Timed Exercise and Clocks: Does a Minimally Functional Suprachiasmatic Clock Support 24h Behavioral Rhythms?
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ABSTRACT:
PROVIDER: PRJNA857926 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20084826_1.fastq.gz | Fastqsanger.gz | |||
| SRR20084826_2.fastq.gz | Fastqsanger.gz | |||
| SRR20084827_1.fastq.gz | Fastqsanger.gz | |||
| SRR20084827_2.fastq.gz | Fastqsanger.gz | |||
| SRR20084828_1.fastq.gz | Fastqsanger.gz |
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Project description:The brain’s suprachiasmatic nucleus (SCN) is the master clock driving circadian rhythms in mammals. Vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are expressed in SCN neurons and mice with genetically targeted deletion of VPAC2 (Vipr2 -/-animals) show aberrant resetting to light, abnormal behavioral rhythms, and diminished SCN clock gene expression. Timed daily access to a running-wheel (scheduled voluntary exercise; SVE) promotes Vipr2 -/- SCN clock cell synchrony and 24h behavioral rhythms. We hypothesized that timed exercise alters the SCN transcriptome. Here, in control (Vipr2+/+) and Vipr2-/- mice under freely exercising and SVE conditions, RNAseq and qRT-PCR were used to measured gene expression of laser-dissected SCN. Compared to Vipr2+/+ mice, hundreds of genes were differentially expressed in the SCN from Vipr2-/- mice rhythmic in the freely exercising condition. Unexpectedly, SVE did not promote a Vipr2+/+-like SCN transcriptome in Vipr2-/- mice and many transcripts involved in SCN function including Avp, C1ql3, Gpr176, Prok2, Sst, Per2, and Nr1d1 remained dysregulated in the SVE condition. By contrast, circadian oscillators in the liver and lung were mostly intact in Vipr2-/- mice. This study indicates that marked molecular deficits in the SCN are sustained in behaviorally rhythmic Vipr2-/- mice, raising the possibility that a minimal functional SCN circadian clock can underpin whole animal rhythms.
2023-01-20 | GSE207992 | GEO
Project description:Circadian clocks are essential for generating and coordinating rhythms in animals’ physiology, behaviour, and metabolism. These activities are regulated by intracellular molecular clocks that operate with a ~24 hour periodicity. The African striped mouse, Rhabdomys pumilio, is notable for undergoing temporal niche switching from ancestrally nocturnal to diurnal, although the molecular components of its’ circadian organization remain unknown. We undertook transcriptome profiling of daily rhythms in the suprachiasmatic nucleus (SCN) and in the liver, lung and retina of Rhabdomys stably housed under a stable 12h:12h light:dark cycle with bright (n=10) or dim (n=10) daytime light intensity. Tissues were collected at two time points: two hours after lights on (Zeitgeber Time (ZT2)) coinciding with high behavioural activity, or two hours after lights off (ZT14) during the animal’s resting/sleep period, and RNA-sequencing performed.
2023-07-31 | E-MTAB-12024 | biostudies-arrayexpress
Project description:Circadian disruption, as shift work, is associated with metabolic diseases, including obesity and fatty liver, often attributed to discordance between internal clocks and environmental timekeepers1-5. However, this desynchrony hypothesis has not been rigorously tested. The body’s master clock, located in the suprachiasmatic nucleus (SCN), synchronizes peripheral clocks and ultimately metabolism2,6. Molecular clocks are comprised of transcriptional translational feedback loops involving gene activation by BMAL1, which is rhythmically repressed by separate mechanisms involving PER/CRY and REV-ERB nuclear receptors. Mice harboring whole body deletion of REV-ERBa/b have been reported to be arrhythmic7. However, we report here that mice lacking REV-ERBs specifically in the SCN maintain free-running and metabolic rhythms, but these are strikingly shortened by nearly 3 hours. When housed under a 24 hours light-dark cycle and fed an obesogenic diet, these mice gained excess weight and accrued more liver fat than controls. Remarkably, these metabolic disturbances were corrected by matching environmental lighting to the shortened endogenous clock period. Thus, SCN REV-ERBs are not required to maintain rhythmicity but powerfully control the free-running period. Moreover, these results support the hypothesis that dissonance between environmental conditions and endogenous period causes metabolic disruption. This has important implications for chronotherapy of metabolic and behavioral disorders.
2021-07-15 | GSE152919 | GEO
Project description:Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders.
| S-EPMC9160956 | biostudies-literature
Project description:Study objectiveWe have previously established that CAST/EiJ (CAST) mice differ from normal mice, such as C57BL/6J (B6), in the timing of wheel-running onset relative to light/dark cycles. These mice provide an animal model for studies of the genetic and neurobiological basis for circadian phase misalignment in humans. Neither differences in endogenous circadian period nor the shape of the photic phase response curve explain the difference in the timing of activity onset between CAST and B6 mice, suggesting a mechanism downstream of the circadian clock. Here, we further test the hypothesis that the two strains differ with respect to circadian oscillations at the molecular level.DesignSleep/wake cycles were examined and rhythms of Period1 (Per1) and Period2 (Per2) expression were measured in the cerebral cortex, suprachiasmatic nucleus (SCN), and other hypothalamic regions.SettingBasic sleep and molecular research laboratory.Patients or participantsMale mice of the B6 and CAST inbred strains.InterventionsNone.Measurements and resultsSleep/wake cycles were advanced by approximately 4 h in CAST mice relative to B6 mice. This was paralleled by phase-advanced rhythms of Per1 and Per2 expression, as measured byin situ hybridization, in the cerebral cortex of CAST relative to B6. By contrast, the timing of circadian oscillations and the photic induction ofPer1 and Per2 expression in the SCN were unaffected by strain.ConclusionThe advanced phase of wheel running and sleep/wake cycles in CAST mice relative to B6 mice is apparently not associated with differences in molecular oscillations in the SCN clock itself, but most likely in mechanisms downstream of the SCN clock. CAST mice may therefore provide a model system to investigate circadian downstream mechanisms underlying unusual patterns of entrainment to the ambient photoperiod.CitationJiang P; Franklin KM; Duncan MJ; O'Hara BF; Wisor JP. Distinct phase relationships between suprachiasmatic molecular rhythms, cerebral cortex molecular rhythms, and behavioral rhythms in early runner (CAST/EiJ) and nocturnal (C57BL/6J) mice. SLEEP 2012;35(10):1385-1394.
| S-EPMC3443765 | biostudies-literature
Project description:The aim of our study was to investigate the circadian regulation of cellular processes in mouse choroid plexus (ChP) and to determine their dependence on signals from the clock in the suprachiasmatic nuclei (SCN). We performed time-resolved transcriptomics of ChP samples from C57Bl6J mice with intact (Ctrl) or surgically removed SCN (SCNx) collected every 4 h over 2 days in constant darkness and from FoxJ1-ERT2-Cre+/-; Bmal1fl/fl mice with ChP-specific clock disruption (Bmal1-KO) collected at 2 time points. We found widespread circadian gene expression in Ctrl mice that was not present in SCNx mice, and the SCNx day/night ratios were reduced similarly to Bmal1-KO.
2023-09-30 | GSE243858 | GEO
Project description:Although the mammalian rest-activity cycle is controlled by a "master clock" in the suprachiasmatic nuclei (SCN) of the hypothalamus, it is unclear how firing of individual SCN neurons gates individual features of daily activity. Here, we demonstrate that a specific transcriptomically identified population of mouse VIP+ SCN neurons is active at the "wrong" time of the day -nighttime- when most SCN neurons are silent. Using chemogenetic and optogenetic strategies, we show that these neurons and their cellular clocks are necessary and sufficient to gate and time nighttime sleep, but have no effect upon daytime sleep. We propose mouse nighttime sleep, analogous to the human siesta, is a "hard-wired" property gated by specific neurons of the master clock to favor subsequent alertness prior to dawn (a circadian "wake maintenance zone"). Thus, the SCN is not simply a 24h metronome: specific populations sculpt critical features of the sleep-wake cycle.
2021-01-21 | GSE154038 | GEO
Project description:Extended consumption of food into the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain and has deleterious effects on health through mechanisms that remain incompletely understood. Beyond the liver, how other metabolic organs respond to hypocaloric diet (amount and timing) is largely unexplored. We investigated how feeding time impacts circadian gene expression in white (eWAT) and brown (BAT) adipose tissues in comparison to liver and hypothalamus. With automated feeders, we restricted food to either daytime or nighttime in C57BL/6J male mice, with or without caloric restriction. We found tissue-specific changes in the phase and amplitude of genome-wide mRNA expression patterns induced by daytime feeding in liver and eWAT, whereas BAT exhibited resilience and remained predominately entrained to the light-dark cycle, similar to hypothalamus. We uncovered an internal split within the BAT in response to conflicting environmental cues, displaying inverted oscillations on a subset of metabolic genes without modifying its local core circadian machinery. Integrating intra- and inter-tissue disruptions in circadian clock-controlled transcriptional networks with metabolic outcomes may help elucidate the mechanism underlying the health burden of eating at the wrong time of the day.
2024-07-25 | GSE266543 | GEO
Project description:The mammalian circadian system consists of a central clock in the brain that synchronizes clocks in peripheral tissues. While the hierarchy between the central and peripheral clocks is well established, peripheral clocks are largely viewed as a group and little is known regarding their specificity and functional organization. We employed feeding paradigms in conjunction with liver-specific clock-deficient murine model to map disparities and potential interactions between peripheral clocks. We found that peripheral clocks largely differ in their response to feeding-time. In view of its prominent role in nutrient processing, we hypothesized that the liver-clock instigate the response of peripheral clocks to feeding. Although the liver-clock did not affect the rhythmicity of clocks in other peripheral tissues, it strongly modulated their transcriptional rhythmicity upon daytime feeding. Overall, our findings suggest a role for the liver-clock in buffering feeding-related signals that affect rhythmicity of other peripheral tissues upon nutrient challenge, irrespective of their clocks.
2021-01-29 | GSE159135 | GEO
Project description:Organisms have adapted to the changing environmental conditions within the 24h cycle of the day by temporally segregating tissue physiology to the optimal time of the day. On the cellular level temporal segregation of physiological processes is established by the circadian clock, a Bmal1 dependent transcriptional oscillator network. The circadian clocks within individual cells of a tissue are synchronised by environmental signals, mainly light, in order to reach temporally segregated physiology on the tissue level. However, how light mediated synchronisation of peripheral tissue clocks is achieved mechanistically and whether circadian clocks in different organs are autonomous or interact with each other to achieve rhythmicity is unknown. Here we report that light can synchronise core circadian clocks in two peripheral tissues, the epidermis and liver hepatocytes, even in the complete absence of functional clocks in any other tissue within the whole organism. On the other hand, tissue extrinsic circadian clock rhythmicity is necessary to retain rhythmicity of the epidermal clock in the absence of light, proving for the first time that the circadian clockwork acts as a memory of time for the synchronisation of peripheral clocks in the absence of external entrainment signals. Furthermore, we find that tissue intrinsic Bmal1 is an important regulator of the epidermal differentiation process whose deregulation leads to a premature aging like phenotype of the epidermis. Thus, our results establish a new model for the segregation of peripheral tissue physiology whereby the synchronisation of peripheral clocks is acquired by the interaction of a light dependent but circadian clock independent pathway with circadian clockwork dependent cues.
2019-03-25 | GSE115104 | GEO