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Circadian Regulation (circadian + regulation)
Selected AbstractsEffects 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] PRECLINICAL STUDY: Circadian regulation of central ethanol sensitivity by the mPer2 geneADDICTION BIOLOGY, Issue 3 2009Stéphanie Perreau-Lenz ABSTRACT The effect of alcohol is known to vary with the time of the day. Although initially it was suggested that this phenomenon may be due to diurnal differences in ethanol metabolism, more recent studies were contradicting. In the present study, we therefore first set out in assessing the diurnal variations in ethanol sensitivity in mice analysing, concurrently, ethanol elimination rates. Ethanol-induced (3.5 g/kg; intraperitoneal) loss of righting reflex (LORR) duration was thus determined at several Zeitgeber time (ZT) points (ZT5, 11, 17 and 23) in C57BL/6N mice. In parallel, the corresponding ethanol elimination rates were also assessed. The results display the existence of a distinct diurnal rhythm in LORR duration peaking at ZT11, whereas no differences could be observed regarding the elimination rates of alcohol. Successively, we checked the involvement of the clock genes mPer1 and mPer2 in conveying this rhythm in sensitivity, testing LORR and hypothermia at the peak and trough previously observed (ZT5 and ZT11). Per1Brdm1 mice demonstrate a similar diurnal pattern as control mice, with enhanced LORR durations at ZT11. In contrast, Per2Brdm1 mice did not exhibit a temporal variation to the depressant effects of ethanol with respect to LORR, revealing a constant high sensitivity to ethanol. The present study reveals a central role of the mPer2 gene in inhibiting alcohol sensitivity at the beginning of the inactive phase. [source] Developmental changes in baseline cortisol activity in early childhood: Relations with napping and effortful controlDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004Sarah E. Watamura Abstract Development of the hypothalamic,pituitary,adrenocortical (HPA) axis was examined using salivary cortisol levels assessed at wake-up, midmorning, midafternoon, and bedtime in 77 children aged 12, 18, 24, 30, and 36 months, in a cross-sectional design. Hierarchical linear modeling (HLM) analyses were used to characterize cortisol production across the day and to examine age-related differences. Using area(s) under the curve (AUC), cortisol levels were higher among the 12-, 18-, and 24-month children than among the 30- and 36-month children. For all five age groups, cortisol levels were highest at wake-up and lowest at bedtime. Significant decreases were noted between wake-up and midmorning, and between midafternoon and bedtime. Unlike adults, midafternoon cortisol levels were not significantly lower than midmorning levels. Over this age period, children napped less and scored increasingly higher on parent reports of effortful control. Among the 30- and 36-month children, shorter naps were associated with more adultlike decreases in cortisol levels from midmorning to midafternoon. Considering all of the age groups together, effortful control correlated negatively with cortisol levels after controlling for age. These results suggest that circadian regulation of the HPA axis continues to mature into the third year in humans, and that its maturation corresponds to aspects of behavioral development. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 45: 125-133, 2004. [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] Clock-dependent and independent transcriptional control of the two isoforms from the mouse Ror,geneGENES TO CELLS, Issue 12 2008Valérie Mongrain Accumulating evidence indicate that molecular mechanisms generating circadian rhythms display some degree of tissue-specificity. More specifically, distinct patterns of expression for nuclear receptors of the ROR family indicate that the transcriptional control of the clock gene Bmal1 differs among tissues. This study aims to investigate the expression of Ror,isoforms (Ror, and Ror,t) and characterize the molecular mechanisms underlying their tissue-specific expression. The expression of Ror, isoforms was assessed in mouse liver, muscle, thymus and testis throughout 24 h using quantitative RT-PCR. Although the expression of Ror, was rhythmic in the liver and thymus, it was constitutively expressed in muscle and testis. In contrast, the expression of Ror,t was constitutive in all four tissues. Furthermore, rhythmic expression of Ror, was impaired in Clock mutant mice whereas the mutation had no effect on Ror,t expression. In line with these findings, luciferase assays revealed that transcription of the Ror, promoter is clock-controlled whereas that of Ror,t promoter is essentially clock-independent. Our results provide insights into the molecular mechanisms that lead to differential expression of Ror, and Ror,t and are suggestive of a framework that might account for tissue-specific circadian regulation. [source] Alterations in Circadian Rhythm Phase Shifting Ability in Rats Following Ethanol Exposure During the Third Trimester Brain Growth SpurtALCOHOLISM, Issue 5 2006Hiromi Sakata-Haga Background: Disruptions in sleep and feeding rhythms are among the consequences of prenatal alcohol exposure. Previously, we reported that ethanol exposure during the second trimester equivalent in rats produces long-lasting impairments in circadian system functioning. In the present study, we examined the effects of ethanol exposure during the third trimester equivalent brain growth spurt on the development of the circadian clock system. Methods: Sprague,Dawley male rat pups were exposed to 6.0 g/kg/d ethanol via an artificial rearing procedure on postnatal days (PD) 4 through 9 (EtOH). An artificially reared gastrostomized control group and a normally reared suckle control group were also included. At 10 to 12 weeks of age, wheel-running behavior was measured continuously under a 12-hour/12-hour light/dark (LD) cycle. Thereafter, subjects were exposed to a 6-hour phase delay of the LD cycle, and the ability to adjust to the new LD cycle was evaluated. Results: Before the phase delay, onset time of activity and acrophases of activity in all 3 groups were not significantly different from one another. After the 6-hour LD cycle delay, EtOH subjects were slower to adapt to the new cycle compared with both control groups, as measured by both activity onset and acrophase. Throughout the experiment, activity levels of EtOH subjects tended to be higher compared to both controls. Conclusions: These data demonstrate that ethanol exposure during the third trimester disrupts the ability to synchronize circadian rhythm to light cues. Disruptions in circadian regulation may cause abnormal behavioral rhythmicity, such as disrupted sleep and feeding patterns, as seen in individuals prenatally exposed to ethanol. [source] The Neurospora circadian clock regulates a transcription factor that controls rhythmic expression of the output eas(ccg-2) geneMOLECULAR MICROBIOLOGY, Issue 4 2001Deborah Bell-Pedersen The circadian clock provides a link between an organism's environment and its behaviour, temporally phasing the expression of genes in anticipation of daily environmental changes. Input pathways sense environmental information and interact with the clock to synchronize it to external cycles, and output pathways read out from the clock to impart temporal control on downstream targets. Very little is known about the regulation of outputs from the clock. In Neurospora crassa, the circadian clock transcriptionally regulates expression of the clock-controlled genes, including the well-characterized eas(ccg-2) gene. Dissection of the eas(ccg-2) gene promoter previously localized a 68 bp sequence containing an activating clock element (ACE) that is both necessary and sufficient for rhythmic activation of transcription by the circadian clock. Using electrophoretic mobility shift assays (EMSAs), we have identified light-regulated nuclear protein factors that bind specifically to the ACE in a time-of-day-dependent fashion, consistent with their role in circadian regulation of expression of eas(ccg-2). Nucleotides in the ACE that interact with the protein factors were determined using interference binding assays, and deletion of the core interacting sequences affected, but did not completely eliminate, rhythmic accumulation of eas(ccg-2) mRNA in vivo, whereas deletion of the entire ACE abolished the rhythm. These data indicate that redundant binding sites for the protein factors that promote eas(ccg-2) rhythms exist within the 68 bp ACE. The ACE binding complexes formed using protein extracts from cells with lesions in central components of the Neurospora circadian clock were identical to those formed with extracts from wild-type cells, indicating that other proteins directly control eas(ccg-2) rhythmic expression. These data suggest that the Neurospora crassa circadian clock regulates an unknown transcription factor, which in turn activates the expression of eas(ccg-2) at specific times of the day. [source] The Arabidopsis SPA1 gene is required for circadian clock function and photoperiodic floweringTHE PLANT JOURNAL, Issue 5 2006Masaki Ishikawa Summary Arabidopsis phytochrome A (phyA) regulates not only seed germination and seedling de-etiolation but also circadian rhythms and flowering time in adult plants. The SUPPRESSOR OF PHYA-105 (SPA1) acts as a negative regulator of phyA-mediated de-etiolation of young seedlings, but its roles in adult plants have not yet been described. Here, we show that SPA1 is involved in regulating circadian rhythms and flowering time in plants. Under constant light, the abundance of SPA1 protein exhibited circadian regulation, whereas under constant darkness, SPA1 protein levels remained unchanged. These results indicate that the SPA1 protein is controlled by the circadian clock and light signals. In addition, the spa1-3 mutation slightly shortened the circadian period of CCA1, TOC1/PRR1 and SPA1 transcript accumulation under constant light. Phenotypic analysis showed that the spa1-3 mutant flowers early under short-day (SD) but not long-day (LD) conditions. Consistent with this finding, transcripts encoding flowering locus T (FT), which promotes flowering, increased in spa1-3 under only SD conditions, although the CONSTANS (CO) transcript level was not affected under either SD nor LD conditions. Our results indicate that SPA1 not only negatively controls phyA-mediated signaling in seedlings, but also regulates circadian rhythms and flowering time in plants. [source] | |||||||||||||