Exercise prevents Parkinson's symptoms in lab model mimicking human form of the disease

October 14, 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.
-end-
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 www.stjude.org.

St. Jude Children's Research Hospital

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.