Cells originally believed to be no more than support for neurons have been getting a second-look lately, and a recent study suggests they may be critical to a fundamental bodily function: breathing.

The finding, published online today (July 15) by Science, further expands scientists' vague understanding how astrocytes -- glial cells in the brain named for their star-shape -- function in the brain, and offers a new way to investigate disorders associated with respiratory failure, such as Sudden Infant Death Syndrome.

Astrocytes Karin Pierre, Institut de Physiologie, UNIL, Lausanne Wikimedia Commons

"This shows us that we are far from understanding the complexity of the brain," said Cendra Agulhon, a researcher at the University of North Carolina-Chapel Hill who recently published a controversial paper suggesting astrocytes don't play a role in neural transmission. "The more we learn, the more we add layers of complexity."

Glial cells outnumber neurons by ten to one in the brain, but for a long time, they were considered simply the glue ('glial' means 'glue' in Greek) that holds the brain together. In recent years, however, scientists have postulated many other functions for these mysterious cells: sculpting neural circuits during development, assisting with brain microcirculation, and, recently, aiding memory formation.

Interested in understanding the central nervous control of breathing, Alexander Gourine at the University College London and collaborators at the University of Bristol surmised that astrocytes might be involved in sensing chemical composition of the blood because they are wrapped around major blood vessels entering the brain. "So they would be first to see changes in blood pH and levels of carbon dioxide," said Gourine. However, the lack of tools to monitor or control astrocytes' activity in a living brain delayed a test of that hypothesis. Until recently.

Unlike neurons, which are electrically excitable, astrocytes react to changes in calcium concentrations. To monitor astrocytes's activity, Gourine and colleagues used a gene transfer technique to express a calcium sensor in astrocytes located in the medulla oblongata of rats, an area known to contain respiratory chemosensors. The cells "sensed" changes in pH, a measure of how much carbon dioxide is in the blood, by rapidly increasing intracellular calcium levels. When these responses were simulated in live animals, the astrocytes released ATP, which stimulated local neurons and increased breathing in rats. The neurons and astrocytes seem to work like partners to regulate breathing, said Agulhon. "It's like a team," she added. "Partnerships of cell [types] in the brain may be working to modulate and maintain physiological mechanisms."

It might be interesting to examine the role of astrocytes in breathing conditions like apnea, a sleep breathing disorder, said Agulhon. "Maybe astrocytes are good targets," she added. The new knowledge could also be relevant for conditions associated with sudden respiratory failure, like SIDS. "We can only speculate at this stage," said Gourine. "Glial dysfunction may be contributing to respiratory failure, but at the moment we have no evidence."

The next step is to find a way to inhibit astrocytes in vivo, said Gourine. Then, researchers will be able to test the numerous hypotheses for the functions of astrocytes in the brain. It is likely astrocytes in various regions of the brain serve different functions, said Agulhon, just as many different types of neurons do many different jobs.

"Depending on where they are and what kind of neurons they are surrounded by, they will function differently," she added. "We are just starting to understand how important astrocytes can be."

A.V. Gourine et al. "Astrocytes control breathing through pH-dependent release of ATP," Science, published online July 15, 2010, doi:10.1126/science.1190721.


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