Stressed-Out Rats

Less stress, more exercise may keep Parkinson's at bay

Joseph Stuckert carefully puts a little harness on the large, nervous white rat—an action that would create considerable stress for any small rodent. Then he places it in a metal bowl. More stress.

As one might expect, the rat takes off, or at least tries to, scrambling around and around and around the bowl in a frenzied, ill-fated escape.

The result: one really stressed-out rat. And that's just what Stuckert wants.

Stuckert, who graduated from the University of Pittsburgh in April with the B.S. degree in neuroscience, was given an opportunity to contribute to a growing body of research at Pitt that is connecting prolonged stress to a deterioration of the brain, particularly as it applies to the progression of Parkinson's disease. Stuckert worked as part of the research team headed by Michael Zigmond, a professor of neurology and psychiatry in Pitt's Department of Neurology who is studying the disease.

Foot shock and lesions of dopamine neurons

So, what does inducing a harnessed rat to run around in circles in a bowl have to do with Parkinson's disease? The answer is hidden in the masses of nerve cells called neurons in the rat's brain. At the very beginning of Stuckert's experiment, the rat was given 6-hydroxy-dopamine, a toxin that kills neurons that contain dopamine, one of the many chemicals in the brain that transfers messages from one neuron to another. These are the neurons that normally are lost in Parkinson's disease.

When a person experiences a shortage of dopamine, many other neurons in the brain cannot communicate well with each other, rendering body movements jerky and limited, with balance thrown off. Ultimately, Parkinson's disease begins to take over the brain.

Later, Stuckert systematically induced stress in each rat by placing some rats in a cage with a floor that randomly shocked their feet. He placed other rats in clear plastic cylinders called restrainers, which left them totally immobile.

"It's more of an annoyance than pain," Stuckert says of the stress. "The idea is to create enough stress so that we can examine whether or not it affects the deterioration of neurons in the brain."

The results of his experiment, he says, show that the foot shocks did not have an effect on the deterioration of the brain, while the prolonged restraint did. He concludes that stress will drastically increase the rate of deterioration in the brain only when it becomes intense or prolonged. Anecdotal evidence suggests that Parkinson's disease tends to progress faster in people who have experienced such significant stress as losing a job or a loved one.

While Stuckert is researching the negative effects of stress on Parkinson's disease, Zigmond is studying the positive effects of exercise on limiting its progression. The preliminary data suggest that, to avoid Parkinson's disease, people should minimize stress and maximize exercise. Zigmond says he doubts that a drug will be developed to block toxins to the brain, but he hopes that his research, combined with Stuckert's, will heighten people's awareness about the dangers of stress and the value of exercise.

Real-world lab experience

Stuckert, who earned class credits along with his hands-on experience, went to work in Zigmond's lab after being awarded a Chancellor's Undergraduate Fellowship for Research.

"I got interested in researching Parkinson's disease after volunteering at a Parkinson's disease clinic last year," Stuckert says. "But I chose this lab because of the national attention it has received and because everyone in here cares about their work."

The research, he adds, has contributed greatly to his desire to go on to medical school. He began his studies at Pitt's School of Medicine this fall.

Stuckert isn't the only one benefiting from this fellowship, however.

"There were several things we liked about Joe when we invited him to join our research group," Zigmond says. "From a practical standpoint, he was a sophomore. He had two full years to work with us. But more important, Joe seemed very enthusiastic and highly motivated. We've never been disappointed."

Zigmond came to the University in 1970 after doing postdoctoral work at the Massachusetts Institute of Technology.

"I took the Pitt job, thinking I'd only be here for a few years." Zigmond says. "This is my 33rd year. But it's a wonderful city-and a great place for research opportunities."

Zigmond acknowledges that such opportunities are enhanced with help from dedicated undergraduate researchers like Stuckert. In return, he tries to give them real-world research experience.

"Real research gives undergraduates a deeper understanding about science," Zigmond says. "In a research lab, you don't know what to expect. You have to be very careful with experiments so you can have faith in the quality of the work you've done."

And that faith, he says, extends to Stuckert.

Says Zigmond: "I think Joe has given us renewed faith in the value of having undergraduates in our lab." •JM