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Degenerative Changes That Mimic Parkinson's Linked To Reduced Dopamine Storage

ScienceDaily (July 28, 2007) — Emory University neuroscientists have discovered what could serve as a model for slowing the progression of Parkinson's disease, a neurodegenerative condition that affects more than 1 million people in the U.S.

The study, published in the July 25 issue of the Journal of Neuroscience, found that mice with a reduced capacity to store the brain chemical dopamine underwent a degenerative process that mimics Parkinson's disease.

"We've uncovered solid evidence that improper storage of dopamine can be harmful to the dopamine neurons in the brain," says Gary W. Miller, PhD, study principal investigator, associate professor in the Emory Center for Neurodegenerative Disease, and associate professor of environmental and occupational health in Emory's Rollins School of Public Health.

The mice observed in the study had a reduced expression of the gene VMAT2 causing progressive loss of dopamine neurons and many of the neurochemical features observed in Parkinson's disease patients, including an increase in oxidative stress.

For many years, scientists have known that the lack of the neurotransmitter dopamine is responsible for many of the symptoms of Parkinson's. The most effective treatment is providing patients with a substance that can be converted by the body into dopamine, called a dopamine precursor, to help restore dopamine levels in the brain.

The transporter VMAT2 packages dopamine into tiny containers for future release by brain cells, or neurons. Dopamine transmits signals between nerve cells. When insufficient VMAT2 is produced by the nerve cells, the improperly stored dopamine causes neurodegenerative changes in the nigrostriatal dopamine system, which is embedded in the deepest structures of the brain. Damage to the nigrostriatal region leads to the movement problems observed in Parkinson's disease.

"The mice in our study that were unable to store sufficient levels of dopamine provide an ideal model of how Parkinson's progresses over time," Dr. Miller says. "We hope to use this model to test compounds aimed at slowing the course of the disease."

The study, titled "Reduced Vesicular Storage of Dopamine Causes Progressive Nigrostriatal Neurodegeneration," also included Emory researchers Mike Caudle, PhD, Tommy Guillot, Jason Richardson, PhD, Tonya Taylor and Min Wang, MD. Scientists at the Parkinson's Institute in Sunnyvale, Calif., and the Babraham Institute in the United Kingdom also contributed to the research. The study was supported by the National Institute of Environmental Health Sciences.


Adapted from materials provided by Emory University.
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