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Association of selected polymorphisms with clock genes with a extreme chronotypes
Turečková, Lucie ; Bendová, Zdeňka (advisor) ; Weissová, Kamila (referee)
The circadian system has evolved in organisms as an adaptation to periodic changes in the environment. Its task is to ensure regular entrainment between the solar cycle and the internal period of the organism, and to generate signals that synchronize behavioral and physiological processes in the body with the solar cycle. The whole mechanism takes place at the cell level, where there are regular oscillations of the transcriptional translation loops of the clock genes occur within 24 hours, thus ensuring a regular rhythm of the organism. However, the circadian system may not generate the same length of period in humans and may differ in the degree of entrainment with the external cycle. Base on that there are developed so-called individual time preferences. These different preferences are referred to as chronotypes, which fall into five categories: extremely evening, moderate evening, intermediate, moderate morning, and extremely morning type. Clock gene polymorphisms are considered to be one of the possible causes of these differences. The association of selected clock gene polymorphisms with extreme chronotypes is the subject of this diploma thesis. We obtained a saliva sample for DNA isolation from volunteers with extreme chronotypes. Using molecular methods of PCR, restriction digest and...
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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...
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Circadian system in astrocytes
Ľalíková, Kristýna ; Bendová, Zdeňka (advisor) ; Honc, Ondřej (referee)
The circadian system affects almost all cells in the mammalian body. These cells include astrocytes, which together with microglia and oligodendrocytes represent the main types of glial cells found in the brain. The first chapter of this thesis presents a summary of circadian system characteristics and focuses mainly on the molecular mechanism underlying its functioning. The second chapter is devoted to astrocytes, astrocyte calcium signaling, and the process of gliotransmission. The third and last chapter connects both topics and discusses the circadian system in astrocytes. It presents evidence of astrocytic circadian oscillations existence and physiological consequences of its action. Great attention is paid to circadian rhythms in gliotransmission, with a focus on gliotransmitters ATP and glutamate. As the most impressive output of the circadian system of astrocytes is presented the participation in maintaining the rhythmic activity of the main circadian oscillator located in the suprachiasmatic nucleus of the hypothalamus. Key words: circadian system, clock genes, astrocytes, gliotransmission, calcium signaling, glutamate, ATP
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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.
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Circadian sleep regulation and sleep deprivation
Zeithamlová, Barbora ; Weissová, Kamila (advisor) ; Honzlová, Petra (referee)
The circadian system is designed to generate circadian rhythms and serve as the human inner clock. This is achieved through the molecular mechanism of autonomous transcriptional-translational feedback loops, in which so-called clock genes are involved. Circadian rhythms regulate the timing of physiological and behavioral processes, including sleep. Sleep is important for the proper functioning of the human organism. As a result of desynchronization of circadian rhythm, disturbances of sleep arise which threaten the mental and physical state of man. One of the examples is sleep deprivation which is deffined as a lack of necessary amount of sleep. Besides its negative effect on human health, there had been also reported positive effect in the treatment of symptoms in patients with unipolar depression. Other studies suggest that deprivation causes a reset of the circadian system, correcting the abnormal functioning of the internal clock. These effects have only a short duration, but it appears that they could be stabilized by combining sleep deprivation therapy with other therapeutic approaches. However, it is crucial to understand the exact mechanism that causes the positive effect in sleep deprivation therapy.
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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
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Molecular mechanisms of mammalian circadian clocks, its sensitivity to constant light and aging
Novosadová, Zuzana ; Sumová, Alena (advisor) ; Doležel, David (referee) ; Mráz, Miloš (referee)
Many processes in mammalian body exhibit circadian rhythms. These rhythms are driven by an intricate system composed of the central pacemaker, suprachiasmatic nuclei (SCN) in the brain, which entrains the peripheral oscillators in various organs, such as pancreas, liver, colon and lungs. Circadian clocks are autonomously driven in each cell based on molecular circuits involving so called clock genes, such as BMAL, CLOCK, PER and CRY. Age- dependent impairment of physiological functions of mammalian body, such as behaviour and metabolic functions, has been well documented. However, it has not been fully elucidated whether the impairment is linked with worsening of the circadian clock function. The aim of our study was to find out whether i) aging affects basic properties of the circadian clock in SCN and peripheral organs, such as pancreas, colon, liver and lungs, ii) aging- induced changes in glucose homeostasis affect the properties of the circadian clock in the pancreas, and iii) the sensitivity of circadian clock in SCN and peripheral organs to disturbances in environmental lightning conditions is altered during aging. We used groups of adult (9 months) and aged (25 months) animals which were subjected to 3 different light regimes, namely to light/dark regime (LD 12:12), constant light (LL) and...
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Circadian clocks in cells of the immune system
Lavrova, Kseniia ; Bendová, Zdeňka (advisor) ; Hájková, Michaela (referee)
Circadian rhythms affect all physiological processes in the body, including immune function. Circadian oscillations are observed in almost all components of the immune system. This oscillation generates molecular clocks that are in each cell and are synchronized by the main CSN pacemaker with help hormone secretion and neuronal innervation. As a result, the immune system is ready for increased responses to pathogens during the active phase when is higher risk of bruising with it. Macrophages are cells of the natural immune system and main modulators of inflammation. Their activity, including cytokine production, phagocytosis and polarization to M1 and M2 phenotypes is closely linked to the molecular clock. This association between circadian and immune systems has implications for the course of a series of inflammatory diseases, such as arthritis and atherosclerosis. The aim of this thesis is to investigate the effect of circadian system on macrophage function in inflammatory response. Keywords: circadian clocks, circadian genes, macrophage, melatonin, glucocorticoids
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Circadian system and it's changes in Lurcher mutant mice
Boubín, Josef ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
The main topic of this thesis are changes in Circadian rhythms caused by cerebellar disorders. Mice with Lurcher mutation, which have specifically degenerated Purkinje cells layer, were choosen as animal model. Our results show that mutation of the glutamate receptor GluRδ2, which causes gradual degeneration of Purkinje cells, leads to damage of Circadian system. Mice with this mutation have reduced capability to adapt to external conditions in different light modes. They are also showing increased variability in endogenous cycle. The mice are also unable to show anticipatory behavior in time-restricted feeding. Compared to control group, affected mice do not show significant rhythm in levels of protein of Bmal1 gene in suprachiasmatic nuclei, paraventricular nuclei nor in habenula. Phosphorylated kinases ERK1/2 and GSK3ß also had distorted rhythms in suprachiasmatic nuclei. Because Circadian oscillations in locomotor activity are partly preserved, Circadian system is likely not damaged on molecular level. Cerebellar mutation hampers synchronization between suprachiasmatic nuclei of neurons and can also affect processes in the ventromedial hypothalamus regulating food intake. Our findings are the first to suggest functional interactions between cerebellum and Circadian pacemaker in suprachiasmatic...
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