National Repository of Grey Literature 71 records found  beginprevious33 - 42nextend  jump to record: Search took 0.00 seconds. 
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.
The expression and regulation of Dexras1 in the rat brain under development
Kyclerová, Hana ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
The Dexras1 gene was identified after induction by glucocorticoid dexamethasone in pituitary tumor cells. Dexras1 has also been found in other brain regions and in the peripheral organs but its expression is rhythmic only in the suprachiasmatic nuclei of the hypothalamus (SCN), where the mammalian main circadian pacemaker is located. Dexras1 expression was also affected by stress, amphetamine or prenatal alcohol exposure. Its role in cells has not yet been explained. Dexras1 GTPase activity has been determined to be dependent on the NMDA receptor stimulation. Dexras1 acts as an activator of G protein signaling in cells. Its role has been detected in neuronal iron homeostasis or in the regulation of main circadian pacemaker sensitivity to photic and nonphotic synchronization cues during the day. The aim of our study was to describe the Dexras1 mRNA expression in the rat brain during ontogeny and during development after visual sensory deprivation by in situ hybridization. The earliest Dexras1 expression was detected on embryonic day 20, in the rat SCN and the ventral posteromedial thalamic nucleus. Postnatally, its expression also appeared in other sensory areas, motor thalamic areas, hypothalamic areas involved in the regulation of water homeostasis, or in limbic system. Our results further show...
Protective effect of pro-cognitive training during adolescence on neuronal coordination deficit in a pharmacological model of schizophrenia.
Krajčovič, Branislav ; Kubík, Štěpán (advisor) ; Bendová, Zdeňka (referee)
Schizophrenia is a severe neuropsychiatric disorder characterized by positive, negative and cognitive symptoms with poor functional outcomes, placing an enormous burden on the individual, caregivers and society. Although deficits in cognition are an integral part of the disease and the best predictor of functional outcomes, there is as yet no established treatment addressing them. Avoidance of a hidden place on a continuously rotating arena (Carousel) requires cognitive control and is a rodent model of cognitive coordination of information from dissociated spatial frames, which is impaired in acute pharmacological and neurodevelopmental model of schizophrenia. Cognitive training on the Carousel during adolescence alleviates adult cognitive deficit in a neurodevelopmental model of schizophrenia and improves neural coordination (oscilations in the beta and gamma band), which is thought to be necessary for cognition. We examined if cognitive training during adolescence eliminates the deficit in neuronal coordination observed in adult rats after acute systemic NMDA receptor antagonist MK-801 (0.15 mg/kg). During adolescence, rats were either trained in spatial avoidance on Carousel or merely handled. As adults, rats received two 5-min exploration sessions in the same (A/A) or in two distinct...
The influence of inflammatory cytokines on depressive disorders
Svobodová, Eva ; Bendová, Zdeňka (advisor) ; Krulová, Magdaléna (referee)
1 Abstract Depressive disorders are one of the three most frequent diseases causing disability of everyday life of humans. Its occurrence in the population is rapidly increasing. Etiology of depression is unclear, and the treatment usually only ameliorates its symptoms. In patients, there were identified signs not only of chronic stress, which has been associated with depression for quite a long time, but also signs of chronic inflammation in the body. This has led to focusing on proinflammatory cytokines and their connection to chronic stress and depressive symptomatology. We are also interested in the causal link between pro-inflammatory markers and stress that has not yet been unequivocally clarified. The aim of this study is to combine the knowledge about the influence of chronic stress on the development of depressive disorder gained from animal and human models. Additionally, to combine the knowledge of the effect of specific proinflammatory cytokines on the development of the depressive disorder and the change in brain structures morphology which may underlie the symptoms of this disease.

National Repository of Grey Literature : 71 records found   beginprevious33 - 42nextend  jump to record:
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