Abnormal colonic motility in mice overexpressing human wild-type alpha-synuclein.

The presynaptic protein alpha-synuclein (alphaSyn) has been implicated in both familial and sporadic forms of Parkinson's disease. We examined whether human alphaSyn-overexpressing mice under Thy1 promoter (Thy1-alphaSyn) display alterations of colonic function. Basal fecal output was decreased in Thy1-alphaSyn mice fed ad libitum. Fasted/refed Thy1-alphaSyn mice had a slower distal colonic transit than the wild-type mice, as monitored by 2.2-fold increase in time to expel an intracolonic bead and 2.9-fold higher colonic fecal content. By contrast, Thy1-alphaSyn mice had an increased fecal response to novelty stress and corticotropin releasing factor injected intraperipherally. These results indicate that Thy1-alphaSyn mice display altered basal and stress-stimulated propulsive colonic motility and will be a useful model to study gut dysfunction associated with Parkinson's disease.