More MS news articles for Nov 2001

Neurons Get Top Billing, But Glia Work Behind Scenes

November 20, 2001
Tom Siegfried
Knight Ridder/Tribune

SAN DIEGO - One of the great dramas of human thought is the story of figuring out how humans think.

During the 20th century, neuroscientists developed a story featuring nerve cells, or neurons, as the main characters. Neurons connect to each other in elaborate networks, sending signals back and forth through a clever combination of electricity and chemistry. Any given neuron receives thousands of messages from its neighbors, and then decides whether to send out a message of its own.

While neurons are the main actors in the drama of brain activity, they are vastly outnumbered by the stagehands, known as glial cells. The glia offer structural support, provide nutrients, and otherwise hang around and watch as the neurons talk to each other.

But lately scientists have discovered that glial cells do much more than watch - they also listen in to neuron chatter and toss in some comments on their own.

"Glial cells are among the most intriguing and mysterious cells in the brain," says neurobiologist Fiona Doetsch of Harvard University.

Doetsch and colleagues at Harvard are among the researchers who have recently shown that some glial cells can transform themselves into neurons. Scientists had previously found reservoirs in the brain of "stem cells" that could change identities. Now the identity of those stem cells themselves has been revealed to be glia.

Some researchers have focused on the young developing brain, where "radial" glial cells project (or radiate) long arms that serve sort of like railroad tracks to guide newborn neurons to their proper brain location. It turns out that the parent cells of the newborn neurons are the radial glia themselves.

Radial glial aren't found in the adult brain, but that's because they mature into astrocytes, another type of glial cell. And Doetsch and others have shown that astrocytes in at least two brain regions can also become neurons.

"There is no evidence yet that astrocytes throughout the brain have this capability," Doetsch said in San Diego last week at the annual meeting of the Society for Neuroscience.

But if most or all astrocytes can become neurons, new strategies arise for treating brain disorders caused by neuron death, such as Alzheimer's disease.

"The hope is maybe that all astrocytes in the brain might have the potential to generate neurons," says Magdalena Gotz, another leading researcher in the field.

Doetsch points out that the research on glial cells has only begun to show how important they might be.

"We've just uncovered one novel function for them, which is to give rise to new neurons," she said at the neuroscience meeting. "This just hints at how much more there is to discover about their function elsewhere in the brain as well."

Other recent research has already turned up new roles for astrocytes. Some astrocytes wind their arms around the communication links, or synapses, where chemical signals swim from one neuron to another. The same astrocyte may have one arm around one synapse and another arm around a second synapse linking two other neurons. And one astrocyte can communicate with neighboring astrocytes, via chemicals or by electrical particles traveling through cell-to-cell tubes called gap junctions.

It turns out that chemicals released from a neuron can induce chemical changes inside one astrocyte. That astrocyte can then signal other astrocytes to change as well. Down the line, an excited astrocyte may signal a nearby neuron, perhaps retarding its inclination to fire a further signal. In this way, the firing of one neuron might alter the messages sent by a second, faraway neuron, because of the influence of the astrocytes.

"Signaling between astrocytes might form the basis of a long-range signaling pathway in the nervous system," writes Philip Haydon, of the zoology and genetics department at Iowa State University in Ames.

So far, such astrocyte signaling has been detected only in some parts of the brain. But the process may be more widespread. If so, it provides an entirely new level of brain interaction to consider in trying to figure out how different parts of the brain communicate. The rapid-fire messages sent by neurons would be subtly altered by the slow-moving signaling between astrocytes.

Scientists are still working out the chemical details of astrocyte signaling. Long-range signals may use a different strategy from short-range signals. But in any case, it may be that communication among astrocytes is a method for the brain to coordinate the action of different groups of neurons, Haydon suggests in a recent issue of Nature Reviews/Neuroscience.

In his view, synapses should be considered not just as the link between two neurons but as a "tripartite" communication junction - the sending neuron, the receiving neuron, and the eavesdropping astrocyte.

"It is time to rethink our understanding of the wiring diagram of the nervous system," he writes.

The role of glia in the brain's wiring may help explain the human mental capacity compared with other animals. In primitive worms, neurons outnumber glia 5-to-1. But in humans and other primates, glia outnumber neurons 10-to-1.

"The more technically sophisticated the performance," writes Haydon, "the greater the number of backstage people needed."

(c) 2001, The Dallas Morning News