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Interplay between adenosine signaling and the circadian system
Škrle, Jan ; Bendová, Zdeňka (advisor) ; Houdek, Pavel (referee)
Sleep is regulated primarily by the two processes, by Process C and S. Process C represents circadian regulation by circadian system; Process S represents the homeostatic sleep drive. Circadian system controls the timing of many physiological functions including body temperature rhythms, locomotor activity rhythms, periodically changing hormones levels etc. Process C contributes to sleep regulation mainly by setting lower and upper thresholds for a sleep pressure. When the sleep pressure reaches one of these thresholds, falling asleep or waking is promoted. However, the sleep architecture is altered by a phase of endogenous oscillators as well. The homeostatic sleep drive is based on a sleep- wake history with the sleep pressure rising during a wakefulness and lowering during sleep. This mechanism is responsible for a modification in structure of a recovery sleep following a sleep deprivation. Due to the effects of adenosine on sleep regulation, adenosine signalling is considered to play a critical role in the homeostatic sleep drive. These two processes were thought to be independent of each other, but new data show that there is a reciprocal regulation between them. The aim of this work was to conclude, where these two processes meet, with a special attention on processes, where the adenosine...
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Circadian system as a modulator of neuroinflammation
Kotková, Eliška ; Spišská, Veronika (advisor) ; Dočkal, Tereza (referee)
The circadian system is involved in the regulation of biological rhythms in physiological, behavioural and immune processes. These rhythms can be found in the central nervous system, including the blood-brain barrier, astrocytes, microglia, and the pineal gland, which produces the hormone melatonin. Neuroinflammation is a complex response of the central nervous system to inflammatory stimuli by rhythmic expression of pro-inflammatory and anti-inflammatory mediators or by rhythmic regulation of immune system cells. Studies have examined the influence of genes and proteins of the circadian system, suprachiasmatic nuclei, melatonin, and glial cell rhythms on neuroinflammation. Lipopolysaccharide was used to induce neuroinflammation in these studies. Based on these studies, the effect of melatonin on mikroglia and endothelial cells, and the responses of suprachiasmatic nuclei was evaluted as the most important circadian modulator of neuroinflammation. This thesis describes the basic principles of the circadian system and neuroinflammation, with the last section presenting the modulation of neuroinflammation by the circadian system. Keywords: astrocytes, blood-brain barrier, circadian system, cytokines, immune system, melatonin, microglia, neuroinflammation, suprachiasmatic nuclei
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Assessment of the influence of artificial lighting simulating a natural photoperiod and spectrum on the parameters of circadian rhythms of healthy volunteers
Gesztesová, Kristina ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
The alternation of light and darkness on planet Earth has led to the development of endogenous systems that operate with a period of roughly 24 hours. We refer to these systems as circadian. For optimal functioning of the human circadian system, regular synchronization by an external stimulus is required. Light is a strong stimulus for synchronization for humans, but it should be noted that the outcome of this light synchronization depends critically on a number of factors. These factors include the timing and duration of the light pulse, as well as light parameters like spectrum and intensity. Commonly used interior lighting is often not optimal for the human endogenous circadian system, which is why the alternative of so-called biodynamic lighting (lighting that adequately stimulates the human organism) is being used more lately. As part of the experiment, we verified the effect of the newly created biodynamic lighting on the parameters of the circadian rhythm of healthy volunteers. Using methods of melatonin profile analysis, analysis of temperature records and actigraphy, we confirmed the influence of our experimental lighting.
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Effect of ketamine on light-induced changes in the circadian system
Kratina, Alex ; Bendová, Zdeňka (advisor) ; Valeš, Karel (referee)
The circadian system is controlled by the suprachiasmatic nuclei of the hypothalamus (SCN) and ensures optimal timing of physiological processes. Synchronization of this system with external light conditions is based on the activation of NMDA receptors during light exposure in the subjective night. Ketamine is a non-competitive antagonist of NMDA receptors used as a safe anesthetic, whose subanesthetic doses act as an antidepressant with a rapid onset of action, and increase proliferation in some parts of the brain. There are hypotheses about the possible effect of subanesthetic doses of ketamine on the circadian system, altough this effect has not yet been tested. This work aims to investigate the effect of a single subanesthetic dose of ketamine on the circadian system of the rat, especially on light-induced changes in locomotor activity and light-induced markers in the SCN and dentate gyrus, which represents one of the strongly proliferative areas of the brain. Our results show that ketamine decreases light pulse-induced c-FOS protein expression in the SCN at the onset of the subjective night, but increases this expression in the dentate gyrus under the same conditions. Reduction of c-FOS expression in the SCN correlates with the behavioral output of the circadian system and thus suppresses the...
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Circadian system and reproduction
Hrubá, Anežka ; Lužná, Vendula (advisor) ; Ladislavová, Lucie (referee)
Due to the alternation of day and night, mammals have developed internal circadian clocks, helping to synchronize physiological processes with the external environment. The circadian system is hierarchically organized, with central clocks located within suprachiasmatic nuclei of the hypothalamus (SCN). The main signal for setting the clocks to the external time is light, which enters the SCN through retina. The SCN communicate with peripheral oscillators in other organs, including reproductive ones, via hormonal signals, thereby synchronizing a variety of physiological processes. At the molecular level, clocks are controlled by clock genes. Cicradian system has a significant impact on reproduction. It is manifested by rythmical expression of clock genes and production of hormones in reproductive organs, as well as a success in reproduction if the clock's function is proper, and problems with reproduction if it is not. From a gender perspective, a several differences between women and men has been found throughout the SCN. Likewise, there are differences in chronotypes between both sexes over the course of their lives. Biological rhythms also include circannual rhythms, contributing to the timing of reproduction at the proper season of the year. Animals mate at different time depending on the length...
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Circadian clock and detoxication processes in the liver
Ludvíková, Tereza ; Pačesová, Dominika (advisor) ; Kolář, David (referee)
The circadian system influences almost all physiological processes in the mammalian body. Among other things, detoxication processes in the liver are under circadian control. Both central and peripheral clock in the liver regulate the expression of genes involved in the detoxication of xenobiotic substances and drugs. The first part of this thesis summarizes the main characteristics of the central and peripheral circadian clocks, including their molecular basis. The second part focuses on the main functions of liver tissue with a focus on detoxification processes. The emphasis of the third section is on circadian rhythms in the expression and activity of enzymes called cytochromes P450, which are the most important system catalyzing phase I detoxication, and also briefly discusses the influence of the circadian system on the expression of nuclear receptors and PAR bZIP transcription factors involved in the regulation of cytochrome P450 transcription. The last section describes the influence of the circadian system on the efficacy and toxicity of selected drugs, on paracetamol metabolism with the main purpose of describing how paracetamol-induced hepatotoxicity is affected by time of administration. Key words: circadian system, liver, detoxication, cytochrome, paracetamol
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Development of the circadian system after systemic potentiation of GABAergic transmission in early ontogenesis
Dušek, Jakub ; Bendová, Zdeňka (advisor) ; Mareš, Pavel (referee)
The circadian system is the evolutionary response of organisms to repetitive geophysical conditions and allows organisms to devote their energy to solving sudden changes. Although the circadian system developed to help organisms survive and thrive in dynamic conditions, system itself is sensitive to external changes. During critical developmental period of the mammalian CNS, the neonatal period, the circadian systém is significantly vulnerable. Benzodiazepines, pharmaceuticals widely prescribed for half a century, interfere with GABAergic transmission, which is critical type of signaling for the functioning of the circadian systém. The purpose of this thesis is to determine whether and how the development and functioning of the circadian system is altered after administration of a drug from the benzodiazepine class, clonazepam, during the critical developmental period. This thesis examines changes in the expression profile of selected genes in the hippocampus, olfactory bulb and frontal cortex of two ontogenetic stages of rats. Results of this work suggest that benzodiazepines administred in the neonatal period disrupt the development of the circadian system and that these changes, particularly in the hippocampus, persist for certain time. Key words: circadian system; circadian rhythms;...
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The effect of long-term morphine application on clock genes expression in the rat brain
Pačesová, Dominika ; Bendová, Zdeňka (advisor) ; Roubalová, Lenka (referee) ; Polidarová, Lenka (referee)
The circadian and opioid systems are systems involved in maintaining homeostasis in the body. Disruption of the circadian system disturbs the proper timing of physiological processes, which can result in the development or exacerbation of pre-existing pathological conditions, including addiction. One of the factors that can influence the precise synchronization of the circadian system is the use and abuse of opioids. The interrelationship between the circadian and opioid systems is poorly studied. To this end, the present study investigated the effect of morphine and methadone on the rat circadian system in adulthood and during development. The aim of this dissertation was to observe the effect of acute morphine administration on the expression of clock genes in the suprachiasmatic nuclei (SCN) of adult rats, and to investigate the effect of long-term morphine or methadone administration and withdrawal on the expression of clock genes in the SCN and on the activity of the enzyme AA-NAT in the pineal gland of adult rats. Proper development of the circadian clock contributes significantly to the maintenance of health in adulthood and ensures good adaptability of the organism to changes in the external environment. No study to date has focused on examining the effects of opioid administration during...
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Physical and mental performance of morning and evening chronotypes in different times of day
Červená, Kateřina ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee) ; Větrovský, Tomáš (referee)
Circadian rhythmicity, which evolved in accordance with the rhythmicity of the external environment tied to the earth's rotation, governs the regular rhythms of our physiology and behavior. The central circadian clock in the suprachiasmatic nuclei of the hypothalamus controls the roughly 24-hour rhythmicity of many peripheral clocks of most cells of the body, that can be observed from the molecular to the behavioral level. The intrinsic circadian period (τ) in humans is on average slightly longer than 24 h, but may also be slightly shorter. Individuals with a short τ are referred to as morning chronotypes, whereas individuals with a long τ are referred to as evening chronotypes. However, the majority of the population belongs to the so-called intermediate chronotype. The molecular mechanism of circadian oscillations controlled by the circadian clock has been shown to be closely linked to cellular metabolism. Many physiological processes important for physical and cognitive performance are also regulated by the circadian system. The main aim of both studies was to quantify the difference in performance during morning and evening testing in subjects of a pronounced evening and morning chronotype. While the motivation for conducting Study A was practical, with the aim of identifying potential biases...
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Significance of the timekeeping system for human health
Pospíšilová, Lucie ; Sumová, Alena (advisor) ; Hejnová, Lucie (referee)
The circadian system evolved as an adaptation to cyclic changes in external conditions on Earth, mainly the alternation of light and dark with a period of solar day. The rhythmic signal is generated at the cellular level and it is controlled by rhythmic expression of clock genes and their protein products. In mammals, the hypothalamic suprachiasmatic nuclei (SCN) are the principal circadian oscillator coordinating daily cycles of physiology and behavior, while in peripheral tissues local oscillators operate. The peripheral oscillators are entrained to the daytime and also among each other, by neuroendocrine signals from the SCN. Mutual synchrony of all the circadian components is necessary for proper function of the organism. The main entraining cue of the circadian system with environment is light, which affect the SCN via retina. In a subgroup of blind people sensing the light in the retina is disturbed and their circadian system cannot be synchronized by light. The SCN controls rhythmic production of melatonin in the pineal gland. This hormone mediates the information about the daytime to other tissues in the body, which are not photosensitive. The circadian system temporally drives many processes, including the cell division cycle. It seems that disruption of the temporal regulation could contribute to...
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