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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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Hormonal synchronization of fetal circadian clocks in suprachiasmatic nuclei
Kapsdorferová, Viktória ; Sumová, Alena (advisor) ; Sehadová, Hana (referee)
Rhythmic non-light maternal signals, such as various behavioral, neurohumoral or metabolic factors, may play a key role in synchronization of the fetal circadian clock. This diploma thesis focuses more closely on the possible role of leptin and dopamine in the hormonal synchronization of the fetal central clock resides in the suprachiasmatic nuclei of the hypothalamus. A transgenic mouse fetus, which has luciferase fused to the clock gene Period 2, was used as an experimental model. This allowed us to monitor the operation of the fetal central clock in real time by recording the bioluminescence of tissue explants. Exogenous administration of dopamine during the decline in bioluminescence at normalized circadian time 15 induces larger phase delays compared to vehicle. Leptin, on the other hand, can participate in the development of spontaneous rhythms by stabilizing the integrity of the circadian rhythm, manifested by slowing down the rhythm dampening. At the level of individual cellular oscillators, significant regional differences in amplitude and period were not observed using bioluminescence microscopy. However, a slight dispersion of cell phases was observed after administration of dopamine during decreasing bioluminescence. In the case of leptin, there was a prolongation of period of the cell...
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Expression of AMPA glutamate receptor subunits in the suprachiasmatic nucleus of the rat
Červená, Kateřina ; Bendová, Zdeňka (advisor) ; Zemková, Hana (referee)
The main mammalian circadian pacemaker stored in suprachiasmatic nuclei of the hypothalamus (SCN) is adapted to changes in the external environement by synchronization of its endogenous period with periodic changes of light and dark during day and night. The information about light travels via glutamatergic retinohypothalamic tract to the ventrolateral part of the SCN. Activation of ionotropic glutamate receptors in this area provably mediates the transfer of information about light on the transcriptional mechanism of light-sensitive cells. The role of the NMDA type of ionotropic glutamate receptors is well studied in this field and it is known that some NMDA receptor subunits show a circadian rhythm and an increased expression after a light pulse. Signalization via AMPA type receptors is much less elucidated. The aim of this thesis was to determine which AMPA receptor subunits are expressed in the SCN of the rat and if these subunits show a daily rhythm of expression and a reactivity to light pulse, as well as to outline the possible roles of distinct AMPA receptor subunits in the SCN. Keywords: circadian rhythms, suprachiasmatic nuclei, glutamate receptors, AMPA
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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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Circadian regulation of sleep during ontogenesis in humans
Grieblová, Adéla ; Sumová, Alena (advisor) ; Soták, Matúš (referee)
The circadian system has evolved as an adaptation to periodically changing conditions on Earth. In mammals, and therefore in humans, the circadian system consists of the central and perip- heral oscillators generating a circadian rhythm. One of the most significant process exhibiting circadian rhythm is the sleep-wake cycle. Sleep is regulated by cooperation of circadian and homeostatic process. There are changes in circadian regulation of sleep during ontogenesis in human. The changes mainly releate to chronotype, i.e., to the diurnal preferences of activity and sleep. In the first years of life, there is a typical morning chronotype. In the end of first decade of life, the circadian phase begins to delay and reaches its maximal eveningness during ado- lescence. In adulthood, the preference changes again toward morning chronotype and reaches extreme morningness in elderly. Changes in circadian regulation of sleep during ontogenesis depend not only on age, but also on sex. 1
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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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The effect of endocannabinoid system on light entrainment of rat circadian system
Filipovská, Eva ; Bendová, Zdeňka (advisor) ; Balík, Aleš (referee)
Circadian system of mammals is generated in suprachiasmatic nuclei of hypothalamus. This system is synchronized with light conditions through phase shifts that occur after light exposition during the subjective night. Recent studies have shown that activation of endocannabinoid receptors attenuates the light-induced phase shifts and influences the ability of circadian system to light entrainment. The aim of this work is to examine this influence on behavioral level and on light-reactive cellular processes within the suprachiasmatic nuclei. Our results show that the activation of endocannabinoid system via CB1 receptor agonist modulates the light-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the expression of c-Fos protein in neurons of suprachiasmatic nuclei in the rat's brain; these cellular processes correlate with the attenuation of light entrainment. Keywords: circadian system, suprachiasmatic nuclei, light entrainment, endocannabinoid system, CB1 receptors, extracellular signal-regulated kinase 1/2, ERK1/2, c-Fos
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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.
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