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New Way to Resprout Severed Axons

16 January 2001 7:00 pm
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Spinal cord injuries leave people paralyzed because damaged spinal neurons can't make new axons, those long tendrils that form the line of communication between the brain and the rest of the body. But now researchers have found that two proteins normally active during development can help damaged neurons regrow. The finding may point to new strategies for reversing the loss of sensation and movement caused by spinal cord injuries.

Like neurons in the brain, spinal neurons can't grow new axons when injured. Molecular cues in the adult nervous system inhibit axon growth, for one thing, and adult neurons suppress the genes that encode growth-inducing proteins such as those that make up the so-called growth cones at the tips of burgeoning axons.

That fact sparked an idea for neurobiologist Pate Skene of Duke University in Durham, North Carolina, and his colleagues. They guessed that giving adult neurons a boost of growth cone proteins might spur the growth of new axons. The team examined spinal neurons in mice engineered to overproduce two growth cone proteins, called GAP-43 and CAP-23. After the mice had matured, the researchers removed neurons from their spinal cords and transferred them to a culture plate. Within 24 hours, 26% of the neurons had extended new axons, compared to 7% of neurons from normal mice. In a second set of experiments, engineered mice with 1- to 4-month-old spinal cord lesions had 60 times as many neurons with new axons as did normal mice, the researchers report in the January issue of Nature Neuroscience.

"It's very cool that just expressing two proteins is enough to get axons to elongate," says Ben Barres, a neurobiologist at Stanford University. Nonetheless, several obstacles must be overcome before the new finding can be applied to treat spinal cord injuries. Getting axons to grow is just one step, Barres says: "The challenge is to get them to grow to the right place."

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