Investigator/Author:Constanza J. Cortes, PhD
Objective: To understand the molecular underpinnings of the neuroprotective effects of exercise.
Background: Physical activity has extensive and well-documented neuroprotective effects, benefitting cognitive function during healthy aging and reducing the risk of age-associated neurodegenerative disorders, including PD. Epidemiological data suggests that aerobic exercise may reduce the risk of PD development, and pre-clinical studies demonstrate that exercise upregulates neurotrophic factors in the substantia nigra and can protect against neurotoxicity. The mechanisms responsible for the brain benefits of exercise however, remain largely unexplored. Interestingly, in animal models, the benefits of exercise have been shown to be transferable between individuals via plasma transfer, suggesting that circulating factors in the blood may be responsible. Identification of the secreted signals that underlie the benefits of exercise can help to identify potential neuroprotective agents in PD.
Methods/Design: In this project, we test the hypothesis that exercise can reduce PD associated pathology in the brain, using behavioral exercise interventions in mice. We will also introduce PD pathology into our unique transgenic mice that are engineered to display neuroprotective effects. We will determine if our mice can withstand PD pathology more than wild type mice. In parallel, we will also determine if aging is a contributing factor to PD-associated toxicity in the brain, by examining established pathological findings of the pre-formed fibril alpha-synuclein model in the aging brain.
Relevance to Diagnosis/Treatment of Parkinson’s Disease: Our studies into the neuroprotective effects of exercise will help to define therapies that harness these effects to benefit people with PD.