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Novel mouse model for autism yields clues to a 50-year-old mystery
Date:3/20/2012

Early disruptions in serotonin signaling in the brain may contribute to autism spectrum disorder (ASD), and other "enduring effects on behavior," Vanderbilt University researchers report.

Serotonin is a brain chemical that carries signals across the synapse, or gap between nerve cells. The supply of serotonin is regulated by the serotonin transporter (SERT). In 2005, a team of Vanderbilt researchers led by Randy Blakely and James Sutcliffe identified rare genetic variations in children with ASD that disrupt SERT function.

In a new study published this week in the Proceedings of the National Academy of Sciences (PNAS), the researchers report the creation of a mouse model that expressed the most common of these variations.

The change is a very small one in biochemical terms, yet it appears to cause SERT in the brain to go into "overdrive" and restrict the availability of serotonin at synapses.

"The SERT protein in the brain of our mice appears to exhibit the exaggerated function and lack of regulation we saw using cell models," said Blakely, director of the Vanderbilt Silvio O. Conte Center for Neuroscience Research.

"Remarkably, these mice show changes in social behavior and communication from early life that may parallel aspects of ASD," noted first author Jeremy Veenstra-VanderWeele, assistant professor of Psychiatry, Pediatrics and Pharmacology.

The researchers conclude that a lack of serotonin during development may lead to long-standing changes in the way the brain is "wired."

In 1961, investigators at Yale discovered that as many as 30 percent of children with autism have elevated blood levels of serotonin, a finding described as "hyperserotonemia."

Since then, these findings have been replicated many times. Indeed, hyperserotonemia is the most consistently reported biochemical finding in autism, and is a highly inherited trait. Yet, the cause or significance of this "
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Contact: Bill Snyder
william.snyder@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert  

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