Effect of dosage duration on oropharyngeal and locomotor in a toxicological rat model of Parkinson’s disease

Abstract

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg of rotenone or vehicle intraperitoneal injections. Animals received daily injections for 17 or 8 days. At the end of the injections in each group brains were perfused and immunostained for striatal tyrosine hydroxylase (TH). High speed (200 fps) videofluoroscopic recording was taken of these rats and average chew cycle length, chewing rate, and total chewing time data were collected from days 0, 1, 4, 7 and 16 of those recordings. The number of rears by a rat in a glass cylinder over 4 minutes was counted on the same days to assess locomotor behavior. We used mixed model ANOVA, controlling for the effect of individual variation, to test the impact of rotenone treatment on feeding and locomotor variables. We used a Kruskall-Wallis non parametric test to test the effect of rotenone treatment on striatal TH levels. Total chewing time, and average chew cycle duration increased in rotenone treated rats from day 0 to day 4, but the difference disappeared from day 7 onwards. However, rearing behavior was consistently reduced in rotenone treated rats for all 16 days. TH staining intensity in the striatum decreased consistently over the course of the injections. These results suggest that rotenone treated rats have temporary/short term deficiency in chewing function, despite sustained reduction in spontaneous locomotor activity. The restoration of function after day 4 may indicate a learned behavior to compensate for this dysfunction in chewing, or point to a different neurological impairment than that seen in locomotor behavior. Further research needs to be undertaken to understand this phenomenon. Internal Rowan funding to F. Gould supported this work. 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.