Impact of targeted tongue exercise on genioglossus sarcomere and mitochondria morphology in a rodent model of hypoglossal motor neuron death

Upper airway dysfunction in motor neuron diseases, such as amyotrophic lateral sclerosis and progressive muscular atrophy, is largely attributed to degeneration of hypoglossal (XII) lower motor neurons (LMNs) which innervate the muscles of the tongue (including the genioglossus) and often results in swallowing and breathing dysfunction due to progressive tongue weakness. A barrier in studying the impact of XII LMN degeneration and developing therapies to improve swallowing and breathing function/coordination has been the lack of an appropriate model. Thus, we established a rodent model of targeted loss of XII LMNs and XII motor output using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP). Prior work with this model has revealed degenerative changes in the genioglossus (e.g., myofiber atrophy which is replaced by increased lipid expression leading to overall tongue hypertrophy) as well as decreased tongue motility and strength that are mitigated by a high-repetition/low-resistance tongue exercise paradigm. Our recent pilot studies have shown significant degenerative changes in genioglossus sarcomere and mitochondria morphology in rats with induced XII LMN death, which align with markers of degeneration found in previous literature; however, the impact of tongue exercise on these morphological changes remains unknown. In this study, we intralingually injected adult male rats with CTB-SAP or control (CTB unconjugated to SAP) and subjected them to either sham or tongue exercise (n=3-6/group). We then studied ultrastructural changes in genioglossus sarcomere and mitochondria morphology using transmission electron microscopy and computational analysis. Our preliminary data suggests that CTB-SAP + exercise rats demonstrate mitigation of degenerative mitochondrial morphology compared to CTB-SAP + sham exercise rats. Analysis of sarcomere structure and lipid droplet number within the same groups is currently underway. Identifying ultrastructural markers that capture genioglossus degeneration and exercise-induced attenuation will enable more efficient and comprehensive evaluation of future therapies for XII neurodegeneration. Sponsored by: NSF DBI 1950787 grant and NIH R01 HL153612 grant This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.