Aging and tumorigenesis are associated with decline and disruption of circadian rhythms in many tissues and accumulating evidence indicates molecular link between circadian clock and cell cycle. The aim of this study was to investigate the effect of aging and tumorigenesis on coupling between cell cycle and circadian clock oscillators in colon, which undergoes regular rhythmicity of cell cycle and expresses peripheral circadian clock. Using healthy 14-week-old mice and 33-week-old mice with and without colorectal tumors, we showed that the 24-h expression profiles of clock genes and clock-controlled genes were mostly unaffected by aging, whereas the genes of cell cycle and cell proliferation were rhythmic in the young colons but were silenced during aging. On the other hand, tumorigenesis completely silenced or dampened the circadian rhythmicity of the clock genes but only a few genes associated with cell cycle progression and cell proliferation. These results suggest that aging impacts the colonic circadian clock moderately but markedly suppresses the rhythms of cell cycle genes and appears to uncouple the cell cycle machinery from circadian clock control. Conversely, tumorigenesis predominantly affects the rhythms of colonic circadian clocks but is not associated with uncoupling of circadian clock and cell cycle.
- MeSH
- buněčný cyklus fyziologie MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní rytmus fyziologie MeSH
- karcinogeneze * metabolismus patologie MeSH
- kolon fyziologie MeSH
- kolorektální nádory * metabolismus patologie MeSH
- myši MeSH
- nádorová transformace buněk MeSH
- proliferace buněk MeSH
- stárnutí * metabolismus patologie MeSH
- střevní sliznice * metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Abandoning daylight saving time in Europe raises the topical issue of proper setting of yearlong social time, which needs mapping of various socio-demographic factors, including chronotype, in specific geographic regions. This study represents the first detailed large scale chronotyping in the Czech Republic based on data collected in the complex panel socio-demographic survey in households (total 8760 respondents) and the socio-physiological survey, in which chronotyped participants also provided blood samples (n = 1107). Chronotype assessment based on sleep phase (MCTQ questions and/or time-use diary) correlated with a self-assessed interval of best alertness. The mean chronotype of the Czech population defined as mid sleep phase (MSFsc) was 3.13 ± 0.02 h. Chronotype exhibited significant east-to-westward, north-to-southward, and settlement size-dependent gradients and was associated with age, sex, partnership, and time spent outdoors as previously demonstrated. Moreover, for subjects younger than 40 years, childcare was highly associated with earlier chronotype, while dog care was associated with later chronotype. Body mass index correlated with later chronotype in women whose extreme chronotype was also associated with lower plasma levels of protective HDL cholesterol. Based on the chronotype prevalence the results favour yearlong Standard Time as the best choice for this geographic region.
- MeSH
- časové faktory MeSH
- chronobiologie (obor) statistika a číselné údaje MeSH
- cirkadiánní hodiny fyziologie MeSH
- demografie statistika a číselné údaje MeSH
- dítě MeSH
- dospělí MeSH
- fotoperioda * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- průzkumy a dotazníky statistika a číselné údaje MeSH
- sexuální faktory MeSH
- spánek fyziologie MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Nearly all organisms evolved endogenous self-sustained timekeeping mechanisms to track and anticipate cyclic changes in the environment. Circadian clocks, with a periodicity of about 24 h, allow animals to adapt to day-night cycles. Biological clocks are highly adaptive, but strong behavioral rhythms might be a disadvantage for adaptation to weakly rhythmic environments such as polar areas [1, 2]. Several high-latitude species, including Drosophila species, were found to be highly arrhythmic under constant conditions [3-6]. Furthermore, Drosophila species from subarctic regions can extend evening activity until dusk under long days. These traits depend on the clock network neurochemistry, and we previously proposed that high-latitude Drosophila species evolved specific clock adaptations to colonize polar regions [5, 7, 8]. We broadened our analysis to 3 species of the Chymomyza genus, which diverged circa 5 million years before the Drosophila radiation [9] and colonized both low and high latitudes [10, 11]. C. costata, pararufithorax, and procnemis, independently of their latitude of origin, possess the clock neuronal network of low-latitude Drosophila species, and their locomotor activity does not track dusk under long photoperiods. Nevertheless, the high-latitude C. costata becomes arrhythmic under constant darkness (DD), whereas the two low-latitude species remain rhythmic. Different mechanisms are behind the arrhythmicity in DD of C. costata and the high-latitude Drosophila ezoana, suggesting that the ability to maintain behavioral rhythms has been lost more than once during drosophilids' evolution and that it might indeed be an evolutionary adaptation for life at high latitudes.
- MeSH
- cirkadiánní hodiny genetika fyziologie MeSH
- cirkadiánní rytmus fyziologie MeSH
- Drosophila fyziologie MeSH
- Drosophilidae genetika fyziologie MeSH
- fenotyp MeSH
- fotoperioda MeSH
- fyziologická adaptace fyziologie MeSH
- kryptochromy fyziologie MeSH
- lokomoce fyziologie MeSH
- nadmořská výška MeSH
- neurony fyziologie MeSH
- pohybová aktivita fyziologie MeSH
- proteiny Drosophily metabolismus MeSH
- tma MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels. Maternal GCs must pass through the placenta to reach the fetal SCN. We show that the maternal but not the fetal part of the placenta harbors the autonomous circadian clock, which is reset by dexamethasone (DEX) and rhythmically expresses Hsd11b2. The results suggest the presence of a mechanism for rhythmic GC passage through the placental barrier, which is adjusted according to actual GC levels. GC receptors are expressed rhythmically in the laser-dissected fetal SCN samples. We demonstrate that hypothalamic explants containing the SCN of the mPer2 Luc mouse prepared at embryonic day (E)15 spontaneously develop rhythmicity within several days of culture, with dynamics varying among fetuses from the same litter. Culturing these explants in media enriched with DEX accelerates the development. At E17, treatment of the explants with DEX induces phase advances and phase delays of the rhythms depending on the timing of treatments, and the shifts are completely blocked by the GC receptor antagonist, mifepristone. The DEX-induced phase-response curve differs from that induced by the vehicle. The fetal SCN is sensitive to GCs in vivo because DEX administration to pregnant rats acutely downregulates c-fos expression specifically in the laser-dissected fetal SCN. Our results provide evidence that the rodent fetal SCN clock may respond to changes in GC levels.
- MeSH
- cirkadiánní hodiny účinky léků genetika fyziologie MeSH
- cirkadiánní proteiny Period genetika MeSH
- dexamethason farmakologie MeSH
- glukokortikoidy farmakologie fyziologie MeSH
- hypothalamus fyziologie MeSH
- krysa rodu rattus MeSH
- myši MeSH
- nucleus suprachiasmaticus účinky léků fyziologie MeSH
- placenta fyziologie MeSH
- plod fyziologie MeSH
- těhotenství MeSH
- vývoj plodu * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
KEY POINTS: In mammals, the mother-offspring interaction is essential for health later in adulthood. The impact of altered timing and quality of maternal care on the offspring's circadian system was assessed using a cross-strain fostering approach. Better maternal care facilitated the development of amplitudes of Bmal1 clock gene expression in the central clock, as well as the clock-driven activity/rest rhythm, and also its entrainment to the external light/dark cycle. Worse maternal care impaired entrainment of the central clock parameters in the Wistar rat during the early developmental stages. Better maternal care remedied the dampened amplitudes of the colonic clock, as well as cardiovascular functions. The results provide compelling evidence that the circadian phenotype of a foster mother may affect the pathological symptoms of the offspring, even if they are genetically programmed. ABSTRACT: In mammals, the mother-offspring interaction is essential for health later in adulthood. Maternal care is determined by the circadian phenotype of the mother. The impact of altered timing and quality of maternal care on the circadian system was assessed using a cross-strain fostering approach, with 'abnormal' (i.e. circadian misaligned) care being represented by spontaneously hypertensive rats (SHR) and 'normal' care by Wistar rats. The SHR mothers worsened synchrony of the central clock in the suprachiasmatic nuclei with the light/dark cycle in Wistar rat pups, although this effect disappeared after weaning. The maternal care provided by Wistar rat mothers to SHR pups facilitated the development of amplitudes of the Bmal1 expression rhythm in the suprachiasmatic nuclei of the hypothalamus, as well as the clock-driven activity/rest rhythm and its entrainment to the external light/dark cycle. The peripheral clocks in the liver and colon responded robustly to cross-strain fostering; the circadian phenotype of the Wistar rat foster mother remedied the dampened amplitudes of the colonic clock in SHR pups and improved their cardiovascular functions. In general, the more intensive maternal care of the Wistar rat mothers improved most of the parameters of the abnormal SHR circadian phenotype in adulthood; conversely, the less frequent maternal care of the SHR mothers worsened these parameters in the Wistar rat during the early developmental stages. Altogether, our data provide compelling evidence that the circadian phenotype of a foster mother may positively and negatively affect the regulatory mechanisms of various physiological parameters, even if the pathological symptoms are genetically programmed.
- MeSH
- chování zvířat fyziologie MeSH
- cirkadiánní hodiny fyziologie MeSH
- druhová specificita MeSH
- fenotyp MeSH
- mateřské chování fyziologie MeSH
- novorozená zvířata MeSH
- nucleus suprachiasmaticus fyziologie MeSH
- potkani inbrední SHR MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Colonic function is controlled by an endogenous clock that allows the colon to optimize its function on the daytime basis. For the first time, this study provided evidence that the clock is synchronized by rhythmic hormonal signals. In rat colon, adrenalectomy decreased and repeated applications of dexamethasone selectively rescued circadian rhythm in the expression of the clock gene Per1. Dexamethasone entrained the colonic clock in explants from mPer2Lucmice in vitro. In contrast, pinealectomy had no effect on the rat colonic clock, and repeated melatonin injections were not able to rescue the clock in animals maintained in constant light. Additionally, melatonin did not entrain the clock in colonic explants from mPer2Lucmice in vitro. However, melatonin affected rhythmic regulation of Nr1d1 gene expression in vivo. The findings provide novel insight into possible beneficial effects of glucocorticoids in the treatment of digestive tract-related diseases, greatly exceeding their anti-inflammatory action.
- MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- epifýza mozková chirurgie MeSH
- fotoperioda * MeSH
- inbrední kmeny myší MeSH
- kolon fyziologie MeSH
- krysa rodu rattus MeSH
- mutace MeSH
- myši MeSH
- nadledviny chirurgie MeSH
- potkani Wistar MeSH
- regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Circadian clock plays an essential role in orchestrating daily physiology, and its disruption can evoke metabolic diseases such as obesity. L-Carnitine can reduce blood lipid levels, and ameliorate fatty liver through regulating lipid metabolism. However, whether L-Carnitine administration may affect the disturbance of lipid metabolism and circadian rhythm of mice induced by prolonged circadian disruption is still unknown. Herein, we investigated the effects of L-Carnitine on conditions of circadian clock and lipid metabolism through a chronic jet-lag mice model which was developed by reversing 12 h light/12 h dark cycle every 4 days for a continuous 12 weeks. Results showed that L-Carnitine administration significantly decreased levels of serum glutamic-oxaloacetic transaminase (GOT) and triglycerides (TG), which were remarkably elevated by chronic jet-lag. More importantly, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that L-Carnitine supplementation would effectively counteract the negative alterations in gene expression which related to lipid metabolism (Srebp1, Acaca, Fasn, and Scd1), metabolic regulator (mTOR) and circadian rhythm (Bmal1, Per1, Cry1 and Dec1) in the liver of mice subjected to the chronic jet-lag. As a conclusion, L-Carnitine was partly effective in preventing the disruption of circadian clock and lipid metabolic disorders induced by the chronic jet-lag.
- MeSH
- chronická nemoc MeSH
- cirkadiánní hodiny účinky léků fyziologie MeSH
- cirkadiánní rytmus účinky léků fyziologie MeSH
- jet lag syndrom krev farmakoterapie genetika MeSH
- karnitin farmakologie terapeutické užití MeSH
- metabolismus lipidů účinky léků fyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- náhodné rozdělení MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- PER,
- MeSH
- biologické hodiny * fyziologie MeSH
- chronobiologie (obor) dějiny MeSH
- cirkadiánní hodiny * fyziologie genetika MeSH
- cirkadiánní rytmus - signální peptidy a proteiny MeSH
- Drosophila MeSH
- lidé MeSH
- odměny a ceny MeSH
- savci fyziologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
Circadian clocks keep organisms in synchrony with external day-night cycles. The free running period (FRP) of the clock, however, is usually only close to-not exactly-24 h. Here, we explored the geographical variation in the FRP of the linden bug, Pyrrhocoris apterus, in 59 field-lines originating from a wide variety of localities representing geographically different environments. We have identified a remarkable range in the FRPs between field-lines, with the fastest clock at ~21 h and the slowest close to 28 h, a range comparable to the collections of clock mutants in model organisms. Similarly, field-lines differed in the percentage of rhythmic individuals, with a minimum of 13.8% and a maximum of 86.8%. Although the FRP correlates with the latitude and perhaps with the altitude of the locality, the actual function of this FRP diversity is currently unclear. With the recent technological progress of massive parallel sequencing and genome editing, we can expect remarkable progress in elucidating the genetic basis of similar geographic variants in P. apterus or in similar emerging model species of chronobiology.
- MeSH
- časové faktory MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní rytmus fyziologie MeSH
- fylogeneze MeSH
- Heteroptera klasifikace genetika fyziologie MeSH
- pohybová aktivita fyziologie MeSH
- Tilia parazitologie MeSH
- zeměpis MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Geografické názvy
- Evropa MeSH
- Izrael MeSH
- východní Evropa MeSH
- Klíčová slova
- modré světlo,
- MeSH
- bdění účinky záření MeSH
- brýle MeSH
- cirkadiánní hodiny * fyziologie MeSH
- fotoperioda MeSH
- kognice * účinky záření MeSH
- lidé MeSH
- melatonin metabolismus MeSH
- nucleus suprachiasmaticus MeSH
- počítačové terminály MeSH
- pozornost účinky záření MeSH
- přenos světelných signálů MeSH
- psychomotorický výkon účinky záření MeSH
- retina fyziologie MeSH
- retinální gangliové buňky fyziologie MeSH
- spánek * účinky záření MeSH
- spánková deprivace MeSH
- světelná stimulace MeSH
- světlo * MeSH
- únava prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH