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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

Il-6-mediated Jak2/Stat3 signaling and brain development

Principal Investigator

Principal Investigator

Tan, Jun

Description

Description

It has been suggested that activation of pregnant mother's immune system by infections can affect the brain of the developing fetus and thus behavior of young and adult offspring. Most recently, it was reported in mice that increased interluekin-6 (IL-6; a chemical messenger of the immune system) in the mother's blood plays a key role in altering fetal brain development and impairing behaviors in social interactions in the offspring. Interestingly, these effects could be avoided by blocking IL-6 chemically with an antibody or by genetically altering mice so they are deficient in IL-6. Preliminary studies showed that natural citrus molecules, luteolin and diosmin, inhibit the signaling mechanism (JAK2/STAT3) in neurons which carries IL-6's signal to the nucleus. When luteolin and diosmin were applied to pregnant mice, researchers found a reduction in inflammatory markers in the brains of newborn mice. In this study, researchers will examine whether or not JAK2/STAT3 signal pathway activation could be specifically involved in brain structural abnormalities in IL-6-induced activation of the maternal immune system (presumably resulting in development of abnormal behavior in adult offspring that mimics features of autism). In addition, they will test diosmin's potential effect on improving abnormal, autistic like behaviors of offspring of IL-6 immune activated mothers. These studies could lay the foundation for diosmin as a prenatal supplement in at-risk mothers to avoid autism development in their children, much like folate is currently in use to avoid neural tube defects.

Funder

Funder

National Institutes of Health

Fiscal Year Funding

Fiscal Year Funding

181913

Current Award Period

Current Award Period

2010-2012

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. 3LC. Determine the effect of at least five environmental factors on the risk for subtypes of ASD in the pre- and early postnatal period of development by 2015. IACC Recommended Budget: $25,100,000 over 7 years.

Project Link

Project Link

Il-6-mediated Jak2/Stat3 signaling and brain development (External web link)

Institution

Institution

University of South Florida

State/Country

State/Country

Florida

Project Number

Project Number

5R21MH087849-02

Federal or Private?

Federal or Private?

Federal

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

N/A

 
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