In an animal model of Parkinson's, exercise prevents degeneration of nerve cells that are normally impaired or destroyed by the disease, according to University of Pittsburgh researchers.
Based on their work, which was presented today at the Annual Meeting of the Society for Neuroscience in San Diego, a small pilot study has been initiated in patients with Parkinson's to determine if regular exercise has an impact on the progression of their disease.
Parkinson's disease belongs to a group of conditions called motor system disorders. The four primary symptoms are tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia or slowness of movement; and postural instability or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks.
The disease is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. It is not contagious nor is it usually inherited — that is, it does not pass directly from one family member or generation to the next.
In Parkinson's, cells in the brain that contain dopamine, a neurotransmitter essential for purposeful and facile muscle control, progressively die until only a small percentage remains. Dopamine carries signals from the nerve cells, or neurons, located deep inside the brain in an area called the substantia nigra along nerve fibers that end in the brain's striatum, an area involved in control of movement. In the absence of dopamine, neurons can't send the appropriate messages for smooth motor control, resulting in the telltale symptoms of Parkinson's: uncontrollable tremors, rigidity of limbs, slow movements and stooped posture.
In one of the studies presented by Annie D. Cohen, a doctoral student in the department of neurology and Center for Neuroscience at the University of Pittsburgh School of Medicine, the researchers examined the brains of rats that had been forced to exercise for seven days before receiving a toxin that normally induces Parkinson's disease. They found that, compared to animals that had not been exercised, significantly fewer dopamine-containing neurons died.
"Whereas a number of explanations could be offered as to why the exercised animals do so well, we have evidence that indicates it's because exercise stimulates production of key proteins that are important for survival of neurons," said the study's senior author, Michael J. Zigmond, Ph.D., professor of neurology, neurobiology and psychiatry, and co-director of the Parkinson's Disease Center of Excellence at the University of Pittsburgh School of Medicine.
Called neurotrophic factors, these proteins protect neurons and promote their survival. According to the researchers' studies, one particular neurotrophic factor, glial cell line-derived neurotropic factor, or GDNF, is increased with exercise by 40 percent. "GDNF, and probably other factors as well, may help offset the cell's vulnerability to the effects of oxidative stress from free radical molecules that are produced by the toxin we use in our rat model," Dr. Zigmond explained.
Parkinson's is induced by giving animals a substance called 6-hydroxydopamine
(6-OHDA). The toxin results in brain pathology that mimics what is seen in human disease - a decrease of dopamine-containing neurons in the substantia nigra and of axon terminals in the striatum, the site where dopamine is usually released.
When delivered to one side of the brain, 6-OHDA causes movement deficits in the limbs on the opposite side. If a cast is placed on the animal's left forelimb, for example, and 6-OHDA is administered to the left side of the brain, the toxin would normally cause the right forelimb to be impaired. But this is not the case. Earlier studies by Timothy Schallert, Ph.D., at the University of Texas in Austin, found that by immobilizing the left arm – the good arm – the rat has no choice but to use its right arm and does so without much difficulty.