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Neuroscience. 2018 Oct 15;390:303-316. doi: 10.1016/j.neuroscience.2018.08.026. Epub 2018 Sep 1.

Hypoglossal Motor Neuron Death Via Intralingual CTB-saporin (CTB-SAP) Injections Mimic Aspects of Amyotrophic Lateral Sclerosis (ALS) Related to Dysphagia.

Author information

1
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, United States.
2
Department of Communication Science and Disorders, University of Missouri, Columbia, MO 65211, United States.
3
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, United States; Department of Communication Science and Disorders, University of Missouri, Columbia, MO 65211, United States; Department of Otolaryngology-Head and Neck Surgery, University of Missouri, Columbia, MO 65211, United States.
4
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, United States; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, United States. Electronic address: nicholsn@missouri.edu.

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to degeneration of motor neurons and skeletal muscles, including those required for swallowing. Tongue weakness is one of the earliest signs of bulbar dysfunction in ALS, which is attributed to degeneration of motor neurons in the hypoglossal nucleus in the brainstem, the axons of which directly innervate the tongue. Despite its fundamental importance, dysphagia (difficulty swallowing) and strategies to preserve swallowing function have seldom been studied in ALS models. It is difficult to study dysphagia in ALS models since the amount and rate at which hypoglossal motor neuron death occurs cannot be controlled, and degeneration is not limited to the hypoglossal nucleus. Here, we report a novel experimental model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to study the impact of only hypoglossal motor neuron death without the many complications that are present in ALS models. Hypoglossal motor neuron survival, swallowing function, and hypoglossal motor output were assessed in Sprague-Dawley rats after intralingual injection of either CTB-SAP (25 g) or unconjugated CTB and SAP (controls) into the genioglossus muscle. CTB-SAP treated rats exhibited significant (p ≤ 0.05) deficits vs. controls in: (1) lick rate (6.0 ± 0.1 vs. 6.6 ± 0.1 Hz; (2) hypoglossal motor output (0.3 ± 0.05 vs. 0.6 ± 0.10 mV); and (3) hypoglossal motor neuron survival (398 ± 34 vs. 1018 ± 41 neurons). Thus, this novel, inducible model of hypoglossal motor neuron death mimics the dysphagia phenotype that is observed in ALS rodent models, and will allow us to study strategies to preserve swallowing function.

KEYWORDS:

motor output; neurodegenerative disease; swallowing; videofluoroscopy

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