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Profiles of cognitive deficit and the use of a short neuropsychological battery in different types of dementia
Bolceková, Eva ; Kulišťák, Petr (advisor) ; Krámská, Lenka (referee) ; Jirák, Roman (referee)
Pro les of cognitive de cit and the use of a short neuropsychological battery in di erent types of dementia Eva Bolceková Abstract This work focuses on cognitive de cit pro les and the use of a short neuropsychological battery in patients with di erent types of dementia. Increasing prevalence of dementia syndromes highlights the need of their e cient diagnostics in clinical-psychological practice. Theoretical part of this work presents an overview of neurodegenerative diseases with em- phasis on their neuropsychological presentation. We describe the cogni- tive domains and their neuropsychological examination. We address in detail the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and its experimental Czech version. Research part of the work is based on neuropsychological examinations of 311 patients with cognitive de cit and 118 healthy controls. Patients' group is comprised of subjects with Alzheimer's disease, mild cognitive impairment, vascular cognitive impairment, Lewy Body disease, frontotemporal lobar degene- ration and patients with depression. We assess their cognitive pro les, present sensitivity, speci city, positive and negativne predictive values of RBANS scores for the groups and compare the results of control subjects with the original normative sample. We...
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Characteristics of the nervous system of mice with a Lurcher mutation
Boubín, Josef ; Bendová, Zdeňka (advisor) ; Tůma, Jan (referee)
The glutamate receptor δ 2 (GluRδ2) is expressed in dendrites of Purkinje cells localized in the cerebellar cortex. Correct function of GluRδ2 is necessary for cerebellar development, synapse formation between parallel fibers of the granular and Purkinje cells and for inducing long term depression important in memory formation. Lurcher mutation, localized to 6th autosomal chromosome, transforms GluRδ2 into constitutively open ion channel by amino acid substitution in third transmembrane domain. As a result, almost complete disappearance of Purkinje cells population and a large degeneration of granular cells and olivary neurons occurs. Mice impaired by Lurcher mutation have lower body weight and reduced litter size. Fertility of males is not affected. Lurcher mutants display extensive behavioral deficits. Mice suffer from ataxia typical for cerebellar neurodegenerations. They have reduced physical performance, impaired spatial orientation and learning capabilities. The aim of this work is to summarize recent knowledge about Lurcher mutation from molecular basis to behavioral manifestation. Specific characteristics of this degeneration allow us to investigate influences of neurodegenerative cerebellar disorders on cognitive functions of the brain as a whole, study causing factors and treatment...
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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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Changes in neuroglia in degenerative disorders of the central nervous system
Kirdajová, Denisa ; Zach, Petr (advisor) ; Hock, Miroslav (referee)
Neurodegenerative diseases are a serious disorders of the central nervous system characterized by neuronal loss with a subsequent damage of the brain. This damage may have diverse consequences like a gradual loss of memory and intellect, problems with musculoskeletal system and not least death. Causes of these diseases are not yet fully understood. In addition to neurons neuroglia also plays an important role in these diseases of the central nervous system. In neurodegenerative diseases are astrocytes, oligodendrocytes, microglia and NG2 cells involved in their many aspects. They participate in the protective as well as in the detrimental aspect of these diseases. This work, therefore, presents an overview of previously acquired knowledge of neuroglia in various types of degenerative disorders of the CNS (Alzheimer`s disease, Parkinson`s disease, amyotrophic lateral sclerosis, multiple sclerosis, Wernicke encephalopathy, HIV associated dementia, frontotemporal dementia, vascular dementia). Powered by TCPDF (www.tcpdf.org)
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Mechanisms involved in neurodegenerative disorders origin and their consequences in neurobiological interactions.
Červinková, Monika ; Kulišťák, Petr (advisor) ; Šivicová, Gabriela (referee)
Neurodegenerative disorders represent due to their still increasing trend serious problem not only medical, but also socio-economic. The most common disorders in human population include Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Underlying ethiopathogenetical mechanisms are not closely clarified yet. Potential conjunction between neurodegenerative disorders and stress is mentioned. Supposed relationship between neurodegenerative disorders and stress is based on knowledge of functional interrelationships among nervous, endocrine and immune systems. Animal models are very helpful for research in objective field and they can contribute to the elucidation of involved biological mechanisms. Knowledge of these processes could enable development of new diagnostic and therapeutic approaches in future.
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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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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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Changes in beta-catenin expression during ontogenesis in the transgenic minipigs for human mutant huntingtin
Žižková, Martina ; Motlík, Jan (advisor) ; Jarkovská, Karla (referee)
Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by an unstable expansion of the CAG repeat sequence within the huntingtin gene. Huntingtin associates with ubiquitin-proteasome system that ensures degradation of particular proteins including β-catenin which is an important molecule whose equilibrated degradation is necessary for the proper functioning of the Wnt signaling pathway. The binding of β-catenin to the destruction complex is altered in HD, leading to the toxic stabilization of β-catenin. The main goal of my thesis was to determine whether the accumulation of β-catenin due to the presence of mutant huntingtin is also characteristic of Liběchov minipigs, a large animal model of Huntington's disease stably expressing N-truncated human mutant huntingtin. Using immunoblot and specific antibodies, we have revealed age-dependent accumulation of mutant huntingtin in transgenic minipigs. Unlike endogenous huntingtin, no decrease of the level of mutant huntingtin was observed in the striatum of transgenic animals. Surprisingly, this was followed by a decrease of phosphorylated β-catenin. Nevertheless, our results demostrate the accumulation of β-catenin in mesenchymal stem cells isolated from the oldest boars during ontogenesis. Furthermore, we have revealed a...
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Targeted differentiation of mesenchymal stem cells and their clinical application
Hámor, Peter ; Kubinová, Šárka (advisor) ; Trošan, Peter (referee)
The goal of this work is to point out possibilities of neuronal differentiation of mesenchymal stem cells and their application for clinical purposes, primary for repairing and regeneration of central nervous system tissues. Because this system works as a control center for functional features of the whole body, and treating this injuries and degenerations often bring many problems and obstacles, the possibility of using autologous cells for a transplantation or inducer of the natural regenerative properties of tissues is worth deeper research. This work progressively focuses on basic characteristics of stem cells and their differentiation potential, characterizing further mesenchymal stem cells together with possibilities of their isolation and cultivation. The main part of the text is formed by studies and methods used for targeted differentiation of mesenchymal stem cells and attempts of their transdifferentiation into neural cell line, together with present and possible future application of these cells in central nervous system therapies.
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Biomedical models of Huntington disease
Žižková, Martina ; Motlík, Jan (advisor) ; Moravec, Jan (referee)
Huntington's diease is a dominant inherited neurodegenerative disorder that is caused by an expansion of a CAG repeats within a huntingtin gene. Mutant protein causes a neuron degeneration in a brain of HD pacients which leads to a motor abnormalities and personality decay. This disease is very malign because of its late onset. An equal therapy does not exist yet, but a lot of research teams focus on designig a suitable medical treatment. It is necessary to create animal models of Huntington disease which can be used for testing the therapies. In my work I aim to summarize the animal models of HD which are used in research. A rodent model is the most common due to its low price and easy breeding. However, more important are human related large animals like sheep, pigs or non-human primates. The principal criterion of animal model is its method of creation. We can divide the models into two categories, genetic and non-genetic. The memebers of the first one are able to reproduce better expression of human Huntington disease. Generation of animal models of HD leads to better comprehension the principles of HD, and developing an equal therapy for HD pacients.
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