Impacts of rotenone induced Parkinsonian pathology on pharyngeal transit in rats

Since 1990, Parkinson’s Disease (PD) prevalence rates have grown nearly 300%, with roughly 10 million people suffering from PD worldwide. Consequences of PD include Parkinsonian dysphagia, or pathological swallowing, often forcing patients on liquid-only diets, greatly diminishing quality of life. This preventative measure intends to mitigate the increased risk of aspiration associated with degradation of oropharyngeal function critical for safe bolus transfer. As a result, aspiration pneumonia remains the leading cause of death amongst PD patients. PD gives rise to progressive motor deficits, a result widely attributed to the degradation of the substantia nigra pars compacta, responsible for supplying dopamine to basal ganglia motor circuitry. However, rates of aspiration in PD are unresponsive to dopamine agonist therapy, suggesting the dysfunction arises from degradation of non-dopaminergic projections. Under typical motor function, the bolus transits through the pharynx, avoiding the larynx, and into the esophagus. The mechanism of aspiration in PD remains unclear due to the spatiotemporal complexity of swallowing. Clinically, prolonged pharyngeal transit time (PTT) is associated with aspiration, providing a measurable parameter to assess aspiration risk in PD. With knowledge of this clinical relationship, we measured longitudinal changes in PTT in rotenone treated rats. For this study, we hypothesized a positive correlation between rotenone treatments and PTT. Rotenone, a complex I mitochondrial inhibitor, recapitulates Parkinsonian progression in rats. Daily rotenone induced mitochondrial failure causes a cascade of Parkinsonian-like cellular dysfunctions including reactive oxygen species buildup, α-synuclein aggregation, and ubiquitin-proteasome system failure. 29 rats were treated daily for 16 days with 15 rats receiving rotenone (2.75 mg/kg) and 14 receiving a vehicle (2.75 mg/kg) as a control. Rats were recorded consuming barium coated Fruit Loops and barium infused water with video-fluoroscopy at 200 frames per second prior to first injection (day 0), and on days 7 and 16. Animals were then euthanized and perfused for histology. Using a linear mixed model analyzing the effects of day, treatment, and their interaction, pairwise tests revealed a statistically significant increase in PTT in rotenone treated animals on day 7 (eating: p < 0.0001; drinking: p = 0.0056) and day 16 (eating: p = 0.0011; drinking: p = 0.0004), compared to their same day controls for both feeding behaviors. The reported results provide evidence that the rotenone PD model can recapitulate dysphagic behaviors clinically linked to aspiration. Identifying the neuromuscular mechanism of reduced pharyngeal motility in rat models of PD will help identify the basis of treatment resistance of dysphagia in this disease. 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.