National Repository of Grey Literature 42 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
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
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
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...
Structural and pharmacological determinants of NMDA receptor channel gating
Ladislav, Marek ; Krůšek, Jan (advisor) ; Bendová, Zdeňka (referee) ; Zemková, Hana (referee)
N-methyl-D-aspartate receptors (NMDARs) are heterotetramers containing two obligatory glycine-binding (GluN1) and two glutamate/glycine-binding (GluN2/3) subunits. These receptors mediate excitatory synaptic transmission in the central nervous system and play a key role in high order neuronal processes as a learning and formation of memory. It has been shown that dysregulation of NMDARs is involved in the pathophysiology of neurological and psychiatric disorders. Each receptor is composed of four protomers exhibiting a conserved domain organization. The most distal part to the cell membrane is the amino-terminal domain that is linked to the ligand binding domain (LBD), which is connected to the pore-forming transmembrane domain (TMD) communicating with the intracellular carboxy-terminal domain. LBD and TMD are connected via three polypeptide chains - linkers. Channel opening is the key step in the NMDAR gating that allows the flux of ions across the membrane. The energy of agonist binding-evoked conformational changes is transferred via linkers to M3 helices forming an ion channel. The rearrangement of M3 helices in activated receptor makes the central cavity of the channel accessible. The details of energy transfer are not yet fully characterized, although accurate knowledge of the receptor gating...
The effect of acute cold and permanent light to left ventricular of the rat heart
Vítková, Ivana ; Žurmanová, Jitka (advisor) ; Bendová, Zdeňka (referee)
Acute cold exposure increases the risk of sudden cardiac events, similarly exposure to constant light negatively affects the cardiovascular system. However, the individual effects of these factors and the effect of their combination on cardiomyocytes are not yet known. The thesis deals with the influence of a 3 day cold exposure and constant light on the expression of β-adrenergic receptors and associated G-proteins in association with apoptotic signals in the left ventricle of the Wistar rat heart. In this work apoptotic proteins BAX, BCL2, caspase 8 and important components of β-adrenergic signalization - β1, β2, G-proteins, Gas, Gi1/2 and Gi3 were determined. The relative expression of the proteins was analyzed by Western blotting. The results confirm the detrimental effect of cold and light exposure. However, the synergistic effect of these two stressors shows surprising results.
The modulation of the circadian rhythm in melatonin production in human induced by experimental lighting conditions
Skálová, Kateřina ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
The circadian system controls the timing of most of the physiological functions and behaviour within approximately 24 hours period. The light/dark cycle aligns this circadian period with the exact length of the solar day. Light information is conveyed via ipRGC cells in the retina, with maximum sensitivity in the blue part light (460-480nm wavelength). The information proceeds to the main circadian clocks located in the suprachiasmatic nuclei. This clock regulates the synthesis of neurohormone melatonin in the pineal gland whose high night level can be rapidly downregulated by the light at night. The major aim of this study was to test the effectiveness of the blue or green light-emitting device, potentially utilized in clinical practice, to suppress the night melatonin level and provide thus the first evidence that this device may affect the circadian system. The results show that the light emitted by this device has the potential to lower melatonin levels in most subjects with the higher efficiency in the blue range. Key words: circadian rhythms, melatonin, light pulse, eyelids, blue and green light
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
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...
Structural determinants of regulation of surface delivery of NMDA receptors in mammalian cells
Danačíková, Šárka ; Horák, Martin (advisor) ; Bendová, Zdeňka (referee)
N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels activated by agonist glutamate and co-agonist glycine. They play a key role in mediating the fast excitatory synaptic neurotransmission in the mammalian central nervous system. To create a functional heterotetrameric receptor, the presence of two GluN1 subunits combined with GluN2 or GluN3 subunits is necessary. Previous studies confirmed the importance of M3 transmembrane helix and extracellularly localized cysteines in regulation of surface expression of functional NMDA receptors. The aim of my thesis is to elucidate an influence of clinically relevant mutations in M3 transmembrane helix and the role of all known cysteines that form disulphide bonds on surface delivery of NMDA receptor expressed in heterologous monkey kidney fibroblasts cell culture (COS-7). Using molecular biology methods, immunocytochemistry and microscopy I found that the clinically relevant mutations M641I and Y647S in GluN1 subunit and also the mutations of particular cysteines forming disulphide bonds caused substantial decrease of surface expression of NMDA receptors. Furthermore, I discovered that the effect of mutated GluN1 subunits on decrease of surface expression depends on the subunit composition. The contribution of my results lies in elucidating the...
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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