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Internal communication within the circadian system and its significance for our health
Honzlová, Petra ; Sumová, Alena (advisor) ; Moravcová, Simona (referee)
Mammalian circadian cycle is generated by hierarchically organized system of internal rhythmical oscillations in clock gene expression (Clock, Bmal1, Per, Cry, Rev-Erb, etc.) which take place in nearly all living cells in our body. The master pacemaker is located in suprachiasmatic nucleus (SCN) in hypothalamus. According to its synchronization to photic and non-photic external stimuli SCN generates signal for entrainment of peripheral clock. Peripheral clock synchronization is maintained via neuronal or hormonal (glucocorticoids, melatonin) pathways, regulation of body temperature or food intake and affects various physiological processes. Desynchronization of central and peripheral clock can be the cause or the manifestation of impaired health condition. Powered by TCPDF (www.tcpdf.org)
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Role of apoptosis in the mechanism of opioid effect
Moravcová, Simona ; Novotný, Jiří (advisor) ; Ostašov, Pavel (referee)
2. Abstract Opioids have been used as effective analgesics for many years. The worst problem is, however, their adverse effects and potential addiction. There are three known types of opioid receptors that differ mainly in their sensitivity to different opioids and their distribution in the CNS. This work also deals with apoptosis. Apoptosis is an important process not just in the embryonic development, e.g. for the right differentation of fingers and toes, but also in the adulthood, e.g. to suppress tumour formation. Whereas an apoptotic pathway can be initiated in many different ways, there is only one mechanism that actually causes the death of a cell. It is important for the cell death and division to be in balance. The breach of this balance may result in pathologic effects. This work summarizes the effects of opioids in connection with apoptosis. The main object of the research of this relationship was morphine which has both pro-apoptotic and anti-apoptotic effects. Another two frequently investigated opioids are methadone and heroin. Heroin is mainly used in the studies researching the impact of this highly addictive opioid on the apoptosis and embryonic development. Keywords: opioids, opioid receptors, G-proteins, apoptosis, morphine
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Regulation of the expression of MHC class I molecules and other immunoactive molecules on tumor cells
Moravcová, Simona ; Reiniš, Milan (advisor) ; Vopálenský, Václav (referee)
4 Abstract Regulation of the expression of MHC class I molecules and other immunoactive molecules on tumor cells The aim of this master thesis project was to characterize the effects of IFNγ, TNFα and of the epigenetic agents 5-azacytidine (5AC) and 5-aza-2'-deoxycytidine (5AZAD) on the expression of molecules important for antigen presentation and modulation of the immune responses against tumors (MHC class I molecules and other immunoactive molecules CD54, CD80, B7-H1, B7-H2 and CD1d) on tumor cells. The experimental model used for this purpose were the HPV16-associated murine tumor cell lines, either MHC class I positive or negative. The goal was to determine the changes in surface expression of these molecules after treatment by FACS studies and also the expression at the mRNA level using qPCR. Expression of these proteins was also compared in the experiments in vitro on tumor cell lines and ex vivo on tumor cells explanted from animals. The most interesting result is the observation that 5AZAD increases the expression of B7-H1 which inhibits T cell mediated immune response and that 5AZAD and IFNγ act synergistically in the induction of the expression of MHC class I, CD54 and B7-H1 molecules. Klíčová slova: imunoeditace, protinádorová imunita, HVP16, MHC glykoproteiny I. třídy, B7-H1, IFNγ, TNFα,...
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Modulation of the JAK/STAT signaling pathway in the suprachiasmatic nucleus of rat hypothalamus
Moravcová, Simona ; Novotný, Jiří (advisor) ; Krulová, Magdaléna (referee) ; Polidarová, Lenka (referee)
Circadian clock in the suprachiasmatic nucleus of the hypothalamus (SCN) regulates daily rhythms in behavior and physiology and is an important part of the mechanisms regulating mammalian homeostasis. SCN are synchronized with a 24hour cycle mainly by light, but they can also be regulated by a variety of nonphotic signals, such as growth factors, opioids, cytokines, or lipopolysaccharide (LPS), which act by inducing the JAK/STAT signaling pathway. STAT family proteins (i.e. signal transducers and activator of transcription) regulate many aspects of cellular physiology, from growth and differentiation to immune response. However, the JAK/STAT signaling pathway has not yet been studied in the SCN and the function of STAT proteins in the SCN has not yet been clarified. In the first part of the thesis, we focused on localization of STAT3 and STAT5 proteins in the rat SCN and determination of rhythm in proteins and mRNA. Our experiments showed the daily rhythm in the levels of STAT3 protein in SCN astrocytes of rat with low but significant amplitude and with maximum in the morning. In addition, we revealed strong but nonrhythmic expression of STAT5A protein in astrocytes and STAT5B protein in nonastrocytic cells of SCN. It was also found that Stat3 mRNA show, similarly to protein, circadian rhythm in...
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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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Default Mode Network: Ontogeny
Jarmar, Jiří Kryštof ; Nekovářová, Tereza (advisor) ; Moravcová, Simona (referee)
Default mode network is a functional network system in a brain, comprising of other sub- components. It is activated during tasks focused on the inner monologue, mentalization, episodical memory or self-reflection. The DMN activity is generally described as default mode functioning of the brain in absence of external stimuli, on the other hand its activity is inhibited during the presence of it. This thesis focuses on the main factors and changes that occur during ontogeny of DMN from birth to adulthood, mainly in structural and functional connectivity and anticorrelation relationships with other brain networks. After a general characterization of DMN, the first part focuses on general characterization of functional brain networks and statistical methodology of measuring their relationships and maturity. It follows by the description of important events in brain development and identification of main anatomical regions of DMN. The most important part is the last one, which provides observations of comparative studies of DMN between children and adults. Here we describe main changes and trends in ontogeny of DMN. Key words: Default mode network, functional network, fMRI, ontogeny
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Disruption of hippocampal-prefrontal connection in animal models of schizophrenia
Černotová, Daniela ; Svoboda, Jan (advisor) ; Moravcová, Simona (referee)
Schizophrenia is a heterogeneous mental disease that afflicts about 1% of population with no treatment available that would ameliorate all of its symptoms. The key structures affected in schizophrenia are the hippocampus and the prefrontal cortex. This work focuses on the interplay between these structures and on the monosynaptic hippocampal-prefrontal connection, the abnormal neural activity of which is the main cause of cognitive, positive and negative symptoms of schizophrenia. This work summarizes existing findings about both normal and impaired function of the hippocampal-prefrontal connection and provides an overview of animal models frequently used in research. Key words: hippocampus, prefrontal cortex, schizophrenia, interneuron, animal model
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Circadian system of the retina
Kozel, Tomáš ; Bendová, Zdeňka (advisor) ; Moravcová, Simona (referee)
Most of the known living organisms have developed an evolutionary adaptation to a 24-hour daily rhythm. This rhythm, known as circadian rhythm, can be preserved even in the environment, in which there is no access to light or other synchronizer. The master organ of circadian rhythm is located in the hypothalamic suprachiasmatic nucleus (SCN) and have been considered the only autonomous circadian oscillator for a long time. The new research, however, has doubted this hypothesis by showing the existence of autonomous circadian clock systems independent of SCN. One of these autonomous clocks is the circadian system in the retina. This bachelor thesis reviews current scientific knowledge on the function of mammalian retinal circadian oscillator, most importantly in the field of its localization, connection with the SCN master circadian oscillator and its influence on retinal physiology.
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