Therapeutic Potential of Tongue Exercise on Tongue Force/Strength During Swallowing in a Rodent Model of Hypoglossal (XII) Motor Neuron Loss

Neuromuscular disorders ( e.g., progressive bulbar palsy and amyotrophic lateral sclerosis) are characterized by the degeneration of motor neurons ( e.g., hypoglossal; XII) and skeletal muscles. Loss of XII lower motor neurons (LMN) causes tongue weakness that compromises critical upper airway functions ( i.e., swallowing and breathing), which significantly impairs quality of life while also increasing the risk of malnutrition, dehydration, and aspiration pneumonia. However, there are currently no effective therapeutic interventions targeting these deficits in affected patients to improve quality of life. To explore potential treatments, we developed a rodent model of XII axis dysfunction by administering intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP). This approach selectively induces XII LMN loss, simulating tongue weakness and upper airway dysfunction, independent of systemic disease effects. Our past studies show that a low-repetition/high-resistance tongue exercise paradigm mitigates deficits in tongue function (motility via videofluoroscopy and lick force via lickometer) in CTB-SAP rats. However, the impact of tongue exercise on tongue force/strength during swallowing remains unexplored. Thus, the goal of this study was to use acute superior laryngeal nerve electrical stimulation in anesthetized rats to evoke repetitive swallowing while using a tongue strain gauge to measure tongue force/strength following a tongue exercise vs. sham exercise protocol. We hypothesize that tongue exercise will enhance tongue force/strength during swallowing in CTB-SAP rats. To study this, adult male rats were intralingually injected with either CTB-SAP or control (CTB unconjugated to SAP) and assigned to sham exercise or exercise protocols (n=9-10/group). Swallows were evoked across ascending (10, 20, 30, and 40 µA) and descending amplitudes (40–10 µA) to determine the optimal stimulus intensity for maximal swallow output. Thus far, our data demonstrate that the number of evoked swallows did not differ between groups (p>0.05), and threshold stimulation (10 µA) elicited fewer swallows compared to suprathreshold intensities (p<0.05). MATLAB coding is now underway for synchronous EMG, tongue strain gauge, and respiratory recordings to quantify swallow rate, tongue force/strength, and swallowing-breathing coordination. If our hypothesis is correct, our findings would provide further evidence that our tongue exercise paradigm may provide a viable dysphagia therapeutic approach to enhance the quality of life and nutritional status of patients with neuromuscular diseases. Further research is needed to elucidate the underlying mechanism(s) of tongue exercise ( e.g., BDNF-dependent mechanisms are currently being studied), and to explore the translation of these findings into clinical practice. R01 HL153612 This abstract was presented at the American Physiology Summit 2025 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.