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Lab publishes findings on serotonin in autism mouse models

Posted on Thursday, April 05, 2012 · Volume: XLV · Issue: 7


(Left to right) W. Anthony Owens, Lynette Daws, Ph.D., and Brent J. Thompson, Ph.D., of the School of Medicine co-authored a report on serotonin transporter activity in a new mouse model of autism spectrum disorder. Dr. Thompson helped develop the mouse model while at Vanderbilt University.
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(Left to right) W. Anthony Owens, Lynette Daws, Ph.D., and Brent J. Thompson, Ph.D., of the School of Medicine co-authored a report on serotonin transporter activity in a new mouse model of autism spectrum disorder. Dr. Thompson helped develop the mouse model while at Vanderbilt University.clear graphic

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Contact: Will Sansom, 210-567-2579

SAN ANTONIO (March 29, 2012) — A UT Health Science Center San Antonio laboratory is one of only a handful worldwide where scientists measure how well serotonin is transported in the brains of living animals. Properly regulated levels of serotonin — which carries signals from one nerve cell to another across gaps called synapses — are associated with feelings of well-being.

This expertise in the School of Medicine at the Health Science Center supported a paper published March 20 in the Proceedings of the National Academy of Sciences on a new mouse model of autism spectrum disorder (ASD). Serotonin is abnormally regulated in some children with ASD. A group at Vanderbilt University developed the mouse model, which expresses a genetic mutation of the serotonin transporter (SERT) that is found in subpopulations of humans with ASD.

Minute alteration
During development of the brain, serotonin plays an important role in the proper growth and connectivity of neurons. “This small genetic mutation in SERT is thought to alter brain serotonin levels during neurodevelopment, resulting in subtle changes in the brain that may underlie some of the behavioral traits of autism," said co-author Brent J. Thompson, Ph.D., assistant professor of cellular and structural biology in the School of Medicine. He helped develop the mouse model at Vanderbilt before moving to San Antonio in 2009.

Co-author W. Anthony Owens is a senior research associate in the lab of Lynette Daws, Ph.D., professor of physiology in the School of Medicine. Owens performs in vivo high-speed chronoamperometry, a state-of-the-art technique in which electrodes are placed in brain regions of anesthetized mice to measure SERT activity in a millisecond (one-thousandth of a second) time scale.

“In collaboration with the team at Vanderbilt, we applied an electrochemical technique to quantify SERT activity in the living brains of these mice,” Dr. Daws, a co-author, said. “By recording clearance of serotonin in brain regions that we think are important in regulating social behavior, we can measure how well these serotonin transporters are working, or not working, in disease states.”

Too many RPMs
The Daws team found that the genetic mutation speeds up SERT activity in the brain. The implication is that serotonin released from one neuron is taken back up by the transporter too efficiently and is less able to get to the next neuron to “transmit” the signal. The Vanderbilt team found this “overactive” SERT was associated with behaviors relevant to autism.

“The Vanderbilt group called on us to show that their molecular manipulations of the mouse SERT gene really mattered as far as the function of the serotonin transporter in the living animal,” Dr. Daws said. “This mouse provides an exciting new model to study autism and potentially guide the development of novel treatments.”

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The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving federal funding. Research and other sponsored program activity totaled $231 million in fiscal year 2011. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced approximately 26,000 graduates. The $736 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

 
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