|
|
Molecular mechanisms of entrainment of the fetal circadian clocks
Lužná, Vendula ; Sumová, Alena (advisor) ; Šauman, Ivo (referee) ; Štaud, František (referee)
In order to adapt to changing external conditions, organisms developed the endogenous biological clock for predicting daily alterations. This so-called circadian system drives functions and processes in the whole body with an approximately 24h period. The central oscillator, located in hypothalamic suprachiasmatic nuclei (SCN), is synchronized by light and subsequently sends the information about the time of the day to the rest of the body. Even in the ontogenesis, the functional SCN clock is crucial for proper development as well as health later in life. Since the maturation of embryonic SCN is not completed before birth, maternal signals seem to play a fundamental role in setting and synchronizing the fetal clock. During my PhD studies, we focused on elucidating the nature of maternal signals and their diverse impact on fetal SCN of rat and mouse models. We have revealed that developing SCN is able to sense distinct signals related to various maternal behavioral regimes. Importantly, we have discovered eminent role of glucocorticoids in synchronizing the fetal SCN, along with their ability to accelerate SCN development. These observations point out the importance of regular daily routine and noxious effect of stress during pregnancy. Since the mother communicates with the fetus through placenta...
|
|
|
Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
|
|
|
Molecular mechanism of circadian clock and its connection to neuropsychiatric disorders
Jandová, Eliška ; Sumová, Alena (advisor) ; Mašek, Tomáš (referee)
Circadian rhythms, which are running with a period of 24 hours, are in mammals controlled via principal clock located in the area of suprachiasmatic nuclei (SCN) and peripheral oscillators. The basic molecular mechanism governing the circadian rhythms is the transcriptional-translational feedback loop of clock genes Clock, Bmal1, Per and Cry. The CLOCK-BMAL1 protein dimer acts as an activator for the transcription of the Per and Cry genes, which retroactively inhibit this dimer and thus its own transcription. This main loop affects other genes that are involved in regulation of the core loop. The function, nuclear localization and stability of clock genes are affected by a number of postranscriptional and postranslational modifications. Sleep disorders, one of the main processes controlled by the clock genes, accompany many neuropsychiatric disorders, including autism spectrum disorder. The development of these disorders have been associated with the clock genes or their interactions with other genes that play a major role in development of these disorders.
|
|
|
The effect of constant light in early development on the circadian system in the adulthood
Kubištová, Aneta ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
Long-term exposure to constant light results in desynchronization of the circadian system in an adult and is associated with reduced efficiency of many physiological functions timed to the exact time of day, or with the development of some of the so-called civilization diseases. Constant light in adults also results in deterioration of the cognitive abilities or changes in the sleep structure. The effect of night light on the health of an adult organism is studied mainly in connection with shift work or with light pollution. The question of what effect the increased level of night light has on the development of the organism, especially on the development of the nervous system and the circadian system itself, is less studied. This diploma thesis focused on the identification of the extent of changes in the expression of Per2, Nr1d1, Stat3, BDNF genes, as well as genes encoding NMDA receptor subunits and some tissue-specific genes in the retina. Our experiments were performed on adult Long-Evans rats, that spent the first 20 days of their postnatal development in low-intensity constant light. Changes in expression were determined by quantification of mRNA by RT-qPCR in the structures of the frontal and parietal cortex, olfactory bulb, hippocampus, suprachiasmatic nucleus and retina. Behavioral tests...
|
|
| |
|
|
The role of Wnt signaling in interaction between circadian clock and cell cycle
Herrmannová, Terezie ; Sumová, Alena (advisor) ; Macůrková, Marie (referee)
The Wnt signaling represents a highly conserved signal transduction cascade that regulates stem cell proliferation and differentiation. It plays an irreplaceable role not only during embryonic development, but also in maintaining homeostasis of adult tissues. The cell division is also influenced by the circadian clock. The clock can interact with the cell cycle either directly within a single cell or regulate it intercellularly. In order to impact surrounding cells, it uses the Wnt signaling pathway that mediates signal transduction through the extracellular space. Both Wnt signaling and the circadian clock are essential for the physiological functioning of the mammalian organism, and their disruption can lead to the development of cancer. Keywords: circadian clock, clock genes, cell cycle, Wnt signaling, cell proliferation, cancer
|
|
|
Circadian clock genes in the circadian clock and photoperiodic timer in Pyrrhocoris apterus
CHODÁKOVÁ, Lenka
This thesis focuses on the circadian clock genes and their involvement in the photoperiodic time measurement in the linden bug, Pyrrhocoris apterus. Application of the molecular biology methods enabled us to propose the architecture of circadian clockwork. We also investigated the role of several previously undescribed players in the circadian clock. Furthermore, by using molecular biology methods we focused on the involvement of core circadian clock genes in the photoperiodism.
|
|
| |
|
|
Impact of circadian system disruption on development of gastrointestinal disorders
Kubištová, Aneta ; Sumová, Alena (advisor) ; Červená, Kateřina (referee)
The ability to sense 24-hour cycles in external environment and to adapt to them is present in a great array of species living on the Earth. Mammals possess internal time-keeping system which is composed of circadian clocks located in the suprachiasmatic nuclei (SCN) of the hypotalamus and peripheral clocks in various tissues and organs of the body. These clocks are adapting to the changes of external environment, such as light and dark cycles or feeding cycles. Peripheral clocks in the organs of the digestive system are synchronized with the signals derived from the central clock in the SCN and also with signals from food intake. Discordance between these signals may result in development of various diseases of the gastrointestinal tract (GIT) related to insufficient digestion or even in higher risk of developing a cancer. This bachelor thesis is generally aimed at circadian rhythms in the body, with the focus on rhythms in the GIT. It will deal with the importance of the circadian rhythms for correct GIT functions. Furthermore, the thesis is focused on connection between the desynchonization of the circadian clock and GIT disease development, namely of obesity and cancer.
|
|
|
Mechanisms of maternal entrainment of the fetal circadian clock
Černá, Barbora ; Sumová, Alena (advisor) ; Balaštík, Martin (referee)
Our body is influenced by many cyclical changes in the environment, such as day and night or seasons. To predict these changes and react to them in time, the organism is equipped with inner clock, which rhythmically influences many physiological processes, such as sleep or metabolic rhythms. Disrupting our inner rhythms at molecular and behavioral levels contributes to many serious disorders. It is necessary that all mechanisms of the inner circadian clock are developed and set up properly. Circadian clocks are set up by the mother, who passes rhythmical information about day and night cycle on to her embryo. Though a great attention is devoted to revealing the nature of this synchronization between the mother and her pup, the mechanisms of this process have not been fully understood yet. The aim of this thesis is to contribute to actual understanding of this synchronization. Experiments, performed in this thesis, relate to studying the ability of maternal signals to synchronize embryos with the environment. Feeding and light regime of pregnant rats was manipulated and the effect of these changes on the neuronal activity within the suprachiasmatic nuclei of 19-day embryos was analyzed.
|
guest ::
