OBJECTIVE: To evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies. METHODS: We assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls. RESULTS: The RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h. CONCLUSIONS: Our results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.

• MeSH
• cirkadiánní proteiny Period genetika   MeSH
• cirkadiánní rytmus genetika   MeSH
• exprese genu * MeSH
• jaderné receptory - podrodina 1, skupina D, člen 1 genetika   MeSH
• lidé MeSH
• melatonin krev   metabolismus   MeSH
• polysomnografie MeSH
• porucha chování v REM spánku genetika   MeSH
• proteiny CLOCK genetika   MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• stadia spánku genetika   MeSH
• transkripční faktory ARNTL genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři 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

Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (Bmal1, Per1-3, Cry1, RevErbα, Rora), clock-output genes (Dbp, E4bp4) and a glucocorticoid- and clock-controlled gene (Gilz) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on the level of Per1 mRNA in VAT, liver and jejunum, but not in kidney and splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of Per2 in splenocytes and VAT, Per3 in jejunum, RevErbα in VAT and Dbp in VAT, kidney and splenocytes, whereas the mRNA amounts of Per1 and Per2 in kidney and Per3 in VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had minimal effects on Rora and E4bp4 mRNAs. Adrenalectomy also resulted in decreased level of Gilz mRNA but did not alter the phase of its diurnal rhythm. Collectively, these findings suggest that adrenalectomy alters the mRNA levels of core clock genes and clock-output genes in peripheral organs and may cause tissue-specific modulations of their circadian profiles, which are reflected in changes of the amplitudes but not phases. Thus, the circulating corticosteroids are necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks in a tissue-specific manner.

• MeSH
• adrenalektomie * MeSH
• cirkadiánní hodiny genetika   MeSH
• cirkadiánní proteiny Period genetika   MeSH
• cirkadiánní rytmus genetika   fyziologie   MeSH
• játra metabolismus   MeSH
• ledviny metabolismus   MeSH
• potkani Wistar MeSH
• proteiny CLOCK genetika   MeSH
• regulace genové exprese genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Molecular clocks present in organs and individual cells throughout the body are central for the temporal coordination of rhythms in internal biological processes among themselves and with external environmental cycles; altered function of specific clock gene (CG) components can have significant impact relevant to health and disease. We herein review current knowledge pertaining to the presence and robustness of circadian rhythms in CGs in the suprachiasmatic nucleus and peripheral organs, and the importance of CGs to general health and the diagnosis and treatment of human disorders and disease. Also discussed are developmental aspects of rhythms in some CGs and tissues, time of day vs. circadian stage, using synchronized vs. constant conditions to monitor a rhythm, and subjective vs. objective interpretations of rhythms. To emphasize the latter, chronobiological statistics (ANOVA, single cosinor) are applied to published circadian CG mRNA expression data (which had been described subjectively) as an example of objectively determining rhythm probability and obtaining estimates for circadian amplitudes and acrophases. The data base consisted of 14 CGs (mPer1,2,3, mCry1,2, mBmal1, mCK1?,?, mClock, mDbp, mNpas2, mRev-erb?,ß, mTim) in each of 7 mouse organs harvested every 4h for 24h from male Balb/c mice on day 3 in continuous darkness. Excluding the usually non–24h-rhythmic testis and CG mTim, rhythms significant at p?0.05 were found in 81% (63/78) of CGs and when including borderline significant at p?0.10, in 97% (76/78) of CGs. A statisticallydetermined circadian amplitude and acrophase for each CG in each tissue can be useful in making objective comparisons of rhythm parameters in CGs between various peripheral organs, species, and/or studies of different conditions (e.g., photoperiods, feeding schedules, aging, disease). Use of these parameters adds new endpoints for diagnoses and approaches for therapeutic interventions in conditions where disturbance of circadian CG expression is an important cause of morbidity associated with chronic illnesses and diseases with a strong circadian component, including cardiovascular disease, epilepsy, cancer, metabolic syndrome, and sleep-related disorders, among others, also reviewed herein.

• MeSH
• biologické hodiny fyziologie   genetika   MeSH
• chronická nemoc MeSH
• chronobiologické poruchy genetika   MeSH
• cykly aktivity fyziologie   genetika   MeSH
• flavoproteiny farmakokinetika   MeSH
• modely u zvířat MeSH
• myši MeSH
• proteiny buněčného cyklu genetika   MeSH
• transportní proteiny genetika   MeSH
• Check Tag
• myši MeSH
• Publikační typ
• grafy a diagramy MeSH
• tabulky MeSH

Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects.

• MeSH
• cirkadiánní rytmus MeSH
• endokrinní systém MeSH
• financování organizované MeSH
• Heteroptera genetika   MeSH
• jaderné proteiny genetika   MeSH
• regulace genové exprese genetika   MeSH
• trans-aktivátory genetika   MeSH
• transkripční faktory bZIP genetika   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH

It has been confirmed that clock genes, as well as the pineal hormone, have a role in the hypothalamic suprachiasmatic nucleus, the circadian endogenous pacemaker. It seems that the peripheral clock genes in the cells of the immune system subtly control biorhythms; their seeming lack of impact only showing that they work well. Some biorhythms even seem to be independent of a light/dark circadian regime. This apparent conflict in the mammalian time structure can be resolved by a two-clocks control model involving: (a) the endogenous gene clock, which is dominant in the neural system and (b) the exogenous clock of the immune system. Interactions between these two clocks can explain both the frequently observed individual differences in circadian rhythms and the subtle role of the peripheral clock genes. The endogenous clock facilitates an alternation in the immune system which counters external attacks in daytime and induces repair and advancement by night.

• MeSH
• apoptóza fyziologie   MeSH
• biologické modely MeSH
• buněčné jadérko fyziologie   ultrastruktura   MeSH
• cirkadiánní rytmus fyziologie   účinky záření   MeSH
• epifýza mozková sekrece   MeSH
• financování organizované MeSH
• hematopoetické kmenové buňky cytologie   ultrastruktura   MeSH
• imunitní systém fyziologie   MeSH
• leukocyty cytologie   MeSH
• lidé MeSH
• melatonin fyziologie   MeSH
• melatoninové receptory fyziologie   MeSH
• neuroimunomodulace fyziologie   MeSH
• neurony cytologie   ultrastruktura   MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• přijímání potravy MeSH
• proteiny CLOCK MeSH
• savci fyziologie   MeSH
• světlo MeSH
• trans-aktivátory fyziologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

In mammals, the principal circadian clock within the suprachiasmatic nucleus (SCN) entrains the phase of clocks in numerous peripheral tissues and controls the rhythmicity in various body functions. During ontogenesis, the molecular mechanism responsible for generating circadian rhythmicity develops gradually from the prenatal to the postnatal period. In the beginning, the maternal signals set the phase of the newly developing fetal and early postnatal clocks, whereas the external light-dark cycle starts to entrain the clocks only later. This minireview discusses the complexity of signaling pathways from mothers and the outside world to the fetal and newborn animals' circadian clocks.

• MeSH
• biologické hodiny MeSH
• financování organizované MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• světlo MeSH
• tma MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• přehledy MeSH

The master circadian clock located in the suprachiasmatic nuclei (SCN) is dominantly entrained by external light/dark cycle to run with a period of a solar day, that is, 24 h, and synchronizes various peripheral clocks located in the body's cells and tissues accordingly. A daily restricted normocaloric feeding regime synchronizes the peripheral clocks but has no effect on SCN rhythmicity. The aim of this study was to elucidate whether feeding regime may affect the molecular mechanism generating SCN rhythmicity under conditions in which the rhythmicity is disturbed, as occurs under constant light. The rats were maintained under constant light for 30 days and were either fed ad libitum during the whole period, or their access to food was restricted to only 6 h a day during the last 2 weeks in constant light. Locomotor activity was monitored during the whole experiment. On the last day in constant light, daily expression profiles of the clock genes Per1, Per2, Bmal1, and Rev-erbα were determined in the SCN of both groups by in situ hybridization. Due to their exposure to constant light, the rats fed ad libitum became completely arrhythmic, while those exposed to the restricted feeding were active mostly during the time of food availability. In the SCN of behaviorally arrhythmic rats, no oscillations in Rev-erbα and Bmal1 gene expression were detected, but very low amplitude, borderline significant, oscillations in Per1 and Per2 persisted. Restricted feeding induced significant circadian rhythms in Rev-erbα and Bmal1 gene expression, but did not affect the low amplitude oscillations of Per1 and Per2 expression. These findings demonstrate that, under specific conditions, when the rhythmicity of the SCN is disturbed and other temporal entraining cues are lacking, the SCN molecular clockwork may likely sense temporal signals from changes in metabolic state delivered by normocaloric food.

• MeSH
• cirkadiánní proteiny Period biosyntéza   genetika   MeSH
• cirkadiánní rytmus genetika   MeSH
• fotoperioda MeSH
• hybridizace in situ MeSH
• jaderné receptory - podrodina 1, skupina D, člen 1 biosyntéza   genetika   MeSH
• krysa rodu rattus MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• potkani Wistar MeSH
• proteiny CLOCK biosyntéza   genetika   MeSH
• stanovení celkové genové exprese MeSH
• stravovací zvyklosti fyziologie   MeSH
• světlo MeSH
• transkripční faktory ARNTL biosyntéza   genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of the study was to investigate clock gene expression in Bos taurus and the alteration of that during two pathological conditions, evaluating the daily expression pattern of four clock genes (Per2, Cry2, Bmal1, Clock) in peripheral blood cells. Five healthy cows, five affected by Brucellosis (BR) and five affected by Bovine Viral Diarrhoea-Mucosal Disease (BVD-MD) were housed in indoor stalls under natural spring conditions, blood samples were collected at 4 h intervals over a 24 h period. Statistical analysis showed rhythmic expression of clock genes mRNAs in healthy cows. Cows affected by BR did not show any rhythmic expression of clock genes mRNAs, cows affected by BDV mRNA levels of Bmal1, Clock and Cry2 changed during the day. These findings highlighted that circadian system could be involved in homeostasis alteration and that clock genes could be considerate as regulatory genes or early response genes during inflammation, so, their regulation should be evaluated in health research and treatment.

• MeSH
• bovinní diarea patofyziologie   MeSH
• brucelóza skotu patofyziologie   MeSH
• cirkadiánní rytmus fyziologie   MeSH
• exprese genu fyziologie   MeSH
• modely nemocí na zvířatech * MeSH
• proteiny CLOCK * fyziologie   krev   MeSH
• proteosyntéza fyziologie   MeSH
• skot * fyziologie   genetika   krev   MeSH
• zánět patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• skot * fyziologie   genetika   krev   MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

Disruption of circadian machinery appears to be associated with the acceleration of tumor development. To evaluate the function of the circadian clock during neoplastic transformation, the daily profiles of the core clock genes Per1, Per2, Rev-Erbα and Bmal1, the clock-controlled gene Dbp and the clock-controlled cell cycle genes Wee1, c-Myc and p21 were detected by real-time RT-PCR in chemically induced primary colorectal tumors, the surrounding normal tissue and in the liver. The circadian rhythmicity of Per1, Per2, Rev-Erbα and Dbp was significantly reduced in tumor compared with healthy colon and the rhythmicity of Bmal1 was completely abolished. Interestingly, the circadian expression of Per1, Per2, Rev-Erbα and Dbp persisted in the colonic tissue surrounding the tumor but the rhythmic expression of Bmal1 was also abolished. Daily profiles of Wee1, c-Myc and p21 did not exhibit any rhythmicity either in tumors or in the colon of healthy animals. The absence of diurnal rhythmicity of cell cycle genes was partially associated with ageing, because young healthy mice showed rhythmicity in the core clock genes as well as in the Wee1 and p21. In the liver of tumor-bearing mice the clock gene rhythms were temporally shifted. The data suggest that the circadian regulation is distorted in colonic neoplastic tissue and that the gene-specific disruption may be also observed in the non-neoplastic tissues. These findings reinforce the role of peripheral circadian clockwork disruption for carcinogenesis and tumor progression.

• MeSH
• CDC geny genetika   MeSH
• cirkadiánní hodiny genetika   MeSH
• cirkadiánní rytmus genetika   MeSH
• exprese genu MeSH
• kolorektální nádory genetika   metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nádorová transformace buněk genetika   metabolismus   MeSH
• proteiny buněčného cyklu biosyntéza   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH