Feeling relaxed? Thank your immune system. A new study suggests that mast cells, which lead the charge against microbial invaders, may also be responsible for tamping down anxiety.
Mast cells have a split personality. They are often the first cells to attack foreign microbes, and they coordinate and control other immune cells. Yet they can also be traitors. Upon encountering pollen or dust, they release histamines and other chemicals that can trigger allergies and asthma. Mast cells may also incite or abet conditions as diverse as atherosclerosis, rheumatoid arthritis, autism, and migraines. Although researchers know the functions of many mast cells in the body, a subset that inhabits the brain has remained mysterious.
To learn more about these cells, neuroscientist Rae Silver of Columbia University and colleagues subjected mice that lack mast cells to a series of behavioral tests. The researchers measured how much the animals moved around and gauged their responses to stimuli such as a puff of air, an odor, or loud sounds. The mice strayed from the rodent norm in only one way: they were particularly anxious. For instance, mice without mast cells hesitated more than 80 seconds longer than did control mice before stepping out into the open. Mast cell–deficient mice were also reluctant to explore unfamiliar sections of a maze, the team reports online today in the Proceedings of the National Academy of Sciences.
The scientists saw similar results when they dosed normal mice with cromolyn, which prevents mast cells from releasing their chemicals. Cromolyn can't enter the brain through the blood, and the researchers found that injecting it into the abdomen had no effect. But injecting it into the brain turned the animals into nervous nellies. Which mast cell product soothes the anxious brain isn't clear, Silver says. Histamine is a candidate, although previous work indicates it can worsen or ease anxiety, depending on which cellular receptor it prods. Mast cells also emit serotonin, a mood-modifying molecule, and a host of other influential compounds.
What's intriguing about the results is that high anxiety appears to be the default condition, at least in the rodents, says neuroscientist Daniel Levy of Harvard Medical School in Boston, whose work connects mast cells to migraines. Mast cells could blunt anxiety by acting on specific neurons or by altering blood flow to particular brain regions, Silver says, although she notes that no one knows where in the brain anxiety originates. Because of the difficulties of studying the cells in the human brain, it will be tricky to determine whether mast cell malfunctions underlie anxiety disorders, she adds. But the researchers hope to glean clues from patients with allergies or mastocytosis, an oversupply of mast cells.
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