Journal of Biological Rhythms最新文献

The recall of conditioned fear extinction exhibits a circadian rhythm in humans and rodents, with optimal extinction recall occurring during the early active phase. However, it remains unclear whether this rhythm depends on the circadian modulation of mechanisms supporting memory consolidation versus memory maintenance and retrieval. Here, adult male rats underwent conditioned fear extinction at one of four times throughout the day and then, starting 24 h after extinction, were repeatedly tested for extinction recall over the next 24 h. Rats undergoing extinction learning during the early active phase tended toward accelerated extinction learning compared with rats in other groups, pointing to rhythms in mechanisms that support extinction memory encoding. The next day, the strength of extinction recall followed a 24-h cycle that depended not on the time of day of extinction learning but, instead, on the time of day of extinction recall. This latter finding indicates a rhythm in mechanisms supporting extinction memory maintenance and/or retrieval. Subsequent testing for fear relapse in the conditioning context suggested reduced fear in rats tested during the early active phase. These results lay the groundwork for mechanistic investigations of circadian rhythms in fear extinction memory.

Immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel disease, and asthma share common pathophysiological pathways characterized by chronic inflammation and subsequent tissue damage involving multiple body sites. Circadian rhythms are 24-h body cycles that regulate immune activity and control the magnitude of immune response based on time of day. Chronotype is a person's individual circadian phase preference, ranging from morningness to eveningness, which is known to influence the risk of cardiometabolic and mental health disease. We systematically reviewed the literature to assess the association of questionnaire-based chronotype and patients with IMID. A comprehensive search of MEDLINE and Embase identified 12 studies meeting the inclusion criteria, conducted in 7 countries and covering 4 IMIDs to include 15,625 IMID patients and 410,783 healthy controls. Results showed that later chronotype may be a risk factor for worse quality of life and increased symptom burden in patients with IMIDs. In addition, chronotype may be a risk factor for IMID incidence, but the direction and magnitude of this effect were not consistent across individual IMIDs. Chronotype assessment could contribute to risk stratification in patients with IMIDs. Cross-disciplinary collaboration to understand the role of circadian rhythms and chronotype in driving common inflammatory pathways could help to improve outcomes for patients with IMIDs.

The human circadian system responds to light as low as 30 photopic lux. Furthermore, recent evidence shows that there are huge individual differences in light sensitivity, which may help to explain why some people are more susceptible to sleep and circadian disruption than others. The biological mechanisms underlying the differences in light sensitivity remain largely unknown. A key variable of interest in understanding these individual differences in light sensitivity is biological sex. It is possible that in humans, males and females differ in their sensitivity to light, but the evidence is inconclusive. This is in part due to the historic exclusion of women in biomedical research. Hormonal fluctuations across the menstrual cycle in women has often been cited as a confound by researchers. Attitudes, however, are changing with funding and publication agencies advocating for more inclusive research frameworks and mandating that women and minorities participate in scientific research studies. In this article, we distill the existing knowledge regarding the relationship between light and the menstrual cycle. There is some evidence of a relationship between light and the menstrual cycle, but the nature of this relationship seems dependent on the timing of the light source (sunlight, moonlight, and electric light at night). Light sensitivity may be influenced by biological sex and menstrual phase but there might not be any effect at all. To better understand the relationship between light, the circadian system, and the menstrual cycle, future research needs to be designed thoughtfully, conducted rigorously, and reported transparently.

Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.

Growing evidence supports a role for rest-activity rhythms (RARs) in metabolic health. Epidemiological studies in adolescents and young adults showed that RAR characteristics consistent with weakened rhythmicity were associated with obesity. However, studies in older adults are lacking. The objective of this study was to examine the cross-sectional and prospective associations between RAR and obesity in older men using the Harmonic Hidden Markov Model (HHMM), a novel analytical approach with several advantages over conventional methods for characterizing RAR. The analysis included nearly 3,000 participants in the Osteoporotic Fractures in Men study with 5-day 24-h actigraphy data. The strength of RAR was measured by rhythmic index (RI), a scaled value between 0 and 1 with higher values indicating better RAR. Multiple linear and logistic regression adjusting for multiple confounders were performed to examine the RI in relation to body mass index (BMI) and obesity status at baseline and after ~3.5 years of follow-up. We showed that the HHMM can derive both meaningful visual profile and quantifier of RAR. A lower RI was associated with higher BMI and obesity at baseline, and an elevated likelihood for developing obesity over follow-up. Specifically, when compared with men in the highest quartile of RI, those in the lowest quartile on average had a higher BMI (β [95% confidence interval (CI)], 1.76 [1.39, 2.13]) and were more likely to be obese at baseline (odds ratio (OR) [95% CI], 2.63 [2.03, 3.43]). Moreover, among nonobese men at baseline, those in the lowest quartile of RI were 2.06 times (OR [95% CI], 2.06 [1.02, 4.27]) more likely to develop obesity over follow-up when compared with those in the highest quartile. In conclusion, our study demonstrated the utility of HHMM in characterizing RAR and showed that rhythmicity strength was associated with BMI and risk of obesity in older men.

Honey bee queens show extreme fecundity, commonly laying more than a thousand eggs in a single day. It has proven challenging to study the temporal organization of egg-laying behavior because queens are typically active around the clock in the dark cavity of a densely populated nest. To contend with this challenge, we developed two novel methods allowing detailed monitoring of queen activity and egg laying. We first adapted a high-resolution, continuous, tracking system allowing to track the position of barcode-tagged queens in observation hives with colonies foraging outside. We found that the queen is active ~96% of the day with typically no diurnal rhythm. Next, we developed a new laboratory procedure to monitor egg laying at single egg resolution under different light regimes. We found that under constant darkness (DD) and temperature conditions, queens laid eggs with no circadian rhythms. Queen fecundity was severely reduced under constant light (LL). Under a 12:12 illumination regime, queen fecundity was comparable to under constant darkness, with a higher number of eggs during the light phase. These daily rhythms in egg laying continued when these queens were released to DD conditions, suggesting that egg-laying rhythms are influenced by endogenous circadian clocks. These results suggest that honey bee queens are active and lay eggs around the clock with no diurnal rhythms. Light has complex influences on these behaviors, but more studies are needed to determine whether these effects reflect the influence of light directly on the queen or indirectly by affecting workers that interact with the queen.

DTNBP1 is a gene associated with schizophrenia. Postmortem studies found a reduced expression of DTNBP1 in regions associated with schizophrenia in patients' brains. Sandy (Sdy) mice have a loss-of-function mutation in Dtnbp1 gene, resulting in behavioral deficits and brain changes similar to those seen in patients with schizophrenia. We previously showed that exposing adult Sdy mice to circadian disruption led to an exacerbation of schizophrenia-relevant behaviors. Here we asked whether the interaction between this genetic risk factor and circadian disruption occurs during adolescence, a period when environmental insults can promote schizophrenia symptoms, and whether sex affects this interaction. Starting at postnatal day 21, wild-type (WT) and Sdy males and females were housed for 4 weeks either in a 12 h light:12 h dark (LD 12:12) cycle or under chronic jetlag (CJL). Then, after 2 weeks in LD 12:12, behavioral assessments were conducted, including elevated plus maze (EPM), novel object recognition (NOR), social interaction, and prepulse inhibition (PPI) of acoustic startle. NOR and social novelty tests showed that, surprisingly, CJL during adolescence had opposite effects on WT and Sdy males, that is, behavioral deficits in WT males while rescuing preexisting deficits in Sdy mice. CJL led to decreased sociability in WT and Sdy mice while decreasing PPI only in females. Sdy mice showed decreased anxiety-like behavior compared with wild-type (WT), which was further accentuated by CJL in males. Thus, circadian disruption during adolescence, on its own or in association with Dtnbp1 mutation, can influence cognition, sociability, sensorimotor gating, and anxiety-like behaviors in a sex-dependent manner.

The molecular mechanisms that maintain circadian rhythms in mammalian as well as non-mammalian systems are well documented in neuronal populations but comparatively understudied in glia. Glia are highly dynamic in form and function, and the circadian clock provides broad dynamic ranges for the maintenance of this homeostasis, thus glia are key to understanding the role of circadian biology in brain function. Here, we highlight the implications of the molecular circadian clock on the homeodynamic nature of glia, underscoring the current gap in understanding the role of the circadian system in oligodendroglia lineage cells and subsequent myelination. Through this perspective, we will focus on the intersection of circadian and glial biology and how it interfaces with global circadian rhythm maintenance associated with normative and aberrant brain function.

The immune system exhibits circadian rhythms, and its response to viral infection is influenced by the circadian clock system. Previous studies have reported associations between the time of day of vaccination against COVID-19 and production of anti-SARS-CoV-2 antibody titer. We examined the effect of vaccination time of day on anti-SARS-CoV-2 antibody titer after the first dose of vaccination with the mRNA-1273 (Moderna) COVID-19 vaccine in an adult population. A total of 332 Japanese adults participated in the present study. All participants were not infected with SARS-CoV-2 and had already received the first dose of mRNA-1273 2 to 4 weeks prior to participating in the study. The participants were asked to provide basic demographic characteristics (age, sex, medical history, allergy, medication, and mean sleep duration), the number of days after the first dose of vaccination, and the time of day of vaccination. Blood was collected from the participants, and SARS-CoV-2 antibody titers were measured. Ordinary least square regression was used for assessing the relationship between basic demographic characteristics, number of days after vaccination, time of day of vaccination, and the log₁₀-transformed normalized antibody titer. The least square mean of antibody titers was not associated with the vaccination time and sleep durations. The least square means of antibody titers was associated with age; the antibody titers decreased in people aged 50 to 59 years and 60 to 64 years. The present findings demonstrate that the vaccination time with mRNA-1273 was not associated with the SARS-CoV-2 antibody titer in an adult population, suggesting that these results do not support restricting vaccination to a particular time of day. The present findings may be useful in optimizing SARS-CoV-2 vaccination strategies.

Circadian rhythms provide daily temporal structure to cellular and organismal biological processes, ranging from gene expression to cognition. Higher-frequency (intradaily) ultradian rhythms are similarly ubiquitous but have garnered far less empirical study, in part because of the properties that define them-multimodal periods, non-stationarity, circadian harmonics, and diurnal modulation-pose challenges to their accurate and precise quantification. Wavelet analyses are ideally suited to address these challenges, but wavelet-based measurement of ultradian rhythms has remained largely idiographic. Here, we describe novel analytical approaches, based on discrete and continuous wavelet transforms, which permit quantification of rhythmic power distribution across a broad ultradian spectrum, as well as precise identification of period within empirically determined ultradian bands. Moreover, the aggregation of normalized wavelet matrices allows group-level analyses of experimental treatments, thereby circumventing limitations of idiographic approaches. The accuracy and precision of these wavelet analyses were validated using in silico and in vivo models with known ultradian features. Experiments in male and female mice yielded robust and repeatable measures of ultradian period and power in home cage locomotor activity, confirming and extending reports of ultradian rhythm modulation by sex, gonadal hormones, and circadian entrainment. Seasonal changes in day length modulated ultradian period and power, and exerted opposite effects in the light and dark phases of the 24 h day, underscoring the importance of evaluating ultradian rhythms with attention to circadian phase. Sex differences in ultradian rhythms were more prominent at night and depended on gonadal hormones in male mice. Thus, relatively straightforward modifications to the wavelet procedure allowed quantification of ultradian rhythms with appropriate time-frequency resolution, generating accurate, and repeatable measures of period and power which are suitable for group-level analyses. These analytical tools may afford deeper understanding of how ultradian rhythms are generated and respond to interoceptive and exteroceptive cues.