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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

Immune p38-alpha MAPK activation: Convergent mechanism linking autism models

Principal Investigator

Principal Investigator

Blakely, Randy

Description

Description

Autism appears to be caused by a complex interplay of genetic and environmental factors. Over the past decade, scientists have established multiple animal models of autism using both genetic and environmental manipulations, demonstrating the presence of communication and social behavior deficits in these animals, as well as the presence of repetitive behaviors characteristic of i0ndividuals with autism. Randy Blakely and his colleagues at Vanderbilt University in Nashville, Tennessee, believe that the activation of a class of enzymes known as p38-alpha MAP kinases (p38-alpha MAPK) may underlie the ability of both genetic and environmental factors to produce autism. Blakely’s efforts in autism research began with the 2005 discovery of multiple rare genetic mutations in individuals with autism that alter the structure of the serotonin transporter, or SERT, protein. SERT is known to many as the brain’s major target for antidepressant medications such as Prozac. Blakely and his team reported the cloning of the human SERT gene in 1993 and, a few years later, demonstrated that SERT is expressed early in brain development, where it could contribute to developmental disorders such as autism. In a search for regulators of SERT, Blakely’s team identified p38-alpha MAPK, a gene known to play critical roles in immune system function, including those arising as a consequence of either maternal or neonatal infection. What’s more, a genetic mouse model Blakely produced to express the most common of the SERT mutations he found in individuals with autism displays not only behavioral features reminiscent of autism but also inappropriate regulation of SERT by p38-alpha MAPK. These findings drive Blakely’s efforts to determine whether p38-alpha MAPK signaling is a key link in how SERT and serotonin control brain development and can link immune system activation to features of autism, as well as be targeted by new autism drugs.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

212061

Current Award Period

Current Award Period

2014-2017

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 2SA. Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010. IACC Recommended Budget: $9,800,000 over 4 years. (Fever studies to be started by 2012.)

Project Link

Project Link

Immune p38-alpha MAPK activation: Convergent mechanism linking autism models (External web link)

Institution

Institution

Florida Atlantic University

State/Country

State/Country

Florida

Project Number

Project Number

323427

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Immune p38-alpha MAPK activation: Convergent mechanism linking autism models | 105403 | 2014 | 323427

 
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