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Entrainment of the circadian system in rodents
Sosniyenko, Serhiy ; Sumová, Alena (advisor) ; Mareš, Jan (referee) ; Šauman, Ivo (referee)
The circadian clock located within the suprachiasmatic nuclei (SCN) of the hypothalamus responds to changes in the duration of day length, i.e. photoperiod, differently in the separate SCN parts. The aim of the study was i) to compare the effect of a long and a short photoperiod with twilight relative to that with rectangular light-to-dark transition on the daily profiles of clock gene expression and their protein levels within the rostral, middle and caudal regions of the mouse SCN; ii) to elucidate the dynamics of adjustment to a change of a long photoperiod to a short photoperiod of clock gene expression rhythms in the mouse SCN and in the peripheral clock in the liver, as well as of the locomotor activity rhythm; iii) to elucidate whether and how swiftly the immature rat fetal and neonatal molecular SCN clocks can be reset by maternal cues and iv) to reveal when and where within the rat SCN the photic sensitivity of clock gene expression develops during the early postnatal ontogenesis and to compare it with development of cfos photoinduction. Mice and rats were used for experiments; their tissues were analyzed by in situ hynridization, immunohistochemistry, RT-PCR. The data indicated that i) the twilight photoperiod provides stronger synchronization among the individual SCN cell subpopulations than the...
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Synchronization of circadian system during prenatal and early postnatal development
Houdek, Pavel ; Sumová, Alena (advisor) ; Novotná, Růžena (referee)
One of the few attributes common to almost all living organisms is an ability to generate and maintain endogenous rhythms, which are controlled by a biological clock. The processes, which recur with a period of about 24 hours, are known as the circadian rhythms. The circadian clock controls rhythms of molecular, physiological as well as behavioral processes and adapts their activity to regularly appearing changes in day and night or season. In case of mammals, central oscillator is located in the hypothalamic suprachiasmatic nuclei (SCN). The SCN clock entrains rhythms of peripheral oscillators located in cells of other tissues. The central oscillator itself is synchronized with external environment mainly by a light-dark cycle, however, other cues can entrain the SCN clock as well. For example, during prenatal development, entrainment of a fetal clock is entirely dependent on non-photic cues derived from maternal organism. This study aimed to investigate a mechanism of the communication between the maternal and fetal central oscillators. A hypothesis was tested whether maternal melatonin may play a role in entrainment of the circadian clock in the fetal SCN. Furthermore, a mechanism, how melatonin may entrain the fetal clock was investigated at molecular level. The results provided evidence, that...
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Mammalian circadian clock in peripheral organs, molecular mechanism and entrainment
Polidarová, Lenka ; Kuthan, Martin (referee) ; Sumová, Alena (advisor)
Mammalian circadian clock in peripheral organs, molecular mechanism and entrainment The circadian system controls timing of behavioral and physiological processes in most organisms. In mammals, central oscillator is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Apart from the SCN, peripheral oscillators are located in numerous organs like liver, heart, lung, muscle, intestine etc. The central and peripheral oscillators need to be synchronized by external cues (Zeitgeber). The SCN coordinates and entrains the phase of the clocks in numerous peripheral tissues via neuronal and humoral signals. For the SCN, dominant synchronizer is external light-dark cycle. Peripheral oscillators are cell-autonomous, they could work also independently of the SCN as a consequence of a feeding cycle. The basic molecular core clock mechanism responsible for generating circadian rhythms in the central and peripheral clocks is composed of transcriptional/translational feedback loops between the clock genes and their protein products. The aim of the present thesis was to ascertain whether the clock gene and protein expressions exhibit circadian rhythms in the rat intestine and whether the core clock mechanism drives expression of a cell cycle regulator rWee1. Next aim was to reveal how the circadian...
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Photoperiodic entraiment of circadian clock in suprachiasmatic nucleus
Parkanová, Daniela ; Vopálenský, Václav (referee) ; Sumová, Alena (advisor)
Most of physiological processes run in the organisms persistently, they begin in a definite rhythm again and again. The greatest attention is paid to the rhythms, whose period is equal to one day - they are called circadian rhythms. In case of mammals, these circadian rhythms are under control of the central circadian clock that resides in the suprachiasmatic nucleus, a part of the anterior hypothalamus. The mechanism of rhythm generation is based on interacting transcriptional-translational feedback loops that control expression of the clock genes in every single cell. Clock-controlled genes transmit these rhythms into the whole organism where they drive many physiological processes. Clock genes are expressed also in the peripheral oscillators (for example in liver, lungs, heart) and are under direct control of the central oscillator. Circadian clock needs to be entrained everyday to the external time to function precisely. The main entraining cue is the light part of the day. The length of the light part of the day, i.e. photoperiod, changes during the year rapidly in our latitudes and the central oscillator has to adapt to the changes all the time. The length of the photoperiod is encoded directly in the central oscillator by the transcriptional-translational relations among the clock genes and...
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Entrainment of the circadian clock within the rat suprachiasmatic nukleus during fetal and early postnatal development
El-Hennamy Essam, Rehab ; Sumová, Alena (advisor) ; Novotná, Růžena (referee) ; Mourek, Jindřich (referee)
All mammals exhibit daily rhythms which persist in non-periodic environment with a period close to 24h. These rhythms are entrained to the 24h day mostly by the light-dark cycle. These circadian rhythms are controlled by a clock (pacemaker) located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In the rat, the circadian clock within the SCN develops gradually from prenatal to postnatal period and is supposed to be synchronized mainly by maternal signals. However, the rat SCN is sensitive to light immediately after birth. The aim of the present work was to investigate the mechanism of entrainment of the circadian clock within the rat SCN during fetal and early postnatal development. The specific questions were whether and when the immature fetal and neonatal molecular SCN clocks can be reset by maternal cues, and whether and when the external light-dark cycle (LD) can affect the developing circadian rhythms. The role of light-dark cycle in the development of the photoperiodic entrainment during early postnatal period was also examined. Experiment no. (1): Pregnant rats were maintained under a light - dark regime with 12 h of light and 12 h of darkness (LD12:12). At gestational day 20 (E20), the fetuses were sampled throughout the day under either LD12:12 or constant darkness (DD). The...
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Development of photic entrainment of the circadian clock of the rat during early postnatal ontogenesis
Matějů, Kristýna ; Sumová, Alena (advisor) ; Höschl, Cyril (referee) ; Langmeier, Miloš (referee) ; Nevšímalová, Soňa (referee)
In most organisms, behavioral and physiological events oscillate with period ± 24 h, i.e. exhibit circadian rhythms. In mammals, circadian rhythms are generated by circadian clock within the suprachiasmatic nuclei of the hypothalamus (SCN). Light entrains circadian rhythms to the 24 h period of solar day. Information about light is conveyed from the retina to the SCN and induces expression of clock genes Period1 (Per1) and Period2 (Per2) that represent photosensitive parts of molecular circadian clockwork within SCN. Light sensitivity of Per1 and Per2 within SCN is temporally restricted to the subjective night phase. In addition, daily profiles of clock gene expression within SCN are modulated by daylenght, i. e. the photoperiod. The aim of our study was to elucidate how the mechanism of photic entrainment of the rat circadian clock develops during prenatal and early postnatal ontogenesis. Our results demonstrate that maternal circadian system provides information about external light to the fetal and early postnatal circadian clock. Circadian clock within the SCN of rat pups is light sensitive already at the first postnatal day. Mechanism gating the light sensitivity is present at postnatal day 3 and gradually maturates until postnatal day 10. The data suggest that the developing retina is responsive to...
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Maternal entrainment during prenatal ontogenesis of the rat
Nováková, Marta ; Sumová, Alena (advisor) ; Novotná, Růžena (referee)
Under constant conditions, many biological processes repeat regularly with a period about 24 hour, i.e., exhibit circadian rhythms. For example, these rhythms are in sleep/wakefulness, locomotor activity, hormonal secretion and body temperature. In mammals, circadian rhythms are controlled centrally from the hypothalamic suprachiasmatic nuclei (SCN). At the molecular level, the periodicity of these rhythms is due to the rhythmic expression of clock genes within individual neurons of the SCN. The expression of the clock genes is controlled by transcriptional-translational feedback loops. Apart form the SCN, the clock genes are rhytmically transcribed also in various peripheral tissues. The peripheral oscillations are synchronized centrally by the SCN clock that is entrained precisely to the 24 hour day by regular changes of the light and dark period, namely by the light period of the day. The central and peripheral circadian clocks drive rhythmic expression of clock-controlled genes and thus affect many physiological processes. Malfunctions in the circadian system may contribute to development of many diseases, such as malignant growth, obesity or sleep disorders. Circadian clock in the SCN develops gradually during prenatal and early postnatal period. In the rat, this period lasts from around 14th day of...
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The role of glucocorticoids in circadian system
Tejkal, Karel ; Sumová, Alena (advisor) ; Forman, Martin (referee)
Glucocorticoids are mammalian steroid hormones secreted from the adrenal gland. The basal levels of glucocorticoids show a pronounced diurnal rhythm with maximum at the beginning of the active period and minimum at its end. Glucocorticoids have an influence over a variety of metabolic functions and their secretion is tightly regulated. This regulation also depends on the circadian system, which utilizes glucocorticoids to entrain the peripheral tissues by inducing rhythmic gene expression. The mechanisms by which glucocorticoids influence mammalian circadian system has not yet been precisely defined, especially concerning the influence of glucocorticoid signalling on gene expression in different tissues and the dynamics of glucocorticoid receptor (GR) occupancy. This thesis studies the influence of ablation of glucocorticoid signalization induced by adrenalectomy on the clock gene expression of in the central clock in the suprachiasmatic nucleus and peripheral clocks in the hippocampus and distal colon. The effect of adrenalectomy on gene expression is compared with the effect of restricting the feeding time, which has also been shown to affect glucocorticoid levels in the body. Other experiments were aimed at elucidating impact of changing the activity of GR on gene expression using synthetic GR...
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