I never understood that actualnerve cells based in the spinal column send axons all the way out to end oflimbs. Thus the steps between the brain andthe ends are potentially very few.
Thus any thing that inhibits theirfunctioning actually losses information quickly as we are not dealing with adistributed network, but a directed network. Here we explore protocols to induce the same symptoms and as should beobvious, we can select for substances that overcome this problem.
We are still early days but weare surely now much closer to a real answer to this riddle and perhaps we willsee the day when this disease no longer quiets so many voices.
Unique Vulnerability Found in Cells Hit by Parkinson's
Released: 5/12/2011 3:50 PM EDT
Newswise — New data offer hints to why Parkinson’s disease soselectively harms brain cells that produce the chemical dopamine, sayresearchers at Washington University School of Medicine in St. Louis.
Dopamine is involved in brain cell communications including the signalsthat control movement. As Parkinson’s kills the dopamine-producing cells,patients begin to develop tremors, problems moving and other symptoms.
The new research shows that a drug known to damage dopamine-producingnerve cells and mimic Parkinson’s disease does so by rapidly damagingcellular energy generators called mitochondria. This damage impairs the abilityof mitochondria to circulate around the cell as they normally would. As aresult, axons, the extended arms nerve cells use to send messages, wither; afew days later, the body or main portion of the cell also dies.
“Much of the research into Parkinson’s disease treatments is focused onsaving the bodies of these cells, but our results suggest that keeping axonshealthy also is essential,”says Karen O’Malley, PhD, of Washington University School of Medicine in St. Louis
The results were published May 11 in The Journal of Neuroscience.
Many processes and facilities for cellular maintenance are in the bodyof the nerve cell, and their products sometimes have to travel a significantdistance to reach the axon’s end.
“If you think, for example, about one of your peripheral nerves, thecell body is located in the spinal column, but some of the axons extend as faras your big toe,” says O’Malley, professor of neurobiology. “That’s like thecell body sits in an office in St. Louis and theend of the axon is in Chicago
O’Malley compares the axon’s system for transporting supplies to arailroad. Mitochondria are part of the railroad’s cargo. They supply the energythat allows the axon to do its work.
For the study, O’Malley gave cultured mouse nerve cells a toxin calledMPP+ that causes Parkinson’s-like symptoms.
“MPP+ is a derivative of a synthetic form of heroin developed inCalifornia in the early 1980s,” O’Malley says. “It came to scientists’attention when teenage abusers of the drug went to the hospital with Parkinson’sdisease symptoms.”
O’Malley found that the toxin stopped the movement of mitochondria inthe axon in 30 minutes. The railroad still functioned, shipping other cargo tothe end of the axon. But most mitochondria either stopped moving or were headedfor the cell body instead of the axon.
O’Malley suspected that this meant the mitochondria were damaged by thechanges caused by the toxin and being shipped back to the cell body for repair.Additional tests supported this theory, showing that the mitochondria had losttheir ability to maintain their membrane potential, a measure of mitochondrialfitness.
The specificity of this toxin for dopamine-producing cells isreinforced by the finding that other types of nerve cells did not have problemstransporting mitochondria after toxin exposure. In a comparison betweendifferent nerve cell types, O’Malley found mitochondria in dopamine-producingnerve cells are smaller in size and travel three times slower. But she can’tyet definitively say that these distinctions play a role in the problems causedby the toxin.
Scientists screened several compounds to see if they could block thetoxin's effects. Only two antioxidants worked, glutathione and N-acetylcysteine. The latter compound has already been shown to be effective in animalmodels of Parkinson’s disease and is used as a treatment for other disorders inpatients.
O’Malley is currently studying whether two genes linked to Parkinson’sdisease affect mitochondria damaged by the toxin.
“We’re going to continue to look for specific differences in thesecells that might help scientists develop better treatments,” O’Malley says.
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Kim-Han JS, Antenor-Dorsey JA, O’Malley KL. The Parkinsonian mimetic,MPP+, specifically impairs mitochondrial transport in dopamine axons. TheJournal of Neuroscience, May 11, 2011.
Funding from the National Institutes of Health (NIH), the NationalInstitutes of Health Neuroscience Blueprint Core Grant and the Bakewell FamilyFoundation supported this research.
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