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Clock genes in mammalian circadian pacemaker
Cimerová, Veronika ; Bendová, Zdeňka (advisor) ; Polidarová, Lenka (referee)
The behavior of mammals and their physiological processes are dependent on the daily rhythms. These rhythms are controlled by an endogenous circadian clock that responds to light/dark cycles of environment. In mammals, the circadian clocks, are arranged hierarchically, and work in almost all cells and tissues. Suprachiasmatic nuclei (SCN) in the hypothalamus are at the top of the hierarchy and work as a major circadian pacemaker. This work presents the clock genes that have been discovered in the last twenty years in the SCN of mammals. The first chapter focuses on the general mechanism of circadian rhythms and structure of the SCN. The second chapter describes the transcriptional-translational feedback loops that are an essential part of the proper function of the circadian clock, and function of individual genes is briefly introduced in this chapter. The following chapters already include a chronological characterization of Clock, Bmal1, Period and Cryptochrome genes, as they were discovered. If the clock gene expresses different function from the clockwork mechanism, it is briefly introduced in the final paragraph on the chapter. The final chapters deal with other molecules, casein kinases, ROR and REV-ERB receptors that affect its function expression and degradation of circadian genes in the...
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Relationship between corticosteroid metabolism, ontogenesis and stress response
Makal, Jakub ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee)
Stress is a widespread phenomenon in the western society of these days. It is a risky factor for health and well-being of the majority of people. Based on these facts, it is the main subject for the field of "stress physiology" research, which aims to study processes occurring during stress response and tries to elucidate mechanisms leading to stress-induced health impairment. The first aim of this thesis was to describe effects of psycho-social stress on organism. The second aim was to find out if can stress applied in juvenile age affect the stress response in adulthood. If so, how is the role of glucocorticoid-metabolism enzyme 11β-HSD1 in this influence? To answer these questions, two different animal models inducing stress response in the laboratory rat were used. The first one is the model of mild social stress based on the resident-intruder paradigm. Our results show efficancy of this model. Fisher 344 male rats treated under this model for seven consecutive days show highly elevated plasma corticosterone concentrations and elevated expression of the glucocorticoid receptor gene in the pituitary. Behavioral analysis demonstrates a decreased social behavioral profile of the intruders, suggesting submisive social position of these animals in the resident-intruder paradigm. The second model used is...
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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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Effect of morphine application on the rat circadian system
Platilová, Michaela ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
Circadian rhythms are controlled by endogenous mammalian biological oscillators. The main oscillator is located in the suprachiasmatic nuclei in the hypothalamus and entrains the phases of slave peripheral oscillators located in many organs and tissues. Under natural conditions, circadian rhythms are synchronized with an external 24-hour day, by light-dark changes during the day. In addition, the circadian system is sensitive to a number of non-photic stimuli, such as arousal or social interactions, severe stress, medicines, alcohol or opiates. Timed application of opioids causes phase shifts of the circadian rhythmicity in behaviour and negatively affects light synchronization. The aim of this work is to explore the effect of acute morphine on the activity of cellular signaling cascades in SCN cells, that are essential for the proper function of the circadian clock, and to elucidate the molecular interaction between opioid and circadian system. Our data suggest that acute activation of opioid signalization affect the circadian clock indirectly, and suprachiasmatic nuclei obtain the information via afferents form other part of brain. Besides that, the side data of our work show the decrease of pERK1/2 a pGSK3β within two hours after the light pulse, which is the observation that has not been yet...
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Structure, function and pharmacology of NMDA receptors
Švehla, Pavel ; Vyklický, Ladislav (advisor) ; Bendová, Zdeňka (referee)
Glutamate is a major excitatory neurotransmitter between neurons in the central nervous system. The effect of glutamate is caused by the activation of distinct ionotropic glutamate channels: AMPA, kainate and NMDA receptors. NMDA receptors play a critical role in the synaptic plasticity and excitotoxicity. Despite the crucial role of these receptors in the right function of the brain, their overexcitation under pathological conditions may result in such neurological disorders as Alzheimers, Parkinsons and Huntingtons diseases. The aim of this work is to review available data concerning the molecular structure of NMDA subtype of ionotropic glutamate receptors, their pharmacology and therapeutic potential.
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Localization of individual opioid receptor subtypes in CNS
Lišháková, Michaela ; Hejnová, Lucie (advisor) ; Bendová, Zdeňka (referee)
In last decades, the research focused on opioid receptors has been intensively conducted in order to determine their role in various homeostatic functions, control of movement, neurotransmission and drug addiction. An important factor determining the pharmacologic role of opioid receptors is their distribution within the brain regions as well as at the cellular level. Over the past 40 years, a great deal of information concerning their distribution in the central nervous system has been collected, allowing us to determine their localization and mechanisms of their action. In general, results obtained from previous studies are in agreement. However, there are some inconsistencies that impede the accurate determination of receptor distribution and need to be clarified. This paper aims to summarize results of the previously published studies observing the localization of opioid receptors in the rat CNS. Emphasis is placed on the comparison of results obtained by all available methods.
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Study of neurosteroid effect on the NMDA subtype of glutamate receptor.
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Bendová, Zdeňka (referee)
N-methyl-D-aspartate (NMDA) receptors are glutamatergic ionotropic receptors involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. They are heteromeric complexes of GluN1 combined with GluN2A-D and/or GluN3A-B subunits that are activated by glutamate and glycine. Many allosteric modulators can influence the activity of these receptors including neurosteroids. Pregnanolone sulfáte (3α5βS) is an endogenous neurosteroid that inhibits NMDA receptors in a use-dependent manner and has neuroprotective effect. Binding site for 3α5βS on the NMDA receptor molecule is still not indentified. The aim of my work was to contribute to the identification of the biding site by kinetic analysis of rate of response return from 3α5βS inhibition. Using the point mutation we also attempted to identify the amino acids residues that could be involved in the neurosteroid binding. In order to study the effect of 3α5βS on NMDA receptors the electropfysiological recordings on human embryonic kidney 293T cells expressing recombinant GluN1/GluN2B receptors was performed. We confirm that the effect of 3α5βS on GluN1/GluN2B receptors is voltage-independent. The results of my work indicate that steroids can reach the binding site on the NMDA receptors through the membrane rather than directly from the aqueous...
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Cellular signaling pathways engaged in the entrainment of mammalian biological clock
Červená, Kateřina ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
The mammalian biological clock is based on endogenous rhythmic oscillations of the so-called clock genes which affects the timing of the external manifestations, such as rhythmic alternations of sleep and activity. This endogenous mechanism, of which the innate period slightly deviates from the solar time, can be adjusted by various external synchronizers to the exact 24 hour period. This thesis is focused on the influence of the most prominent synchronizer, the sunlight, on the molecular basis of changes in the dynamics of internal mechanism of the oscillations in the main mammalian circadian pacemaker, the suprachiasmatic nuclei of the hypothalamus. There are numerous studies which have demonstrated the effect of various cellular signaling pathways on changes of circadian rhythms. The most common methods of assessing the oscillation phase changes, however, measure changes in output rhythms that may not always reflect the changes in the molecular mechanism itself. The aim is to evaluate which components of signaling pathways have provably shown to affect the dynamics of the rhythmic expression of clock genes.
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Ethics of dying and death in intensive care
Bendová, Zdeňka ; Votroubková, Michaela (advisor) ; Kutnohorská, Jana (referee) ; Švecová, Dagmar (referee)
Author: Zdeňka Bendová Theme: Ethics of dying and death in intensive care Keywords: ethics, dying, death, paliative care, intensive care Bachelorś thesis is dealing with ethics of dying and death within the scope of intensive care. Medicine offers many possibilities of treatment and desease diagnostics nowadays. Requirement of paliative medicine use is becoming more important with increasing intensive care. Patiens can live for a much Langer time with a medical machines support as a result of a very high contemporary medical care standard. This situation brings new ethic problems.
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