Author ORCID Identifier
https://orcid.org/0000-0002-8794-8341
Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Nursing
First Advisor
Theresa Swift-Scanlan
Second Advisor
Unsong Oh
Abstract
Females are three times more susceptible to relapsing multiple sclerosis (MS) and males typically have more severe disease, but the molecular underpinnings of these sex-based disease disparities are unknown and represent a critical knowledge gap.Subject Population: Blood samples from a demographically homogenous group of treatment naïve males and females with relapsing-MS and healthy controls. Research Design: Cross-sectional combinatorial omics pilot study. Instruments: Whole transcriptomic analysis with messenger RNA (mRNA) expression profiling using next generation sequencing (RNA-seq) and micro-RNA (miRNA) expression using NanoString technology. Aim 1) Identify and compare the actively expressed mRNAs in the transcriptome of males and females with relapsing-remitting MS and healthy controls using RNA-seq. 2) Analyze the miRNA profiles of males and females with relapsing MS and healthy controls and correlate miRNA and mRNA expression levels to better understand the role of miRNAs in MS etiopathogenesis. Analysis: Differential expression analysis of mRNA and miRNA data was performed, and Ingenuity Pathway Analysis (IPA) was used to explore the functional effects miRNA expression had on mRNA in each sample. MS females and MS males were compared to sex-matched healthy controls, than to each other to better understand the influence of sex on neuroinflammation and neurodegeneration in MS. Results: MS Females had unique expression of miRNA-mRNA pathways associated with neuroinflammation and may have key neuroprotective traits that contribute to their less severe disease course, while males had differential expression of pathways associated with axonal loss, cognitive decline, and increased disability. Conclusions: Overall, these findings revealed significant insights into sex-based differences in the pathogenesis of MS, which has helped illuminate potential biological underpinnings of the clinically observed courses of disease. These results have enhanced our understanding of MS pathophysiology and laid a crucial foundation for future research in this area.
Rights
© Stephanie Buxhoeveden
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-9-2024