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Tracking the progression of Alzheimer's like-pathology in transgenic rat model TgF344-AD
Foltýnová, Alice ; Telenský, Petr (advisor) ; Němec, Pavel (referee)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting dominantly the elderly and it is the most common cause of dementia. AD is characterized by many pathological events such as amyloid plaques, neurofibrillary tangles, inflammation, neurotransmitter dysregulation and many others. These disruptive processes ultimately lead to synaptic and cell loss which human brain. According to literaure, cell loss in AD is apparent especially in the cortex and hippocampus. However, it is unclear at which timepoint the loss becomes significant and in which other structures. There are many other important structures such as olfactory bulbs or entorhinal cortex where the cell loss has not been fully quantified. With new methods like isotropic fractionator it has become possible for scientists to quantify large number of structures more quickly. Since human brains are not easy to obtain shortly after death, use of transgenic animal models, mostly rodents, is a good way to obtain more information about cell and especially neuronal loss occurring in AD. Key words: Alzheimer's disease, cell loss, isotropic fractionator, hippocampus, neurofibrillary tangles, beta amyloid
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The role of aquaporins in the Alzheimer's disease
Kubísková, Monika ; Turečková, Jana (advisor) ; Vlachová, Viktorie (referee)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex pathophysiology affecting the central nervous system (CNS). In progress of the disease, various pathological changes occur in the brain, leading to neurodegeneration and subsequent impairment of physiological and cognitive functions. Although it is the most common cause of dementia in elderly, currently, there is no effective treatment for AD that that targets its underlying mechanisms. There are different theories as to which process is the key trigger for the development of AD. The generally accepted theory considers increased production of amyloid β (Aβ), its accumulation in the ECS and the formation of amyloid plaques as the main cause of the disease. However, recent studies show that the primary cause of amyloid plaque formation is not increased Aβ production, but rather its impaired clearance through the glymphatic system, the main component of which are aquaporin water channels, specifically aquaporin-4 (AQP4). The goal of this thesis is to provide an overview of the available knowledge on the involvement of aquaporins in AD pathophysiology, with a particular focus on AQP4 and its role in the glymphatic system. Key words: Alzheimer's disease, neurodegeneration, central nervous system, astrocytes, aquaporins,...
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The role of endothelin receptors type A and B in the model of focal cerebral ischemia in immature rats
Vondráková, Kateřina ; Tsenov, Grygoriy (advisor) ; Říčný, Jan (referee)
Hypoxic-ischemic insult is a most common form of perinatal brain damage that threatens a newborn's life and can leads to permanent neurological sequelae. However, detailed aspects of the cerebral ischemia in the immature brain stay unanswered. We decide to use the model of focal cerebral ischemia induced by intrahippocampal endothelin-1 (ET-1) in 12-days-old rats. The knowledge about consequences of ET-1 induced ischemia and the role of endothelin receptors (ETA and ETB) in ischemia-induced consequences in immature brain are poor at present. Agonists and selective antagonists of the ETA and ETB receptors were used to determine the role of these receptors in the development of ischemia, changes in regional blood flow and tissue oxygenation, local changes of biochemical parameters and acute neuronal death. Our results indicates, that activation of the ETA receptors causes a strong decrease of the blood flow, induced related hypoxia and subsequent neuronal degeneration, whereas activation of ETB receptors has likely modulatory role. Moreover, ischemia causes increase of excitatory amino acids concentration, whereas inhibitory amino acid, except taurine, decreased after ischemia. These facts provides new insights in a case of perinatal ischemia. This thesis demonstrates the wide range of different effects of...
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Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease
Červinková, Tereza ; Červený, Lukáš (advisor) ; Musílek, Kamil (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Tereza Červinková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title: Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease The increased life expectancy goes hand in hand with ageing-related cognitive impairments. Alzheimer's disease (AD) is the most common type of dementia being an irreversible and progressive brain disorder with loss of cognitive functions. Recent studies suggest that excess of glucocorticoid (GC) action exerts deleterious effects on the hippocampus and causes impaired spatialmemory. In addition, it has been demonstrated that aged mice with cognitive deficits show increased gene expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampus and parietal cortex. The Senescence-Accelerated Mouse Prone 8 (SAMP8) strain is a spontaneous animal model of accelerated ageing. Many studies indicate that SAMP8 harbour the behavioural and histopathological signatures of AD. In the present study, we evaluated the neuroprotective effects of 11β-HSD1 inhibition by a potent pyrrolidine-based compound RL-118 and/or effects of diet on cognitive performance in different groups of SAMP8 by conducting behavioural and...
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The role of nitric oxide during in pathophysiology of neurodegenerative diseases
Sikora Marečková, Věra ; Otáhal, Jakub (advisor) ; Konopková, Renata (referee)
Title: The role of nitric oxide in the pathophysiology of neurodegenerative diseases Objectives: The main objective of this thesis is to evaluate the effect of nitric oxide on the formation and development of neurodegenerative diseases. Another objective was to determinate, whether NO affects by its impact processes involved in apoptosis in the CNS. Methods: The thesis is prepared in the form of research, drawing from available relevant resources. Results: Nitric oxide is widely applied in the pathophysiology of selected neurodegenerative diseases, either directly or through other reactive nitrogen and oxygen. It also affects other factors that are involved in apoptosis in the CNS. Keywords: Nitric oxide, NMDA receptors, neurodegenerative diseases, excitotoxicity, apoptosis
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Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease
Červinková, Tereza ; Červený, Lukáš (advisor) ; Musílek, Kamil (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Tereza Červinková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title: Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease The increased life expectancy goes hand in hand with ageing-related cognitive impairments. Alzheimer's disease (AD) is the most common type of dementia being an irreversible and progressive brain disorder with loss of cognitive functions. Recent studies suggest that excess of glucocorticoid (GC) action exerts deleterious effects on the hippocampus and causes impaired spatialmemory. In addition, it has been demonstrated that aged mice with cognitive deficits show increased gene expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampus and parietal cortex. The Senescence-Accelerated Mouse Prone 8 (SAMP8) strain is a spontaneous animal model of accelerated ageing. Many studies indicate that SAMP8 harbour the behavioural and histopathological signatures of AD. In the present study, we evaluated the neuroprotective effects of 11β-HSD1 inhibition by a potent pyrrolidine-based compound RL-118 and/or effects of diet on cognitive performance in different groups of SAMP8 by conducting behavioural and...
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The role of accumulation of iron and other metals in the pathophysiology of neurodegenerative diseases
Mašková, Jana ; Dušek, Petr (advisor) ; Vymazal, Josef (referee) ; Bártová, Petra (referee)
The role of metal accumulation in the pathophysiology of neurodegenerative diseases has been a hot topic in recent years due to the possibility of its treatment by chelating agents. Although the mechanisms of neurodegeneration are well known, the role of metal accumulation is still unclear. The main limitation are unsatisfactory methods for in vivo metal imaging; the most widely used technique is magnetic resonance imaging (MRI). Our aim was to assess the possibility of using transcranial sonography (TCS) in differential diagnosis of neurodegenerative diseases and to further explore the underlying factors of echogenicity. In the first study, using TCS fusion with MRI, we focused on location verification of the commonly assessed structures (substantia nigra and nucleus lentiformis) and exclusion of possible focal structural changes affecting the echogenicity in WD and PD patients. Moreover, obtained MRI were used for semi-quantitative comparison with TCS images. Although TCS has been confirmed to be highly beneficial in differential diagnosis of Wilson's disease and it should be recommended as a screening method for extrapyramidal patients with atypical course of the disease, the direct relationship between TCS and metal deposits could not be proven. The obtained results from the ultrasound fusion...
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The role of mitochondria in the pathogenesis
Marková, Lenka ; Doležal, Pavel (advisor) ; Verner, Zdeněk (referee)
This thesis is focused on the existing data referring to role of mitochondria in the pathogenesis of several important diseases. It introduces mitochondrial proteins, their role and metabolism, dysfunction of which is behind pathogenetic processes. The thesis also summarizes possible mitochondrial damage, its progress and consequences, which can lead to diseases or aggravate their process. It also pays attention to the role of mitochondria during oncogenesis as well as important neurodegenerative disorders such as Alzheimer's or Parkinson's disease, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis or autosomal dominant optic atrophy. The thesis mentions the role of disrupted mitochondrial dynamics in type 2 Diabetes. In conclusion the thesis mentions the role of mitochondria and their damage in relation to infection by the parasites Toxoplasma gondii and Trypanosoma cruzi.
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Influence of intestinal microbiota on development of neurodegenerative diseases
Hakenová, Kristina ; Valeš, Karel (advisor) ; Vodička, Martin (referee)
Aging is associated with natural biological changes, which result in a decrease in the functional capacity of the body, which is also accompanied by an increased incidence of inflammatory processes that contribute to the development of neurodegeneration. The intestinal microbiota and its interaction with the intestine and the central nervous system play a key role in maintaining the function of biological homeostatic systems at an older age. This opens the possibility of influencing or modifying human microbiota for the development of therapeutic strategies. Based on the analysis of stool samples by HPLC MS / MS, the study confirmed the effect of selected probiotics on the modification of metabolic pathways and the proper functioning of the microbiota per se. The greatest effects were observed on tyrosine metabolism, tryptophan metabolism, arachidonic acid metabolism and bile acid biosynthesis metabolism. A positive effect of selected probiotic bacteria was found in the memory component of cognitive functions. Significant improvements were observed in verbal learning and verbal memory. In subjects with mild cognitive impairment, the progression of cognitive deficit has been slowed. Significant improvement was also observed for executive functions. These findings were not followed by a subjective...
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Involvement of cellular signal systems controlled by small G-proteins in neuroregenerative processes
Dušek, Jakub ; Novotný, Jiří (advisor) ; Košek, Dalibor (referee)
G-proteins repeatedly seem as significant signal mediators according to actual "cellular signal during neuroregeneration" reviews. This thesis aimed to find out how much small G-proteins correlate with neural tissue regeneration and which molecular mechanisms induce the regeneration. The thesis mentions pathologies of nervous system which are caused by traumas or neurodegenerative diseases in wider social perspective. Pivotal part of the text describes principles of functioning for each small GTPase family and its involvement in nervous tissue repair. This thesis demonstrates crucial role of small GTPases in neuroregeneration and points to considerable therapeutic potential of these GTPases. Key words: neuroregeneration; small GTPase; small G-protein; Ras; signal systems; neurodegeneration
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