Tongue exercise-induced plasticity in upper airway EMG activity in a model of hypoglossal 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 due to pathology of the hypoglossal (XII) axis ( e.g., XII lower motor neurons, LMNs). These co-dependent, vital functions require reciprocal roles of the tongue during swallowing, and impaired control and coordination of these opposing behaviors can lead to aspiration pneumonia and respiratory failure. Due to a lack of research, available treatments for patients with MNDs are largely palliative, and there is a critical need for therapies targeting the preservation of upper airway function and coordination. The extensive tongue muscle weakness in patients with MNDs suggests a potential role for therapeutic exercise, but suffcient 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 therefore developed a novel rodent model of XII LMN loss using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP), which has tongue motility and swallowing deficits that are mitigated by a high-repetition/low resistance tongue exercise paradigm for muscle growth. Here, we simultaneously studied upper airway (geniohyoid) and diaphragm EMG activity with swallowing ( via videofluoroscopy swallow studies; VFSS) and breathing ( via plethysmography) to discern whether CTB-SAP induced XII LMN loss results in upper airway deficits and discoordination of swallowing and breathing functions. We hypothesized that geniohyoid (not diaphragm) EMG activity would be decreased and swallow-breathing coordination would be altered in unanesthetized and spontaneously breathing CTB-SAP rats vs. controls, and that tongue exercise would mitigate these deficits. Using custom-made headcap implants, we embedded EMG electrodes into the geniohyoid and diaphragm muscles in adult male rats prior to intralingual injection of CTB-SAP or control (CTB unconjugated to SAP) and studied chronic EMG activity during VFSS or during plethysmography studies +/- tongue exercise (N=4-6/group). Our preliminary findings show decreased geniohyoid (but not diaphragm) EMG activity as well as swallow/breathing discoordination that appears to be reversed with tongue exercise in CTB-SAP rats vs. controls. In conclusion, tongue exercise appears to enhance XII 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. R01 HL153612 and Phi Zeta. This is the full abstract presented at the American Physiology Summit 2024 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.