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The role of striatal cholinergic signalling in the control of behaviour
Abbondanza, Alice ; Jakubík, Jan (advisor) ; Bellone, Camilla (referee) ; Svoboda, Jan (referee)
Cholinergic transmission regulates many behavioural domains, ranging from motor activity to cognition. Acetylcholine signalling is mediated by muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively). While mAChRs are slow responding metabotropic receptors, nAChRs are ion channels, mediating fast neurotransmission. There is a growing body of evidence suggesting a role of nAChRs as important modulators of behavioural functions. However, as nAChRs consist of many subtypes, depending on their composition in subunits, and as they are expressed by various neuronal populations in different brain regions, their contribution to behavioural control is very complex. To decipher their contribution, it is necessary to selectively target nAChRs expressed not only in particular regions but also by particular neurons with a defined effect on local microcircuits. The goal of the present thesis was to use different genetic strategies to induce regional- and cell-specific deletion of β2-containing nAChRs in the mouse brain, in order to characterize the functional role of these receptors. We focused our work in two brain areas, the striatum and the prefrontal cortex (PFC). In the striatum, we identified the striatal neurons that express one of the most common nicotinic subunits, the β2...
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Monitoring of the development of the Huntington's disease in transgenic minipigs with N-terminal part of human mutated huntingtin: biochemical and motoric changes of F0, F1 and F2 generation
Kučerová, Šárka ; Ellederová, Zdeňka (advisor) ; Klempíř, Jiří (referee)
Huntington's disease (HD) belongs to neurodegenerative disorders. It is a monogenic disease caused by trinucleotic CAG expansion in exon 1 of gene coding protein huntingtin. Even though the cause of HD is known since 1993, the pathophysiology and cure for HD reminds to be found. The animal models are being used for better understanding of HD. The most common animal models for HD are rodents, especially mice but it was also important to create large animal models, which will be more like human. Therefore, TgHD minipig was created in Academic of Science in Liběchov in 2009. This model was created by microinjection of lentiviral vector carrying N-terminal part of human HTT with 124 repetitive CAG in exon 1. This model is viable and in every generation, is part of the offspring transgenic. In this thesis, I specialized to biochemical and behavioral changes of this model. I compared transgenic and wild type siblings. I found that biochemical changes are manifested mostly by increased level of mtHtt fragments in testes and brain. In behavioral part of this thesis I established new methods for testing behavioral changes in this model. The introduced methods showed some changes between wild type and transgenic animals at the tested ages but these changes were not significant due to the low number of...
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Monitoring of the development of the Huntington's disease in transgenic minipigs with N-terminal part of human mutated huntingtin: biochemical and motoric changes of F0, F1 and F2 generation
Kučerová, Šárka ; Ellederová, Zdeňka (advisor) ; Klempíř, Jiří (referee)
Huntington's disease (HD) belongs to neurodegenerative disorders. It is a monogenic disease caused by trinucleotic CAG expansion in exon 1 of gene coding protein huntingtin. Even though the cause of HD is known since 1993, the pathophysiology and cure for HD reminds to be found. The animal models are being used for better understanding of HD. The most common animal models for HD are rodents, especially mice but it was also important to create large animal models, which will be more like human. Therefore, TgHD minipig was created in Academic of Science in Liběchov in 2009. This model was created by microinjection of lentiviral vector carrying N-terminal part of human HTT with 124 repetitive CAG in exon 1. This model is viable and in every generation, is part of the offspring transgenic. In this thesis, I specialized to biochemical and behavioral changes of this model. I compared transgenic and wild type siblings. I found that biochemical changes are manifested mostly by increased level of mtHtt fragments in testes and brain. In behavioral part of this thesis I established new methods for testing behavioral changes in this model. The introduced methods showed some changes between wild type and transgenic animals at the tested ages but these changes were not significant due to the low number of...
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