The University Record, October 29, 1997

U-M scientists use insulin-like growth factor
to grow new membranes around neurons

This magnified image shows rat nerve fibers and Schwann cells after 72 hours in a culture with IGF-I. Most cells have already moved to the fiber and attached to it; many are beginning to wrap around and sp read along the fiber.

This magnified image shows rat nerve fibers (white arrows) and Schwann cells after 72 hours in a culture without IGF-I. Only a few of the Schwann cells have moved toward or attached to the fibers.

By Sally Pobojewski
Medical Center Public Relations

U-M scientists have used an insulin-like growth factor called IGF-I to stimulate growth of a myelin membrane sheath, similar to a sausage casing, around neurons in a culture dish.

"This is the first evidence to indicate that IGF-I can promote growth of new myelin sheaths around neurons," says Eva L. Feldman, associate professor of neurology.

If U-M scientists are able to use IGF-I to regenerate myelin in animals, it will be extremely significant because without myelin, neurons cannot transmit signals from the brain to peripheral nerves or from nerves back to the brain.

Feldman and research fellow Hsin-Lin Cheng presented the first results from their experiments with IGF-I at the Society for Neuroscience Meeting in New Orleans. James W. Russell, lecturer in neurology, is a co-investigator on the project.

Because they stimulate growth of nerves, bone and muscle tissue, growth factors have been the subject of intensive research for the past decade. Scientists believe understanding how growth factors affect neural development could lead to new treatment s for neurodegenerative diseases like diabetic neuropathy, multiple sclerosis and amyotrophic lateral sclerosis (ALS). The devastating symptoms of these diseases are caused by the death or degeneration of peripheral nerves. Although several growth facto rs are currently under study, IGF-I appears to be most effective at inducing myelination and preventing neural cell death, according to Cheng.

Named for its structural similarity to insulin and its ability to simulate insulin's glucose-lowering properties, IGF-I is produced in the liver and is present in blood serum. During embryological development, IGF-I is found in high concentrations n ear tiny "bud cells" called Schwann cells, which grow long fibers and wrap around neurons to form myelin sheaths. The U-M experiments were designed to determine whether IGF-I triggers this transformation in Schwann cells.

First, U-M scientists removed dorsal root ganglion neurons from newborn rats. The neurons were chemically treated to strip away the myelin sheath and any naturally occurring Schwann cells. The dissected nerves were maintained in a nutrient-rich cult ure medium. After undifferentiated Schwann cells from rat embryos were added to the cultures, half were bathed in a solution containing high levels of IGF-I.

"After six hours Schwann cells in the IGF-I solution started extending long feelers toward the rat neurons," Feldman said. "After 12 hours, most feelers were attached and had started wrapping around the fibers. After 48 hours, 50 percent of the neur ons in the IGF-I-supplemented cultures had a myelin sheath and looked just like freshly dissected dorsal rat ganglia. No myelination occurred in control cultures that did not receive IGF-I."

"The results suggest IGF-I promotes myelination by triggering a series of biochemical changes which help Schwann cells move and attach to nerve fibers," Russell said.

U-M scientists are currently testing IGF-I's ability to stimulate myelination and regenerate nerves in adult rats with neural damage, according to Feldman. "One major problem is targeting delivery of the growth factor to the injured area in the anima l," she said. "If we can find a delivery mechanism to get the right concentration of IGF-I to the site of injury, we may be able to regenerate nerves or prevent them from dying."

Research funding for the study was provided by the National Institutes of Health, the American Diabetes Association and the Juvenile Diabetes Foundation.