Publication Date
2016
Document Type
Thesis
Committee Members
Sherif Elbasiouny (Committee Chair), David Ladle (Committee Member), Keiichiro Susuki (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease that currently has no cure and extremely limited treatment options. The specific mechanisms that underlie motoneuron degeneration and death, which are classical features of this disease, are mostly unknown. This thesis tests the hypothesis that small-conductance calcium-activated potassium channels (SK) may be downregulated in ALS motoneurons, as suggested by computational modelling. SK channel expression was measured in spinal alpha-motoneuron cell bodies or somata of wildtype (WT) and mutant (mt) SOD1-G93A mice, a transgenic animal model of ALS. Quantitative immunohistochemical analysis of the developmental expression of SK channel isoforms SK2 and SK3 at various postnatal time points was performed to assess the effects of motoneuron degeneration on the level and/or pattern of protein expression on the somata of lower lumbar motor nuclei. Results indicate that the selective expression of SK3 may be gradually reduced over development in WT and mutant SOD1 mice but is affected by disease pathogenesis. In addition, SK channels appear to be clustered in both WT and mutant SOD1 motoneurons throughout development. However, SK clusters appear to be significantly smaller in mutant SOD1 motoneurons compared to their WT littermates. These changes indicate that the activity of SK channels, which regulate the firing rate of motoneurons, may be affected in ALS.
Page Count
100
Department or Program
Department of Neuroscience, Cell Biology, and Physiology
Year Degree Awarded
2016
Copyright
Copyright 2016, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
