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A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis

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Abstract

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.

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Acknowledgments

The authors gratefully acknowledge Elena Pak, Waseem Ahmed, Vladim Bobrovnikov, Mohamed Raafat, and Di Wu for their invaluable assistance with data collection. We also thank Drs. Richard Ray, Timothy A. Jones, Monica Carrion-Jones, and Edward Lieberman for their insightful comments and suggestions regarding our electrophysiological methods and data interpretation. We express our gratitude to Ms. Joani Zary and Dr. Hubert Burden for their expert guidance in histological methods. Our highest gratitude extends to the veterinary staff who kindly maintained the mouse colony for this study.

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Authors and Affiliations

  1. Department of Communication Sciences and Disorders, College of Allied Health Sciences, East Carolina University, 600 Moye Blvd., Suite 3310, Greenville, NC, 27858, USA

    Teresa E. Lever, Kathleen T. Cox & Monica S. Hough

  2. Department of Biology, Thomas Harriet College of Arts and Sciences, East Carolina University, Greenville, NC, 27858, USA

    Emmanuelle Simon

  3. Department of Biomedical Sciences, Baltimore College of Dental Surgery, University of Maryland Dental School, Baltimore, MD, 21201, USA

    Norman F. Capra

  4. Department of Biostatistics, College of Allied Health Sciences, East Carolina University, Greenville, NC, 27858, USA

    Kevin F. O’Brien

  5. Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA

    Alexander K. Murashov

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  1. Teresa E. Lever
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Correspondence to Teresa E. Lever.

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Lever, T.E., Simon, E., Cox, K.T. et al. A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis. Dysphagia 25, 112–126 (2010). https://doi.org/10.1007/s00455-009-9232-1

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