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Title: Lowly Glia Strengthen Brain Connections
URL: http://www.pslgroup.com/dg/3A0EE.htm
Doctor's Guide
September 24, 1997


STANFORD, CT. -- September 24, 1997 -- Once dismissed as mere padding, cells known as glia may be essential for the correct wiring of the brain. This is the conclusion of a study reported in the September 12 issue of Science by researchers from the Stanford University School of Medicine.

Postdoctoral fellow Frank Pfrieger and Dr. Barbara Barres, associate professor of neurobiology, used pure populations of nerve cells and glia to show that the nerve cells connected together poorly when acting individually but, when combined, the two cell types resulted in strong connections between nerve cells.

In the brain, such connections allow nerve cells to pass along messages about our every sensation, thought and movement. Weakening of these connections could be responsible for memory loss and other symptoms of strokes and Alzheimer's disease.

On their own, the nerve cells appear to do the right thing -- forming the connections, called synapses and even using them to pass along electrical messages -- but the transfer of messages is inefficient and often fails. With glia around, the connections rarely fail and the nerve cells pass on more and stronger signals, the researchers found.

"The brain is the only tissue in the body where we don't know the function of the major cell type," Barres said. Glia make up approximately 90 percent of the cells in the human brain and yet researchers have assigned mainly passive functions to them. Some glia wrap around nerve cells and insulate them with a protein called myelin. Glia at synapses act both as a physical barrier that prevents crossed wires and as a disposal unit that mops up extra messenger molecules released by nerve cells.

The new study is one of the first to assign an active role to glia. Barres and Pfrieger demonstrated that the glia provide a protein or chemical factor that strengthens the lines of communication between nerve cells. They found that it is this factor -- not necessarily the glial cells -- that is needed.

The researchers produced the still-unidentified factor by first growing glia in isolation. The glial cells made the factor and pumped it out into the surrounding growth solution. The researchers then added this growth solution to nerve cells without adding the glia. They found that the nerve cells responded to the addition of the solution almost as strongly as they had previously responded to the addition of glia.

In the presence of glia or the glial factor, nerve cells made more connections among themselves, but this effect alone could not fully account for the increased transfer of messages, Barres said. The more significant change occurred inside each nerve cell transmitting the message to its neighbors. For some reason, the glial factor made the transmitting nerve cell release its chemical messengers more readily in response to an electrical signal.

The nerve cells chosen for the Stanford study -- retinal ganglion cells -- lead from the eyes deep into the brain. Barres is using them as representatives of a large class of nerve cells in the brain: those that use a chemical messenger called glutamate to send a positive, or excitatory, signal. The study did not address any effect of the glia on the less prevalent nerve cells that send negative, or inhibitory, signals.

Barres said glia are almost certainly needed for the formation of strong synapses as the brain develops, but the importance of this effect in the intact brain has yet to be demonstrated. It is also possible, she said, that glia control the strength of synapses in the fully developed brain, beefing up some circuits and turning down others. Identification of the glial factor will allow researchers to address these questions, she said.

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