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Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease
Červinková, Tereza ; Červený, Lukáš (advisor) ; Musílek, Kamil (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Tereza Červinková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title: Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease The increased life expectancy goes hand in hand with ageing-related cognitive impairments. Alzheimer's disease (AD) is the most common type of dementia being an irreversible and progressive brain disorder with loss of cognitive functions. Recent studies suggest that excess of glucocorticoid (GC) action exerts deleterious effects on the hippocampus and causes impaired spatialmemory. In addition, it has been demonstrated that aged mice with cognitive deficits show increased gene expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampus and parietal cortex. The Senescence-Accelerated Mouse Prone 8 (SAMP8) strain is a spontaneous animal model of accelerated ageing. Many studies indicate that SAMP8 harbour the behavioural and histopathological signatures of AD. In the present study, we evaluated the neuroprotective effects of 11β-HSD1 inhibition by a potent pyrrolidine-based compound RL-118 and/or effects of diet on cognitive performance in different groups of SAMP8 by conducting behavioural and...
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Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease
Červinková, Tereza ; Červený, Lukáš (advisor) ; Musílek, Kamil (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Tereza Červinková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title: Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease The increased life expectancy goes hand in hand with ageing-related cognitive impairments. Alzheimer's disease (AD) is the most common type of dementia being an irreversible and progressive brain disorder with loss of cognitive functions. Recent studies suggest that excess of glucocorticoid (GC) action exerts deleterious effects on the hippocampus and causes impaired spatialmemory. In addition, it has been demonstrated that aged mice with cognitive deficits show increased gene expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampus and parietal cortex. The Senescence-Accelerated Mouse Prone 8 (SAMP8) strain is a spontaneous animal model of accelerated ageing. Many studies indicate that SAMP8 harbour the behavioural and histopathological signatures of AD. In the present study, we evaluated the neuroprotective effects of 11β-HSD1 inhibition by a potent pyrrolidine-based compound RL-118 and/or effects of diet on cognitive performance in different groups of SAMP8 by conducting behavioural and...
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Inter-individual differences in behaviour of laboratory rats
Rudolfová, Veronika ; Nekovářová, Tereza (advisor) ; Sedláček, František (referee)
Number of studies report that even when experimental animals are subjected to the exact same conditions, they differ in their behaviour. If these differences were stable in time and across several experimental procedures, we could talk about personality. This diploma thesis studies inter-individual differences in behaviour of laboratory rats (Long Evans strain) in a series of experiments conducted in early ontogeny and in adult age. Apart from analysing inter-individual differences in behaviour and personality of experimental animals, this thesis has two main aims. The first aim is assessing stability of inter-individual differences in behaviour throughout ontogeny. The second aim is to explore possible link between inter-individual differences in behaviour and performance in cognitive tests. We confirmed the existence of inter-individual difference in behaviour in laboratory rats. In this thesis we were, however, not able to assess personality of experimental animals. The differences in behaviour were best described by behaviour in Open field test and Elevated plus maze test. Our results also show marked differences between successive trials of these experiments. We also report that performance in Active allothetic place avoidance is not linked to performance in Morris water maze, even though both...
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Curcumin in the treatment of traumatic spinal cord injury
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Martončíková, Marcela (referee)
Spinal cord injury is a very significant clinical as well as social problem with extensive consequences, affecting the patient and also his/her family. Great efforts have been devoted to searching for an effective treatment, which would improve their situation. This thesis evaluated the effects of the natural compound curcumin on spinal cord injury using an experimental balloon compression model. Male Wistar rats were randomized into two groups following the lesion induction, namely vehicle- or curcumin-treated. The behavioral recovery was evaluated using a set of locomotor and sensory tests and a histological and imunohistochemical analysis was performed. The qPCR method was used to observe the expression of some genes related to regeneration and immune response. It was demonstrated that curcumin improved locomotor recovery after the spinal cord injury, particularly in the early stages. Morphometric analysis of the gray and white matter sparing didn't confirm any differences between the two groups. Nevertheless, the glial scar formation was significantly reduced around the central part of the lesion in the curcumin treated group and also the NF-κB activity was substantially inhibited. The gene expression analysis demontrated downregulation of Gfap and Rantes genes and upregulation of the Irf5 gene...
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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 influence of corticosterone and corticoliberin on damage of the hippocampus and their relation to cognition
Řezáčová, Lenka ; Mareš, Pavel (advisor) ; Mejsnar, Jiří (referee) ; Šusta, Marek (referee)
Dissertation "The influence of corticosterone and corticoliberin on damage of the hippocampus and their relation to cognition" deals with the cognitive, behavioral and histological changes in experimental rat strain long-evans that closer describe the consequences of long-term continuous application of corticoliberin and/or corticosterone. Testing of the behavioral changes was divided into two phases. The first one - within three or fourweeks respectively administration of these hormones, therefore until their early effects - and the second phase - after four weeks of completion of the first phase at the time of the possible late effects. In the twelfth week the experimental animals were killed and in the group which had exogenously elevated corticosterone, the morphological changes in the hippocampus were monitored and measured. In all experimental groups alteration of behavior was observed. Histological and morphological changes in the brain we have found. Layout of experiments in two testing phases allowed differentiation of the early changes and the late and persistent changes. The arrangement of experiments allowed the choice of tests to compare not only individual effects of both hormones (corticoliberin and corticosterone) but also their coactioning and biological responses to them. Using a wider...
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