Journal of Circadian Rhythms最新文献

Human circadian rhythmicity is driven by a circadian clock comprised of two distinct components: the central clock, located in the suprachiasmatic nucleus (SCN) within the hypothalamus, and the peripheral clocks, located in almost all tissues and organ systems in the body. Entrainment, or alignment, of circadian rhythmicity is dependent upon time of day and can occur through environmental influences such as light cues and physical activity exerted on skeletal muscle. Entrainment of the circadian clock through exercise has been reported to improve health by reducing risk of conditions such as cardiovascular disease (CVD), but further research is still needed. The purpose of this review is to discuss the effects exercise has on the regulation of circadian rhythmicity, specifically with respect to CVD risk factors - including hormonal levels, sleep/wake cycles, blood pressure, and heart rate. Additionally, the impact of exercise-induced circadian entrainment is discussed relative to hormone regulation, nocturnal blood pressure dipping, post-exercise hypotension, and overall cardiovascular health.

In mammals, circadian rhythmicity is sustained via a transcriptional/translational feedback loop referred to as the canonical molecular circadian clock. Circadian rhythm is absent in undifferentiated embryonic stem cells; it begins only after differentiation. We used pluripotent P19 embryonal carcinoma stem cells to check the biological clock before and after differentiation into neurons using retinoic acid. We show that the central clock genes ARNTL (Bmal), Per2 and Per3, and the peripheral clock genes Rev-erb-α and ROR-α, oscillate before and after differentiation, as does the expression of the neuronal differentiation markers Hes5, β-3-tubulin (Tubb3) and Stra13, but not Neurod1. Furthermore, the known clock-modulating compounds ERK, EGFR, Pi3K, p38, DNA methylation and Sirtiun inhibitors, in addition to Rev-erb-α ligands, modulate the expression of central and peripheral clock genes. Interestingly Sirtinol, Sirt1 and Sirt2 inhibitors had the greatest significant effect on the expression of clock genes, and increased Hes5 and Tubb3 expression during neuronal differentiation. Our findings reveal a new frontier of circadian clock research in stem cells: contrary to what has been published previously, we have shown the clock to be functional and to oscillate, even in undifferentiated stem cells. Modulating the expression of clock genes using small molecules could affect stem cell differentiation.

The pathogenesis and therapeutics of depression are linked to the operation of the circadian system. Here, we studied the chronopharmacological action of a tricyclic antidepressant, imipramine. Male adult Wistar-Hannover rats were administered imipramine acutely or chronically in the morning or in the evening. The antidepressant action of imipramine was analyzed using the forced swim test (FST). A single dose of imipramine (30 mg/kg) in the morning, but not in the evening, reduced immobility and increased climbing in the FST. The plasma concentrations of imipramine and its metabolite, desipramine, were slightly higher in the morning than in the evening, which might explain the dosing time-dependent action of imipramine. Next, we analyzed the effect of chronic imipramine treatment. Rats received imipramine in the morning or in the evening for 2 weeks. The morning treatment resulted in larger effects in the FST than the evening treatment, and was effective at a dose that was ineffective when administered acutely. The levels of brain α-adrenergic receptors tended to decrease after chronic imipramine treatment. Imipramine might interact with noradrenergic neurons, and this interaction might chronically alter receptor expression. This alteration seemed greater in the morning than in the evening, which might explain the dosing time-dependent action of imipramine.

In recent years, there has been an increased prevalence of type 2 diabetes mellitus (T2DM) and depression across the world. This growing public health problem has produced an increasing socioeconomic burden to the populations of all affected countries. Despite an awareness by public health officials and medical researchers of the costs associated with these diseases, there still remain many aspects of how they develop that are not understood. In this article, we propose that the circadian clock could be a factor that coordinates both the neurobehavioral and metabolic processes that underlie depression and T2DM. We propose further that this perspective, one which emphasizes the regulatory effects of clock gene activity, may provide insights into how T2DM and depression interact with one another, and may thus open a new pathway for managing and treating these disorders.

Introduction: A two-shift work schedule with different rotations is common among firefighters in Iranian petrochemical companies. This study compared salivary melatonin and sleepiness on the last night before turning to day shift at 19:00, 23:00, 3:00, and 7:00 among petrochemical firefighters (PFFs) working seven and four consecutive night shifts.

Methods: Sixty four PFFs working in the petrochemical industry were selected. To measure melatonin, saliva samples were taken, whereas the KSS index was used to assess sleepiness. Chi-square and independent samples t-test were carried out to analyze the data, and generalized linear model (GLM) was employed to determine the effect of confounding factors such as lighting and caffeine.

Results: The levels of melatonin at 3:00 and 7:00, and the overall changes during the shift in the two shift patterns under the study were different (P < 0.05). Sleepiness was significantly different only at 3:00 in the two studied shift patterns, while the effects of lighting and caffeine on melatonin changes were not significant (P > 0.05).

Conclusion: It seems that a slow shift rotation is better because it reduces the secretion of melatonin (hence reducing sleepiness during the night) and changes the peak of melatonin secretion to the daytime, which is a sign of adaptation.

The purpose of the study was to investigate seasonal variation in mood and behavior among a group of office workers in Sweden (56°N). Thirty subjects participated in this longitudinal study. The subjects kept a weekly log that included questionnaires for ratings of psychological wellbeing and daily sleep-activity diaries where they also noted time spent outdoors. The lighting conditions in the offices were subjectively evaluated during one day, five times over the year. There was a seasonal variation in positive affect and in sleep-activity behavior. Across the year, there was a large variation in the total time spent outdoors in daylight. The subjects reported seasonal variation concerning the pleasantness, variation and strength of the light in the offices and regarding the visibility in the rooms. Finally, the subjects spent most of their time indoors, relying on artificial lighting, which demonstrates the importance of the lighting quality in indoor environments.

Affective disorders impact women's health, with a lifetime prevalence of over twelve per cent. They have been correlated with reproductive cycle factors, under the regulation of hormonal circadian rhythms. In affective disorders, circadian rhythms may become desynchronized. The circadian rhythms of cortisol and estradiol may play a role in affective disorders. The purpose of this study was to explore the temporal relationship between the rhythms of cortisol and estradiol and its relationship to affect. It was hypothesized that a cortisol-estradiol phase difference (PD) exists that correlates with optimal affect. A small scale, comparative, correlational design was used to test the hypothesis. Twenty-three women were recruited from an urban university. Salivary samples were collected over a twenty-four-hour period and fitted to a cosinor model. Subjective measures of affect were collected. Relationships between the cortisol-estradiol PD and affect were evaluated using a second-degree polynomial equation. Results demonstrated a significant correlation in affect measures (p < 0.05). An optimal PD was identified for affect to be 3.6 hours. The phase relationship between cortisol and estradiol may play a role in the development of alterations in affective disorders.

The expression of clock genes ARNTL2, NPAS2 and DEC2 are disturbed in rheumatoid arthritis, an autoimmune disease with circadian variation of symptoms. We have shown that TNF is a potent inducer of these genes. We investigated the regulation of ARNTL2 and NPAS2 by TNF and elucidated their effect on other clock gene expressions. Additionally, we studied the effect of DEC1 and DEC2 on ARNTL, ARNTL2 and NPAS2. Cultured primary human fibroblasts were stimulated with TNF and the effects on ARNTL2 and NPAS2 were studied with RT-qPCR and immunofluorescence staining. The role of NF-κB was analyzed using IKK-2 inhibitor IMD-0354. TNF promoted ARNTL2 localization into the nuclei. Similar to DEC2, the effects of TNF on ARNTL2 and NPAS2 expressions were mediated via NF-κB. Cloned ARNTL, ARNTL2, NPAS2, DEC1 and DEC2 were transfected into HEK293. The ARNTL2/NPAS2 dimer was a weaker inducer of PER3 and DBP than ARNTL/NPAS2. ARNTL2 and NPAS2 are regulated by TNF via the same mechanism as DEC2. Compared to their paralogs they have unique effects on other circadian components. Our data suggest that these genes are responsible, at least in fibroblasts, for the accurate adaptation of circadian timekeeping in individual cells during inflammation.

Several studies carried out on humans and other mammals show that the temporal organisation of haematological parameters in the blood exhibit daily rhythms; however, such studies have been rare in poultry reared under a natural photoperiod. The present study investigated the occurrence of daily rhythms in blood parameters of broiler chickens kept under tropical climatic conditions. Ten 6-7-week-old broiler chickens served as subjects of the study. They were kept in standard individual cages under natural light-dark cycle and given access to feed and water ad libitum. Two milliliters of blood was collected from each bird via intravenous cannulae inserted into the wing vein. The blood samples were collected every 4 h over a 24-h period, starting from 09:00 h on the first day and completed at 09:00 h on the second day. The blood samples were analysed for erythrocyte, total and differential leucocyte counts. A trigonometric statistical model according to the single cosinor procedure was used to describe the periodic parameters and their acrophases, and ANOVA was used to determine significant differences. The results demonstrated the existence of daily rhythms in packed cell volume, haemoglobin, white blood cell, red blood cell, heterophil, lymphocyte, eosinophil and monocyte counts, while total protein displayed no rhythm. The characteristics of the haematological parameters showed that the acrophases were restricted to the light phase of the light/dark cycle, precisely at 09:00 h, except for eosinophil and heterophil counts, which had acrophases at 21:00 h. The amplitudes of the blood parameters varied, with packed cell volume having the greatest amplitude of 4.2 ± 0.5, closely followed by lymphocyte (3.4 ± 0.5) and heterophil (2.3 ± 0.2) counts. In conclusion, the results of the study demonstrated the existence of daily rhythms with diurnal acrophases in blood parameters of broiler chickens kept under natural photoperiods and tropical conditions.

Previous work from our laboratory has shown that a measure of attention to emotionally-charged stimuli, the late positive potential (LPP) event related potential (ERP), distinguished neutral from emotional pictures on a baseline day, but not after sleep deprivation. Here we sought to extend these findings and address the uncertainty about the effect of time-of-day on emotion processing by testing a morning group (8:00-10:00 a.m., n = 30) and an evening group (8:00-10:00 p.m., n = 30). We also examined the extent of diurnal changes in cortisol related to the emotion processing task. Results from this study mirrored those found after one night of sleep deprivation. Compared to the morning group, the LPP generated by the evening group (who had a greater homeostatic sleep drive) did not distinguish neutral from emotionally-charged stimuli. New to this study, we also found that there was a time-of-day effect on positive, but not negative pictures. While, as expected, cortisol levels were higher in the morning relative to the evening group, there was no relationship between cortisol and the LPP ERP emotion measure. In addition, neither time-of-day preference nor sleep quality was related to the LPP measure. These findings show that, similar to what occurs after sleep deprivation, increased sleep pressure throughout the day interferes with attention processing to emotional stimuli.