Journal Of Biological Rhythms[JOURNAL]
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200 papers
Impact of Light Schedules and Model Parameters on the Circadian Outcomes of Individuals.
Mayer C, Walch O, Forger DB … +1 more , Hannay K
J Biol Rhythms · 2023 Aug · PMID 37350312 · Publisher ↗
Key differences exist between individuals in terms of certain circadian-related parameters, such as intrinsic period and sensitivity to light. These variations can differentially impact circadian timing, leading to chall...
Key differences exist between individuals in terms of certain circadian-related parameters, such as intrinsic period and sensitivity to light. These variations can differentially impact circadian timing, leading to challenges in accurately implementing time-sensitive interventions. In this work, we parse out these effects by investigating the impact of parameters from a macroscopic model of human circadian rhythms on phase and amplitude outputs. Using in silico light data designed to mimic commonly studied schedules, we assess the impact of parameter variations on model outputs to gain insight into the different effects of these schedules. We show that parameter sensitivity is heavily modulated by the lighting routine that a person follows, with darkness and shift work schedules being the most sensitive. We develop a framework to measure overall sensitivity levels of the given light schedule and furthermore decompose the overall sensitivity into individual parameter contributions. Finally, we measure the ability of the model to extract parameters given light schedules with noise and show that key parameters like the circadian period can typically be recovered given known light history. This can inform future work on determining the key parameters to consider when personalizing a model and the lighting protocols to use when assessing interindividual variability.
Chronotype, Social Jetlag, and Nicotine Use.
Ghotbi N, Rabenstein A, Pilz LK … +2 more , Rüther T, Roenneberg T
J Biol Rhythms · 2023 Aug · PMID 37345295 · Full text
Late chronotype, which often leads to higher social jetlag (SJL), is strongly associated with the prevalence of smoking. Any circadian disruption, strain, or misalignment, results in people not being able to live accordi...
Late chronotype, which often leads to higher social jetlag (SJL), is strongly associated with the prevalence of smoking. Any circadian disruption, strain, or misalignment, results in people not being able to live according to their biological time as is described by SJL, which we will therefore use as umbrella term. We hypothesized two scenarios potentially explaining the association between smoking and SJL: (A) If smoking delays the clock, circadian phase should advance upon quitting. (B) If people smoke more to compensate the consequences of SJL, circadian phase should not change upon quitting. To distinguish between these two hypotheses, we accompanied participants of a smoking cessation program (not involving nicotine replacement products) across the cessation intervention (3 weeks prior and 6 weeks after) by monitoring their circadian behavior, sleep quality, and daytime sleepiness via questionnaires and actimetry. Our results show no effects of cessation on SJL, chronotype, sleep quality, or daytime sleepiness, thereby favoring scenario (B). Thus, smoking may be a consequence of rather than a cause for SJL. Daytime sleepiness was a significant predictor for the outcome in our model but did not improve with cessation.
Reduced Plasticity in Coupling Strength in the Aging SCN Clock as Revealed by Kuramoto Modeling.
van Beurden AW, Meylahn JM, Achterhof S … +5 more , Buijink R, Olde Engberink A, Michel S, Meijer JH, Rohling JHT
J Biol Rhythms · 2023 Oct · PMID 37329153 · Full text
The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consists of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase coherence of the neurons is...
The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consists of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase coherence of the neurons is plastic and driven by the duration of daylight. With aging, the capacity to behaviorally adapt to seasonal changes in photoperiod reduces. The mechanisms underlying photoperiodic adaptation are largely unknown, but are important to unravel for the development of novel interventions to improve the quality of life of the elderly. We analyzed the phase coherence of single-cell PERIOD2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN of young and old mice entrained to either long or short photoperiod. The phase coherence was used as input to a 2-community noisy Kuramoto model to estimate the coupling strength between and within neuronal subpopulations. The model revealed a correlation between coupling strength and photoperiod-induced changes in the phase relationship among neurons, suggesting a functional link. We found that the SCN of young mice adapts in coupling strength over a large range, with weak coupling in long photoperiod (LP) and strong coupling in short photoperiod (SP). In aged mice, we also found weak coupling in LP, but a reduced capacity to reach strong coupling in SP. The inability to respond with an increase in coupling strength suggests that manipulation of photoperiod is not a suitable strategy to enhance clock function with aging. We conclude that the inability of aged mice to reach strong coupling contributes to deficits in behavioral adaptation to seasonal changes in photoperiod.
Estradiol Regulates Circadian Responses to Acute and Constant Light Exposure in Female Mice.
Michaud JM, Waring CT, Medeiros Contini F … +6 more , Burns ME, Price JC, Quintana J, Concepcion HA, Deane HV, Seggio JA
J Biol Rhythms · 2023 Aug · PMID 37282496 · Publisher ↗
Sex hormones are well known to modulate circadian timekeeping as well as the behavioral and physiological responses to circadian disruption. Gonadectomy, reducing the amount of circulating gonadal hormones, in males and...
Sex hormones are well known to modulate circadian timekeeping as well as the behavioral and physiological responses to circadian disruption. Gonadectomy, reducing the amount of circulating gonadal hormones, in males and females produces alterations to the free-running rhythm and the responses to light exposure by the central oscillator of the suprachiasmatic nucleus (SCN). In this study, we tested whether estradiol plays a role in regulating the circadian responses to acute (light pulses) and chronic light exposure (constant light [LL] vs standard light:dark [LD] cycle) in female C57BL6/NJ mice. Mice were either ovariectomized or given sham surgery and given a placebo (P) or estradiol (E) pellet for hormone replacement so that there were 6 groups: (1) LD/Sham, (2) LL/Sham, (3) LD/OVX + P, (4) LL/OVX + P, (5) LD/OVX + E, and (6) LL/OVX + E. After 65 days of light cycle exposure, blood and SCNs were removed and serum estradiol plus SCN estradiol receptor alpha (ERα) and estradiol receptor beta (ERβ) were measured via ELISA. The OVX + P mice exhibited shorter circadian periods and were more likely to become arrhythmic in LL compared with mice with intact estradiol (sham or E replacement mice). The OVX + P mice exhibited reduced circadian robustness (power) and reduced circadian locomotor activity in both LD and LL compared with sham controls or OVX + E mice. The OVX + P mice also exhibited later activity onsets in LD and attenuated phase delays, but not advances, when given a 15-min light pulse compared with estradiol intact mice. LL led to reductions in ERβ, but not ERα, regardless of the surgery type. These results indicate that estradiol can modulate the effects of light on the circadian timing system and that estradiol can enhance responses to light exposure and provide protection against a loss of circadian robustness.
Molecular and Neural Mechanisms of Temperature Preference Rhythm in .
Goda T, Umezaki Y, Hamada FN
J Biol Rhythms · 2023 Aug · PMID 37222551 · Full text
Temperature influences animal physiology and behavior. Animals must set an appropriate body temperature to maintain homeostasis and maximize survival. Mammals set their body temperatures using metabolic and behavioral st...
Temperature influences animal physiology and behavior. Animals must set an appropriate body temperature to maintain homeostasis and maximize survival. Mammals set their body temperatures using metabolic and behavioral strategies. The daily fluctuation in body temperature is called the body temperature rhythm (BTR). For example, human body temperature increases during wakefulness and decreases during sleep. BTR is controlled by the circadian clock, is closely linked with metabolism and sleep, and entrains peripheral clocks located in the liver and lungs. However, the underlying mechanisms of BTR are largely unclear. In contrast to mammals, small ectotherms, such as , control their body temperatures by choosing appropriate environmental temperatures. The preferred temperature of increases during the day and decreases at night; this pattern is referred to as the temperature preference rhythm (TPR). As flies are small ectotherms, their body temperature is close to that of the surrounding environment. Thus, TPR produces BTR, which exhibits a pattern similar to that of human BTR. In this review, we summarize the regulatory mechanisms of TPR, including recent studies that describe neuronal circuits relaying ambient temperature information to dorsal neurons (DNs). The neuropeptide diuretic hormone 31 (DH31) and its receptor (DH31R) regulate TPR, and a mammalian homolog of DH31R, the calcitonin receptor (CALCR), also plays an important role in mouse BTR regulation. In addition, both fly TPR and mammalian BTR are separately regulated from another clock output, locomotor activity rhythms. These findings suggest that the fundamental mechanisms of BTR regulation may be conserved between mammals and flies. Furthermore, we discuss the relationships between TPR and other physiological functions, such as sleep. The dissection of the regulatory mechanisms of TPR could facilitate an understanding of mammalian BTR and the interaction between BTR and sleep regulation.
S-Cone Photoreceptors Regulate Daily Rhythms and Light-Induced Arousal/Wakefulness in Diurnal Grass Rats ().
Kim AB, Beaver EM, Collins SG … +4 more , Kriegsfeld LJ, Lockley SW, Wong KY, Yan L
J Biol Rhythms · 2023 Aug · PMID 37222434 · Full text
Beyond visual perception, light has non-image-forming effects mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). The present study first used multielectrode array recordings...
Beyond visual perception, light has non-image-forming effects mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). The present study first used multielectrode array recordings to show that in a diurnal rodent, Nile grass rats (), ipRGCs generate rod/cone-driven and melanopsin-based photoresponses that stably encode irradiance. Subsequently, two ipRGC-mediated non-image-forming effects, namely entrainment of daily rhythms and light-induced arousal, were examined. Animals were first housed under a 12:12 h light/dark cycle (lights-on at 0600 h) with the light phase generated by a low-irradiance fluorescent light (F12), a daylight spectrum (D65) stimulating all photoreceptors, or a narrowband 480 nm spectrum (480) that maximized melanopsin stimulation and minimized S-cone stimulation (λ 360 nm) compared to D65. Daily rhythms of locomotor activities showed onset and offset closer to lights-on and lights-off, respectively, in D65 and 480 than in F12, and higher day/night activity ratio under D65 versus 480 and F12, suggesting the importance of S-cone stimulation. To assess light-induced arousal, 3-h light exposures using 4 spectra that stimulated melanopsin equally but S-cones differentially were superimposed on F12 background lighting: D65, 480, 480 + 365 (narrowband 365 nm), and D65 - 365. Compared to the F12-only condition, all four pulses increased in-cage activity and promoted wakefulness, with 480 + 365 having the greatest and longest-lasting wakefulness-promoting effects, again indicating the importance of stimulating S-cones as well as melanopsin. These findings provide insights into the temporal dynamics of photoreceptor contributions to non-image-forming photoresponses in a diurnal rodent that may help guide future studies of lighting environments and phototherapy protocols that promote human health and productivity.
A Cannabinoid Receptor 1 Agonist Reduces Light-induced Phase Delays in Male But Not Female Mice.
Niepokny TD, Mintz EM
J Biol Rhythms · 2023 Aug · PMID 37190758 · Full text
Animals adapt to a changing environment by synchronizing their circadian rhythms to different stimuli, the strongest and most reliable being the daily light-dark cycle. Photic information reaches the central circadian pa...
Animals adapt to a changing environment by synchronizing their circadian rhythms to different stimuli, the strongest and most reliable being the daily light-dark cycle. Photic information reaches the central circadian pacemaker, the suprachiasmatic nucleus (SCN), which drives rhythms in physiology and behavior throughout the brain and body. The endocannabinoid system (ECS) is a neuromodulatory system that is present within the SCN, including the primary receptor, cannabinoid receptor 1 (CB1). Exogenous cannabinoids that target CB1 inhibit the phase-shifting effects of light in hamsters, mice, and rats. Furthermore, there is evidence in cultured microglial cells that cannabidiol (CBD), a constituent of , alters core circadian clock genes, while the CB1 agonist delta-9-tetrahydrocannabinol (THC) does not. The CB1 agonist studies were conducted using male animals only, but cannabinoids exhibit sex-dependent effects in various aspects of physiology and behavior. In addition, the effects of CBD on circadian behavioral rhythms have yet to be investigated. Therefore, we decided to test the effects of acute injections of CBD or the CB1 agonist CP 55,940 on light-induced phase delays in male and female C57BL/6J mice. Animals received a single injection at circadian time (CT) 15.5, followed by a 10-min light or dark (sham) pulse at CT 16. Running-wheel activity was monitored to determine activity levels and the behavioral phase shifts from different treatments. We observed a sex difference in the magnitude of phase delay size in response to CP 55,940 administration. Males had attenuated phase delays with increasing doses of CP 55,940, while females did not differ from control. Various doses of CBD had no effect on the phase-delaying effects of light in either sex. Our results show a sex difference in the gating of photic phase shifts by CB1 activation.
A Subset of Circadian Neurons Expressing Enables Appropriate Phasing of Activity Rhythms in Under Warm Temperatures.
Iyengar AS, Rao S, Sheeba V
J Biol Rhythms · 2023 Aug · PMID 37102578 · Publisher ↗
Under conditions of prolonged durations of warmth, flies counter potential temperature stress by shifting their locomotor activity from day into night when the conditions are likely to be less harsh. Modulation of a rhyt...
Under conditions of prolonged durations of warmth, flies counter potential temperature stress by shifting their locomotor activity from day into night when the conditions are likely to be less harsh. Modulation of a rhythmic behavior such as this in response to the environment would require interaction between at least 2 neuronal systems: (1) a system to receive input from the environment, and (2) the to correctly time rhythmic activity in response to this thermosensory input. Our previous studies found that a thermosensory mutant of the ion channel Transient Receptor Potential-A1 () failed to shift activity into the dark like control flies do and also identified the role of a specific cluster of the -expressing neurons, the neurons necessary for this. In this study, we extended our previous findings and characterized the identity of these neurons based on their overlap with circadian neurons. Utilizing various genetic manipulations, we asked whether the overlapping neurons could be potential points of intersection between the 2 circuits that modulate behavior under warm temperature, meaning whether they function as both-sensory and clock neurons. We found that the molecular clock within the cluster was not necessary, but the expression of in a subset of circadian neurons, the small ventrolateral neurons (sLNvs), was necessary in modulating phasing of behavior under warm temperature. Furthermore, attempting to identify the neuronal circuit, we were able to uncover the potential roles of serotonin and acetylcholine in modulating this temperature-dependent behavior. Finally, we also discuss possible parallel neuronal pathways that may exist to give rise to this modulation of behavior under warm temperature, thereby supporting and expanding the knowledge of the field about circuits that control temperature-mediated behavioral outcomes.
Persistence of Nocturnality in Decapitated and Bisected Flatworms.
Omond SET, Lesku JA
J Biol Rhythms · 2023 Jun · PMID 36960836 · Full text
The ability of flatworms to regenerate entire brain structures, and indeed much of their body from mere fragments of the whole animal, presents the unique opportunity to observe the development of day-night rhythms in ad...
The ability of flatworms to regenerate entire brain structures, and indeed much of their body from mere fragments of the whole animal, presents the unique opportunity to observe the development of day-night rhythms in adult animals. In many animals, young are arrhythmic, and their species-specific timing of activity develops as the animal matures. In this study, we created two flatworm cohorts, housed in isolation, that were regenerating either (1) the brain in a decapitated animal, or (2) major body structures in a bisected, tailless animal. In this way, we observed how bisection influenced the level of activity and diel rhythmicity, and how these developed as each flatworm regenerated. Here, we demonstrate that intact flatworms were predominantly active at night, with peaks in activity seen in the hours after lights-off and before lights-on. While decapitated and tailless flatworms could still move, both were less active than the original animal, and both segments retained a nocturnal lifestyle. Furthermore, decapitated flatworms, once regenerated, again showed a U-shaped pattern of nocturnal activity reminiscent of the two night-time peaks seen in the original animal. These results could be used to further investigate how regeneration may affect motor control and motor output, or to further investigate the presence of a clock in the flatworm brain.
Temporal Dissociation Between Activity and Body Temperature Rhythms of a Subterranean Rodent () in Field Enclosures.
Jannetti MG, Tachinardi P, Valentinuzzi VS … +1 more , Oda GA
J Biol Rhythms · 2023 Jun · PMID 36924450 · Publisher ↗
Several wild rodents, such as the subterranean tuco-tucos (), switch their time of activity from diurnal to nocturnal when they are transferred from field to the laboratory. Nevertheless, in most studies, different metho...
Several wild rodents, such as the subterranean tuco-tucos (), switch their time of activity from diurnal to nocturnal when they are transferred from field to the laboratory. Nevertheless, in most studies, different methods to measure activity in each of these conditions were used, which raised the question of whether the detected change in activity timing could be an artifact. Because locomotor activity and body temperature (Tb) rhythms in rodents are tightly synchronized and because abdominal Tb loggers can provide continuous measurements across field and laboratory, we monitored Tb as a proxy of activity in tuco-tucos transferred from a semi-field enclosure to constant lab conditions. In the first stage of this study ("Tb-only group," 2012-2016), we verified high incidence (55%, = 20) of arrhythmicity, with no consistent diurnal Tb rhythms in tuco-tucos maintained under semi-field conditions. Because these results were discrepant from subsequent findings using miniature accelerometers (portable activity loggers), which showed diurnal activity patterns in natural conditions ( = 10, "Activity-only group," 2016-2017), we also investigated, in the present study, whether the tight association between activity and Tb would be sustained outside the lab. To verify this, we measured activity and Tb simultaneously across laboratory and semi-field deploying both accelerometers and Tb loggers to each animal. These measurements ( = 11, "Tb + activity group," 2019-2022) confirmed diurnality of locomotor activity and revealed an unexpected loosening of the temporal association between Tb and activity rhythms in the field enclosures, which is otherwise robustly tight in the laboratory.
Antisense Transcription of the Frequency Gene Is Rhythmically Regulated by CSP-1 Repressor but Dispensable for Clock Function.
Cemel IA, Diernfellner ACR, Brunner M
J Biol Rhythms · 2023 Jun · PMID 36876962 · Full text
The circadian clock of is based on a negative transcriptional/translational feedback loops. The () gene controls the morning-specific rhythmic transcription of a sense RNA encoding FRQ, the negative element of the core...
The circadian clock of is based on a negative transcriptional/translational feedback loops. The () gene controls the morning-specific rhythmic transcription of a sense RNA encoding FRQ, the negative element of the core circadian feedback loop. In addition, a long noncoding antisense RNA, , is rhythmically transcribed in an evening-specific manner. It has been reported that the rhythm relies on transcriptional interference with transcription and that complete suppression of transcription impairs the circadian clock. We show here that transcription is dispensable for circadian clock function. Rather, the evening-specific transcriptional rhythm of is mediated by the morning-specific repressor CSP-1. Since CSP-1 expression is induced by light and glucose, this suggests a rhythmic coordination of transcription with metabolism. However, a possible physiological significance for the circadian clock remains unclear, as suitable assays are not available.
Associations Between Multidimensional Sleep Health Parameters and Adolescents' Self-reported Light Exposure in the Free-living Environment.
Gauthier-Gagné G, Saha S, Jensen J … +2 more , Sommerville G, Gruber R
J Biol Rhythms · 2023 Jun · PMID 36843359 · Publisher ↗
The objective of this study was to characterize the associations between light exposure in the free-living environment and multiple dimensions of sleep health of typically developing adolescents. Fifty-six (29 girls, 27...
The objective of this study was to characterize the associations between light exposure in the free-living environment and multiple dimensions of sleep health of typically developing adolescents. Fifty-six (29 girls, 27 boys) typically developing adolescents (mean age = 13.59, SD = 0.89, range = 12-17 years) participated. For six consecutive nights, sleep was assessed in the home environment using actigraphy. During the same period, participants were asked to fill out a daily sleep log and a daily light exposure log, and to complete questionnaires regarding their alertness and subjective sleep satisfaction. Longer self-reported exposure to daylight in the morning was associated with longer objectively measured sleep duration. Longer self-reported exposures to electronic devices in the evening were associated with later objectively measured sleep onset and offset times, shorter sleep duration, and greater day-to-day sleep variability. Longer morning exposure to outdoor light was associated with a longer sleep duration. Self-reported light exposure was not associated with sleep satisfaction, alertness/sleepiness, or sleep efficiency. Among the covariates, circadian preference accounted for the highest percentage of variance. Adolescents' sleep health is associated with the self-reported duration of exposure to daylight in the morning and to electronic devices in the evening.
Voluntary Wheel Running Exercise Does Not Attenuate Circadian and Cardiac Dysfunction Caused by Conditional Deletion of .
Yusifova M, Yusifov A, Polson SM … +3 more , Todd WD, Schmitt EE, Bruns DR
J Biol Rhythms · 2023 Jun · PMID 36802963 · Full text
Circadian misalignment occurs with age, jet lag, and shift work, leading to maladaptive health outcomes including cardiovascular diseases. Despite the strong link between circadian disruption and heart disease, the cardi...
Circadian misalignment occurs with age, jet lag, and shift work, leading to maladaptive health outcomes including cardiovascular diseases. Despite the strong link between circadian disruption and heart disease, the cardiac circadian clock is poorly understood, prohibiting identification of therapies to restore the broken clock. Exercise is the most cardioprotective intervention identified to date and has been suggested to reset the circadian clock in other peripheral tissues. Here, we tested the hypothesis that conditional deletion of core circadian gene would disrupt cardiac circadian rhythm and function and that this disruption would be ameliorated by exercise. To test this hypothesis, we generated a transgenic mouse with spatial and temporal deletion of only in adult cardiac myocytes (Bmal1 cardiac knockout [cKO]). Bmal1 cKO mice demonstrated cardiac hypertrophy and fibrosis concomitant with impaired systolic function. This pathological cardiac remodeling was not rescued by wheel running. While the molecular mechanisms responsible for the profound cardiac remodeling are unclear, it does not appear to involve activation of the mammalian target of rapamycin (mTOR) signaling or changes in metabolic gene expression. Interestingly, cardiac deletion of disrupted systemic rhythms as evidenced by changes in the onset and phasing of activity in relationship to the light/dark cycle and by decreased periodogram power as measured by core temperature, suggesting cardiac clocks can regulate systemic circadian output. Together, we suggest a critical role for cardiac in regulating both cardiac and systemic circadian rhythm and function. Ongoing experiments will determine how disruption of the circadian clock causes cardiac remodeling in an effort to identify therapeutics to attenuate the maladaptive outcomes of a broken cardiac circadian clock.
Modern Language for Modern Circadian Biologists: The End of the "Slave" Oscillator.
Berezin CT
J Biol Rhythms · 2023 Aug · PMID 36789723 · Publisher ↗
Abstract loading — click title to view on PubMed.
Steve Brown.
Schibler U, Dibner C, Ripperger J
J Biol Rhythms · 2023 Apr · PMID 36762620 · Full text
Abstract loading — click title to view on PubMed.
Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice.
Akyel YK, Ozturk Civelek D, Ozturk Seyhan N … +6 more , Gul S, Gazioglu I, Pala Kara Z, Lévi F, Kavakli IH, Okyar A
J Biol Rhythms · 2023 Apr · PMID 36762608 · Full text
The circadian timing system controls absorption, distribution, metabolism, and elimination processes of drug pharmacokinetics over a 24-h period. Exposure of target tissues to the active form of the drug and cytotoxicity...
The circadian timing system controls absorption, distribution, metabolism, and elimination processes of drug pharmacokinetics over a 24-h period. Exposure of target tissues to the active form of the drug and cytotoxicity display variations depending on the chronopharmacokinetics. For anticancer drugs with narrow therapeutic ranges and dose-limiting side effects, it is particularly important to know the temporal changes in pharmacokinetics. A previous study indicated that pharmacokinetic profile of capecitabine was different depending on dosing time in rat. However, it is not known how such difference is attributed with respect to diurnal rhythm. Therefore, in this study, we evaluated capecitabine-metabolizing enzymes in a diurnal rhythm-dependent manner. To this end, C57BL/6J male mice were orally treated with 500 mg/kg capecitabine at ZT1, ZT7, ZT13, or ZT19. We then determined pharmacokinetics of capecitabine and its metabolites, 5'-deoxy-5-fluorocytidine (5'DFCR), 5'-deoxy-5-fluorouridine (5'DFUR), 5-fluorouracil (5-FU), in plasma and liver. Results revealed that plasma and AUC (area under the plasma concentration-time curve from 0 to 6 h) values of capecitabine, 5'DFUR, and 5-FU were higher during the rest phase (ZT1 and ZT7) than the activity phase (ZT13 and ZT19) ( < 0.05). Similarly, and AUC values of 5'DFUR and 5-FU in liver were higher during the rest phase than activity phase ( < 0.05), while there was no significant difference in liver concentrations of capecitabine and 5'DFCR. We determined the level of the enzymes responsible for the conversion of capecitabine and its metabolites at each ZT. Results indicated the levels of carboxylesterase 1 and 2, cytidine deaminase, uridine phosphorylase 2, and dihydropyrimidine dehydrogenase ( < 0.05) are being rhythmically regulated and, in turn, attributed different pharmacokinetics profiles of capecitabine and its metabolism. This study highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects.
Prolonged Light Exposure Induces Circadian Impairment in Aquaporin-4-Knockout Mice.
Murakami A, Tsuji K, Isoda M … +5 more , Matsuo M, Abe Y, Yasui M, Okamura H, Tominaga K
J Biol Rhythms · 2023 Apr · PMID 36694941 · Publisher ↗
Astrocytes are densely present in the suprachiasmatic nucleus (SCN), which is the master circadian oscillator in mammals, and are presumed to play a key role in circadian oscillation. However, specific astrocytic molecul...
Astrocytes are densely present in the suprachiasmatic nucleus (SCN), which is the master circadian oscillator in mammals, and are presumed to play a key role in circadian oscillation. However, specific astrocytic molecules that regulate the circadian clock are not yet well understood. In our study, we found that the water channel aquaporin-4 (AQP4) was abundantly expressed in SCN astrocytes, and we further examined its circadian role using AQP4-knockout mice. There was no prominent difference in circadian behavioral rhythms between and mice subjected to light-dark cycles and constant dark conditions. However, exposure to constant light induced a greater decrease in the mice rhythmicity. Although the damped rhythm in long-term constant light recovered after transfer to constant dark conditions in both genotypes, the period until the reappearance of original rhythmicity was severely prolonged in mice. In conclusion, AQP4 absence exacerbates the prolonged light-induced impairment of circadian oscillations and delays their recovery to normal rhythmicity.
as a Promising Model Organism in Chronobiology.
Migliori ML, Goya ME, Lamberti ML … +4 more , Silva F, Rota R, Bénard C, Golombek DA
J Biol Rhythms · 2023 Apr · PMID 36680418 · Publisher ↗
Circadian rhythms represent an adaptive feature, ubiquitously found in nature, which grants living beings the ability to anticipate daily variations in their environment. They have been found in a multitude of organisms,...
Circadian rhythms represent an adaptive feature, ubiquitously found in nature, which grants living beings the ability to anticipate daily variations in their environment. They have been found in a multitude of organisms, ranging from bacteria to fungi, plants, and animals. Circadian rhythms are generated by endogenous clocks that can be entrained daily by environmental cycles such as light and temperature. The molecular machinery of circadian clocks includes a transcriptional-translational feedback loop that takes approximately 24 h to complete. has been a model organism of choice to understand the molecular basis of circadian clocks. However, alternative animal models are also being adopted, each offering their respective experimental advantages. The nematode provides an excellent model for genetics and neuro-behavioral studies, which thanks to its ease of use and manipulation, as well as availability of genetic data and mutant strains, is currently used as a novel model for circadian research. Here, we aim to evaluate as a model for chronobiological studies, focusing on its strengths and weaknesses while reviewing the available literature. Possible zeitgebers (including light and temperature) are also discussed. Determining the molecular bases and the neural circuitry involved in the central pacemaker of the ' clock will contribute to the understanding of its circadian system, becoming a novel model organism for the study of diseases due to alterations of the circadian cycle.
School Attendance, Chronotype, and Day-of-the-Week Effect in Adolescent Male Basketball Players.
Bruno S, Benedetti D, Bazzani A … +7 more , Ferri F, Granieri I, Cruz-Sanabria F, Fiori S, d'Ascanio P, Frumento P, Faraguna U
J Biol Rhythms · 2023 Apr · PMID 36680409 · Publisher ↗
Adolescents' conflict between circadian rhythm and early school start time is more pronounced in evening chronotypes, who tend to reduce sleep duration during school days compensating during the free days by oversleeping...
Adolescents' conflict between circadian rhythm and early school start time is more pronounced in evening chronotypes, who tend to reduce sleep duration during school days compensating during the free days by oversleeping (i.e., social jetlag). Cumulative weekly sleep debt may impair sport performance, which relies on physical and cognitive skills modulated by sleep. We hypothesized that chronotype predicts sport performance, and that it may interact with the day of the week. Moreover, given the role sleep plays in motor memory consolidation, we tested the hypothesis that school attendance, and the related chronic sleep deprivation, might be detrimental for participants in a training phase. Ninety-three adolescent male basketball players performed multiple free throw sessions ( = 7880) during both the school and holiday periods. Chronotype and its interaction with the day of the week significantly predicted shooting accuracy when attending school, but not on holidays. Evening types' performance gradually decreased from Monday to Friday. Participants with a more unstable performance (i.e., who did not complete the acquisition of the free throw motor scheme) worsened their accuracy when attending school. Our results suggest that the impact of chronotype and day of the week on sport performance is related to the presence of an externally imposed sleep/wake schedule and is consistent with evening types' increased likelihood of experiencing social jetlag. Possibly due to early school start time, attending school worsened the performance of participants in a training phase. Further investigations are required to assess whether reducing the mismatch between biological and social clocks might improve sport performance, along with other aspects of adolescents' life.
Validation of the Self-Rating of Biological Rhythm Disorder for Adolescents (SBRDA) Scale by Dim Light Melatonin Onset in Healthy Young Adults.
Xie Y, Wu X, Mou X … +4 more , Wang M, Tao S, Wan Y, Tao F
J Biol Rhythms · 2023 Apr · PMID 36635893 · Publisher ↗
Understanding the biological rhythms that influence young adult health is vital because the combination of biological changes and a circadian phase delay lead to young adults being at high risk of circadian misalignment....
Understanding the biological rhythms that influence young adult health is vital because the combination of biological changes and a circadian phase delay lead to young adults being at high risk of circadian misalignment. We have previously established a self-rating of biological rhythm disorder for adolescents (SBRDA). However, we did not externally validate the SBRDA against objective measures of biological rhythms such as dim light melatonin onset (DLMO)-the gold standard of the endogenous circadian phase. The purpose of this study was to verify the effectiveness of SBRDA in identifying individuals with biological rhythm disorders. Our participants were 42 (47.2%) boys and 47 (52.8%) girls with an average age of 18.5 ± 1.2 years. Saliva samples were collected from 4 h before bed time to 2 h after sleep every 60 min in a dim-light (<50 lx) laboratory environment. Biological rhythm parameters were assessed using questionnaires, including SBRDA, MEQ, and MCTQ. The mean DLMO time (h) was 22.2 ± 1.9. The DLMO correlated significantly with the SBRDA score ( = 0.33, < 0.001), MEQ score ( = -0.24, < 0.05), and MSFsc ( = 0.26, < 0.05). ROC curve analysis showed that SBRDA was of diagnostic value for biological rhythm disorder ( < 0.05). Our observations demonstrate that SBRDA, which is consistent with MEQ and MCTQ, can be used to reflect endogenous circadian rhythm disorders in young adults. Exposure to dim light may activate melatonin secretion and lead to an earlier peak in young adults with biological rhythm disorder.
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