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Impact of NMDA antagonists on neuroplasticity as a biological phenomenon
Kalivodová, Michaela ; Valeš, Karel (advisor) ; Krůšek, Jan (referee)
Neuroplasticity is a fundamental biological phenomenon that accompanies us throughout our lives, both in health and illness. By studying neuroplasticity, we can understand serious neurodegenerative diseases, help remodel the nervous system after damage, or make our actions more efficient in today's world. The first chapter of this thesis will discuss neuroplasticity in the physiological state, describing the development of nervous system, learning and memory, different types of neuroplasticity, and other ways to modify neurogenesis. The following chapter deals with the role of neuroplasticity in disease, its impairment in neuropsychiatric diseases. The most common ones will be described, such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease. The next part of the thesis will discuss the molecular biology of NMDA receptor including structure, activation and excitotoxicity of the NMDA receptor, which is distinct from other receptors. Subsequently, selected NMDA antagonists competitive, non-competitive, uncompetitive, as well as glycine agonists and other selected natural modulators of the NMDA receptor will be described. Finally, this thesis will present the molecular and cellular mechanisms of the BDNF and mTOR pathways, knowledge of which provides a basis for further...
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Genetic knockout of CS4 sulfation of perineuronal nets as a source of juvenile like plasticity in processes of memory and learning
Gmiterková, Lenka ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
Extracellular matrix affects the functioning of the brain. Among others, learning and memory can be affected by the changes in the composition and properties of the extracellular matrix. Different sulfation patterns on the chondroitin sulfate proteoglycans, one of the extracellular matrix components, can either enhance or reduce synaptic plasticity and neuronal growth. This leads to the changes in the formation of memory. In my thesis I defined the role of 4-O-sulfation of the chondroitin sulfate proteoglycans in the learning and memory in the young and early adult animals. To do so I used Chondroitin sulfotransferase 11 knockout mice strain, which has decreased amount of 4-O-sulfation. I tested their long-term, short-term, and working memory using behavioural tests. I also monitored the morphological changes in the perineuronal nets and changes in the number of synapses using immunohistochemical methods and confocal microscopy.
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The role of whiskers in compensation of visual deficit and the influence of a neurodegenerative disorder on cross-modal compensation in a mousse model of retinal and olivocerebellar degeneration
Voller, Jaroslav ; Vožeh, František (advisor) ; Jagla, Fedor (referee) ; Mysliveček, Jaromír (referee)
Sensory deprivation in one modality can enhance the development of the remaining modalities via mechanisms of synaptic plasticity. Mice of C3H strain suffers from RD1 retinal degeneration that leads to visual impairment at weaning age. Independently on the retinal degeneration there is also present olivocerebellar degeneration caused by Lurcher mutation. This neurodegenerative disorder causes motor deficits, increased CNS excitability as well as changes in synaptic plasticity. The aim of this study was to evaluate a role of whiskers in compensation of the visual deficit and to assess the influence of the olivocerebellar degeneration on this process. To differentiate contribution of the whiskers from other mechanisms that can take part in the compensation, we investigated the effect of both chronic and acute tactile deprivation. We focused on motor skills (rotarod, beam walking test), gait control (CatWalk system), spontaneous motor activity (open field) and the CNS excitability (audiogenic epilepsy). In the seeing mice without olivocerebellar degeneration, the removal of the whiskers had no effect. In the blind animals without olivocerebellar degeneration, chronic tactile deprivation caused changes in gait and impaired the performance in motor tests. Some other compensatory mechanisms were involved but the...
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The role of whiskers in compensation of visual deficit and the influence of a neurodegenerative disorder on cross-modal compensation in a mousse model of retinal and olivocerebellar degeneration
Voller, Jaroslav ; Vožeh, František (advisor) ; Jagla, Fedor (referee) ; Mysliveček, Jaromír (referee)
Sensory deprivation in one modality can enhance the development of the remaining modalities via mechanisms of synaptic plasticity. Mice of C3H strain suffers from RD1 retinal degeneration that leads to visual impairment at weaning age. Independently on the retinal degeneration there is also present olivocerebellar degeneration caused by Lurcher mutation. This neurodegenerative disorder causes motor deficits, increased CNS excitability as well as changes in synaptic plasticity. The aim of this study was to evaluate a role of whiskers in compensation of the visual deficit and to assess the influence of the olivocerebellar degeneration on this process. To differentiate contribution of the whiskers from other mechanisms that can take part in the compensation, we investigated the effect of both chronic and acute tactile deprivation. We focused on motor skills (rotarod, beam walking test), gait control (CatWalk system), spontaneous motor activity (open field) and the CNS excitability (audiogenic epilepsy). In the seeing mice without olivocerebellar degeneration, the removal of the whiskers had no effect. In the blind animals without olivocerebellar degeneration, chronic tactile deprivation caused changes in gait and impaired the performance in motor tests. Some other compensatory mechanisms were involved but the...
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Antidepressant effect of ketamine
Revayová, Anna ; Valeš, Karel (advisor) ; Šóš, Peter (referee)
Ketamine is used as an anaesthetic mainly in veterinary medicine and paediatrics. Thirteen years ago, interest in ketamine as an antidepressant emerged. Ketamine as an antidepressant works rapidly and is also effective in the case of patients suffering from treatment resistant depression.The main disadvantage of ketamine as an antidepressant is its psychotomimetic effect. Ketamine is an antagonist of the NMDA receptor, which has an important influence in brain activity. Through antagonism of this receptor, a large amount of processes can be affected, for example levels of glutamate, excitotoxicity, or density of other receptors. In addition, ketamine probably also affects the D2 receptors, but its role in this is uncertain. Ketamine influences synaptic plasticity and its effect can be modulated by repeated application, co-application with other drugs and other methods. Also gender seems to play role in the effect of ketamine. The aim of this work is to summarise possible mechanisms of effect of ketamine, its effect on synaptic plasticity and also possibilities of modulation of its effect. This thesis mentions the most important studies concerning ketamine as an antidepressant and possible future directions of research. Keywords: major depressive disorder, ketamine, antidepressant, NMDA antagonism,...
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