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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