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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Evaluating hyperserotonemia as a biomarker of sensory dysfunction in autism spectrum disorder

Principal Investigator

Principal Investigator

Muller, Christopher

Description

Description

Autism spectrum disorder (ASD) is a group of developmental disorders that share the core features of impairment in social communication and interaction, as well as restricted, repetitive behavior. Although there are several lines of evidence supporting a strong genetic basis for ASD, research has largely been hindered by the disorder's genetic and behavioral heterogeneity. One avenue into unraveling the complexity of ASD is to identify biological traits that may define a particular group of affected individuals. One of the most consistently replicated findings in individuals with ASD is elevated whole blood serotonin (5-HT), found in 25-30% of children. Platelets contain 99% of blood 5-HT, which is taken up via the serotonin transporter (SERT), a key regulator of 5-HT homeostasis in the periphery and the brain. Despite the consistent findings of peripheral 5-HT dysfunction in ASD, it is currently unknown how this biological trait connects to brain development. There is mounting evidence that 5-HT plays a role in a number of developmental processes that could impact the formation of brain circuits relevant to ASD features. Interestingly, several rare gain-of-function SERT mutations have been reported that associate with autism and rigid-compulsive behavior in males. The most common of these SERT mutations, Gly56Ala, also shows a strong association with sensory aversion. Sensory dysfunction is common in ASD, with 45-95% of individuals presenting with abnormal sensory behavior. However, the underlying causes of sensory dysfunction in ASD remain unknown. In an effort to understand how 5-HT dysfunction can impact the formation of brain circuits relevant to ASD, our lab generated a mouse carrying the ASD-associated SERT Gly56Ala mutation. Previous studies have indicated that manipulating brain levels of 5-HT during development can disrupt the formation of cortical sensory maps involved in processing stimuli in our environment. This project hypothesizes that the SERT Ala56 mutation alters 5-HT signaling during development and disrupts the formation and function of sensory maps in the brain, resulting in the abnormal sensory behavior observed in ASD. The project will use the SERT Gly56Ala mouse model to examine 1) the progression of 5-HT dysfunction in the brain across development; 2) the organization and physiology of thalamocortical axons that establish sensory maps; and 3) the patterns of brain activation upon sensory stimulation.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

28600

Current Award Period

Current Award Period

2012-2014

Strategic Plan Question

Strategic Plan Question

Question 4: Which Treatments And Interventions Will Help?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.

Project Link

Project Link

Evaluating hyperserotonemia as a biomarker of sensory dysfunction in autism spectrum disorder (External web link)

Institution

Institution

Vanderbilt University

State/Country

State/Country

Tennessee

Project Number

Project Number

7847

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Evaluating hyperserotonemia as a biomarker of sensory dysfunction in autism spectrum disorder | 28600 | 2013 | 7847
Evaluating hyperserotonemia as a biomarker of sensory dysfunction in autism spectrum disorder | 0 | 2014 | 7847

 
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