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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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Consequences of desynchronization of the circadian system by constant light
Petrželková, Lucie ; Bendová, Zdeňka (advisor) ; Honzlová, Petra (referee)
The circadian clock exists in every organism and their period is approximately 24 hours. This circadian rhythm is maintained even in a completely non-periodic environment but must be adapted to a precise 24-hour solar cycle using a synchronizer, called zeitgeber. The main controlling organ of the circadian rhythm are the suprachiasmatic nuclei (SCN) in the ventral hypothalamus. There are also peripheral clocks, for example in the liver or lungs. These peripheral clocks operate autonomously but the SCNs synchronize them with their own period and phase. The most important zeitgeber is the light and dark alternation. This bachelor thesis describes the consequences of conditions where there is no regular light and dark alternation and constant light conditions are established instead. Constant light can disturb the circadian rhythm and desynchronize the circadian clocks. This bachelor thesis summarizes the scientific knowledge of desynchronization by the effect of constant light and briefly describes the selected pathologies resulting from the desynchronization of the circadian system. Selected pathologies include ovarian tumour and breast cancer, obesity and insulin resistance, immunosenescense and schizophrenia. Key words constant light, circadian system, suprachiasmatic nucleus
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The effect of melatonin on the immune system
Hrubcová, Leona ; Moravcová, Simona (advisor) ; Boháčová, Pavla (referee)
Melatonin is an important hormone which is known to have very diverse functions. It was originally discovered as a product of the pineal gland synthesized in a 24 hour rhythm, but in later studies was found to be synthesized in many different tissue types. Melatonin is an important part of the circadian system and its effects on sleep rhythm are well known. The effects of melatonin on the circadian system are briefly covered in the opening chapters of this thesis. Furthermore, the basic mechanism of inflammation and the diverse effects of melatonin on the immune system are described in this thesis. Melatonin acts in an anti-inflammatory as well as pro-inflammatory manner and is part of many research projects focusing on curing for example diseases associated with chronic inflammation. This thesis presents studies regarding the effects of melatonin on pathological conditions like neurodegenerative diseases, rheumatoid arthritis and sepsis. This thesis also describes how changes in immune system activity can change the expression of melatonin, as it is not a one way effect. However, this interaction is not well known yet. Key words: melatonin, circadian system, immune system, inflammation
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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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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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Circadian system in mitochondria
Šemíková, Johana ; Bendová, Zdeňka (advisor) ; Moravcová, Radka (referee)
The rhythms of circadian clocks throughout our bodies are not governed only by the light/dark cycle, but in many peripheral tissues circadian clocks are reset based on availability of nutrients and timing of food intake. The circadian system responds to changes in the levels of two metabolites (AMP and NAD+ ) that are central to biochemical reactions involved in energy production, storage, and utilization through the metabolic sensors AMPK and SIRT1. The aim of this review is to summarize mechanisms for energetic metabolism known to date that are connected with the regulation of circadian rhythms and explain their function in maintaining their stability. Last but not least, to show possible dysregulation of these mechanisms and their impact on the circadian system.
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The expression and regulation of Dexras1 in the rat brain under development
Kyclerová, Hana ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
The Dexras1 gene was identified after induction by glucocorticoid dexamethasone in pituitary tumor cells. Dexras1 has also been found in other brain regions and in the peripheral organs but its expression is rhythmic only in the suprachiasmatic nuclei of the hypothalamus (SCN), where the mammalian main circadian pacemaker is located. Dexras1 expression was also affected by stress, amphetamine or prenatal alcohol exposure. Its role in cells has not yet been explained. Dexras1 GTPase activity has been determined to be dependent on the NMDA receptor stimulation. Dexras1 acts as an activator of G protein signaling in cells. Its role has been detected in neuronal iron homeostasis or in the regulation of main circadian pacemaker sensitivity to photic and nonphotic synchronization cues during the day. The aim of our study was to describe the Dexras1 mRNA expression in the rat brain during ontogeny and during development after visual sensory deprivation by in situ hybridization. The earliest Dexras1 expression was detected on embryonic day 20, in the rat SCN and the ventral posteromedial thalamic nucleus. Postnatally, its expression also appeared in other sensory areas, motor thalamic areas, hypothalamic areas involved in the regulation of water homeostasis, or in limbic system. Our results further show...
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Circadian clock in hippocampus
Šuchmanová, Karolína ; Sumová, Alena (advisor) ; Mareš, Pavel (referee)
Hippocampus is one of the main components of the limbic system. It plays an important role in the process of memory formation and recent literature shows that, like in other peripheral organs and brain structures, there is a circadian clock present in the hippocampus. The aim of the thesis was to study the hippocampal circadian clock under various conditions. The first part of the thesis examines the influence of glucocorticoid hormones on the clock gene expression in the hippocampus. Glucocorticoids are mammalian steroid hormones secreted from the adrenal glands that affect many processes in the organism. The glucocorticoid secretion is under the control of the circadian system, causing their levels to exhibit a pronounced diurnal rhythm. The hippocampus provides feedback to the hypothalamo-pituitary-adrenal (HPA) axis and is thus involved in the regulation of glucocorticoid hormone secretion. Hippocampal neurons also express glucocorticoid hormone receptors (GR). This thesis explores the effect of the absence of glucocorticoid hormones on the clock gene expression in the hippocampus. The absence of glucocorticoids was due to adrenalectomy and its effect was further compared with the effect of endogenous glucocorticoid replacement by daily injections of the GR agonist dexamethasone, emulating...
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The disruption of the circadian system in bipolar disorder and its association with the polymorphism of L-type calcium channel
Filipovská, Eva ; Bendová, Zdeňka (advisor) ; Novosadová, Zuzana (referee)
Bipolar affective disorder is a serious psychiatric disease with prevalence of about 1% in general population. Typical symptoms are mood changes: manic periods are followed by depressions, with possible asymptomatic period of variable duration between them. It alters patient's everyday life and often leads to suicidal tendencies. Bipolar disorder is related to impaired circadian rhytms that are regulated from suprachiasmatic nuclei in hypothalamus. Impaired circadian rhytms in bipolar disorder are manifested by abnormalities of sleep and daily activity and by disrupted circadian secretion of several hormons. One of many factors that link bipolar disorder to circadian system at molecular level is the function of voltage-dependent calcium channels of L-type. Expression of these channels is regulated by the clock genes and their proper function is important for maintaining endogenous oscillations in the main oscillator located in suprachiasmatic nuclei. A common finding in patients with bipolar disorder is polymorphism of the gene for 1 subunit of the Cav1.2 channel. Abnormal function of calcium channels, consequent to the polymorphism, may be one of the causes that alter circadian rhytms in bipolar disorder. Key words: circadian system, suprachiasmatic nucleus, bipolar disorder, L-type calcium...
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The relationship between circadian system and cell cycle
Vrtílková, Andrea ; Bendová, Zdeňka (advisor) ; Fárková, Eva (referee)
The circadian system is able to oscillate by itself owing to the transcriptional-translation feedback loop. Components of this loop do not affect just their own run, but they also have an impact on some other functions of the cell, for example cell cycle. This interaction is made by clock proteins (PER, CRY etc.) and by clock-controlled proteins (WEE1, TIM, XPA etc.). These proteins participate in the cell cycle run and have an impact on check-points. Disruption of the circadian clock can cause faults in cell cycle check-points, storing of DNA damages and increased cell apoptosis or tumor progression. Key words: circadian systém, cell cycle, WEE1, XPA, P21, C-Myc, TIM, PER
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