Study Rationale: In people with Parkinson's disease (PD), nerve cells that make and release the chemical dopamine start to die. This loss affects the striatum, a brain region that normally receives the dopamine signal. We and others think that a balance between dopamine and another neural messenger, acetylcholine, is important for movement and behavior, and that other cell types of cells and molecules in the striatum help control this balance. We will explore how these messengers, cells and molecules work together to balance dopamine and acetylcholine. Learning more about these interactions could reveal new ways to help treat people with PD.
Hypothesis: We hypothesize that particular cells and molecules in the striatum are important for controlling dopamine and acetylcholine signals and that their interactions are disturbed in PD.
Study Design: We will combine cutting-edge methods in mice and in human cells to better understand PD pathology. We will measure dopamine and acetylcholine signaling and other key molecules and cells in different areas of the striatum and work out what they do and how they interact. This project will uncover important differences between vulnerable and resistant areas of striatum, and reveal whether exploiting these differences might help fix the problems with striatal function in PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our discoveries will provide fresh knowledge that may facilitate the discovery of new and improved ways of treating PD with drugs that target the key cells, messengers and molecules in the striatum that control dopamine and acetylcholine function.
Next Steps for Development: The results from this project could be used in the future to motivate new drug-discovery efforts and other therapeutic approaches aimed at brain cells, messengers or molecules that until now have been overlooked for their ability to treat PD.