Impact of selective motor neuron death on hypoglossal motor neuron survival and tongue morphology in a novel model of dysphagia

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive loss of motor neurons and paralysis of the muscles they innervate. Hypoglossal motor neurons supply the tongue and seem particularly vulnerable to this disease. As a result, tongue weakness is often detectable at diagnosis, and most patients with ALS eventually develop dysphagia (difficulty swallowing). Dysphagia is associated with reduced quality of life and increased mortality secondary to malnutrition, dehydration, and aspiration pneumonia. Despite the severity of the problem, dysphagia has seldom been studied in animal models of ALS. Current models are challenging to analyze because 1) the rate and amount of hypoglossal motor neuron death is inconsistent amongst individuals, and 2) the degeneration of neurons is not limited to those involved in swallowing. To address these issues, we have developed an inducible rat model of dysphagia using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to cause the selective death of hypoglossal motor neurons. All Sprague-Dawley rats in the study received intralingual injections of either CTB-SAP (25 [microgram]) or CTB unconjugated to saporin (controls) and were then evaluated 9 days later. CTB-SAP treated rats showed deficits in hypoglossal motor neuron survival, hypoglossal motor output, lick rate, swallow rate, and tongue muscle fiber size (genioglossus muscle). We thus conclude that this inducible model mimics several aspects of dysphagia seen in ALS and will provide a useful tool for testing therapies aimed at preserving swallowing function in these patients.