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by ROSIE MESTEL, Times Medical Writer
The
brain is a miraculous organ, but for decades neuroscientists
have written off 90% of its cells as--well, rather boring.
Neurons,
they knew, were the exciting cells of the brain--the ones
sending electrical signals flitting here and there, helping
to forge memories, move limbs, frame thoughts. But the cells
making up the bulk of the brain were deemed just about as
sexy as the sound of their name: glia.
The
jobs of glia, when even known, were important but humdrum:
supporting and insulating neurons, nourishing them, soaking
up chemicals that might harm them.
But
today glia are hot. New findings from a Stanford research
team show that they're needed for properly forging and maintaining
the intricate web of contacts between neurons. Such contacts,
called synapses, allow neurons to communicate with each
other and are crucial for brain function.
Glia,
in other words, aren't just supporting actors in the workings
of the brain: They're central players.
The
discovery should help neuroscientists understand how synapses
are made, strengthened or broken. (Brains forge a billion
such synapses per microliter of tissue.) Number and size
of the synapses dictate much of brain function, not least
how memories are forged or forgotten.
"Whatever
it is that glia are doing will give us a clue to what regulates
the number of synapses and how big they are," said
Dr. Chuck Stevens, neuroscientist at the Salk Institute
in La Jolla and an investigator with the Howard Hughes Medical
Institute.
The
discovery also opens up a new line of inquiry into brain
damage and diseases such as Alzheimer's. It's possible--though
still unproved--that malfunctioning glia lie behind at least
some of these maladies.
"Any
number of diseases could be glial diseases--but we just
don't know it yet," Stevens said.
Formerly
Considered the Brain's 'Glue'
The
cells' very name comes from the Greek word for "glue"--because
they used to be thought of as cells that just glued the
brain together.
Then,
over the years, other roles for glia were unearthed. One
major kind of glial cell wraps itself around nerve fibers
and creates an insulation that allows electric signals to
travel more quickly. In multiple sclerosis, this fatty sheath
of cells gets destroyed.
The
other class of glial cell--called an astrocyte, because
it's shaped like a tiny star--was thought, until two experiments
suggested otherwise, only to feed, guide and protect neurons.
In the
first, published in Science three years ago, Ben Barres
and co-workers at the Stanford University School of Medicine
discovered that neurons in a test tube, without glia, send
weak, wimpy signals to each other--10 times weaker than
when glia are there in the test tube as well.
"It
was a very, very important paper," said Joshua Sanes,
a neuroscientist at Washington University in St. Louis.
In the second paper, published last month, Barres' group
figured out the reason why. Neurons, on their own, make
very few synapses--seven times fewer--and the ones that
get made are small and immature. No synapses, no electrical
signaling.
"We
were just in shock when we figured out what was going on,"
said Barres, associate professor of neurobiology at Stanford.
"We were just not used to thinking about glia this
way."
Given
all the fancy things neuroscientists know about the brain,
it may seem odd that it took so long to figure out this
fundamental fact. The explanation is simple: Separating
neurons from glia was a technical nightmare, and, once separated,
the neurons had an annoying habit of dying before people
had time to perform experiments with them.
"It's
amazing. You'd work hours to purify these things, make a
culture, go away, come back the next day and they'd all
be dead," said Barres.
Barres'
lab has tackled both problems, gently sifting through tiny
slices of rat brain to get neurons away from glia, then
figuring out how to keep the neurons alive.
To get
95% pure cultures of neurons, they first use an enzyme derived
from papaya to lightly chew up the glue that sticks brain
cells together.
Next,
they "pan" the mix of separated cells, much as
a prospector pans for gold, in specially designed plates.
The plates are coated with chemicals to which one type of
cell--glia or neuron--sticks. Cells that don't stick stay
in the liquid. By selecting stuck cells or floating cells,
scientists can select neuron, or glia, as they choose.
Barres'
lab has also concocted a simple soup of chemicals that keep
the neurons alive and kicking when the glia aren't around
to nourish them any more.
In the
most recent experiment, postdoctoral researcher Erik Ullian
and co-workers carefully panned their neurons and allowed
them to grow and send out thousands of delicate fibers.
They stained the cells so the synapses would glow brightly,
viewed the cells under a microscope--and noted many fewer
synapses than was normal.
Only
after they'd looked at the cells again and again, in a set
of successive experiments, were they absolutely sure they
were right.
Now
Barres' lab is working hard to find out just how glia promote
synapse formation. What signals do they send to the neurons?
What chemicals do they secrete? Researchers are also thinking
about the role glia play in disease. Anything that causes
glia to wither and die might cause synapses to wither and
die too.
Another
prime possibility: When brains are injured, or when brains
are damaged by conditions such as epilepsy, it's very common
for too many glia to grow. These, in turn, could cause extra
synapses to grow. And while synapses are important, making
too many of them could be dangerous--since neurons, when
over-excited, tend to die.
Barres'
discovery, in fact, creates a whole new avenue for neuroscientists
to explore.
"We
should stop being neuron chauvinists," Barres said.
"We should start realizing that everything our brain
does is a dialogue between the neurons and the glia."
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