Scientists Win $1.2M Grant to Study How Stress Can Worsen Parkinson’s

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by Margarida Maia, PhD |

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A team of scientists at the University of Cincinnati, in Ohio, has received a grant worth $1.2 million from the U.S. Department of Defense (DOD) to study how stress can affect — and worsen the progression of — Parkinson’s disease.

The researchers, led by Kim Seroogy, PhD, previously showed that chronic exposure to stress can make brain cells more vulnerable to die, at a faster rate, and cause animals to lose control of their movements more quickly.

Now, the goal is to find out how. The team will focus on stress hormone receptors — proteins that bind certain hormones involved in the body’s response to stress — that they think may make cells die in areas of the brain involved in motor and non-motor function.

Whether blocking these receptors could help to slow or stop the progression of Parkinson’s, even under chronic stress, is also a key focus of the study.

“Many Parkinson’s patients have high levels of stress hormones,” Seroogy said in a press release. “So we think that elevated levels of stress hormones and chronic life stress accelerates the course of their disease. If we can block that receptor, maybe that can slow the progression of the disease.” Seroogy is a professor and directs the Selma Schottenstein Harris Lab for Research in Parkinson’s in the department of neurology and rehabilitation medicine at UC’s College of Medicine.

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The studies will be done in animal models of the disease. One of these models was developed by another UC professor, James Herman, PhD, who used gene editing to manipulate the DNA and delete the instructions required to make stress hormone receptors in the 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.

“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,” he said.

Seroogy also will be using a relatively newer model that better reflects how Parkinson’s progresses in a clinical situation over a longer period of time.

“This newer model generates a gradual cell loss that is more clinically relevant,” Seroogy said, noting that older models “produced relatively quick cell death, which is not what happens in Parkinson’s.”

“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,” he said

Parkinson’s is a disease of the nervous system that is mainly marked by motor symptoms such as resting tremor, muscle rigidity, and slowness of movement. There also are non-motor symptoms such as mood and cognitive changes.

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People with Parkinson’s experience more stress than those without this disease, and high levels of stress are linked to harsher symptoms, both motor and non-motor.

“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,” Herman said.

“When we treat patients, we tend to treat the primary symptoms that you can see and put your hands on, but some of the cognitive and mood symptoms tend to get swept under the rug. If anything, this research is also going to help shed light on that particular problem,” he said.

Teresa Reyes, PhD, a professor in the department of pharmacology and systems physiology, will use the animal models to test cognitive functions like attention and the ability to change how a task is completed.

“Sometimes the rules for solving a puzzle change, and an animal needs to modify their response strategy. This is known as ‘cognitive flexibility,’” Reyes said. “We will examine behaviors such as cognitive flexibility and attention to determine whether there are any higher-order cognitive deficits in these animals.”

The findings could provide evidence for the development of potential therapies such as stress hormone blockers or medications that target the receptors with more tailored treatment and fewer side effects, according to researchers.

According to the office of the assistant secretary of defense for health affairs at the DOD, this research is supported through the Neurotoxin Exposure Treatment Parkinson’s Program.