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Pathological pain states, the role of synaptic modulation at spinal cord level
Nerandžič, Vladimír ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee)
(English) Modulation of synaptic transmission in dorsal horn of spinal cord plays a key role in nociceptive signalling. Recent studies have indicated a great importance of presynaptic TRPV1 receptors (transient receptor potential vanilloid) in spinal cord. These receptors act as molecular integrator of nociceptive stimulation on periphery. The way of their activation and the effect on modulation of the synaptic transmission are not clarified yet. Previous studies demonstrated the influence of many inflammatory mediators and cytokins on TRPV1 receptors. The aim of our research was to show changes in activation of presynaptic TRPV1 receptors in the spinal cord following the application of endogenous agonist N-oleoyl dopamine (OLDA) in a model of peripheral neuropathy, after incubation with cytokine TNFα and to show the effect of precursor of anandamide N-acylphosphatidylethanolamine (NAPE). In our experiments, we have recorded miniature excitatory postsynaptic currents (mEPSC) from neurons of acute spinal cord slices by the patch-clamp method. The first series of experiments tested sensitivity to application of the endogenous agonist OLDA 5 days after evoking peripheral neuropathy. The frequency of mEPSC increased significantly - to 250 % of base level after applying a low concentration of OLDA (0,2...
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Molecular mechanisms engaged in the development of drug addiction
Pallag, Gergely ; Novotný, Jiří (advisor) ; Nerandžič, Vladimír (referee)
Drug use is part of the human life from the ancient times. Besides their recreational utilization, sustained misuse of these substances can lead to the development of drug addiction especially in susceptible individuals and thus cause serious health and social problems. The aim of this thesis is to briefly introduce brain structures which are affected by addictive substances, and describe some of the mechanisms and molecules that contribute to addiction. A crucial brain structure which plays a role in drug addiction is the reward system, with dopamine as the main neurotransmitter. After repeated use of drugs, in neurons of this system certain molecules and epigenetic changes are accumulating that promote chronic nature of addiction. Especially important is the highly stable transcription factor ΔFosB, which in cooperation with other molecules promotes relapse even after several months or years of the last drug use. Powered by TCPDF (www.tcpdf.org)
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Induction of neurogenesis and gliogenesis after ischemic CNS injury - the role of Wnt signaling pathway
Koleničová, Denisa ; Anděrová, Miroslava (advisor) ; Nerandžič, Vladimír (referee)
This bachelor thesis is focused on ischemic injury of the central nervous system (CNS), one of the most frequent causes of death and disability in the world, and its possible treatment via the induction of neurogenesis. It consists of three different parts. In the first part, main neurogenic regions of the CNS, the subventricular zone and gyrus dentatus (GD) of the hippocampus, are described at the cellular, as well as molecular level. The second part is mainly dedicated to ischemic injury, to the global and focal brain ischemia. A particular chapter of this part describes changes in neurogenesis and gliogenesis after ischemic injury of the brain, changes in the induction of radial glial cells, proliferation and migration of neural progenitor cells and neuroblasts. In this chapter, we also describe the activation of astrocytes, microglia and NG2 glia (also known as polydendrocytes) after ischemic injury of the CNS. The last, third part of the bachelor thesis, is focused on signaling pathways, which significantly influence neurogenesis: Shh (Sonic hedgehog homolog), Notch and Wnt (Wingles/Integrated) signaling pathways. Special attention is devoted to the Wnt signaling pathway, which is an essential part of molecular mechanisms in nerve cells. Keywords: neurogenesis, gliogenesis, hippocampus, gyrus...
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Modulation of nociceptive synaptic transmission
Nerandžič, Vladimír ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee) ; Hejnová, Lucie (referee)
Modulation of synaptic transmission in the spinal cord dorsal horn plays an important role in development and maintenance of pathological pain states. The indisputable part of this modulation is conducted via activity of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and the cannabinoid receptor 1 (CB1), expressed on presynaptic endings of primary afferents in the superficial spinal cord dorsal horn. Under physiological conditions, activation of TRPV1 receptors is pronociceptive while CB1 receptor activation leads to attenuation of nociceptive signalling. However, both receptors share also one endogenous agonist anandamide (AEA) that may be produced from N-arachidonoyl phosphatidylethanolamine (20:4-NAPE). Main objective of this thesis focuses on the effect of 20:4-NAPE on nociceptive synaptic transmission in spinal cord slices under naïve and inflammatory conditions and consequent on the possible interaction of TRPV1 and CB1 receptors. First, 20:4-NAPE application induced significant release of anandamide from spinal cord slices under in vitro conditions. Next, patch- clamp recordings of excitatory postsynaptic currents (mEPSC and sEPSC) from superficial dorsal horn (DH) neurons in acute spinal cord slices were used. 20:4-NAPE application under the physiological...
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Modulation of nociceptive synaptic transmission
Nerandžič, Vladimír ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee) ; Hejnová, Lucie (referee)
Modulation of synaptic transmission in the spinal cord dorsal horn plays an important role in development and maintenance of pathological pain states. The indisputable part of this modulation is conducted via activity of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and the cannabinoid receptor 1 (CB1), expressed on presynaptic endings of primary afferents in the superficial spinal cord dorsal horn. Under physiological conditions, activation of TRPV1 receptors is pronociceptive while CB1 receptor activation leads to attenuation of nociceptive signalling. However, both receptors share also one endogenous agonist anandamide (AEA) that may be produced from N-arachidonoyl phosphatidylethanolamine (20:4-NAPE). Main objective of this thesis focuses on the effect of 20:4-NAPE on nociceptive synaptic transmission in spinal cord slices under naïve and inflammatory conditions and consequent on the possible interaction of TRPV1 and CB1 receptors. First, 20:4-NAPE application induced significant release of anandamide from spinal cord slices under in vitro conditions. Next, patch- clamp recordings of excitatory postsynaptic currents (mEPSC and sEPSC) from superficial dorsal horn (DH) neurons in acute spinal cord slices were used. 20:4-NAPE application under the physiological...
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Molecular mechanisms engaged in the development of drug addiction
Pallag, Gergely ; Novotný, Jiří (advisor) ; Nerandžič, Vladimír (referee)
Drug use is part of the human life from the ancient times. Besides their recreational utilization, sustained misuse of these substances can lead to the development of drug addiction especially in susceptible individuals and thus cause serious health and social problems. The aim of this thesis is to briefly introduce brain structures which are affected by addictive substances, and describe some of the mechanisms and molecules that contribute to addiction. A crucial brain structure which plays a role in drug addiction is the reward system, with dopamine as the main neurotransmitter. After repeated use of drugs, in neurons of this system certain molecules and epigenetic changes are accumulating that promote chronic nature of addiction. Especially important is the highly stable transcription factor ΔFosB, which in cooperation with other molecules promotes relapse even after several months or years of the last drug use. Powered by TCPDF (www.tcpdf.org)
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β-Arrestin and its role in signal transduction
Marková, Vendula ; Novotný, Jiří (advisor) ; Nerandžič, Vladimír (referee)
β-Arrestin is a ubiquitous protein in cells, where it is involved in signal transduction and can affect different cellular processes. β-Arrestin cooperates with G protein-coupled receptors (GPCRs). Binding of β-arrestin to a receptor after its activation by a relevant ligand results in attenuation of signal transduction through the cognate G proteins, the process called desensitization, which can be associated with receptor intrenalization. Besides that, β-arrestin acts as adaptor for different molecules, which participate in signal transduction. β-Arrestin also has a role in a regulation of transcription in the cell nucleus. Finally, β-arrestin is explored in research focused on the development of a new type of drugs, so called biased ligands. After binding to a GPCR, these ligands can initiated only one specific activity of the receptor and affect relevant signaling cascades. Powered by TCPDF (www.tcpdf.org)
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Role of cannabinoids in the neuropathic pain.
Markup, Emil ; Hejnová, Lucie (advisor) ; Nerandžič, Vladimír (referee)
Pain is for mankind necessary tool for survival. Although pain is associated with unpleasant sensoric and emotional experience, its informations about real or potential tissue damage is critical to our well being. If pain becomes long-term and is no longer associated with tissue damage or healing process, then the pain becomes neuropathic pain, which have no physiological meaning and is considered a disease. Endocannabinoids system receptors affect many physiological functions, but they are the most famous for analgesic properties. Phytocannabinoids contained in cannabis plant and synthetic cannabinoids made by people bind to receptors in central nervous system and in body periphery and disrupt transmission of nociceptive signal. This paper reviews basic informations about cannabioids and their role in treatment of neuropathic pain. Understanding of endocannabinoid system mechanisms can lead to better and precisely targeted analgesics. Key words: neuropathic pain, cannabinoid receptors, natural cannabinoids, endocannabinoids, marijuana
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