Changes in enteric cellular environment of the parkinsonian mice induced by chronic subcutaneous administeration with low-dose rotenone

Abstract

We previously established an animal model of Parkinson’s disease (PD) induced by chronic low-dose rotenone as an environmental neurotoxic pesticide that reproducible behavioral and central and enteric neurodegenerative features of PD, and revealed that rotenone-induced enteric neurodegeneration is caused by dysfunction of enteric glia using primary cultured enteric cells. However, the mechanism of enteric neurodegeneration and inflammation are still obscure. In this study, we examined changes in enteric cellular environment in the enteric epithelium and myenteric plexus of the rotenone-induced PD model mice. Chronic subcutaneous administration with low-dose rotenone (2.5 mg/kg/day) for 4 weeks using an osmotic mini pump reduced the number of dopamine neurons in the substantia nigra and the intestinal myenteric neurons and glial cells of mice. Furthermore, it produced translocation of HMGB1 to cytosol towards the bowel lumen. These results suggest that the epithelial barrier disruption, inflammatory reactions and dysfunction of enteric glia would be involved in the rotenone-induced enteric neurodegeneration.