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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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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 Maternal Synchronization of the Fetal Biological Clock in Laboratory Rat
Houdek, Pavel ; Bendová, Zdeňka (referee)
2 Abstract In mammals, the central biological clock is located in the suprachiasmatic nuclei of the hypothalamus (SCN). Neurons of the SCN display circadian rhythmic activity and coordinate physiological functions within a day. At the molecular level, the rhythmicity of these neurons is based on transcriptional-translational feedback loops in the expression of so-called clock genes. During ontogenesis, the spontaneous rhythmicity evolves in the SCN gradually from the prenatal period and is affected by the maternal organism signals. The mechanisms of the maternal entrainment were investigated in two publications, which this thesis is based on. The first publication aimed to determine when the clock gene expression begins to be rhythmic in the SCN during the prenatal development of the laboratory rat. Two 24-hour clock gene expression profiles in the fetal SCN were compared under physiological conditions at two different development stages. The result showed that all three measured clock genes (Bmal1, Per2 and Rev-erbα) were expressed rhythmically on the 21st day of the embryonic development. However, only the expression of gene Rev-erbα was found to be rhythmic at the embryonic day 19. In the second publication, we investigated the effect of the maternal hormone melatonin on the entrainment of the circadian...
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