Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss

Abstract

Motor neuron diseases (MNDs) are a group of neuromuscular disorders in which motor neurons (MNs) required for activities of daily living are lost. Patients with MNDs often develop swallowing and breathing dysfunction, leading to aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting the preservation of upper airway function. Upper airway dysfunction in MNDs is largely attributed to degeneration of XII lower MNs (LMNs) which innervate the genioglossus muscle of the tongue and often results in progressive tongue weakness. The extensive tongue muscle weakness in patients with MNDs suggests a potential role for therapeutic exercise, but sufficient evidence is lacking to conclude if tongue exercise is beneficial or harmful. 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. We developed a novel rodent model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to induce targeted loss of XII MNs and XII motor output. CTB-SAP rats have degenerative changes in the XII nerve and genioglossus, as well as decreased tongue motility and swallowing deficits that are mitigated by tongue exercise. We hypothesize that upper airway function/coordination can be improved in the face of XII LMN degeneration by tongue exercise-induced XII-tongue axis plasticity. Here, we intralingually injected adult male rats with CTB-SAP or control (CTB unconjugated to SAP), and studied the following parameters +/- tongue exercise: 1) XII motor output in anesthetized and ventilated rats via in vivo neurophysiology; and 2) structural changes via magnetic resonance imaging. Thus far, our data suggests that tongue exercise in CTB-SAP rats results in enhanced XII motor plasticity and mitigates structural airway changes (p<0.05 vs. sham-treated CTB-SAP rats). We have also started collecting pilot data to determine if upper airway (geniohyoid) EMG activity is decreased in unanesthetized and spontaneously breathing CTB-SAP rats, and if tongue exercise mitigates these deficits while diaphragm EMG activity remains unaffected +/- tongue exercise. In conclusion, tongue exercise appears to cause XII-tongue axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration. Studies are now underway to understand the underlying mechanism of tongue exercise-induced neuroplasticity, which may help guide future translational studies in patients with MNDs. Funded by: R01 HL153612 and Phi Zeta This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.