Lowly glial cells
strengthen brain connections
BY WILLIAM A. WELLS
Once dismissed as mere
padding, cells known as glia may be essential for the
correct wiring of the brain, according to a study
reported by two School of Medicine researchers in the
Sept. 12 Science.
Postdoctoral fellow Frank
Pfrieger and Dr. Barbara Barres, associate professor of
neurobiology, used pure populations of nerve cells and
glia to show that, by themselves, the nerve cells
connected together poorly, whereas the combination of 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," said Barres. Glia make up
approximately 90 percent of the cells in the human brain,
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, and 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 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.
The work was funded by the
Searle Scholar program, administered by the Chicago
Community Trust. Pfrieger was supported by fellowships
from the Deutsche Forschungegemeinschaft and the Human
Frontier Science Program Organization. SR
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