|
|
Synchronization of circadian clock in hippocampus
Kubátová, Eliška ; Sumová, Alena (advisor) ; Liška, Karolína (referee)
Circadian rhythms refer to the physiological, biochemical and behavioral changes of the organism with a period of about 24 hours, such as the cycle of sleep and wakefulness, the release of hormones, enzymatic activity or gene expression. Apart from the central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, we find many other peripheral oscillators in which we observe the rhythmic expression of clock genes. In this study, we focused on one of the peripheral brain oscillators located in the hippocampus. The hippocampus is best known for its role in memory formation through the mechanism of long- term potentiation (LTP). The formation of LTP is another process that exhibits circadian variation. Although the rhythmic expression of genes in the hippocampus has already been demonstrated, the mechanisms of synchronization of these clocks remain a subject of investigation. In this study, we studied the effect of candidate substances - N-methyl-D- aspartate (NMDA) and leptin on the circadian clock of the hippocampus. Genetically modified mPer2Luc mice were used as a model. The main goal of the work was to introduce a method of preparing organotypic explants of the hippocampus of these mice for monitoring the circadian clock in real time using the LumiCycle device. Next goal was...
|
|
|
Circadian regulation of digestive system function and its disturbances due to external factors
Běloušková, Klára ; Sumová, Alena (advisor) ; Balounová, Kateřina (referee)
Circadian clocks regulate the behavior of cells in living organisms in 24hour periods. They react to environmental influences and, by synchronizing with them, ensure optimal cell function and the overall health of the organism. Biological clocks in the gastrointestinal tract and their functions can be influenced by several factors, including the timing of food intake or the influence of the microbiome. The correct timing of food intake can be essential in maintaining the functional physiology of the organism as well as the appropriate composition of the gut microbiome. Disruption of the synchronization between these factors and the biological clock in the gastrointestinal tract leads to disharmony of the organism, its improper function and the development of disease. The timing of food intake and the cultivation of an appropriate microbiome is critical to maintaining optimal health and should not be neglected by the public.
|
|
|
Rhythmic function of placenta and the impact of disruption in maternal-placental-fetal axis
Světlíková, Nela ; Sumová, Alena (advisor) ; Pačesová, Dominika (referee)
In mammals, the circadian rhythms result of a complex endogenous system consisting of hierarchically organized oscillators. The system enables the synchronization of the organism's internal processes with the external environment. It consists of the main component, the central clock, located in the suprachiasmatic nuclei in the hypothalamus, and peripheral clocks in other cells, tissues and organs. The placenta is a temporary, specialized mammalian organ that is part of the mother-placenta-fetus axis and exhibits rhythmicity in its functions. The aim of this thesis is to summarize the rhythmic functions of the placenta, such as immunity, protection, and production of hormones and other mediators that play an important role in fetal development and pregnancy. In addition, the thesis also describes rhythmic changes, that occur during pregnancy in the mother-placenta-fetus axis and how these rhythms influence each other. Keywords Placenta, circadian clock, ontogenesis, fetus, maternal synchronization, hormones, enzymes, immunity
|
|
|
Effect of maternal obesity on postnatal development of circadian clocks
Sejrková, Veronika ; Sumová, Alena (advisor) ; Spišská, Veronika (referee)
This thesis focuses on the synchronizing effect of obesity in mothers on ontogenesis of the circadian system in their offspring during gestation and postnatal life. Additionally, the work summarizes its impact on health of offspring in adulthood. During postnatal life, the central clock oscillator (SCN) is synchronized with external conditions through alternating period of light and darkness, but during prenatal ontogenesis of the main oscillator and peripheral oscillators, the SCN is synchronized with maternal signals, both behavioral, metabolic and hormonal. In the event of disruption of the maternal circadian and metabolic systems due to obesity, the circadian clocks of the offspring are incorrectly synchronized during gestation and breastfeeding, which may have a long-term effect on their health later during postnatal life. Maternal obesity is considered the main trigger for obesity occurring later.
|
|
|
The role of posttranslational modifications in the molecular mechanism of the circadian clock
Janáčová, Klára ; Sumová, Alena (advisor) ; Sládek, Martin (referee)
The timing of the biological processes of organism is controlled by an endogenous circadian clock. The molecular clock is present in almost every cell and is synchronized with the external environment. The main mechanism of the clock is a transcription-translation feedback loop. The 24-hour circadian rhythm period is provided by reversible posttranslational modifications (PTMs) of the clock proteins and another regulators of the circadian clock. PTMs are further important for clock entrainment, their regulation by metabolic state in the cell, and reciprocal regulation of the circadian clock end cell cycle. Phosphorylation, histones PTMs, acetylation, SUMOylation, ubiquitination, O-linked N-acetylglucosamination and polyADP-ribosylation play a crucial role. The molecular mechanism of the biological clock is an evolutionarily conserved mechanism found in most organisms. This bachelor thesis summarizes the knowledge about the role of PTMs in the molecular mechanism of the mammalian and human circadian clocks. Key words: circadian clock, clock genes, clock proteins, posttranslational modifications
|
|
|
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.
|
|
|
Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee) ; Herichová, Iveta (referee)
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 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.
|
guest ::
