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Brain's bubble wrap may be lots more

Boston researchers are putting the focus on cells long thought to be minor players but which might help neuroscience advance

By Carolyn Y. Johnson
Globe Staff / May 31, 2010

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They have long been dismissed as the brain’s Bubble Wrap, packing material to protect precious cells that do the real work of the mind. But glial cells — the name literally means “glue’’ — are now being radically recast as neuroscientists explore the role they play in disease and challenge longstanding notions about how the brain works.

More than a century ago, scientists proposed the “neuron doctrine,’’ a theory that individual brain cells called neurons are the main players in the nervous system. It became an underpinning of modern neuroscience and led to major advances in understanding the brain, but it has become increasingly apparent that the other 85 percent of brain cells, glia, do more than just housekeeping.

“In a play in a theater, it’s not just the actors on the stage, but the whole ensemble that is critical for that production to be perfect,’’ said Philip Haydon, chairman of the neuroscience department at Tufts University School of Medicine. “The players on the stage are neurons, but if you don’t have every person backstage, you don’t have a production, and what we’re now realizing is this whole support cast [of glia] is essential for normal brain function.’’

Haydon became curious about glia nearly two decades ago as an unintentional consequence of an experiment. He killed neurons in a dish of brain cells and left the glia, expecting to see the chemical signals that neurons use to communicate with one another disappear. To his surprise, the signals did not stop — suggesting the glia were not passive.

From there, he and others have found that the glia take part in an expanding number of roles in the brain, with research groups across the country now focusing on the part they play in everything from normal brain development to disease.

Haydon and Beth Stevens, a neuroscientist at Children’s Hospital Boston, are planning to launch a “glia group’’ in Boston, bringing together researchers interested in this relatively neglected area of neuroscience.

“For a long time, people studying glia hung out with glia people,’’ while the rest of the neuroscientists — the vast majority — studied neurons, Stevens said. “For the field to move forward, you couldn’t just talk about glia in isolation.’’

There are three main types of glia in the brain.

The most prevalent, called astrocytes, have branching feet that wrap around blood vessels and deliver nutrients to neurons.

Another type, oligodendrocytes, create the myelin sheath, electrical insulation around parts of neurons.

The last type of glial cell is microglia, the immune system cells of the brain.

New studies are uncovering additional roles for the cells, with much excitement and questions sparked by the finding that glia can send and receive signals and even influence neuron behavior.

In a study published last year in the journal Neuron, Haydon and colleagues found that glia are involved in causing sleepiness. They blocked the activity of glia in sleep-deprived mice and discovered the mice did not need as much catch-up sleep and had the memory abilities of well-rested mice.

A study published this month in Nature Neuroscience found that a reaction that occurs in glial cells in brain diseases such as epilepsy seems to cause changes in the way they interact with neurons, potentially creating the kinds of problems typical of neurological diseases — such as those involving cognition, learning, memory, and movement.

Other researchers are looking at the role these cells might play in chronic pain, in the developing brain, and in a range of diseases.

“This has completely opened up our ideas about a new dimension of brain function — that’s what’s so exciting,’’ said R. Douglas Fields, chief of the nervous system development and plasticity section at the National Institute of Child Health and Human Development, and author of “The Other Brain,’’ a book about glial cells.

Still, the field is not without controversy. In March, a paper in the journal Science challenged one of its fundamental findings — the mechanism by which astrocytes interact with neurons. Using new tools, scientists found that astrocytes did not influence neuron function as researchers previously thought.

“Things are not as simplistic as we have been thinking so far,’’ said Cendra Agulhon, a research associate at the University of North Carolina at Chapel Hill, the lead author of the paper that challenged current thinking about glial cells.

Many of the questions about the cells are likely to be untangled in coming years as researchers work toward a better understanding and consider them as new targets for neurological disease. What may ultimately change, however, is the conventional notion that the brain is just a complicated computer.

“People tend to view neurons as circuit elements and completely interchangeable parts — as if the brain is really just bits and it doesn’t matter what its made of,’’ said Christopher Moore, a neuroscientist at the Massachusetts Institute of Technology. “The brain doesn’t work like that. . . . There’s some really beautiful evidence suggesting they [glial cells] are doing something far more interesting than what they get credit for.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.