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Nobelist discovers antidepressant protein in mouse brain

ty and similar psychiatric illnesses thought to involve faulty serotonin receptors. To test this idea, the researchers examined p11 levels in the brains of depressed humans and "helpless" mice, considered a model of depression since they exhibit behaviors similar to those of depressed humans. They compared these two groups to non-depressed humans and control mice. Levels of p11 were found to be substantially lower in depressed humans and helpless mice, which suggests that altered p11 levels may be involved in the development of depression-like symptoms.

The researchers also examined the effect of treatments designed to boost weak serotonin systems on p11 levels in brain cells by administering to mice two types of antidepressants ?a tricyclic, a monoamine oxidase (MAO) inhibitor ?and electroconvulsive therapy (ECT).

"These three different ways of treating depression all caused an increase in the amount of p11 in the brains of these mice," said Greengard. "They all work in totally different ways, but in all cases they caused the same biochemical change. So, it's pretty convincing that p11 is associated with the main therapeutic action of antidepressant drugs."

Since humans and mice with symptoms of depression were found to have substantially lower levels of p11 in brain cells compared to non-depressed animals, Greengard and colleagues hypothesized that if p11 levels were increased, mice would exhibit antidepressant-like behaviors, and if p11 were reduced, mice would exhibit depression-like symptoms.

As hypothesized, mice with over-expressed p11 genes, compared to control mice, had increased mobility in a test that is used to measure antidepressant-like activity. They also had more 5-HT1B receptors at the cell surface that were capable of increased serotonin transmission.

The opposite occurred when researchers molecularly knocked out the p11 gene in mice. Compared to control mice, knockout mice had fewer receptors at the ce
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Source:NIH/National Institute of Mental Health


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