The main topic of this thesis are changes in Circadian rhythms caused by cerebellar disorders. Mice with Lurcher mutation, which have specifically degenerated Purkinje cells layer, were choosen as animal model. Our results show that mutation of the glutamate receptor GluRδ2, which causes gradual degeneration of Purkinje cells, leads to damage of Circadian system. Mice with this mutation have reduced capability to adapt to external conditions in different light modes. They are also showing increased variability in endogenous cycle. The mice are also unable to show anticipatory behavior in time-restricted feeding. Compared to control group, affected mice do not show significant rhythm in levels of protein of Bmal1 gene in suprachiasmatic nuclei, paraventricular nuclei nor in habenula. Phosphorylated kinases ERK1/2 and GSK3ß also had distorted rhythms in suprachiasmatic nuclei. Because Circadian oscillations in locomotor activity are partly preserved, Circadian system is likely not damaged on molecular level. Cerebellar mutation hampers synchronization between suprachiasmatic nuclei of neurons and can also affect processes in the ventromedial hypothalamus regulating food intake. Our findings are the first to suggest functional interactions between cerebellum and Circadian pacemaker in suprachiasmatic...

Thesis (M.A.)--Memorial University of Newfoundland, 2001. / Bibliography: leaves 222-229.

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...

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...

The mechanical loading affects the long bone cross-section geometry (CSG). The aim of this thesis was to examine experimentally the relationship between the locomotory parameters and cross-sectional properties of long bones, and to test some partial knowledge of the bone mechanical adaptation. Two groups of B6CBA mice were examined: (a) Lurcher type (model of olivocerebellar degeneration; n = 10) and (b) control (normal mice; n = 10). We analyzed the motor characteristics and the bone cross-sectional geometric properties. The motor tests included the test of spontaneous motor activity (Open field), strength properties (horizontal bar) and motor coordination (rotarod). Cross-sections were taken in 50 % of the left tibia biomechanical length and further processed for fluorescence confocal microscopy. We analyzed the biomechanical properties of cortical bone cross-sections (software ImageJ). There were nonsignificant differences in CSG parameters (TA, CA, Imax, Imin, J, Imax/Imin) between Lurcher and control mice. The results did not support our assumption about the effect of motor disorder on CSG properties. We did not demonstrate the effect of local factors on the bone biomechanical adaptation. The results of this thesis may be useful to find new testing possibilities of cortical bone in...

The cerebellum affects a number of important and complex processes in the organism. It ensures coordination, motor learning and plays an important role in cognitive and affective functions. In the case of cerebellar degeneration, we find not only the movement disorders but also behavioral abnormalities, collectively referred to as cognitive-affective syndrome. The aim of this work was to investigate motor functions during ontogenesis in animal models of hereditary cerebellar degeneration - mutant mice Lurcher and Purkinje cell degeneration using the device for quantitative gait analysis and rotarod. In addition, the effect of physical activity on the extent of ataxia and manifestations in classical behavioral tests was monitored. The results confirmed significant differences in motor skills between mutant and healthy mice; differences were also observed in some gait parameters, especially in walking speed and parameters that correlate with it. The motor functions of most groups of mice did not change during ontogenesis, pcd mice deteriorated their performance on the rotarod. The effect of physical activity was not found, with the exception of Forced swimming test. Physical activity of set intensity did not have any beneficial effect on the motoric manifestations of the mice.