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Tolerogenic dendritic cells as immune interventions in prevention or therapy of type 1 diabetes
Petrovčíková, Diana ; Funda, David (advisor) ; Hrdý, Jiří (referee)
The main aim of this work is to refer a recent summary of the opportunities and pitfalls of the application of tolerogenic dendritic cells in the prevention or therapy of type 1 diabetes (T1D). Tolerogenic dendritic cells (TolDCs) represent a potential tool for the treatment of allergies, transplant rejections and autoimmune diseases, including T1D, due to their capability to specifically inhibit autoimmune reactions without causing general immunosuppression. TolDCs represent a specific group of dendritic cells and are essential in establishing central and peripheral tolerance. This work presents a helpful guide to better understanding the physiology of tolerogenic DCs and an overview of in vitro generation attempts. In addition, the route of application and migration to target organs has been described. Type 1 diabetes (T1D) is a chronic disease resulting from immune-mediated destruction of the insulin-producing beta cells in the pancreas. Animal models have been invaluable in testing innovative medical treatments since the early testing of insulin in dogs almost a century ago. Animal models of type 1 diabetes (T1D) enable the study of the mechanisms underlying its pathogenesis and the potential development of therapeutic interventions. However, there are still significant gaps in our general...
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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 modification of gut microbiota composition by dietary intervention: the effect of plant-based and western-type diet
Ďásková, Nikola ; Cahová, Monika (advisor) ; Beneš, Jiří (referee) ; Tlaskalová - Hogenová, Helena (referee)
This thesis explores the relationship between diet, gut microbiota, and metabolic health, with a particular focus on their association with non-communicable metabolic diseases (NCDs) such as obesity and type 2 diabetes (T2D). The aim of the first study is to assess compositional and metabolic differences in gut microbiota between healthy lean long-term vegans and omnivores. The study reveals that while the gut microbiota composition is not significantly different between the two groups, there are significant differences in the fecal, serum and urinary metabolome. These differences may be attributed to the different availability of substrates in the diet, as the vegan diet is associated with a shift from a proteolytic to a saccharolytic fermentation program. Our results support the hypothesis of both resilience and metabolic flexibility of the adult gut microbiota. In addition to taxonomic analyses, this dissertation also includes metabolomics to evaluate the functional manifestations of the gut microbiota. We introduce a novel method to assess the ability of the gut microbiota to produce beneficial metabolites with a specific focus on butyrate synthesis using qPCR quantification of bacterial butyryl-CoA:acetate CoA-transferase. In silico, we identified bacteria among the human gut microbiota that...
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Cognitive flexibility in selected animal models of psychiatric disorders
Janíková, Martina ; Stuchlík, Aleš (advisor) ; Rokyta, Richard (referee) ; Ježek, Karel (referee)
Cognitive flexibility is the ability to adjust thinking and behavior based on changing conditions. Cognitive rigidity has been described in a variety of psychiatric and neurodevelopmental disorders and has been suggested to contribute to symptom maintenance. Therefore, we aimed to study cognitive flexibility and other behavioral characteristics in several rodent models relevant to schizophrenia, obsessive-compulsive disorder, and autism spectrum disorder. In a two-hit mice model relevant to schizophrenia, we found the between-group difference in set- shifting and decreased number of parvalbumin interneurons in the hippocampus of stressed female mice. Interestingly, we found no impairment in any other behavioral task. In two pharmacological rat models relevant to OCD, we showed that sensitization to D2/D3 receptor agonist quinpirole and serotonin 1A/7 agonist 8-OH-DPAT produced severe spatial learning and memory impairment in the Active Allothetic Place Avoidance task. The impairment was so severe that the reversal couldn't be tested. Surprisingly, drugs decreasing glutamatergic neurotransmission, memantine and riluzole, further impaired the performance in both models, although no such effect was observed when they were applied alone. Lastly, we showed that the knockout of a collapsin response...
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Use of animal models in Leishmania research
Pekařová, Julie ; Vojtková, Barbora (advisor) ; Pacáková, Lenka (referee)
Leishmaniasis is a disease caused by parasitic protozoa of the genus Leishmania, whose life cycle includes a mammalian host and an insect vector, typically of the genus Phlebotomus or Lutzomyia. While the number of vectors is limited, the spectrum of hosts is wide. Therefore, there are also many animal models that can be used for the study of different aspects of leishmaniasis. These include the study of the host's immune response, pathological manifestations of diseases, virulence factors or testing drugs and vaccines. Commonly used animal models are mainly rodents, which make up a large part of reservoir hosts of leishmaniasis. Examples of standard rodent models are the laboratory mouse (Mus musculus) and the golden hamster (Mesocricetus auratus), however, higher models such as non-human primates or dogs are also being used. Animals that are relatively new to leishmaniasis research are wild rodents, which appear to be ideal experimental models for studying the natural dynamics of infections. Key words: animal models, laboratory animals, rodents, Leishmania, leishmaniasis
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Parvalbumin and somatostatin interneurons in Alzheimer's disease
Beranová, Kristýna ; Svoboda, Jan (advisor) ; Málková, Petra (referee)
It is becoming increasingly clear that disruption of different types of cortical interneurons is crucially involved in various brain pathologies, even though interneurons constitute only a relatively small fraction (15-20 %) of all cortical neurons. The aim of this thesis is to describe, using a literature review, the role of parvalbumin and somatostatin neurons in the development of Alzheimer's disease, both in human patients and in experimental animal models. Keywords: Alzheimer's disease, animal models, interneurons
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Use of animal models in the study of the mechanisms of subjective tinnitus.
Dittrichová, Jana ; Tureček, Rostislav (advisor) ; Kašík, Petr (referee)
Tinnitus, phantom hearing sensation, is one of the major audiological disorders affecting a significant proportion of the human population. However, the mechanisms underlying this condition remain unclear. Animal models represent an important tool in the investigation of the pathogenesis of hearing diseases. The present bachelor thesis reviews the most important findings on the possibilities of detecting tinnitus in laboratory animals, especially rats and mice, its neural correlates in the mammalian auditory system, as well as the risk factors that lead to its development and maintenance. It was found that the most common causes of tinnitus are sensorineural hearing loss induced by exposure of animals to excessive noise or ototoxic agents, as well as their genetic predisposition. These factors cause maladaptive changes in the central auditory pathway that are likely responsible for the chronic course of the disease. The changes found include, in particular, hyperactivity of neurons of the auditory nuclei of the brainstem and increased synchrony in the area of the primary auditory cortex. Using animal models, it was also found that a significant proportion of the observed pathophysiological changes result from attenuated GABAergic inhibition in the auditory pathway. This suggested a direction for...
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Antidepressant potential of serotonergic psychedelics in preclinical research
Dušková, Valentýna ; Vejmola, Čestmír (advisor) ; Skálová, Kateřina (referee)
The treatments for depression available in contemporary medicine have a number of drawbacks. Modern antidepressants, despite fewer side effects than conventional ones, have a slow onset of action and their effectiveness is often individual. Recent studies of psychedelics have indicated their promising to extraordinary potential in the treatment of depression. Clinical research has made significant progress in this direction, as have a growing number of preclinical studies. Psychedelics potentiate signaling pathways and protein expression related to neurogenesis and cell viability and induce an increase in dendritic spines and dendritic branching. At the behavioural level, psychedelics have been shown to attenuate depressive behavioural changes, suppressing anxiety and anhedonia. This paper summarizes the effects of psychedelics in preclinical in vitro and in vivo studies, taking into account the neurobiology of depression, i.e., mainly at the level of neuroplasticity and observed behavioural changes. The first part of the thesis is devoted to the general characteristics of depression and psychedelics, followed by an introduction to preclinical experimental approaches. The central part then describes and discusses individual studies. Keywords: depression; animal models; psychedelics; LSD;...
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Plasticity after focal brain ischemia
Hanáková, Helena ; Mareš, Pavel (advisor) ; Zounková, Irena (referee)
The thesis is focused on brain ischemic injury with an accent on subsequent spontaneous and rehabilitation-induced plastic changes related to motor recovery. General part of thesis describes cortical anatomy and pathophysiology of brain ischaemia including classification of ischemia, ischemic cascade and reperfusion injury. There is also a chapter about spontaneous plasticity and recovery. The main part gives a survey of rat models of focal cortical ischemia, of functional assessment and rehabilitation. Results of rehabilitation-induced cortical plasticity are also presented.
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Experimental rat models in traumatic spinal cord injury research
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Mrózková, Petra (referee)
A large number of spinal injuries that cause damage to the spinal cord occur every year. Such damage to spinal cord tissue leads to a number of dysfunctions that significantly reduce quality of life and therefore the development of effective therapies remains a very important issue. The use of animal models is considered the major tool of this research field, enabling the testing of new treatments as well as observing ongoing pathophysiological processes. Rats are the most frequently used animal model due to the many possible ways of creating a spinal cord lesion on them. The contusion model uses a computer-controlled device to simulate the spinal cord contusion and therefore is highly precise. However, a compression model seems to be the most suitable model for pathophysiological studying. Besides contusion it enables persistent compression to the spinal cord. Transection and hemisection methods are intended for axonal regeneration research, as only these models can reliably distinguish new growing fibers from the preserved ones. Less often photochemical and excitotoxic models are used. Lastly, dislocation and distraction of vertebrae or damage to the spinal cord using heat or cold can be carried out. Each of the models have their own unique features that make them optimal to use in different...
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