Publication Date

2023

Document Type

Thesis

Committee Members

Sherif Elbasiouny, Ph.D. (Advisor); Keiichiro Susuki, M.D., Ph.D. (Committee Member); Jaime Ramirez-Vick, Ph.D. (Committee Member)

Degree Name

Master of Science in Biomedical Engineering (MSBME)

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease which targets motoneurons (MNs), yet underlying disease mechanisms are not well understood. Evaluating the intrinsic excitability of MNs in ALS could lead to a better understanding of mechanisms causing neurodegeneration. The SOD1-G93A (SOD) model is the most commonly studied animal model of ALS. However, past studies have shown highly conflicting results on SOD MN excitability. Interestingly, I show that depending on the level of membrane depolarization, SOD MNs show opposite results of both hyper- and hypo-excitability. This reveals that differences in the methodology of measuring excitability can heavily impact the study results. Finally, I have investigated the firing abnormalities leading to hypoexcitability in SOD MNs at high levels of membrane depolarization. Results indicate that these firing abnormalities are due to decreased Kv2.1 channel conductance. Furthermore, these firing abnormalities could be the basis for developing a biomarker which could be used to diagnose ALS earlier.

Page Count

42

Department or Program

Department of Biomedical, Industrial & Human Factors Engineering

Year Degree Awarded

2023


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