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Scripps Florida Scientists Identify Key Neurotransmitter Receptor as Potential Target for Individualized Treatment of Autism Spectrum Disorder

Grant of $2.4 Million Will Support Further Research

JUPITER, FL – September 30, 2015 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have uncovered a significant—and potentially treatable—relationship between a chemical that helps transmit signals in the brain and genetic mutations present in a subset of individuals with autism spectrum disorder.

The new research findings, which were published recently in the journal PLoS One, focus on the role that the neurotransmitter serotonin plays in the development of social behavior. Serotonin, together with the serotonin receptors it activates in the brain, plays a significant role in neurological processes, including mood, anxiety, aggression and memory.

The study made use of an animal model of mutations in the gene Pten, a risk factor present in a subgroup of individuals with autism. Treatment of this model with a drug that suppresses the activity of a particular serotonin receptor, 5-HT2cR, can have a dramatic effect.

“Our research shows that targeting one specific serotonin receptor can reverse social deficits in a mouse model of the autism risk gene Pten,” said Julien Séjourné, the first author of the new study. “This discovery is important for understanding the role of this specific subtype of serotonin receptor in autism-relevant behaviors and could lead to new therapeutic strategies.”

“We found a striking contrast between the effects of dialing down the activity of the receptor using a drug, which improved social deficits in the Pten model, versus removing the receptor completely by mutation, which actually impaired social behavior,” added TSRI Assistant Professor Damon Page, who led the study. “Important issues will be uncovering the mechanism by which modulating serotonin receptor activity can influence autism-relevant symptoms and identifying the time window and dose range where targeting serotonin receptors is most effective.”

Page was recently awarded a $2.4 million, five-year grant from the National Institute of Mental Health of The National Institutes of Health (NIH) to further study the relationship between abnormal patterns of brain growth, neurotransmitter signaling and the behavioral and cognitive symptoms in individuals with autism spectrum disorder.

“The new grant will let us expand our research into the relationship between specific risk factors, altered brain development and key neurotransmitter systems, with the ultimate goal of moving toward individualized treatments for particular subgroups of individuals with autism spectrum disorder,” he said.

In addition to Page and Séjourné, other authors of the study, “Social Behavioral Deficits Coincide with the Onset of Seizure Susceptibility in Mice Lacking Serotonin Receptor 2c,” are Danielle Llaneza of TSRI and Orsolya J. Kuti of The Massachusetts Institute of Technology. See http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136494

The work was supported by Ms. Nancy Lurie Marks and the National Institutes of Health.

The number of the grant is 1R01MH105610.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates and 20 members of the National Academy of Science, Engineering or Medicine—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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Damon Page is a biologist at the Florida campus of The Scripps Research Institute. (High-res image)


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