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The role of intestinal microbiota in the development of Alzheimer's dementia
Hakenová, Kristina ; Valeš, Karel (advisor) ; Vodička, Martin (referee)
Preserving health at a higher age depends on the function of biological homeostatic systems (neural endocrine and immune activities), where the biological interaction between these systems and the intestinal microflora plays a key role. One of the most serious diseases associated with aging is Alzheimer's dementia (AD) and it is the most common cause of dementia in the world. This disease is accompanied by cognitive impairment associated with accumulation of amyloid plaques and neurofibrillary fibres in brain tissue. Naturally, biological changes occur during the process of aging, resulting in reduced functional capacity of the organism, accompanied by an increased risk of inflammatoryprocesses involved in the etiology of several chronic, pathologies, including neurodegenerative processes. These modulatory processes are associated with oxidative stress and intestinal dysbiosis. It is already well documented in the scientific literature that significant changes in the composition of intestinal microbiota occur in aging. These changes can lead to several biological changes, including increased permeability of the intestinal barrier, thereby causing the increased penetration of many biologically active substances into the body. This may be a risk factor for the development of inflammation in both...
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Analysis of oxidative stress markers in rat brain: the effect of maternal separation
Pallag, Gergely ; Novotný, Jiří (advisor) ; Vodička, Martin (referee)
Adverse events that cause stress during the early stages of life may alter the normal development of the brain and neuroendocrine system and increase the vulnerability of the individual to various disorders. Chronic stress and subsequent releasing of stress mediators can lead to oxidative stress and cell damage. The first aim of this work was to determine selected oxidative stress markers in the cerebral cortex, hippocampus, and cerebellum after the exposure of rats to early life stress. To model the stressful situation, we used maternal separation of the offspring for three hours a day during the first three weeks of life. We choose reduced glutathione, protein carbonyls, lipid peroxides and hydroperoxides as typical markers. These markers were determined in the brains of rats aged 22 days. Any significant changes were found in the levels of the studied markers after maternal separation. Damage to brain cells may also be reflected in behavior. Studies of numerous neuropsychiatric and neurodegenerative diseases have indicated that oxidative stress is a promising candidate for inducing changes at the cellular level. The second aim of this work was to monitor the behavior of rats by the light/dark box test after maternal separation along with administration of N-acetylcysteine (NAC), a drug with...
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The effect of morphine on neurogenesis and neurodegeneration in rat brain
Rydzyková, Tereza ; Novotný, Jiří (advisor) ; Vodička, Martin (referee)
Morfin is a clinically used analgesic drug but also an abusive drug. It has an impact on a wide range of CNS regions (nucleus accumbens, ventral tegmentum, hippocampus, etc.) and affects their functions, e.g. cognitive functions or anxiety. Although the results of so far published studies are often contradictory, the effects on cell death and proliferation in the CNS have been demonstrated. In this work, we focused on how chronic administration of morphine and subsequent withdrawal of this drug affects neurogenesis and neurodegeneration in the rat brain and how it affects some markers involved in the addiction and post-drug-induced condition. We have succeeded in introducing immunohistochemical markers for monitoring neurogenesis (bromodeoxyuridine and doublecortin) and neurodegeneration (Fluoro-Jade C) and for detection of selected neuromodulatory peptides (cholecystokinin and neuropeptide Y). We have found that morphine may influence the process of neurogenesis and neurodegeneration, but its effects differ in different CNS structures (nucleus accumbens, hippocampus, and amygdala). Key words: Morphine, brain, rat, withdrawal syndrom, neurogenesis, neurodegeneration
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Interaction between gastrointestinal tract and central nervous system: Mechanisms and pathology
Dušková, Petra ; Nekovářová, Tereza (advisor) ; Vodička, Martin (referee)
This work summarizes relevant information about bacterial ecosystem of human intestine with an emphasis on microbiome-host communication. I describe physiological mechanisms influencing so as distant as the intestine and the brain. Neuropsychiatrical and neurodevelopmental disorders, especially autism, are used as a model. Human gut microbiome influences function and development of the brain in many ways. The intestinal barrier permeability increases and decreases by the consequences of microbes contact with epithelium. Many bacterial species produce neuroactive molecules, neurotransmiters, their precursors and fatty acids. These molecules enter the bloodstream depending on intestinal barrier tightness. Disruption of microecosystem and host communication may cause pathological inflammations and increase cytokine production. Cytokines are able to weaken the blood-brain barrier and enable penetration of potentially harmful substances into the brain. The main goal of this bachelor thesis is to summarize and logically organise current information and point out important questions about the relations between the microbiome composition and mental health. In conclusion, bacterial microbiome influences brain functions in health and disease. Ecological destabilisation of microbiome is one of the factors...
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Effect of early stress on neuroendocrine regulation, behavior and immnunity
Langová, Veronika ; Vodička, Martin (advisor) ; Buchtová, Helena (referee)
Levels of initial hormones of the hypothalamic-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and arginin-vasopressin, can be altered in adulthood with a context of early-life stress. The effect can be stronger after an acute stress. Some authors suggest that higher levels can be caused by hypomethylation of that genes promotors. High level of default hormones often results in high concentration of corticosterone. Higher concentration of corticosterone in blood can also be supported by a lower level of transcortine, which has been observed in adulthood after a prenatal malnutrition. Locally in tisues is the concentration of corticosterone regulated by 2 types of 11β-hydroxysteroid dehydrogenase. Hyperreactivity of HPA axis can cause an anxiety-like behavior. Anxiety-like behavior is regulated by binding CRH to its receptors. Mice with knockouted gene of the first type receptor (CRHR1) shows generally less anxiety-like behavior. Conversely, some author say that binding CRH to its second type receptor (CRHR2) can inhibit an anxiety-like behavior. Prenatally stressed males show increased expression of CRHR1, prenatally stressed females show reduced expression of CRHR2. Early- life stressed animals also shows a depression-like behavior. It can be related to the presence of some pro-...
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Forced swimming test and mechanisms of depression
Janďourková, Pavla ; Nekovářová, Tereza (advisor) ; Vodička, Martin (referee)
Depression is a severe psychical disorder belonging to affective disorders. Nowadays, it belongs to the most common psychical disorders and prevalence is between 5 % to 16 %. An animal research is essential to study mechanisms of depression. One of the models of the depression uses a forced swimming test in the animal research. Even though this test does not claim to model depression in all complexity, it has very predictive validity and mostly it is used to assess effects of antidepressant (on the basis of observation of changes in the behaviour of the experimental animals). The aim of this thesis is to review the neural mechanisms of depression and to compare them with mechanism which can be applied in the forced swimming test and affected by the antidepressants. Key words: forced swimming test, depression, neurotransmitters, antidepressants, hypothalamic-pituitary-adrenal axis
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Use of dynamic environments in the study of spatial memory
Staňková, Anna ; Svoboda, Jan (advisor) ; Vodička, Martin (referee)
Spatial memory allows movable organisms to orientate and stay therefore alive in an environment. At the beginning of previous century general rules of spatial memory were studied in static experimental conditions. Today's goal is to extend knowledge about its function also in dynamic environment. As a part of declarative memory, spatial memory depends on proper functionality of hippocampus. Hippocampus is considered to be centre of spatial memory not only because of spatial impairment when damaged, but also thanks to presence of place-specific neurons in several areas of hippocampus. In research of spatial memory experimental mazes are used with possibility to manipulate with orientation cues, maze itself and surrounding conditions. It is possible to make one-shot changes or continual changes. It could be rotation of cues and landmarks, transition of maze across the room, rotation of maze etc. Tasks in dynamic environment are more demanding on cognition and so spatial orientation, which makes them more sensitive to damages of spatial memory. This could be the way of using them as a diagnostic method in medicine.
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The effect of prefrontal and posterior parietal lesion on behavior in behavioral tests of spatial cognition
Vodička, Martin ; Telenský, Petr (advisor) ; Svoboda, Jan (referee)
The effect of prefrontal and posterior parietal lesion on behavior in behavioral tests of spatial cognition In this thesis we examined the effect of prefrontal and posterior parietal cortex lesions on rat behavior. Medial prefrontal cortex is involved in working memory, behavioral flexibility and coding of spatial goals. Rats were tested in carousel maze in room frame reversal task and consequently in arena frame task on dark arena. We observed, that the lesion of medial prefrontal cortex did not disrupt the reversal learning task, but the rats were impaired in initial learning of the task. No difference was found in arena frame task. Posterior parietal cortex has a role in attention processes and takes part in processing spatial information and long term memory. Rats with bilateral lesion of posterior parietal cortex were tested in battery of tests on carousel maze (reversal learning, double avoidance) and in Morris water maze (distal landmark version and modified version with intramaze landmarks). Lesioned animals were impaired in carousel maze task in reversal learning of room frame represetation. This effect was confirmed in double avoidance task, where lesioned animals had more entrances into room frame than the controls. In Morris water maze task, lesioned animals were impaired in intramaze...
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Single cell expression analysis of genes with potential mrna gradient in mouse oocytes
Dorosh, Andriy ; Margaryan, Hasmik ; Vodička, Martin ; Ergang, Peter ; Šídová, Monika ; Dvořáková-Hortová, Kateřina
In frogs, there are clearly visible differently pigmented animal and vegetal poles of the egg determined before fertilization and leading to asymmetrical divisions. Mammalian egg does not show any comparable differentiation and it has been generally accepted that even the individual blastomeres in 2-cell and 4-cell embryos are homogenous. However, recent findings suggest that those blastomeres display different gene expression patterns and might already possess some inclinations to specific cell lineages. We therefore raised a question, whether there could be any mRNA or protein gradients in pre-fertilization oocytes similar to a previously described amphibian egg one. In mammalian eggs, there is a membrane region that is poor in microvilli, cortical granules are absent beneath plasma membrane and sperm cells generally do not bind to this location. This microvilli free region also covers the egg nucleus, and cytoskeleton localization differs markedly to the rest of the cortical space, forming actin –myosin II cortical cap/ring and is considered as animal pole. The purpose of this study was to determine gene products that can be detected at single cell level using qPCR and display gradient like distribution in mature oocytes. We checked expression of 12 selected genes in a pool of 10 oocytes and single mature oocytes. Then, we analysed gene expression in fixed intact oocytes and those undergoing laser capture microdissection procedure (LCMD). Eventually, we have determined six candidate genes for the study of intracellular spatial gene expression in mature mammalian oocytes by subcellular qPCR and in situ hybridization.
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