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The effect of methamphetamine on the neuroimmune system
Petrášová, Blanka ; Hejnová, Lucie (advisor) ; Lapka, Marek (referee)
Metamphetamine is worldwide problem and in the Czech republic is 2-3 % of people older than 15 years exposed to it. There are 34,7 thousand long-term users in Czech republic and 19 methamphetamine-related deaths in 2022. The impact on the neuroimmune system has only started to be studied in recent years. Understanding its effect on the neuroimmune system may outline new treatment options, as there is no cure for methamphetamine addiction to date. This paper summarizes its effects on the different components of the neuroimmune system and outlines some substances that could be used in treatment. Key words: methamphetamine, neuroimmune system, inflammation, microglia, astrocytes
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Designer drugs derived from phenethylamine in relation to the dopaminergic system
Leová, Mara ; Hejnová, Lucie (advisor) ; Lapka, Marek (referee)
The focus of this thesis is on designer drugs structurally derived from phenylethylamine, a trace amine that is a component of dopamine's structure and plays a crucial role in its functioning within the human organism. The dopaminergic system, in general, is vital for regulating mood, motivation, and, last but not least, the mechanisms of addiction. The ratio by which different substances affect the concentration of dopamine and serotonine in the synaptic cleft serves as a significant marker for determining the likelihood of developing addiction to a particular substance. The main body of this thesis comprises groups of phenylethylamine derivatives, their structural descriptions, metabolism, and their potential for abuse. Key words: dopamine, dopaminergic system, phenethylamine, designer drugs, novel psychoactive substances
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Involvement of the neuroimmune system in Alzheimer's disease
Chaloupková, Barbora ; Hejnová, Lucie (advisor) ; Vašek, Daniel (referee)
Alzheimer's disease afflicts more and more people with increasing life expectancy. The causes of this disease are still not fully understood and explained. An effective treatment is still lacking. One of the reasons is a lack of effective biomarkers of the disease in its early stages before the onset of cognitive deficits. Current research focuses on the neuroimmune system. Emerging evidence shows that changes in its function play a significant role in Alzheimer's disease. This bachelor's thesis describes the interaction of components of the neuroimmune system in the preclinical stages and progression of Alzheimer's disease, their use as biomarkers in the diagnosis of preclinical and clinical stages of AD, and subsequently their potential use in the therapeutic treatment of AD. Key words: Alzheimer's disease, neuroimmune system, neuroinflammation, therapeutic treatment, biomarkers
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Molecular mechanisms of morphine action on the immune system
Zeťková, Anna ; Hejnová, Lucie (advisor) ; Vašek, Daniel (referee)
This paper focuses on the molecular effect of morphine, which is widely used for its analgesic and sedative properties. This makes it an important drug for the treatment of chronic and severe pain. In addition to its positive effects, the long-term administration of morphine in particular has its drawbacks, such as the rapid development of tolerance and dependence on it. Other negative effects include constipation, respiratory stagnation or vomiting. These effects are caused not only by the influence of morphine on nerve cells, but also on other cells of the body. This thesis is primarily concerned with the effect of morphine on microglia, which are not only involved in the immune response in the central nervous system, but also have an effect on pain perception or the development of tolerance. This is one of the main areas of research in the field of opioids, therefore, the aim of this thesis is to summarize the findings on the effect of morphine on microglia, which happens mainly through opioid receptors, toll-like receptors and purinoceptors.
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Effect of morphine preconditioning and mKATP channel activity on survival of differentiated SH-SY5Y cell line after oxidative stress
Paluba, Michal ; Hejnová, Lucie (advisor) ; Kolář, David (referee)
Morphine as one of the most effective analgesics has been used in medicine for more than a century. However, morphine is also known for its neuroprotective and cardioprotective effect in ischemic disorders, where it induces increased cellular resistance to oxidative stress. One of the aims of our study was to analyze the effect of chronic morphine treatment on the viability of differentiated cells of the neuroblastoma cell line SH-SY5Y after induction of oxidative stress by tert butyl hydroperoxide (tBHP). However, the detailed mechanism of the protective effect of morphine is still unknown. Current research on this topic, and in particular on morphine-induced preconditioning, has focused much attention on mitochondrial ATP- sensitive potassium channels (mKATPs). There is evidence that morphine, through activation of opioid receptors, mimics the protective effect of ischemic preconditioning precisely through activation of mKATP channels. Modulation of mKATP channel activity is thought to be responsible for the functional state of the mitochondria by altering mitochondrial membrane potential and regulating reactive oxygen species (ROS) production. Thus, the next aim of our work was to reveal the role of mKATP channels in morphine preconditioning and the effect of their activity on cell survival. The...
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Significance of the timekeeping system for human health
Pospíšilová, Lucie ; Sumová, Alena (advisor) ; Hejnová, Lucie (referee)
The circadian system evolved as an adaptation to cyclic changes in external conditions on Earth, mainly the alternation of light and dark with a period of solar day. The rhythmic signal is generated at the cellular level and it is controlled by rhythmic expression of clock genes and their protein products. In mammals, the hypothalamic suprachiasmatic nuclei (SCN) are the principal circadian oscillator coordinating daily cycles of physiology and behavior, while in peripheral tissues local oscillators operate. The peripheral oscillators are entrained to the daytime and also among each other, by neuroendocrine signals from the SCN. Mutual synchrony of all the circadian components is necessary for proper function of the organism. The main entraining cue of the circadian system with environment is light, which affect the SCN via retina. In a subgroup of blind people sensing the light in the retina is disturbed and their circadian system cannot be synchronized by light. The SCN controls rhythmic production of melatonin in the pineal gland. This hormone mediates the information about the daytime to other tissues in the body, which are not photosensitive. The circadian system temporally drives many processes, including the cell division cycle. It seems that disruption of the temporal regulation could contribute to...
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Importance of particular regions of CNS in the development of opioid addiction
Vyvadilová, Tereza ; Hejnová, Lucie (advisor) ; Roubalová, Lenka (referee)
Opiods are used as the most powerful painkillers in the medicine. The mechanism of their effect is determined by binding to the opioids receptors located in the central nervous system and peripheral nervous system. The opioids have high potential to develop addiction. Significance of psychical addiction belongs to losing control above using and compulsive desire to obtain drug of abuse to achieve certain psychical state. The somatic part is increase tolerance demonstrating need of dose increasing to achieve required effect. This thesis summarizes knowledge about particular regions of the central nervous system which participate on developing of addiction as ventral tegmental area, nucleus accumbens, locus coeruleus, ventral pallidum and amygdala. It seems that main role in developing of addiction acts the mesolimbic reward system which relates with increased release of dopamine resulting in stimulation of the brain reward system.
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Antinociceptive and neurotoxic effects of opioids
Moravcová, Radka ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
2. Abstract The curative actions of opioids have been known over two millenia. However, the mechanisms of their analgesic effects were only decoded in the last 20 years. There are 3 main types of opioid receptors (µ, κ, δ), that are together with the opioid peptidic system involved in antinociceptive processes and are widespread in the nervous system. Calcium plays a very important role in the pain perception and antinociception. Changes in its concentration are crucial for the neurotransmitter release. The relationship between the analgetic actions of opioids and the availability of Ca2+ in the CNS is explained in the way that, decreasing extracellular concentration of Ca2+ and/or by passaging through the membrane, antinociception will increase. Opioid analgesic effects are limited by their relatively high ability to create tolerance or addiction. Since these effects only result from heavy doses and long-term usage, severe complications should not arise during the right usage of these drugs. However, opioids can also have neurotoxic effects. The opioid-induced toxicity occurs in case when opioids release toxic metabolites during the process of their degradation in the liver. The neurotoxicity can be induced by the oxidation of the double bond in the opioid's chemical structure, thus producing free radicals...
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Molecular physiology of opioid receptors
Valný, Martin ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
The opioid receptors (OR) belong to the family of G protein-coupled receptors (GPCRs). ORs mediate the effects of the opioids, leading primarily to inhibition of neuroexcitability, predominantly through the class of the inhibitory G proteins Gi/Go. Cloning of ORs confirmed the existence of four subtypes of ORs, which mediate effects of different classes of opioid ligands. The major aim of this work is to summarize the current knowledge about characteristics and function of ORs at the molecular level. Acute exposition of ORs to their agonists results in activation of the signaling cascades that trigger mechanisms leading to analgesia. Chronic exposition of ORs to their agonists leads to desensitization and internalization of the receptors and induces adaptive changes in signal transduction system that suppresses the opioid action, and may result in the development of opioid tolerance and dependence. Although a big progress has been made in the field of understanding the molecular mechanisms of the OR-mediated signaling, there are still a lot of unresolved questions that are necessary to answer.
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Signal transduction in olfactory sensory neurons of vertebrates and tools for the computer simulation
Beneš, Martin ; Zápotocký, Martin (advisor) ; Hejnová, Lucie (referee)
The purpose of this thesis is summing up the information about olfactory transduction of vertebrates. This review is divided into four parts, each part focuses on a different aspect of olfactory transduction. First there is an overview of basic electrophysiological methods used for transduction research, followed by a description of a complete transduction on a molecular level. Next is a summary of model types and their use in olfactory transduction simulation, including a detailed description of two models: One of them describes the beginning of olfactory transduction, from the odorant binding on the receptor to the cAMP production, the other deals with the negative feedback of Ca2+. Finally there is an overview of software products designed to create and analyze the models from the preceding section.
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