Examining how stress affects Parkinson’s disease

Kim Seroogy, PhD, said previous research from his team has shown that chronic stress can exacerbate Parkinson’s disease and lead to degeneration of brain cells and motor functions at a faster rate.

Now, Seroogy and his research collaborators at the University of Cincinnati have received a $1.2 million grant from the U.S. Department of Defense (DOD) to examine how stress hormone receptors affect cell degeneration.

Collaborator James Herman, PhD, said improved animal models that better replicate the progression of Parkinson’s disease will be crucial to better understanding the relationship between stress hormones and neuron death. 

Using gene-editing technology, Herman’s lab has developed an animal model that can specifically delete the stress hormone receptors in brain cells associated with Parkinson’s.

“One of the beauties of the model is that we are able to essentially target the gene, leaving the rest of the brain unaffected,” said Herman, director of the UC Neurobiology Research Center and Flor van Maanen professor and chair of the Department of Pharmacology and Systems Physiology in the College of Medicine. “It’s a very precise manipulation. We can ask very specific questions about the role of this receptor and these important dopamine neurons that are killed off in Parkinson's disease.”

Seroogy will also be using a relatively new leading model that better mirrors how Parkinson’s progresses in a clinical situation over a prolonged period of time.

“Previous models produced relatively quick cell death, which is not what happens in Parkinson’s,” he said. “This newer model generates a gradual cell loss that is more clinically relevant. And importantly, by combining the two sophisticated animal models in the current study, we now have the means to understand the mechanism by which key stress hormones act on vulnerable midbrain dopamine cells to cause loss of normal function and cell degeneration ”

If the study shows that removing the stress receptors can stop or reverse the effects of Parkinson’s, Seroogy said next steps over the coming years could include working toward treatments through stress hormone blockers or next-generation therapeutics that target the receptors with more specificity and fewer side effects.

Herman said as the research continues, it is paramount to emphasize the importance of stress management to Parkinson’s patients since stress has been found to be a prominent factor of disease progression.

“We need to let patients and their families know the importance of stress management, including cognitive behavioral therapies, hobbies, things that can kind of engage positively with the patient,” he said.

Seroogy said prior to the current DOD grant, the research has been supported through the UC Gardner Neuroscience Institute pilot grant program and by generous philanthropy through the UC Foundation’s Kerman Family Fund for Parkinson's Research, the Parkinson’s Disease Support Network of Ohio, Kentucky & Indiana, Northern Kentucky Putting for Parkinson’s and the Morris Braun Fund. Herman credited the $25,000 pilot grant, in particular, as helping generate and test the new animal models which led to a large return on investment in the form of the DOD grant.  

Seroogy said he is grateful to be part of a collaborative team.

“This is a great example of interdepartmental collaboration across different fields and different departments,” Seroogy said. “I’m a systems neurobiologist with expertise in Parkinson’s basic research, then there’s [Herman] with his expertise in stress and other behaviors, and then [Reyes] with her expertise in cognitive function. Interdepartmental collaboration clearly leads to success.”

This work is supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Neurotoxin Exposure Treatment Parkinson’s Program under Award No. W81XWH-21-1-0877. Opinions, interpretations, conclusions and recommendations are those of the researchers and are not necessarily endorsed by the Department of Defense. The researchers cite no conflicts of interest.

Featured photo at top courtesy of Pixabay.