Investigator:
Jeff Eells, PhD
Name of Institution:
East Carolina University, Greenville, NC
Project Title:
Mechanisms of SARS-CoV-2 infection induced dopamine neuron damage
Investigator Bio:
Dr. Eells is an Associate Professor in the Department of Anatomy and Cell Biology at East Carolina University Brody School of Medicine. His research experience and interests relate to molecular mechanisms that affect dopamine neuron function with particular interest in how environmental variables alter the vulnerability of dopamine and alter the risk of developing Parkinson’s disease (PD). Dr. Eells obtained his Ph.D. from Southern Illinois University. He worked as a postdoctoral fellow at the University of North Carolina and the National Institute of Environmental and Health Sciences from 1997-1998. He continued his post-doctoral training at the National Institute for Diabetes Digestive and Kidney Diseases in the laboratory of Dr. Vera Nikodem from 1998-2003. Dr. Nikodem’s laboratory was one of the groups to show the requirement of the nuclear transcription factor Nurr1 for the development of mesencephalic dopamine neurons. Dr. Eells research has previously focused on how Nurr1 affects the survival and function of mature dopamine neurons. As expression and function of Nurr1 can be altered by environmental conditions, this provides a potential mechanistic link for how environmental variables may contribute to PD risk. His most recent studies suggest that COVID-19 could be a risk factor for PD. It is unclear, however, how COVID-19 contributes to PD.
Objective:
This project aims to uncover the mechanisms by which SARS-CoV-2 infection could harm dopamine neurons in a preclinical model of COVID-19.
Background:
Early data from both epidemiology and experiments suggest that SARS-CoV-2 infection might be a potential risk factor for PD. However, there is currently limited knowledge about how SARS-CoV-2 can damage dopamine neurons or influence the accumulation of the protein a-synuclein, which is critical in the pathology of PD. Since SARS-CoV-2 infections in humans vary widely, from asymptomatic/mild cases to severe outcomes, understanding the specific aspects of the infection that could harm dopamine neurons is crucial for identifying individuals at greater risk of developing PD following infection. One essential factor to consider is whether the virus can infect the brain, as this might play a significant role in the potential risk.
Methods/Design:
In this research project, we will compare the susceptibility of dopamine neurons and the accumulation of a-synuclein across two distinct mouse models of COVID-19. One model allows viral infection in the brain, while the other lacks brain infection. By using these models, we can distinguish between the direct effects of brain infection and the broader impact of systemic inflammation in causing damage to dopamine neurons and PD-related pathology.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If it turns out that SARS-CoV-2 infection needs to involve the brain to damage dopamine neurons and increase vulnerability to a neurotoxin, then individuals with SARS-CoV-2 infection associated with viral infection in the brain might indeed be at a higher risk of developing PD. This knowledge is significant for both diagnosis and potential treatment strategies. It can help healthcare professionals identify those at greater risk after a SARS-CoV-2 infection, and it could lead to more targeted interventions to prevent or mitigate the development of PD in these individuals.