| dc.description.abstract | Calcium ion (Ca2+) homeostasis is a critical component normal neuronal development. Abnormal Ca2+ concentrations can disrupt neuron development and nervous system function and lead to various neurological disorders, such as epilepsy. Leaner and tottering mice, which are spontaneous animal models of human absence epilepsy, exhibit reduced Ca2+ current density in neurons known as Purkinje cells within their cerebellum. This is a result of unique mutations that each type of mutant mouse carry in the P/Q-type calcium channel 1A subunit gene, and highly expressed in Purkinje cells. Consequently, both mutant mice exhibit severe juvenile onset of ataxia, paroxysmal dyskinesia, and absence seizures. Previous studies have revealed significant loss of Purkinje cells in leaner mice. However, the specific structural effects of these mutations on existing cerebellar neurons remain unclear. We examined the neuronal morphology of Purkinje cells in adult (6-8 months) male and female mice of both mutant genotypes. We found significant reduction in dendritic growth and arborization in Purkinje cells of leaner mice and a trend towards reduction in dendritic growth and arborization in Purkinje cells of tottering mice when compared to wild type mice. No difference in somatic area was observed between any two of the genotypes. Hence, we conclude that there are significant morphological deficits present in Purkinje cells of leaner mice compared to wild type mice that could, in part, explain the symptoms seen in the mice, but the lack of structural differences in Purkinje cells of tottering mice indicate that there are likely to be underlying functional impairments present that require study beyond the structural level. | en |
