Mechanisms of SARS-CoV-2 infection induced dopamine neuron damage
Grant
Overview
abstract
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SARS-CoV-2 infections and the resulting COVID-19 are still very common. The consequences of these infections on long term health are not known; however, early epidemiology and experimental data suggests that SARS-CoV-2 infection could be a Parkinson's disease (PD) risk factor. Therefore, these unprecedented and widespread infection rates could dramatically increase the number of future PD cases. Currently, there is an important gap in our understanding of how SARS-CoV-2 infection damages dopamine neurons, the loss of which result in the motor symptoms of PD. Our current hypothesis is that the virus can infect the brain, disrupting the blood brain barrier and causing neuroinflammation resulting in elevated ?-synuclein aggregation, a pathologic process that damages dopamine neurons. To test this hypothesis, we will use two mouse models of COVID-19 which both produce systemic infections but only one that results in infection of the brain. Using these models, we will compare the effects of SARS-CoV-2 infection on damaging dopamine neurons and the associated changes in the brain. Understanding how SARS-CoV-2 infection damages dopamine neurons will help to determine which patients could be at elevated risk for PD as well as tests approaches to mitigate this risk.
date/time interval
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September 2023 - December 2024
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