Selma Schottenstein Harris Lab

Kim Seroogy, PhD, Director of the Selma Schottenstein Harris Lab for Research in Parkinson’s.

Researchers in the Selma Schottenstein Harris Lab for Research in Parkinson’s have two areas of focus: 1) the effects of stress on Parkinson’s disease and 2) the potential for growth factors to protect or restore neurons. The researchers’ findings have the potential to be translated into new therapies for people with Parkinson’s disease.

Already, patients at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders are routinely screened for stress and depression because of ground-breaking research performed in the Schottenstein Harris Lab. In 2013 the lab provided the first tangible demonstration that life stress accelerates the progression of Parkinson’s disease.

Drs. Kim Seroogy, left, and James Herman

The research was led by Lab Director Kim Seroogy, PhD, Professor of Neurology and Director of UC’s Neuroscience Graduate Program, and James Herman, PhD, Professor of Psychiatry and Behavioral Neuroscience.“You might assume that it’s obvious that adverse life stress worsens Parkinson’s,” Dr. Seroogy says. “But it had never been explored experimentally.

“It’s not just that the stress is causing someone to feel more emotional, uncomfortable or sad. Stress or depression superimposed on Parkinson’s actually impacts the disease process by worsening the health of brain cells. Parkinson’s involves the death of dopamine-producing cells inside the brain, and stress makes dopamine cells die faster and causes more of them to die. That’s the take-home message.”

It is a message that is starting to resonate with physicians.

“Until recently, many Parkinson’s doctors didn’t treat for depression when patients came in,” Dr. Seroogy says. “It wasn’t entirely their fault, because many symptoms of depression – such as slowness of movement and loss of facial expressions -– are masked by the symptoms of Parkinson’s. People chalked it up to a symptom of Parkinson’s, when actually it was a symptom of depression.”

In addition to yielding valuable information, the research by Drs. Seroogy and Herman illustrates the value of small pilot projects.  The research team began with a $14,000 pilot grant funded by the Sunflower Revolution Encore, a private fund-raiser hosted by Melody Sawyer Richardson in 2005. The team was further supported by a $50,000 grant from the Davis Phinney Foundation and $20,000 from the Parkinson’s Disease Support Network of Ohio, Kentucky and Indiana.  Data acquired from these early rounds of small studies was ultimately used to secure a $1.7 million grant from the National Institutes of Health, enabling the team to conduct an in-depth study that produced meaningful results.

Drs. Seroogy and Herman and their team members performed their research with rodents that 1) were given a lesion that modeled Parkinson’s disease and 2) were exposed to random stressors that resulted in their displaying the characteristics of stress-induced depression. The scientists discovered that the lesioned rodents that were exposed to stressors suffered significantly more loss of dopamine cells than the lesioned rodents that were not exposed to stressors. They also showed that chronic stress alone did not cause a loss of dopamine cells.

Dr. Seroogy cautions that treating depression with anti-depressants will not cure Parkinson’s, which is a progressive disease. However, treatment with proper anti-depressant medication does have the potential to prevent acceleration of the course of Parkinson’s disease.

Growth Factor therapies in Parkinson’s

The Schottenstein Lab also studies growth factors in animal models of Parkinson’s. Growth factors are naturally occurring proteins that play a role in some aspects of neuronal growth and development. Dr. Seroogy and his team have experimented by bathing injured neurons in the brains of rodents, delivering the growth factors through a tiny flexible tube (canula). “Fewer neurons died,” Dr. Seroogy says.

Of course, pumping growth factors directly into a person’s brain is not practical over the long term. But trying to deliver the growth factors via an injection failed to work (in rodents) “because growth factors are big proteins and cannot penetrate the blood brain barrier,” Dr. Seroogy explains. “It didn’t work. We got some funny results – including improved behavior – but the cells still died.”

Compound X

The team is now testing another unnamed compound that has not been previously investigated. They hope to learn whether the compound, a protein, will prevent brain cells from dying (is neuroprotective) or will restore cells once a Parkinson’s lesion has already occurred (is neurorestorative). “It’s fun for scientists when we have a new compound,” Dr. Seroogy says. “We don’t even know what it is.”