I never understood that actual
nerve cells based in the spinal column send axons all the way out to end of
limbs. Thus the steps between the brain and
the ends are potentially very few.
Thus any thing that inhibits their
functioning actually losses information quickly as we are not dealing with a
distributed network, but a directed network.
Here we explore protocols to induce the same symptoms and as should be
obvious, we can select for substances that overcome this problem.
We are still early days but we
are surely now much closer to a real answer to this riddle and perhaps we will
see 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 so
selectively harms brain cells that produce the chemical dopamine, say
researchers at Washington University School of Medicine in St. Louis.
Dopamine is involved in brain cell communications including the signals
that 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-producing
nerve cells and mimic Parkinson’s disease does so by rapidly damaging
cellular energy generators called mitochondria. This damage impairs the ability
of mitochondria to circulate around the cell as they normally would. As a
result, axons, the extended arms nerve cells use to send messages, wither; a
few days later, the body or main portion of the cell also dies.
“Much of the research into Parkinson’s disease treatments is focused on
saving the bodies of these cells, but our results suggest that keeping axons
healthy 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 body
of the nerve cell, and their products sometimes have to travel a significant
distance to reach the axon’s end.
“If you think, for example, about one of your peripheral nerves, the
cell body is located in the spinal column, but some of the axons extend as far
as your big toe,” says O’Malley, professor of neurobiology. “That’s like the
cell body sits in an office in St. Louis and the
end of the axon is in Chicago
O’Malley compares the axon’s system for transporting supplies to a
railroad. Mitochondria are part of the railroad’s cargo. They supply the energy
that allows the axon to do its work.
For the study, O’Malley gave cultured mouse nerve cells a toxin called
MPP+ that causes Parkinson’s-like symptoms.
“MPP+ is a derivative of a synthetic form of heroin developed in
California in the early 1980s,” O’Malley says. “It came to scientists’
attention when teenage abusers of the drug went to the hospital with Parkinson’s
disease symptoms.”
O’Malley found that the toxin stopped the movement of mitochondria in
the axon in 30 minutes. The railroad still functioned, shipping other cargo to
the end of the axon. But most mitochondria either stopped moving or were headed
for the cell body instead of the axon.
O’Malley suspected that this meant the mitochondria were damaged by the
changes caused by the toxin and being shipped back to the cell body for repair.
Additional tests supported this theory, showing that the mitochondria had lost
their ability to maintain their membrane potential, a measure of mitochondrial
fitness.
The specificity of this toxin for dopamine-producing cells is
reinforced by the finding that other types of nerve cells did not have problems
transporting mitochondria after toxin exposure. In a comparison between
different nerve cell types, O’Malley found mitochondria in dopamine-producing
nerve cells are smaller in size and travel three times slower. But she can’t
yet definitively say that these distinctions play a role in the problems caused
by the toxin.
Scientists screened several compounds to see if they could block the
toxin's effects. Only two antioxidants worked, glutathione and N-acetyl
cysteine. The latter compound has already been shown to be effective in animal
models of Parkinson’s disease and is used as a treatment for other disorders in
patients.
O’Malley is currently studying whether two genes linked to Parkinson’s
disease affect mitochondria damaged by the toxin.
“We’re going to continue to look for specific differences in these
cells that might help scientists develop better treatments,” O’Malley says.
###
Kim-Han JS, Antenor-Dorsey JA, O’Malley KL. The Parkinsonian mimetic,
MPP+, specifically impairs mitochondrial transport in dopamine axons. The
Journal of Neuroscience, May 11, 2011.
Funding from the National Institutes of Health (NIH), the National
Institutes of Health Neuroscience Blueprint Core Grant and the Bakewell Family
Foundation supported this research.
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