A mouse model of pharyngeal dysphagia in amyotrophic lateral sclerosis.
We recently established that the SOD1-G93A transgenic mouse is a suitable model for oral-stage dysphagia in amyotrophic lateral sclerosis (ALS). The purpose of the present study was to determine whether it could serve as a model for pharyngeal-stage dysphagia as well. Electrophysiological and histological experiments were conducted on end-stage SOD1-G93A transgenic mice (n = 9) and age-matched wild-type (WT) littermates (n = 12). Transgenic mice required a twofold higher stimulus frequency (40 Hz) applied to the superior laryngeal nerve (SLN) to evoke swallowing compared with WT controls (20 Hz); transgenic females required a significantly higher (P < 0.05) stimulus frequency applied to the SLN to evoke swallowing compared with transgenic males. Thus, both sexes demonstrated electrophysiological evidence of pharyngeal dysphagia but symptoms were more severe for females. Histological evidence of neurodegeneration (vacuoles) was identified throughout representative motor (nucleus ambiguus) and sensory (nucleus tractus solitarius) components of the pharyngeal stage of swallowing, suggesting that pharyngeal dysphagia in ALS may be attributed to both motor and sensory pathologies. Moreover, the results of this investigation suggest that sensory stimulation approaches may facilitate swallowing function in ALS.
Lever
Teresa E
TE
Department of Communication Sciences and Disorders, College of Allied Health Sciences, East Carolina University, 600 Moye Blvd., Greenville, NC 27858, USA. levert@ecu.edu
Simon
Emmanuelle
E
Cox
Kathleen T
KT
Capra
Norman F
NF
O'Brien
Kevin F
KF
Hough
Monica S
MS
Murashov
Alexander K
AK
D000690:Amyotrophic Lateral Sclerosis / Q000150:complications*; D000704:Analysis of Variance; D000818:Animals; D003680:Deglutition Disorders / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010614:Pharynx / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics
C109415:SOD1 G93A protein; D013482:Superoxide Dismutase