CINCINNATIóChronic stress-induced depression exacerbated an experimental model of Parkinsonís disease, researchers at the University of Cincinnati (UC) have shown.
The research underlines the link between Parkinsonís and depression, the researchers say, and shows that chronic stress can be a complicating factor in progression or severity of the disease.
The findings were published online ahead of print in Molecular Psychiatry, a leading scientific journal that is part of Nature Publishing Group. The lead researchers were Kim Seroogy, PhD, professor and vice chair of basic research in UCís neurology and rehabilitation medicine department and director of UCís Neuroscience Graduate Program, and James Herman, PhD, professor of psychiatry and behavioral neuroscience and director of UCís Network for Neuroscience Discovery. Ann Hemmerle, PhD, a postdoctoral researcher in Seroogyís lab, was first author of the article.
Parkinsonís disease is a degenerative neurological disorder involving the death of dopamine-producing cells, or neurons, deep within the brain. Depression is highly prevalent in Parkinsonís disease, previous research has found, and stress was long ago hypothesized to contribute to the neuropathology of Parkinsonísópossibly by increasing the vulnerability of dopamine cells to degeneration.
Seroogy and Herman, however, observed that research was lacking on co-morbidity of Parkinsonís and depressionóin other words, does stress-induced depression contributes to the development of Parkinsonís, and would it also make Parkinsonís worse once it already has developed?
"Studies have shown that up to 50 percent of Parkinsonís patients experience debilitating depression, so itís a huge quality of life issue,Ē Seroogy says. "In fact, many people with Parkinsonís complain more of depression symptoms than they do of the actual disease symptoms.
"Our research indicates that adverse life stress on top of Parkinsonís disease could be negatively modifying the disease itself.Ē
Parkinsonís disease is a chronic and progressive movement disorder, meaning that symptoms continue and worsen over time. It develops when certain cells in a region of the brain begin to die. These cells produce a chemical called dopamine that is responsible for transmitting signals within the brain that contribute to the coordination of movement.
The cause of Parkinsonís disease is unknown, and there is no known cure. Treatment options such as medication and surgery are used to manage its symptoms, which include shaking, rigidity, slowness of movement and difficulty walking.
Nearly 1 million people in the U.S. are living with Parkinson's disease, according to the Parkinsonís Disease Foundation.
"In addition to its critical role in movement, dopamine is very important in modifying how you feel about the world,Ē Herman says. "Dopamine is considered to be hedonicóit gives pleasure and reward. So the loss of dopamine in Parkinsonís may very well be affecting the regions of the brain that control the ability to appreciate pleasure and reward, and by doing that could be hitting both the depression circuits and the motor circuits.Ē
In conducting their research, Seroogy and Herman examined rodents that were stressed in a variety of ways, such as being placed briefly in a cold room or a crowded setting. With chronic variable stress, the rodents never knew what form the stress would take or when it was coming, recreating the notion of helplessness in individuals with Parkinsonís disease. A lesion to one side of the brain provided a model of Parkinsonís disease in some of the rodents.
"When we combine chronic variable stress with experimental Parkinsonís, more cells die, they die faster, and the rodentsí behavior worsens,Ē Seroogy says. (The behavior is measured by observing and recording the ratsí natural exploratory behavior.)
The next step, Seroogy and Herman say, is to further investigate the mechanisms of how stress interacts with Parkinsonís disease, particularly looking at glucocorticoid hormones that balance the stress response. Moreover, these findings underscore the importance clinically of screening and treating Parkinsonís patients for depression.
The research resulted from a collaboration of two UC labs: the Selma Schottenstein Harris Laboratory for Research in Parkinsonís, directed by Seroogy, and the Stress Neurobiology Laboratory, directed by Herman and based at UCís Reading Campus. The Selma Schottenstein Harris lab is affiliated with the Gardner Family Center for Parkinsonís Disease and Movement Disorders at the UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health.
The study was funded by grants from the National Institutes of Health, the Gardner Family Center, the Sunflower Revolution, the Davis Phinney Foundation, the Morris Braun Foundation and the Parkinsonís Disease Support Network of Ohio, Kentucky and Indiana. The authors report no conflicts of interest.