scholarly journals Optimization of Dosing Schedule of Daily Inhalant Dexamethasone to Minimize Phase Shifting of Clock Gene Expression Rhythm in the Lungs of the Asthma Mouse Model

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3316-3326 ◽  
Author(s):  
Naomi Hayasaka ◽  
Tsuyoshi Yaita ◽  
Tomoyuki Kuwaki ◽  
Sato Honma ◽  
Ken-ichi Honma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Activity Rhythm ◽  
Phase Shifts ◽  
Time Of Day ◽  
Phase Shifting ◽  
Peak Time ◽  
Dosing Schedule ◽  
Clock Gene Expression

Glucocorticoid receptor agonists such as dexamethasone (DEXA) have been recommended for the treatment of asthma. An increased frequency of dosing with these drugs seems preferable for cases of severe or uncontrolled asthma. The purpose of this experiment was to find the appropriate dosing schedule (frequency and timing) for DEXA inhalation based on chronotherapeutic dosing to minimize phase shifts of clock function in the lungs of the ovalbumin-treated asthmatic mouse. The daily rhythm of clock gene expression was similar between control and ovalbumin-treated mice. Acute inhalation of DEXA significantly increased mPer1 gene expression in the lungs but not the liver of mice. Daily exposure of DEXA at zeitgeber time 0 (lights on) or at zeitgeber time 18 (6 h after lights off) for 6 d caused a phase advance or phase delay of bioluminescence rhythm in the lungs, respectively, similar to light-induced phase shifts in locomotor activity rhythm. Daily zeitgeber time 0 exposure to DEXA attenuated the expression level of the mClca3 gene, which is associated with mucus overproduction, and there was a phase-advancing peak time of the mClca3 rhythm. The present results denote the importance of selecting the most appropriate time of day for nebulizer administration of DEXA to minimize adverse effects such as the phase shifting of clock function in asthmatic lungs. This is the first report of a successful protocol that could obtain phase shifts of clock gene expression rhythm in isolated peripheral organs in vivo.

scholarly journals Reciprocal Regulation of Brain and Muscle Arnt-Like Protein 1 and Peroxisome Proliferator-Activated Receptor α Defines a Novel Positive Feedback Loop in the Rodent Liver Circadian Clock

2006 ◽  
Vol 20 (8) ◽  
pp. 1715-1727 ◽  
Author(s):  
Laurence Canaple ◽  
Juliette Rambaud ◽  
Ouria Dkhissi-Benyahya ◽  
Béatrice Rayet ◽  
Nguan Soon Tan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Rhythm ◽  
Feedback Loop ◽  
Clock Gene ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Reciprocal Regulation ◽  
Clock Gene Expression ◽  
Regulatory Feedback Loop

Abstract Recent evidence has emerged that peroxisome proliferator-activated receptor α (PPARα), which is largely involved in lipid metabolism, can play an important role in connecting circadian biology and metabolism. In the present study, we investigated the mechanisms by which PPARα influences the pacemakers acting in the central clock located in the suprachiasmatic nucleus and in the peripheral oscillator of the liver. We demonstrate that PPARα plays a specific role in the peripheral circadian control because it is required to maintain the circadian rhythm of the master clock gene brain and muscle Arnt-like protein 1 (bmal1) in vivo. This regulation occurs via a direct binding of PPARα on a potential PPARα response element located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPARα gene expression. We further demonstrate that fenofibrate induces circadian rhythm of clock gene expression in cell culture and up-regulates hepatic bmal1 in vivo. Together, these results provide evidence for an additional regulatory feedback loop involving BMAL1 and PPARα in peripheral clocks.

Abstract P639: Attenuation of Renal Inner Medullary Circadian Clock Gene Expression in Response to High Salt Intake is Dependent on the Endothelin B Receptor

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Joshua S Speed ◽  
Kelly A Hyndman ◽  
Malgorzata Kasztan ◽  
Jermaine G Johnston ◽  
Martin E Young ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Salt Intake ◽  
Time Of Day ◽  
High Salt ◽  
Circadian Clock Gene ◽  
Clock Gene Expression ◽  
High Salt Intake ◽  
Renal Inner Medulla

Our lab has recently shown that ETB deficient (ETB def) rats have a time of day dependent impairment in their ability to excrete a Na+ load. These observations suggest an interaction between renal ETB receptors and circadian mechanisms that regulate renal tubular Na+ transport and excretion. Given that knockout of the circadian clock gene Bmal1 reduces blood pressure in mice, we hypothesized that a high salt intake impairs the clock mechanism in the renal inner medulla in an ETB dependent manner. Transgenic control (Tg con) or ETB def rats were fed normal (NS, 0.8% NaCl) or high (HS, 4% NaCl) salt for two weeks. In one group, rats were euthanized every 4 hours beginning at zeitgeber time 0 (lights on) for tissue collection (and subsequent assessment of circadian clock genes), while in a second group of rats urine was collected in 12-hour intervals (active vs. inactive). Consistent with our hypothesis, we observed that HS abolished the normal oscillation in Bmal1 expression in the renal inner medulla of Tg con rats, and effect not observed in ETB def rats. Interestingly, renal production of ET-1, was significantly higher during the active period vs. inactive period in both NS (3.6±1.1 vs. 0.8±0.2 pg/12hr respectively) and HS (9.2±4.1 vs. 1.6±0.3 pg/12hr respectively) fed Tg con rats. There was no time-of-day-dependent difference in ET-1 excretion in ETB def rats on NS (6.6±2.2 vs. 4.6±1.7 pg/12hr respectively), although this pattern was restored in ETB def rats fed HS (2.2±1.0 vs. 9.2±2.5 pg/12hr inactive vs. active). Taken together, these data indicate that an increase in renal ET-1/ETB activation in response to HS modulates inner medullary clock gene expression to promote renal Na+ excretion.

Different mechanisms of adjustment to a change of the photoperiod in the suprachiasmatic and liver circadian clocks

2010 ◽  
Vol 298 (4) ◽  
pp. R959-R971 ◽  
Author(s):  
Serhiy Sosniyenko ◽  
Daniela Parkanová ◽  
Helena Illnerová ◽  
Martin Sládek ◽  
Alena Sumová
Keyword(s):  
Gene Expression ◽  
Locomotor Activity ◽  
Clock Gene ◽  
Activity Rhythm ◽  
Locomotor Activity Rhythm ◽  
Clock Gene Expression ◽  
Activity Onset ◽  
The Individual ◽  
Long Photoperiod ◽  
Short Days

Changes in photoperiod modulate the circadian system, affecting the function of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The aim of the present study was to elucidate the dynamics of adjustment to a change of a long photoperiod with 18 h of light to a short photoperiod with 6 h of light of clock gene expression rhythms in the mouse SCN and in the peripheral clock in the liver, as well as of the locomotor activity rhythm. Three, five, and thirteen days after the photoperiod change, daily profiles of Per1, Per2, and Rev-erbα expression in the rostral, middle, and caudal parts of the SCN and of Per2 and Rev-erbα in the liver were determined by in situ hybridization and real-time RT-PCR, respectively. The clock gene expression rhythms in the different SCN regions, desynchronized under the long photoperiod, attained synchrony gradually following the transition from long to short days, mostly via advancing the expression decline. The photoperiodic modulation of the SCN was due not only to the degree of synchrony among the SCN regions but also to different waveforms of the rhythms in the individual SCN parts. The locomotor activity rhythm adjusted gradually to short days by advancing the activity onset, and the liver rhythms adjusted by advancing the Rev-erbα expression rise and Per2 decline. These data indicate different mechanisms of adjustment to a change of the photoperiod in the central SCN clock and the peripheral liver clock.

scholarly journals In vivo endotoxin synchronizes and suppresses clock gene expression in human peripheral blood leukocytes*

2010 ◽  
Vol 38 (3) ◽  
pp. 751-758 ◽  
Author(s):  
Beatrice Haimovich ◽  
Jacqueline Calvano ◽  
Adrian D. Haimovich ◽  
Steve E. Calvano ◽  
Susette M. Coyle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Clock Gene ◽  
Human Peripheral Blood ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Clock Gene Expression

scholarly journals Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1522-1534 ◽  
Author(s):  
Elizabeth R. Woodruff ◽  
Lauren E. Chun ◽  
Laura R. Hinds ◽  
Robert L. Spencer
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Clock Gene ◽  
Expression Patterns ◽  
Time Of Day ◽  
Male Rat ◽  
Mrna Levels ◽  
Diurnal Pattern ◽  
Peripheral Tissues ◽  
Clock Gene Expression

Abstract Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation.

scholarly journals The Circadian Oscillator of the Cerebellum: Triiodothyronine Regulates Clock Gene Expression in Granule Cells in vitro and in the Cerebellum of Neonatal Rats in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Tenna Bering ◽  
Henrik Hertz ◽  
Martin Fredensborg Rath
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Granule Cells ◽  
Clock Genes ◽  
Circadian Oscillator ◽  
Neonatal Rats ◽  
Clock Gene Expression ◽  
Mixed Gender

The central circadian clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, but an SCN-dependent molecular circadian oscillator is present in the cerebellar cortex. Recent findings suggest that circadian release of corticosterone is capable of driving the circadian oscillator of the rat cerebellum. To determine if additional neuroendocrine signals act to shape cerebellar clock gene expression, we here tested the role of the thyroid hormone triiodothyronine (T3) in regulation of the cerebellar circadian oscillator. In cultured cerebellar granule cells from mixed-gender neonatal rats, T3 treatment affected transcript levels of the clock genes Per2, Arntl, Nr1d1, and Dbp, suggesting that T3 acts directly on granule cells to control the circadian oscillator. We then used two different in vivo protocols to test the role of T3 in adult female rats: Firstly, a single injection of T3 did not influence clock gene expression in the cerebellum. Secondly, we established a surgical rat model combining SCN lesion with a programmable micropump infusing circadian physiological levels of T3; however, rhythmic infusion of T3 did not reestablish differential clock gene expression between day and night in SCN lesioned rats. To test if the effects of T3 observed in vitro were related to the developmental stage, acute injections of T3 were performed in mixed-gender neonatal rats in vivo; this procedure significantly affected cerebellar expression of the clock genes Per1, Per2, Nr1d1, and Dbp. Developmental comparisons showed rhythmic expression of all clock genes analyzed in the cerebellum of adult rats only, whereas T3 responsiveness was limited to neonatal animals. Thus, T3 shapes cerebellar clock gene profiles in early postnatal stages, but it does not represent a systemic circadian regulatory mechanism linking the SCN to the cerebellum throughout life.

Sign in / Sign up

Export Citation Format

Share Document