Journal Of Biological Rhythms[JOURNAL]
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200 papers
From Bench to Bedside and Back Again: Translating Circadian Science to Medicine.
Klerman EB, Kramer A, Zee PC
J Biol Rhythms · 2023 Apr · PMID 36583523 · Full text
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Chronic Alcohol Consumption Disrupts the Skeletal Muscle Circadian Clock in Female Mice.
Tice AL, Laudato JA, Gordon BS … +1 more , Steiner JL
J Biol Rhythms · 2023 Apr · PMID 36579773 · Publisher ↗
The intrinsic skeletal muscle core clock has emerged as a key feature of metabolic control and influences several aspects of muscle physiology. Acute alcohol intoxication disrupts the core molecular clock, but whether ch...
The intrinsic skeletal muscle core clock has emerged as a key feature of metabolic control and influences several aspects of muscle physiology. Acute alcohol intoxication disrupts the core molecular clock, but whether chronic consumption, like that leading to alcoholic myopathy, is also a zeitgeber for skeletal muscle remains unknown. The purpose of this work was to determine whether chronic alcohol consumption dysregulates the skeletal muscle core molecular clock and clock-controlled genes (CCGs). C57BL/6Hsd female mice (14 weeks old) were fed a control (CON) or alcohol (EtOH) containing liquid diet for 6 weeks. Gastrocnemius muscles and serum were collected from CON and EtOH mice every 4-h for 24-h. Chronic alcohol consumption disrupted genes of the core clock including suppressing the rhythmic peak of expression of , , and . Genes involved in the regulation of also exhibited lower rhythmic peaks including α and . The CCGs, , and were also suppressed by alcohol. The nuclear expression patterns of MYOD1, DBP, and REVERBα were shifted by alcohol, while no change in BMAL1 was detected. Overall, these data indicate that alcohol disrupted the skeletal muscle core clock but whether these changes in the core clock are causative or a consequence of alcoholic myopathy requires future mechanistic confirmation.
Inducible Reporter Lines for Tissue-specific Monitoring of Circadian Clock Transcriptional Activity.
Mather LM, Cholak ME, Morfoot CM … +3 more , Curro KC, Love J, Cavanaugh DJ
J Biol Rhythms · 2023 Feb · PMID 36495136 · Publisher ↗
Organisms track time of day through the function of cell-autonomous molecular clocks. In addition to a central clock located in the brain, molecular clocks are present in most peripheral tissues. Circadian clocks are coo...
Organisms track time of day through the function of cell-autonomous molecular clocks. In addition to a central clock located in the brain, molecular clocks are present in most peripheral tissues. Circadian clocks are coordinated within and across tissues, but the manner through which this coordination is achieved is not well understood. We reasoned that the ability to track in vivo molecular clock activity in specific tissues of the fruit fly, , would facilitate an investigation into the relationship between different clock-containing tissues. Previous efforts to monitor clock gene expression in single flies in vivo have used regulatory elements of several different clock genes to dictate expression of a luciferase reporter enzyme, the activity of which can be monitored using a luminometer. Although these reporter lines have been instrumental in our understanding of the circadian system, they generally lack cell specificity, making it difficult to compare molecular clock oscillations between different tissues. Here, we report the generation of several novel lines of flies that allow for inducible expression of a luciferase reporter construct for clock gene transcriptional activity. We find that these lines faithfully report circadian transcription, as they exhibit rhythmic luciferase activity that is dependent on a functional molecular clock. Furthermore, we take advantage of our reporter lines' tissue specificity to demonstrate that peripheral molecular clocks are able to retain rhythmicity for multiple days under constant environmental conditions.
An External Coincidence Model for the Lunar Cycle Reveals Circadian Phase-Dependent Moonlight Effects on Coral Spawning.
Komoto H, Lin CH, Nozawa Y … +1 more , Satake A
J Biol Rhythms · 2023 Apr · PMID 36461677 · Publisher ↗
Many marine organisms synchronously spawn at specific times to ensure the success of external fertilization in the ocean. Corals are famous examples of synchronized spawning at specific lunar phases, and two distinct spa...
Many marine organisms synchronously spawn at specific times to ensure the success of external fertilization in the ocean. Corals are famous examples of synchronized spawning at specific lunar phases, and two distinct spawning patterns have been observed in two dominant taxa: merulinid corals spawn at regular lunar phases, several days after the full moon, whereas corals spawn at more irregular lunar phases around the full moon. Although it has been suggested that the two coral taxa have different responses to moonlight and seawater temperature, their spawning times have never been analyzed by integrating the two environmental factors, resulting in an incomplete understanding of the regulatory mechanisms of spawning. In this study, we developed a new predictive model of coral spawning days by integrating moonlight and temperature effects based on the external coincidence model for the lunar cycle. We performed model fitting using a 10-year monitoring record of coral spawning time in Taiwan. Our model successfully demonstrated the synergistic effects of moonlight and temperature on coral spawning time (days) and provided two testable hypotheses to explain the different spawning patterns regarding the preparation (maturation) process for spawning and the sensitivity to moonlight at different circadian phases: (1) corals may have an earlier onset and longer period of preparation for spawning than merulinid corals; and (2) merulinid corals may use moonlight signals near sunset, while corals may have a similar onset at approximately midnight. This is the first study to indicate the difference in circadian phase-dependent moonlight sensitivities between coral taxa, providing a basis for underlying coral spawning mechanisms for rhythmic studies.
Sex Inclusion in Transcriptome Studies of Daily Rhythms.
Obodo D, Outland EH, Hughey JJ
J Biol Rhythms · 2023 Feb · PMID 36419398 · Full text
Biomedical research on mammals has traditionally neglected females, raising the concern that some scientific findings may generalize poorly to half the population. Although this lack of sex inclusion has been broadly doc...
Biomedical research on mammals has traditionally neglected females, raising the concern that some scientific findings may generalize poorly to half the population. Although this lack of sex inclusion has been broadly documented, its extent within circadian genomics remains undescribed. To address this gap, we examined sex inclusion practices in a comprehensive collection of publicly available transcriptome studies on daily rhythms. Among 148 studies having samples from mammals in vivo, we found strong underrepresentation of females across organisms and tissues. Overall, only 23 of 123 studies in mice, 0 of 10 studies in rats, and 9 of 15 studies in humans included samples from females. In addition, studies having samples from both sexes tended to have more samples from males than from females. These trends appear to have changed little over time, including since 2016, when the US National Institutes of Health began requiring investigators to consider sex as a biological variable. Our findings highlight an opportunity to dramatically improve representation of females in circadian research and to explore sex differences in daily rhythms at the genome level.
Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Body Mass Index in Older Men: A Novel Analysis Using Harmonic Hidden Markov Models.
Heckler B, Lee M, Stone K … +2 more , Bauer C, Xiao Q
J Biol Rhythms · 2023 Feb · PMID 36416436 · Full text
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 ass...
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.
Evening Light Intensity and Phase Delay of the Circadian Clock in Early Childhood.
Hartstein LE, Diniz Behn C, Wright KP … +3 more , Akacem LD, Stowe SR, LeBourgeois MK
J Biol Rhythms · 2023 Feb · PMID 36415902 · Full text
Late sleep timing is prevalent in early childhood and a risk factor for poor behavioral and health outcomes. Sleep timing is influenced by the phase of the circadian clock, with later circadian timing linked to delayed s...
Late sleep timing is prevalent in early childhood and a risk factor for poor behavioral and health outcomes. Sleep timing is influenced by the phase of the circadian clock, with later circadian timing linked to delayed sleep onset in young children. Light is the strongest zeitgeber of circadian timing and, in adults, evening light produces circadian phase delay in an intensity-dependent manner. The intensity-dependent circadian phase-shifting response to evening light in children, however, is currently unknown. In the present study, 33 healthy, good-sleeping children aged 3.0 to 4.9 years (M = 4.14 years, 39% male) completed a 10-day between-subjects protocol. Following 7 days of a stable sleep schedule, an in-home dim-light circadian assessment was performed. Children remained in dim-light across 3 days (55 h), with salivary melatonin collected in regular intervals throughout each evening. Phase-shifting effects of light exposure were determined via changes in the timing of the dim-light melatonin onset (DLMO) prior to (Day 8) and following (Day 10) a light exposure stimulus. On Day 9, children were exposed to a 1 h light stimulus in the hour before their habitual bedtime. Each child was randomly assigned to one intensity between 5 and 5000 lux (4.5-3276 melanopic EDI). Across light intensities, children showed significant circadian phase delays, with an average phase delay of 56.1 min (SD = 33.6 min), and large inter-individual variability. No relationship between light intensity and magnitude of the phase shift was observed. However, a greater percentage of melatonin suppression during the light exposure was associated with a greater phase delay ( = -0.73, < 0.01). These findings demonstrate that some young children may be highly sensitive to light exposure in the hour before bedtime and suggest that the home lighting environment and its impact on circadian timing should be considered a possible contributor to behavioral sleep difficulties.
Modified Wavelet Analyses Permit Quantification of Dynamic Interactions Between Ultradian and Circadian Rhythms.
Riggle JP, Kay LM, Onishi KG … +4 more , Falk DT, Smarr BL, Zucker I, Prendergast BJ
J Biol Rhythms · 2022 Dec · PMID 36380564 · Full text
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...
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 and 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.
Chronotype in Patients With Immune-Mediated Inflammatory Disease: A Systematic Review.
Butler TD, Mohammed Ali A, Gibbs JE … +1 more , McLaughlin JT
J Biol Rhythms · 2023 Feb · PMID 36377205 · Full text
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 dama...
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 Association of Time of Day of ChAdOx1 nCoV-19 Vaccine Administration With SARS-CoV-2 Anti-Spike IgG Antibody Levels: An Exploratory Observational Study.
Erber AC, Wagner A, Karachaliou M … +11 more , Jeleff M, Kalafatis P, Kogevinas M, Pepłońska B, Santonja I, Schernhammer E, Stockinger H, Straif K, Wiedermann U, Waldhör T, Papantoniou K
J Biol Rhythms · 2023 Feb · PMID 36367167 · Full text
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 da...
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.
: A Review of Sex and Menstrual Cycle Differences in the Physiological Effects of Light in Humans.
Vidafar P, Spitschan M
J Biol Rhythms · 2023 Feb · PMID 36367137 · Full text
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 mo...
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.
The Effect of Night Shifts on 24-h Rhythms in the Urinary Metabolome of Police Officers on a Rotating Work Schedule.
Kervezee L, Koshy A, Cermakian N … +1 more , Boivin DB
J Biol Rhythms · 2023 Feb · PMID 36346168 · Full text
Shift workers face an increased risk of metabolic health problems, but the direct metabolic response to working nights is not fully understood. The aim of this study was to investigate the effect of night shifts on the 2...
Shift workers face an increased risk of metabolic health problems, but the direct metabolic response to working nights is not fully understood. The aim of this study was to investigate the effect of night shifts on the 24-h urinary metabolome of shift workers. Eleven police officers working rotating shifts completed two 24-h laboratory visits that took place before and after they worked 7 consecutive nights. Sleep and meals were scheduled on a day schedule in the first visit and then on a night schedule (i.e., sleep and meals shifted by approximately 12 h) in the second visit. Targeted metabolomic analysis was performed on urine samples collected throughout these laboratory visits. Differential rhythmicity analysis was used to compare 24-h rhythms in urinary metabolites in both conditions. Our results show that on the day schedule, 24-h rhythms are present in the urinary levels of the majority of metabolites, but that this is significantly reduced on the night schedule, partly due to loss of organic acid rhythmicity. Furthermore, misalignment of 24-h metabolite rhythms with the shifted behavioral cycles in the night schedule was observed in more than half of the metabolites that were rhythmic in both conditions (all acylcarnitines). These results show that working nights alters the daily rhythms of the urinary metabolome in rotating shift workers, with the most notable impact observed for acylcarnitines and organic acids, 2 metabolite classes involved in mitochondrial function. Further research is warranted to study how these changes relate to the increased metabolic risks associated with shift work.
Circadian Rhythms in Fear Extinction Recall Depend on the Time of Day of Extinction Recall, Not the Time of Day of Extinction Learning.
Hartsock MJ, Brennan NA, Spencer RL
J Biol Rhythms · 2023 Feb · PMID 36281735 · Full text
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...
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.
The Influences of Illumination Regime on Egg-laying Rhythms of Honey Bee Queens.
Shpigler HY, Yaniv A, Gernat T … +2 more , Robinson GE, Bloch G
J Biol Rhythms · 2022 Dec · PMID 36226630 · Full text
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...
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.
Coupling Between Subregional Oscillators Within the Suprachiasmatic Nucleus Determines Free-Running Period in the Rat.
Schwartz MD, Cambras T, Díez-Noguera A … +4 more , Campuzano A, Oda GA, Yamazaki S, de la Iglesia HO
J Biol Rhythms · 2022 Dec · PMID 36181312 · Full text
Rats housed in a 22-h light-dark cycle (11:11, T22) exhibit 2 distinct circadian locomotor activity (LMA) bouts simultaneously: one is entrained to the LD cycle and a second dissociated bout maintains a period greater th...
Rats housed in a 22-h light-dark cycle (11:11, T22) exhibit 2 distinct circadian locomotor activity (LMA) bouts simultaneously: one is entrained to the LD cycle and a second dissociated bout maintains a period greater than 24 h. These 2 activity bouts are associated with independent clock gene oscillations in the ventrolateral (vl-) and dorsomedial (dm-) suprachiasmatic nucleus (SCN), respectively. Previous results in our laboratory have shown that the vl- and dm-SCN oscillators are weakly coupled under T22 and that the period of the dissociated bout depends on coupling between the 2 subdivisions. Here, we sought to study the behavior of the T22 SCN pacemaker upon release into free-running conditions and compare it to the behavior of the system upon release from typical 24-h (12:12, T24) entrainment. T22-desynchronized rats or T24-entrained rats were released into constant darkness (DD). Activity rhythms in T22 rats rapidly resynchronized upon release into DD, and the free-running period (FRP) of the fused rhythm was longer than the FRP of T24 rats. We then asked whether the in vivo period changes were also present in the ex vivo SCN. rats were desynchronized in T22 for assessment of SCN ex vivo. Similar to behavioral FRP, the period of ex vivo SCN explanted from T22 rats was longer than that for T24 animals. Mathematical models supported the observed behavior of the dual oscillator system as the result of mutual coupling between the vl- and dm-SCN oscillators. This bidirectionally coupled model predicted both the FRP of the T22 system and its phase-shifting response to light. Together, these data support a model of pacemaker organization in which a light-sensitive vl-SCN oscillator is mutually coupled with a light-insensitive dm-SCN oscillator, and together they determine the period of the coupled system as a whole and its response to light pulses.
Attention-Deficit/Hyperactivity Disorder and Delayed Sleep Phase Syndrome in Adults: A Randomized Clinical Trial on the Effects of Chronotherapy on Sleep.
van Andel E, Bijlenga D, Vogel SWN … +2 more , Beekman ATF, Kooij JJS
J Biol Rhythms · 2022 Dec · PMID 36181304 · Publisher ↗
Delayed sleep phase syndrome (DSPS) is the most common sleep disturbance in adults with attention-deficit/hyperactivity disorder (ADHD). We previously showed that chronotherapy with melatonin effectively advanced the dim...
Delayed sleep phase syndrome (DSPS) is the most common sleep disturbance in adults with attention-deficit/hyperactivity disorder (ADHD). We previously showed that chronotherapy with melatonin effectively advanced the dim-light melatonin onset (DLMO), a biomarker for the internal circadian rhythm, by 1.5 h and reduced ADHD symptoms by 14%. Melatonin combined with bright light therapy (BLT) advanced the DLMO by 2 h, but did not affect ADHD symptoms. This article explores whether sleep times advanced along with DLMO, leading to longer sleep duration and better sleep in general, which might explain the working mechanism behind the reduction in ADHD symptoms after treatment with melatonin. This article presents exploratory secondary analysis on objective and self-reported sleep characteristics from a three-armed double-blind randomized placebo-controlled clinical trial (RCT), which included 49 adults (18-55 years) with ADHD and DSPS. Participants were randomized to receive sleep education and 3 weeks of (1) 0.5 mg/day placebo, (2) 0.5 mg/day melatonin, or (3) 0.5 mg/day melatonin plus 30 min of bright light therapy (BLT) between 0700 and 0800 h. Sleep was assessed at baseline, directly after treatment, and 2 weeks after the end of treatment. Objective measures were obtained by actigraphy, self-reported measures by various sleep questionnaires and a sleep diary. Melatonin with or without BLT did not advance sleep times, improve sleep in general, or strengthen wake-activity rhythms. So even though the DLMO had advanced, sleep timing did not follow. Adding extensive behavioral coaching to chronotherapy is necessary for advancing sleep times along with DLMO and to further alleviate ADHD symptoms.
Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner.
Cloutier MÈ, Srivastava LK, Cermakian N
J Biol Rhythms · 2022 Dec · PMID 36168739 · Full text
is a gene associated with schizophrenia. Postmortem studies found a reduced expression of in regions associated with schizophrenia in patients' brains. Sandy (Sdy) mice have a loss-of-function mutation in gene, resulti...
is a gene associated with schizophrenia. Postmortem studies found a reduced expression of in regions associated with schizophrenia in patients' brains. Sandy (Sdy) mice have a loss-of-function mutation in 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 mutation, can influence cognition, sociability, sensorimotor gating, and anxiety-like behaviors in a sex-dependent manner.
Time of Day of Vaccination Does Not Associate With SARS-CoV-2 Antibody Titer Following First Dose of mRNA COVID-19 Vaccine.
Yamanaka Y, Yokota I, Yasumoto A … +2 more , Morishita E, Horiuchi H
J Biol Rhythms · 2022 Dec · PMID 36154515 · Full text
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 CO...
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 log-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.
Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.
Martin RA, Esser KA
J Biol Rhythms · 2022 Dec · PMID 36129164 · Full text
Circadian rhythms drive our daily behaviors to coincide with the earth's rotation on an approximate 24-h cycle. The circadian clock mechanism present in nearly every cell is responsible for our circadian rhythms and is c...
Circadian rhythms drive our daily behaviors to coincide with the earth's rotation on an approximate 24-h cycle. The circadian clock mechanism present in nearly every cell is responsible for our circadian rhythms and is comprised of a transcriptional-translational feedback loop in mammals. The central clock resides in the hypothalamus responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from feeding and activity. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue with the ability to influence and adjust the muscle clock phase in response to exercise timing. Since the skeletal muscle clock is also involved in the expression of tissue-specific gene expression-including glucoregulatory genes-this might suggest a role for exercise timing as a therapeutic strategy in metabolic diseases, like type 2 diabetes. Notably, those with type 2 diabetes have accompanied disruptions in their skeletal muscle clock mechanism which may also be related to the increased risk of type 2 diabetes seen among shift workers. Therefore, the direct influence of exercise on the skeletal muscle clock might support the use of exercise timing to provide disease-mitigating effects. Here, we highlight the potential use of time-of-day exercise as a chronotherapeutic tool within circadian medicine to improve the metabolic profile of type 2 diabetes and support long-term glycemic control, potentially working through the skeletal muscle clock and circadian physiology.
A Naturalistic Actigraphic Assessment of Changes in Adolescent Sleep, Light Exposure, and Activity Before and During COVID-19.
Rynders CA, Bowen AE, Cooper E … +5 more , Brinton JT, Higgins J, Nadeau KJ, Wright KP, Simon SL
J Biol Rhythms · 2022 Dec · PMID 36124632 · Full text
The majority of high school-aged adolescents obtain less than the recommended amount of sleep per night, in part because of imposed early school start times. Utilizing a naturalistic design, the present study evaluated c...
The majority of high school-aged adolescents obtain less than the recommended amount of sleep per night, in part because of imposed early school start times. Utilizing a naturalistic design, the present study evaluated changes in objective measurements of sleep, light, and physical activity before (baseline) and during the first wave of the COVID-19 pandemic (during COVID-19) in a group of US adolescents. Sixteen adolescents (aged 15.9 ± 1.2 years, 68.8% female) wore an actigraphy monitor for 7 consecutive days during an in-person week of school before the pandemic (October 2018-February 2020) and again during the pandemic when instruction was performed virtually (May 2020). Delayed weekday sleep onset times of 1.66 ± 1.33 h ( < 0.001) and increased sleep duration of 1 ± 0.87 h ( < 0.001) were observed during COVID-19 compared with baseline. Average lux was significantly higher during COVID-19 compared with baseline ( < 0.001). Weekday physical activity parameters were not altered during COVID-19 compared with baseline, except for a delay in the midpoint of the least active 5 h ( value = 0.044). This analysis provides insight into how introducing flexibility into the traditional school schedule might influence sleep in adolescents.
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