primate so that when the animal drank, the lights went out. Despite the seemingly adverse predicament, the monkeys maintained regular circadian drinking rhythms. Furthermore, just as the period of the free-running activity rhythms of nocturnal rodents exposed to continuous light or feedback lighting were similar, the period of the drinking rhythms of the squirrel monkeys in continuous light and feedback lighting were comparable (25.6 +/- 0.1 and 25.9 +/- 0.1 hours, respectively), despite a substantial decrease in the total amount of light exposure associated with feedback lighting. The free-running period of monkeys exposed to continuous dark (24.5 +/- 0.1 hours) was significantly shorter than either of the two lighting conditions (P < 0.001). The results presented for the drinking rhythm were confirmed by examination of the temperature and activity rhythms. Therefore, discrete light pulses given predominately during the subjective night are capable of simulating the effects of continuous light on the free-running period of the circadian rhythms of a diurnal primate. The response of squirrel monkeys to feedback lighting thus lends further support for the model and suggests that the major entrainment mechanisms are similar in nocturnal rodents and diurnal primates.

  3. 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.

  4. Effects of Respiratory Inhibitors on Respiration, ATP Contents, and the Circadian Conidiation Rhythm of Neurospora crassa.

    PubMed

    Nakashima, H

    1984-11-01

    Effects of respiratory inhibitors on the circadian clock, respiratory activity, and ATP content were examined in Neurospora crassa. All inhibitors, potassium cyanide, sodium azide, antimycin A, and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), shifted the phase of the conidiation rhythm. All the phase response curves were similar and resembled that for cycloheximide, but were different from the phase response curve for light. Phase shifting by azide and CCCP was proportional to the lowering of respiratory activity and ATP content, but such a correlation was not observed for cyanide and antimycin A. In particular, cyanide at a concentration of 0.5 millimolar completely depleted ATP of the cultures but did not significantly shift their phase. Their results suggest that large shifts caused by these inhibitors are not due to a decrease in energy from respiratory activity. PMID:16663893

  5. 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.

  6. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report.

    PubMed

    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

    2007-11-01

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

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

    PubMed

    Duarte, D P F; Silva, V L; Jaguaribe, A M; Gilmore, D P; Da Costa, C P

    2003-02-01

    Blood pressure (BP) profiles were monitored in nine free-ranging sloths (Bradypus variegatus) by coupling one common carotid artery to a BP telemetry transmitter. Animals moved freely in an isolated and temperature-controlled room (24 degrees C) with 12/12-h artificial light-dark cycles and behaviors were observed during resting, eating and moving. Systolic (SBP) and diastolic (DBP) blood pressures were sampled for 1 min every 15 min for 24 h. BP rhythm over 24 h was analyzed by the cosinor method and the mesor, amplitude, acrophase and percent rhythm were calculated. A total of 764 measurements were made in the light cycle and 721 in the dark cycle. Twenty-four-hour values (mean +/- SD) were obtained for SBP (121 +/- 22 mmHg), DBP (86 +/- 17 mmHg), mean BP (MBP, 98 +/- 18 mmHg) and heart rate (73 +/- 16 bpm). The SBP, DBP and MBP were significantly higher (unpaired Student t-test) during the light period (125 +/- 21, 88 +/- 15 and 100 +/- 17 mmHg, respectively) than during the dark period (120 +/- 21, 85 +/- 17 and 97 +/- 17 mmHg, respectively) and the acrophase occurred between 16:00 and 17:45 h. This circadian variation is similar to that observed in cats, dogs and marmosets. The BP decreased during "behavioral sleep" (MBP down from 110 +/- 19 to 90 +/- 19 mmHg at 21:00 to 8:00 h). Both feeding and moving induced an increase in MBP (96 +/- 17 to 119 +/- 17 mmHg at 17:00 h and 97 +/- 19 to 105 +/- 12 mmHg at 15:00 h, respectively). The results show that conscious sloths present biphasic circadian fluctuations in BP levels, which are higher during the light period and are mainly synchronized with feeding. PMID:12563531

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

    PubMed

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

    2015-01-12

    Melatonin secretion is usually increased during the daytime and decreased at night in Smith-Magenis syndrome (SMS) and consequently is not a pertinent marker of the circadian phase of the clock in these cases. No data on temperature rhythm is available in SMS, another reliable marker of circadian clock activity. For this reason, we assessed the 24h profiles of core temperature, sleep-wake cycle, hormones (plasma cortisol and melatonin) and plasma and urine 6sulfatoxy-melatonin, the main hepatic melatonin metabolism in a 31-year-old man diagnosed with a SMS. All circadian rhythms, especially temperature rhythm showed a phase-advance, associated with reverse melatonin secretion. Plasma and urine 6sulfatoxy-melatonin profiles showed normal melatonin catabolism and confirmed the reversed melatonin secretion. Taking in consideration the reverse melatonin secretion and the phase-advanced temperature rhythm, which is driven by the suprachiasmatic nucleus, we hypothesize that the central clock is more sensitive to afternoon than to morning melatonin. This different responsiveness to melatonin according to the time of the day (i.e. chronaesthesia) corroborates the phase response curve of melatonin secretion to exogenous melatonin. PMID:25434872

  9. Relationship between psychosomatic complaints and circadian rhythm irregularity assessed by salivary levels of melatonin and growth hormone

    PubMed Central

    2011-01-01

    Background In university health care settings, students with psychosomatic complaints often have chronotypic problems. For this reason, we investigated a potential connection between psychosomatic complaints and circadian rhythm irregularity assessed by salivary levels of melatonin and growth hormone. Methods Fifteen healthy students between 21 and 22 years of age were examined for physiological parameters of chronotypes based on melatonin and growth hormone secretion patterns, using a fluorescence enzyme immunoassay. Salivary samples were collected from subjects at home five times each day (20:00, 24:00, 04:00, 08:00, and 12:00 h). In addition, the subjects rated their psychosomatic symptoms twice (at 08:00 and 20:00 h). Results A group with irregular circadian rhythm of melatonin (ICR) showed more psychosomatic complaints than a group with the regular circadian rhythm (RCR), especially for anxiety. Conclusion Psychosomatic symptoms, particularly anxiety, may be associated with irregularity in melatonin and growth hormone rhythms, which can be altered by basic lifestyle habits even in healthy students. PMID:21914213

  10. Circadian rhythm in the visual system of the lizard Anolis carolinensis.

    PubMed

    Shaw, A P; Collazo, C R; Easterling, K; Young, C D; Karwoski, C J

    1993-01-01

    The electroretinogram (ERG) was recorded from free-moving Anolis lizards once per hour for 5 days. As in our previous work, the b-wave, but not the a-wave, showed a reliable circadian rhythm (CR) in amplitude, with an acrophase near projected noon. Both the a- and b-waves showed a CR in peak time (implicit time, or IT), with the a-wave IT being longest near midnight, and the b-wave IT at midday. Acrophases were shifted when animals were housed on a phase-shifted light-dark cycle. The ERG CR was unaffected by removal of the parietal organ, but it was virtually abolished by removal of the pineal gland, thus suggesting that pineal output (probably melatonin) modulates retinal responses. In addition to the ERG, the tectal light-evoked potential exhibited a CR--a finding compatible with a circadian variation in retinal output. Lastly, the amplitude of the ERG component waveforms showed a seasonal variation, but the ERG CR was constant across the year. PMID:8369548

  11. The influence of circadian rhythms on pre- and post-prandial metabolism in the snake Lamprophis fuliginosus.

    PubMed

    Roe, J H; Hopkins, W A; Snodgrass, J W; Congdon, J D

    2004-10-01

    Measuring standard metabolic rate (SMR) and specific dynamic action (SDA) has yielded insight into patterns of energy expenditure in snakes, but less emphasis has been placed on identifying metabolic variation and associated energy cost of circadian rhythms. To estimate SMR, SDA, and identify metabolic variation associated with circadian cycles in nocturnally active African house snakes (Lamprophis fuliginosus), we measured oxygen consumption rates (VO2) at frequent intervals before and during digestion of meals equaling 10%, 20% and 30% of their body mass. Circadian rhythms in metabolism were perceptible in the VO2 data during fasting and after the initial stages of digestion. We estimated SMR of L. fuliginosus (mean mass=16.7+/-0.3 g) to be 0.68+/-0.02 (+/-SEM) mL O2/h at 25 degrees C. Twenty-four hours after eating, VO2 peaked at 3.2-5.3 times SMR. During digestion of meals equaling 10-30% of their body mass, the volume of oxygen consumed ranged from 109 to 119 mL O2 for SMR, whereas extra oxygen consumed for digestion and assimilation ranged from 68 to 256 mL O2 (equivalent to 14.5-17.0% of ingested energy). The oxygen consumed due to the rise in metabolism during the active phase of the daily cycle ranged from 55 to 66 mL O2 during digestion. Peak VO2, digestive scope, and SDA increased with increasing meal size. Comparisons of our estimates to estimates derived from methods used in previous investigations resulted in wide variance of metabolic variables (up to 39%), likely due to the influence of circadian rhythms and activity on the selection of baseline metabolism. We suggest frequent VO2 measurements over multiple days, coupled with mathematical methods that reduce the influence of undesired sources of VO2 variation (e.g., activity, circadian cycles) are needed to reliably assess SMR and SDA in animals exhibiting strong circadian cycles. PMID:15528164

  12. Circadian Rhythms in Neurospora Crassa: Farnesol or Geraniol Allow Expression of Rhythmicity in the Otherwise Arrhythmic Strains frq 10, wc-1, and wc-2

    Microsoft Academic Search

    Tabitha Granshaw; Michelle Tsukamoto; Stuart Brody

    2003-01-01

    In Neurospora crassa, the circadian rhythm can be seen in the bd (band) strain as a series of “bands” or conidiation (spore-forming) regions on the surface of an agar medium. Certain mutations at 3 different genes (frq, wc-1,or wc-2) lead to the loss of the circadian rhythm. In this study, it was found that the addition of 10-4 to 10-5

  13. Serotonin phase-shifts the circadian rhythm of locomotor activity in the cockroach.

    PubMed

    Page, T L

    1987-01-01

    Serotonin, a putative neurotransmitter in insects, was found to cause consistent phase shifts of the circadian rhythm of locomotor activity of the cockroach Leucophaea maderae when administered during the early subjective night as a series of 4-microliters pulses (one every 15 min) for either 3 or 6 hr. Six-hour treatments with dopamine also caused significant phase shifts during the early subjective night, but 3-hr treatments with dopamine had no phase-shifting effect. Other substances tested in early subjective night (norepinephrine, octopamine, gamma-aminobutyric acid, glutamate, carbachol, histamine, tryptophan, tryptamine, N-acetyl serotonin, or 5-hydroxyindole-3-acetic acid) did not consistently cause phase shifts. The phase-shifting effect of serotonin was found to be phase-dependent. The phase response curve (PRC) for serotonin treatments was different from the PRC for light. Like light, serotonin caused phase delays in the late subjective day and early subjective night, but serotonin did not phase-shift rhythms when tested at phases where light causes phase advances. PMID:2979649

  14. Restricted feeding entrains circadian wheel-running activity rhythms of the kowari.

    PubMed

    Kennedy, G A; Coleman, G J; Armstrong, S M

    1991-10-01

    The effect of daily restricted feeding (RF) on the circadian wheel-running rhythms of the kowari, Dasyuroides byrnei, was examined in two experiments. Kowaris were presented with a preferred food (determined in a pilot study) during a daily 2-h meal in the light period of a 14:10 light-dark (LD) cycle (expts 1 and 2), during constant dark (DD) immediately after termination of the LD cycle (expt 1), and during DD when kowaris were free running (expt 1). Results showed that 1) RF elicited anticipatory activity similar in duration and phasing to that observed in the rat; 2) cycles of meal-associated activity free ran for up to 6 days after the termination of RF; 3) activity persists at a phase near that of the former mealtime during periods of food deprivation; and 4) activity indicative of beating between two pacemakers occurred when feeding was restricted to the L period of LD cycles. Together these observations suggest that the activity rhythms of the kowari may be controlled by separate, but possibly coupled, light-entrainable and food-entrainable pacemakers, as are those of the rat. PMID:1928428

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

    PubMed Central

    St. Hilaire, Melissa A.; Lockley, Steven W.

    2015-01-01

    Objective/Background Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep–wake disorder. Patients/Methods Three totally blind males (63.0?±?7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48?h every 1–2 weeks. Participants completed daily sleep–wake logs, and rated their alertness and mood using nine-point scales every ~2–4?h while awake on urine sampling days. Caffeine capsules (150?mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period ? and compared to placebo (n?=?2) or no treatment (n?=?1) in a single-masked manner. Results Non-24-h aMT6s rhythms were confirmed in all three participants (? range?=?24.32–24.57?h). Daily administration of 150?mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p?circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep–Wake Disorder in the blind appropriately. PMID:25891543

  16. Circadian rhythms of the spontaneous meal pattern, macronutrient intake, and mood of humans.

    PubMed

    de Castro, J M

    1987-01-01

    Circadian (24-hour) rhythms in the feeding behavior of humans were investigated using diary self-reports of spontaneous food intake. Eight male and 30 female undergraduate students recorded what they ate, when they ate it, and their mood at the time of ingestion in a diary over a consecutive nine day period. Self-ratings of depression, energy, and anxiety were made at the beginning of each meal on three seven-point scales. The total amount of food energy in each meal as well as the amount of protein, carbohydrate, and fat, the intervals prior to and following the meals, and the satiety and deprivation ratios were calculated. The food energy contained in the stomach at the beginning and end of each meal was estimated with a mathematical model. These variables were evaluated in relation to the time of meal occurrence during the day. Fluctuations in the levels of self-rated energy and anxiety, but not depression, were detected during the day. Clear 24-hour rhythms were identified for the amount eaten and the macronutrients ingested during the day with decreases for males and increases for females. The amount eaten per meal and the meal's content of carbohydrate or fat, but not protein, varied over the day with peaks at the lunch and dinner periods. A clear sex difference without circadian variation was apparent with the deprivation ratios. This suggests that males eat larger meals than females because of a heightened responsivity to deprivation and not to a smaller response to the satiating properties of food. Preprandial correlations were found for meals occurring either during the breakfast or the dinner periods. No postprandial correlations were found. These data demonstrate that the preprandial correlations are not an artifact produced by the 24-hour rhythm and suggests that they reflect a basic regulatory strategy employed by humans. As the day progressed, postmeal intervals and satiety ratios decreased, while premeal intervals increased. This suggests that humans obtain less satiety from a given amount of food later in the day than earlier. It is postulated that this represents eating which anticipates the overnight fast. These data clearly demonstrate the efficacy of the approach and the orderly, analyzable nature of the spontaneous eating behavior of humans. PMID:3628541

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Destruction of Serotonergic Neurons in the Median Raphe Nucleus Blocks Circadian Rhythm Phase Shifts to Triazolam but Not to Novel Wheel Access

    Microsoft Academic Search

    Elizabeth L. Meyer-Bernstein; Lawrence P. Morin

    1998-01-01

    Systematic treatment of hamsters with triazolam (TRZ) or novel wheel (NW) access will yield PRCs similar to those for neuropeptide Y. Both TRZ and NW access require an intact intergeniculate leaflet (IGL) to modulate circadian rhythm phase. It is commonly suggested that both stimulus types influence rhythm phase response via a mechanism associated with drug-induced or wheel access-associated locomotion. Furthermore,

  2. Ramelteon (TAK-375) Accelerates Reentrainment of Circadian Rhythm after a Phase Advance of the Light-Dark Cycle in Rats

    Microsoft Academic Search

    Keisuke Hirai; Muneto Kita; Hiroyuki Ohta; Hisao Nishikawa; Yuu Fujiwara; Shigenori Ohkawa; Masaomi Miyamoto

    2005-01-01

    In vivo pharmacological effects of ramelteon (TAK-375), a novel, highly MT1\\/MT2-selective receptor agonist, were studied in rats to determine ramelteon’s ability to reentrain the circadian rhythm after an abrupt phase advance. Experiments were also conducted to assess the potential cognitive side effects of ramelteon and its potential to become a drug of abuse. After an abrupt 8-h phase shift, ramelteon

  3. Circannual and circadian rhythms in the snail Helix aspersa Müller and the photoperiodic control of annual activity and reproduction

    Microsoft Academic Search

    Stuart E. R. Bailey

    1981-01-01

    1.Individual adultHelix aspersa show a circadian rhythm of locomotor activity when kept in constant darkness, temperature, and high humidity.2.When kept for 14 months at temperatures with little annual variation from a mean of 17.4 °C, but with photoperiod varying in step with the seasons, snails moved and fed least during the short days from October to April. This is the

  4. Effect of precocene II on circadian rhythms of feeding and mating behavior in the milkweed bug, Oncopeltus fasciatus

    Microsoft Academic Search

    H. D. Woodard; M. A. Rankin

    1980-01-01

    Summary Oncopeltus fasciatus adults were treated with the antiallatotropin, precocene II and the circadian rhythms of feeding and mating behavior were monitored at 2-h intervals from lights on to lights off under 2 photoperiod regimes. Females ovariectomized as 5th instars were monitored for feeding and mating behavior at 2–3-h intervals from lights on to lights off as well. Neither precocene

  5. Determination of Salivary Cortisol by ELISA and Its Application to the Assessment of the Circadian Rhythm in Children

    Microsoft Academic Search

    Mieko Shimada; Kiyohisa Takahashi; Tomi Ohkawa; Masaya Segawa; Makoto Higurashi

    1995-01-01

    In 35 young children, circadian rhythms of salivary cortisol levels were determined by ELISA using a commercially available kit with a minor modification. The concentration of labeled cortisol in the serum kit was reduced in order to measure cortisol in 10 ?l of saliva. Intra- and interassay coefficients of variation for salivary cortisol ranged from 2.4 to 9.9 and 3.2

  6. Lack of social entrainment of free-running circadian activity rhythms in the Australian sugar glider ( Petaurus breviceps : Marsupialia)

    Microsoft Academic Search

    Sabine Kleinknecht

    1985-01-01

    Social influence on circadian activity rhythms was investigated in the nocturnal Australian marsupial Petaurus breviceps. The activity of two ?? and two ?? was recorded electroacoustically and observed by an IR television camera in LD 12:12 (101:10-1lx) and in LL (10-1lx) when housed isolated and in pairs (?+?). In LD-entrained animals the average duration of locomotion, orientation movements, grooming and

  7. Minireview: The circadian clockwork of the suprachiasmatic nuclei--analysis of a cellular oscillator that drives endocrine rhythms

    Microsoft Academic Search

    Elizabeth S. Maywood; John S. O'Neill; Johanna E. Chesham; Michael H. Hastings

    2007-01-01

    The secretion of hormones is temporally precise and periodic, oscillating over hours, days, and months. The circadian timekeeper within the suprachiasmatic nuclei (SCN) is central to this coordination, modulating the frequency of pulsatile release, maintaining daily cycles of secretion, and defining the time base for longer-term rhythms. This central clock is driven by cell-autonomous, transcriptional\\/posttranslational feedback loops incorporating Period (Per)

  8. 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 adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk. PMID:24810091

  9. Cardiac-specific mutation of Clock alters the quantitative measurements of physical activities without changing behavioral circadian rhythms.

    PubMed

    Ko, Michael L; Shi, Liheng; Tsai, Ju-Yun; Young, Martin E; Neuendorff, Nichole; Earnest, David J; Ko, Gladys Y-P

    2011-10-01

    Even though peripheral circadian oscillators in the cardiovascular system are known to exist, the daily rhythms of the cardiovascular system are mainly attributed to autonomic or hormonal inputs under the control of the central oscillator, the suprachiasmatic nucleus (SCN). In order to examine the role of peripheral oscillators in the cardiovascular system, we used a transgenic mouse where the Clock gene is specifically disrupted in cardiomyocytes. In this cardiomyocyte-specific CLOCK mutant (CCM) mouse model, the circadian input from the SCN remains intact. Both CCM and wild-type (WT) littermates displayed circadian rhythms in wheel-running behavior. However, the overall wheel-running activities were significantly lower in CCM mice compared to WT over the course of 5 weeks, indicating that CCM mice either have lower baseline physical activities or they have lower physical adaptation abilities because daily wheel running, like routine exercise, induces physical adaptation over a period of time. Upon further biochemical analysis, it was revealed that the diurnal oscillations of phosphorylation states of several kinases and protein expression of the L-type voltage-gated calcium channel (L-VGCC) ?1D subunit found in WT hearts were abolished in CCM hearts, indicating that in mammalian hearts, the daily oscillations of the activities of these kinases and L-VGCCs were downstream elements of the cardiac core oscillators. However, the phosphorylation of p38 MAPK exhibited robust diurnal rhythms in both WT and CCM hearts, indicating that cardiac p38 could be under the influence of the central clock through neurohormonal signals or be part of the circadian input pathway in cardiomyocytes. Taken together, these results indicate that the cardiac core oscillators have an impact in regulating circadian rhythmicities and cardiac function. PMID:21921295

  10. A sex difference in circadian food-anticipatory rhythms in mice: Interaction with dopamine D1 receptor knockout.

    PubMed

    Michalik, Mateusz; Steele, Andrew D; Mistlberger, Ralph E

    2015-06-01

    Restricted daily feeding schedules induce circadian rhythms of food-anticipatory activity (FAA) in mice and other species. The entrainment pathway(s) and location(s) of circadian oscillators driving these rhythms have not been definitively established. An important role for dopamine signaling and the dorsal striatum is suggested by a confluence of observations, including shifting of FAA rhythms by dopamine receptor agonists and attenuation by antagonists and D1 receptor knockout (D1R KO). The dopamine reward system exhibits sexual dimorphisms in structure and function; if FAA rhythms are regulated by this system, then FAA may also be sexually dimorphic. To assess this prediction, disk running and general activity were recorded continuously in male and female C57BL/6J mice with food available ad libitum and then restricted to a 4-hr daily meal in the middle of the light period. Compared with male mice, FAA in female mice was significantly reduced in duration, total count, peak level, and ratio relative to nocturnal activity. To determine whether these differences were mediated by D1 receptors, male and female homozygous D1R KO mice were examined. Compared with wild type and heterozygous mice, female and male D1R KO mice exhibited a marked attenuation of FAA parameters. The magnitude of the attenuation was greater in female mice. These results confirm an important role for dopamine D1 receptors in the circadian mechanism by which mice anticipate a daily meal, and they reveal a previously unreported sexual dimorphism in the expression of food-anticipatory rhythms that is amplified by D1R KO. (PsycINFO Database Record PMID:26030433

  11. [Circadian rhythm of the renin-angiotensin-aldosterone system: a summary of our research studies].

    PubMed

    Cugini, P; Lucia, P

    2004-01-01

    The renin-angiotensin-aldosterone system (RAAS) is characterized by a circadian rhythm (CR) whose acrophase is detectable early in the morning. The prorenin and angiotensin converting enzyme (ACE) show a CR as well. However, while the prorenin is in phase with the RAAS the ACE shows its circadian acrophase in the afternoon suggesting a negative feed-back. The RAAS CR is influenced by many factors. Its mesor is modified by sodium intake. The physical activity and rest affect both the mesor and acrophase. The variations in mesor amplitude and acrophase in aged subjects are conditioned by sex and physical activity. Moreover, the RAAS CR seems to be influenced by the race. In addition, it is abolished by the beta-adrenergic blockade, suggesting the existence of an adrenergic clock. Interestingly, the RAAS CR seems not to be a pacemaker for the blood pressure CR, whose acrophase is early in the afternoon. The RAAS CR is not substantially modified has in essential hypertension. However, the CR of plasma renin activity is disappeared in the low-renin essential hypertension, while the CR of plasma aldosterone is detectable. On the contrary, the aldosterone CR is not detectable in ascitic liver cirrhosis; but, it is restored when the ascites is removed by peritoneal-jugular shunt. No significant variation of the RAAS CR seems to occur in obesity and Cushing's syndrome. The RAAS CR has disappeared in Conn's disease as well as in Bartter's syndrome and Liddle's syndrome. The administration of indomethacine in Bartter's syndrome and of triamterene in Liddle's syndrome is able to restore the RAAS CR. Finally, the RAAS CR is not detectable in the heart or kidney transplanted patients; such a phenomenon could be attributed to cyclosporine and corticosteroids administration and to the denervation of the transplanted organs. PMID:15553256

  12. Circadian rhythms in exercise performance: implications for hormonal and muscular adaptation.

    PubMed

    Teo, Weipeng; Newton, Michael J; McGuigan, Michael R

    2011-01-01

    Almost all physiological and biochemical processes within the human body follow a circadian rhythm (CR). In humans, the suprachiasmatic nucleus regulates sleep- wake cycle and other daily biorhythms in line with solar time. Due to such daily physiological fluctuations, several investigations on neuromuscular performance have reported a distinct CR during exercise. Generally, peak performances have been found to occur in the early evening, at approximately the peak of core body temperature. The increase in core body temperature has been found to increase energy metabolism, improve muscle compliance and facilitate actin-myosin crossbridging. In addition, steroidal hormones such as testosterone (T) and cortisol (C) also display a clear CR. The role of T within the body is to maintain anabolism through the process of protein synthesis. By contrast, C plays a catabolic function and is involved in the response of stress. Due to the anabolic and catabolic nature of both T and C, it has been postulated that a causal relationship may exist between the CR of T and C and muscular performance. This review will therefore discuss the effects of CR on physical performance and its implications for training. Furthermore, this review will examine the impact of muscular performance on CR in hormonal responses and whether could variations in T and C be potentially beneficial for muscular adaptation. Key pointsA distinct CR can be observed in physical performance.CR of exercise performance is highly associated with CR in core body temperatureBoth T and C display a clear CR, however, the current evidence does not show a clear relationship with neuromuscular adaptations.TST is able to induce changes in physical performance variables at the particular time point, but not for the circadian profile of T and C. PMID:24149547

  13. Phase-dependent phase shift of methamphetamine-induced circadian rhythm by haloperidol in SCN-lesioned rats.

    PubMed

    Honma, S; Honma, K

    1995-03-20

    Haloperidol, a non-selective dopamine receptor antagonist, was injected intraperitoneally in to suprachiasmatic nucleus (SCN)-lesioned rats at various phases of the locomotor activity rhythm induced by methamphetamine (MAP) treatment. A single injection of haloperidol shifted the phase of MAP-induced locomotor rhythm phase dependently, while saline injection had no effect on the phase. A phase-response curve of MAP-induced rhythm for haloperidol had a small phase-advancing area at CT 13 to 15, a large phase-delaying area at CT 3 to 7 and a dead zone at CT 17 to 1. Although the day-to-day variation of MAP-induced locomotor rhythm was about 2.5-times as great as that of light entrainable circadian rhythm, the phase shifts of both directions were statistically significant. Phase delay shifts at CT 5 depended on the dose of haloperidol. In addition to the phase-shifting effect, haloperidol suppressed the MAP-induced locomotor activity for activity for about 10 h regardless of the phase of the injection. Pentobarbital also suppressed ther locomotor activity for a similar duration. However, significant phase shift was not detected with pentobarbital injected at CT 5 or CT 13, at the phase where haloperidol induced the maximal phase delay or advance, respectively. Present findings suggest that the dopaminergic mechanism is involved in the entrainment and/or oscillatory mechanism of the MAP-induced rhythm. PMID:7796108

  14. Potentiation of the resetting effects of light on circadian rhythms of hamsters using serotonin and neuropeptide Y receptor antagonists.

    PubMed

    Lall, G S; Harrington, M E

    2006-09-01

    Circadian rhythms are entrained by light/dark cycles. In hamsters, the effects of light on circadian rhythms can be modulated by serotonergic input to the suprachiasmatic nucleus from the raphe nuclei and by neuropeptide Y containing afferents to the suprachiasmatic nucleus from the intergeniculate leaflet in the thalamus. In this study we measured effects of compounds acting on serotonergic 1A and neuropeptide Y Y5 receptors to determine if combined serotonergic-neuropeptide Y inhibition could synergistically potentiate effects of light on rhythms. We used mixed serotonergic agonist/antagonists BMY 7378 or NAN-190 as well as a neuropeptide Y Y5 antagonist CP-760,542. Both BMY 7378 and NAN-190 are thought to block serotonin release via acting as agonists at the 5-hydroxytryptamine 1A (5-HT1A) autoreceptors on cells in the raphe, and also block response of target cells by acting as antagonists at post-synaptic 5-HT1A receptors, for example, in the suprachiasmatic nuclei or the intergeniculate leaflet. Replicating prior work, we found that pretreatment with either drug alone increased the phase shift to light at circadian time 19. The combined effect of BMY 7378 and CP-760,542 given prior to light at circadian time 19 was to further potentiate the subsequent phase shift in wheel-running rhythms (the phase shift was 317% of controls; light alone: 1.35 h phase shift vs. BMY 7378, CP-760,542, and light: 4.27 h phase shift). Combined treatment with NAN-190 and CP-760,542 produced a light-induced phase shift 576% of controls (phase shift to light alone: 1.23 h vs. NAN-190, CP-760,542, and light: 7.1 h phase shift). These results suggest that the resetting effects of light on circadian rhythms can be greatly potentiated in hamsters by using pharmacological treatments that block both serotonergic and neuropeptide Y afferents to the suprachiasmatic nuclei. PMID:16750888

  15. Sleep and heart rate circadian rhythm in depression: the necessity to separate.

    PubMed

    Taillard, J; Lemoine, P; Boule, P; Drogue, M; Mouret, J

    1993-02-01

    In order to determine whether a decrease in the amplitude of heart rate circadian rhythm (HRCR) could represent a chronobiological marker of depression and to answer the question of the possible role of this alteration in the reduction of rapid eye movement sleep latency (REM latency) observed in depression, 22 major depressed patients (DSM III R, Montgomery Asberg Depression Rating Scale) and 11 healthy volunteers entered this study, which included the simultaneous recordings of sleep and heart rate (HR) during two consecutive 24-h periods. After a smoothing procedure, the HR data, obtained from a portable device providing mean HR/min, were computed with the single cosinor method for the classical circadian parameters. We also determined the cosinor fitting index (CFI = percentage to fit). When studied as a single group and compared to the control group, the depressed patients, who had difficulties in sleep initiation and whose REM latencies were within normal limits, were characterized by a dampening of the amplitude HRCR and of the day-night HR difference. This was linked to a lesser increase of HR during the day and a reduced decrease at night. No significant phase modification of HRCR was observed in this group of depressives. In a second step, the depressives were divided into a depressed arrhythmic group (DAG, CFI < 50%, 11 patients) and a depressed rhythmic group (DRG, CFI > 50%, 11 patients) who did not differ on MADRS scores. Even though the amplitude of HRCR was reduced in the DAG only, with HR higher at night and lower during the daytime than for controls, both DAG and DRG significantly differed from controls on those items related to sleep induction and maintenance. In the DAG only was there a tendency toward a reduction of total sleep time and REM sleep time while REM latency was normal. This finding suggests that sleep problems are not responsible for the differences in HRCR parameters between the two depressed groups. These differences in HR and sleep parameters between two groups of similarly depressed patients also suggest that a short REM latency does not systematically imply a disruption of all circadian clocks. PMID:8443845

  16. Comparison of circadian gene expression among different oscillator models: identification of critical output signals of the SCN pacemaker 

    E-print Network

    Menger, Gus John, III

    2009-05-15

    Diverse forms of life have evolved 24-hour or circadian timekeeping systems serving to coordinate internal biological events with the daily solar cycle. The generation of circadian rhythms by this timekeeping system ensures that internal processes...

  17. Altitudinal variation in the circadian rhythm of oviposition in Drosophila ananassae.

    PubMed

    Khare, P V; Satralkar, M K; Vanlalnghaka, C; Keny, V L; Kasture, M S; Shivagaje, A J; Barnabas, R J; Joshi, D S

    2005-01-01

    The effect of altitude on four basic properties of the pacemaker controlling the circadian rhythm of oviposition in two strains of Drosophila ananassae was determined. The high altitude (HA) strain from Badrinath (5123 m above sea level) had a low amplitude peak in the forenoon while the low altitude (LA) strain from Firozpur (179 m a.s.l.) had a high amplitude peak after the lights-off of LD 12:12 cycles. Free running periods in continuous darkness were about 22.6 and 27.4 h in the HA and LA strains, respectively. The light pulse phase response curve (PRC) for the HA strain showed a low amplitude and a dead zone of 8h; the ratio for the advance to delay region (A/D) was less than 1, while the PRC for the LA strain had a high amplitude, which was devoid of a dead zone and showed a ratio of A/D > 1. The magnitude of the delay phase shifts at CT 18 evoked by light pulses of 1 h duration, but varying light intensity was significantly different in the HA and LA strain, which suggests that the photic sensitivity of the clock photoreceptors mediating the phase shifts had been affected by the altitude. PMID:15865320

  18. Cognitive abilities of Alzheimer's disease transgenic mice are modulated by social context and circadian rhythm.

    PubMed

    Kiryk, Anna; Mochol, Gabriela; Filipkowski, Robert K; Wawrzyniak, Marcin; Lioudyno, Victoria; Knapska, Ewelina; Gorkiewicz, Tomasz; Balcerzyk, Marcin; Leski, Szymon; Leuven, Fred Van; Lipp, Hans-Peter; Wojcik, Daniel K; Kaczmarek, Leszek

    2011-12-01

    In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12- and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model. PMID:22171952

  19. Disruption of melatonin circadian rhythm production is related to multiple sclerosis severity: A preliminary study.

    PubMed

    Damasceno, Alfredo; Moraes, Adriel Santos; Farias, Alessandro; Damasceno, Benito Pereira; Dos Santos, Leonilda Maria Barbosa; Cendes, Fernando

    2015-06-15

    Sunlight can influence the immune system independently of vitamin D, such as through melatonin production in the pineal gland. Inflammatory disorders can suppress nocturnal melatonin production, but only a few studies have investigated melatonin status in multiple sclerosis (MS). We aimed to study melatonin production in association with clinical and immunological data in MS patients. Eleven treated relapsing-remitting MS (RRMS) patients and eight controls underwent neurological examination and were assessed for fatigue severity and depressive symptoms. Inflammatory cytokines were analyzed in blood samples and concentration of 6-sulfatoxymelatonin (6-SMT) was determined in 24h urine. Patients with an abnormal proportion of overnight 6-SMT (n=8, 72.7%) had higher disability and fatigue severity (p<0.05). Overnight 6-SMT was inversely related with fatigue severity (p=0.016), number of relapses in the previous 12months (p=0.010) and EDSS scores (p=0.049). In conclusion, disruption of melatonin circadian rhythm production is frequent among RRMS patients and seemingly related to higher disability and fatigue scores. Future studies with larger sample size are necessary to establish melatonin status as a biomarker of disease severity in MS. PMID:25930714

  20. Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm

    PubMed Central

    Negoro, Hiromitsu; Kanematsu, Akihiro; Doi, Masao; Suadicani, Sylvia O.; Matsuo, Masahiro; Imamura, Masaaki; Okinami, Takeshi; Nishikawa, Nobuyuki; Oura, Tomonori; Matsui, Shigeyuki; Seo, Kazuyuki; Tainaka, Motomi; Urabe, Shoichi; Kiyokage, Emi; Todo, Takeshi; Okamura, Hitoshi; Tabata, Yasuhiko; Ogawa, Osamu

    2012-01-01

    Summary Nocturnal enuresis in children and nocturia in the elderly are two highly prevalent clinical conditions characterized by a mismatch between urine production rate in the kidneys and storage in the urinary bladder during the sleep phase. Here we demonstrate, using a novel method for automated recording of mouse micturition, that connexin43 (Cx43), a bladder gap junction protein, is a negative regulator of functional bladder capacity. Bladder Cx43 levels and functional capacity show circadian oscillations in wild-type mice, but such rhythms are completely lost in Cry-null mice having a dysfunctional biological clock. Bladder muscle cells have an internal clock, and show oscillations of Cx43 and gap junction function. A clock regulator, Rev-erb?, upregulates Cx43 transcription as a co-factor of Sp1 using Sp1 cis-elements of the promoter. Therefore, circadianoscillation of Cx43 is associated with the biological clock and contributes to diurnal changes in bladder capacity, which avoids disturbance of sleep by micturition. PMID:22549838

  1. Rice WNK1 is regulated by abiotic stress and involved in internal circadian rhythm.

    PubMed

    Kumar, Kundan; Rao, Kudupudi Prabhakara; Biswas, Dipul Kumar; Sinha, Alok Krishna

    2011-03-01

    In Mammalian system the WNK (with no lysine kinase) serine-threonine protein kinase gene family is suggested to be involved in regulating ion homeostasis and other pathophysiological processes including cancer, hypertension and renal ion transport. In plant system the information about WNK genes is very poor. However, WNK-like genes have also been identified in plants, including ten in Arabidopsis, designated AtWNK1-AtWNK10. Here we report the cloning and characterization of a homologue of AtWNK1 gene from Oryza sativa indica cultivar Pusa Basmati-1 rice and designated as OsWNK1. The specific feature of this gene is lysine residue in kinase subdomain II, which is essential for the coordination of ATP in the active center and conserved among all other kinases, is absent. OsWNK1 was found to respond differentially under various abiotic stresses like cold, heat, salt, drought. OsWNK1 gene showed rhythmic expression profile under diurnal and circadian conditions at the transcription level. Our data indicates that OsWNK1 in rice might play a role in abiotic stress tolerance and that it is involved in internal rhythm. PMID:21178395

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

    PubMed

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

    2010-11-01

    Bed bugs must avoid detection when finding hosts and returning to hidden harborages. Their stealthy habits include foraging when hosts are asleep. Characteristics of spontaneous locomotor activity rhythm of bed bugs with different feeding histories were studied. In the absence of host stimuli, adults and nymphs were much more active in the dark than in the light. The onset of activity in the scotophase commenced soon after lights-off. The free-running period (tau) for all stages was longer in continuous darkness (DD) than in continuous light (LL). The lengthening of tau in DD is an exception for the circadian rule that predicts the opposite in nocturnal animals. Activity in all stages was entrained to reverse L:D regimes within four cycles. Short-term starved adults moved more frequently than recently fed adults. While bed bugs can survive for a year or more without a blood meal, we observed a reduction in activity in insects held for five weeks without food. We suggest that bed bugs make a transition to host-stimulus dependent searching when host presence is not predictable. Such a strategy would enable bed bugs to maximize reproduction when resources are abundant and save energy when resources are scarce. PMID:20452356

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

    PubMed

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

    1995-09-01

    The nocturnal versus diurnal feeding patterns of sea bass under controlled experimental conditions were studied in order to investigate the existence of such a dualistic feeding behavior. The animals (six groups of 4 animals and 8 single fish) were held in tanks filled with recirculating salt water and installed in a "chronolab" under constant conditions (23.5 degrees C and 2.4% salinity). The fish were given access to self-demand feeders and first exposed to a photoperiod regime of 12:12 (12 h light, 70 lx, and 12 h dark, complete darkness) and then to light:dark (LD) pulses (40 min light, 40 min dark). The LD 12:12 cycle was reversed by doubling the light period in day 16, and reversed again in day 27 by doubling the dark period. The circadian rhythm of food demand was strongly synchronized with the LD cycle, and fish exhibited both diurnal and nocturnal patterns. In most fish, the shift of the feeding rhythm to the new LD cycle was very fast for each reversal (bringing forward or delaying their feeds 12 h), indicating a weak participation of an endogenous circadian rhythm. However, when submitted to LD pulses, fish began to free-run with a periodicity of about 23 h and kept feeding in the light or dark phase according to their prior behavior. The existence of a dualism in the diel feeding pattern in sea bass was thus clearly demonstrated and it appeared that the diurnal and nocturnal behavior did not depend exclusively on a circadian phase inversion of the feeding rhythms as this pattern of behavior was enhanced under ultradian LD pulses. The ecological implications of such dual capacity and the switch from one type of phasing to another are hitherto unknown and need further field and laboratory investigation. PMID:7488763

  4. Functional genomics of the avian circadian system 

    E-print Network

    Bailey, Michael J

    2006-04-12

    The genetic identification of molecular mechanisms responsible for circadian rhythm generation has advanced tremendously over the past 25 years. However the molecular identities of the avian clock remain largely unexplored. ...

  5. Lack of circadian rhythm of plasma concentrations of vasoactive intestinal peptide in patients with orthotopic heart transplants.

    PubMed Central

    Cugini, P; Lucia, P; Scibilia, G; Di Palma, L; Cioli, A R; Cianetti, A; Gasbarrone, L; Canova, R; Marino, B

    1993-01-01

    OBJECTIVE--To study the circadian pattern of plasma concentrations of vasoactive intestinal peptide (VIP) in patients with orthotopic heart transplants. Circulating VIP is known to have neural and immunological sources. PATIENTS AND METHODS--13 patients with orthotopic heart transplants were studied 12-53 months (mean 31.8 months) after operation. All were haemodynamically compensated and had no histological evidence of rejection. They were being treated with cyclosporin, azathioprine, and prednisone. Ten healthy individuals were studied as controls. Circulating VIP was assayed six times within a 24h period. Time qualified data were analysed by ANOVA and the cosinor method. Student's t test for unpaired data and Bingham's test for cosinor-derived parameters were used for statistical comparisons. RESULTS--Plasma concentrations of VIP were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively showed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants. DISCUSSION--The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VIPergic fibres, a reduction of VIP release by the pharmacologically suppressed immune system, the inhibitory effects of cyclosporin on neural function and humoral secretions, and the effects of negative feedback on VIP release of high concentrations of atrial natriuretic peptide. The lack of the circadian rhythm suggests a structural disorder, which should be further investigated. PMID:8217446

  6. Ramelteon (TAK-375) accelerates reentrainment of circadian rhythm after a phase advance of the light-dark cycle in rats.

    PubMed

    Hirai, Keisuke; Kita, Muneto; Ohta, Hiroyuki; Nishikawa, Hisao; Fujiwara, Yuu; Ohkawa, Shigenori; Miyamoto, Masaomi

    2005-02-01

    In vivo pharmacological effects of ramelteon (TAK-375), a novel, highly MT1/MT2-selective receptor agonist, were studied in rats to determine ramelteon's ability to reentrain the circadian rhythm after an abrupt phase advance. Experiments were also conducted to assess the potential cognitive side effects of ramelteon and its potential to become a drug of abuse. After an abrupt 8-h phase shift, ramelteon (0.1 and 1 mg/kg, p.o.) and melatonin (10 mg/kg, p.o.) accelerated reentrainment of running wheel activity rhythm to the new lightdark cycle. Ramelteon (3-30 mg/kg, p.o.) and melatonin (10-100 mg/kg, p.o.) did not affect learning or memory in rats tested by the water maze task and the delayed match to position task, although diazepam and triazolam impaired both of the tasks. Neither ramelteon (3-30 mg/kg, p.o.) nor melatonin (10-100 mg/kg, p.o.) demonstrated a rewarding property in the conditioned place-preference test, implying that MT1/MT2 receptor agonists have no abuse potential. In contrast, benzodiazepines and morphine showed rewarding properties in this test. The authors' results suggest that ramelteon may be useful for treatment of circadian rhythm sleep disorders without adverse effects typically associated with benzodiazepine use, such as learning and memory impairment, and drug dependence. PMID:15654068

  7. The benzodiazepine triazolam phase-shifts circadian activity rhythms in a diurnal primate, the squirrel monkey (Saimiri sciureus).

    PubMed

    Mistlberger, R E; Houpt, T A; Moore-Ede, M C

    1991-03-11

    Triazolam can shift the phase of circadian rhythms in hamsters recorded in constant light or dark. This effect is apparently mediated by physical activity stimulated by the drug. We examined whether triazolam can shift the phase of circadian rhythms in a diurnal primate, the squirrel monkey, that is sedated by triazolam. Single injections of triazolam at 0.15-0.20 mg/kg induced phase advances or delays of monkey activity rhythms recorded in constant light. The phase-response curve is similar to that obtained for hamsters. Behavioral activation is evidently not necessary for a phase-shifting action of triazolam in this primate. A companion study in which triazolam was administered to squirrel monkeys in the dark in a light-dark cycle reentrainment paradigm failed to find evidence for a phase shifting action of triazolam. Shifts induced by triazolam in monkeys recorded in constant light may thus reflect changes in light exposure as a consequence of sedation or altered retinal processing of light. PMID:1857540

  8. Effects of estrogen replacement therapy on the circadian rhythms of serum cortisol and body temperature in postmenopausal women.

    PubMed

    Gudmundsson, A; Goodman, B; Lent, S; Barczi, S; Grace, A; Boyle, L; Ershler, W B; Carnes, M

    1999-09-01

    Estrogen replacement therapy (ERT) seems to enhance longevity in women. Both gender and aging have been shown to influence the regulation of circadian rhythms, yet little is known about the effect of ERT on circadian regulation. The aim of this study was to determine the effects of ERT (oral conjugated estrogen: Premarin, 0.625 mg) for 6-8 weeks on circadian serum cortisol by continuous blood sampling every 15 min for 24 h with simultaneous measurements of body temperature in six healthy postmenopausal women (range, 54-61 years). The results are presented as median values (range in quartiles). The circadian amplitude of cortisol increased during ERT from 20.20 (18.35, 23.61) to 25.97 (24.94, 27.74) microg/dL (p = 0.016), whereas the timing of nocturnal nadir and morning acrophase did not differ significantly. ERT lowered the 24-h body temperature from 37.03 degrees C (36.95 degrees C, 37.07 degrees C) to 36.90 degrees C (36.77 degrees C, 36.97 degrees C) (p = 0.038), but did not alter the peak and trough body temperatures significantly. These findings are noteworthy because the increased circadian amplitude of serum cortisol during ERT contrasts with the reduction in circadian amplitude seen with normal aging. The reduction in body temperature confirms the regulatory effect of ERT in thermoregulation and has implications regarding the correlation between basal metabolic rate and life span. PMID:10579640

  9. In Vivo Monitoring of Multi-Unit Neural Activity in the Suprachiasmatic Nucleus Reveals Robust Circadian Rhythms in Period1?/? Mice

    PubMed Central

    Takasu, Nana N.; Pendergast, Julie S.; Olivas, Cathya S.; Yamazaki, Shin; Nakamura, Wataru

    2013-01-01

    The master pacemaker in the suprachiasmatic nucleus (SCN) controls daily rhythms of behavior in mammals. C57BL/6J mice lacking Period1 (Per1?/?) are an anomaly because their SCN molecular rhythm is weak or absent in vitro even though their locomotor activity rhythm is robust. To resolve the contradiction between the in vitro and in vivo circadian phenotypes of Per1?/? mice, we measured the multi-unit activity (MUA) rhythm of the SCN neuronal population in freely-behaving mice. We found that in vivo Per1?/? SCN have high-amplitude MUA rhythms, demonstrating that the ensemble of neurons is driving robust locomotor activity in Per1?/? mice. Since the Per1?/? SCN electrical activity rhythm is indistinguishable from wild-types, in vivo physiological factors or coupling of the SCN to a known or unidentified circadian clock(s) may compensate for weak endogenous molecular rhythms in Per1?/? SCN. Consistent with the behavioral light responsiveness of Per1?/? mice, in vivo MUA rhythms in Per1?/? SCN exhibited large phase shifts in response to light. Since the acute response of the MUA rhythm to light in Per1?/? SCN is equivalent to wild-types, an unknown mechanism mediates enhanced light responsiveness of Per1?/? mice. Thus, Per1?/? mice are a unique model for investigating the component(s) of the in vivo environment that confers robust rhythmicity to the SCN as well as a novel mechanism of enhanced light responsiveness. PMID:23717599

  10. Influence of the circadian rhythm of body temperature on the physiological response to microwaves: Day versus night exposure

    SciTech Connect

    Lotz, W.G.

    1981-10-01

    The results of this study demonstrate an influence of the circadian rhythm on the effects of microwave exposure on plasma cortisol and rectal temperature. The lower rectal temperature during night exposures was presumably due to the lower sham-condition temperature at night, since the temperature increase over sham levels was similar for either day or night exposures. The absence of a cortisol response during night exposures may be simply related to the absolute body temperature reached, although more complex circadian influences cannot be eliminated by these data. Although the results were insufficient to provide a clear understanding of the mechanisms involved, it was shown conclusively that the responses studied depended not only on the independent variables of microwave exposure selected, but also on the baseline levels of the normal physiological state that existed at the time of exposure.

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

    PubMed

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

    2012-01-01

    Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P?.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P?=?.025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed. PMID:23284821

  12. Increasing external K+ blocks phase shifts in a circadian rhythm produced by serotonin or 8-benzylthio-cAMP.

    PubMed

    Eskin, A

    1982-05-01

    Serotonin (5-HT) phase shifts the circadian rhythm from the isolated eye of Aplysia. The discovery of the mechanisms involved in phase shifting by 5-HT may help elucidate the nature of the circadian oscillator. We have found that 5-HT appears to phase shift by causing a change in membrane K+ conductance. Solutions containing zero K+(0-K+) phase shift the rhythm and the phase response curve (PRC) for 0-K+ is similar to one previously obtained for 5-HT. The similarity in PRCs for 0-K+ and 5-HT suggested that these treatments may be phase shifting the rhythm through a common mechanism. The nonadditivity of phase shifting by 0-K+ and 5-HT supports this suggestion. A common mechanism of action of 5-HT and 0-K+ might be effects on membrane potentials. The possible involvement of a membrane potential change in mediating the effect of 5-HT and the lack of an effect of large reductions in Na+, Cl-, and Ca2+ ions on phase shifting by 5-HT led us to examine the role of K+ ions in phase shifting by 5-HT. A change in K+ conductance may mediate the effects of 5-HT on the rhythm because HiK (30mM) solutions blocked the phase shift normally produced by 5-HT. The conductance change produced by 5-HT may be an increase in K+ conductance which would produce a hyperpolarization and not a decrease in K+ conductance which would produce a depolarization since depolarizing treatments, HiK (30-110mM), had no effect on the rhythm at the phase where 5-HT produces its largest phase shifts. Since we previously found that the effects of 5-HT appear to be mediated by cAMP, we examined whether HiK solutions could block the effects of 8-benzylthio-cAMP on the rhythm. HiK (40mM) blocked the phase shifts normally produced by 8-benylthio-cAMP. Our working hypothesis for the 5-HT phase-shifting pathway based on these results is 5-HT leads to increased cAMP leads to elevates K+ conductance leads to membrane hyperpolarization leads to phase shifts the rhythm. PMID:6281380

  13. Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

    PubMed

    Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

    2015-06-01

    The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate < 0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. PMID:25805767

  14. Pigment-Dispersing Factor Signaling and Circadian Rhythms in Insect Locomotor Activity.

    PubMed

    Shafer, Orie T; Yao, Zepeng

    2014-07-01

    Though expressed in relatively few neurons in insect nervous systems, pigment-dispersing factor (PDF) plays many roles in the control of behavior and physiology. PDF's role in circadian timekeeping is its best-understood function and the focus of this review. Here we recount the isolation and characterization of insect PDFs, review the evidence that PDF acts as a circadian clock output factor, and discuss emerging models of how PDF functions within circadian clock neuron network of Drosophila, the species in which this peptide's circadian roles are best understood. PMID:25386391

  15. GENERATION AND MAINTENANCE OF THE RESPIRATORY RHYTHM

    Microsoft Academic Search

    D. W. RICHTER

    1983-01-01

    SUMMARY Activities of the phrenic and internal intercostal nerves show that the central nervous rhythm of respiration consists of 3 phases: inspiratory, postinspiratory and expiratory. The discharge patterns of medullary respira- tory neurones of the anaesthetized, paralysed cat can be correlated with these phases of the central respiratory cycle, and the postsynaptic activity of indivi- dual cells can be analysed

  16. Expression profiling of skeletal muscle following acute and chronic ?2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

    PubMed Central

    Pearen, Michael A; Ryall, James G; Lynch, Gordon S; Muscat, George EO

    2009-01-01

    Background Systemic administration of ?-adrenoceptor (?-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of ?-AR signaling has been highlighted by the inability of ?1-3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic (acute and chronic) administration of the ?2-AR agonist formoterol. Results Skeletal muscle gene expression (from murine tibialis anterior) was profiled at both 1 and 4 hours following systemic administration of the ?2-AR agonist formoterol, using Illumina 46K mouse BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress. Differentially expressed genes relevant to the regulation of muscle mass and metabolism (in the context of the hypertrophic phenotype) were further validated by quantitative RT-PCR to examine gene expression in response to both acute (1-24 h) and chronic administration (1-28 days) of formoterol at multiple timepoints. In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling (including differential expression of myostatin, activin receptor IIB, phospho-Smad3 etc) was observed following acute and chronic administration of formoterol. Acute (but not chronic) administration of formoterol also significantly induced the expression of genes involved in oxidative metabolism, including hexokinase 2, sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly, formoterol administration also appeared to influence some genes associated with the peripheral regulation of circadian rhythm (including nuclear factor interleukin 3 regulated, D site albumin promoter binding protein, and cryptochrome 2). Conclusion This is the first study to utilize gene expression profiling to examine global gene expression in response to acute ?2-AR agonist treatment of skeletal muscle. In summary, systemic administration of a ?2-AR agonist had a profound effect on global gene expression in skeletal muscle. In terms of hypertrophy, ?2-AR agonist treatment altered the expression of several genes associated with myostatin signaling, a previously unreported effect of ?-AR signaling in skeletal muscle. This study also demonstrates a ?2-AR agonist regulation of circadian rhythm genes, indicating crosstalk between ?-AR signaling and circadian cycling in skeletal muscle. Gene expression alterations discovered in this study provides insight into many of the underlying changes in gene expression that mediate ?-AR induced skeletal muscle hypertrophy and altered metabolism. PMID:19772666

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

    PubMed Central

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

    2013-01-01

    In an earlier published telephone interview study (n > 1,000) we have shown that retired shift workers subjectively report worse sleep than retired day workers. This laboratory study sought to determine whether these findings held up when objective polysomnograhic (PSG) measures of sleep were taken and whether retirees' circadian temperature rhythms differed as a function of shift work exposure. All completers of the telephone interview were invited to attend a 36-hour laboratory study for which participants were paid. This involved continuous core body temperature measurement (using an ingestible pill-based system) and 2 nights of PSG. Shift work exposure (plus other measures) was collected by taking a detailed work history. The second laboratory night was scored into sleep stages. Post hoc, we divided participants into 4 shift work exposure groups: 0 years (ie, no exposure to shift work), 1 to 7 years, 7 to 20 years, and >20 years. Sample sizes were 11, 16, 15, and 15, respectively, with approximate equality in mean age (71.7 years of age, 69.1 years of age, 70.0 years of age, and 70.4 years of age, respectively) and percent male (63%, 50%, 67%, and 73%, respectively). Shift work exposure was associated with worse PSG sleep in a dose-related fashion. The percentages of participants with sleep efficiency, 80% for the 0 years, 1 to 7 years, 7 to 20 years, and >20 years groups were 36%, 63%, 67%, and 73%, respectively (P < 0.01), and the percentages with total sleep time (TST), 6 hours were 36%, 56%, 53%, and 73%, respectively (P < 0.01). From the circadian rhythm record, shift work exposure appeared to result (P = 0.06) in an increased spread of phase angles (difference between habitual bedtime and time of temperature trough). In conclusion, it appears likely that shift work may be related to a scarring of sleep and circadian rhythms. This may be associated with a change in the relationship between habitual sleep timing and the phase of the circadian pacemaker. PMID:24062618

  18. Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction

    PubMed Central

    Li, Ai-Jun; Dinh, Thu T.; Jansen, Heiko T.; Ritter, Sue

    2013-01-01

    Previously, we investigated the role of neuropeptide Y and leptin-sensitive networks in the mediobasal hypothalamus in sleep and feeding and found profound homeostatic and circadian deficits with an intact suprachiasmatic nucleus. We propose that the arcuate nuclei (Arc) are required for the integration of homeostatic circadian systems, including temperature and activity. We tested this hypothesis using saporin toxin conjugated to leptin (Lep-SAP) injected into Arc in rats. Lep-SAP rats became obese and hyperphagic and progressed through a dynamic phase to a static phase of growth. Circadian rhythms were examined over 49 days during the static phase. Rats were maintained on a 12:12-h light-dark (LD) schedule for 13 days and, thereafter, maintained in continuous dark (DD). After the first 13 days of DD, food was restricted to 4 h/day for 10 days. We found that the activity of Lep-SAP rats was arrhythmic in DD, but that food anticipatory activity was, nevertheless, entrainable to the restricted feeding schedule, and the entrained rhythm persisted during the subsequent 3-day fast in DD. Thus, for activity, the circuitry for the light-entrainable oscillator, but not for the food-entrainable oscillator, was disabled by the Arc lesion. In contrast, temperature remained rhythmic in DD in the Lep-SAP rats and did not entrain to restricted feeding. We conclude that the leptin-sensitive network that includes the Arc is required for entrainment of activity by photic cues and entrainment of temperature by food, but is not required for entrainment of activity by food or temperature by photic cues. PMID:23986359

  19. SRC-2 is an essential coactivator for orchastrating metabolism and circadian rhythm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:C...

  20. Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels

    Microsoft Academic Search

    W. P. Colquhoun; J. Rutenfranz; H. Goethe; B. Neidhart; R. Condone; R. Plett; P. Knauth

    1988-01-01

    The safety of a ship depends substantially on its bridge watchkeepers, whose alertness and efficiency must be maintained at all hours of the day and night. Fatigue, circadian rhythms, and sleep disruption occasioned by the unusual working hours of these personnel may all affect their performance. A methodology for assessing the magnitude of this problem is proposed. The application of

  1. Effects of environmental enrichment on behavioral responses to novelty, learning, and memory, and the circadian rhythm in cortisol in growing pigs

    Microsoft Academic Search

    Ingrid C. de Jong; Ina T. Prelle; Johan A. van de Burgwal; Elbert Lambooij; S. Mechiel Korte; Harry J. Blokhuis; Jaap M. Koolhaas

    2000-01-01

    Previously we showed that pigs reared in an enriched environment had higher baseline salivary cortisol concentrations during the light period than pigs reared under barren conditions. In the present experiment, it was investigated whether these higher baseline salivary cortisol concentrations were a real difference in cortisol concentration or merely represented a phase difference in circadian rhythm. The effects of different

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  3. Arterioscler Thromb Vasc Biol . Author manuscript Nuclear receptors linking circadian rhythms and cardiometabolic control

    E-print Network

    Paris-Sud XI, Université de

    between circadian disorders and altered metabolic responses and cardiovascular events. Shiftwork ; Animals ; Cardiovascular Agents ; therapeutic use ; Cardiovascular Diseases ; drug therapy ; genetics effects ; genetics ; Energy Metabolism ; drug effects ; genetics ; Humans ; Receptors, Cytoplasmic

  4. Effects of sleep and circadian rhythm on the human immune system.

    PubMed

    Lange, Tanja; Dimitrov, Stoyan; Born, Jan

    2010-04-01

    Many immune parameters show systematic fluctuations over the 24-h day in human blood. Circulating naive T-cells and production of proinflammatory cytokines, like interleukin-12 (IL-12), peak during nighttime, whereas cytotoxic effector leukocytes and production of the anti-inflammatory cytokine IL-10 peak during daytime. These temporal changes originate from a combined influence of the circadian system and sleep. Both brain functions act synergistically and share neuroendocrine effector mechanisms to convey control over immune functions. Sympathetic tone and cortisol levels show a circadian nadir during nighttime and are further suppressed by sleep, whereas growth hormone and prolactin show a circadian peak during nighttime and are further enhanced by sleep. Thus, the circadian system and sleep jointly evoke a unique endocrine constellation that is extremely effective in inducing changes in leukocyte traffic and a shift toward proinflammatory type 1-cytokines during the nocturnal period of sleep, that is, an action with strong clinical implications. PMID:20398008

  5. Mid-range Ultradian Rhythms in Drosophila and the Circadian Clock Problem

    Microsoft Academic Search

    H. B. Dowse

    The current molecular model of the circadian timer presumes a 24-h escapement based on a transcription\\/translation oscillator\\u000a (TTO) as the ultimate frequency source. The output of a very accurate mammalian circadian clock functioning both in free-run\\u000a and LD-entrained mode is here analyzed using clock-theory methodology. The results are used to ask whether this postulated\\u000a molecular oscillator is consistent in theory

  6. Continuous Exposure to a Novel Stressor Based on Water Aversion Induces Abnormal Circadian Locomotor Rhythms and Sleep-Wake Cycles in Mice

    PubMed Central

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

    2013-01-01

    Psychological stressors prominently affect diurnal rhythms, including locomotor activity, sleep, blood pressure, and body temperature, in humans. Here, we found that a novel continuous stress imposed by the perpetual avoidance of water on a wheel (PAWW) affected several physiological diurnal rhythms in mice. One week of PAWW stress decayed robust circadian locomotor rhythmicity, while locomotor activity was evident even during the light period when the mice are normally asleep. Daytime activity was significantly upregulated, whereas nighttime activity was downregulated, resulting in a low amplitude of activity. Total daily activity gradually decreased with increasing exposure to PAWW stress. The mice could be exposed to PAWW stress for over 3 weeks without adaptation. Furthermore, continuous PAWW stress enhanced food intake, but decreased body weight and plasma leptin levels, indicating that sleep loss and PAWW stress altered the energy balance in these mice. The diurnal rhythm of corticosterone levels was not severely affected. The body temperature rhythm was diurnal in the stressed mice, but significantly dysregulated during the dark period. Plasma catecholamines were elevated in the stressed mice. Continuous PAWW stress reduced the duration of daytime sleep, especially during the first half of the light period, and increased nighttime sleepiness. Continuous PAWW stress also simultaneously obscured sleep/wake and locomotor activity rhythms compared with control mice. These sleep architecture phenotypes under stress are similar to those of patients with insomnia. The stressed mice could be entrained to the light/dark cycle, and when they were transferred to constant darkness, they exhibited a free-running circadian rhythm with a timing of activity onset predicted by the phase of their entrained rhythms. Circadian gene expression in the liver and muscle was unaltered, indicating that the peripheral clocks in these tissues remained intact. PMID:23383193

  7. Circadian Rhythms of Glucocorticoid Hormone Actions in Target Tissues: Potential Clinical Implications

    NSDL National Science Digital Library

    Tomoshige Kino (NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development REV)

    2012-10-02

    Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations—including obesity, metabolic syndrome, and cardiovascular disease—by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids.

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

    PubMed Central

    Stashi, Erin; Lanz, Rainer B.; Mao, Jianqiang; Michailidis, George; Zhu, Bokai; Kettner, Nicole M.; Putluri, Nagireddy; Reineke, Erin L.; Reineke, Lucas C.; Dasgupta, Subhamoy; Dean, Adam; Stevenson, Connor R.; Sivasubramanian, Natarajan; Sreekumar, Arun; DeMayo, Francesco; York, Brian; Fu, Loning; O'Malley, Bert W.

    2014-01-01

    SUMMARY Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1: CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circa-dian clock. PMID:24529706

  9. Socially synchronized circadian oscillators

    PubMed Central

    Bloch, Guy; Herzog, Erik D.; Levine, Joel D.; Schwartz, William J.

    2013-01-01

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian ‘clock’). The alternation of environmental light and darkness synchronizes (entrains) these rhythms to the natural day–night cycle, and underlying mechanisms have been investigated using singly housed animals in the laboratory. But, most species ordinarily would not live out their lives in such seclusion; in their natural habitats, they interact with other individuals, and some live in colonies with highly developed social structures requiring temporal synchronization. Social cues may thus be critical to the adaptive function of the circadian system, but elucidating their role and the responsible mechanisms has proven elusive. Here, we highlight three model systems that are now being applied to understanding the biology of socially synchronized circadian oscillators: the fruitfly, with its powerful array of molecular genetic tools; the honeybee, with its complex natural society and clear division of labour; and, at a different level of biological organization, the rodent suprachiasmatic nucleus, site of the brain's circadian clock, with its network of mutually coupled single-cell oscillators. Analyses at the ‘group’ level of circadian organization will likely generate a more complex, but ultimately more comprehensive, view of clocks and rhythms and their contribution to fitness in nature. PMID:23825203

  10. Circadian rhythm of some parameters of body composition in the elderly investigated by means of bioelectrical impedance analysis.

    PubMed

    Cugini, P; Salandri, A; Celli, V; Leonetti Luparini, R; De Rosa, R; Marigliano, V

    2002-09-01

    We studied the within-day determinations of some body composition (BC) parameters in clinically healthy elderly subjects with the aim of investigating their circadian rhythms (CR), which are known to vary in a circadian manner in clinically healthy young adults. The study involved six non-smoking, clinically healthy elderly males (mean age: 75 +/- 4 years; mean weight: 71.07 +/- 10.26 kg; mean height: 170 +/- 5 cm, mean BMI: 24 +/- 1 kg/m2). The BC parameters were determined by means of bioelectrical impedance analysis (BIA) at 2-hour intervals during the day and night, with the subjects lying horizontally in bed. The time-qualified BC estimates were analysed using the Cosinor method. The analysis revealed that the healthy elderly subjects had lost the CR of a number of the BC parameters, including fat body mass, cell body mass, extracellular body mass, total body water, extracellular body water, intracellular body water, and the Na and K exchangeable pools. However, they still retained the CR of body weight and lean body mass, with the expected nocturnal phase of oscillation. The abolition of the CR of the majority of BC parameters in the elderly suggests that human senescence is characterised by consistent changes in the daily rhythmic patterns of fat, water and electrolyte metabolism. PMID:12452249

  11. Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm.

    PubMed

    Broda, H; Gooch, V D; Taylor, W; Aiuto, N; Hastings, J W

    1986-01-01

    During measurements of the circadian (approximately 24-hr) rhythms of spontaneous bioluminescence in the marine dinoflagellate Gonyaulax polyedra, the individual cultures in vials were shielded from otherwise constant dim light for 1-3 min every 20-60 min by a photomultiplier housing that was moved from vial to vial. The high-frequency dark pulses caused a small but consistent shortening of the free-running circadian period, but there was no indication that the dark pulses caused entrainment. Hardware and software components of the microcomputer-controlled data collection system are described. A microcomputer controlled the movement of the photomultiplier and acquired the data via an analog-to-digital converter. The algorithms distinguished and separately recorded background glow, intermittent flashes, and total light from populations ranging in number from 10(3) to 10(5) cells in volumes from 1 to 10 ml. Fast video display techniques allowed continuous on-line viewing of incoming data, together with a display of the data recorded over the preceding day or two. Detection of mechanical and software errors coupled with recovery systems maintained high reliability of data collection. PMID:2979588

  12. Effects of circadian rhythm and cAMP on retinomotor movements in the green sunfish, Lepomis cyanellus.

    PubMed

    Burnside, B; Ackland, N

    1984-05-01

    The photoreceptors and retinal pigmented epithelium (RPE) of teleosts undergo diurnal changes in position in response to day/night changes in light conditions. These position changes, called retinomotor movements, may also persist under conditions of constant darkness. In this study, the authors have compared the retinomotor movements of rods, cones, and RPE under conditions of constant darkness and constant temperature in the green sunfish, Lepomis cyanellus . In this species, cones undergo circadian cycles of retinomotor movements in constant darkness but rods and RPE do not. Also cone contraction commences in early morning before the expected time of light onset, thus suggesting that circadian rhythms may play an important regulatory role in these cells even under cyclic light conditions. Since treatments that elevate cAMP previously have been shown to induce dark-adaptive retinomotor positions, the authors also have compared the effects of exogenous cAMP analogs on retinomotor positions of rods, cones, and RPE pigment in cultured green sunfish retinas. The authors found that concentrations of cAMP analogs required to produce extreme dark-adaptive retinomotor positions were at least fivefold higher for cones than for rods and RPE. PMID:6325366

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  15. Realistically Coupled Neural Mass Models Can Generate EEG Rhythms

    Microsoft Academic Search

    Roberto C. Sotero; Nelson J. Trujillo-barreto; Yasser Iturria-medina; Felix Carbonell; Juan C. Jimenez

    2007-01-01

    We study the generation of EEG rhythms by means of realistically coupled neural mass models. Previous neural mass models were used to model cortical voxels and the thalamus. Interactions between voxels of the same and other cortical areas and with the thalamus were taken into account. Voxels within the same cortical area were coupled (short-range connections) with both excitatory and

  16. Drosophila peptidyl-prolyl isomerase Pin1 modulates circadian rhythms via regulating levels of PERIOD.

    PubMed

    Kang, So Who; Lee, Euna; Cho, Eunjoo; Seo, Ji Hye; Ko, Hyuk Wan; Kim, Eun Young

    2015-07-31

    In animal circadian clock machinery, the phosphorylation program of PERIOD (PER) leads to the spatio-temporal regulation of diverse PER functions, which are crucial for the maintenance of ?24-hr circadian rhythmicity. The peptidyl-prolyl isomerase PIN1 modulates the diverse functions of its substrates by inducing conformational changes upon recognizing specific phosphorylated residues. Here, we show that overexpression of Drosophila pin1, dodo (dod), lengthens the locomotor behavioral period. Using Drosophila S2 cells, we demonstrate that Dod associates preferentially with phosphorylated species of PER, which delays the phosphorylation-dependent degradation of PER. Consistent with this, PER protein levels are higher in flies overexpressing dod. Taken together, we suggest that Dod plays a role in the maintenance of circadian period by regulating PER metabolism. PMID:25998391

  17. Characteristics of the circadian rhythm in diffusive resistance of Abutilon theophrasti leaves in humid and dry environments.

    PubMed

    Fuhrman, M H; Koukkari, W L

    1982-01-01

    Diffusive resistance of the upper and lower leaf surfaces of Abutilon theophrasti Medic, was measured with an automatic diffusive resistance meter. Plants were maintained in growth chambers under 4 different environments: 1. high humidity, well-watered, 2. high humidity, dry, 3. low humidity, well-watered, 4. low humidity, dry. Diffusive resistance measurements were obtained every 4 h for up to 3 days when the plants were subjected to either daily regimes consisting of 15 h of light followed by 9 h of darkness or to continuous illumination. Leaf movements were also monitored. Diffusive resistance was rhythmic (circadian) under all the environmental conditions examined. The pattern of diffusive resistance was the same regardless of whether the humidity and/or soil moisture were high or low. The rhythms of diffusive resistance of the upper and lower leaf surfaces differed, however, in amplitude and in the phase at which the minimum value was reached. Diffusive resistance of the leaf was highest (peak of the rhythm) when the leaf blade was in a nearly horizontal position. PMID:7140475

  18. Rhythm Generation through Period Concatenation in Rat Somatosensory Cortex

    PubMed Central

    Kramer, Mark A.; Roopun, Anita K.; Carracedo, Lucy M.; Traub, Roger D.; Whittington, Miles A.; Kopell, Nancy J.

    2008-01-01

    Rhythmic voltage oscillations resulting from the summed activity of neuronal populations occur in many nervous systems. Contemporary observations suggest that coexistent oscillations interact and, in time, may switch in dominance. We recently reported an example of these interactions recorded from in vitro preparations of rat somatosensory cortex. We found that following an initial interval of coexistent gamma (?25 ms period) and beta2 (?40 ms period) rhythms in the superficial and deep cortical layers, respectively, a transition to a synchronous beta1 (?65 ms period) rhythm in all cortical layers occurred. We proposed that the switch to beta1 activity resulted from the novel mechanism of period concatenation of the faster rhythms: gamma period (25 ms)+beta2 period (40 ms)?=?beta1 period (65 ms). In this article, we investigate in greater detail the fundamental mechanisms of the beta1 rhythm. To do so we describe additional in vitro experiments that constrain a biologically realistic, yet simplified, computational model of the activity. We use the model to suggest that the dynamic building blocks (or motifs) of the gamma and beta2 rhythms combine to produce a beta1 oscillation that exhibits cross-frequency interactions. Through the combined approach of in vitro experiments and mathematical modeling we isolate the specific components that promote or destroy each rhythm. We propose that mechanisms vital to establishing the beta1 oscillation include strengthened connections between a population of deep layer intrinsically bursting cells and a transition from antidromic to orthodromic spike generation in these cells. We conclude that neural activity in the superficial and deep cortical layers may temporally combine to generate a slower oscillation. PMID:18773075

  19. Free Access to a Running-Wheel Advances the Phase of Behavioral and Physiological Circadian Rhythms and Peripheral Molecular Clocks in Mice

    PubMed Central

    Yasumoto, Yuki; Nakao, Reiko; Oishi, Katsutaka

    2015-01-01

    Behavioral and physiological circadian rhythms are controlled by endogenous oscillators in animals. Voluntary wheel-running in rodents is thought to be an appropriate model of aerobic exercise in humans. We evaluated the effects of chronic voluntary exercise on the circadian system by analyzing temporal profiles of feeding, core body temperature, plasma hormone concentrations and peripheral expression of clock and clock-controlled genes in mice housed under sedentary (SED) conditions or given free access to a running-wheel (RW) for four weeks. Voluntary wheel-running activity advanced the circadian phases of increases in body temperature, food intake and corticosterone secretion in the mice. The circadian expression of clock and clock-controlled genes was tissue- and gene-specifically affected in the RW mice. The temporal expression of E-box-dependent circadian clock genes such as Per1, Per2, Nr1d1 and Dbp were slightly, but significantly phase-advanced in the liver and white adipose tissue, but not in brown adipose tissue and skeletal muscle. Peak levels of Per1, Per2 and Nr1d1 expression were significantly increased in the skeletal muscle of RW mice. The circadian phase and levels of hepatic mRNA expression of the clock-controlled genes that are involved in cholesterol and fatty acid metabolism significantly differed between SED and RW mice. These findings indicated that endogenous clock-governed voluntary wheel-running activity provides feedback to the central circadian clock that systemically governs behavioral and physiological rhythms. PMID:25615603

  20. Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.

    PubMed

    van de Luit, L; van der Meulen, J; Cleophas, T J; Zwinderman, A H

    1998-11-01

    Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms. Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded. The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02). Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be. PMID:9822046

  1. The calcium rhythms of different cell types oscillate with different circadian phases.

    PubMed

    Wood, N T; Haley, A; Viry-Moussaïd, M; Johnson, C H; van der Luit, A H; Trewavas, A J

    2001-02-01

    Transgenic tobacco (Nicotiana plumbaginifolia) seedlings containing the Ca(2+)-sensitive luminescent protein aequorin have been shown to exhibit circadian variations in cytosolic calcium. Concomitant measurements of cytosolic and nuclear calcium show that circadian variations in the cytoplasm are not expressed in the nucleus. To investigate whether all cells of transgenic seedlings contribute equally to circadian variations in cytosolic calcium, different promoters eliciting different expression patterns have been placed upstream of aequorin and used for transformation. The circadian peak occurred at different times in the three transgenic lines constructed. Luminescence imaging of these transgenic lines indicated that aequorin was differentially accumulated among the main tissues and cells of the seedlings and overcoat technology with applied epidermal strips indicated that the surface cell layers contribute the vast majority of luminescent light. We conclude that the Ca(2+) rhythmicities of cells and tissues oscillate with distinct differences in phase, that this might represent different underlying cellular control mechanisms and that these observations have significant implications for our understanding and study of Ca(2+) mediated signal transduction in plant cells. PMID:11161036

  2. The Calcium Rhythms of Different Cell Types Oscillate with Different Circadian Phases

    PubMed Central

    Wood, Nicola T.; Haley, Ann; Viry-Moussaïd, Martine; Johnson, Carl H.; van der Luit, Arnold H.; Trewavas, Anthony J.

    2001-01-01

    Transgenic tobacco (Nicotiana plumbaginifolia) seedlings containing the Ca2+-sensitive luminescent protein aequorin have been shown to exhibit circadian variations in cytosolic calcium. Concomitant measurements of cytosolic and nuclear calcium show that circadian variations in the cytoplasm are not expressed in the nucleus. To investigate whether all cells of transgenic seedlings contribute equally to circadian variations in cytosolic calcium, different promoters eliciting different expression patterns have been placed upstream of aequorin and used for transformation. The circadian peak occurred at different times in the three transgenic lines constructed. Luminescence imaging of these transgenic lines indicated that aequorin was differentially accumulated among the main tissues and cells of the seedlings and overcoat technology with applied epidermal strips indicated that the surface cell layers contribute the vast majority of luminescent light. We conclude that the Ca2+ rhythmicities of cells and tissues oscillate with distinct differences in phase, that this might represent different underlying cellular control mechanisms and that these observations have significant implications for our understanding and study of Ca2+ mediated signal transduction in plant cells. PMID:11161036

  3. High-salt diet advances molecular circadian rhythms in mouse peripheral tissues

    Microsoft Academic Search

    Hideaki Oike; Kanji Nagai; Tatsunobu Fukushima; Norio Ishida; Masuko Kobori

    2010-01-01

    Dietary compounds influence the expression of various genes and play a major role in changing physiological and metabolic states. However, little is known about the role of food ingredients in the regulation of circadian gene expression. Here, we show that feeding mice with a high-salt (HS) diet ad libitum for over 2weeks advanced the phase of clock gene expression by

  4. Circadian rhythm of the urinary crosslinks pyridinoline and deoxypyridinoline in normal human and involutional osteoporosis

    Microsoft Academic Search

    Hiroe Aoshima; Kazuhiro Kushida; Masaaki Takahashi; Tsuyoshi Ohishi; Kouichi Kawana; Tetsuo Inoue

    1996-01-01

    Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are collagen crosslinks found in bone and cartilage and are sensitive bone resorption markers. In this study, values of urinary Pyr and Dpyr during 24-h periods in 6 normal men, 10 normal women, and 10 osteoporotic patients were measured. In these three groups, urinary Pyr and Dpyr showed significant circadian variations only in normal

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

    Microsoft Academic Search

    Diane B. Boivin

    2000-01-01

    Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pace- maker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for ana- lyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major

  6. Tracking Circadian Rhythms of Bone Mineral Deposition in Murine Calvarial Organ Cultures

    PubMed Central

    McElderry, John-David P.; Zhao, Guisheng; Khmaladze, Alexander; Wilson, Christopher G.; Franceschi, Renny T.; Morris, Michael D.

    2013-01-01

    Osteoblasts, which orchestrate the deposition of small apatite crystals through the expression of nucleating proteins, have been shown to also express clock genes associated with the circadian signaling pathway. We hypothesized that protein-mediated bone mineralization may be linked to circadian oscillator mechanisms functioning in peripheral bone tissue. In this study, Per1 expression in ex vivo neonatal murine calvaria organ cultures was monitored for 6 days using a Per1-luciferase transgene as a bioluminescent indicator of clock function. Fluctuations in Per1 expression had a period of 25±4 hours (n=14) with early expression at CT09:59±03:37 (circadian time). We also established the kinetics of mineral deposition in developing bone by using non-invasive Raman microscopy to track mineral accumulation in calvarial tissue. The content and quality of newly deposited mineral was continually examined at the interparietal bone/fontanel boundary for a period of 6 days with 1 hour temporal resolution. Using this approach, mineralization over time exhibited bursts of mineral deposition followed by little or no deposition, which was recurrent with a periodicity of 26.8±9.6 hours. As many as 6 near-daily mineralization events were observed in the calvaria before deposition ceased. Earliest mineralization events occurred at CT16:51±03:45, which is 6 hours behind Per1 expression. These findings are consistent with the hypothesis that mineralization in developing bone tissue is regulated by a local circadian oscillator mechanism. PMID:23505073

  7. Biological rhythms

    NASA Technical Reports Server (NTRS)

    Halberg, F.

    1975-01-01

    An overview is given of basic features of biological rhythms. The classification of periodic behavior of physical and psychological characteristics as circadian, circannual, diurnal, and ultradian is discussed, and the notion of relativistic time as it applies in biology is examined. Special attention is given to circadian rhythms which are dependent on the adrenocortical cycle. The need for adequate understanding of circadian variations in the basic physiological indicators of an individual (heart rate, body temperature, systolic and diastolic blood pressure, etc.) to ensure the effectiveness of prophylactic and therapeutic measures is stressed.

  8. 2,2,2-Trichloroethanol lengthens the circadian period of Bmal1-driven circadian bioluminescence rhythms in U2OS cells.

    PubMed

    Gao, Jie; Yang, Caixia; Ding, Hui; Zhang, Yanli; Xue, Jinhua; Cai, Yanning

    2015-07-01

    2,2,2-Trichloroethanol (TCOH) is responsible for the pharmacological actions of chloral hydrate (CH), and is a major metabolite of trichloroethylene. Human exposure to TCOH is known to be increasing. Recently, it was reported that TCOH causes a significant phase delay of Per2 expression in mouse liver when injected daily over the course of several days. However, it is not clear whether TCOH directly modulates the molecular clock. In the present study we used a cell-based assay system to test this possibility. We found that the daily oscillation period of Bmal1 was lengthened to 3 h following treatment with 1.5 mM TCOH, and increased to 5 h with 3 mM TCOH treatment. However, low concentrations of TCOH had no noticeable effects. The effect of TCOH on Per2 oscillation was marginal. Interestingly, serum from rats anesthetized with CH also modulated Bmal1 period, suggesting that exposure to anesthesia should be taken into consideration for circadian rhythm studies. In summary, our study reveals a direct regulation of TCOH on molecular clock. PMID:25956065

  9. Significance of nonparametric light effects in entrainment of circadian rhythms in owl monkeys (Aotus lemurinus griseimembra) by light-dark cycles.

    PubMed

    Rauth-Widmann, B; Thiemann-Jäger, A; Erkert, H G

    1991-01-01

    In a total of 12 adult Colombian owl monkeys, Aotus lemurinus griseimembra, the significance of nonparametric light effects for the entrainment of the circadian system by light-dark (LD) cycles was studied by carrying out (a) phase-response experiments testing the phase-shifting effect of 30-min light pulses (LPs) of 250 lx applied at various phases of the free-running circadian activity rhythm (LL 0.2 lx) and (b) synchronization experiments testing the entraining effect of 24-h single LP photoperiods consisting of 30-min L of 80 lx and 23.5-h D of 0.5 lx (sP 0.5) and skeleton photoperiods consisting of two 30-min LPs of 80 lx, given against a background illuminance of 0.5 lx either symmetrically at 12-h intervals (PP 12:12) or asymmetrically at 9- and 15-h intervals (PP 9:15). The phase-response characteristics in Aotus, as evidenced by the phase-response curve, generally correspond to those of nocturnal rodents, providing that this neotropical simian primate chronobiologically is a genuine nocturnal species. When free-running with a spontaneous period close to 24 h (24.3 +/- 0.1 h), the PP 12:12 produced entrainment in only two of five owl monkeys, whereas the sP 0.5 entrained four of them. The PP 9:15, however, brought about stable entrainment of the circadian rhythms of locomotor activity, feeding activity, and core temperature in all animals tested (n = 8). Changes in phase position of the activity time with the endogenous rhythm entrained by a PP 12:12, by an sP 0.5, or by a PP 9:15 give evidence that both LPs of a skeleton photoperiod contribute to the phase setting of the circadian system. When free-running with a considerably lengthened spontaneous period (tau greater than or equal to 25.5 h), even the sP 0.5 and the PP 9:15 failed to entrain the owl monkeys' circadian rhythms, whereas a 24-h photoperiod with a very long LP of 3 h caused entrainment. The results indicate that in Aotus lemurinus griseimembra, in addition to the nonparametric light effects, parametric light effects play a significant role in the entrainment of circadian rhythms by LD cycles. PMID:1797415

  10. Noise-Induced Coherence in Multicellular Circadian Clocks

    Microsoft Academic Search

    Ekkehard Ullner; Javier Buceta; Antoni Díez-Noguera; Jordi García-Ojalvo

    2009-01-01

    In higher organisms, circadian rhythms are generated by a multicellular genetic clock that is entrained very efficiently to the 24-h light-dark cycle. Most studies done so far of these circadian oscillators have considered a perfectly periodic driving by light, in the form of either a square wave or a sinusoidal modulation. However, in natural conditions, organisms are subject to nonnegligible

  11. OutPatient Screening for Cushing's Syndrome: The Sensitivity of the Combination of Circadian Rhythm and Overnight Dexamethasone Suppression Salivary Cortisol Tests

    Microsoft Academic Search

    MARGARET CASTRO; PAULA C. L. ELIAS; ANA R. P. QUIDUTE; FERNANDA P. B. HALAH; AYRTON C. MOREIRA

    Screening tests have been used to support a biochemical diagnosis of Cushing's syndrome (CS). Measurements of salivary cortisol offer facilities for studying out-patients. This study assessed salivary cor- tisol in screening for CS by evaluating hypercortisolism based on circadian rhythm and the overnight 1-mg dexamethasone (DEX) sup- pression test for out-patients. We evaluated 33 patients with CS. Thirty normal volunteers

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

    NASA Technical Reports Server (NTRS)

    Dijk, Derk-Jan; Lockley, Steven W.

    2002-01-01

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

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

    Microsoft Academic Search

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

    2010-01-01

    Bed bugs must avoid detection when finding hosts and returning to hidden harborages. Their stealthy habits include foraging when hosts are asleep. Characteristics of spontaneous locomotor activity rhythm of bed bugs with different feeding histories were studied. In the absence of host stimuli, adults and nymphs were much more active in the dark than in the light. The onset of

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

    NASA Technical Reports Server (NTRS)

    Moore-Ede, M. C.

    1976-01-01

    The mechanisms underlying the internal synchronization of the circadian variations in electrolyte content in body compartments were investigated, and the significance of these oscillations for manned spaceflight were examined. The experiments were performed with a chair-acclimatized squirrel monkey system, in which the animal sits in a chair, restrained only around the waist. The following information was given: (1) experimental methodology description, (2) summary of results obtained during the first contract year, and (3) discussion of the research performed during the second contract year. This included the following topics: physiological mechanisms promoting normal circadian internal synchronization, factors precipitating internal desynchronization, pathophysiological consequences of internal desynchronization of particular relevance to spaceflight, and validation of a chair-acclimatized system.

  15. SLEEPAND CIRCADIAN NEUROBIOLOGY (SCN)

    E-print Network

    Kay, Mark A.

    STANFORD SLEEPAND CIRCADIAN NEUROBIOLOGY (SCN) LABORATORY STANFORD SLEEP DISORDERS CLINIC SLEEPAND CIRCADIAN NEUROBIOLOGY LABORATORY (SCN LAB) The SCN lab is an integrated, multidisciplinary research facility dedicated to: (1) understanding sleep-wake control and biological rhythms at all levels

  16. Fos expression in the suprachiasmatic nucleus during photic entrainment of circadian rhythms in retinally damaged rats

    Microsoft Academic Search

    Christian Beaulé; Jane Barry-Shaw; Shimon Amir

    2004-01-01

    The protein product of the immediate-early gene c-fos is expressed rhythmically in the shell region of the suprachiasmatic nucleus (SCN), the mammalian circadian clock. Recently,\\u000a we found that exposure to an entraining light pulse caused a suppression of Fos expression in the SCN shell in rats. To study\\u000a the hypothesis that suppression of Fos in the shell is a correlate

  17. Long?Term Renal Denervation Normalizes Disrupted Blood Pressure Circadian Rhythm and Ameliorates Cardiovascular Injury in a Rat Model of Metabolic Syndrome

    PubMed Central

    Katayama, Tetsuji; Sueta, Daisuke; Kataoka, Keiichiro; Hasegawa, Yu; Koibuchi, Nobutaka; Toyama, Kensuke; Uekawa, Ken; MingJie, Ma; Nakagawa, Takashi; Maeda, Masanobu; Ogawa, Hisao; Kim?Mitsuyama, Shokei

    2013-01-01

    Background Although renal denervation significantly reduces blood pressure in patients with resistant hypertension, the role of the renal nerve in hypertension with metabolic syndrome is unknown. We investigated the impact of long?term renal denervation on SHR/NDmcr?cp(+/+) (SHRcp) rats, a useful rat model of metabolic syndrome, to determine the role of the renal nerve in hypertension with metabolic syndrome. Methods and Results SHRcp rats were divided into (1) a renal denervation (RD) group and (2) a sham operation group (control) to examine the effects of long?term RD on blood pressure circadian rhythm, renal sodium retention?related molecules, the renin?angiotensin?aldosterone system, metabolic disorders, and organ injury. RD in SHRcp rats not only significantly reduced blood pressure but also normalized blood pressure circadian rhythm from the nondipper to the dipper type, and this improvement was associated with an increase in urinary sodium excretion and the suppression of renal Na+?Cl? cotransporter upregulation. RD significantly reduced plasma renin activity. RD significantly prevented cardiovascular remodeling and impairment of vascular endothelial function and attenuated cardiovascular oxidative stress. However, RD failed to ameliorate obesity, metabolic disorders, and renal injury and failed to reduce systemic sympathetic activity in SHRcp rats. Conclusions By including the upregulation of the Na+?Cl? cotransporter, the renal sympathetic nerve is involved in the disruption of blood pressure circadian rhythm as well as hypertension in metabolic syndrome. Thus, RD seems to be a useful therapeutic strategy for hypertension with metabolic syndrome. PMID:23974905

  18. Periodicity, Mixed-Mode Oscillations, and Quasiperiodicityin a Rhythm-Generating Neural Network

    Microsoft Academic Search

    Christopher A. Del Negro; Christopher G. Wilson; Robert J. Butera; Henrique Rigatto; Jeffrey C. Smith

    2002-01-01

    We studied patterns of oscillatory neural activity in the network that generates respiratory rhythm in mammals. When isolated in vitro, this network spontaneously generates an inspiratory-related motor rhythm, with stable amplitude from cycle to cycle. We show that progressively elevating neuronal excitability in vitro causes periodic modulation of this inspiratory rhythm, evoking (in order): mixed-mode oscillations, quasiperiodicity, and ultimately disorganized

  19. Thermoperiodic regulation of the circadian eclosion rhythm in the flesh fly, Sarcophaga crassipalpis.

    PubMed

    Miyazaki, Yosuke; Goto, Shin G; Tanaka, Kazuhiro; Saito, Osamu; Watari, Yasuhiko

    2011-09-01

    We recorded the eclosion time of the flesh fly, Sarcophaga crassipalpis, at different depths in the outdoor soil and under temperature cycles with various amplitudes in the laboratory, to examine the timing adjustment of eclosion in response to temperature cycles and their amplitudes in the pupal stage. In the soil, most eclosions occurred in the late morning, which was consistent with the eclosion time under pseudo-sinusoidal temperature cycles in the laboratory. The circadian clock controlling eclosion was reset by temperature cycles and free-ran with a period close to 24h. This clock likely helps pupae eclose at an optimal time even when the soil temperature does not show clear daily fluctuations. The eclosion phase of the circadian clock progressively advanced as the amplitude of the pseudo-sinusoidal temperature cycle decreased. This response allows pupae located at any depth in the soil to eclose at the appropriate time despite the depth-dependent phase delay of the temperature change. In contrast, the abrupt temperature increase in square-wave temperature cycles reset the phase of the circadian clock to the increasing time, regardless of the temperature amplitude. The rapid temperature increase may act as the late-morning signal for the eclosion clock. PMID:21704630

  20. Detecting KaiC phosphorylation rhythms of the cyanobacterial circadian oscillator in vitro and in vivo.

    PubMed

    Kim, Yong-Ick; Boyd, Joseph S; Espinosa, Javier; Golden, Susan S

    2015-01-01

    The central oscillator of the cyanobacterial circadian clock is unique in the biochemical simplicity of its components and the robustness of the oscillation. The oscillator is composed of three cyanobacterial proteins: KaiA, KaiB, and KaiC. If very pure preparations of these three proteins are mixed in a test tube in the right proportions and with ATP and MgCl2, the phosphorylation states of KaiC will oscillate with a circadian period, and these states can be analyzed simply by SDS-PAGE. The purity of the proteins is critical for obtaining robust oscillation. Contaminating proteases will destroy oscillation by degradation of Kai proteins, and ATPases will attenuate robustness by consumption of ATP. Here, we provide a detailed protocol to obtain pure recombinant proteins from Escherichia coli to construct a robust cyanobacterial circadian oscillator in vitro. In addition, we present a protocol that facilitates analysis of phosphorylation states of KaiC and other phosphorylated proteins from in vivo samples. PMID:25662456

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

    PubMed Central

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

    2010-01-01

    The circadian clock is an evolutionarily, highly conserved feature of most organisms. This internal timing mechanism coordinates biochemical, physiological and behavioral processes to maintain synchrony with the environmental cycles of light, temperature and nutrients. Several studies have shown that light is the most potent cue used by most organisms (humans included) to synchronize daily activities. In mammals, light perception occurs only in the retina; three different types of photoreceptors are present within this tissue: cones, rods and the newly discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). Researchers believe that the classical photoreceptors (e.g., the rods and the cones) are responsible for the image-forming vision, whereas the ipRGCs play a key role in the non-image forming vision. This non-image-forming photoreceptive system communicates not only with the master circadian pacemaker located in the suprachiasmatic nuclei of the hypothalamus, but also with many other brain areas that are known to be involved in the regulation of several functions; thus, this non-image forming system may also affect several aspects of mammalian health independently from the circadian system. PMID:19777353

  2. CLOCK-Controlled Polyphonic Regulation of Circadian Rhythms through Canonical and Noncanonical E-Boxes

    PubMed Central

    Yoshitane, Hikari; Ozaki, Haruka; Terajima, Hideki; Du, Ngoc-Hien; Suzuki, Yutaka; Fujimori, Taihei; Kosaka, Naoki; Shimba, Shigeki; Sugano, Sumio; Takagi, Toshihisa

    2014-01-01

    In mammalian circadian clockwork, the CLOCK-BMAL1 complex binds to DNA enhancers of target genes and drives circadian oscillation of transcription. Here we identified 7,978 CLOCK-binding sites in mouse liver by chromatin immunoprecipitation-sequencing (ChIP-Seq), and a newly developed bioinformatics method, motif centrality analysis of ChIP-Seq (MOCCS), revealed a genome-wide distribution of previously unappreciated noncanonical E-boxes targeted by CLOCK. In vitro promoter assays showed that CACGNG, CACGTT, and CATG(T/C)G are functional CLOCK-binding motifs. Furthermore, we extensively revealed rhythmically expressed genes by poly(A)-tailed RNA-Seq and identified 1,629 CLOCK target genes within 11,926 genes expressed in the liver. Our analysis also revealed rhythmically expressed genes that have no apparent CLOCK-binding site, indicating the importance of indirect transcriptional and posttranscriptional regulations. Indirect transcriptional regulation is represented by rhythmic expression of CLOCK-regulated transcription factors, such as Krüppel-like factors (KLFs). Indirect posttranscriptional regulation involves rhythmic microRNAs that were identified by small-RNA-Seq. Collectively, CLOCK-dependent direct transactivation through multiple E-boxes and indirect regulations polyphonically orchestrate dynamic circadian outputs. PMID:24591654

  3. Effect of substance P on circadian rhythms of firing activity and the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro.

    PubMed

    Shibata, S; Tsuneyoshi, A; Hamada, T; Tominaga, K; Watanabe, S

    1992-12-01

    The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Although substance P (SP) fibers from retina are found to terminate the SCN, the physiological role of this peptide is uncertain. The 2-deoxyglucose (2-DG) uptake and firing activity in the SCN show a robust circadian change. SP causes an increase in 2-DG uptake by SCN during the subjective night but not during subjective day. SP-induced increase in 2-DG uptake is blocked by co-treatment with the SP receptor antagonist, spantide. Treatment with SP produces phase shifts of circadian rhythm in spontaneous neural activity in SCN neurons with a phase-response curve that is similar to the effect of light pulses to animals under constant darkness. SP-induced phase change is also blocked by pretreatment with spantide. SP-induced increase in 2-DG uptake and phase changes in firing activity occur only during subjective night, at circadian times when photic phase shifting of activity occurs. The present results suggest that SP may be an important transmitter for conveying environmental light-dark information from retina to the SCN. PMID:1282077

  4. Molecular cloning and characterization of the light-regulation and circadian-rhythm of the VDE gene promoter from Zingiber officinale.

    PubMed

    Zhao, Wenchao; Wang, Shaohui; Li, Xin; Huang, Hongyu; Sui, Xiaolei; Zhang, Zhenxian

    2012-08-01

    Ginger (Zingiber officinale Rosc.) is prone to photoinhibition under intense sunlight. Excessive light can be dissipated by the xanthophyll cycle, where violaxanthin de-epoxidase (VDE) plays a critical role in protecting the photosynthesis apparatus from the damage of excessive light. We isolated ~2.0 kb of ginger VDE (GVDE) gene promoter, which contained the circadian box, I-box, G-box and GT-1 motif. Histochemical staining of Arabidopsis indicated the GVDE promoter was active in almost all organs, especially green tissues. ?-glucuronidase (GUS) activity driven by GVDE promoter was repressed rather than activated by high light. GUS activity was altered by hormones, growth regulators and abiotic stresses, which increased with 2,4-dichlorophenoxyacetic acid and decreased with abscisic acid, salicylic acid, zeatin, salt (sodium chloride) and polyethylene glycol. Interestingly, GUS activities with gibberellin or indole-3-acetic acid increased in the short-term (24 h) and decreased in the long-term (48 and 72 h). Analysis of 5' flank deletion found two crucial functional regions residing in -679 to -833 and -63 to -210. Northern blotting analysis found transcription to be regulated by the endogenous circadian clock. Finally, we found a region necessary for regulating the circadian rhythm and another for the basic promoter activity. Key message A novel promoter, named GVDE promoter, was first isolated and analyzed in this study. We have determined one region crucial for promoter activity and another responsible for keeping circadian rhythms. PMID:22484860

  5. Circadian adaptations to meal timing: neuroendocrine mechanisms

    PubMed Central

    Patton, Danica F.; Mistlberger, Ralph E.

    2013-01-01

    Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is directly entrained by daily light-dark (LD) cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs) that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this system. PMID:24133410

  6. Gonadotropic regulation of circadian clockwork in rat granulosa cells

    Microsoft Academic Search

    Pei-Jian He; Masami Hirata; Nobuhiko Yamauchi; Seiichi Hashimoto; Masa-aki Hattori

    2007-01-01

    The circadian clock is responsible for the generation of circadian rhythms in hormonal secretion and metabolism. These peripheral\\u000a clocks could be reset by various cues in order to adapt to environmental variations. The ovary can be characterized as having\\u000a highly dynamic physiology regulated by gonadotropins. Here, we aimed to address the status of circadian clock in the ovary,\\u000a and to

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

    PubMed

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

    2013-08-01

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

  8. Stem Extension Rate in Light-Grown Plants : Effects of Photo- and Thermoperiodic Treatments on the Endogenous Circadian Rhythm in Chenopodium rubrum.

    PubMed

    Lecharny, A; Schwall, M; Wagner, E

    1985-11-01

    Low temperature pulses have two effects on the circadian rhythm exhibited by stem extension rate of green Chenopodium rubrum plants. First, low temperature pulses have the same effect on the phasing of the rhythm as a dark period interrupting continuous light. Second, low temperature pulses stimulate stem extension rate during the 10 hours immediately following the end of the pulse. A difference in temperature between soil and air increases this effect. In any case, it is the change in temperature which is essential and not a specific temperature. Effects of light and temperature on phasing and amplitude of the rhythm explain why the maximal stem growth is observed under normal photo-thermoperiodic conditions, i.e. a high temperature during the photoperiod and a low temperature during the dark period. PMID:16664462

  9. Reentrainment of the Circadian Pacemaker through Three Distinct Stages

    Microsoft Academic Search

    Tiecheng Liu; Jimo Borjigin

    2005-01-01

    Circadian rhythms are endogenously generated by a central pacemaker and are synchronized to the environmental LD cycle. The rhythms can be resynchronized, or reentrained, after a shift of the LD cycle, as in traveling across time zones. The authors have performed high-resolution mapping of the pacemaker to analyze the reentrainment process using rat pineal melatonin onset (MTon) and melatonin offset

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

    PubMed Central

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

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

    PubMed

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

  12. Quantifying the Rhythm of KaiB-C Interaction for In Vitro Cyanobacterial Circadian Clock

    PubMed Central

    Ma, Lan; Ranganathan, Rama

    2012-01-01

    An oscillator consisting of KaiA, KaiB, and KaiC proteins comprises the core of cyanobacterial circadian clock. While one key reaction in this process—KaiC phosphorylation—has been extensively investigated and modeled, other key processes, such as the interactions among Kai proteins, are not understood well. Specifically, different experimental techniques have yielded inconsistent views about Kai A, B, and C interactions. Here, we first propose a mathematical model of cyanobacterial circadian clock that explains the recently observed dynamics of the four phospho-states of KaiC as well as the interactions among the three Kai proteins. Simulations of the model show that the interaction between KaiB and KaiC oscillates with the same period as the phosphorylation of KaiC, but displays a phase delay of ?8 hr relative to the total phosphorylated KaiC. Secondly, this prediction on KaiB-C interaction are evaluated using a novel FRET (Fluorescence Resonance Energy Transfer)-based assay by tagging fluorescent proteins Cerulean and Venus to KaiC and KaiB, respectively, and reconstituting fluorescent protein-labeled in vitro clock. The data show that the KaiB?KaiC interaction indeed oscillates with ?24 hr periodicity and ?8 hr phase delay relative to KaiC phosphorylation, consistent with model prediction. Moreover, it is noteworthy that our model indicates that the interlinked positive and negative feedback loops are the underlying mechanism for oscillation, with the serine phosphorylated-state (the “S-state") of KaiC being a hub for the feedback loops. Because the kinetics of the KaiB-C interaction faithfully follows that of the S-state, the FRET measurement may provide an important real-time probe in quantitative study of the cyanobacterial circadian clock. PMID:22900029

  13. Circadian control of tissue homeostasis and adult stem cells.

    PubMed

    Janich, Peggy; Meng, Qing-Jun; Benitah, Salvador Aznar

    2014-12-01

    The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. Accordingly, perturbation of the machinery that generates circadian rhythms is associated with metabolic disorders, premature ageing, and various diseases including cancer. Importantly, it is now possible to target circadian rhythms through systemic or local delivery of time cues or compounds. Here, we summarize recent findings in peripheral tissues that link the circadian clock machinery to tissue-specific functions and diseases. PMID:25016176

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

    PubMed Central

    Maibam, Punyakishore; Nawkar, Ganesh M.; Park, Joung Hun; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

    2013-01-01

    Low temperature adversely affects crop yields by restraining plant growth and productivity. Most temperate plants have the potential to increase their freezing tolerance upon exposure to low but nonfreezing temperatures, a process known as cold acclimation. Various physiological, molecular, and metabolic changes occur during cold acclimation, which suggests that the plant cold stress response is a complex, vital phenomenon that involves more than one pathway. The C-Repeat Binding Factor (CBF) pathway is the most important and well-studied cold regulatory pathway that imparts freezing tolerance to plants. The regulation of freezing tolerance involves the action of phytochromes, which play an important role in light-mediated signalling to activate cold-induced gene expression through the CBF pathway. Under normal temperature conditions, CBF expression is regulated by the circadian clock through the action of a central oscillator and also day length (photoperiod). The phytochrome and phytochrome interacting factor are involved in the repression of the CBF expression under long day (LD) conditions. Apart from the CBF regulon, a novel pathway involving the Z-box element also mediates the cold acclimation response in a light-dependent manner. This review provides insights into the progress of cold acclimation in relation to light quality, circadian regulation, and photoperiodic regulation and also explains the underlying molecular mechanisms of cold acclimation for introducing the engineering of economically important, cold-tolerant plants. PMID:23722661

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

    PubMed Central

    Pereira, D. S.; van der Veen, D. R.; Gonçalves, B. S. B.; Tufik, S.; von Schantz, M.; Archer, S. N.; Pedrazzoli, M.

    2014-01-01

    The aim of this study was to analyse the circadian behavioural responses of mice carrying a functional knockout of the Per3 gene (Per3?/?) to different light?:?dark (L?:?D) cycles. Male adult wild-type (WT) and Per3?/? mice were kept under 12-hour light?:?12-hour dark conditions (12L?:?12D) and then transferred to either a short or long photoperiod and subsequently released into total darkness. All mice were exposed to both conditions, and behavioural activity data were acquired through running wheel activity and analysed for circadian characteristics during these conditions. We observed that, during the transition from 12L?:?12D to 16L?:?8D, Per3?/? mice take approximately one additional day to synchronise to the new L?:?D cycle compared to WT mice. Under these long photoperiod conditions, Per3?/? mice were more active in the light phase. Our results suggest that Per3?/? mice are less sensitive to light. The data presented here provides further evidence that Per3 is involved in the suppression of behavioural activity in direct response to light. PMID:24982860

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

    PubMed

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

    2013-03-01

    Agomelatine is a novel antidepressant acting as an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist. Because of its peculiar pharmacological profile, this drug caters the potential to correct the abnormalities of circadian rhythms associated with mood disorders, including abnormalities of the sleep/wake cycle. Here, we examined the effect of chronic agomelatine treatment on sleep architecture and circadian rhythms of motor activity using the rat model of prenatal restraint stress (PRS) as a putative 'aetiological' model of depression. PRS was delivered to the mothers during the last 10 d of pregnancy. The adult progeny ('PRS rats') showed a reduced duration of slow wave sleep, an increased duration of rapid eye movement (REM) sleep, an increased number of REM sleep events and an increase in motor activity before the beginning of the dark phase of the light/dark cycle. In addition, adult PRS rats showed an increased expression of the transcript of the primary response gene, c-Fos, in the hippocampus just prior to the beginning of the dark phase. All these changes were reversed by a chronic oral treatment with agomelatine (2000 ppm in the diet). The effect of agomelatine on sleep was largely attenuated by treatment with the MT1/MT2 melatonin receptor antagonist, S22153, which caused PRS-like sleep disturbances on its own. These data provide the first evidence that agomelatine corrects sleep architecture and restores circadian homeostasis in a preclinical model of depression and supports the value of agomelatine as a novel antidepressant that resynchronizes circadian rhythms under pathological conditions. PMID:22310059

  17. Plant-pathogen interaction, circadian rhythm, and hormone-related gene expression provide indicators of phytoplasma infection in Paulownia fortunei.

    PubMed

    Fan, Guoqiang; Dong, Yanpeng; Deng, Minjie; Zhao, Zhenli; Niu, Suyan; Xu, Enkai

    2014-01-01

    Phytoplasmas are mycoplasma-like pathogens of witches' broom disease, and are responsible for serious yield losses of Paulownia trees worldwide. The molecular mechanisms of disease development in Paulownia are of considerable interest, but still poorly understood. Here, we have applied transcriptome sequencing technology and a de novo assembly approach to analyze gene expression profiles in Paulownia fortunei infected by phytoplasmas. Our previous researches suggested that methyl methane sulfonated (MMS) could reverse the effects of the infection. In this study, leaf samples from healthy, infected, and both infected and methyl methane sulfonate treated plants were analyzed. The results showed that the gene expression profile of P. fortunei underwent dramatic changes after Paulownia witches' broom (PaWB) phytoplasma infection. Genes that encoded key enzymes in plant-pathogen interaction processes were significantly up-regulated in the PaWB-infected Paulownia. Genes involved in circadian rhythm and hormone-related genes were also altered in Paulownia after PaWB infection. However, after the PaWB-infected plants were treated with MMS, the expression profiles of these genes returned to the levels in the healthy controls. The data will help identify potential PaWB disease-resistance genes that could be targeted to inhibit the growth and reproduction of the pathogen and to increase plant resistance. PMID:25514414

  18. Plant-Pathogen Interaction, Circadian Rhythm, and Hormone-Related Gene Expression Provide Indicators of Phytoplasma Infection in Paulownia fortunei

    PubMed Central

    Fan, Guoqiang; Dong, Yanpeng; Deng, Minjie; Zhao, Zhenli; Niu, Suyan; Xu, Enkai

    2014-01-01

    Phytoplasmas are mycoplasma-like pathogens of witches’ broom disease, and are responsible for serious yield losses of Paulownia trees worldwide. The molecular mechanisms of disease development in Paulownia are of considerable interest, but still poorly understood. Here, we have applied transcriptome sequencing technology and a de novo assembly approach to analyze gene expression profiles in Paulownia fortunei infected by phytoplasmas. Our previous researches suggested that methyl methane sulfonated (MMS) could reverse the effects of the infection. In this study, leaf samples from healthy, infected, and both infected and methyl methane sulfonate treated plants were analyzed. The results showed that the gene expression profile of P. fortunei underwent dramatic changes after Paulownia witches’ broom (PaWB) phytoplasma infection. Genes that encoded key enzymes in plant-pathogen interaction processes were significantly up-regulated in the PaWB-infected Paulownia. Genes involved in circadian rhythm and hormone-related genes were also altered in Paulownia after PaWB infection. However, after the PaWB-infected plants were treated with MMS, the expression profiles of these genes returned to the levels in the healthy controls. The data will help identify potential PaWB disease-resistance genes that could be targeted to inhibit the growth and reproduction of the pathogen and to increase plant resistance. PMID:25514414

  19. Circadian rhythm disruption by a novel running wheel: Roles of exercise and arousal in blockade of the luteinizing hormone surge

    PubMed Central

    Duncan, Marilyn J.; Franklin, Kathleen M.; Peng, Xiaoli; Yun, Christopher; Legan, Sandra J.

    2014-01-01

    Exposure of proestrous Syrian hamsters to a new room, cage, and novel running wheel blocks the luteinizing hormone (LH) surge until the next day in ~75% of hamsters (Legan et al, 2010) [1]. The studies described here tested the hypotheses that 1) exercise and/or 2) orexinergic neurotransmission mediate novel wheel blockade of the LH surge and circadian phase advances. Female hamsters were exposed to a 14L:10D photoperiod and activity rhythms were monitored with infra-red detectors. In Expt. 1, to test the effect of exercise, hamsters received jugular cannulae and on the next day, proestrus (Day 1), shortly before zeitgeber time 5 (ZT 5, 7 hours before lights-off) the hamsters were transported to the laboratory. After obtaining a blood sample at ZT 5, the hamsters were transferred to a new cage with a novel wheel that was either freely rotating (unlocked), or locked until ZT 9, and exposed to constant darkness (DD). Blood samples were collected hourly for 2 days from ZT 5–11 under red light for determination of plasma LH levels by radioimmunoassay. Running rhythms were monitored continuously for the next 10–14 days. The locked wheels were as effective as unlocked wheels in blocking LH surges (no Day 1 LH surge in 6/9 versus 8/8 hamsters, P>0.05) and phase advances in the activity rhythms did not differ between the groups (P= 0.28), suggesting that intense exercise is not essential for novel wheel blockade and phase advance of the proestrous LH surge. Expt. 2 tested whether orexin neurotransmission is essential for these effects. Hamsters were treated the same as in Expt. 1 except they were injected (i.p.) at ZT 4.5 and 5 with either the orexin 1 receptor antagonist SB334867 (15 mg/kg per injection) or vehicle (25% DMSO in 2-hydroxypropyl-beta-cyclodextrin (HCD). SB-334867 inhibited novel wheel blockade of the LH surge (surges blocked in 2/6 SB334867-injected animals versus 16/18 vehicle-injected animals, P<0.02) and also inhibited wheel running and circadian phase shifts, indicating that activation of orexin 1 receptors is necessary for these effects. Expt. 3 tested the hypothesis that novel wheel exposure activates orexin neurons. Proestrous hamsters were transferred at ZT 5 to a nearby room within the animal facility and were exposed to a new cage with a locked or unlocked novel wheel or left in their home cages. At ZT 8, the hamsters were anesthetized, blood was withdrawn, they were perfused with fixative and brains were removed for immunohistochemical localization of Fos, GnRH, and orexin. Exposure to a wheel, whether locked or unlocked, suppressed circulating LH concentrations at ZT 8, decreased the proportion of Fos-activated GnRH neurons, and increased Fos-immunoreactive orexin cells. Unlocked wheels had greater effects than locked wheels on all three endpoints. Thus in a familiar environment, exercise potentiated the effect of the novel wheel on Fos expression because a locked wheel was not a sufficient stimulus to block the LH surge. In conclusion, these studies indicate that novel wheel exposure activates orexin neurons and that blockade of orexin 1 receptors prevents novel wheel blockade of the LH surge. These findings are consistent with a role for both exercise and arousal in mediating novel wheel blockade of the LH surge. PMID:24727338

  20. Spotlight on fish: light pollution affects circadian rhythms of European perch but does not cause stress.

    PubMed

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Preuer, Torsten; Kloas, Werner

    2015-04-01

    Flora and fauna evolved under natural day and night cycles. However, natural light is now enhanced by artificial light at night, particularly in urban areas. This alteration of natural light environments during the night is hypothesised to alter biological rhythms in fish, by effecting night-time production of the hormone melatonin. Artificial light at night is also expected to increase the stress level of fish, resulting in higher cortisol production. In laboratory experiments, European perch (Perca fluviatilis) were exposed to four different light intensities during the night, 0 lx (control), 1 lx (potential light level in urban waters), 10 lx (typical street lighting at night) and 100 lx. Melatonin and cortisol concentrations were measured from water samples every 3h during a 24 hour period. This study revealed that the nocturnal increase in melatonin production was inhibited even at the lowest light level of 1 lx. However, cortisol levels did not differ between control and treatment illumination levels. We conclude that artificial light at night at very low intensities may disturb biological rhythms in fish since nocturnal light levels around 1 lx are already found in urban waters. However, enhanced stress induction could not be demonstrated. PMID:25577738

  1. Melanopsin in the circadian timing system

    Microsoft Academic Search

    Christian Beaulé; Barry Robinson; Elaine Waddington Lamont; Shimon Amir

    2003-01-01

    In mammals, circadian rhythms are generated by a light-entrainable oscillator located in the hypothalamic suprachiasmatic\\u000a nucleus (SCN). Light signals reach the SCN via a dedicated retinal pathway, the retinohypothalamic tract (RHT). One question\\u000a that continues to elude scientists is whether the circadian system has its own dedicated photoreceptor or photoreceptors.\\u000a It is well established that conventional photoreceptors, rods and cones,

  2. Light pulses induce "singular" behavior and shorten the period of the circadian phototaxis rhythm in the CW15 strain of Chlamydomonas.

    PubMed

    Johnson, C H; Kondo, T

    1992-01-01

    While measuring action spectra for phase-shifting the circadian clock of Chlamydomonas, we observed that light pulses started near the phase response curve (PRC) "breakpoint" caused a reduction of the amplitude of the phototactic rhythm and two unexpected effects: (1) nonmonotonic fluence response curves (FRCs), and (2) shortening of the period of the subsequent free-running rhythm. The reduction of the rhythm's amplitude is dependent upon both the fluence and wavelength of the light pulse. The results are consistent with the amplitude being dependent upon the perceived "strength" of the stimulus, and with the nonmonotonic FRCs and reduced amplitude reflecting a light-induced change of the pacemaker's state variables to a region of the phase plane close to the "singularity." The period change that is evoked by single stimuli exhibits novel characteristics: large changes in period and a phase specificity that correlates with "singular" behavior. These period changes also appear to be a function of the stimulus strength, but indirectly; the magnitude of the period change is most strongly correlated with the magnitude of the light-induced phase shift. These results are interpreted in the context of limit cycle models of circadian clocks, and are used to suggest new tactics for measuring action spectra of light-induced clock resetting. PMID:1286203

  3. Mechanisms of action of light on circadian rhythms in the monkey

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Rosenblatt, L. S.; DeRoshia, C. W.; Hetherington, N. W.

    1970-01-01

    Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.

  4. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    PubMed

    Hughes, Michael E; Hong, Hee-Kyung; Chong, Jason L; Indacochea, Alejandra A; Lee, Samuel S; Han, Michael; Takahashi, Joseph S; Hogenesch, John B

    2012-01-01

    The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(?19) mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms are driven by interactions between central and peripheral circadian oscillators. PMID:22844252

  5. Circadian endocrine rhythms: the hypothalamic–pituitary–adrenal axis and its actions

    PubMed Central

    Nicolaides, Nicolas C.; Charmandari, Evangelia; Chrousos, George P.; Kino, Tomoshige

    2014-01-01

    The stress system effectively restores the internal balance––or homeostasis––of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors—the stress response—through coordinated activation of the hypothalamic–pituitary–adrenal (HPA) axis and the locus coeruleus/norepinephrine (LC/NE) autonomic nervous systems. In addition to stressors, life is influenced by daily light/dark changes due to the 24-h rotation of Earth. To adjust to these recurrent day/night cycles, the biological clock system employs the heterodimer of transcription factors CLOCK/BMAL1, along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling. PMID:24890877

  6. IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Neuronal Firing in the Suprachiasmatic Nucleus and Circadian Rhythms in Locomotor Activity

    PubMed Central

    Norris, Aaron J.; Carrasquillo, Yarimar; Nerbonne, Jeanne M.; Herzog, Erik D.

    2012-01-01

    Neurons in the suprachiasmatic nucleus (SCN) display coordinated circadian changes in electrical activity that are critical for daily rhythms in physiology, metabolism, and behavior. SCN neurons depolarize spontaneously and fire repetitively during the day and hyperpolarize, drastically reducing firing rates, at night. To explore the hypothesis that rapidly activating and inactivating A-type (IA) voltage-gated K+ (Kv) channels, which are also active at subthreshold membrane potentials, are critical regulators of the excitability of SCN neurons, we examined locomotor activity and SCN firing in mice lacking Kv1.4 (Kv1.4?/?), Kv4.2 (Kv4.2?/?), or Kv4.3 (Kv4.3?/?), the pore-forming (?) subunits of IA channels. Mice lacking either Kv1.4 or Kv4.2 ? subunits have markedly shorter (0.5 h) periods of locomotor activity than wild-type (WT) mice. In vitro extracellular multi-electrode recordings revealed that Kv1.4?/? and Kv4.2?/? SCN neurons display circadian rhythms in repetitive firing, but with shorter periods (0.5 h) than WT cells. In contrast, the periods of wheel-running activity in Kv4.3?/? mice and firing in Kv4.3?/? SCN neurons were indistinguishable from WT animals and neurons. Quantitative real-time PCR revealed that the transcripts encoding all three Kv channel ? subunits, Kv1.4, Kv4.2, and Kv4.3, are expressed constitutively throughout the day and night in the SCN. Together, these results demonstrate that Kv1.4- and Kv4.2-encoded IA channels regulate the intrinsic excitability of SCN neurons during the day and night and determine the period and amplitude of circadian rhythms in SCN neuron firing and locomotor behavior. PMID:22815518

  7. Robust circadian clocks from coupled protein-modification and transcription-translation cycles

    Microsoft Academic Search

    D. Zwicker; D. K. Lubensky; P. R. Ten Wolde

    2010-01-01

    The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  9. Characteristics of the light-induced phase response of circadian activity rhythms in common marmosets, Callithrix j. jacchus [primates-Cebidae].

    PubMed

    Wechselberger, E; Erkert, H G

    1994-10-01

    Phase-response experiments using 1-h light pulses (LPs) of 1,100 lux applied under constant dim light of 0.3 lux were conducted with common marmosets, Callithrix j. jacchus, in order to obtain a complete phase-response curve established according to the common experimental procedure in a diurnal primate. Maximal phase delays of the free-running circadian activity rhythm (-90 min) were induced by LPs delivered at circadian time (CT) 12; e.g., during the beginning of the marmosets' rest time, maximal advances (+25 min) were elicited by pulses administered during the late subjective night at CT 21. In contrast to rodents, neither regular transient cycles nor regular period responses resulted from LP applications at different phases. To check whether the underlying period length affects the phase response in primates as well, the marmosets' circadian timing system was entrained to 25 h by a light:dark (LD) cycle of 12.5:12.5 h. The 1-h LPs were delivered during the first circadian cycle produced under constant dim light after the entraining LD periods. Here, LPs applied at CT 21 led to phase advances exceeding those measured during the steady-state free run. At CT 12, minor or no phase delays could be elicited. These findings show that the phase-shifting effect of LPs on the circadian system of marmosets is similar to that observed in other diurnal mammals. Some of the results indicate that in this diurnal primate, LP-induced phase shifts may be mediated in part by a light-induced increase in locomotor activity (arousal). PMID:7828210

  10. Advanced light-entrained activity onsets and restored free-running suprachiasmatic nucleus circadian rhythms in per2/dec mutant mice.

    PubMed

    Bode, Brid; Taneja, Reshma; Rossner, Moritz J; Oster, Henrik

    2011-11-01

    Many behavioral and physiological processes display diurnal (24-h) rhythms controlled by an internal timekeeping system?the circadian clock. In mammals, a circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronizes peripheral oscillators found in most other tissues with the external light-dark (LD) cycle. At the molecular level, circadian clocks are regulated by transcriptional translational feedback loops (TTLs) involving a set of clock genes. The mammalian core TTL includes the transcriptional modulators PER?(1?3) and CRY?(1/2) that inhibit their own expression by interaction with CLOCK/NPAS2 and BMAL1 (ARNTL). The basic helix-loop-helix transcription factors DEC1 (BHLHE40) and DEC2 (BHLHE41) can interact with this core TTL, forming an accessory feedback mechanism. The authors measured circadian locomotor behavior and clock gene expression in the SCN of Per2/Dec double- and triple-mutant mice to analyze the functional interaction of PER2 and DEC feedback on circadian pacemaker function in the SCN. The data suggest a synergistic interaction of Per2 and Dec1/2 in activity entrainment to a standard LD cycle, correlating with a cumulative deficiency in negative-masking capacities in Per2/Dec double- and triple-mutant mice and suggesting an involvement of Per2-Dec1/2 interactivity in activity-onset regulation and masking under LD, but not under constant conditions. In contrast, under constant darkness (DD) conditions, a deletion of either Dec1 or Dec2 partially rescued the Per2 mutant short-period/arrhythmicity phenotype, accompanied by a restoration of time-of-day effects on clock gene expression in the SCN. Together, these results show an interaction of Per2 and Dec1/2 feedback processes in the SCN with differential modes of interactivity under entrained and free-run conditions. (Author correspondence: henrik.oster@mpibpc.mpg.de ). PMID:22080784

  11. A lower level of entropy in circadian rhythm of the sinus R-R intervals suggests a prevalence of the cardiac sympathetic regulation in early physiological pregnancy.

    PubMed

    Curione, M; Cugini, P; Napoli, A; Colatrella, A; Di Bona, S; Cammarota, C; Amato, S; Castro, C; Fallucca, F

    2005-01-01

    The study estimates the unpredictable disorder (chaos) within the 24 h pattern of sinus R-R intervals (SRRI) in clinically healthy pregnant women (CHPW) and clinically healthy non-pregnant women (CHNPW), in order to evaluate the early gestational changes in neurovegetative cardiac pacing. SRRI were provided by the 24-h Holter ECG of 10 CHPW and 10 CHNPW. SRRI were investigated by descriptive conventional statistics by means of the Time and Frequency Domain Analysis, and subsequently, in their chaotic component by means of entropy analysis. Both the SRRI and entropy were tested via the Cosinor method to better decipher whether or not the periodic disorder in heart rate variability is modified in pregnancy as a result of a gestational tonic resetting of the cardiac sympatho-vagal regulation. Cosinor analysis documented that the circadian rhythm of both the SRRI and entropy were preserved in CHNPW and CHPW. However, the circadian rhythm of SRRI and entropy in CHPW exhibited a significantly decreased 24 h mean. Via the analysis of the rhythmicity of entropy, this study has documented that the chaos in the 24 h pattern of SRRI is less prominent in CHPW than in CHNPW. Such a reduction of level in the deterministic periodic chaos of heart rate variability provides evidence that, in early pregnancy, a tonic elevation of the sympathetic activity regulates cardiac pacing. PMID:16147901

  12. Circadian organization of the mammalian retina: from gene regulation to physiology and diseases.

    PubMed

    McMahon, Douglas G; Iuvone, P Michael; Tosini, Gianluca

    2014-03-01

    The retinal circadian system represents a unique structure. It contains a complete circadian system and thus the retina represents an ideal model to study fundamental questions of how neural circadian systems are organized and what signaling pathways are used to maintain synchrony of the different structures in the system. In addition, several studies have shown that multiple sites within the retina are capable of generating circadian oscillations. The strength of circadian clock gene expression and the emphasis of rhythmic expression are divergent across vertebrate retinas, with photoreceptors as the primary locus of rhythm generation in amphibians, while in mammals clock activity is most robust in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules to entrain circadian rhythms in the retina and also in other ocular structures. Recent studies have also suggested GABA as an important component of the system that regulates retinal circadian rhythms. These transmitter-driven influences on clock molecules apparently reinforce the autonomous transcription-translation cycling of clock genes. The molecular organization of the retinal clock is similar to what has been reported for the SCN although inter-neural communication among retinal neurons that form the circadian network is apparently weaker than those present in the SCN, and it is more sensitive to genetic disruption than the central brain clock. The melatonin-dopamine system is the signaling pathway that allows the retinal circadian clock to reconfigure retinal circuits to enhance light-adapted cone-mediated visual function during the day and dark-adapted rod-mediated visual signaling at night. Additionally, the retinal circadian clock also controls circadian rhythms in disk shedding and phagocytosis, and possibly intraocular pressure. Emerging experimental data also indicate that circadian clock is also implicated in the pathogenesis of eye disease and compelling experimental data indicate that dysfunction of the retinal circadian system negatively impacts the retina and possibly the cornea and the lens. PMID:24333669

  13. Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

    NASA Technical Reports Server (NTRS)

    Dijk, D. J.; Duffy, J. F.

    1999-01-01

    The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

  14. Fast delayed rectifier potassium current is required for circadian neural activity

    Microsoft Academic Search

    Jason N Itri; Stephan Michel; Mariska J Vansteensel; Johanna H Meijer; Christopher S Colwell

    2005-01-01

    In mammals, the precise circadian timing of many biological processes depends on the generation of oscillations in neural activity of pacemaker cells in the suprachiasmatic nucleus (SCN). The ionic mechanisms that underlie these rhythms are largely unknown. Using the mouse brain slice preparation, we show that the magnitude of fast delayed rectifier (FDR) potassium currents has a diurnal rhythm that

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

    PubMed

    van der Veen, Daan R; Shao, Jinping; Xi, Yang; Li, Lei; Duffield, Giles E

    2012-01-01

    Circadian rhythms in cardiac function are apparent in e.g., blood pressure, heart rate, and acute adverse cardiac events. A circadian clock in heart tissue has been identified, but entrainment pathways of this clock are still unclear. We cultured tissues of mice carrying bioluminescence reporters of the core clock genes, period 1 or 2 (per1(luc) or PER2(LUC)) and compared in vitro responses of atrium to treatment with medium and a synthetic glucocorticoid (dexamethasone [DEX]) to that of the suprachiasmatic nucleus (SCN) and liver. We observed that PER2(LUC), but not per1(luc) is rhythmic in atrial tissue, while both per1(luc) and PER2(LUC) exhibit rhythmicity in other cultured tissues. In contrast to the SCN and liver, both per1(luc) and PER2(LUC) bioluminescence amplitudes were increased in response to DEX treatment, and the PER2(LUC) amplitude response was dependent on the time of treatment. Large phase-shift responses to both medium and DEX treatments were observed in the atrium, and phase responses to medium treatment were not attributed to serum content but the treatment procedure itself. The phase-response curves of atrium to both DEX and medium treatments were found to be different to the liver. Moreover, the time of day of the culturing procedure itself influenced the phase of the circadian clock in each of the cultured tissues, but the magnitude of this response was uniquely large in atrial tissue. The current data describe novel entrainment signals for the atrial circadian clock and specifically highlight entrainment by mechanical treatment, an intriguing observation considering the mechanical nature of cardiac tissue. PMID:23110090

  16. Circadian Rhythm Sleep Disorders

    MedlinePLUS

    ... to self-medicate with drugs or alcohol. • Bright light therapy: This therapy synchronizes the body clock by ... the eyes to safe levels of intense, bright light for brief durations at strategic times of day. • ...

  17. Stability and Noise in the Cyanobacterial Circadian Clock

    Microsoft Academic Search

    Irina Mihalcescu

    2008-01-01

    By monitoring single cyanobacterial cells in vivo we show that individual cells generate impressively stable circadian rhythms.\\u000a In multicellular organisms, the circadian clock accuracy is achieved via intercellular coupling of the individual noisy oscillators.\\u000a Here we demonstrate that cyanobacterial clock stability is a built-in property. We first theoretically design our experiment\\u000a to be able to distinguish coupling, even weak, from

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

    NASA Technical Reports Server (NTRS)

    Nishino, H.

    1977-01-01

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

  19. Circadian clock: linking epigenetics to aging.

    PubMed

    Orozco-Solis, Ricardo; Sassone-Corsi, Paolo

    2014-06-01

    Circadian rhythms are generated by an intrinsic cellular mechanism that controls a large array of physiological and metabolic processes. There is erosion in the robustness of circadian rhythms during aging, and disruption of the clock by genetic ablation of specific genes is associated with aging-related features. Importantly, environmental conditions are thought to modulate the aging process. For example, caloric restriction is a very strong environmental effector capable of delaying aging. Intracellular pathways implicating nutrient sensors, such as SIRTs and mTOR complexes, impinge on cellular and epigenetic mechanisms that control the aging process. Strikingly, accumulating evidences indicate that these pathways are involved in both the modulation of the aging process and the control of the clock. Hence, innovative therapeutic strategies focused at controlling the circadian clock and the nutrient sensing pathways might beneficially influence the negative effects of aging. PMID:25033025

  20. Interplay between circadian rhythm, time of the day and osmotic stress constraints in the regulation of the expression of a Solanum Double B-box gene

    PubMed Central

    Kie?bowicz-Matuk, Agnieszka; Rey, Pascal; Rorat, Tadeusz

    2014-01-01

    Background and Aims Double B-box zinc finger (DBB) proteins are recently identified plant transcription regulators that participate in the response to sodium chloride-induced stress in arabidopsis plants. Little is known regarding their subcellular localization and expression patterns, particularly in relation to other osmotic constraints and the day/night cycle. This study investigated natural variations in the amount of a Solanum DBB protein, SsBBX24, during plant development, and also under various environmental constraints leading to cell dehydration in relation to the circadian clock and the time of day. Methods SsBBX24 transcript and protein abundance in various organs of phytotron-grown Solanum tuberosum and S. sogarandinum plants were investigated at different time points of the day and under various osmotic constraints. The intracellular location of SsBBX24 was determined by western blot analysis of subcellular fractions. Key Results Western blot analysis of SsBBX24 protein revealed that it was located in the nucleus at the beginning of the light period and in the cytosol at the end, suggesting movement (‘trafficking’) during the light phase. SsBBX24 gene expression exhibited circadian cycling under control conditions, with the highest and lowest abundances of both transcript and protein occurring 8 and 18 h after dawn, respectively. Exposing Solanum plants to low temperature, salinity and polyethylene glycol (PEG), but not to drought, disturbed the circadian regulation of SsBBX24 gene expression at the protein level. SsBBX24 transcript and protein accumulated in Solanum plants in response to salt and PEG treatments, but not in response to low temperature or water deficit. Most interestingly, the time of the day modulated the magnitude of SsBBX24 expression in response to high salt concentration. Conclusions The interplay between circadian rhythm and osmotic constraints in the regulation of the expression of a Solanum DBB transcriptional regulator is demonstrated. It is proposed that stress-dependent, post-transcriptional mechanisms alter the regulation by the circadian clock of the amount of SsBBX24. PMID:24562097

  1. Shifting the Circadian Rhythm of Feeding in Mice Induces Gastrointestinal, Metabolic and Immune Alterations Which Are Influenced by Ghrelin and the Core Clock Gene Bmal1

    PubMed Central

    Laermans, Jorien; Broers, Charlotte; Beckers, Kelly; Vancleef, Laurien; Steensels, Sandra; Thijs, Theo; Tack, Jan; Depoortere, Inge

    2014-01-01

    Background In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF), a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. Methods Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD). Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test). Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. Results The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1? expression and promoted gastric contractility changes. Conclusions This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and immune-related gastrointestinal disorders among shift workers. PMID:25329803

  2. The melatonin receptor agonist is effective for free-running type circadian rhythm sleep disorder: case report on two sighted patients.

    PubMed

    Yanagihara, Mariko; Nakamura, Masaki; Usui, Akira; Nishida, Shingo; Ito, Eiki; Okawa, Masako; Inoue, Yuichi

    2014-01-01

    Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at first and the free-running cycle stopped after treatment day 15. Triazolam was added from the day 25 to promote earlier sleep onset. And the sleep-wake schedule was normalized by the day 34. Patient 2 (33-year-old male) had suffered from FRT for nearly 8 months after starting to take a leave of absence from his job. He was given sleep hygiene education and was treated with ramelteon and methylcobalamin. His sleep-wake schedule was normalized from the first treatment day. By the combined treatment with ramelteon, both patients have maintained favorable sleep-wake schedules. The agonist action of ramelteon at the melatonin 2 receptor may have primarily contributed to the cessation of the free-running cycle in these patients. PMID:25253260

  3. The effect of blue-blocking intraocular lenses on circadian biological rhythm: protocol for a randomised controlled trial (CLOCK-IOL colour study)

    PubMed Central

    Nishi, Tomo; Saeki, Keigo; Obayashi, Kenji; Miyata, Kimie; Tone, Nobuhiro; Tsujinaka, Hiroki; Yamashita, Mariko; Masuda, Naonori; Mizusawa, Yutarou; Okamoto, Masahiro; Hasegawa, Taiji; Maruoka, Shinji; Ueda, Tetsuo; Kojima, Masashi; Matsuura, Toyoaki; Kurumatani, Norio; Ogata, Nahoko

    2015-01-01

    Introduction Blue light information plays an important role in synchronising internal biological rhythm within the external environment. Circadian misalignment is associated with the increased risk of sleep disturbance, obesity, diabetes mellitus, depression, ischaemic heart disease, stroke and cancer. Meanwhile, blue light causes photochemical damage to the retina, and may be associated with age-related macular degeneration (AMD). At present, clear intraocular lenses (IOLs) and blue-blocking IOLs are both widely used for cataract surgery; there is currently a lack of randomised controlled trials to determine whether clear or blue-blocking IOLs should be used. Methods and analysis This randomised controlled trial will recruit 1000 cataract patients and randomly allocate them to receive clear IOLs or blue-blocking IOLs in a ratio of 1:1. The primary outcomes are mortality and the incidence of cardiovascular disease, cancer and AMD. Secondary outcomes are fasting plasma glucose, triglycerides, cholesterol, glycated haemoglobin, sleep quality, daytime sleepiness depressive symptoms, light sensitivity, the circadian rhythm of physical activity, wrist skin temperature and urinary melatonin metabolite. Primary outcomes will be followed until 20?years after surgery, and secondary outcomes will be assessed at baseline and 1?year after surgery. Ethics and dissemination Ethical approval has been obtained from the Institutional Review Board of Nara Medical University (No. 13-032). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) home page. Trial registration number UMIN000014680. PMID:25968007

  4. Fast delayed rectifier potassium current is required for circadian neural activity.

    PubMed

    Itri, Jason N; Michel, Stephan; Vansteensel, Mariska J; Meijer, Johanna H; Colwell, Christopher S

    2005-05-01

    In mammals, the precise circadian timing of many biological processes depends on the generation of oscillations in neural activity of pacemaker cells in the suprachiasmatic nucleus (SCN). The ionic mechanisms that underlie these rhythms are largely unknown. Using the mouse brain slice preparation, we show that the magnitude of fast delayed rectifier (FDR) potassium currents has a diurnal rhythm that peaks during the day. Notably, this rhythm continues in constant darkness, providing the first demonstration of the circadian regulation of an intrinsic voltage-gated current in mammalian cells. Blocking this current prevented the daily rhythm in firing rate in SCN neurons. Kv3.1b and Kv3.2 potassium channels were widely distributed within the SCN, with higher expression during the day. We conclude that the FDR is necessary for the circadian modulation of electrical activity in SCN neurons and represents an important part of the ionic basis for the generation of rhythmic output. PMID:15852012

  5. Opioid-Induced Quantal Slowing Reveals Dual Networks for Respiratory Rhythm Generation

    Microsoft Academic Search

    Nicholas M. Mellen; Wiktor A. Janczewski; Christopher M. Bocchiaro; Jack L. Feldman

    2003-01-01

    Current consensus holds that a single medullary network generates respiratory rhythm in mammals. Pre-Bötzinger Complex inspiratory (I) neurons, isolated in transverse slices, and preinspiratory (pre-I) neurons, found only in more intact en bloc preparations and in vivo, are each proposed as necessary for rhythm generation. Opioids slow I, but not pre-I, neuronal burst periods. In slices, opioids gradually lengthened respiratory

  6. Effects of anabolic androgenic steroids on the development and expression of running wheel activity and circadian rhythms in male rats

    PubMed Central

    McGinnis, Marilyn Y.; Lumia, Augustus R.; Tetel, Marc J.; Molenda-Figuiera, Heather A.; Possidente, Bernard

    2010-01-01

    In humans, anabolic androgenic steroid (AAS) use has been associated with hyperactivity and disruption of circadian rhythmicity. We used an animal model to determine the impact of AAS on the development and expression of circadian function. Beginning on day 68 gonadally intact male rats received testosterone, nandrolone, or stanozolol via constant release pellets for 60 days; gonadally intact controls received vehicle pellets. Wheel running was recorded in a 12:12 LD cycle and constant dim red light (RR) before and after AAS implants. Post-AAS implant, circadian activity phase, period and mean level of wheel running wheel activity were compared to baseline measures. Post-AAS phase response to a light pulse at circadian time 15h was also tested. To determine if AAS differentially affects steroid receptor coactivator (SRC) expression we measured SRC-1 and SRC-2 protein in brain. Running wheel activity was significantly elevated by testosterone, significantly depressed by nandrolone, and unaffected by stanozolol. None of the AAS altered measures of circadian rhythmicity or phase response. While SRC-1 was unaffected by AAS exposure, SRC-2 was decreased by testosterone in the hypothalamus. Activity levels, phase of peak activity and circadian period all changed over the course of development from puberty to adulthood. Development of activity was clearly modified by AAS exposure as testosterone significantly elevated activity levels and nandrolone significantly suppressed activity relative to controls. Thus, AAS exposure differentially affects both the magnitude and direction of developmental changes in activity levels depending in part on the chemical composition of the AAS. PMID:17716697

  7. Glycogen synthase kinase 3, circadian rhythms, and bipolar disorder: a molecular link in the therapeutic action of lithium

    Microsoft Academic Search

    Sevag A Kaladchibachi; Brad Doble; Norman Anthopoulos; James R Woodgett; Armen S Manoukian

    2007-01-01

    BACKGROUND: Bipolar disorder (BPD) is a widespread condition characterized by recurring states of mania and depression. Lithium, a direct inhibitor of glycogen synthase kinase 3 (GSK3) activity, and a mainstay in BPD therapeutics, has been proposed to target GSK3 as a mechanism of mood stabilization. In addition to mood imbalances, patients with BPD often suffer from circadian disturbances. GSK3, an

  8. Acute exposure to 2G phase shifts the rat circadian timing system

    NASA Technical Reports Server (NTRS)

    Hoban-Higgins, T. M.; Murakami, D. M.; Tandon, T.; Fuller, C. A.

    1995-01-01

    The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

  9. Human circadian rhythm synchronization by social timers: The role of motivation: IV. Individual features of the free-running 24-hour sleep-wake cycle under simulated conditions of vital activity

    Microsoft Academic Search

    A. A. Sorokin; A. L. Maksimov; J. Jermain

    2000-01-01

    The possibility of simulating a free-running 24-h sleep-wake cycle was studied in the group of three subjects under rigid\\u000a motivation conditions, including a strictly specified sleep time in a free daily routine. In this case, the effect of motivation-dependent\\u000a social timer (clock) on synchronizing the human 25-h circadian rhythm was studied depending on the individual typological\\u000a features; whereas the test

  10. Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation and circadian body temperature rhythm.

    PubMed

    Jeong, Keun-Yeong; Seong, Jinsil

    2014-06-15

    The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1. PMID:24746025

  11. A diurnal rhythm of stimulatory input to the hypothalamo-pituitary-adrenal system as revealed by timed intrahypothalamic administration of the vasopressin V1 antagonist

    Microsoft Academic Search

    Andries Kalsbeek; Joop J. van Heerikhuize; Joke Wortel; Ruud M. Buijs

    1996-01-01

    The mammalian suprachiasmatic nuclei (SCN) contain an en- dogenous pacemaker that generates daily rhythms in behavior and secretion of hormones. We hypothesized that the SCN imposes its circadian rhythm on the rest of the brain via a rhythmic release of its transmitters in its target areas. Previ- ously, we demonstrated a pronounced inhibitory effect of va- sopressin (VP), released from

  12. Slow dorsal-ventral rhythm generator in the lamprey spinal cord.

    PubMed

    Aoki, F; Wannier, T; Grillner, S

    2001-01-01

    In the isolated lamprey spinal cord, a very slow rhythm (0.03-0.11 Hz), superimposed on fast N-methyl-D-aspartate (NMDA)-induced locomotor activity (0.26-2.98 Hz), could be induced by a blockade of GABA(A) or glycine receptors or by administration of (1 s, 3 s)-l-aminocyclopentane-1,3-dicarboxylic acid a metabotropic glutamate receptor agonist. Ventral root branches supplying dorsal and ventral myotomes were exposed bilaterally to study the motor pattern in detail. The slow rhythm was expressed in two main forms: 1) a dorsal-ventral reciprocal pattern was the most common (18 of 24 preparations), in which bilateral dorsal branches were synchronous and alternated with the ventral branches, in two additional cases a diagonal dorsal-ventral reciprocal pattern with alternation between the left (or right) dorsal and the right (or left) ventral branches was observed; 2) synchronous bursting in all branches was encountered in four cases. In contrast, the fast locomotor rhythm occurred always in a left-right reciprocal pattern. Thus when the slow rhythm appeared in a dorsal-ventral reciprocal pattern, fast rhythms would simultaneously display left-right alternation. A longitudinal midline section of the spinal cord during ongoing slow bursting abolished the reciprocal pattern between ipsilateral dorsal and ventral branches but a synchronous burst activity could still remain. The fast swimming rhythm did not recover after the midline section. These results suggest that in addition to the network generating the swimming rhythm in the lamprey spinal cord, there is also a network providing slow reciprocal alternation between dorsal and ventral parts of the myotome. During steering, a selective activation of dorsal and ventral myotomes is required and the neural network generating the slow rhythm may represent activity in the spinal machinery used for steering. PMID:11152721

  13. Pre-Botzinger Complex: A Brainstem Region That May Generate Respiratory Rhythm in Mammals

    NASA Astrophysics Data System (ADS)

    Smith, Jeffrey C.; Ellenberger, Howard H.; Ballanyi, Klaus; Richter, Diethelm W.; Feldman, Jack L.

    1991-11-01

    The location of neurons generating the rhythm of breathing in mammals is unknown. By microsection of the neonatal rat brainstem in vitro, a limited region of the ventral medulla (the pre-Botzinger Complex) that contains neurons essential for rhythmogenesis was identified. Rhythm generation was eliminated by removal of only this region. Medullary slices containing the pre-Botzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties were identified in this region. Thus, the respiratory rhythm in the mammalian neonatal nervous system may result from a population of conditional bursting pacemaker neurons in the pre-Botzinger Complex.

  14. Effects of music composed by Mozart and Ligeti on blood pressure and heart rate circadian rhythms in normotensive and hypertensive rats.

    PubMed

    Lemmer, Björn

    2008-11-01

    There is continuing discussion on the effect of music ("Mozart effect") on numerous functions in man and experimental animals. Radiotelemetry now allows one to monitor cardiovascular functions in freely-moving unrestrained experimental animals. Radiotelemetry was used to monitor systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and motor activity (MA) in male normotensive WKY and hypertensive SHR animals. Rats were synchronized to a 12 h light (L): 12 h dark (D) regimen in an isolated, ventilated, light-controlled, sound-isolated animal container. Music (Mozart, Symphony # 40; Ligeti, String Quartet # 2) were played for 2 h at 75 dB in the animal cabin starting at the onset of L or D in a cross-over design. Data were collected every 5 min for 24 h under control conditions and during and after music. In addition, plasma concentrations of norepinephrine (NE) were determined in unrestrained animals at 3 h intervals over 24 h. In both WKY and SHR, highly significant circadian rhythms were obtained in SBP, DBP, HR, and MA under control conditions; HR was lower and BP higher in SHR than in WKY. NE was circadian rhythmic in both strains with higher values in D; the increase in NE with immobilization was much more pronounced in SHR than in WKY. The music of Mozart had no effect on either parameter in WKY, neither in L nor in D. In contrast, in SHR, the music of Mozart presented in L significantly decreased HR and left BP unaffected, leading to a small decrease in cardiac output. The music of Ligeti significantly increased BP both in L and in D and reflexively reduced HR in L, the effects being long-lasting over 24 h. Interestingly, white noise at 75 dB had no effect at all on either function in both strains. The effects of both Mozart and Ligeti cannot be attributed to a stress reaction, as stress due to cage switch increased HR and BP both in WKY and SHR. The study clearly demonstrates that music of different character (tempo, rhythm, pitch, tonality) can modify cardiovascular functions in freely-moving rats, with SHR being more sensitive than normotensive animals. The relative contribution of the characteristics of the two pieces of music, however, needs further evaluation. PMID:19005899

  15. Circadian oscillation of gibberellin signaling in Arabidopsis

    PubMed Central

    Arana, María Verónica; Marín-de la Rosa, Nora; Maloof, Julin N.; Blázquez, Miguel A.; Alabadí, David

    2011-01-01

    Circadian clocks are endogenous timekeeping mechanisms that allow organisms to anticipate rhythmic, daily environmental changes. Temporal coordination of transcription results in a set of gene expression patterns with peak levels occurring at precise times of the day. An intriguing question is how a single clock can generate different oscillatory rhythms, and it has been proposed that hormone signaling might act in plants as a relay mechanism to modulate the amplitude and the phase of output rhythms. Here we show that the circadian clock gates gibberellin (GA) signaling through transcriptional regulation of the GA receptors, resulting in higher stability of DELLA proteins during daytime and higher GA sensitivity at night. Oscillation of GA signaling appears to be particularly critical for rhythmic growth, given that constitutive expression of the GA receptor expands the daily growth period in seedlings, and complete loss of DELLA function causes continuous, arrhythmic hypocotyl growth. Moreover, transcriptomic analysis of a pentuple della KO mutant indicates that the GA pathway mediates the rhythmic expression of many clock-regulated genes related to biotic and abiotic stress responses and cell wall modification. Thus, gating of GA sensitivity by the circadian clock represents an additional layer of regulation that might provide extra robustness to the diurnal growth rhythm and constitute a regulatory module that coordinates the circadian clock with additional endogenous and environmental signals. PMID:21576475

  16. Development of a configurable growth chamber with a computer vision system to study circadian rhythm in plants.

    PubMed

    Navarro, Pedro J; Fernández, Carlos; Weiss, Julia; Egea-Cortines, Marcos

    2012-01-01

    Plant development is the result of an endogenous morphogenetic program that integrates environmental signals. The so-called circadian clock is a set of genes that integrates environmental inputs into an internal pacing system that gates growth and other outputs. Study of circadian growth responses requires high sampling rates to detect changes in growth and avoid aliasing. We have developed a flexible configurable growth chamber comprising a computer vision system that allows sampling rates ranging between one image per 30 s to hours/days. The vision system has a controlled illumination system, which allows the user to set up different configurations. The illumination system used emits a combination of wavelengths ensuring the optimal growth of species under analysis. In order to obtain high contrast of captured images, the capture system is composed of two CCD cameras, for day and night periods. Depending on the sample type, a flexible image processing software calculates different parameters based on geometric calculations. As a proof of concept we tested the system in three different plant tissues, growth of petunia- and snapdragon (Antirrhinum majus) flowers and of cladodes from the cactus Opuntia ficus-indica. We found that petunia flowers grow at a steady pace and display a strong growth increase in the early morning, whereas Opuntia cladode growth turned out not to follow a circadian growth pattern under the growth conditions imposed. Furthermore we were able to identify a decoupling of increase in area and length indicating that two independent growth processes are responsible for the final size and shape of the cladode. PMID:23202214

  17. Lysosomal enzyme activities are decreased in the retina and their circadian rhythms are different from those in the pineal gland of rats fed an alpha-linolenic acid-restricted diet.

    PubMed

    Ikemoto, A; Fukuma, A; Fujii, Y; Okuyama, H

    2000-12-01

    The retinal rod outer segment (ROS) is shed and digested daily by phagosomes in retinal pigment epithelial (RPE) cells. We previously observed significantly fewer large phagosomes in rats fed an alpha-linolenic acid (ALNA)-deficient diet. Rats fed a safflower oil diet (ALNA-restricted) or a perilla oil diet (ALNA-sufficient) through two generations were adapted to a 24-h cycle with light from 0700 to 1900 h. They were killed at 0500, 0900, 1300 and 1700 h to determine the activities of four lysosomal enzymes in retina, including beta-glucosidase, beta-glucuronidase, hexosaminidase and acid phosphatase. The enzyme activities at 0500 h were the lowest and then increased gradually until 1700 h, exhibiting similar circadian rhythms in the two dietary groups. However, the activities at each time point were significantly lower in the safflower group. In the pineal gland, the activities were maximum at 1300 h, except for beta-glucosidase, and were not different between groups. These diets had qualitatively similar but quantitatively different effects on the fatty acid compositions of the retina and the pineal gland. These results indicate that decreased amplitudes in electroretinogram and altered size distribution of phagosomes, as induced by a restricted intake of ALNA, are associated with decreased lysosomal enzyme activities in the retina but not in the pineal gland. PMID:11110869

  18. Circadian Dysrhythmias in the Intensive Care Unit.

    PubMed

    Billings, Martha E; Watson, Nathaniel F

    2015-07-01

    Circadian rhythms underlie nearly all physiologic functions and organ systems. Circadian abnormalities have attendant implications for critical illness survival. The intensive care unit (ICU) environment, with its lack of diurnal variation in sound, light, and social cues, may precipitate circadian dysrhythmias. Additional features of critical care, including mechanical ventilation and sedation, likely perpetuate circadian misalignment. Critical illness itself, from sepsis to severe brain injury, can compromise circadian health. Use of daylight, time-restricted feedings, and administration of melatonin can possibly restore circadian rhythm. However, further study is necessary to assess the effectiveness of these interventions and their impact on ICU outcomes. PMID:26118911

  19. Genes encoding glycine-rich Arabidopsis thaliana proteins with RNA-binding motifs are influenced by cold treatment and an endogenous circadian rhythm.

    PubMed Central

    Carpenter, C D; Kreps, J A; Simon, A E

    1994-01-01

    We have characterized the expression of two members of a class of Arabidopsis thaliana glycine-rich, putative RNA-binding proteins that we denote Ccr1 and Ccr2. Southern blot analysis indicates that Ccr1 and Ccr2 are members of a small gene family. Both Ccr1 and Ccr2 mRNA levels were influenced by a circadian rhythm that has an unusual phase for plants, with maximal accumulation at 6:00 PM and minimal accumulation at 10:00 AM. The level of CCR1 protein, however, remained relatively constant throughout the cycle. The transcript accumulation patterns of the Ccr1 and Ccr2 genes differed considerably from conditions that affect the expression of similar genes from maize, sorghum, and carrot. Levels of Ccr1 and Ccr2 mRNAs were unchanged in wounded plants, increased at least 4-fold in cold-stressed plants, and decreased 2- to 3-fold in abscisic acid-treated plants. Ccr1 transcript levels decreased in response to drought, whereas Ccr2 transcript levels increased under the same conditions. Based on the presence of additional Ccr transcripts in dark-grown plants, we propose that Ccr transcripts may be subjected to a light- or dark-mediated regulation. PMID:7513083

  20. Robust circadian clocks from coupled protein-modification and transcription-translation cycles.

    PubMed

    Zwicker, David; Lubensky, David K; ten Wolde, Pieter Rein

    2010-12-28

    The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and compensating synthesis rates), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely posttranslational clock ceases to function well when the cell doubling time drops below the 24-h clock period. At higher growth rates, a transcription-translation cycle becomes essential for generating robust circadian rhythms. Interestingly, although a transcription-translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription-translation cycle at lower protein decay or dilution rates. In fact, the full oscillator built from these two tightly intertwined cycles far outperforms not just each of its two components individually, but also a hypothetical system in which the two parts are coupled as in textbook models of coupled phase oscillators. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions. PMID:21149676

  1. Modeling Neural Mechanisms for Genesis of Respiratory Rhythm and Pattern. II. Network Models of the Central Respiratory Pattern Generator

    Microsoft Academic Search

    ILYA A. RYBAK; JULIAN F. R. PATON; JAMES S. SCHWABER

    Rybak, Ilya A., Julian F. R. Paton, and James S. Schwaber. Model- respiratory rhythm and pattern generation at the cellular, ing neural mechanisms for genesis of respiratory rhythm and pattern. network, and system levels employing modeling methods. II. Network models of the central respiratory pattern generator. J. Neu- The preceding paper ( Rybak et al. 1997a ) described models rophysiol.

  2. Neonatal monosodium glutamate treatment counteracts circadian arrhythmicity induced by phase shifts of the light-dark cycle in female and male Siberian hamsters

    PubMed Central

    Prendergast, Brian J.; Onishi, Kenneth G.; Zucker, Irving

    2013-01-01

    Studies of rats and voles suggest that distinct pathways emanating from the anterior hypothalamic-retrochiasmatic area and the mediobasal hypothalamic arcuate nucleus independently generate ultradian rhythms (URs) in hormone secretion and behavior. We evaluated the hypothesis that destruction of arcuate nucleus (ARC) neurons, in concert with dampening of suprachiasmatic nucleus (SCN) circadian rhythmicity, would compromise the generation of ultradian rhythms (URs) of locomotor activity. Siberian hamsters of both sexes treated neonatally with monosodium glutamate (MSG) that destroys ARC neurons were subjected in adulthood to a circadian disrupting phase-shift protocol (DPS) that produces SCN arrhythmia. MSG treatments induced hypogonadism and obesity, and markedly reduced the size of the optic chiasm and primary optic tracts. MSG-treated hamsters exhibited normal entrainment to the light-dark cycle, but MSG treatment counteracted the circadian arrhythmicity induced by the DPS protocol: only 6% of MSG-treated hamsters exhibited circadian arrhythmia, whereas 50% of control hamsters were circadian disrupted. In MSG-treated hamsters that retained circadian rhythmicity after DPS treatment, quantitative parameters of URs appeared normal, but in the 2 MSG-treated hamsters that became circadian arrhythmic after DPS, both dark-phase and light-phase URs were abolished. Although preliminary, these data are consistent with reports in voles suggesting that the combined disruption of SCN and ARC function impairs the expression of behavioral URs. The data also suggest that light thresholds for entrainment of circadian rhythms may be lower than those required to disrupt circadian organization. PMID:23701725

  3. Spinal Cord Modular Organization and Rhythm Generation: An NMDA Iontophoretic Study in the Frog

    E-print Network

    Bizzi, Emilio

    Spinal Cord Modular Organization and Rhythm Generation: An NMDA Iontophoretic Study in the Frog, and Emilio Bizzi. Spinal Furthermore, on systematic exploration of the spinal cord cord modular organization for the limb in space. This observation has existence of modules subserving limb posture in the spinal cord

  4. PREBOTZINGER COMPLEX AND PACEMAKER NEURONS: Hypothesized Site and Kernel for Respiratory Rhythm Generation

    Microsoft Academic Search

    Jens C. Rekling; Jack L. Feldman

    1998-01-01

    Identification of the sites and mechanisms underlying the generation of respiratory rhythm is of longstanding interest to physiologists and neurobiologists. Recently, with the development of novel experimental preparations, especially in vitro en bloc and slice preparations of rodent brainstem, progress has been made. In particular, a site in the ventrolateral medulla, the preBotzinger Complex, is hypothesized to contain neuronal circuits

  5. Perinatal maturation of the respiratory rhythm generator in mammals: from experimental results to computational simulation

    Microsoft Academic Search

    Pablo Achard; Roger Rodriguez

    2005-01-01

    The survival of neonatal mammals requires a correct function of the respiratory rhythm generator (RRG), and therefore, the processes that control its prenatal maturation are of vital importance. In humans, lambs and rodents, foetal breathing movements (FBMs) occur early during gestation, are episodic, sensitive to bioamines, central hypoxia and inputs from CNS upper structures, and evolve with developmental age. In

  6. Effects of ?2-adorenoceptor agonist dexmedetomidine on respiratory rhythm generation of newborn rats.

    PubMed

    Tsuzawa, Kayo; Minoura, Yoshino; Takeda, Shinhiro; Inagaki, Katsunori; Onimaru, Hiroshi

    2015-06-15

    Dexmedetomidine, an ?2-adrenoceptor agonist which has a slight side effect on breathing, is clinically used as an analgesic and sedative agent. Previous studies have shown depressing or modest effects of ?2-adorenoceptor agonists on respiratory rhythm generation in newborn rat preparation in vitro. In contrast, it was recently reported that dexmedetomidine induced long-lasting activation of respiratory rhythm in brainstem-spinal cord preparation isolated from neonatal mice. In the present study, we examined whether dexmedetomidine induces any effects on respiratory rhythm in brainstem-spinal cord preparation isolated from newborn rats. We also examined the effects of dexmedetomidine on reflex response in the spinal cord, which is presumed to be an indication of nociceptive response. We found that the administration of dexmedetomidine, at the range of 0.1-10?M, dose-dependently depressed respiratory rhythm and that the inhibitory effect was reversed by atipamezole, an ?2-adorenoceptor antagonist. Spinal cord reflex responses were depressed by the application of dexmedetomidine at the range of 0.1-1nM, a lower concentration than that affecting respiratory rhythm. The inhibitory effect was also reversed by atipamezole. Our findings provide neuronal mechanisms that support the clinical use of dexmedetomidine, which shows sedative and antinociceptive effects with minimal side effects on breathing. PMID:25916879

  7. Cancer/Testis Antigen PASD1 Silences the Circadian Clock.

    PubMed

    Michael, Alicia K; Harvey, Stacy L; Sammons, Patrick J; Anderson, Amanda P; Kopalle, Hema M; Banham, Alison H; Partch, Carrie L

    2015-06-01

    The circadian clock orchestrates global changes in transcriptional regulation on a daily basis via the bHLH-PAS transcription factor CLOCK:BMAL1. Pathways driven by other bHLH-PAS transcription factors have a homologous repressor that modulates activity on a tissue-specific basis, but none have been identified for CLOCK:BMAL1. We show here that the cancer/testis antigen PASD1 fulfills this role to suppress circadian rhythms. PASD1 is evolutionarily related to CLOCK and interacts with the CLOCK:BMAL1 complex to repress transcriptional activation. Expression of PASD1 is restricted to germline tissues in healthy individuals but can be induced in cells of somatic origin upon oncogenic transformation. Reducing PASD1 in human cancer cells significantly increases the amplitude of transcriptional oscillations to generate more robust circadian rhythms. Our results describe a function for a germline-specific protein in regulation of the circadian clock and provide a molecular link from oncogenic transformation to suppression of circadian rhythms. PMID:25936801

  8. Prospective influences of circadian clocks in adipose tissue and metabolism

    Microsoft Academic Search

    Gregory M. Sutton; Bruce A. Bunnell; Andrey A. Ptitsyn; Z. Elizabeth Floyd; Jeffrey M. Gimble

    2010-01-01

    Circadian rhythms make a critical contribution to endocrine functions that involve adipose tissue. These contributions are made at the systemic, organ and stem cell levels. The transcription factors and enzymes responsible for the maintenance of circadian rhythms in adipose depots and other peripheral tissues that are metabolically active have now been identified. Furthermore, the circadian regulation of glucose and lipid

  9. JOURNAL OF BIOLOGICAL RHYTHMS / December 2001Gorman and Lee / SPLIT ACTIVITY RHYTHMS IN HAMSTERS Daily Novel Wheel Running Reorganizes and

    E-print Network

    Lee, Theresa

    JOURNAL OF BIOLOGICAL RHYTHMS / December 2001Gorman and Lee / SPLIT ACTIVITY RHYTHMS IN HAMSTERS Daily Novel Wheel Running Reorganizes and Splits Hamster Circadian Activity Rhythms Michael R. Gorman1 circadian oscillators. Exposure of male Syrian hamsters to novel running wheels also induces splitting

  10. Ambient Light Intensity, Actigraphy, Sleep and Respiration, Circadian Temperature and Melatonin Rhythms and Daytime Performance of Crew Members During Space Flight on STS-90 and STS-95 Missions

    NASA Technical Reports Server (NTRS)

    Czeisler, Charles A.; Dijk, D.-J.; Neri, D. F.; Hughes, R. J.; Ronda, J. M.; Wyatt, J. K.; West, J. B.; Prisk, G. K.; Elliott, A. R.; Young, L. R.

    1999-01-01

    Sleep disruption and associated waking sleepiness and fatigue are common during space flight. A survey of 58 crew members from nine space shuttle missions revealed that most suffered from sleep disruption, and reportedly slept an average of only 6.1 hours per day of flight as compared to an average of 7.9 hours per day on the ground. Nineteen percent of crewmembers on single shift missions and 50 percent of the crewmembers in dual shift operations reported sleeping pill usage (benzodiazepines) during their missions. Benzodiazepines are effective as hypnotics, however, not without adverse side effects including carryover sedation and performance impairment, anterograde amnesia, and alterations in sleep EEG. Our preliminary ground-based data suggest that pre-sleep administration of 0.3 mg of the pineal hormone melatonin may have the acute hypnotic properties needed for treating the sleep disruption of space flight without producing the adverse side effects associated with benzodiazepines. We hypothesize that pre-sleep administration of melatonin will result in decreased sleep latency, reduced nocturnal sleep disruption, improved sleep efficiency, and enhanced next-day alertness and cognitive performance both in ground-based simulations and during the space shuttle missions. Specifically, we have carried out experiments in which: (1) ambient light intensity aboard the space shuttle is assessed during flight; (2) the impact of space flight on sleep (assessed polysomnographically and actigraphically), respiration during sleep, circadian temperature and melatonin rhythms, waking neurobehavioral alertness and performance is assessed in crew members of the Neurolab and STS-95 missions; (3) the effectiveness of melatonin as a hypnotic is assessed independently of its effects on the phase of the endogenous circadian pacemaker in ground-based studies, using a powerful experimental model of the dyssomnia of space flight; (4) the effectiveness of melatonin as a hypnotic is assessed during the STS-90 (Neurolab) and STS-95 missions in a double-blind placebo-controlled trial. In both flight-based experiments, the effects of melatonin on sleep stages and spectral composition of the EEG during sleep will be determined as well as its effects on daytime alertness and performance; (5) the impact of space flight on sleep and waking neurobehavioral alertness and performance in 30-45-year-old astronauts is compared with its impact in a 77-year-old astronaut. This case study is the first to assess the effects of space flight on an older individual. Because the investigators are still blind to the treatment in this double-blind, placebo-controlled trial, preliminary results will be presented independent of the drug condition.

  11. The effects of feedback lighting on the circadian rhythm of locomotor activity and the reproductive maturation of the male Djungarian hamster (Phodopus sungorus)

    NASA Technical Reports Server (NTRS)

    Ferraro, J. S.

    1988-01-01

    The non-parametric model of entrainment suggests that brief pulses of light, delivered between dusk and dawn can simulate the phasing effects of full photoperiods or even constant light (LL). Feedback lighting (LDFB) is a lighting condition where individual animals, otherwise in constant darkness (DD), are exposed to light in response to a monitored behavior. The specific purpose of this type of illumination is to expose the circadian cycle to light only during the subjective night. LDFB has been used to support this hypothesis in several species of nocturnal rodents and one species of diurnal primate by producing similar free-running periods in LDFB as in LL. This lighting condition has also been used to test the hypothesis that exposing the subjective night to even short duration light pulses will maintain reproductive function in long day breeders. In the Syrian hamster (Mesocricetus auratus), however, LDFB is not as photostimulatory as LL despite extensive light exposure during the subjective night. In the experiments presented here, a group of immature male Djungarian hamsters (Phodopus sungorus) were placed in individual light-tight sound attenuated chambers where they had free access to food, water and an activity wheel. The animals were exposed to one of four lighting conditions [DD, LL, LDFB or a neighbor control of feedback lighting (LDFB NC)] for approximately 30 days shortly after weaning. LDFB NC is a lighting condition where a neighbor control hamster receives the identical lighting regime as a paired animal exposing itself to LDFB, yet the neighbor has no control over it. A fifth group was exposed to a light-dark cycle of 16 hours of light and 8 hours of dark (LD16:8). This group was housed in cages in a colony room and did not have access to a running wheel. The free-running periods of the locomotor activity rhythms for hamsters exposed to LDFB and LL were not similar, unlike the results for rats, Syrian hamsters, mice, monkeys and even mature Djungarian hamsters. Immature hamsters exposed to DD and LDFB NC developed more slowly than animals exposed to LL or LD16:8, while hamsters in LDFB developed at an intermediate rate. Thus, it appears that LDFB, although capable of inducing reproductive function in immature Djungarian hamsters, is not as photostimulatory as may have been expected from current photoperiodic models, despite substantial light exposure during the subjective night. Furthermore, this data may suggest that the circadian system of 18-48 day old Djungarian hamsters are still undergoing organizational maturation.

  12. The brain's master circadian clock: implications and opportunities for therapy of sleep disorders.

    PubMed

    Zee, Phyllis C; Manthena, Prasanth

    2007-02-01

    The suprachiasmatic nuclei (SCN) residing in the anterior hypothalamus maintains a near-24-h rhythm of electrical activity, even in the absence of environmental cues. This circadian rhythm is generated by intrinsic molecular mechanisms in the neurons of the SCN; however, the circadian clock is modulated by a wide variety of influences, including glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from the retinohypothalamic tract, melatonin from the pineal gland, and neuropeptide Y from the intergeniculate leaflet. By virtue of these and other inputs, the SCN responds to environmental cues such as light, social and physical activities. In turn, the SCN controls or influences a wide variety of physiologic and behavioral functions, including attention, endocrine cycles, body temperature, melatonin secretion, and the sleep-wake cycle. Regulation of the sleep-wake cycle by the SCN has important implications for development of therapies for sleep disorders, including those involving desynchronization of circadian rhythms and insomnia. PMID:16973392

  13. Metabolism and cancer: the circadian clock connection

    Microsoft Academic Search

    Saurabh Sahar; Paolo Sassone-Corsi

    2009-01-01

    Circadian rhythms govern a remarkable variety of metabolic and physiological functions. Accumulating epidemiological and genetic evidence indicates that the disruption of circadian rhythms might be directly linked to cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with regulators of the cell cycle, and alterations in clock function could lead to aberrant cellular

  14. Large phase-shifts of circadian rhythms caused by induced running in a re-entrainment paradigm: the role of pulse duration and light.

    PubMed

    Reebs, S G; Mrosovsky, N

    1989-10-01

    Bouts of induced wheel-running, 3 h long, accelerate the rate of re-entrainment of hamsters' activity rhythms to light-dark (LD) cycles that have been phase-advanced by 8 h (Mrosovsky and Salmon 1987). The bouts of running are given early in the first night of the new LD cycle, and by the second night the phase advance in activity onset already averages 7 h. Such large shifts contrast with the mean phase advance of less than 1 h at the peak of the phase response curve when hamsters in constant darkness (DD) experience 2-h pulses of induced activity (Reebs and Mrosovsky 1989). The present paper investigates pulse duration and light as possible causes for the discrepancy in shift amplitude between these two studies. In a first experiment, pulses of induced wheel-running 1 h, 3 h, or 5 h long were given at circadian times (CT) 6 and 22-2 to hamsters free-running in DD. Pulses given at CT 6 caused phase-advances of up to 2.8 h, whereas pulses at CT 22-2 resulted in delays of up to 1.0 h. Shifts after 3-h and 5-h pulses did not differ, but were larger than after 1-h pulses, and larger than after the 2-h pulses given in DD by Reebs and Mrosovsky (1989). Thus 3 h appears to be the minimum pulse duration necessary to obtain maximum phase-shifting effects. In a second experiment, the re-entrainment design of Mrosovsky and Salmon (1987) was repeated with the light portion of the shifted LD cycle eliminated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2810152

  15. Drugs that prevent mouse sleep also block light-induced locomotor suppression, circadian rhythm phase shifts and the drop in core temperature.

    PubMed

    Vivanco, P; Studholme, K M; Morin, L P

    2013-12-19

    Exposure of mice to a brief light stimulus during their nocturnal active phase induces several simultaneous behavioral or physiological responses, including circadian rhythm phase shifts, a drop in core body temperature (Tc), suppression of locomotor activity and sleep. Each response is triggered by light, endures for a relatively fixed interval and does not require additional light for expression. The present studies address the ability of the psychostimulant drugs, methamphetamine (MA), modafinil (MOD) or caffeine (CAF), to modify the light-induced responses. Drug or vehicle (VEH) was injected at CT11 into constant dark-housed mice then exposed to 5-min 100?W/cm(2) light or no light at CT13. Controls (VEH/Light) showed approximately 60-min phase delays. In contrast, response was substantially attenuated by each drug (only 12-15min delays). Under a 12-h light:12-h dark (LD12:12) photoperiod, VEH/light-treated mice experienced a Tc drop of about 1.3°C coincident with locomotor suppression and both effects were abolished by drug pre-treatment. Each drug elevated activity during the post-injection interval, but there was also evidence for CAF-induced hypoactivity in the dark prior to the photic test stimulus. CAF acutely elevated Tc; MA acutely lowered it, but both drugs reduced Tc during the early dark (ZT12.5-ZT13). The ability of the psychostimulant drugs to block the several effects of light exposure is not the result of drug-induced hyperactivity. The results raise questions concerning the manner in which drugs, activity, sleep and Tc influence behavioral and physiological responses to light. PMID:24056197

  16. Drugs that prevent mouse sleep also block light-induced locomotor suppression, circadian rhythm phase shifts and the drop in core temperature

    PubMed Central

    Vivanco, P.; Studholme, K.M.; Morin, L.P.

    2013-01-01

    Exposure of mice to a brief light stimulus during their nocturnal active phase induces several simultaneous behavioral or physiological responses, including circadian rhythm phase shifts, a drop in core body temperature (Tc), suppression of locomotor activity and sleep. Each response is triggered by light, endures for a relatively fixed interval and does not require additional light for expression. The present studies address the ability of the psychostimulant drugs, methamphetamine (MA), modafinil (MOD) or caffeine (CAF), to modify the light-induced responses. Drug or vehicle (VEH) was injected at CT11 into constant dark-housed mice then exposed to 5 min 100 ?W/cm2 light or no light at CT13. Controls (VEH/Light) showed approximately 60 min phase delays. In contrast, response was substantially attenuated by each drug (only 12-15 min delays). Under a LD12:12 photoperiod, VEH/light-treated mice experienced a Tc drop of about 1.3 °C coincident with locomotor suppression and both effects were abolished by drug pretreatment. Each drug elevated activity during the post-injection interval, but there was also evidence for CAF-induced hypoactivity in the dark prior to the photic test stimulus. CAF acutely elevated Tc; MA acutely lowered it, but both drugs reduced Tc during the early dark (ZT12.5-ZT13). The ability of the psychostimulant drugs to block the several effects of light exposure is not the result of drug-induced hyperactivity. The results raise questions concerning the manner in which drugs, activity, sleep and Tc influence behavioral and physiological responses to light. PMID:24056197

  17. Temporal organization of activity in the brown bear (Ursus arctos): roles of circadian rhythms, light, and food entrainment.

    PubMed

    Ware, Jasmine V; Nelson, O Lynne; Robbins, Charles T; Jansen, Heiko T

    2012-11-01

    Seasonal cycles of reproduction, migration, and hibernation are often synchronized to changes in daylength (photoperiod). Ecological and evolutionary pressures have resulted in physiological specializations enabling animals to occupy a particular temporal niche within the diel cycle leading to characteristic activity patterns. In this study, we characterized the annual locomotor activity of captive brown bears (Ursus arctos). Locomotor activity was observed in 18 bears of varying ages and sexes during the active (Mar-Oct) and hibernating (Nov-Feb) seasons. All bears exhibited either crepuscular or diurnal activity patterns. Estimates of activity duration (?) and synchronization to the daily light:dark cycle (phase angles) indirectly measured photoresponsiveness. ? increased as daylength increased but diverged near the autumnal equinox. Phase angles varied widely between active and hibernating seasons and exhibited a clear annual rhythm. To directly test the role of photoperiod, bears were exposed to controlled photoperiod alterations. Bears failed to alter their daily activity patterns (entrain) to experimental photoperiods during the active season. In contrast, photic entrainment was evident during hibernation when the daily photocycle was shifted and when bears were exposed to a skeleton (11:1:11:1) photoperiod. To test whether entrainment to nonphotic cues superseded photic entrainment during the active season, bears were exposed to a reversed feeding regimen (dark-fed) under a natural photocycle. Activity shifted entirely to a nocturnal pattern. Thus daily activity in brown bears is highly modifiable by photoperiod and food availability in a stereotypic seasonal fashion. PMID:22972838

  18. Divergent roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillators.

    PubMed

    Ruan, Guo-Xiang; Gamble, Karen L; Risner, Michael L; Young, Laurel A; McMahon, Douglas G

    2012-01-01

    The retina is both a sensory organ and a self-sustained circadian clock. Gene targeting studies have revealed that mammalian circadian clocks generate molecular circadian rhythms through coupled transcription/translation feedback loops which involve 6 core clock genes, namely Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1 and that the roles of individual clock genes in rhythms generation are tissue-specific. However, the mechanisms of molecular circadian rhythms in the mammalian retina are incompletely understood and the extent to which retinal neural clocks share mechanisms with the suprachiasmatic nucleus (SCN), the central neural clock, is unclear. In the present study, we examined the rhythmic amplitude and period of real-time bioluminescence rhythms in explants of retina from Per1-, Per2-, Per3-, Cry1-, Cry2-, and Clock-deficient mice that carried transgenic PERIOD2::LUCIFERASE (PER2::LUC) or Period1::luciferase (Per1::luc) circadian reporters. Per1-, Cry1- and Clock-deficient retinal and SCN explants showed weakened or disrupted rhythms, with stronger effects in retina compared to SCN. Per2, Per3, and Cry2 were individually dispensable for sustained rhythms in both tissues. Retinal and SCN explants from double knockouts of Cry1 and Cry2 were arrhythmic. Gene effects on period were divergent with reduction in the number of Per1 alleles shortening circadian period in retina, but lengthening it in SCN, and knockout of Per3 substantially shortening retinal clock period, but leaving SCN unaffected. Thus, the retinal neural clock has a unique pattern of clock gene dependence at the tissue level that it is similar in pattern, but more severe in degree, than the SCN neural clock, with divergent clock gene regulation of rhythmic period. PMID:22701739

  19. The effect of circadian rhythm on pharmacokinetics and metabolism of the Cdk inhibitor, roscovitine, in tumor mice model.

    PubMed

    Sallam, Hatem; El-Serafi, Ahmed T; Filipski, Elisabeth; Terelius, Ylva; Lévi, Francis; Hassan, Moustapha

    2015-06-01

    Roscovitine is a selective Cdk-inhibitor that is under investigation in phase II clinical trials under several conditions, including chemotherapy. Tumor growth inhibition has been previously shown to be affected by the dosing time of roscovitine in a Glasgow osteosarcoma xenograft mouse model. In the current study, we examined the effect of dose timing on the pharmacokinetics, bio