Influence of the maternal immune response on the development of autism

Completed

Ponzio, Nicholas

University of Medicine and Dentistry

$417,497.00

3 years

Basic & Clinical

Newark

NJ

United States

2008

http://www.umdnj.edu

City: 
Newark
State/Province: 
NJ
State/Province Full: 
New Jersey
Country: 
United States

Clinical and experimental evidence points to a role for the immune system during pregnancy in the development of autism spectrum disorders (ASD). Both T cells and cytokines (proteins which are produced by and regulate the behavior of immune cells) are implicated in various neurological disorders. Cytokines present in the maternal immune system can cross the placenta and enter fetal tissues, and this may affect fetal development. Preliminary results from the Ponzio laboratory have shown that the one such cytokine, interleukin-2 (IL-2) may affect fetal brain development, as the offspring of pregnant mice injected with IL-2 display abnormal behaviors. In the present study, these researchers will examine the role of maternal cytokines and immune cells as an environmental trigger for ASD. Cytokines will be administered to pregnant mice by injection, and the effects on fetal brain development will be examined by behavioral testing of offspring for features selectively found in autism. IL-2 may act directly on the developing brain, or it may stimulate other components of the mother's immune system which in turn affects brain development. To determine which subsets of maternal immune cells and cytokines are stimulated by Il-2 treatment, the maternal immune system will be characterized by molecular and cell immunological techniques. Correlating the activations of the immune system during pregnancy and the development of autistic-like characteristics in offspring will have clinical relevance for understanding the underlying causes of autism.