Nerves that control the highest level of voluntary movements have been isolated and secrets of their growth revealed for the first time.
During development, these nerves extend themselves from the brain to all levels of the spine with the help of a potent growth factor called IGF-1. This factor is well known to scientists. However, the discovery of its role in guiding the extension of the longest nerves in the body was a big surprise.
The discovery has researchers talking about new ways to treat ALS, or Lou Gehrig’s disease, and other paralyzing disorders, as well as regenerating spinal nerves that have been damaged by falls, crashes, and combat.
“Our experiments are highly relevant to understanding the basic development of the central nervous system of humans and other mammals,” says Jeffrey Macklis, director of the Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair. “Learning how these nerves, known as corticospinal motor neurons (CSMN), establish connections between the brain and spinal cord could help find new treatments for ALS and other diseases caused by nerve degeneration. Such knowledge might also contribute to efforts to repair spinal-cord injuries.” These goals, still many years away, might be accomplished by regrowing damaged nerves or recruiting new nerves from adult stem cells.
Macklis and postdoctoral fellow Hande Ozdinler isolated the long motor neurons from a tangle of look-alike nerve cells in the brains of mice. They kept the cells alive in laboratory dishes then bathed them in IGF-1. They also put tiny beads carrying the growth factor next to the nerves and made microscopic movies of what happened. “The results were immediate,” Macklis recalls. “Within 30 seconds, we saw a dramatic outgrowth of the axons [nerve extensions]. IFG-1 increased their rate of growth a striking 15 to 20 fold.”
Since these kinds of experiments cannot be done on humans, mice were used. “Mice mimic many aspects of human biology on molecular and genetic levels,” Macklis points out. He sees the cells that survive but do not grow in lab dishes as mimicking motor neurons in adults. Reintroducing them to IGF-1 is like turning the biological clock back to infancy, when brain development is at its swiftest, and a baby is moving from uncoordinated flailing to drawing with crayons.