|
|
Mitochondrial bioamarkers in Huntington's disease
Vizelka, Vera ; Hansíková, Hana (advisor) ; Dračínská, Helena (referee)
Huntington' s disease (HD) is a severe hereditary neurodegenerative disorder. The cause of this disease is a mutation of the gene that codes the protein huntingtin (htt). The mutation manifests itself as an abnormal extension of CAG triplets. In this way, a polyglutamine chain is formed in the htt molecule, which causes its fragmentation and aggregation. The result is a misfolded protein and this results in damage of neurons, especially in the area of striatum. The biochemical basis of neuronal death has not yet been clarified. Today, there is no effective treatment for HD. Htt participates in many different cellular processes, for example it participates in the regulation of transport events in the cell, participates in the transcription of some genes and also controls apoptosis. Mutated htt can be the cause of mitochondrial dysfunction. The consequence of the action of mutated htt is the occurrence of oxidative stress and subsequently the onset of the neurodegeneration process, but the exact state of mitochondria during the development of the HD has not yet been carefully investigated. Previous studies have studied mitochondrial disorders not only in the brain, but also in other extraneuronal tissues. The aim of the bachelor's thesis was to optimize the preparation of a sample from buccal smear...
|
|
|
Mitochondrial structure and energetic metabolism changes in patients with Huntington's disease and in transgenic minipig model
Vanišová, Marie ; Hansíková, Hana (advisor) ; Kalous, Martin (referee) ; Mühlbäck, Alžbeta (referee)
Huntington's disease (HD) is a severe neurodegenerative disease with autosomal dominant inheritance. HD is caused by the expansion of the CAG triplet in the gene for the huntingtin protein (Htt), which leads to damage and loss of its functions. Htt is essential in the development of the nervous system, it is involved in axonal transport, regulation of mitochondrial metabolism gene expression or spermiogenesis. In HD, the nerve tissue is most significantly damaged, but pathological changes associated with the disease are detected throughout the organism. There is currently no satisfactory treatment. Mitochondrial damage has been shown to significantly affect the progression of HD in patients with HD, but the mechanisms of mitopathy and its development with all the effects on tissue physiology in HD are still not fully understood. The aim of the dissertation theses was to study mitochondrial energy metabolism impairment, mitochondrial network organization and mitochondrial ultrastructure in HD in selected tissues of patients with HD and in a minipig model transgenic for HD (TgHD). Furthermore, the effort was to find and characterize a mitochondrial biomarker of HD, which would well reflect the patient's current clinical phenotype state and it would be possible to monitor changes in its parameters...
|
|
|
Functional and Pathophysiological-morphological Correlates of Neurodegenerative Diseases
Dušek, Pavel ; Roth, Jan (advisor) ; Baláž, Marek (referee) ; Menšíková, Kateřina (referee)
This doctoral thesis pictures neurodegenerative diseases as a multilevel process, describes various correlates on each pathophysiological level, and presents selected correlates in Huntington's disease and mitochondrial membrane protein-associated neurodegeneration (MPAN). It uses various methodological approaches such as basic laboratory research, clinical work, imaging, database formation, and database summary. Changes in the amount of respiratory chain complex I and respiratory chain complex IV in buccal ep- ithelial cells of Huntington's disease patients are described. The insufficient power of optical coherence tomography as a biomarker in Huntington's disease is demonstrated. Various phenotypes of MPAN are summarized, and an association between C19orf12 mutation and visual impairment is confirmed. A phenotype of a well-documented case of MPAN is presented. Keywords: C19orf12 mutation; color discrimination; contrast sensitivity; huntingtin; Huntington's disease; iron accumulation; mitochondrial membrane-protein associated neurodegeneration; multilevel process; neurodegeneration; optical coherence tomogra- phy; parkinsonism; respiratory chain complex; retinal nerve fiber layer thickness
|
|
|
Monitoring of mutant huntingtin influence on autophagy in human neural stem cells
Zezulová, Kristýna ; Vodička, Petr (advisor) ; Kohoutek, Jiří (referee)
Huntington's disease is an inherited neurodegenerative disease caused by a mutation in the huntingtin gene. Its expressed product, mutated huntingtin protein, aggregates in the cell and affects wide range of cellular processes, including proteostasis mechanisms. Autophagy, classified among the mechanisms of cellular degradation and recycling of proteins and other cellular components, is one of the processes disrupted by the presence of mutated huntingtin. The goal of the project was to prepare a tandem genetic construct (fusion protein LC3-EGFP-mCherry) using chemically competent bacteria by molecular cloning methods, transfect it into prepared human lines carrying both normal and mutated huntingtin, and thus modify the lines to transiently, and if possible also constantly express this sensor of autophagy activity. Such modified lines allow monitoring the effect of the presence of normal and mutated HTT on the course of autophagy and also provide experimentally suitable conditions for influencing autophagy in these cells using inhibitors and activators from the group of small molecules. Two types of LC3-GFP-mCherry/RFP fusion proteins were successfully prepared by molecular cloning and transiently introduced by lipofection into the control ARPE19 lines. Expression of the constructs in human H9 NSC...
|
|
|
Clinical Applicability of Cognitive Testing in Huntington Disease
Mühlbäck, Alžbeta ; Klempíř, Jiří (advisor) ; Rusina, Robert (referee) ; Horáková, Hana (referee)
Introduction: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder manifested by motor, behavioural and cognitive deficits with fatal consequences. Aims: This study aims to validate the psychometric properties of a standard cognitive battery used in HD and establish language-specific normative values. Methods: In the first study, cognitive performance was compared in 106 patients at different stages of HD and 100 healthy controls matched for age, sex, and education. The neuropsychological battery included the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Colour Naming Test, Stroop Interference Test, Trail Making Test-A and B, Category and Letter Verbal Fluency. In addition, patients were comprehensively assessed for motor and functional status. In the second study, the cognitive performance of 3,267 healthy subjects was assessed. The work focused on the stratification of cognitive performance concerning age, gender, language and level of education. Another aim was to establish the language-specific normative values and implement a web-based normative calculator to assess the degree of cognitive deficit in different languages (English, German, Spanish, Italian, Polish, French, Dutch, Danish). Results: In the first study, analysis of variance showed that healthy...
|
|
|
Nutritional disorders in patients with Huntington's disease
Procházková, Tereza ; Klempíř, Jiří (advisor) ; Kosheleva, Svetlana (referee)
OF THE BACHELOR THESIS This thesis deals with the issue of nutritional disorders in Huntington's disease. Huntington's disease is an incurable, neurodegenerative, autosomal dominant inherited disease. The prevalence of Huntington's disease in Western society is 10.6-13.7 / 100,000 individuals. The disease is manifested by disorders of free motor control, speech, swallowing, postural instability, cognitive deterioration and various behavioral changes. An integral part of the disease is unwanted weight loss. In the various stages of the disease, the causes of the development of nutritional disorders may differ and combine with each other. In the theoretical part, the chapters are devoted to the etiology and pathogenesis, pathology, clinical manifestations, forms and stages of the disease, nutritional disorders and their classification, methods of nutritional status examination and specific causes of nutritional disorders that occur in each stage of the disease. A special chapter focuses on the classification of nutritional disorders according to the European Society for Clinical Nutrition and Metabolism, which was applied in the research. The practical part aims to examine the nutritional status and evaluate eating habits in a group of patients with Huntington's disease through clinical and...
|
|
|
Sarcopenia in patients with Huntington's disease
Šoltésová, Mária ; Klempíř, Jiří (advisor) ; Růžičková, Lucie (referee)
Introduction: This cross-sectional, non-interventional, non-randomized, prospective and observational study aims to determine whether sarcopenia and its types occur in a cohort of 16 patients with Huntington's disease and, if so, at which stages of the disease. The study also aspives to identify patients with Huntington's disease who are at risk of sarcopenia (so-called presarcopenia). In addition, the study also compares the results of nutritional and functional status tests between a group of patients and healthy controls who were of the same sex, age and with no further acute or chronic disease that could significantly affect their nutritional and functional status. This was done to determine to what extent the patients exhibit reduced nutritional and functional parameters as compared with the healthy population. Methods: Individuals with clinically diagnosed Huntington's disease who agreed to participate were recruited. These individuals are outpatients of the Department of Neurology, VFN in Prague and the 1st Faculty of Medicine, Charles University in Prague. A series of tests were performed to assess the nutritional and functional status of the individual - questionnaires of functional status, self-sufficiency and sarcopenia, bioimpedance testing, strength tests using a hand dynamometer and...
|
|
|
The Role of the Occupational Therapist in the Treatment of Patients with Huntington's Disease
Sýkorová, Jitka ; Čábelková, Alžběta (advisor) ; Dlouhá Maršálková, Alexandra (referee)
The Role of the Occupational Therapist in the Treatment of Patients with Huntington's Disease Abstract: This thesis is focused on the possible potential of occupational therapy in patients with Huntington's disease, a neurodegenerative brain disease. Currently, Huntington's disease is incurable, but there are some therapeutic methods and approaches which have positive influence on a progress of the disease. Also, early intervention of occupational therapy is needed and the occupational therapist is an irreplaceable specialist as a part of an interdisciplinary team. However, in the Czech Republic there is a little experience with occupational therapy in patients with Huntington's disease. The thesis consists of a theoretical part and a practical part. The theoretical part provides basic information about the condition and by having used specialized foreign literature it also focuses on the opportunities and goals of occupational therapy in patients with Huntington's disease. In the practical part, questionnaires which were distributed among patients and patient care providers were evaluated. Results of the questionnaires provide besides other things a brief outline of patient's problematic areas. Occupational therapy evaluation of patients with Huntington's disease includes the Montreal Cognitive Assessment...
|
|
|
Psychosocial Aspects of Huntington's Disease
Uhrová, Tereza ; Roth, Jan (advisor) ; Zvolský, Petr (referee) ; Benetin, Ján (referee)
Huntington's disease (HD) is an autosomal dominant inherited neuro-psychiatric disease with usual onset in the middle age. The mutation, located on the short shoulder of chromosome 4, is an expansion of a nucleotide triplet, containing cytosine, adenine, guanine (CAG), with critical limit of 40+ repetitions. The principal symptoms include motor symptoms (chorea, dystonia, disorders of voluntary movements), progressive cognitive deterioration and neuropsychiatric symptoms (behaviour disorders, affective symptoms and so on). The clinical diagnosis is confirmed by a genetic test, which may also be carried out presymptomatically in offsprings of the diseased person. The objective of the 1st study consisted in the characterization of differences in psychiatric examination and neuropsychological testing among the people at risk (PAR), in whom it was recommended to delay the test, and people at risk, who were recommended to continue in the so-called predictive protocol. The total of 52 people have been examined (32 females, 20 males). In addition to the common psychiatric examination we have also administered the Eysenck Personality Questionnaire (EPQ-A), self-rating scale of general psychopathology (SCL- 90), three short cognitive tests - Trail making test, test of Verbal fluency and...
|
|
|
Nutritional Status in Patients with Huntington's Disease and Nutritional Support
Kosheleva, Svetlana ; Klempíř, Jiří (advisor) ; Růžičková, Lucie (referee)
Huntington's disease is a dominantly-inherited autosomal neurodegenerative disease manifested by disorders of motility, cognitive function, behaviour, and weight loss, which is conditioned multifactorially. The aim of the study was to determine whether there are eating disorders in Huntington's disease, as well as its etiology and severity. Neurological scaling, anthropometric examinations, evaluation of three-day diet records, measurements with a manual dynamometer, bioimpedance analyses, indirect colorimetry and predictions of energy expenditure were performed on 10 patients. Algorithms were applied for the diagnosis of sarcopenia and malnutrition. Unwanted weight loss was observed in all patients and 4 out of 10 showed malnutrition. No difference was found between the values of measured resting metabolism and calculated according to the predictive equation. However, it has been shown that strict nutritional recommendations based on this data can be misleading for some patients with HN, as real energy consumption can be significantly higher. All our patients had a positive energy balance. A new diagnostic algorithm for the early diagnosis of sarcopenia has proven its worth. Using bioimpedance analysis and examination of the force of the handshake, we identified possible sarcopenia and already-present...
|
guest ::
