Social defeat stress affects behavior and changes the expression of the genes underlying neuronal plasticity in the brain. The circadian clock regulates most neuronal processes in the brain, which results in daily variations of complex behavior, and any disturbance in circadian clock oscillations increases the risk of mood and cognitive disbalance. In this study, we assessed the effect of acute and repeated social defeat stress on Per2 and Nr1d1 expression in prefrontal cortexes, hippocampi, pineal glands, olfactory bulbs, cerebella, and pituitary glands. We also evaluated the effect of our experimental setting on levels of Bdnf and plasma corticosterone, two markers widely used to asses the impact of stress on mammalian physiology. Our data show that single and repeated social defeat stress upregulates the expression of both clock genes and Bdnf in all brain structures, and corticosterone in the blood. While the general pattern of Bdnf upregulation suggests higher sensitivity in the intruder group, the clock genes are induced more significantly in residents, especially by repeated stress sessions. Our work thus suggests that the model of stress-induced anxiety and depression should consider a group of residents because, for some parameters, they may respond more distinctively than intruders.LAY SUMMARYThe resident/intruder experimental paradigm affects the expression of clock genes Per2, Nr1d1and Bdnf in the brain structures and plasma corticosterone level. The induction of clock genes is evident in both experimental groups; however, it is more marked in residents. Together with the significant increase in Bdnf levels in the majority of brain structures and plasma corticosterone in residents, our data suggest that in the model of social defeat stress, the utility of an experimental group of residents could be contributive.

• MeSH
• kortikosteron MeSH
• mozek metabolismus   MeSH
• mozkový neurotrofický faktor * genetika   metabolismus   MeSH
• potkani Wistar MeSH
• proteiny CLOCK * genetika   metabolismus   MeSH
• psychický stres * genetika   MeSH
• sociální chování MeSH
• sociální porážka MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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

The physiological function of the pancreas is controlled by the circadian clock. The aim of this study was to determine whether aging-induced changes in glucose homeostasis affect properties of the circadian clock in the pancreas and/or its sensitivity to disturbances in environmental lighting conditions. mPer2Luc mice aged 24-26 months developed hyperinsulinemic hypoglycaemia, which was likely due to the Pclo-mediated insulin hyper-secretion and Slc2a2-mediated glucose transport impairment in the pancreas, and due to the alterations in Pp1r3c-related glycogen storage and Sgk1-related glucose transport in the liver. In the pancreatic tissue, aging affected clock gene expression only marginally, it upregulated Bmal1 and downregulated Clock expression. Whereas aging significantly impaired the circadian clock in lung explants, which were used as a control tissue, the properties of the pancreatic clock in vitro were not affected. The data suggest a non-circadian role of Bmal1 in changes of pancreatic function that occur during aging. Additionally, the pancreatic clock was more sensitive to exposure of animals to constant light conditions. These findings provide an explanation for the previously demonstrated relationship between disturbances in the circadian system and disordered glucose homeostasis, including diabetes mellitus type 2, in subjects exposed to long-term shift work.

• MeSH
• cirkadiánní hodiny * účinky záření   MeSH
• cirkadiánní proteiny Period metabolismus   MeSH
• glukosa metabolismus   MeSH
• homeostáza * MeSH
• játra metabolismus   MeSH
• kolon metabolismus   MeSH
• myši MeSH
• orgánová specificita genetika   MeSH
• pankreas metabolismus   účinky záření   MeSH
• proteiny CLOCK genetika   metabolismus   MeSH
• regulace genové exprese účinky záření   MeSH
• stárnutí metabolismus   MeSH
• světlo MeSH
• transkripční faktory ARNTL genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• cirkadiánní hodiny MeSH
• cirkadiánní rytmus * MeSH
• cytochrom P-450 CYP2E1 MeSH
• exprese genu MeSH
• genetická transkripce MeSH
• hepatocyty MeSH
• léková chronoterapie MeSH
• lékové interakce MeSH
• lidé MeSH
• paracetamol škodlivé účinky   MeSH
• péče orientovaná na pacienta MeSH
• proteiny CLOCK MeSH
• transkripční faktory ARNTL MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• hodinové geny,
• MeSH
• biologické hodiny fyziologie   genetika   MeSH
• bipolární porucha farmakoterapie   MeSH
• chlorid lithný farmakologie   terapeutické užití   MeSH
• cirkadiánní proteiny Period genetika   MeSH
• cirkadiánní rytmus * fyziologie   genetika   MeSH
• depresivní poruchy farmakoterapie   MeSH
• epigenomika MeSH
• ketamin farmakologie   terapeutické užití   MeSH
• lidé MeSH
• melatonin metabolismus   MeSH
• mikro RNA MeSH
• poruchy cirkadiánního rytmu (spánek) MeSH
• poruchy nálady * etiologie   farmakoterapie   MeSH
• proteiny CLOCK genetika   MeSH
• schizofrenie * etiologie   farmakoterapie   MeSH
• sliny chemie   metabolismus   MeSH
• spánková deprivace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy 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

Adaptace člověka na život v periodicky proměnném prostředí zahrnuje časové řízení fyziologických funkcí tak, že mnohé z nich vykazují rytmy s cirkadiánní periodou. Porucha časového systému může mít vážné následky pro zdraví člověka a je v současnosti spojována se vznikem řady civilizačních chorob. Cílem projektu je zavést novou neinvazivní metodu stanovení stavu vnitřního časového systému člověka a následně ověřit její vhodnost ke zjištění účasti tohoto systému u některých psychických chorob, jako je rekurentní depresivní porucha a bipolární afektivní porucha. U zdravých a nemocných jedinců bude sledován denní rytmus v expresi hodinových genů ve vzorcích z ústní sliznice. Získané výsledky umožní u každého jedince přímo na genové úrovni rozpoznat případné abnormality funkčního stavu cirkadiánního systému. Výsledky těchto stanovení mohou sloužit jako diagnostické kritérium poruch cirkadiánního systému, které jsou součástí řady patofyziologických stavů, a případně pomoci při jejich léčbě a prevenci.; Adaptation to periodically varying environment includes temporal control of physiological functions, so that many of them exhibit circadian rhythms. Failure of the temporal control may have serious consequences for human health and is currently associated with the emergence of a number of lifestyle diseases. The project aims to introduce a new non-invasive method of analyzing the overall state of the human circadian system and test its suitability to assess involvement of this system in certain diseasessuch as recurrent depression and bipolar affective disorder. The clock gene expression rhythms will be monitored in samples from the oral mucosa in healthy subjects and patients. The profiles will allow direct detection of any abnormalities in functional status of the circadian system of each individual at genetic level. The results may serve as a diagnostic criterion of circadian disorders, which are involved in various pathological states, and possibly help with their treatment and prevention.

• MeSH
• bipolární porucha diagnóza   patofyziologie   terapie   MeSH
• cirkadiánní rytmus - signální peptidy a proteiny MeSH
• depresivní poruchy diagnóza   patofyziologie   terapie   MeSH
• melatonin analýza   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteiny CLOCK MeSH
• ústní sliznice fyziologie   MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• fyziologie
• psychiatrie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

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

The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF) leads to the development of food anticipatory activity (FAA) and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR). The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase), in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock.

• MeSH
• cirkadiánní hodiny genetika   fyziologie   MeSH
• cirkadiánní rytmus genetika   fyziologie   MeSH
• exprese genu genetika   MeSH
• játra metabolismus   fyziologie   MeSH
• kolon metabolismus   fyziologie   MeSH
• krysa rodu rattus MeSH
• pohybová aktivita genetika   fyziologie   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• potraviny MeSH
• proteiny CLOCK genetika   metabolismus   MeSH
• stravovací zvyklosti fyziologie   MeSH
• transkripční faktory ARNTL genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Individuals differ in their preferred timing of sleep and activity, which is referred to as a chronotype. The timing shows a wide distribution; extremely early chronotypes may wake up when the extremely late chronotypes fall asleep. The chronotype is supposed to be determined by the central circadian clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus because the phasing of the pineal melatonin rhythm, which is driven by the SCN, correlates with the sleep timing preference. In addition to the SCN, circadian oscillators are also present in most if not all bodily cells. These peripheral clocks are synchronized by the central SCN clock and by other tissue-specific entraining cues. At the molecular level, the circadian oscillations are based on a complex, self-sustaining mechanism that drives the rhythmical expression of clock genes and their proteins. The aim of the present field study was to elucidate whether the changes in the internal timing of early and late chronotypes, as expressed by changes in the phases of their mid-sleep and melatonin secretion, can also be detected at the molecular clockwork level in subjects examined under real-life conditions. Ninety-five adult volunteers were chronotyped using an adapted Munich chronotype questionnaire to assess their mid-sleep phase, and 6 subjects with early chronotypes and 6 with late chronotypes were chosen for the study. For the assessment of the circadian phase, the subjects provided samples of saliva for the melatonin assay and samples of oral mucosa for the determination of clock gene Per1, Per2, and Rev-erbα mRNA levels every 4 h during a 24-h period. The significant correlation between the phase of the melatonin profile and timing of mid-sleep confirmed the classification of the subjects according to their chronotype. The circadian phases of the Per1, Per2, and Rev-erbα expression profiles in the oral mucosa were advanced in the early chronotypes compared with those in the late chronotypes (p < .001) and correlated significantly with the mid-sleep phase of the individual subjects. Moreover, the circadian phases of the Per1 expression profiles of individual subjects correlated significantly with the phases of their melatonin profiles (p < .05), whereas the correlation for the Per2 and Rev-erbα phases was nonsignificant, although the trend was the same. Our results demonstrate that the individual chronotype in humans living in real-life conditions affects not only the phasing of the daily melatonin rhythm in saliva but also the phasing of Per1, Per2, and Rev-erbα clock gene expression profiles in buccal mucosa cells. This report represents the first demonstration that the human peripheral circadian clock may sense the individual's chronotype under field study conditions. The data contribute to our understanding of the mechanisms underlying human chronotypes in real life.

• MeSH
• cirkadiánní rytmus fyziologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• melatonin genetika   metabolismus   MeSH
• mladý dospělý MeSH
• proteiny CLOCK genetika   metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• spánek fyziologie   MeSH
• transkriptom MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH