Study Rationale:
Inflammation represents a major hallmark in patients with Parkinson’s disease. However, the mechanisms connecting inflammation to the death of neurons remain insufficiently characterized, representing a critical gap in current knowledge. Filling this gap is required to develop better treatments.
Hypothesis:
We hypothesize that in PD patients, inflammation can change how neurons work, make them more fragile. It can also activate nearby support cells, called glial cells. Activated glial cells may help immune cells, such as lymphocytes enter the brain and contribute to the loss of these vulnerable neurons.
Study Design:
To test our hypothesis, we will use a special sensor that lights up when neurons release their chemical messengers, and a fiber-optic system to record this activity in live mice. This will allow us to see, in real time, how inflammation changes the activity of vulnerable neurons. Moreover, we will use patient-derived cell cultures to see how glial cells and lymphocytes interact with vulnerable neurons. Finally, a “brain-on-a-chip” model will test how patients-derived brain cells control the entry of immune cells from the blood to the neurons in inflammatory conditions.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Our study could reveal how inflammation makes certain brain cells more vulnerable in Parkinson’s disease, showing the early changes that lead to neuronal loss. This understanding may uncover new ways to protect neurons and develop treatments targeting the disease at its initial stages.
Next Steps for Development:
By identifying how immune signals contribute to neuronal vulnerability in PD, this work may inform early intervention strategies to slow or prevent disease progression. We could for example devise new ways to prevent glial cells from boosting the neurotoxic effects of peripheral immune cells.