Grant: CIHR Fellowship

Parkinson's disease can be debilitating to affected individuals. The disease places a substantial burden on care-givers and society. It affects approximately 0.3 % of the population. To develop effective new treatments requires a greater understanding of the underlying disease-causing mechanisms. The use of appropriate animal models that have been shown to capture the salient aspects of the disease will also be required. LRRK2 G2019S transgenic rats carry a mutated form of the LRRK2 gene. This mutation substantially increases the risk of Parkinson's disease in humans. The study of these rats will help us understand the disease-causing mechanisms in Parkinson's, which will facilitate the design of new treatments to slow the disease progression of to prevent it. To achieve these ambitions requires the detailed study of these rats. We need to directly compare, at the molecular level, the disease in humans with the deficits produced in the transgenic animals. This direct comparison can be achieved using positron emission tomography (PET), an imaging technique that is commonly used in both species and which provides a key link between the animal model and the human disease. This project will study the transgenic rats using a variety of methods, including: i) Non-invasive PET imaging, with various radiotracers that measure the function of the dopaminergic system (a system known to be affected in Parkinson's). ii) microdialysis, which directly measures neurotransmitter levels in the brain. iii) behavioural tests to assess Parkinsonian-like movement deficits in the rodents. iv) a variety of post-mortem tissue assays. The findings will be directly compared to the results from human PET imaging; several such studies are currently in progress at our research centre. The proposed project will further our understanding of the disease and will determine the extent to which the LRRK2 G2019S rat is a good model for future research and treatment development.