Journal of Circadian Rhythms最新文献

Background: Expression of the clock family of genes in the suprachiasmatic nuclei (SCN) regulates the molecular control of circadian timing. Increasing evidence also implicates clock gene activity in the development of mood disorders. In particular, variation in the PER3 clock gene has been shown to influence diurnal preference and sleep homeostasis. However, there is not currently a clear association between PER3 polymorphisms and mood. This is possibly because the PER3 gene has been shown to influence homeostatic sleep drive, rather than circadian timing, and the PER3 gene may be behaviorally relevant only under chronic sleep loss conditions.

Methods: To test the association between PER3 allele status and impaired mood, a total of 205 healthy women were genotyped for PER3 allele status and responded to previously-validated psychological questionnaires surveying self-reported sleep habits (MEQ, PSQI) and mood. Our mood measures included two measures of short-term, transient mood (state anxiety and mood disturbance) and two measures of longer term, ongoing mood (trait anxiety and depressive symptomology).

Results: The PER3 genotype distribution was 88 (42.9%) for PER3(4/4), 98 (47.8%) for PER3(4/5), and 19 (9.3%) for PER3(5/5). Our sleep duration x genotype interaction analyses showed that, relative to longer allele carriers, PER3(4/4) genotypes were at greater risk for transient psychological effects (mood and state anxiety) when they reported reduced sleep durations.

Conclusion: Sleep duration plays a critical role in understanding the extent to which PER3 allele status relates to mood states.

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210-2340 h, (2) treadmill exercise alone from 2210-2340 h, or (3) bright light (2210-2340 h) followed by exercise from 0410-0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect.

Shift work is associated with both sleepiness and reduced performance. The aim of this study was to examine cognitive performance, sleepiness, and sleep quality among petrochemical control room shift workers. Sixty shift workers participated in this study. Cognitive performance was evaluated using a number of objective tests, including continuous performance test, n-back test, and simple reaction time test; sleepiness was measured using the subjective Karolinska Sleepiness Scale (KSS); and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. ANCOVA, t-test, and repeated-measures ANOVA were applied for statistical analyses, and the significance level was set at p < 0.05. All variables related to cognitive performance, except for omission error, significantly decreased at the end of both day and night shifts (p < 0.0001). There were also significant differences between the day and night shifts in terms of the variables of omission error (p < 0.027) and commission error (p < 0.036). A significant difference was also observed between daily and nightly trends of sleepiness (p < 0.0001) so that sleepiness was higher for the night shift. Participants had low sleep quality on both day and night shifts, and there were significant differences between the day and night shifts in terms of subjective sleep quality and quantity (p < 0.01). Long working hours per shift result in fatigue, irregularities in the circadian rhythm and the cycle of sleep, induced cognitive performance decline at the end of both day and night shifts, and increased sleepiness in night shift. It, thus, seems necessary to take ergonomic measures such as planning for more appropriate shift work and reducing working hours.

Background: Circadian rhythms are daily changes in our physiology and behavior that are manifested as patterns of brain wave activity, periodic hormone production, recurring cell regeneration, and other oscillatory biological activities. Their importance to human health is becoming apparent; they are deranged by shift work and jet-lag and in disparate conditions such as insomnia, sleep syndromes, coronary heart attacks, and depression, and are endogenous factors that contribute to cancer development and progression.

Discussion: As evidence of the circadian connection to human health has grown, so has the number of Americans experiencing disruption of circadian rhythms due to the demands of an industrialized society. Today, there is a growing work force that experiences night shift work and time-zone shifts shaping the demands on physicians to best meet the needs of patients exposed to chronic circadian disruptions. The diverse range of illness associated with altered rhythms suggests that physicians in various fields will see its impact in their patients. However, medical education, with an already full curriculum, struggles to address this issue.

Summary: Here, we emphasize the need for incorporating the topic of circadian rhythms in the medical curriculum and propose strategies to accomplish this goal.

Background: The increased risk of obesity among short sleepers is most likely explained by increased energy intake. However, food intake could not only be altered quantitavely but also qualitatively. Therefore, we performed a correlational analysis on self-reported food intake and sleep in 51 students from Maastricht and surroundings.

Results: Students that slept longer had a lower caloric intake: ρ = -0.378, p = 0.006, the amount of calories consumed per minute awake remaining relatively stable. However, sleep duration did not correlate with intake of percentage fat, saturated fat, carbohydrates or protein. Average energy intake during the reported breakfasts, lunches, dinners or snacks separately did also not correlate with total sleep time.

Conclusion: It seems that shorter sleep correlates with absolute caloric intake, but not with the intake of specific dietary components.

Background: Daily feeding and locomotion are interrelated behaviours. The time spent in feeding and rate of food intake depends on food availability. In low food condition, the birds would show intense movement (locomotion) for a longer time throughout the day however during abundant food supply they may chose higher activity and food intake in the morning and evening only. In the present study we hypothesized that in Spotted Munia (Lonchura punctulata), intermittent food availability during day would reallocate their interrelated behaviors, the feeding (food intake) and locomotor activity patterns.

Methods: Two groups of birds (N = 6 each) were kept individually in activity cages under 12L:12D. Group 1 (Control; C) had ad libitum food but group 2 (Treatment; T) had food for 6 hours only (2 h presence followed by 2 h absence; 2P:2A) during 12 hour light period. In the first week, group 2 received food with 'lights on' (TI; ZT 0-2, 4-6 and 8-10; where ZT 0= zeitgeber time 0, time of lights ON). In the following week, the food was given 2 hours after 'lights on' (TII; ZT 2-4, 6-8, 10-12). The food intake and locomotor activity under each condition were observed.

Results: The results showed that locomotor activity was induced during food deprivation and suppressed during food availability. Also the food deprivation led to increased food intake.

Conclusion: Our results suggest that intermittent food availability/deprivation reallocates the locomotor activity and food intake in Spotted Munia.

Background: Circadian rhythms play an integral role in human behavior, physiology and health. Individual differences in daily rhythms (chronotypes) can affect individual sleep-wake cycles, activity patterns and behavioral choices. Diurnal preference, the tendency towards morningness or eveningness among individuals, has been associated with interpersonal variation in circadian clock-related output measures, including body temperature, melatonin levels and clock gene mRNA in blood, oral mucosa, and dermal fibroblast cell cultures.

Methods: Here we report gene expression data from two principal clock genes sampled from hair follicle cells, a peripheral circadian clock. Hair follicle cells from fourteen individuals of extreme morning or evening chronotype were sampled at three time points. RNA was extracted and quantitative PCR assays were used to measure mRNA expression patterns of two clock genes, Per3 and Nr1d2.

Results: We found significant differences in clock gene expression over time between chronotype groups, independent of gender or age of participants. Extreme evening chronotypes have a delay in phase of circadian clock gene oscillation relative to extreme morning types. Variation in the molecular clockwork of chronotype groups represents nearly three-hour phase differences (Per3: 2.61 hours; Nr1d2: 3.08 hours, both: 2.86) in circadian oscillations of these clock genes.

Conclusions: The measurement of gene expression from hair follicles at three time points allows for a direct, efficient method of estimating phase shifts of a peripheral circadian clock in real-life conditions. The robust phase differences in temporal expression of clock genes associated with diurnal preferences provide the framework for further studies of the molecular mechanisms and gene-by-environment interactions underlying chronotype-specific behavioral phenomena, including social jetlag.

Background: Longitudinal or time-dependent activity data are useful to characterize the circadian activity patterns and to identify physical activity differences among multiple samples. Statistical methods designed to analyze multiple activity sample data are desired, and related software is needed to perform data analysis.

Methods: This paper introduces a functional data analysis (fda) approach to perform a functional analysis of variance (fANOVA) for longitudinal circadian activity count data and to investigate the association of covariates such as weight or body mass index (BMI) on physical activity. For multiple age group adolescent school girls, the fANOVA approach is developed to study and to characterize activity patterns. The fANOVA is applied to analyze the physical activity data of three grade adolescent girls (i.e., grades 10, 11, and 12) from the NEXT Generation Health Study 2009-2013. To test if there are activity differences among girls of the three grades, a functional version of the univariate F-statistic is used to analyze the data. To investigate if there is a longitudinal (or time-dependent activity count) difference between two samples, functional t-tests are utilized to test: (1) activity differences between grade pairs; (2) activity differences between low-BMI girls and high-BMI girls of the NEXT study.

Results: Statistically significant differences existed among the physical activity patterns for adolescent school girls in different grades. Girls in grade 10 tended to be less active than girls in grades 11 & 12 between 5:30 and 9:30. Significant differences in physical activity were detected between low-BMI and high-BMI groups from 8:00 to 11:30 for grade 10 girls, and low-BMI group girls in grade 10 tended to be more active.

Conclusions: The fda approach is useful in characterizing time-dependent patterns of actigraphy data. For two-sample data defined by weight or BMI values, fda can identify differences between the two time-dependent samples of activity data. Similarly, fda can identify differences among multiple physical activity time-dependent datasets. These analyses can be performed readily using the fda R program.

The mammalian circadian clock is composed of single-cell oscillators. Neurochemical and electrical signaling among these oscillators is important for the normal expression of circadian rhythms. Prokineticin 2 (PK2), encoding a cysteine-rich secreted protein, has been shown to be a critical signaling molecule for the regulation of circadian rhythms. PK2 expression in the suprachiasmatic nucleus (SCN) is highly rhythmic, peaking during the day and being essentially absent during the night. Mice with disrupted PK2 gene or its receptor PKR2 display greatly reduced rhythmicity of broad circadian parameters such as locomotor activity, body temperature and sleep/wake patterns. PK2 has been shown to increase the firing rate of SCN neurons, with unknown molecular mechanisms. Here we report that TRPV2, an ion channel belonging to the family of TRP, is co-expressed with PKR2 in the SCN neurons. Further, TRPV2 protein, but not TRPV2 mRNA, was shown to oscillate in the SCN in a PK2-dependent manner. Functional studies revealed that TRPV2 enhanced signaling of PKR2 in calcium mobilization or ion current conductance, likely via the increased trafficking of TRPV2 to the cell surface. Taken together, these results indicate that TRPV2 is likely part of the downstream signaling of PK2 in the regulation of the circadian rhythms.

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker. The pineal hormone melatonin is involved in the regulation of circadian phase. As a part of the circadian system, its synthesis and secretion is under SCN control. On the other hand, melatonin feeds back on the SCN to regulate its function. Melatonin has two specific windows of time at which it regulates SCN function, namely dusk and dawn. It has been suggested that melatonin exerts its effect on the SCN during that specific window of time via one or both of its specific receptors, MT1 or MT2. The hypothesis that the density of these receptors varies across the circadian cycle was tested. Using immunohistochemistry with receptor-specific antibodies, the localization and distribution of melatonin receptors MT1 and MT2 was studied in the SCN at different Zeitgeber times (ZT): ZT 11-13 (dusk), 23-01 (dawn), 5-7 (mid-day), and 17-19 (midnight). Our results show that MT1 receptor density significantly increased at dusk relative to dawn and midnight (p<0.01 and p<0.001 respectively). Although MT1 receptors were widespread in the SCN and parts of the optic chiasm at dusk, they were restricted to the SCN during the mid-day period. MT2 receptors were not detected in the SCN. Thus, we find that melatonin receptor MT1 density and distribution varies with circadian time. This creates a time window during which melatonin can affect the operation of the SCN. We also find that melatonin regulates SCN function via MT1 receptors with a minimal role for MT2.