Long unappreciated and ignored, brain’s glial cells get their dueJune 1, 2005
USC College neuroscientist’s studies reveal critical role of “support” cells in brain and nervous system—and provide a reason for hope in the battle against neurological disease and injury.
By Katherine Leitzell
If the old saying, “We only use ten percent of our brain,” is true, then what are we doing with the other 90 percent?
That’s the question that drives the work of neuroscientist Chien-Ping Ko, professor of biological sciences at USC College. Figuring out the answer could bring scientists closer to understanding how to restore brain and nervous system functions destroyed by disease and injury.
“Ninety percent of the cells in your brain are glial cells, not neurons,” says Ko, who was initially drawn to neuroscience by his fascination with how neurons communicate. Scientists long thought that glial cells were nothing more than a support network for neurons, which do the real work of the brain. But Ko and others have turned this idea on its head, showing that glial cells play vitally important roles in the brain and body.
Historically, glial cells were difficult to study because there was no easy way to study them in living animals. This changed about 10 years ago when Ko, whose shy demeanor is suddenly replaced by an enthusiastic smile when he speaks about his research, stumbled across a specific marker for the type of glial cell that surrounds the synapses, or connections, between motor neurons and muscles. This fortuitous discovery led him to shift the focus of his investigations and allowed him to start answering the question, “What are all these glial cells for, anyway?”
Glial cells are located all over the nervous system, but the ones of most interest to neuroscientists like Ko are those that surround the synapses between neurons and their targets—critical junctures in the neuron-to-neuron communication network that underlies brain activity.
Ko focuses on a specific type of glial cell that surrounds the synapse between motor neurons and the muscles they control. Like the more complicated synapses of the brain, the so-called neuromuscular junction has several glial cells wrapped around it, but its large size and simpler structure have made it a favorite in the lab.
“For many years, we totally ignored glial cells,” says Ko “If you looked in a textbook, you would see the neuromuscular junction as just a nerve making contact with muscle.” Because the glial cell’s function was not clear, researchers assumed it had no active role at the synapse.
But, as Ko went on to show using the highly specific glial cell probe he had developed, that assumption was wrong. With the probe, Ko viewed the synapses under a microscope and, for the first time, clearly saw what the glial cells were doing in living animals.
Ko, working with his students and collaborators, Yoshie Sugiura, research assistant professor, and Albert Herrera, professor of biological sciences in the College, found that glial cells play a number of critical roles at synapses. They help guide young or damaged nerves to the correct spots to form synapses, and once they get there, they help maintain that connection.
“Normally, after a neuron makes contact with a muscle, it stops growing.” says Ko. However, when nerves in the body are damaged, they begin to grow again, often returning to exactly the same spot where the synapse had been. The signals that neurons use to return to this spot are a mystery, but Ko’s findings suggested an answer. Images of the glial cells showed them growing in front of the damaged nerve end, apparently guiding its growth. Further experiments suggested that glial cells similarly guide neural growth in the developing nervous system, leading the nerve to the right spot.
Ko’s team made another breakthrough when M.D./Ph.D. student Vinay Reddy, now completing his residency in neurology at the Medical College of Wisconsin suggested using an immunological method common in medical research to remove the glial cells from around the synapse, allowing the team to study what happens to the synapse without the glial cell.
“One week later, we found that nerve function was decreased, and that some of the nerve terminals had retracted,” says Ko. “This suggests that glial cells play a long-term maintenance role for the structure and function of the synapse.”
These experiments showed that glial cells affect neurons in a variety of keys ways—acting on the development and maintenance of synaptic connections as well as mending damaged synapses. “Glial cells act like parents. They nurture the young neurons and step back as they grow up. But if the neurons get into trouble, get damaged, they’ll step in to help,” Ko says.
University Professor Caleb Finch, the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging and a leading expert on aging and Alzheimer’s disease at USC, points out that Ko’s research has established a new role for glial cells in the adult nervous system. “We knew that glial cells were fundamental to establish migration of developing neurons, but this research shows that they have an active role in the mature nervous system as well,” says Finch, a professor of gerontology, biological sciences and psychology.
The realization that glial cells can guide the regeneration of adult nerves in the peripheral nervous system has prompted a surge of scientific interest in the cells. Ko believes it might just hold the key to finding a way to restore the connections between damaged neurons. “We know that glial cells make synapses bigger, stronger and more stable,” says Ko. “Many diseases, including Alzheimer’s, may be partially due to a failure of the synapse. If we can identify these factors, it’s bound to have clinical implications.”
Currently, Ko and his students are working to find the molecular signals that the cells use to guide neural growth and maintain the critical synaptic connections between neurons. Identifying the molecules glia use to guide and protect neurons could prove important in the understanding and treatment of neurodegenerative diseases like Alzheimer’s as well as conditions such as paralysis.