Objective/Rationale:
Parkinson’s disease (PD) pre-clinical models carrying relevant human PD gene mutations can provide important insights into the molecular mechanisms implicated in PD and also serve as a critical platform to screen and test new therapeutic strategies. In this study, we apply CLARITY, a new technology enabling comprehensive analysis of intact brain, for structural and molecular phenotyping of PD models.
Project Description:
We will develop and apply a high-throughput CLARITY platform for generating global degeneration maps of dopaminergic neurons and other key molecules in whole brains of PD models. We will quantitatively characterize the progressive loss of dopamine neurons and link the map to relevant behavioral measures.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The goal of this study is to expand our understanding of PD pathogenesis using PD models. In addition, this study could offer a new platform to rapidly screen new therapeutic strategies, bringing treatments to people with the disease faster.
Anticipated Outcome:
We expect the proposed study would enable us to statistically link behavioral measures to dopamine neuronal loss and accumulation of alpha-synuclein, all spatially defined through the brain. We believe this comprehensive study will serve as a guide to subsequent investigation.