Journal of Biological Rhythms最新文献

To assess the consistency of biological rhythms across studies, 57 public mouse liver tissue timeseries totaling 1096 RNA-seq samples were obtained and analyzed. Only the control groups of each study were included, to create comparable data. Technical factors in RNA-seq library preparation were the largest contributors to transcriptome-level differences, beyond biological or experiment-specific factors such as lighting conditions. Core clock genes were remarkably consistent in phase across all studies. Overlap of genes identified as rhythmic across studies was generally low, with no pair of studies having over 60% overlap. Distributions of phases of significant genes were remarkably inconsistent across studies, but the genes that consistently identified as rhythmic had acrophase clustering near ZT0 and ZT12. Despite the discrepancies between single-study analyses, cross-study analyses found substantial consistency. Running compareRhythms on each pair of studies identified a median of only 11% of the identified rhythmic genes as rhythmic in only 1 of the 2 studies. Data were integrated across studies in a joint and individual variance estimate (JIVE) analysis, which showed that the top 2 components of joint within-study variation are determined by time of day. A shape-invariant model with random effects was fit to the genes to identify the underlying shape of the rhythms, consistent across all studies, including identifying 72 genes with consistently multiple peaks.

Synchronizing the circadian timing system (CTS) to external light/dark cycles is crucial for homeostasis maintenance and environmental adaptation. The CTS is organized hierarchically, with the central pacemaker located in the suprachiasmatic nuclei (SCN) generating coherent oscillations that are entrained to light/dark cycles. These oscillations regulate the release of glucocorticoids by the hypothalamus-pituitary-adrenal (HPA) axis, which acts as a systemic entrainer of peripheral clocks throughout the body. The SCN adjusts its network plasticity in response to variations in photoperiod, leading to changes in the rhythmic release of glucocorticoids and ultimately impacting peripheral clocks. However, the effects of photoperiod-induced variations of glucocorticoids on the synchronization of peripheral clocks are not fully understood, and the interaction between jetlag adaption and photoperiod changes is unclear. This study presents a semi-mechanistic mathematical model to investigate how the CTS responds to changes in photoperiod. Specifically, the study focuses on the entrainment properties of a system composed of the SCN, HPA axis, and peripheral clocks. The results show that high-amplitude glucocorticoid rhythms lead to a more coherent phase distribution in the periphery. In addition, our study investigates the effect of photoperiod exposure on jetlag recovery time and phase shift, proposing different interventional strategies for eastward and westward jetlag. The findings suggest that decreasing photic exposure before jetlag during eastward traveling and after jetlag during westward traveling can accelerate jetlag readaptation. The study provides insights into the mechanisms of CTS organization and potential recovery strategies for transitions between time zones and lighting zones.

Both the circadian clock and sex hormone signaling can strongly influence brain function, yet little is known about how these 2 powerful modulatory systems might interact during complex neural processes like memory consolidation. Individually, the molecular components and action of each of these systems have been fairly well-characterized, but there is a fundamental lack of information about how these systems cooperate. In the circadian system, clock genes function as timekeeping molecules that convey time-of-day information on a well-stereotyped cycle that is governed by the suprachiasmatic nucleus. Keeping time is particularly important to synchronize various physiological processes across the brain and body, including those that regulate memory consolidation. Similarly, sex hormones are powerful modulators of memory, with androgens, estrogens, and progestins, all influencing memory consolidation within memory-relevant brain regions like the hippocampus. Despite clear evidence that each system can influence memory individually, exactly how the circadian and hormonal systems might interact to impact memory consolidation remains unclear. Research investigating either sex hormone action or circadian gene function within memory-relevant brain regions has unveiled several notable places in which the two systems could interact to control memory. Here, we bring attention to known interactions between the circadian clock and sex hormone signaling. We then review sex hormone-mediated control of memory consolidation, highlighting potential nodes through which the circadian system might interact during memory formation. We suggest that the bidirectional relationship between these two systems is essential for proper control of memory formation based on an animal's hormonal and circadian state.

The circadian clock regulates multiple aspects of human physiology including immunity. People have a circadian preference termed chronotype. Those with an evening preference may be better suited to shift work, but also carry higher risk of adverse health. Shift work leads to misalignment of circadian rhythms and is associated with increased risk of inflammatory disease such as asthma and cancer. Here, we investigate the association between chronotype, shift work, and rheumatoid arthritis (RA). The associations between exposures of shift work and chronotype on risk of RA were studied in up to 444,210 U.K. Biobank participants. Multivariable logistic regression models were adjusted for covariates: age, sex, ethnicity, alcohol intake, smoking history, Townsend Deprivation Index (TDI), sleep duration, length of working week, and body mass index (BMI). After adjusting for covariates, individuals with a morning chronotype had lower odds of having rheumatoid arthritis (RA; odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88-0.99) when compared to intermediate chronotypes. The association between morning chronotype and RA persisted with a more stringent RA case definition (covariate-adjusted OR: 0.89, 95% CI: 0.81-0.97). When adjusted for age, sex, ethnicity, and TDI, shift workers had higher odds of RA (OR: 1.22, 95% CI: 1.1-1.36) compared to day workers that attenuated to the null after further covariate adjustment (OR: 1.1, 95% CI: 0.98-1.22). Morning chronotypes working permanent night shifts had significantly higher odds of RA compared to day workers (OR: 1.89, 95% CI: 1.19-2.99). These data point to a role for circadian rhythms in RA pathogenesis. Further studies are required to determine the mechanisms underlying this association and understand the potential impact of shift work on chronic inflammatory disease and its mediating factors.

In early childhood, consolidation of sleep from a biphasic to a monophasic sleep-wake pattern, that is, the transition from sleeping during an afternoon nap and at night to sleeping only during the night, represents a major developmental milestone. Reduced napping behavior is associated with an advance in the timing of the circadian system; however, it is unknown if this advance represents a standard response of the circadian clock to altered patterns of light exposure or if it additionally reflects features of the developing circadian system. Using a mathematical model of the human circadian pacemaker, we investigated the impact of napping and non-napping patterns of light exposure on entrained circadian phases. Simulated light schedules were based on published data from 20 children (34.2 ± 2.0 months) with habitual napping or non-napping sleep patterns (15 nappers). We found the model predicted different circadian phases for napping and non-napping light patterns: both the decrease in afternoon light during the nap and the increase in evening light associated with napping toddlers' later bedtimes contributed to the observed circadian phase difference produced between napping and non-napping light schedules. We systematically quantified the effects on phase shifting of nap duration, timing, and light intensity, finding larger phase delays occurred for longer and earlier naps. In addition, we simulated phase response curves to a 1-h light pulse and 1-h dark pulse to predict phase and intensity dependence of these changes in light exposure. We found the light pulse produced larger shifts compared with the dark pulse, and we analyzed the model dynamics to identify the features contributing to this asymmetry. These findings suggest that napping status affects circadian timing due to altered patterns of light exposure, with the dynamics of the circadian clock and light processing mediating the effects of the dark pulse associated with a daytime nap.

The cyanobacterial circadian oscillator, consisting of KaiA, KaiB, and KaiC proteins, drives global rhythms of gene expression and compaction of the chromosome and regulates the timing of cell division and natural transformation. While the KaiABC posttranslational oscillator can be reconstituted in vitro, the Kai-based oscillator is subject to several layers of regulation in vivo. Specifically, the oscillator proteins undergo changes in their subcellular localization patterns, where KaiA and KaiC are diffuse throughout the cell during the day and localized as a focus at or near the pole of the cell at night. Here, we report that the CI domain of KaiC, when in a hexameric state, is sufficient to target KaiC to the pole. Moreover, increased ATPase activity of KaiC correlates with enhanced polar localization. We identified proteins associated with KaiC in either a localized or diffuse state. We found that loss of Rbp2, found to be associated with localized KaiC, results in decreased incidence of KaiC localization and long-period circadian phenotypes. Rbp2 is an RNA-binding protein, and it appears that RNA-binding activity of Rbp2 is required to execute clock functions. These findings uncover previously unrecognized roles for Rbp2 in regulating the circadian clock and suggest that the proper localization of KaiC is required for a fully functional clock in vivo.

Circadian clocks confer 24-h periodicity to biological systems, to ultimately maximize energy efficiency and promote survival in a world with regular environmental light cycles. In mammals, circadian rhythms regulate myriad physiological functions, including the immune, endocrine, and central nervous systems. Within the central nervous system, specialized glial cells such as astrocytes and microglia survey and maintain the neuroimmune environment. The contributions of these neuroimmune cells to both homeostatic and pathogenic demands vary greatly across the day. Moreover, the function of these cells changes across the lifespan. In this review, we discuss circadian regulation of the neuroimmune environment across the lifespan, with a focus on microglia and astrocytes. Circadian rhythms emerge in early life concurrent with neuroimmune sculpting of brain circuits and wane late in life alongside increasing immunosenescence and neurodegeneration. Importantly, circadian dysregulation can alter immune function, which may contribute to susceptibility to neurodevelopmental and neurodegenerative diseases. In this review, we highlight circadian neuroimmune interactions across the lifespan and share evidence that circadian dysregulation within the neuroimmune system may be a critical component in human neurodevelopmental and neurodegenerative diseases.