Abstract
Relatively little is known about the underlying neuropathology of dysphagia in amyotrophic lateral sclerosis (ALS); thus, effective treatments remain elusive. Tremendous progress toward understanding and treating dysphagia in ALS may be possible through the use of an animal model of dysphagia in ALS research; however, no such animal model currently exists. The most logical candidate to consider is the SOD1-G93A transgenic mouse, the most widely investigated animal model of ALS. To investigate whether this animal model develops dysphagia, oral behaviors (lick and mastication rates) of SOD1-G93A transgenic mice (n = 30) were evaluated at three time points based on hind limb motor function: asymptomatic (60 days), disease onset (~110 days), and disease end-stage (~140 days). Age-matched nontransgenic littermates (n = 30) served as controls. At each time point, lick and mastication rates were significantly lower (p < 0.05) for transgenic mice compared with controls. Histologic analysis of the brainstem showed marked neurodegeneration (vacuolation) of the trigeminal and hypoglossal nuclei, two key motor components involved in mastication and licking behaviors. These results demonstrate a clinicopathologic correlation of oral dysfunction in SOD1-G93A transgenic mice, thereby establishing the SOD1-G93A transgenic mouse as a bona fide animal model of oral dysphagia in ALS.
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Acknowledgments
The authors gratefully acknowledge Elena Pak, Tiepha Renee Cooper, Cory Morris, Sameer Dongre, Emmanuelle Simon, Waseem Ahmed, Emily Barrett, Vladim Bobrovnikov, Mohamed Raafat, and Di Wu for their invaluable assistance with data collection. We also express our gratitude to Ms. Joani Zary and Dr. Hubert Burden from the Department of Anatomy and Cell Biology at East Carolina University for their expert guidance in histologic methods. We also are grateful to the veterinarians and animal technicians in the Department of Comparative Medicine at East Carolina University who kindly maintained the mouse colony for this investigation.
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Lever, T.E., Gorsek, A., Cox, K.T. et al. An Animal Model of Oral Dysphagia in Amyotrophic Lateral Sclerosis. Dysphagia 24, 180–195 (2009). https://doi.org/10.1007/s00455-008-9190-z
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DOI: https://doi.org/10.1007/s00455-008-9190-z