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Comparison of transgenic and streptozotocin models of Alzheimer in rats: validation of IntelliCage system for behavioral phenotypization
Svobodová, Eva ; Telenský, Petr (advisor) ; Svoboda, Jan (referee)
Animal models of Alzheimer's disease display cognitive insufficiencies which mimic human symptoms and occur at a given age or post-treatment time. Animals are typically tested using canonical behavioral tests, lasting minutes and taking place mostly in the non-active period of the daily cycle. Animals are exposed to certain amounts of manipulation-induced stress. Our work represents a validation study for the rat behavioral system IntelliCage. The tested individuals live freely in a group and their behavior is monitored continuously. It is however possible to set up individual tests for each animal or a group of animals. The rats are not subject to human manipulation and hence the results are not affected by manipulation-induced stress. We tested early cognitive impairment in the transgenic rat model TgF344-AD at 6 - 8 months of age. Further, we tested two most common protocols of the streptozotocin model, i.e. single dose of intracerebroventricular 3 mg/kg streptozotocin and double dose 48 hrs apart. Results were compared with the canonical Morris Water Maze (MWM) test. In the MWM test, transgenic animals did not differ from controls in any of the studied parameters. The streptozotocin model displayed a deficit only in the double dose group. However in the IntelliCage, transgenic animals displayed...
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Study of biomolecular interactions by the method of surface plasmon resonance
Bocková, Markéta ; Homola, Jiří (advisor)
Title: Study of biomolecular interactions by the method of surface plasmon resonance Author: Markéta Bocková Department: Department of Biochemistry, Faculty of Science Supervisor: Prof. Jiří Homola, Ph.D., DSc., Institute of Photonics and Electronics of the Czech Academy of Sciences Abstract: In this diploma work, a surface plasmon resonance (SPR) biosensor technology was exploited to study two different classes of molecular interactions: hybridization of partially complementary oligonucleotides (ONs) and interactions between enzymes and peptides involved in pathogenesis of Alzheimer disease (AD). In particular, the study of interactions between ONs was focused on determining kinetic parameters of the hybridization proces. It was found that the association equilibrium constant decreases with the increasing surface probe density. An SPR biosensor-based method for rapid and sensitive detection of the 17-HSD10 enzyme and its complex with amyloid β (Aβ) peptides was designed and developed. It was demonstrated that the developed method is capable of detecting 17β-HSD10/Aβs complex in real cerebrospinal fluid (CSF) samples and that CSF samples from AD patients exhibited elavated levels of 17β- HSD10/Aβs complex compared to the control groups. The research reported in this thesis resulted in two publications in...
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Expression of cholinergic gene locus in a mouse model of Alzheimer's disease
Zimčík, Pavel
(anglický jazyk) The most common senile dementia, Alzheimer disease (AD), is characterized by a decline of memory and high cognitive functions. Typical post-mortem brain lesions are extracellular amyloid deposits, intracellular neurofibrilary tangles and ruined cholinergic and other neurotransmitters systems. Connection between damaged central cholinergic system and beta-amyloid accumulation remains obscure. We examined parietal cortex of young adult (7- month-old) female APPswe/PS1dE9 double transgenic mice which develope beta-amyloid fragments at high rate. Cholinergic synapses of these mice demonstrate functional presynaptic (stimulated acetylcholine release) as well as postsynaptic (muscarinic receptor-induced Gprotein activation) deficits and reduction of cholinergic markers. The mRNA levels of choline acetyltransferase, vesicular acetylcholine transporter and M1 to M4 subtypes of muscarinic receptors were determined in transgenic and littermate controls using qPCR. Obtained experimental data does not show any changes in measured mRNA levels. These observations indicate that reduction of cholinergic synaptic markers and function is due to posttranscriptional events.
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Segmentation of amyloid plaques in brains of trangenic rats based on microCT image data
Kačníková, Diana ; Kolář, Radim (referee) ; Chmelík, Jiří (advisor)
The presence of amyloid plaques in the hippocampus highlights the incidence of Alzheimer’s disease. Manual segmentation of amyloid plaques is very time consuming and increases the time that can be used to monitor the distribution of amyloid plaques. Distribution carries significant information about disease progression and the impact of potential therapy. The automatic or semi-automatic segmentation method can lead to significant savings in the time which are required when the disease has rapid progression. The description of amyloid plaques and the computed tomography are included in this work. In this diploma thesis are three implemented algorithms, two of them are based on published articles and one’s own methodological solution. The conclusion of the thesis is a quantitative evaluation of the accuracy of implemented segmentation procedures.
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Use of non-pharmacological approaches in the care for elderly with dementia
Čížková, Anna ; Marádová, Eva (advisor) ; Bartoňová, Miroslava (referee)
Use of non-pharmacological approaches in the care for elderly with dementia Anna Čížková ABSTRACT Subject of the present work is use of non-pharmacological methods in care about seniors with dementia in residential care homes for the elderly. The theoretical part of the work describes the problem of dementia and issues of professional and non-professional care. Five selected non-pharmacological methods, namely reminiscence, validation, pre-therapy, basal stimulation and Montessori approach, are described as well. The aim of the present work is to examine the awareness of nursing staff about the five non- pharmacological methods and to evaluate to what extend are these approaches used in residential care homes for the elderly. The level of personnel training in these approaches was investigated as well. A questionnaire survey method was selected for obtaining data about the investigated problem. A dedicated questionnaire was sent out to all residential care homes for the elderly in the Czech Republic. Filled questionnaires were received from 134 respondents. Statistical analysis of responses revealed that non-pharmacological approaches are known and used by the majority of personnel. The data showed that basal stimulation and reminiscence are best known theoretically by the staff, while the Montessori...
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Pharmacological evaluation of potencial drugs for Alzheimer's disease treatment
Matoušková, Lenka ; Vopršalová, Marie (advisor) ; Říha, Michal (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lenka Matoušková Supervisor: PharmDr. Marie Vopršalová, CSc. Consultant: PharmDr. Vendula Šepsová, Ph.D. Title of diploma thesis: Pharmacological evaluation of potencial drugs for Alzheimer's disease treatment Alzheimer's disease (AD) is a neurodegenerative disease characterized by aggregates of beta-amyloid, neurofibrillary tangles of tau protein and by the loss of cholinergic neurons in the basal forebrain and hippocampus. Cause of AD is still unknown and only symptomatic treatment is available thanks to inhibitors of acetylcholinesterase (AChE) and memantine, inhibitor of glutamate receptors. M1 muscarinic positive allosteric modulators (PAM) represent another variant of treatment that can improve cholinergic transmission. Thanks to their selectivity, they are able to decrease side effects. The aim of the study was to measure novel compounds' abilities to inhibit AChE and BChE and simultaneously act as PAM of M1 receptors. Enzymes inhibition was measured according to Ellman's method and IC50 values were determined. For fluorescent measurement of compounds interaction with muscarinic receptor the CHO cell line stably expressing the M1 receptor subtype was used. Statistical analysis...
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The role of autophagy in neurodegenerative processes
Marková, Veronika ; Novotný, Jiří (advisor) ; Čermák, Vladimír (referee)
The characteristics of many neurodegenerative diseases including Alzheimer's, Parkinson's and Huntington's disease is the accumulation of proteins and damaged organelles in the cytoplasm. Unfortunately, they are not sufficiently eliminated by autophagy. The basal autophagy, that maintains the cellular homeostasis, is disturbed in neurodegeneration. The process of autophagy becomes saturated and unable to remove all the toxic substances. Therefore, other degradation mechanisms are activated, aiming to restore the homeostasis. However, the neuronal cells are damaged under certain conditions leading to their death. The reduction in the number of neurons in specific brain areas may cause severe ataxias and dementias. Better understanding of autophagocytosis and its role v pathogenesis of neurodegenerative diseases may contribute to more effective treatment of these serious diseases in the future. Key words: autophagy, neurodegeneration, Alzheimer's disease, Parkinson's disease, Huntington's disease
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Alzheimer disease: care in the hands of family members
Schmidová, Martina ; Di Cara, Veronika (advisor) ; Trávníčková, Ivana (referee)
The theme of this graduate thesis is Alzheimer disease: care in the hands of family members. The thesis is divided into two main parts. The first part is on a theoretical base and the second part is practical. The theoretical part defines ageing, dementia and Alzheimer disease. The theoretical part establishes a framework that served as a basis for the practical part, which describes a care in family environment. This theme was chosen because of the increase in the population with the disease. Is possible that medical facilities will not be able to handle that many patients, but children and grandchildren might be willing to take responsibility for their diseased parents and grandparents. The object of the thesis is to describe the care of patients with Alzheimer's disease at home, including the possible pitfalls, which can experience family members in the role of lay caregivers. The practical part describes a case-study of a patient - nursing process and the possibility of using the services of different organizations so that the patient can live as long as possible with his family. The thesis will be able to serve as an auxiliary material for families caring for loved ones with Alzheimer's disease at home and can also inform healthcare professionals in the relevant fields about the possibilities...
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Study of biomolecular interactions by the method of surface plasmon resonance
Bocková, Markéta ; Homola, Jiří (advisor)
Title: Study of biomolecular interactions by the method of surface plasmon resonance Author: Markéta Bocková Department: Department of Biochemistry, Faculty of Science Supervisor: Prof. Jiří Homola, Ph.D., DSc., Institute of Photonics and Electronics of the Czech Academy of Sciences Abstract: In this diploma work, a surface plasmon resonance (SPR) biosensor technology was exploited to study two different classes of molecular interactions: hybridization of partially complementary oligonucleotides (ONs) and interactions between enzymes and peptides involved in pathogenesis of Alzheimer disease (AD). In particular, the study of interactions between ONs was focused on determining kinetic parameters of the hybridization proces. It was found that the association equilibrium constant decreases with the increasing surface probe density. An SPR biosensor-based method for rapid and sensitive detection of the 17-HSD10 enzyme and its complex with amyloid β (Aβ) peptides was designed and developed. It was demonstrated that the developed method is capable of detecting 17β-HSD10/Aβs complex in real cerebrospinal fluid (CSF) samples and that CSF samples from AD patients exhibited elavated levels of 17β- HSD10/Aβs complex compared to the control groups. The research reported in this thesis resulted in two publications in...
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