The brain and spinal cord are bad at fixing themselves, a limitation that certain brainy characters in lab coats and neurology wards would very much like to overcome. Part of the problem is that chemicals in the central nervous system (CNS) stifle the growth of axons--neurons' long transmission cables. Now it appears that CNS neurons also have a built-in mechanism to inhibit axon growth. The finding presents a new hurdle for potential therapies for brain and spinal cord injuries.
Next time you slice open your finger with a kitchen knife, take some comfort in the fact that peripheral nervous system neurons regrow their axons at the same clip they did when you were an embryo, about a millimeter per day. Unfortunately, CNS neurons do not retain their prenatal zeal. That's because glia--the nervous system's "noncomputing" cells--put out chemical signals that inhibit axon growth in the CNS. But that turns out to be only half the story.
The new finding comes from neurons called retinal ganglion cells, taken from the retina and grown without glia or any other cells. Neurobiologist Ben Barres and colleagues at Stanford University School of Medicine in California noticed that neurons from 8-day-old rats slowed their axon growth considerably and diverted their energies to sprouting dendrites--the branching thickets of filament that neurons use to receive signals from each other. In contrast, the embryonic neurons happily cranked out new axons well past the age at which their postnatal counterparts switched over to dendritic growth mode, the team reports in the 7 June issue of Science.
Older neurons lost their gusto for axon growth because they had been cued by other retinal cells, called amacrine cells, before being isolated. Even brief contact with amacrine cells turns off axon growth, the researchers found. Barres interprets this as evidence that postnatal axon growth in the eye--and presumably elsewhere in the central nervous system--isn't just blocked by the neurons' chemical context, but by some intrinsic mechanism that, once triggered, is evidently locked in for life.
This obstacle to growth has big implications. "Understanding what regulates the ability of neurons to send out axons is key," says Nicholas Spitzer, a neurobiologist at the University of California, San Diego. "Both for regeneration research and for this marvelous new field we think is opening up with stem cells, it's vital to understand all the molecular mechanisms that stand in the way of regenerative repair."