The Mechanism of the Maternal Infection Risk Factor for Autism

Active

Mazmanian, Sarkis

California Institute of Technology

$449,999.97

3 years

Basic & Clinical

Pasadena

CA

United States

2011

http://www.caltech.edu

City: 
Pasadena
State/Province: 
CA
State/Province Full: 
California
Country: 
United States

Although there is a strong genetic contribution to autism, it is clear that environmental factors such as maternal infection can also increase the risk for this disorder. In a mouse model of this risk factor, we find that offspring born to immune-activated pregnant mice display the core behavioral symptoms of autism: stereotyped and repetitive behaviors, and deficits in social interaction and communication. These offspring also display neuropathology characteristic of autism. Therefore, illuminating the pathway by which maternal immune activation (MIA) causes autism-like symptoms is likely to enhance the understanding of autism pathophysiology. A recent study of over 10,000 ASD cases found an association between first trimester viral infection in pregnant women and ASD in the offspring. In an animal model of this risk factor, the research team found that the offspring of flu-infected pregnant mice display mouse versions of the core behavioral symptoms of autism. These offspring also display a neuropathology commonly found in autism. How does maternal infection alter fetal brain development to cause these abnormalities? Prior research in this laboratory has found that activation of the mother’s immune system increases the level of a protein, termed IL-6, which is important for fighting infection. Moreover, this elevation of IL-6 is critical for the development of autism-like symptoms in the offspring. The investigators next showed that IL-6 alters the function of the placenta. They now wish to discover where IL-6 is acting in the fetal brain, and to determine the relative importance of IL-6 action in the fetal brain versus the placenta. That is, where does IL-6 exert its most important actions that lead to autism-like behavior and pathology in the offspring? Delineation of the cellular pathway of IL-6 action will help in understanding the steps that lead to development of the autistic brain.