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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

Interactions of environment and molecular pathways on brain overgrowth in autism: Maternal inflammation and the PI3/AKT pathway

Principal Investigator

Principal Investigator

Lebelle, Janel

Description

Description

It has been recently reported that some individuals with autism show premature brain overgrowth early in development. Recent studies have demonstrated that brain overgrowth can be caused by the interaction of environmental factors such as maternal inflammatory response (MIR) with genetic susceptibility during periods of vulnerability in fetal development. This research seeks to understand mechanisms of MIR-induced macrocephaly in autism spectrum disorder (ASD). One mechanism by which genes and environment might interact in maternal inflammatory response is through the production of reactive oxygen species (ROS). While it is well known that high levels of ROS are toxic to cells, the effects of low levels of ROS are unknown. Maternal and embryonic ROS levels can be influenced by many environmental factors including viral infection and allergic/immune disorders which have also been positively associated with macrocephaly. This lab has previously shown that low levels of ROS produced by NADPH oxidases (NOX) enhance neural stem cell self-renewal, at least in part due to disruption of PTEN function. Here, they will determine whether there is a pathogenic link between NOX-generated ROS and brain size in a rodent model.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

211200

Current Award Period

Current Award Period

na

Strategic Plan Question

Strategic Plan Question

Question 3: What Caused This To Happen And Can This Be Prevented?

Strategic Plan Objective

Strategic Plan Objective

Yellow dot: Objective has some degree of funding, but less than the recommended amount. 3SE. Support at least two studies to determine if there are subpopulations that are more susceptible to environmental exposures (e.g., immune challenges related to infections, vaccinations, or underlying autoimmune problems) by 2012. IACC Recommended Budget: $8,000,000 over 2 years.

Project Link

Project Link

Interactions of environment and molecular pathways on brain overgrowth in autism: Maternal inflammation and the PI3/AKT pathway (External web link)

Institution

Institution

University of California, Los Angeles

State/Country

State/Country

California

Project Number

Project Number

4954

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Interactions of environment and molecular pathways on brain overgrowth in autism: Maternal inflammation and the PI3/AKT pathway | 211200 | 2008 | 4954

 
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