Primitive Fish Hold Key to Healing Spinal Cords?

The sea lamprey, unlike a person or any other higher vertebrate for that matter, can repair its spinal cord when it is severed. Now researchers have a hint of where this primitive fish gets its regenerative powers. The lamprey's axons—the tendrils that transmit signals from one neuron to the next and from the spinal cord to the body's muscles—have an unusual means of locomotion. Growing rods of protein called neurofilaments prod them forward from inside. The finding, reported in the 1 July issue of The Journal of Neuroscience, could revise neuroscientists' understanding of neuron regrowth and, perhaps, shed light on how to heal humans with injured spinal cords.

Over the decades, researchers have shown that during embryonic development axons are pulled on their long journeys—which can stretch from the spinal cord to the big toe—by prickly, fanlike structures called growth cones. Axons in the peripheral nervous systems of mammals retain some of this embryonic wanderlust throughout life, which is why surgery to reconnect severed fingers and other body parts often succeeds. But the central nervous system (the brain, eyes, and spinal cord) in adult mammals is soaked through with proteins that inhibit axon growth.

Knowing that lamprey axons are packed with neurofilaments, a group led by University of Pennsylvania neurologist Mickey Selzer and Alan Jacobs of the University of California, San Francisco, decided to trace neurofilament protein in regenerating lamprey neurons. Jacobs cloned the gene encoding lamprey neurofilament protein and constructed complementary DNA probes that would bind to the gene's messenger RNA (mRNA) product, indicating how much protein was being made. He then cut halfway through several lampreys' spinal cords, and while the fish convalesced he tracked neurofilament mRNA levels.

In axons that were "bad regenerators," Jacobs and Selzer found, neurofilament mRNA production fell after the axons were cut and stayed low. In "good regenerators," however, neurofilament expression showed a smaller decrease and then—about 4 weeks later—climbed back up. The mRNA levels recovered even when the spinal cord gap was so broad that axons couldn't grow across it, suggesting that neurofilament revitalization isn't merely a consequence of axon regeneration but helps drive it.

"It's pure speculation at this point," says Selzer, "but it may be that temporarily overexpressing neurofilament in people with central nervous system injuries would help the nerve fibers to grow, if we also can eliminate some of the extracellular barriers to regeneration." Many scientists remain skeptical of neurofilaments' healing potential, however, pointing to the large evolutionary and physiological gap between sea lampreys and humans. Says molecular biologist Nisson Schechter of the State University of New York, Stony Brook, "It's certainly more complicated than saying 'If we could turn on this [neurofilament] molecule, Christopher Reeve would walk.' "

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