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The role of TRPV1 receptors in nociceptive signalling at spinal cord level
Mrózková, Petra
Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn plays a key role in the development and maintenance of pathological pain states and chronic pain diseases. Important role in this process play Transient receptor potential Vanilloid 1 receptors (TRPV1), present on presynaptic endings of primary afferents in the superficial spinal cord dorsal horn. Changes in TRPV1 activity have significant impact on nociceptive transmission. There are number of processes that influence the function of spinal TRPV1 receptors. This work is focused on the role of protease-activated receptors type 2 (PAR2), C-C motif chemokine ligand 2 (CCL2) and the effect of chemotherapeutic drug paclitaxel in modulation of synaptic nociceptive transmission and activation of TRPV1 receptors. PAR2 receptors belong to a family of four G-protein-coupled receptors activated by proteases. The role of PAR2 receptors in pain perception is closely related to their presence in a population of dorsal root ganglion neurons, where they are also co-expressed with TRPV1. Activation of PAR2 may lead to peripheral and central sensitization. Chemokine CCL2 and its main receptor CCR2 were suggested to be an important factor in the development of neuropathic pain after peripheral nerve injury. In our study we focused on the...
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The role of miRNA in injury and regeneration of spinal cord tissue
Šprincl, Vojtěch ; Romanyuk, Natalyia (advisor) ; Mrózková, Petra (referee)
MicroRNAs are small non-coding RNA molecules of a length about 20-24 nucleotides, that regulate gene expression post-transcriptionally. They interfere mRNA molecules via base- pairing with complementary sequences. Recently it was shown that they play an important role in injury and regeneration of nervous tissue. The aim of this bachelor thesis is to describe possible role of miRNAs in central nervous system injury with focus on spinal cord injury.
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Localization of cytosolic isoforms of creatine kinase and hexokinase in hypertrophied heart
Heleš, Mário ; Žurmanová, Jitka (advisor) ; Mrózková, Petra (referee)
Hypertrophy of the heart is tightly bound to the metabolic adaptations and a cellular remodeling. An important and dynamic system contributing to the maintenance of energy homeostasis is the creatine kinase system (CK). The microcompartmentalization of CK isoforms maintains the flux of ATP between energy production and consumption sites and ensures the effectiveness of the CK system. Changes in expression and activity of CK isoforms during hypertrophy are already well described - to extend this knowledge, this thesis quantified changes in association of cytosolic CK isoforms and sarcomeres. Another essential system, maintaining homeostasis in overloaded heart is composed of the hexokinase (HK) isoforms, located also in cytosol and in mitochondrial compartment. HK1 is associated with mitochondria under physiological conditions, maintaining mitochondrial membrane potential, while HK2 is located mainly in the cytosol. Under stress conditions translocation of HK2 into mitochondrial membrane occurs, which increases the direct supply of ADP to complex V of the respiratory chain and decreases the probability of apoptosis activation. We analyzed association of individual HK isoforms with mitochondria within the second aim of this thesis. Third aim of the thesis was to characterize changes in the CK and M...
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Effects of sulfated neurosteroids on proteins involved in excitatory synaptic transmission
Naimová, Žaneta ; Smejkalová, Terézia (advisor) ; Mrózková, Petra (referee)
The discovery of steroid compounds capable of synthesize or accumulation in CNS and PNS led to a question about their function. Neurosteroid compounds are capable of modulating synaptic transmission. Effect is direct and fast mediated through nongenomic mechanisms. They are known to affect wide array of channels and receptors - both excitatory and inhibitory. This thesis summarizes findings about effect of sulfated neurosteroid on proteins involved in excitatory synaptic transmission. Thesis covers findings about ionotropic glutamate receptors, TRP channels, metabotropic receptors, sodium and potassium channels. Excessive or insufficient activity of these proteins involved in synaptic transmission can lead to a pathological condition. The purpose of this thesis is to summarize findings about effect of these compounds, point out structural and function characteristic probably responsible for their action and to outline possible pharmacological usage.
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The role of TRPV1 receptors in nociceptive signalling at spinal cord level
Mrózková, Petra
Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn plays a key role in the development and maintenance of pathological pain states and chronic pain diseases. Important role in this process play Transient receptor potential Vanilloid 1 receptors (TRPV1), present on presynaptic endings of primary afferents in the superficial spinal cord dorsal horn. Changes in TRPV1 activity have significant impact on nociceptive transmission. There are number of processes that influence the function of spinal TRPV1 receptors. This work is focused on the role of protease-activated receptors type 2 (PAR2), C-C motif chemokine ligand 2 (CCL2) and the effect of chemotherapeutic drug paclitaxel in modulation of synaptic nociceptive transmission and activation of TRPV1 receptors. PAR2 receptors belong to a family of four G-protein-coupled receptors activated by proteases. The role of PAR2 receptors in pain perception is closely related to their presence in a population of dorsal root ganglion neurons, where they are also co-expressed with TRPV1. Activation of PAR2 may lead to peripheral and central sensitization. Chemokine CCL2 and its main receptor CCR2 were suggested to be an important factor in the development of neuropathic pain after peripheral nerve injury. In our study we focused on the...
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Nootropics and molecular mechanisms of their action
Staněk, Petr ; Novotný, Jiří (advisor) ; Mrózková, Petra (referee)
Nootropics have become the standart in the field of treating memory impairments and decline of cognition which are still more frequent problem when we consider aging of population in the western world. To better understand the capabilities and dangers of these drugs, it is necessary to widen our knowledge of the mechanism of their action. In this thesis I focus on the nootropics with the widespread use across the world (nicotine, caffeine) and on the drugs with long clinical prescription history and deeply explored effects on the cognition (methylphenidate, modafinil, piracetam, ampakines). Some categories of substances currently in the pre-clinical studies with good potential for future utilization are also briefly mentioned. The emphasis is laid mainly on summarization of the present knowledge concerning the mechanisms of action on the level of molecules, cells and the brain as a whole. The results of preclinical and clinical studies evaluating effects of these compounds on psychological values, memory and cognition are also considered here not only for CNS pathologies correction but also regarding healthy individuals.
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Methods using preference in pain research
Komárková, Lucia ; Vaculín, Šimon (advisor) ; Mrózková, Petra (referee)
The thesis deals with neuropathic pain measurement in laboratory mice and rats. Neuropathic pain is characterized besides evoked allodynia and hyperalgesia also by spontaneous pain and anhedonia, further motivational-affective part of pain is highlighted. Traditional pain threshold testing is not appropriate method to measure these aspects of pain. Therefore, the aim of the thesis is to describe preference methods in pain research. We focused on three methods - conditioned place preference, sucrose preference test and thermal place preference. The first mentioned method creates an association between pain relief and a specific place, which afterwards the animal prefers. The conditioned place preference can be used to detect spontaneous pain. Sucrose preference test monitors decrease in consumption of sugar water after exposure to chronic pain, which can be interpreted as a sign of depression, so thanks to this method we have the opportunity to explore the interaction between pain and depression. The thermal place preference method studies changes of preferences between the cold and hot plate after induction of pain or analgesics. The findings based on preference methods help us to examine all aspects of neuropathic pain and develop more options for pain treatment.
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Experimental rat models in traumatic spinal cord injury research
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Mrózková, Petra (referee)
A large number of spinal injuries that cause damage to the spinal cord occur every year. Such damage to spinal cord tissue leads to a number of dysfunctions that significantly reduce quality of life and therefore the development of effective therapies remains a very important issue. The use of animal models is considered the major tool of this research field, enabling the testing of new treatments as well as observing ongoing pathophysiological processes. Rats are the most frequently used animal model due to the many possible ways of creating a spinal cord lesion on them. The contusion model uses a computer-controlled device to simulate the spinal cord contusion and therefore is highly precise. However, a compression model seems to be the most suitable model for pathophysiological studying. Besides contusion it enables persistent compression to the spinal cord. Transection and hemisection methods are intended for axonal regeneration research, as only these models can reliably distinguish new growing fibers from the preserved ones. Less often photochemical and excitotoxic models are used. Lastly, dislocation and distraction of vertebrae or damage to the spinal cord using heat or cold can be carried out. Each of the models have their own unique features that make them optimal to use in different...
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Thermally gated TRP channels in nociceptive neurones
Chvojka, Štěpán ; Vlachová, Viktorie (advisor) ; Mrózková, Petra (referee)
Transduction ion channels are gated in response to a variety of external stimuli and this process is critical for the proper functioning of sensory neurons. These specialized proteins enable the survival of any organism, which depends on having adequate information about the external environment. The thermosensitive TRP (transient receptor potential) ion channels, whose molecular structure has been identified during last decades, enable the transduction of thermal stimuli in primary nociceptive neurons. During the last decade, molecular biological techniques have provided new tools for studying the structure of these specialized transduction ion channels in relation to their function and to understand more deeply their physiological roles. The aim of this bachelor thesis is to give an overview of recent evidence regarding the functional and physiological properties of sensory-neuron specific mammalian TRP ion channels that are activated by thermal stimuli: heat and cold.
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