Pink1-/- Rats Demonstrate Swallowing and Gastrointestinal Dysfunction in a Model of Prodromal Parkinson Disease.

Abstract

Early motor and non-motor signs of Parkinson disease (PD) include dysphagia, gastrointestinal dysmotility, and constipation. However, because these often manifest prior to formal diagnosis, the study of PD-related swallow and GI dysfunction in early stages is difficult. To overcome this limitation, we used the Pink1-/- rat, a well-established early-onset genetic rat model of PD to assay swallowing and GI motility deficits. Thirty male rats were tested at 4months (Pink1-/- = 15, wildtype (WT) control = 15) and 6months (Pink1-/- = 7, WT = 6) of age; analogous to early-stage PD in humans. Videofluoroscopy of rats ingesting a peanut-butter-barium mixture was used to measure mastication rate and oropharyngeal and pharyngoesophageal bolus speeds. Abnormal swallowing behaviors were also quantified. A second experiment tracked barium contents through the stomach, small intestine, caecum, and colon at hours 0-6 post-barium gavage. Number and weight of fecal emissions over 24h were also collected. Compared to WTs, Pink1-/- rats showed slower mastication rates, slower pharyngoesophageal bolus speeds, and more abnormal swallowing behaviors. Pink1-/- rats demonstrated significantly delayed motility through the caecum and colon. Pink1-/- rats also had significantly lower fecal pellet count and higher fecal pellet weight after 24h at 6months of age. Results demonstrate that swallowing dysfunction occurs early in Pink1-/- rats. Delayed transit to the colon and constipation-like signs are also evident in this model. The presence of these early swallowing and GI deficits in Pink1-/- rats are analogous to those observed in human PD.