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Jeremy Veenstra-VanderWeele, M.D., left, Randy Blakely, Ph.D., and colleagues are studying how disrupting serotonin signaling in the brain can impact behavior. (photo by Susan Urmy)

Study explores link between serotonin signaling, autism

BY: BILL SNYDER

3/22/2012 - 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, Ph.D., and James Sutcliffe, Ph.D., 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, M.D., 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.”

As many as 30 percent of children with autism have elevated blood levels of serotonin, a finding described as “hyperserotonemia.” The mice created by Veenstra-VanderWeele, Blakely and their colleagues also display hyperserotonemia, the first instance that a mouse model of autism has been shown to exhibit this biomarker.

No mouse model can completely explain or reproduce the human condition. Neither does a single genetic variation cause autism. Experts believe the wide spectrum of autistic behaviors represents a complex web of interactions between many genes and environmental factors.

But animal models are critical to exploring more deeply the basis for the developmental changes that are observed in ASD. The scientists are using these mice to explore how altered brain serotonin levels during development may produce long-lasting changes in behavior and impact the risk for autism.

Scientists from the National Institute of Mental Health, the Medical University of South Carolina and the University of Texas Health Science Center in San Antonio contributed to the study.

The research was supported by the National Institutes of Health, the advocacy organization Autism Speaks and the American Academy of Child and Adolescent Psychiatry.

©2014 Vanderbilt University Medical Center
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