Optimization of Nigrostriatal Degeneration in the α-synuclein preformed fibril Rat Model

2016  -  Michigan, USA


Michigan State University, Grand Rapids

Supervising Advisor: Dr. Caryl Sortwell

Project summary:

The hallmarks of Parkinson’s disease (PD) are motor impairments, progressive degeneration of the nigrostriatal dopamine neurons, and the accumulation of inclusions containing the protein α-synuclein called Lewy Bodies. In the past modeling these individual features of the disease in animal models has been achieved, however, the ultimate goal is to be able to simultaneously model these three features of the disease in a single model. Injection of α-synuclein preformed fibrils (α-syn PFFs) into the striatum has been shown in mice and rats to lead to α-synuclein positive inclusions, as well as nigrostriatial degeneration (Luk et al., 2012; Paumier et al., 2015). The current goal of our studies is to optimize the protocol for the use of α-syn PFFs in rats. Optimization will include identification of surgical parameters and amount of α-syn PFF required to yield robust nigrostriatal degeneration resulting in significant motor impairment. Once optimized, the α-syn PFF seeded synucleinopathy model can be used by researchers to identify therapeutic strategies to provide neuroprotection in PD. In particular, we plan to use the rat α-syn PFF model to identify gene expression profiles related to particular stages of neurodegeneration.