Oct. 19, 2004 Exercise might one day provide a non-invasive, non-pharmaceutical way to protect adults against the onset of symptoms of Parkinson's disease (PD). These findings, by investigators at St. Jude Children's Research Hospital, are published in a current, special issue of Molecular Brain Research, called "Molecular Aspects of Parkinson's Disease."
PD affects more than 2 percent of the world's adult population, including 1 million adults in the United States. In addition, experts agree that in most cases, PD is caused by long-term exposure to toxins in the environment. PD is a progressive neurodegenerative disorder caused by loss of dopamine-containing nerves in the part of the brain called the substantia nigra (SN). Common symptoms of PD include tremors, muscular stiffness and other movement problems. Dopamine is a signaling molecule released by nerves in the SN and is critical to the brain's ability to control movement.
The St. Jude study showed that sustained exercise for at least three months prevented cell death in the SN of adult mice that otherwise occurs following injection of a toxin called MPTP. Once in the SN, MPTP is converted into a highly reactive molecule called MPP+, which triggers the production of molecules called free radicals. The free radicals, in turn, damage the brain cells. The key to the protective effect of exercise was the increased production of a protein called glial-derived neurotrophic factor (GDNF), which helps maintain the health of nerves and protects them against MPP+. Glia are special supportive cells in the brain that help to maintain nerve health.
The researchers used MPTP to produce PD symptoms in adult mice because this toxin is known to cause identical results in people who have abused so-called "designer drugs" that contain this toxin as a contaminant. The finding that exercise protects the SN in mice from damage caused by MPP+ suggests that exercise might also protect humans from the same type of damage caused by environmental toxins, said Richard J. Smeyne, Ph.D., associate member in St. Jude Developmental Neurobiology. Smeyne is senior author of the Molecular Brain Research report.
"If we can extend these findings to humans we could suggest that it's never too late for adults to benefit from the protection exercise offers against damage to the substantia nigra caused by environmental toxins," said Smeyne, who is the editor of the special Molecular Brain Research issue.
Moreover, increasing GDNF levels through exercise might also confer protection against stroke, seizures and other brain disorders that are also caused by free radical damage. Although GDNF is found only in the brain, previous research by others has found that exercise somehow protects the heart from free radical damage.
"So exercise, one way or the other, seems to be an extremely good investment in one's health," Smeyne said.
The study initially investigated whether a so-called enriched environment (EE) could protect mice treated with MPTP. The EE included exercise wheels, companionship of other mice and a tunnel with a configuration that researchers changed weekly to provide mental stimulation. The researchers found that mice using the exercise wheels ran about two kilometers a day.
The St. Jude researchers raised female mice in standard cages without running wheels before placing them into cages with wheels. Control mice were kept in standard cages without running wheels throughout the study. After three months, the amount of GDNF in the SN of mice in the EE cages increased 350 percent over the level found in the control mice kept in standard cages.
Subsequently, animals were injected with MPTP at 5-7 months of age--about a third of their normal life span. This triggered an additional 180 percent increase in GDNF over the already increased level in EE animals. The St. Jude team found that, while 40 percent of the nerves in the SN of non-exercising mice died following MPTP injection, only 5 percent of those cells died in animals that had experienced sustained exercise for at least three months.
In a subsequent study, the St. Jude team found that exercise alone could account for virtually all of the protective effect of the enriched environment.
"Future studies might show that sustained exercise can also stop the progression of Parkinson's disease in adult humans," said Ciaran Faherty, Ph.D., first author of the paper and a former postdoctoral researcher in Smeyne's lab. "If exercise is started early enough, it might be possible to prevent the neurons from dying in the first place. It will be important to find out how much exercise is effective." Other authors of the paper are Kennie Raviie Shepherd and Anna Herasimtschuk.
This work was supported in part by the National Institutes of Health and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tennessee, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org.
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