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Researchers find molecule that inhibits regrowth of spinal nerve cells

rin-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 spinal-cord injury.

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 results.

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," he said.

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
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Source:UT Southwestern Medical Center


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