Journal of Biological Rhythms最新文献

The role of the hierarchical organization of the suprachiasmatic nucleus (SCN) in its functioning, jet lag, and the light treatment of jet lag remains poorly understood. Using the core-shell model, we mimic collective behavior of the core and shell populations of the SCN oscillators in transient states after rapid traveling east and west. The existence of a special region of slow dynamical states of the SCN oscillators can explain phenomena such as the east-west asymmetry of jet lag, instances when entrainment to an advance is via delay shifts, and the dynamics of jet lag recovery time. If jet lag brings the SCN state into this region, it will take a long time to leave it and restore synchronization among oscillators. We show that the population of oscillators in the core responds quickly to a rapid phase shift of the light-dark cycle, in contrast to the shell, which responds slowly. A slow recovery of the synchronization among the shell oscillators in transient states may strongly affect reentrainment in peripheral tissues and behavioral rhythms. We discuss the relationship between molecular, electrical, and behavioral rhythms. We also describe how light pulses affect the SCN and analyze the efficiency of the light treatment in facilitating the adaptation of the SCN to a new time zone. Light pulses of a moderate duration and intensity reduce the recovery time after traveling east, but not west. However, long duration and high intensity of light pulses are more detrimental than beneficial for speeding up reentrainment. The results of the core-shell model are compared with experimental data and other biologically motivated models of the SCN.

Environmental light conditions during development can have long-lasting effects on the physiology and behavior of an animal. Photoperiod, a clear example of environmental light conditions, is detected by and coded in the suprachiasmatic nucleus. It is therefore possible that differences observed in behavior in adulthood after exposure to different perinatal photoperiods are caused by lasting changes in the suprachiasmatic nucleus or alternatively, in other nuclei affected by perinatal photoperiod. It can then be expected that behavior with strong circadian aspects, like rest-activity and sleep, are affected by difference in photoperiod during development as well. To investigate this further, we exposed mice to different photoperiods during their development in the womb until weaning (long: 16 h of light, 8 h of darkness; short: 8 h of light, 16 h of darkness). After weaning, the animals were exposed to a 12 h:12 h light:dark cycle for at least 3 more weeks and some animals were subsequently exposed to constant darkness. We assessed their rest-activity patterns by recording voluntary locomotor activity and used EEG recordings to determine sleep architecture and electroencephalographic spectral density. Perinatal long photoperiod animals showed a shorter duration of locomotor activity than short photoperiod-developed mice in a 12:12 light-dark cycle. This difference disappeared in constant darkness. In the light phase, that is, during the day, perinatal long photoperiod mice spent less time awake and more time in NREM sleep than short photoperiod-developed mice. No effects of perinatal photoperiod were observed in the EEG spectral density or in response to sleep deprivation. We see lasting differences in behavioral locomotor activity and sleep in female and male mice after exposure to different perinatal photoperiods. We conclude that perinatal photoperiod programs a developing mammal for different external conditions and changes brain physiology, which in turn results in long-lasting, possibly even permanent, changes in the sleep and locomotor activity.

Circadian rhythms, intrinsic 24-h cycles that drive rhythmic changes in behavior and physiology, are important for normal physiology and health. Previous work in adults has identified sex differences in circadian rhythms of melatonin, temperature, and the intrinsic period of the human circadian timing system. However, less is known about sex differences in circadian rhythms at other developmental stages. To address this gap, we considered a secondary analysis of sleep and circadian data from two studies involving adolescent participants during the academic year: (n = 32, 15 females). We collected 1 week of in-home actigraphy data to calculate sleep-wake parameters and in-laboratory salivary melatonin data collection in dim-light conditions was used to compute dim-light melatonin onset (DLMO) and offset (DLMOff) using a threshold of 4 pg/mL. We found that DLMO was an average of 96 min earlier, the time between DLMO and bedtime was an average of 56 min greater, and the biological night (time between DLMO and DLMOff) was 60 min longer in females compared to males, even though bedtimes and waketimes were not statistically different between the groups. In addition, after accounting for differences in bedtime, sex was still a significant predictor of DLMO. Conversely, no evidence was found indicating a difference in DLMOff or the phase angle between DLMOff and waketime by sex. These findings suggest that sex differences in circadian rhythms are present in adolescents and may have implications for circadian health during this important developmental period.

The present study aimed to develop a TaqMan genotyping card for molecular chronotype assessment based on a predictive panel of 35 previously identified genetic variants. A reliable TaqMan assay was successfully developed for 33 out of the 35 chronotype-predictive variants. The resulting TaqMan genotyping card was utilized to genetically characterize 196 new individuals (in addition to the previously studied 96) and the Morningness-Eveningness Questionnaire was utilized for their phenotypical chronotype assessment. The predictive panel performance was validated on (a) a group of morning and evening individuals (logistic regression model), (b) a representative sample of the original study population also including intermediate chronotypes (linear regression model) and, (c) 25,986 individuals from the Estonian Biobank, for whom Munich Chronotype Questionnaire scores were available. The validation of the morningness-eveningness logistic regression model on 25 morning and 21 evening types resulted in a predictive value of 72%, confirming the reliability of the predictive panel and the success of its conversion into a TaqMan genotyping card. By contrast, the inclusion of intermediate individuals in the model led to a significant decrease in predictive performance (45% on 100 individuals [25 morning, 54 intermediate, and 21 evening]), with intermediate types being the most affected. No significant associations were observed between the genotype panel and chronotype in the Estonian Biobank sample. In conclusion, our genotyping card might represent a promising molecular chronotyping tool for the Italian population. Its performance in other populations is worthy of further study.

Cardiovascular health requires the orchestration of the daily rhythm of blood pressure (BP), which responds to changes in light exposure and dietary patterns. Whether rhythmic light and feeding can modulate daily BP rhythm directly or via modulating intrinsic core clock gene Bmal1 is unknown. Using inducible global Bmal1 knockout mice (iBmal1KO), we explored the impact of rhythmic light, rhythmic feeding, or their combination on various physiological parameters. Daily rhythms of BP, heart rate, and locomotor activity were monitored via radiotelemetry, while food intake patterns were tracked using the BioDAQ system. Respiratory exchange ratio (RER) and energy expenditure (EE) were assessed through indirect calorimetry. In addition, spectrum analysis was employed to analyze spontaneous baroreflex sensitivity and heart rate variability, and urinary norepinephrine excretion was quantified using high-performance liquid chromatography (HPLC). Neither rhythmic feeding nor rhythmic light alone was sufficient to reinstate the daily BP rhythm in arrhythmic iBmal1KO mice. However, combining the light and feeding cues in synchrony partially restored the daily BP rhythm. Interestingly, rhythmic feeding alone robustly reinstated RER and EE rhythms, even without rhythmic light. Similar to BP, the partial reinstatement of the daily rhythms in heart rate and locomotor activity was observed only when rhythmic light and feeding were applied in tandem. Rhythmic light by itself did not restore the light-dark phase difference in baroreflex sensitivity, urinary norepinephrine excretion, or the daily rhythm of heart rate variability. However, rhythmic feeding, alone or in combination with rhythmic light, successfully reinstated the light-dark phase differences in these parameters. In the absence of Bmal1, the synergy between rhythmic light and feeding can partially restore daily BP rhythm.

In both diurnal and nocturnal species, the neurons in the suprachiasmatic nucleus (SCN) generate a daily pattern in which the impulse frequency peaks at midday and is lowest during the night. This pattern, common to both day-active and night-active species, has led to the long-standing notion that their functional difference relies merely on a sign reversal in SCN output. However, recent evidence shows that the response of the SCN to the animal's physical activity is opposite in nocturnal and diurnal animals. This finding suggests the presence of additional differences in the circadian system between nocturnal and diurnal species. We therefore attempted to identify these differences in neuronal network organization using the A-B two-oscillator model, which is comprised of Poincaré like oscillators. Based on this model, we infer that in diurnal animals the feedback from physical activity acts on neuronal subpopulations in the SCN that do not receive light input; in contrast, in nocturnal animals, physical activity acts on light-receptive neurons in the SCN in order to produce high-amplitude circadian rhythms.