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The effect of stress on regulation and regeneration of glucocorticoids in animal models differing in response of hypothalamo-pituitary-adrenal axis
Vodička, Martin ; Pácha, Jiří (advisor) ; Svoboda, Jan (referee) ; Bendová, Zdeňka (referee)
Stress reaction is usually activated by the brain, when homeostasis is or perceived to be threatened. The stress signals are transmitted from the brain by two main branches; the sympathoadrenomedullary and the hypothalamo-pituitary-adrenal (HPA) axes and employ neural, humoral and immune pathways to cope with the stressor. Because of its potency, the stress reaction has to be precisely regulated. The HPA axis is regulated by feedback loops where its end product, corticosterone in laboratory rat and mouse, inhibits its activity. The effect of corticosterone does not depend only on the concentration of corticosterone but also on local metabolism of glucocorticoids via oxo-reduction catalyzed by the enzyme 11β -hydroxysteroid dehydrogenase 1 (encoded by the Hsd11b1 gene), which intracellularly regenerates active corticosterone from inactive 11-dehydrocorticosterone, or by extra-adrenal de novo steroidogenesis of glucocorticoids. We focused on analysis of stress response in experimental animals differing in HPA axis responsivity (Fischer 344 rats (F344) vs. Lewis rats (LEW) and germ-free (GF) vs. specific pathogen free mice (SPF)) with special emphasis on regulation of stress response, glucocorticoid regeneration and influence of gut microbiota. We found that stress modulated local regeneration of...
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Association of selected polymorphisms with clock genes with a extreme chronotypes
Turečková, Lucie ; Bendová, Zdeňka (advisor) ; Weissová, Kamila (referee)
The circadian system has evolved in organisms as an adaptation to periodic changes in the environment. Its task is to ensure regular entrainment between the solar cycle and the internal period of the organism, and to generate signals that synchronize behavioral and physiological processes in the body with the solar cycle. The whole mechanism takes place at the cell level, where there are regular oscillations of the transcriptional translation loops of the clock genes occur within 24 hours, thus ensuring a regular rhythm of the organism. However, the circadian system may not generate the same length of period in humans and may differ in the degree of entrainment with the external cycle. Base on that there are developed so-called individual time preferences. These different preferences are referred to as chronotypes, which fall into five categories: extremely evening, moderate evening, intermediate, moderate morning, and extremely morning type. Clock gene polymorphisms are considered to be one of the possible causes of these differences. The association of selected clock gene polymorphisms with extreme chronotypes is the subject of this diploma thesis. We obtained a saliva sample for DNA isolation from volunteers with extreme chronotypes. Using molecular methods of PCR, restriction digest and...
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Evaluation of Biological Efficiency of Pilot Installation of Biodynamic Lighting in a Retirement Home
Halászová, Andrea ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
Many actions we observe in nature show some kind of regularity, therefore we call them rhytms. Rhytms with a period of approximately 24 hours, so called circadian rhytms, can be distinguished in many physiological processes, with the sleep-wake cycle being one of the most prominent ones. Light is the main exogenous circadian synchronizator and thanks to the circadian rhytm influence on physiological function, it's also often spoken about an influence of light on the entire organism. Nowadays, when we spend most of the day indoors under artificial light, we often suffer from a lack of natural daylight and its synchronizing potential. This is even more prominent in elderly population living in nursing homes and in other social facilities. Lately, a new type of lighting, so called biodynamic, has been introduced. Biodynamic lighting can simulate changes in natural light conditions throughout the day and therefore partially compensate for the lack of natural daylight we suffer from, and also minimize risks of the night light. In this study we aimed to test changes in the circadian system of seniors living in the Retirement Home of TGM in Beroun using questionnaires and circadian markers. We have shown a positive effect of the installed biodynamic lighting on our participants' circadian markers and...
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Development of the rat circadian system under constant light conditions
Petrželková, Lucie ; Bendová, Zdeňka (advisor) ; Kopřivová, Jana (referee)
The circadian system is a mechanism designed to generate circadian time and to synchronize it with the solar cycle. Its function is to adjust to behavioral and physiological function with the 24-hour period. The adjustment is performed using a so-called zeitgeber or synchronizer. The main circadian clock is in the suprachiasmatic nuclei (SCN) in the hypothalamus. Prolonged exposure of the organism to constant light conditions results in desynchronization of the circadian clock, which can lead to many pathologies. The impact of light at night on the organism has been studied for a long time, but the question of the impact of constant light on the development of the circadian system of the organism has been less studied. My thesis deals with this issue. Using RT-qPCR I investigated how the rhytm changes in the expression of selected clock genes in selected parts of the rat's brain, which has been kept in constant light sice birth. I also tested the impact of exposure to constant light on the early development of rhytm in locomotor activity later in the rat's life. Keywords: circadian system, photic entrainment, desynchronization under constant light, development, rat
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Circadian system in astrocytes
Ľalíková, Kristýna ; Bendová, Zdeňka (advisor) ; Honc, Ondřej (referee)
The circadian system affects almost all cells in the mammalian body. These cells include astrocytes, which together with microglia and oligodendrocytes represent the main types of glial cells found in the brain. The first chapter of this thesis presents a summary of circadian system characteristics and focuses mainly on the molecular mechanism underlying its functioning. The second chapter is devoted to astrocytes, astrocyte calcium signaling, and the process of gliotransmission. The third and last chapter connects both topics and discusses the circadian system in astrocytes. It presents evidence of astrocytic circadian oscillations existence and physiological consequences of its action. Great attention is paid to circadian rhythms in gliotransmission, with a focus on gliotransmitters ATP and glutamate. As the most impressive output of the circadian system of astrocytes is presented the participation in maintaining the rhythmic activity of the main circadian oscillator located in the suprachiasmatic nucleus of the hypothalamus. Key words: circadian system, clock genes, astrocytes, gliotransmission, calcium signaling, glutamate, ATP
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Expression of enzymes of kynurenine and methoxyindole pathway in the rat pineal gland, liver and heart in circadian profile and after lipopolysacharide administration
Hrubcová, Leona ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
Tryptophanis anaminoacidwhichhasmanyfunctionsinthebody. Besidesitsparticipationin theproductionofproteins,itactsasasubstrateforthekynurenineandmethoxyindolemetabolic pathways. The kynurenine pathway ends with the production of nikotinamid e adenin dinukleotide ( NAD + ) ,whichisneededfortheproductionofcellularenergy. Thus,withincreased energy demand during immune system activation, the activity of the kynurenine pathway is increased. Dueto increasedactivity,itproduces more immunoactiveandneuroactivemetab olites suchaskynurenicacidandquinolinicacid.Thesemetabolitesareinvolvedinmanyprocessesin the body and affect the pathology of many diseases. Studies show that regulation of these metabolites could be a key innovation in the treatment of cance r, cardiovascular or neurodegenerative diseases. The methoxyindole pathway is another important tryptophan processingpathway.Itsbest - knownmetabolitesareserotonin,whichactsasaneurotransmitter, andmelatonin,ahormonewithimmunomodulatoryeffect sregulatedby thecircadianclock . This workdeals with thecircadian rhythmicityofenzymeexpressionofthesetwo metabolic pathways.Italsodescribestheeffectofsystemicadministrationoflipopolysaccharideendotoxin ontheexpressionofgenesoft heseenzymes.OurexperimentsusedWistarratsat30daysofage. The lipopolysaccharide was administered...
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The effect of constant light in early development on the circadian system in the adulthood
Kubištová, Aneta ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
Long-term exposure to constant light results in desynchronization of the circadian system in an adult and is associated with reduced efficiency of many physiological functions timed to the exact time of day, or with the development of some of the so-called civilization diseases. Constant light in adults also results in deterioration of the cognitive abilities or changes in the sleep structure. The effect of night light on the health of an adult organism is studied mainly in connection with shift work or with light pollution. The question of what effect the increased level of night light has on the development of the organism, especially on the development of the nervous system and the circadian system itself, is less studied. This diploma thesis focused on the identification of the extent of changes in the expression of Per2, Nr1d1, Stat3, BDNF genes, as well as genes encoding NMDA receptor subunits and some tissue-specific genes in the retina. Our experiments were performed on adult Long-Evans rats, that spent the first 20 days of their postnatal development in low-intensity constant light. Changes in expression were determined by quantification of mRNA by RT-qPCR in the structures of the frontal and parietal cortex, olfactory bulb, hippocampus, suprachiasmatic nucleus and retina. Behavioral tests...
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Inflammation-associated changes in cannabinoid receptor expression in avian brain
Divín, Daniel ; Vinkler, Michal (advisor) ; Bendová, Zdeňka (referee)
(EN) Research in interactions between the nervous and immune systems is focused mainly on mammals, while in other vertebrates, including birds, it remains neglected. Two types of cannabinoid receptors interconnect the nervous and immune systems: CB1, which is in mammals involved in regulation of neural processes, and CB2, which is in mammals involved in regulation of immune processes. However, little is presently known about the roles of these receptors in nervous and especially immune processes in birds. Therefore, in this work I focus on the expression of cannabinoid receptors in cognitively advanced bird species (parrots, passerines) during induced sterile peritoneal inflammation. Unlike passerines, parrots appear to lack the gene for CB2, which may affect the inflammation regulation. I have revealed no changes in the expression of these receptors during peritoneal inflammation neither in parrots, nor in songbirds. Nevertheless, the increase in expression of the proinflammatory cytokine IL- 1β in the brain in parrots confirms the importance of neuroimmune interaction and mutual influences along the gut-brain axis. This work suggests that even in birds, the central nervous system is affected by inflammation through the gut-brain axis. The expression of cannabinoid receptors does not change much...
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Impact of light on cognition and mood
Křivohlavá, Tereza ; Bendová, Zdeňka (advisor) ; Růžička, Jiří (referee)
Circadian rhythms are cyclically repeating biorhythms with an approximate period of 24 hours. The main circadian pacemaker located in the suprachiasmatic nuclei in the hypothalamus controls the correct timing of physiological processes and behaviors and works to synchronize the whole body into a single period. The circadian clock works correctly if the period and phase are adjusted daily by environmental stimuli consistent with the solar cycle. The alternation of light and dark is the primary synchronizer of circadian rhythms and one that people mostly do not adhere nowadays. At nighttime they are usually exposed to strong lights while during the daytime they spend many hours in a dark room without receiving enough (sun)light. This disruption of biological and environmental clocks causes the desynchronization of the organism and the periodic misalignment of physiological or mental processes in the body. Long lasting desynchronization could have a serious impact on the human body, including emotions and cognitive functions.
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Molecular mechanisms of regulation of trafficking and function of different subtypes of NMDA receptors in hippocampal neurons
Skřenková, Kristýna ; Horák, Martin (advisor) ; Balík, Aleš (referee) ; Bendová, Zdeňka (referee)
of Ph.D. thesis Molecular mechanisms of regulation of trafficking and function of different subtypes of NMDA receptors in hippocampal neurons Mgr. Kristýna Skřenková N-methyl-D-aspartate (NMDA) receptors are ionotropic glutamate receptors that play a key role in the mammalian central nervous system. Under physiological conditions, these receptors are important for excitatory synaptic transmission and memory formation. However, under pathological conditions, their abnormal regulation or activation may lead to many neurological and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy or schizophrenia. Previous studies have shown that the number and type of NMDA receptors on the cell surface are regulated at multiple levels, including their synthesis, folding, internalization or degradation. During the trafficking of NMDA receptors to the cell surface membrane, both the agonist binding and receptor activation are examined. Moreover, NMDA receptors undergo many posttranslational modifications such as palmitoylation, phosphorylation or N-glycosylation. In this thesis, we studied the molecular mechanisms that may affect the trafficking and functional properties of NMDA receptors in mammalian cells and rat hippocampal neurons. Specifically, we studied i)...
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