Protein Linked to Depression

New antidepressants might result from this discovery, researchers say

THURSDAY, Jan. 5, 2006 (HealthDay News) -- Researchers have identified a protein that seems to play a key role in fighting depression.

The protein, called p11, appears to help regulate signaling of the brain chemical serotonin. A target of the antidepressants called selective serotonin reuptake inhibitors (SSRIs), which include Prozac, serotonin has been linked to depression and anxiety disorders, the study noted.

"Mice deficient in this protein, called p11, display depression-like behaviors, while those with sufficient amounts behave as if they have been treated with antidepressants," study author Paul Greengard, a Nobel Prize-winning neuroscientist at Rockefeller University in New York City, said in a prepared statement.

The experiments with mice revealed how p11 works with the serotonin receptor 5-HT1B, which has also been associated with obsessive-compulsive disorder, drug addiction, anxiety and aggression, as well as depression.

The findings appear in the Jan. 6 issue of Science.

"P11 can be viewed as a protein that links the pathophysiology of depression with the serotonin system," said lead study author Per Svenningsson, from the department of physiology and pharmacology at the Karolinska Institute, in Stockholm, Sweden.

Depression is often treated with compounds such as SSRIs, which increase levels of serotonin. "The released serotonin acts on 14 serotonin receptors, some of which mediate therapeutic actions and some of which mediate side effects," he added.

The researchers studied one specific serotonin receptor, the 5-HT1B receptor, and found that it interacts with p11. The protein is depleted in tissue in so-called "helpless" mice, which exhibit behaviors similar to depressed humans. It's also depleted in the brain tissue of depressed patients, the researchers said.

"Mice that over-express p11 are hyperactive, and act as if they are on antidepressant medication," Svenningsson said. Conversely, mice that have no p11 "act as they are somewhat depressed and show less responsivity towards antidepressant medications," he added.

While there's no immediate clinical application for this finding, Svenningsson said "this study emphasizes that 5-HT1B receptor, with its interaction with p11, may be linked to depression."

"It may turn out that future antidepressants could target this 5-HT receptor, and probably some additional 5-HT receptors, but not necessarily all 5-HT receptors. Hopefully, such antidepressants will have fewer side effects," Svenningsson said.

One expert agrees that p11 might become a target for antidepressants in the future.

"Whilst p11 is a potential source of new therapies, unfortunately at the moment we do not know enough about p11 to target it selectively with drugs," said Trevor Sharp, a reader in pharmacology at the University of Oxford, Great Britain, and author of an accompanying perspective article in the journal.

"However, p11 is functionally linked to a serotonin receptor, and there are a number of drugs in development that act selectively on this receptor, and some of these drugs show antidepressant potential in laboratory models," Sharp said. "We will know in a few years whether these kinds of drugs are better than the antidepressant treatments that we already have."

More information

The U.S. National Institute of Mental Health can tell you more about depression.

SOURCES: Per Svenningsson, Ph.D., department of physiology and pharmacology, Karolinska Institute, Stockholm, Sweden; Trevor Sharp, Ph.D., reader, pharmacology, University of Oxford, Great Britain; Jan. 6, 2006, Science
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