Publication Date
2020
Document Type
Thesis
Committee Members
Sherif M. Elbasiouny, Ph.D., P.E. (Advisor); Mary Fendley, Ph.D. (Committee Member); Matt Sherwood, Ph.D. (Committee Member)
Degree Name
Master of Science in Biomedical Engineering (MSBME)
Abstract
Kv2.1 channels mediate slow-activating K+ rectifier current within the membrane of spinal motoneurons (MNs), and they are known to co-localize with other synapses and ion channels. Although Kv2.1 channels are suggested to regulate MN excitability, little research has gone into investigating its potential contribution to MN-altered excitability in Amyotrophic Lateral Sclerosis (ALS). Using the male SOD1-G93A mouse model of ALS, we examined Kv2.1 cluster area and density in lumbar MNs at four key stages of disease progression. In our experiments, MNs were separated by type via SK3 immunoreactivity in order to isolate and compare the responses of disease-resistant (slow; SK3+) vs. disease-vulnerable (fast; SK3-) MNs at postnatal (P) days P10, P30, P90, and end-stage (ES; P120-140). Our results show that in disease-resistant MNs cluster area does not change relative to wild-type until ES when it significantly decreases. In disease-vulnerable MNs cluster area is increased at P90 before also significantly decreasing at ES. Additionally, no changes were found in cluster density throughout disease progression. Electrophysiological recordings using the whole-cord in-vitro spinal cord preparation supported an increase in cluster area at P90 by demonstrating lower net excitability in SOD MNs relative to wild-type, further suggesting pathologically decreased MN activity. These results provide critical, novel information on how disease-resistant vs. disease-vulnerable MNs regulate their excitability throughout ALS.
Page Count
60
Department or Program
Department of Biomedical, Industrial & Human Factors Engineering
Year Degree Awarded
2020
Copyright
Copyright 2020, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
