30th March 05:00
Inhibiting regrowth of spinal nerve cells (myelin isolation down)
Contact: Amanda Siegfried
UT Southwestern Medical Center
Researchers find molecule that inhibits regrowth of spinal nerve cells
DALLAS - July 11, 2005 - A molecule that helps the body's motor
nerve cells grow along proper paths during embryonic development also
plays a major role in inhibiting spinal-cord neurons from regenerating
after injury, researchers at UT Southwestern Medical Center have found.
In cultured cells, the researchers found that a component of myelin -
a substance that normally insulates and stabilizes long nerve fibers in
adult vertebrates - chemically blocks the ability of nerve cells to
grow through myelin that is released when the spinal cord is damaged.
While other myelin components also block nerve growth, a component
called ephrin-B3 inhibits such activity as well or better than that of
other known blocking agents combined, UT Southwestern researchers
report in an upcoming issue of the Proceedings of the National Academy
"I believe that to the extent that overcoming myelin-based inhibition
is going to provide some sort of functional recovery for spinal cord
injury patients, understanding ephrins is a major step forward," said
Dr. Luis Parada, senior author on the paper and director of the Center
for Developmental Biology and the Kent Waldrep Center for Basic
Research on Nerve Growth and Regeneration at UT Southwestern. A mixture
of molecules and proteins, myelin insulates nerve fibers and impedes
them from having contact with other nerve cells. After a spinal-cord
injury, myelin is released into the tissues. Not only does myelin
encourage the growth of scars - called glial scars - which
physically block nerve cells from regrowing in the damaged area, but
components of myelin also chemically prevent nerve cells from regrowing
there as well.
Considerable research has been done in the past 10 years to identify
elements in myelin that chemically inhibit the regeneration of nerve
cells, Dr. Parada said. Three individual components - the molecules
Nogo, MAG and OMgp - have been shown to do so in isolation.
Developmental biologists at UT Southwestern have been studying how
ephrin-B3 helps control how and where nerve fibers grow during early
development. They previously showed that the molecule throws up
"fences" that repel developing nerves and guide them along the pathways
to their appropriate connections to muscles.
In 2002 Dr. Mark Henkemeyer, associate professor in the Center for
Developmental Biology and of cell biology and one of the authors of the
PNAS study, found that such a "fence" is erected specifically down the
middle of the cortical spinal tract, which is damaged during
In the current study, Dr. Parada and his colleagues asked: What is this
molecule, whose normal function is to be repellent during embryonic
development, doing in the mature system?
"To our surprise, we found that ephrin-B3, which normally is present as
a 'wall' down the middle of adult spinal cords, also is found in very
high levels in adult myelin," said Dr. Parada.
The researchers knew from previous work that ephrin-B3 interacts with
receptors on neurons in the cortical spinal cord. So, in the lab, led
by the study's lead author Dr. M. Douglas Benson, a postdoctoral
research fellow, they cultured neurons together with isolated ephrin-B3
and confirmed that the molecule activated the neuron's receptors. They
then cultured normal myelin together with the neurons and got the same
However, when they cultured neurons with myelin from which the
ephrin-B3 had been removed, the receptors were not activated. The
findings suggest that there is much more to be learned about
myelin-based inhibition, Dr. Parada said. "We firmly believe that
ephrin-B3 is an important, functional, relevant component of myelin,
although there may be other elements that are left to be discovered,"
Dr. Parada added that several factors must be overcome before
spinal-cord regeneration and recovery from injury can occur in a
meaningful way for patients.
"We have to figure out how to dissolve the glial scars or impede their
formation," he said. "We also need to get mature neurons to be better
at growing, similar to the way they do during embryonic development.
And finally, we have to remove myelin-based inhibition. If and when we
achieve those three things, then we'll have robust regeneration of
Other Center for Developmental Biology researchers involved with the
study were Dr. Mark Lush, postdoctoral research fellow, and Dr. Q.
Richard Lu, assistant professor. Dr. Mario Romero, assistant professor
of neurology, also contributed.
The research was supported by the National Institute of Neurological
Disorders and Stroke and the Christopher Reeve Paralysis Foundation
Consortium on Spinal Cord Injury.
This news release is available on our World Wide Web home page at
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