Many rodent models of PD are based on administration of toxins to the brains of the animals. These toxins can lead to relatively quick cell death in some brain areas relevant to PD. However, the development of PD in humans is a decades-long process. Even though brain cells are slowly dying over time, many years will pass before symptoms of PD appear. In our goal to investigate disease mechanisms and novel drugs in relevant rodent models, we have started work on a slow, progressive mouse model of PD. In these mice, the cells of interest become sick in adulthood and slowly die over many weeks, more closely mirroring the human disease. During these studies, we aim to determine why these cells get sick and die and whether we can prevent the cell death by treating the mice with specific drugs in early adulthood. Our studies have the potential to lead to new drug targets in PD.
Studies in animal models are beneficial in order to see how the whole animal responds to challenges or treatments. Complementary to animal studies are those we perform in cells. We use a cell line that derives from human midbrain, where the dopamine cells that become sick and die in PD are found. When we grow these cells in the lab, we observe that they are sensitive to particular stresses and become sick and die. The goal of this project is to determine whether a known neuroprotective agent currently in use in diabetes treatment can rescue these dopamine-containing cells from PD-like stresses. If the cells respond positively to the neuroprotective agent, then we will use the agent as one of our treatments in project one. This unique dopaminergic cell line serves as a starting point for many of our studies with stressors and beneficial agents.