Publication Date

2024

Document Type

Thesis

Committee Members

Hongmei Ren, Ph.D. (Advisor); Michael Craig, Ph.D. (Committee Member); Weiwen Long, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Duchenne Muscular Dystrophy (DMD) is a devastating progressive muscular disorder caused by a mutation in the dystrophin gene affecting approximately 1 in 3,500 males. However, despite its prevalence, there is currently no cure for this disease. Mutations in dystrophin lead to enhanced inflammation, fibrosis, cell death, development, and decreased skeletal muscle function. Phosphatidylcholine, synthesized by choline, is a major phospholipid that functions in maintaining and synthesizing cell membranes and has previously been found to be decreased in DMD patients. This led us to hypothesize that the dystrophic phenotype could be improved through treatment with choline. In this study, we used concentrated choline to treat B10 wildtype and mdx mice for both short-term and long-term treatments. We found that compared to untreated groups, treatment with choline showed less inflammation, fewer macrophage markers, and reduced fibrosis development within the skeletal and cardiac tissue of mdx mice. We also found that within skeletal muscle, necroptotic protein markers were downregulated as a result of choline treatment. We further evaluated the effects of choline treatment on dystrophic skeletal and cardiac muscle function to explore the potential mechanism of action. This study determined whether choline could be a potential therapeutic agent for the treatment of DMD.

Page Count

50

Department or Program

Department of Biochemistry and Molecular Biology

Year Degree Awarded

2024


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