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Circadian Rhythm (circadian + rhythm)
Kinds of Circadian Rhythm Terms modified by Circadian Rhythm Selected AbstractsMetabolic Heat Production, Heat Loss and the Circadian Rhythm of Body Temperature in the RatEXPERIMENTAL PHYSIOLOGY, Issue 3 2003Roberto Refinetti Metabolic heat production (calculated from oxygen consumption), dry heat loss (measured in a calorimeter) and body temperature (measured by telemetry) were recorded simultaneously at 6 min intervals over five consecutive days in rats maintained in constant darkness. Robust circadian rhythmicity (confirmed by chi square periodogram analysis) was observed in all three variables. The rhythm of heat production was phase-advanced by about half an hour in relation to the body temperature rhythm, whereas the rhythm of heat loss was phase-delayed by about half an hour. The balance of heat production and heat loss exhibited a daily oscillation 180 deg out of phase with the oscillation in body temperature. Computations indicated that the amount of heat associated with the generation of the body temperature rhythm (1.6 kJ) corresponds to less than 1% of the total daily energy budget (172 kJ) in this species. Because of the small magnitude of the fraction of heat balance associated with the body temperature rhythm, it is likely that the daily oscillation in heat balance has a very slow effect on body temperature, thus accounting for the 180 deg phase difference between the rhythms of heat balance and body temperature. [source] CPT-11 Alters the Circadian Rhythm of Dihydropyrimidine Dehydrogenase mRNA in Mouse LiverCANCER SCIENCE, Issue 5 2001Mikiko Shimizu Combination chemotherapy consisting of 5-fluorouracil (5-FU) and 7-ethyl-10-[4-(l-piperidino)-l-piperidino]carboxycamptothecin (CPT-11) is a promising regimen for gastrointestinal cancer. The circadian-dependent efficacy and toxicity of 5-FU are related to the circadian variation in the activity of dihydropyrimidine dehydrogenase (DPD), which is a rate-limiting enzyme in the pyrimidine catabolic pathway. To optimize the schedule of the CPT-11 plus 5-FU combination, we investigated the effect of CPT-11 on the circadian rhythm of DPD in vivo. In control mice, the DPD mRNA level in the liver was significantly higher at 14:00 than that at 02:00. After intravenous administration of CPT-11 (30 mg/kg) at 20:00, the circadian rhythm of the DPD mRNA level in the liver was no longer observed 18 h later (14:00), but it was unaffected 6 and 18 h later (at 14:00 and 02:00) when CPT-11 was given at 08:00. In addition, a dose-dependent lengthening of the period of the circadian rhythm of DPD was observed for 42 h after intravenous injection of CPT-11 at 20:00. The levels of DPD protein and activity at 21 h after administration of CPT-11 (at 17:00) were significantly higher than at 9 h (at 05:00). These results suggest that CPT-11 may influence the circadian rhythm of DPD at the transcriptional level. Modulation of the circadian rhythm of DPD by CPT-11 may be a factor in optimizing the combination of 5-FU and CPT-11. [source] Effect of Light Treatment on Sleep and Circadian Rhythms in Demented Nursing Home PatientsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2002Sonia Ancoli-Israel PhD First page of article [source] Crayfish Procambarus clarkii Retina and Nervous System Exhibit Antioxidant Circadian Rhythms Coupled with Metabolic and Luminous Daily CyclesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2009María Luisa Fanjul-Moles Based on previous work in which we proposed midgut as a putative peripheral oscillator responsible for circadian reduced glutathione (GSH) crayfish status, herein we investigated the retina and optic lobe-brain (OL-B) circadian GSH system and its ability to deal with reactive oxygen species (ROS) produced as a consequence of metabolic rhythms and light variations. We characterized daily and antioxidant circadian variations of the different parameters of the glutathione system, including GSH, oxidized glutathione (GSSG), glutathione reductase (GR) and glutathione peroxidase (GPx), as well as metabolic and lipoperoxidative circadian oscillations in retina and OL-B, determining internal and external GSH-system synchrony. The results demonstrate statistically significant bi- and unimodal daily and circadian rhythms in all GSH-cycle parameters, substrates and enzymes in OL-B and retina, as well as an apparent direct effect of light on these rhythms, especially in the retina. The luminous condition appears to stimulate the GSH system to antagonize ROS and lipid peroxidation (LPO) daily and circadian rhythms occurring in both structures, oscillating with higher LPO under dark conditions. We suggest that the difference in the effect of light on GSH rhythmic mechanisms of both structures for antagonizing ROS could be due to differences in glutathione-system coupling strength with the circadian clock. [source] Circadian rhythm of aromatic l -amino acid decarboxylase in the rat suprachiasmatic nucleus: gene expression and decarboxylating activity in clock oscillating cellsGENES TO CELLS, Issue 5 2002Yoshiki Ishida Background: Aromatic l -amino acid decarboxylase (AADC) is the enzyme responsible for the decarboxylation step in both the catecholamine and indoleamine synthetic pathways. In the brain, however, a group of AADC containing neurones is found outside the classical monoaminergic cell groups. Since such non-monoaminergic AADC is expressed abundantly in the suprachiasmatic nucleus (SCN), the mammalian circadian centre, we characterized the role of AADC in circadian oscillation. Results : AADC gene expression was observed in neurones of the dorsomedial subdivision of the SCN and its dorsal continuant in the anterior hypothalamic area. These AADC neurones could uptake exogenously applied L-DOPA and formed dopamine. AADC was co-expressed with vasopressin and the clock gene Per1 in the neurones of the SCN. Circadian gene expression of AADC was observed with a peak at subjective day and a trough at subjective night. The circadian rhythm of AADC enzyme activity in the SCN reflects the expression of the gene. Conclusions: Non-monoaminergic AADC in the SCN is expressed in clock oscillating cells, and the decarboxylating activity of master clock cells are under the control of the circadian rhythm. [source] Disturbance of circadian gene expression in hepatocellular carcinomaMOLECULAR CARCINOGENESIS, Issue 12 2008Yueh-Min Lin Abstract Circadian rhythm plays an important role in the regulation of digestive system. The human circadian rhythm is controlled by at least nine circadian genes. The aims of this study are to understand the expression of the circadian genes between hepatocellular carcinoma tissues and nontumor tissues, and to explore the possible mechanism(s) contributing to the difference. We analyzed differential expression of the 9 circadian genes in 46 hepatocellular carcinoma and paired noncancerous tissues by real-time quantitative RT-PCR and immunohistochemical detection. We also tested the possible regulatory mechanism(s) by direct sequencing and methylation PCR analysis. Our results showed that decreased expression levels of PER1, PER2, PER3, CRY2, and TIM in hepatocellular carcinomas were observed. Decreased-expression of these genes was not caused by genetic mutations, but by several factors, such as promoter methylation, overexpression of EZH2 or other factors. The downexpression of more circadian genes may result in disturbance of cell cycle, and it is correlated with the tumor size. Downregulation of circadian genes results in disturbance of circadian rhythm in hepatocellular carcinoma which may disrupt the control of the central pacemaker and benefit selective survival of cancerous cells and promote carcinogenesis. © 2008 Wiley-Liss, Inc. [source] Circadian rhythm of restless legs syndrome: Relationship with biological markersANNALS OF NEUROLOGY, Issue 3 2004Martin Michaud PhD Recently, it was suggested that the intensity of restless legs syndrome (RLS) symptoms may be modulated by a circadian factor. The objective of this study was to evaluate, during a 28-hour modified constant routine, the nycthemeral or circadian variations in subjective leg discomfort and periodic leg movements (PLMs) and to parallel these changes with those of subjective vigilance, core body temperature, and salivary melatonin. Seven patients with primary RLS and seven healthy subjects matched for sex and age entered this study. Although the symptoms were more severe in patients than in controls, a significant circadian variation in leg discomfort and PLM (p < 0.01) was found for both groups. In both groups, the profiles of leg discomfort and PLM were significantly correlated with those of subjective vigilance, core body temperature, and salivary melatonin. However, among these variables, the changes in melatonin secretion were the only ones that preceded the increase in sensory and motor symptoms in RLS patients. This result and those of others studies showing that melatonin exerts an inhibitory effect on central dopamine secretion suggest that melatonin might be implicated in the worsening of RLS symptoms in the evening and during the night. [source] Circadian rhythm of stroke onset during the month of RamadanACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010A. El-Mitwalli El-Mitwalli A, Zaher AA, El Menshawi E. Circadian rhythm of stroke onset during the month of Ramadan. Acta Neurol Scand: 2010: 122: 97,101. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background and purpose,,, The onset of acute stroke exhibits a circadian pattern occurring more frequently in late morning hours. The objective of this study was to investigate the diurnal pattern of stroke during the month of Ramadan. Patients and methods,,, We studied consecutive stroke patients 1 month before Ramadan (BR) and during Ramadan (DR) over two successive years 2007 and 2008. The age, gender, risk factor profiles were analyzed. The National Institute of Health and Stroke Scale Score (NIHSS) was used for clinical assessment at admission. The exact time of stroke onset in both groups was obtained. Results,,, A total of 507 patients were studied: 245 patients in the DR group and 262 patients in the BR group. The age distribution of patients was not significantly different between the two groups. There was no statistically significant difference in the sex ratio, risk factors, and NIHSS score between the two groups (P > 0.05). The higher frequency of stroke onset time in the BR group was in the time between 6:00 a.m. and noon; whereas the frequency was higher between noon and 6:00 p.m. in the DR group. Conclusion,,, A significant shift of the circadian pattern of stroke onset time from the period between 6:00 a.m. and noon to that between noon and 6:00 pm has been found during the month of Ramadan. [source] Ecological implications of plants' ability to tell the timeECOLOGY LETTERS, Issue 6 2009Víctor Resco Abstract The circadian clock (the endogenous mechanism that anticipates diurnal cycles) acts as a central coordinator of plant activity. At the molecular and organism level, it regulates key traits for plant fitness, including seed germination, gas exchange, growth and flowering, among others. In this article, we explore current evidence on the effect of the clock for the scales of interest to ecologists. We begin by synthesizing available knowledge on the effect of the clock on biosphere,atmosphere interactions and observe that, at least in the systems where it has been tested, the clock regulates gas exchange from the leaf to the ecosystem level, and we discuss its implications for estimates of the carbon balance. Then, we analyse whether incorporating the action of the clock may help in elucidating the effects of climate change on plant distributions. Circadian rhythms are involved in regulating the range of temperatures a species can survive and affects plant interactions. Finally, we review the involvement of the clock in key phenological events, such as flowering time and seed germination. Because the clock may act as a common mechanism affecting many of the diverse branches of ecology, our ultimate goal is to stimulate further research into this pressing, yet unexplored, topic. [source] Food-entrainable circadian oscillators in the brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2009M. Verwey Abstract Circadian rhythms in mammalian behaviour and physiology rely on daily oscillations in the expression of canonical clock genes. Circadian rhythms in clock gene expression are observed in the master circadian clock, the suprachiasmatic nucleus but are also observed in many other brain regions that have diverse roles, including influences on motivational and emotional state, learning, hormone release and feeding. Increasingly, important links between circadian rhythms and metabolism are being uncovered. In particular, restricted feeding (RF) schedules which limit food availability to a single meal each day lead to the induction and entrainment of circadian rhythms in food-anticipatory activities in rodents. Food-anticipatory activities include increases in core body temperature, activity and hormone release in the hours leading up to the predictable mealtime. Crucially, RF schedules and the accompanying food-anticipatory activities are also associated with shifts in the daily oscillation of clock gene expression in diverse brain areas involved in feeding, energy balance, learning and memory, and motivation. Moreover, lesions of specific brain nuclei can affect the way rats will respond to RF, but have generally failed to eliminate all food-anticipatory activities. As a consequence, it is likely that a distributed neural system underlies the generation and regulation of food-anticipatory activities under RF. Thus, in the future, we would suggest that a more comprehensive approach should be taken, one that investigates the interactions between multiple circadian oscillators in the brain and body, and starts to report on potential neural systems rather than individual and discrete brain areas. [source] Nerve growth factor-induced circadian phase shifts and MAP kinase activation in the hamster suprachiasmatic nucleiEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005Gastón A. Pizzio Abstract Circadian rhythms are entrained by light and by several neurochemical stimuli. In hamsters housed in constant darkness, i.c.v. administration of nerve growth factor (NGF) at various times in their circadian cycle produced phase shifts of locomotor activity rhythms that were similar in direction and circadian timing to those produced by brief pulses of light. Moreover, the effect of NGF and light were not additive, indicating signalling points in common. These points include the immediate-early gene c-fos and ERK1/2, a component of the mitogen-activated protein kinases (MAPK) family. NGF activates c-FOS and ERK1/2-MAPK in the suprachiasmatic nuclei, the site of a circadian clock in mammals, when administered during the subjective night but not during the day. The effect of NGF on ERK1/2 activation was not inhibited by the administration of MK-801, a glutamate/NMDA receptor antagonist. These results suggest that NGF, acting through MAPK activation, plays a role in photic entrainment of the mammalian circadian clock. [source] Mind, Brain, Education, and Biological TimingMIND, BRAIN, AND EDUCATION, Issue 1 2008Diego A. Golombek ABSTRACT, Circadian rhythms, in particular the sleep,wake cycle, modulate most, if not all, aspects of physiology and behavior. Their impact on education has recently begun to be understood, including a clear positive relationship between sleep and learning. In fact, sleep deprivation, common to adolescents throughout the world, has a deep effect on academic performance, and this fact is often increased by inadequate school schedules. This special issue of Mind, Brain, and Education deals with the relation between biological rhythms and learning, as discussed in an International Mind, Brain, and Education Society meeting that took place in Erice, Italy in May 2007. The articles (with contributors from Brazil, Croatia, Sweden, Spain, United Kingdom, United States, and Argentina) cover several aspects of this fundamental link between timing and education and suggest strategies to optimize school and sleep schedules for a better quality of life and improved academic performance of students. [source] Circadian rhythms in plants: a millennial viewPHYSIOLOGIA PLANTARUM, Issue 4 2000C. Robertson McClung Circadian rhythms are endogenous rhythms with periods of approximately 24 h. These rhythms are widespread both within any given organism and among diverse taxa. As genetic and molecular biological studies, primarily in a subset of model organisms, have begun to identify the components of circadian systems, there is optimism that we will soon achieve a detailed molecular understanding of circadian timing mechanisms. Although plants have provided many examples of rhythmic outputs, and our understanding of photoreceptors of circadian input pathways is well-advanced, plants have lagged behind other groups of organisms in the identification of components of the central circadian oscillator. However, there are now a number of promising candidates for components of plant circadian clocks, and it seems probable that we will soon know the details of a plant central oscillator. Moreover, there is also accumulating evidence that plants and other organisms house multiple circadian clocks, both in different tissues and, quite probably, within individual cells. This provides an unanticipated level of complexity with the potential for interaction among these multiple oscillators. [source] Circadian rhythms and the evolution of photoperiodic timing in insectsPHYSIOLOGICAL ENTOMOLOGY, Issue 4 2009DAVID S. SAUNDERS Abstract. This review discusses possible evolutionary trends in insect photoperiodism, mainly from a chronobiological perspective. A crucial step was the forging of a link between the hormones regulating diapause and the systems of biological rhythms, circadian or circannual, which have independently evolved in eukaryotes to synchronize physiology and behaviour to the daily cycles of light and darkness. In many of these responses a central feature is that the circadian system resets to a constant phase at the beginning of the subjective night, and then ,measures' the duration of the next scotophase. In ,external coincidence', one version of such a clock, light now has a dual role. First, it serves to entrain the circadian system to the stream of pulses making up the light/dark cycle and, second, it regulates the nondiapause/diapause switch in development by illuminating/not illuminating a specific light sensitive phase falling at the end of the critical night length. Important work by A. D. Lees on the aphid Megoura viciae using so-called ,night interruption experiments' demonstrates that pulses falling early in the night lead to long-day effects that are reversible by a subsequent dark period longer than the critical night length and also show maximal sensitivity in the blue,green range of the spectrum. Pulses falling in the latter half of the night, however, produce long-day effects that are irreversible by a subsequent long-night and show a spectral sensitivity extending into the red. With movement to higher latitudes, insects develop genetic clines in various parameters, including critical night length, the number of long-night cycles needed for diapause induction, the strength of the response, and the ,depth' or intensity of the diapause thus induced. Evidence for these and other types of photoperiodic response suggests that they provided strong selective advantages for insect survival. [source] The ups and downs of daily life: Profiling circadian gene expression in DrosophilaBIOESSAYS, Issue 6 2002Paul D. Etter Circadian rhythms are responsible for 24-hour oscillations in diverse biological processes. While the central genes governing circadian pacemaker rhythmicity have largely been identified, clock-controlled output molecules responsible for regulating rhythmic behaviors remain largely unknown. Two recent reports from McDonald and Rosbash1 and Claridge-Chang et al.2 address this issue. By identifying a large number of genes whose mRNA levels show circadian oscillations, the reports provide important new information on the biology of circadian rhythm. In addition, the reports illustrate both the power and limitations of microarray-based methods for profiling mRNA expression on a genomic scale. BioEssays 24:494,498, 2002. © 2002 Wiley Periodicals, Inc. [source] Timeless in lung morphogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2003Jing Xiao Abstract The Clock gene, timeless, regulates circadian rhythm in Drosophila, but its vertebrate homolog is critical to embryonic development. Timeless was shown to be involved in murine urethral bud branching morphogenesis. We generated a polyclonal antibody to mouse TIMELESS (mTIM) and studied its distribution and its potential role during lung development, which also requires branching morphogenesis. In the early mouse embryo, TIM was localized to all organs, especially the neural epithelium. In embryonic day (E) 9.5 embryos, TIM was present in both epithelial and mesenchymal cells at the onset of lung morphogenesis. In E15 embryos, TIM decreased in the mesenchyme but remained pronounced in the epithelium of both large and small airways. Later, TIM was localized to a specific subset of epithelial cells with alveolar type 2 phenotype. This finding was verified by immunostaining of isolated alveolar type 2 cells. In the proximal airways, TIM was colocalized with CCSP to nonciliated columnar epithelial cells. Antisense oligonucleotides to mTim specifically inhibited branching morphogenesis of embryonic lungs in explant culture without affecting SpC expression an alveolar type 2 cell marker. In cultured lung cells, expression of TIM is independent of cell cycle and proliferation. These studies indicate that the function of Timeless is highly conserved in organs whose formation requires branching morphogenesis. Developmental Dynamics 228:82,94, 2003. © 2003 Wiley-Liss, Inc. [source] Circadian changes in Drosophila motor terminalsDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2007Kerstin I. Mehnert Abstract In Drosophila melanogaster, as in most other higher organisms, a circadian clock controls the rhythmic distribution of rest/sleep and locomotor activity. Here we report that the morphology of Drosophila flight neuromuscular terminals changes between day and night, with a rhythm in synaptic bouton size that continues in constant darkness, but is abolished during aging. Furthermore, arrhythmic mutations in the clock genes timeless and period also disrupt this circadian rhythm. Finally, these clock mutants also have an opposing effect on the nonrhythmic phenotype of neuronal branching, with tim mutants showing a dramatic hyperbranching morphology and per mutants having fewer branches than wild-type flies. These unexpected results reveal further circadian as well as nonclock related pleiotropic effects for these classic behavioral mutants. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapyDRUG DEVELOPMENT RESEARCH, Issue 3 2005N. Zisapel Abstract Disturbances in circadian rhythm have been linked to chronic diseases such as insomnia, hypertension, diabetes, and depression. Here we review recent studies on the age-related changes in cortisol and melatonin rhythms and then present descriptive statistics on our preliminary findings on the rectification of the cortisol rhythms by melatonin therapy in elderly patients with insomnia. In adults, the melatonin onset typically occurs during low cortisol secretion. Administration of exogenous melatonin around dusk will shift the phase of the human circadian clock to earlier hours (advance phase shift) leading to phase advances in circadian rhythms (e.g., sleep, endogenous melatonin, cortisol). With aging, the production of melatonin declines and is shifted to later hours while the production of cortisol increases and its peak occurs earlier in the night. In a randomized placebo-controlled crossover study with 8 patients with insomnia aged 55 years and older, a group characterized by low and delayed melatonin production, administration of prolonged-release melatonin in the evening was able to rectify the early onset cortisol production. This delay in nocturnal cortisol onset may explain in part the improvement in sleep quality in elderly patients with insomnia, in schizophrenics, and in depressed patients. Support of circadian pacemaker function by melatonin may provide a new strategy in the treatment of disorders related to impairments in the internal temporal order. The clinical benefit from a decrease in cortisol during the early part of the night may lie beyond the improvement of sleep into a better control of blood pressure, metabolism, and mood. Drug Dev. Res. 65:119,125, 2005. © 2005 Wiley-Liss, Inc. [source] Effects of Circadian Regulation and Rest,Activity State on Spontaneous Seizures in a Rat Model of Limbic EpilepsyEPILEPSIA, Issue 5 2000Mark Quigg Summary: Purpose: Circadian regulation via the suprachiasmatic nuclei and rest,activity state may influence expression of limbic seizures. Methods: Male rats (n = 14) were made epileptic by electrical stimulation of the hippocampus, causing limbic status epilepticus and subsequent seizures. We monitored seizures with intrahippocampal electrodes in 12,12-h light/dark (LD) cycles and in continuous dark (DD). We used radiotelemetry monitoring of activity to measure state and body temperature to determine circadian phase. Cosinor analysis and ,2 tests determined whether seizures occurred rhythmically when plotted by phase. State was defined as inactive or active in 10-min epochs based on whether activity count was below or above a cut-off value validated from video observation. Results: In LD, the peak seizure occurrence was 14:59 h after circadian temperature peak (95% confidence limit, 13:37,16:19). Phasic seizure occurrence persisted in DD for 14:05 (12:31,15:38), p < 0.0001, against uniform mean distribution. In LD, 14,787 epochs contained 1,268 seizures; seizures preferentially occurred during inactive epochs (965 observed, 878 expected in proportion to the overall distribution of inactive versus active epochs; p < 0.001). In DD, 20,664 epochs contained 1,609 seizures; seizures had no preferential occurrence by state (999 observed, 1,025 expected; p = 0.16). Conclusions: Limbic seizures occurred with an endogenous circadian rhythm. Seizures preferentially struck during inactivity during entrainment to the light,dark cycle. [source] Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002G. Williams Abstract Background Patients with chronic fatigue syndrome (CFS) show evidence of circadian rhythm disturbances. We aimed to determine whether CFS symptoms were alleviated by melatonin and bright-light phototherapy, which have been shown to improve circadian rhythm disorders and fatigue in jet-lag and shift workers. Design Thirty patients with unexplained fatigue for > 6 months were initially assessed using placebo and then received melatonin (5 mg in the evening) and phototherapy (2500 Lux for 1 h in the morning), each for 12 weeks in random order separated by a washout period. Principal symptoms of CFS were measured by visual analogue scales, the Shortform (SF-36) Health Survey, Mental Fatigue Inventory and Hospital Anxiety and Depression Scale. We also determined the circadian rhythm of body temperature, timing of the onset of melatonin secretion, and the relationship between these. Results Neither intervention showed any significant effect on any of the principal symptoms or on general measures of physical or mental health. Compared with placebo, neither body temperature rhythm nor onset of melatonin secretion was significantly altered by either treatment, except for a slight advance of temperature phase (0·8 h; P = 0·04) with phototherapy. Conclusion Melatonin and bright-light phototherapy appear ineffective in CFS. Both treatments are being prescribed for CFS sufferers by medical and alternative practitioners. Their unregulated use should be prohibited unless, or until, clear benefits are convincingly demonstrated. [source] Hypothalamic,endocrine aspects in Huntington's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Åsa Petersén Abstract Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic,pituitary,adrenal axis occurs as well as pancreatic ,-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions. [source] Daytime variations of interleukin-1, in gingival crevicular fluidEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 1 2008Angela Bergmann Interleukin-1, (IL-1,) is an important parameter in periodontal research because of its role in inflammation and bone resorption. One measure used to assess local IL-1, concentrations is analysis of its levels in gingival crevicular fluid (GCF). While studies on serum IL-1, concentrations indicate a circadian rhythm of this parameter, nothing is known about daytime variations of IL-1, in GCF. The present study thus aimed to analyse such variations. Daytime variations of GCF-IL-1, between 08:00 and 22:00 h were assessed, with a time resolution of 2 h, in 28 periodontally healthy subjects. The data showed a significant variation throughout the day, with the lowest concentrations and total amounts in the morning and the highest in the evening. The effect sizes of comparisons between morning and evening samples were medium to high and corresponded in magnitude to those reported in other published research comparing healthy sites and those affected by periodontitis. The smallest daytime variations were found to occur between 12:00 h and 18:00 h. It is concluded that daytime variations in GCF-IL-1, are large enough to be able to mimic or mask differences caused by clinical factors. [source] Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulationFEBS JOURNAL, Issue 22 2004Interaction with BMAL The basic helix-loop-helix transcription factor DEC1 is expressed in a circadian manner in the suprachiasmatic nucleus where it seems to play a role in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoter. The interaction of DEC1 with BMAL1 has been suggested as one of the molecular mechanisms of the suppression [Honma, S., Kawamoto, T., Takagi, Y., Fujimoto, K., Sato, F., Noshiro, M., Kato, Y. & Honma, K. (2002) Nature419, 841,844]. Deletion analysis of DEC1 demonstrated that its N-terminal region, which includes the basic helix-loop-helix domain, was essential for both the suppressive activity and the interaction with BMAL1, as DEC1 lacking the basic region did not show any suppression or interaction. Furthermore, we found that Arg65 in the basic region, which is conserved among group B basic helix-loop-helix proteins, was responsible for the suppression, for the interaction with BMAL1 and for its binding to CACGTG E-boxes. However, substitution of His57 for Ala significantly reduced the E-box binding activity of DEC1, although it did not affect the interaction with BMAL1 or suppression of CLOCK/BMAL1-induced transcription. On the other hand, the basic region-deleted DEC1 acted in a dominant-negative manner for DEC1 activity, indicating that the basic region was not required for homodimer formation of DEC1. Moreover, mutant DEC1 also counteracted DEC2-mediated suppressive activity in a dominant-negative manner. The heterodimer formation of DEC1 and DEC2 was confirmed by pull-down assay. These findings suggest that the basic region of DEC1 participates in the transcriptional regulation through a protein,protein interaction with BMAL1 and DNA binding to the E-box. [source] Circadian rhythm of aromatic l -amino acid decarboxylase in the rat suprachiasmatic nucleus: gene expression and decarboxylating activity in clock oscillating cellsGENES TO CELLS, Issue 5 2002Yoshiki Ishida Background: Aromatic l -amino acid decarboxylase (AADC) is the enzyme responsible for the decarboxylation step in both the catecholamine and indoleamine synthetic pathways. In the brain, however, a group of AADC containing neurones is found outside the classical monoaminergic cell groups. Since such non-monoaminergic AADC is expressed abundantly in the suprachiasmatic nucleus (SCN), the mammalian circadian centre, we characterized the role of AADC in circadian oscillation. Results : AADC gene expression was observed in neurones of the dorsomedial subdivision of the SCN and its dorsal continuant in the anterior hypothalamic area. These AADC neurones could uptake exogenously applied L-DOPA and formed dopamine. AADC was co-expressed with vasopressin and the clock gene Per1 in the neurones of the SCN. Circadian gene expression of AADC was observed with a peak at subjective day and a trough at subjective night. The circadian rhythm of AADC enzyme activity in the SCN reflects the expression of the gene. Conclusions: Non-monoaminergic AADC in the SCN is expressed in clock oscillating cells, and the decarboxylating activity of master clock cells are under the control of the circadian rhythm. [source] Effect on Sleep of Posterior Hypothalamus Stimulation in Cluster HeadacheHEADACHE, Issue 7 2007Roberto Vetrugno MD Objective.,To evaluate the structure and quality of sleep and the circadian rhythm of body core temperature (BcT°) in patients with drug-resistant chronic cluster headache (CH) before and during deep brain stimulation (DBS) of the posterior hypothalamus. Background.,Chronic CH is a severe primary headache and frequently associated with disturbances in sleep. Posterior hypothalamus DBS is performed as an effective treatment of drug-resistant chronic CH. The effects of posterior hypothalamus DBS on sleep and the circadian rhythm of BcT° are unknown. Methods.,Three male patients with chronic drug-resistant CH underwent 48-hour consecutive polysomnography (PSG) by means of the VITAPORT® system with determination of BcT° by means of a rectal probe. Recordings were done before electrode implantation in the posterior hypothalamus and after optimized DBS of posterior hypothalamus. Results.,Before electrode implantation PSG showed nocturnal CH attacks, reduced sleep efficiency, fragmented sleep and increased periodic limb movements in sleep (PLMS). During DBS nocturnal CH attacks were abolished and sleep efficiency and PLMS improved. BcT° circadian rhythm was normal both before and during DBS. Conclusions.,Our data show that DBS of posterior hypothalamus in drug-resistant chronic CH is effective in curtailing nocturnal CH attacks, and is associated with improved sleep structure and quality. Chronic CH displays a normal circadian rhythm of BcT°, unchanged during hypothalamic DBS. [source] ,Suicide' of crickets harbouring hairworms: a proteomics investigationINSECT MOLECULAR BIOLOGY, Issue 6 2006D. G. Biron Abstract Despite increasing evidence of host phenotypic manipulation by parasites, the underlying mechanisms causing infected hosts to act in ways that benefit the parasite remain enigmatic in most cases. Here, we used proteomics tools to identify the biochemical alterations that occur in the head of the cricket Nemobius sylvestris when it is driven to water by the hairworm Paragordius tricuspidatus. We characterized host and parasite proteomes during the expression of the water-seeking behaviour. We found that the parasite produces molecules from the Wnt family that may act directly on the development of the central nervous system (CNS). In the head of manipulated cricket, we found differential expression of proteins specifically linked to neurogenesis, circadian rhythm and neurotransmitter activities. We also detected proteins for which the function(s) are still unknown. This proteomics study on the biochemical pathways altered by hairworms has also allowed us to tackle questions of physiological and molecular convergence in the mechanism(s) causing the alteration of orthoptera behaviour. The two hairworm species produce effective molecules acting directly on the CNS of their orthoptera hosts. [source] Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non-Hodgkin's lymphomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Yong Zhu Abstract Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51,0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47,0.80, p ,, 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation. © 2006 Wiley-Liss, Inc. [source] The normal circadian pattern of blood pressure: implications for treatmentINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2004J. Redon Summary Blood pressure fluctuates over 24 h following a circadian rhythm that reaches a peak in the morning shortly after awakening. The onset of many acute cardiovascular and cerebrovascular events shows a synchronous cyclical pattern, with the highest incidence of morbidity and mortality in the early morning hours. Strong, although circumstantial, evidence suggests that the early morning surge in blood pressure may contribute to the onset of acute cardiovascular episodes. Sustained blood pressure control that blunts the early morning blood pressure surge may help to reduce the incidence of these events. Antihypertensive agents are needed that provide smooth and sustained blood pressure control for the full 24 h, including the risky early morning hours. The angiotensin II receptor blocker telmisartan given once daily, because of its long half-life and mechanism of action, is likely to confer benefit in terms of 24-h blood pressure control and may reduce cardiovascular risk at the time of greatest patient vulnerability. [source] Nocturia in older people: A review of causes, consequences, assessment and managementINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2004A. Ali Summary Nocturia is common in older people and it may be bothersome for both patients and carers. It is most commonly related to bladder storage difficulties and nocturnal polyuria. The former results most frequently from an uninhibited overactive bladder. The latter occurs as a consequence of age-associated changes in the circadian rhythm of urine excretion. The management of an overactive bladder includes both behavioural and drug treatment. The management options for nocturnal polyuria include an afternoon diuretic and desmopressin, but caution is required, particularly with the latter, as it can cause significant hyponatraemia. [source] Circadian phase entrainment via nonlinear model predictive controlINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 17 2007N. Bagheri Abstract A nonlinear model predictive control algorithm is developed to investigate the phase-resetting properties of robust nonlinear biological oscillators; in particular, those of the circadian rhythm. This pacemaker is an autonomous biochemical oscillator with a free-running period close to 24 h. Research in chronobiology indicates that light stimuli may delay or advance the phase of the oscillator, allowing it to synchronize physiological processes and entrain to the environment. In this paper, a closed-loop optimal phase tracking control algorithm is developed and applied to a mammalian circadian model. The integration of MPC-based light pulses, coupled with environmental light:dark cycles, allows the circadian system to recover phase differences within 1.5 days,a fraction of the natural open-loop simulated mammalian recovery time. Accelerated phase entrainment may alleviate disorders caused by circadian rhythms that are out of phase with the environment, and improve performance. Copyright © 2007 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||