Study Rationale:
In Parkinson’s disease, damage caused by disease processes leads to the death of certain brain cells, but not all cells are equally affected. Some are more vulnerable, while others seem to resist damage. Recent research has shown that certain gene activity patterns are linked to this resilience, but we don’t yet know how brain activity and communication between cells influence these protective programs. This project will explore how brain stimulation shapes gene activity that may help cells survive, with the goal of identifying protective pathways we can target in the future.
Hypothesis:
We hypothesize that specific patterns of brain activity can trigger protective gene programs in neurons threatened by Parkinson’s disease pathology, and that modeling these effects will allow us to predict and test which inputs and genes make brain cells more resilient.
Study Design:
We will first use computer modeling to predict how different patterns of brain activity change gene activity linked to resilience in brain cells affected by Parkinson’s disease. We will then test these predictions in mouse models by stimulating specific brain circuits and measuring how genes respond using advanced tools like optogenetics and single-cell sequencing. Finally, we will directly alter key genes to see whether they truly protect neurons, refining our model along the way.
Impact on Diagnosis/Treatment of Parkinson’s disease:
This project could reveal which brain circuits and genes naturally protect neurons from Parkinson’s disease pathology, paving the way for new treatments that boost resilience rather than only addressing symptoms. In the long run, this may help slow or prevent disease progression.
Next Steps for Development:
If successful, the next steps would be to test whether the protective circuits and genes identified in mice also work in human brain tissue. This could guide the development of new therapies — such as targeted stimulation or gene-based treatments — for patients with Parkinson’s disease.