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Worm neuron research may lead to powerful model for Parkinson's study

NASHVILLE, Tenn., It was a warm summer night that Tuesday a night not unlike many others he had spent working in the lab when Richard Nass, Ph.D. walked down the empty hallway and entered a small, darkened room. Settling himself onto a stool, he placed a shallow dish on the stage of the microscope before him and peered through the eyepieces. What he saw there or, rather, didnt see took him aback.

Nass saw the host of wriggling, transparent worms that he expected, but missing was the distinctive green glow that should have lit up the bodies of the worms like neon.

"I almost couldnt believe it," he said, shaking his head. The loss of green fluorescence that Nass observed in his worms told him that their dopamine neurons, which had been genetically altered to fluoresce green, had been destroyed by exposure to a chemical, 6-hydroxydopamine (6-OHDA). The results of the study, published this week in the journal Proceedings of the National Academy of Sciences, suggest that this tiny roundworm, named C.elegans, can serve as a powerful model for studying the molecular mechanisms underlying degeneration of dopamine neurons in the brains of patients with Parkinsons disease (PD).

The paper, co-authored by Nass, a post-doctoral research fellow in Pharmacology; Randy D. Blakely, Ph.D., Alan D. Bass Professor of Pharmacology; and David M. Miller, III, Ph.D., associate professor of Cell Biology, presents evidence for why and how the C. elegans model can be used to visually screen for genetic and environmental events that influence dopamine transporter expression and trigger dopamine neuron cell death.

Although rare genetic forms of PD have been identified, the molecular basis of dopamine neuron vulnerability and cell death in the majority of PD cases is poorly understood. Some theories on the cause involve exposure to environmental toxins, the generation of reactive oxygen species in brain cells, and inhibition of mitochondria, the sub
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Contact: John Howser
john.howser@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
26-Feb-2002


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