Study Rationale:
Parkinson’s disease (PD) has traditionally been defined by people having trouble moving — walking, standing up, etc., but non-movement related symptoms reported by PD patients include pain, depression, and anxiety. The death of specific brain cells called dopamine neurons explains the movement symptoms, but the underlying cause of non-movement related symptoms is less clear. Our study proposes that there are different types of dopamine neurons, the known movement related type, and others related to feelings and moods. We think that when these other types of dopamine neurons die, they could lead to the pain and depression symptoms suffered by PD patients.
Hypothesis:
We hypothesize that there are different types of dopamine neurons, the known movement related type, and others related to positive and negative feelings, and in PD, an imbalance in the activity of these DA neurons leads to pain and depression.
Study Design:
Our expert group, specializing in different and complementary areas of science, will examine changes taking place in the brains of human PD patients and preclinical models of PD. By looking at the genes and molecules in individual nerve cells in these brains, we hope to find evidence supporting our hypothesis that some types of dopamine cells die and others survive. We will connect these findings with human patient brain imaging experiments detailing how brain activity is disrupted. Then, using modern neuroscience techniques, we will establish how the activity of individual living neurons and circuits changes in a PD mouse model.
Impact on Diagnosis/Treatment of Parkinson’s disease:
First, our human brain imaging studies will provide a way to identify and characterize brain activity related to pain, and possibly anxiety and depression. Second, we will identify molecules on the different dopamine neurons that can be targeted by drugs to blunt non-motor symptoms like pain.
Next Steps for Development:
Our human brain imaging results could be used to clinically diagnose and distinguish pain, depression and anxiety, which then in turn would be useful for testing specific treatments for each of these conditions, including new drugs to target the different types of dopamine neurons.