Behavioral characterization of bulbar sensorimotor function in a rat model of Alexander disease

Alexander disease (AxD) is a neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein (GFAP) gene and is associated with bulbar sensorimotor impairments including dysphagia, dysphonia, and dysarthria. This study assessed oromotor and laryngeal function in the R237H rat model of AxD compared with wild-type (WT) controls. Rats underwent behavioral assessments of tongue strength and press rate, mastication, swallowing, and ultrasonic vocalizations. Compared with WT controls, the R237H group exhibited significantly reduced tongue force and press rates, with a decline in performance over time, indicating lingual weakness and reduced capacity for sustained performance. During mastication, the R237H group required longer consumption times and more chewing events despite similar bite counts, reflecting inefficient oral processing. Videofluoroscopic swallow studies revealed prolonged oral-phase duration and an increased number of jaw cycles prior to swallow initiation in the R237H group, suggesting impaired oromotor coordination during swallow, while bolus area, jaw cycle rate, and bolus velocity were preserved. Ultrasonic vocalization analyses revealed shorter durations among the longest calls in the R237H group, suggesting reduced vocal performance. Collectively, these findings demonstrate that the R237H rat model of AxD exhibits significant deficits in tongue function, mastication, swallowing, and vocalization. These behavioral impairments are consistent with bulbar symptoms observed in individuals with AxD and extend prior characterization of this model. This study provides a behavioral foundation for future mechanistic and translational investigations of bulbar dysfunction in this model.