Taking astrocytes seriously

May 17 2006

By blowing gentle puffs of air onto a mouse's whiskers and watching how its brain reacts, scientists are discovering that a long-overlooked signaling system in the brain is crucial to our everyday activity.

The work is the latest in a growing body of evidence that star-shaped brain cells known as astrocytes aren't simply support cells but are stars of the brain in their own right, say researchers at the University of Rochester Medical Center who did the study. The work will be reported in a paper in the June issue of Nature Neuroscience and is now available online.

"Now people have to take astrocytes seriously," said Maiken Nedergaard, M.D., Ph.D., professor in the Department of Neurosurgery and a member of the Center for Aging and Developmental Biology, whose team did the research. In the past few years she has found that the cells, long thought to simply nourish other cells and clean up their wastes, are central to diseases like epilepsy, spinal cord injury, and maybe even Alzheimer's disease.

For decades scientists have studied the swift signaling activity of the brain's better-known cells, the neurons, by recording their electrical activity. But astrocytes don't fire in the same way, and conventional techniques don't record their activity. Many scientists looked at this "silence" as evidence that astrocytes weren't communicating much, and they assumed that astrocytes, which are 10 times as plentiful as neurons, simply don't make up an important signaling network.

So Nedergaard devised a new way to "listen" for astrocyte activity, developing a sophisticated laser system to look at their activity by measuring the amount of calcium inside the cells. By listening in the right way, her team has made a series of discoveries that have brought the once-obscure astrocyte and its signaling capability into prominence.

In the latest work, graduate student Xiaohai Wang, M.D., led a team that focused the laser system on the brain cells of mice as their whiskers were gently pushed about with gentle puffs of air. Whiskers make up one of the most important information-gathering mechanisms that many animals have, used in much the same way that people rely on their hands and eyes to learn about their environment. A large part of a mouse's brain is devoted to processing the information their whiskers send its way - a change in air current might indicate a nearby predator, for instance, or a certain texture might indicate a yummy bite of cheese nearby. Scientists have found that the way an animal's brain learns information from its whiskers mirrors the way people learn from their senses.

Wang and Nedergaard found that with a puff of air on a whisker, astrocytes become activated - pumped with calcium - in the section of the brain that processes sensory input. The chemical step is a sign that the cell has been triggered in some way and is ready to send out a signal itself. While it's been shown before that astrocytes can become activated under extreme conditions in the laboratory, Nedergaard said this is the first time that such activity has been seen in an organism during everyday circumstances.

"This opens the door to whether these cells are part of everyday higher cognitive functioning that defines who we are as humans," she said.

For years astrocytes have been related to the status of helper to the neurons, which rely on astrocytes to bring nutrients and to clean up after them. While scientists have known that neurons fire electrically in spectacular fashion to send signals, it's only recently that the slower chemical signaling network of the more numerous astrocytes has become widely appreciated by scientists.

Wang's work is the latest in a series of papers by Nedergaard and colleagues scuttling the notion that astrocytes are merely support cells for neurons. More than a decade ago Nedergaard discovered that astrocytes send signals to the neurons, and the neurons respond. Since then she has made a series of findings that neurons and astrocytes talk back and forth, indicating that astrocytes are full partners in the basic working of the brain.

"Our take on this is that astrocytes really are part of higher brain function," said Nedergaard, noting that astrocytes are much more complex in people than in rodents, while neurons aren't that much different - just longer.

"For years, people have considered the astrocyte like a housekeeper that cleans up after the neurons. But perhaps astrocytes are more like the parents who don't just clean up after their children but actually have some influence over them. Perhaps the astrocytes at times tell the neurons what to do."