Videofluoroscopic characterization of dysphagia in the low copy number SOD1-G93A transgenic mouse model of ALS

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The goal of this study was to determine if the SOD1-G93A low copy number mouse model of ALS is a suitable model for studying dysphagia (i.e., swallowing impairment) specific to ALS. To accomplish this goal, this study improved upon our lab’s already established videofluoroscopic swallow study (VFSS) protocol for mice that permits identification of functional biomarkers of swallowing impairment in mouse models of human conditions. A total of 36 mice (13 transgenic and 23 controls) were tested at one time point (i.e., disease end-stage) using our murine VFSS protocol. Videos were analyzed to quantify seven swallow metrics: swallow rate, inter-swallow interval, pharyngeal transit time (PTT), jaw movement rate (lick rate), jaw movement-swallow ratio (lick-swallow ratio), bolus area, and esophageal transit time (ETT). Significant differences between end-stage SOD1-G93A low copy number transgenic mice and healthy controls were identified for all metrics tested, except jaw movement-swallow ratio. Specifically, end-stage transgenic mice swallowed significantly fewer timers per two seconds, had a longer latency between two successive swallows, exhibited longer pharyngeal and esophageal transit times, licked fewer times per second, and exhibited smaller bolus sizes. This study provides novel videofluoroscopic evidence of disease-related changes in swallow function of the SOD1-G93A low copy number transgenic mice. Future research in our lab will work on further characterizing dysphagia onset in the SOD1-LCN mice to better understand dysphagia onset in people with ALS.