National Repository of Grey Literature 9 records found  Search took 0.00 seconds. 
Intracellular domain of glutamate ion channels and its role in the emergence of pathophysiological states
Sadílková, Lucie ; Balík, Aleš (advisor) ; Kolář, David (referee)
Glutamate mediates most of the excitatory neurotransmissions in the central nervous system of mammals. Its effect depends on the presence of glutamate receptors on postsynaptic neurons. NMDA receptors are class of the ionotropic glutamate receptors and are necessary for normal brain function such as synaptic plasticity, learning, memory and correct development of neu- rons. NMDA receptors are also involved in the pathophysiology of many neurodevelopmental and neuropsychiatric diseases. The aim of this work is to evaluate the current knowledge of the role of the intracellular part of NMDA receptors for their function, particularly with respect to the regulation of their localization at excitatory synapses. In addition, it also provides an over- view of the genetic changes found in this part of the receptor, their effect on the functional properties of the receptor and then also a possible link to specific disease.
Iontropic glutamate receptors and their RNA processing in the mammalian suprachaismatic nuclei
Kuchtiak, Viktor ; Balík, Aleš (advisor) ; Sládek, Martin (referee)
Suprachiasmatic nuclei (SCN) are primary center of mammalian circadian rhythms. To maintain a 24 hour period of its rhythms, SCN are synchronized with phase of external environment. Regular changes of light and darkness are known to be the main external synchronizer that determines the period of SCN rhythms. Information about light is being transferred from retina to the ventrolateral region of SCN through excitatory synapses where ionotropic glutamate receptors (iGluRs) play a primary role in the signal transduction. Posttranscriptional modifications of RNA can alter the functional properties of iGluRs, thus this process contributes to synaptic plasticity. The extent of posttranscriptional modifications of iGluRs can be in vitro affected by neuronal activity altered by pharmacological manipulation. The aim of this study was to determine possible changes of posttranscriptional modifications of iGluRs in in vivo rat SCN model and how this process can be regulated. RNA posttranscriptional modifications of GluA2 subunit of AMPA receptor (AMPAR) and GluK2 subunit of kainate receptor were assessed using PCR and subsequent sequencing of amplified DNA. Using quantitative PCR, we also determined mRNA expression of GluA1 and GluA2 subunits of AMPAR and the editing enzyme ADAR2 in SCN. Our results showed...
The analysis of structural details of the NMDA receptor
Radilová, Kateřina ; Balík, Aleš (advisor) ; Jakubík, Jan (referee)
NMDA receptor is necessary for excitatory transmission in the central nervous system. Altered funtion of the NMDA receptors is associated with many neurodegenerative and neuropsychiatric diseases. All available crystal structures of the NMDAR meant great shift towards our understanding of details of the receptor and its function. Unfortunately, these up- to-date available structures present only certain functional states of receptors and also a few structural data are still missing. For complete comprehension of the process of activation and deactivation of NMDA receptors, we need to supplement the current information with more data. The aim of this thesis was to employ a combination of different approaches (computational modelling, cloning, biochemistry, protein expression and purification and mass spectrometry) to obtain new structural data, by which we would be able to fill in the gaps in current receptor models, especially at various functional states of the receptor. Key words: NMDA receptor, glutamate receptor, computational modelling, structure, cloning, protein expression
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
Genetic changes in the regulatory regions of NMDA receptors and their association possible connection the development of schizophrenia
Hrychová, Šárka ; Balík, Aleš (advisor) ; Moravcová, Radka (referee)
Schizophrenia is a serious neuropsychiatric disorder with a severe impact on patients' lives. Based on the experiments in animal models and also from the observations of the influence of the drug in humans it was concluded that the decreased activity of N-methyl-D- aspartate (NMDA) receptor gives rise to behaviour that is associated with the clinical manifestation of schizophrenia. Therefore, it is hypothesized that genetically determined variations in NMDA receptor activity contributes to the emergence and development of schizophrenia. The aim of this bachelor thesis is to summarize current knowledge on genetic alternations particularly in the regulatory regions of NMDA receptors in schizophrenia. Key words: schizophrenia, NMDA receptor, genetic changes
Alzheimer's disease-related changes in phosphorylation of collapsin response mediator protein 2 (CRMP2) and their effect on neuronal function
Škrlantová, Alice ; Balaštík, Martin (advisor) ; Balík, Aleš (referee)
CRMP2 was first identified in 1995 as a mediator of Sema3A signalization pathway which leads to axon growth cone collapse. Since then CRMP2 was designated as an essential cue during neuronal polarity estabilishment and neuronal growth in embryonic life. CRMP2 was also found hyperphosphorylated in NFT's and this finding led to further research of CRMP2 function in the pathogenesis of AD. The activity and proper function of CRMP2 is regulated by phosphorylation and a deeper look into the mechanism of this modification is necessary for understanding how CRMP2 influences the function of neural cells. In this thesis I focus on signaling pathways, kinases and interaction partners of CRMP2 and describe how aberrant regulation of these interactions leads to Alzheimerʼs disease development.
The role of D-amino acids in central nervous system
Pangrácová, Marie ; Konvalinka, Jan (advisor) ; Balík, Aleš (referee)
Only recently, the presence of D-amino acids in the mammalian central nervous system has been confirmed and their biological functions revealed. D-serine and D-aspartate, the best described D-amino acids, have been found to be the co-agonists activating NMDA receptors. In this way D-serine and D-aspartate, among other functions, affect synaptic plasticity which is the basic cellular mechanism for learning and memory. Pathological changes in the levels of these D-amino acids and their metabolical enzymes can lead to the development of epilepsy, schizophrenia, and neurodegenerative diseases such as amyotrophic lateral sclerosis, Huntington disease or Alzheimer disease. The main role in the D-serine synthesis is played by serin racemase while D-aspartate is synthetised with the help of aspartate racemase. The key enzymes for the degradation of D-amino acids are DAAO (D-amino acid oxidase) and DAspO (D-aspartate oxidase). This thesis presents an overview of available knowledge on the individual amino acids and their respective metabolical enzymes in the mammalian central nervous system, i.e. their distribution, cell localizations, metabolism and functions. Furthermore, the emphasis is put on the possibilities of inhibition and activation of the metabolical enzymes and their importance with respect to...
Spontaneous calcium permeability of ionic channel of P2X receptor after substitution ofconserved tyrosine in the 1st transmembrae domajn
Rupert, Marian ; Zemková, Hana (advisor) ; Balík, Aleš (referee)
Purinergic receptors are membrane ion channels that are activated by extracellular ATP. In vertebrates, seven genes encode subunits of P2X receptors. The subunits, designated P2X1-7, are 40 - 50% identical in amino acid sequences. P2X receptors are composed of three subunits and are found as homo- and heterotrimers in tissues of vertebrates. P2X receptors have a wide distribution in the organism, functional receptors are found in neurons, glial cells, muscle cells and also in nonexcitable tissues as epithelial, endothelial, and in hemopoietic tissue. Purinergic signalling plays an important role in pain transmission, at CNS injury and immune processes. P2X receptor subunit consists of two transmembrane domains, extracellular domain and intracellular N-and C-termini. Each transmembrane domain contains two amino acids conserved across all P2X subunits. In the first transmembrane domain receptor P2X2 are that Gly30 and Tyr43. In previous experiments performed on P2X2 receptor, electrophysiological measurements demonstrated that substitution of conserved Tyr43 in the first transmembrane domain with alanine prolongs the deactivation time of ion channel after agonist wash out. This work is focused on clarifying the role of conserved tyrosine in the process of opening and closing of ion channel of P2X...
Glutamate ion channels - their function, structure and mechanism of action
Navrátil, Jiří ; Balík, Aleš (advisor) ; Lichnerová, Katarína (referee)
Glutamate gated ion channels mediate the excitatory signal transduction in the central nervous system. They are essential in the processing of external stimuli, in the process of learning and during the formation of memory. Molecular mechanism of action single channels is not still fully understood. However increasing number of structural and electrophysiological data provides new details describing the mechanism for ion channel action.

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