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Nobelist discovers antidepressant protein in mouse brain

A protein that seems to be pivotal in lifting depression has been discovered by a Nobel Laureate researcher funded by the National Institutes of Health's National Institute of Mental Health (NIMH).

"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," explained Paul Greengard, Ph.D., a Rockefeller University neuroscientist who received the 2000 Nobel Prize in Physiology or Medicine for discoveries about the workings of such neuronal signaling systems. He and his colleagues found that p11 appears to help regulate signaling of the brain messenger chemical serotonin, a key target of antidepressants, which has been implicated in psychiatric illnesses such as depression and anxiety disorders. They report on their findings in the January 6, 2005 issue of Science.

Brain cells communicate with each other by secreting messengers, such as serotonin, which bind to receptors located on the surface of receiving cells. Serotonin selective reuptake inhibitors (SSRIs), medications commonly prescribed for anxiety and depression, compensate for reduction in serotonin signaling by boosting levels and binding of serotonin to receptors. Previous studies have suggested that serotonin receptors are essential in regulating moods and in mediating the effects of SSRIs, but given the complexity of the serotonin system, exactly how these receptors work remains a mystery.

To explore how a particular serotonin receptor (5-HT1B) functions, Greengard and colleagues conducted tests to find out what proteins these receptors interact with in brain cells. They found that 5-HT1B interacts with p11, and according to Greengard, p11 plays a role in the recruitment of receptors to the cell surface where they are more functional.

This finding led the researchers to suspect that p11 levels might be directly involved in the development of depression, anxie
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Source:NIH/National Institute of Mental Health


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