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Graduation Term

2018

Degree Name

Master of Science (MS)

Department

School of Biological Sciences

Committee Chair

Andrés Vidal-Gadea

Abstract

Duchenne muscular dystrophy (DMD) is a degenerative disorder that leads to loss of ambulation, shortened lifespan, as well as higher incidence of neurological disorders. DMD is caused by mutations in the gene encoding the dystrophin protein, which provides structural support for muscle cells and neurons. We seek to understand both the effects of muscular exertion and the neurological components of DMD using Caenorhabditis elegans. When burrowing, C. elegans lacking functional copies of the dystrophin gene (dys-1(eg33)) recapitulate DMD skeletal muscle impairments. We used dys-1(eg33) mutants to determine if exercise had protective effects on dystrophic muscles by subjecting dys-1(eg33) mutants to burrowing (control), swimming (low exertion), and crawling regimens (moderate exertion). We assessed effects of exercise on animal health by measuring changes in mobility (velocity), muscular exertion (through calcium imaging), muscular integrity (through immunohistochemistry), and animal lifespan. We found burrowing had negative effects on dystrophic musculature, where dys-1(eg33) mutants had progressive loss of mobility, muscular exertion, progressive degeneration of muscular integrity, and shortened lifespan. Conversely, swimming and crawling delayed these negative effects and extended lifespan, although not to WT levels. Our data suggest low exertion exercise may delay the degeneration of dystrophic skeletal muscle and extend lifespan. We next investigated if lack of the functional dystrophin produces any neurological deficiencies consistent with the effects seen in human patients. We ran dys-1(eg33) mutants through a battery of neurologically based tests, and we found dys-1(eg33) mutants were impaired at sensory processing. This suggests C. elegans has the potential be used to model the neurological aspects of DMD. Understanding all aspects of DMD can lead to therapeutic methods that target muscular and neural components, greatly improving quality of life.

Access Type

Thesis-ISU Access Only

DOI

http://doi.org/10.30707/ETD2018.Rodriguez.A

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