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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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Specifics of the use of opioids as important immunomodulators in the treatment of pain
Švubová, Veronika ; Hejnová, Lucie (advisor) ; Vašek, Daniel (referee)
This work deals with the specifics associated with the use of opioid analgesics in pain relief. In terms of antinociceptive effects, opioids have not yet been surpassed by other available drugs. However the use of these analgesics is quite problematic in many respects. For over 30 years, studies have shown that opioids can adversely affect components of the immune system (IS) and thus the overall condition of the patient. To understand the relationship between opioids and IS, it is necessary to know the mechanisms leading to immunomodulatory processes. Contact with opioids occurs at the cellular interface through interactions with opioid receptors (ORs). Within IS, we encounter all three basic types of OR - μ (MOR), δ (DOR), κ (KOR) and non-classical nociceptin receptors (NOP). Stimulation of these receptors induces activation of signaling cascades in target cells which can lead to dysregulation of cellular processes, thus modulating the immune response. However, the effect of opioids on IS cells may not be exclusively direct. More complex regulatory pathways have been found, involving parts of the central nervous system (CNS), the sympathetic nervous system (SNS), and endocrine-active tissues. Activation of these pathways then affects the activity of whole lymphoid organs. Each cell type within an...
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The role of metabolism and immune system in pulmonary hypertension
Křivonosková, Monika ; Plecitá, Lydie (advisor) ; Vašek, Daniel (referee)
Pulmonary arterial hypertension is a low-incidence, fatal, disease that affects the pulmonary vessels, which remodel, thicken and gradually reduce lumen. During this signaling molecules are excreted from endothelial cells, which act vasoconstrictively and proliferatively on smooth muscle cells. There is also a reduction in the production of vaodilators, which again has a vasoconstrictive effect. Accumulation of immune cells in adventitia promotes smooth muscle cell proliferation, migration and differentiation of fibroblasts into myofibroblasts, which causes changes in the composition of the extracellular matrix. Changes in metabolism within all artery layers related to the transition to glycolysis and increased glucose uptake promote cell proliferation and modulate signaling leading to infiltration and activation of immune cells resulting in artery remodeling.
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The effect of cold adaptation on the immune system
Vašek, Daniel ; Krulová, Magdaléna (advisor) ; Filipp, Dominik (referee)
Maintaining energy homeostasis at reduced temperatures is essential for the survival of the organisms. In this diploma thesis, we determined the impact of cold stress and cold adaptation on the rat immune system. A number of different factors participate at the process of thermoregulation, but the adrenergic signalling plays a crucial role. The binding of norepinephrine to β-adrenergic receptors leads to the formation of brown adipose tissue, which is necessary for non-shivering thermogenesis, as well as for energy balance. Bioactive products of adipocytes subsequently modulate the immune system, this process is significantly influenced by signalling of nerve cells. In order to understand neuro-immune interaction during the cold adaptation, we monitored changes in immune cell populations and the production of soluble products in rats treated with specific inhibitors of β-adrenergic receptors. Relationship between the immune and nervous system seems to be very important in many biological processes. Deciphering basic mechanisms of the influence of cold adaptation on immune cells can therefore explain other clinically relevant topics, such as treatment of obesity. Key words: immune system, cold adaptation, norepinephrine, adrenergic receptor, cytokines, brown adipose tissue, non-shivering thermogenesis
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Immune mechanisms in inflammatory pain
Vašek, Daniel ; Krulová, Magdaléna (advisor) ; Melkes, Barbora (referee)
Pain is one of the five symptoms of inflammation. Activation and regulation of pain are affected both by the nervous system and the immune system. The production of inflammatory mediators decreases the threshold for activation of the ion channels of peripheral nociceptors, which then result in painful sensations caused by otherwise innocuous stimuli. Such mediators are cytokines, bradykinin, prostaglandins or various neurotrophic factors. This work aims to explain the function of immune cells in the production of these inflammatory and painful modulators. The study of activation and sensitization of nociceptors in inflammation is important for the understanding of the whole mechanism of inflammatory pain as well as for a comprehensive understanding of the neuroimmune system. Understanding inflammatory pain can lead to the development of specific drugs against it. Key words: inflammation, pain, inflammatory pain, immune system, neuroimmune system
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