A new study from Vanderbilt Medical Center illustrates the power of the in silico — or computer-based — research method to study the connection between iron levels and the neurotransmitter serotonin. Serotonin is one of the brain's major players and is involved in depression, mood, learning and memory, sleep, and sexual behavior, to name just a few.

'[B]ecause SERT is such an important drug target in treating anxiety, depression and OCD, we need to stop and think about how iron might be influencing these disorders.'

The serotonin transporter protein SERT is crucial in regulating serotonin activity by helping move the serotonin molecules from the spaces between nerve cells back into the cell that released it. This process allows for a kind of serotonin recycling program. Variation in SERT levels have been shown to be involved in alcoholism and depression, and these proteins are often the target of popular medications like selective serotonin reuptake inhibitors, or SSRIs.

Researcher Randy Blakely and his team discovered that, by a fortuitous mix-up in ordering mice, the animals they had been using had a variation in the SERT gene known as SERT GK. By doing some quick searching on Mouse Phenome Database, they learned that the function of the SERT transporter is actually diminished in these mice.

Blakely and his partners found that mice of all different genetic backgrounds, but all possessing the SERT GK variant, performed differently on depression and anxiety tests — this was not terribly surprising given the already-established role of a similar gene in humans. By combing a database of mouse traits ranging from biochemical to anatomical, the team was able to determine new differences between the SERT GK mice and those with the normal version of the gene.

One of their key findings was that iron levels in the brains of the GK mice were significantly higher than in other mice. This discovery is important because not only is iron needed to generate serotonin, but the SERT gene has been shown to be important in regulating iron levels in the brain.

Blakely says that "[b]ecause SERT is such an important drug target in treating anxiety, depression and OCD, we need to stop and think about how iron might be influencing these disorders."

The study also points to the importance of the internet in scientific research these days: "[t]he broader number of findings in our paper derives not from (experiments) we did, but from what the (scientific) community collectively did to populate the database," adds Blakely. This, he says, is even more beneficial because it limits the number of animals needed to carry out this type of important research.