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Key Immune System Mediator of Abnormal Brain Development Identified

October 08, 2007

Unfortunately the causes of autism are not yet known, but ongoing research is exploring many different possibilities. The involvement of the immune system in either initiating or perpetuating autism is one relatively new avenue of exploration. However, exactly how (or if) the immune system can be related to altered brain development is not well-understood. A new paper published this week in the Journal of Neuroscience uses pregnant mice as a model system to identify a signaling molecule produced by the immune system that, when present in high doses during pregnancy, even for a brief time, may be responsible for causing altered behavior of the offspring when they grow up.

Previous research has shown that activating the immune system of pregnant mice results in babies that show several abnormalities, including some signs reminiscent of schizophrenia and autism such as anxiety, altered startle responses and changes in social behavior. This new research, carried out by Paul Patterson, Ph.D. and colleagues at the California Institute of Technology and co-sponsored in part with grants from Autism Speaks and Cure Autism Now, was carried out to determine how an activated immune system in a pregnant mother is translated into a later behavioral change in her offspring. The researchers found that one of a group of molecules known as cytokines, produced by the mother when her immune system is stimulated, appears to specifically be responsible for setting in motion the cascade of events that impacts the developing fetus. By blocking this particular cytokine, known as IL-6, the scientists could block the detrimental effects normally caused by maternal immune activation. Moreover, the researchers also found that simply administering IL-6 to the mother during pregnancy can cause the same negative effects on the offspring as an infection.

Exactly how IL-6 is producing these effects is the next step of this research. However, having identified that exposure to this single immune system molecule changes brain development is both proof-of-principle that events that impact the mother's immune system can cause later abnormalities in her children, and importantly, that these abnormalities can be prevented if the signaling pathways causing the damage can be identified and blocked.

Dr. Patterson is a member of the Autism Speaks Scientific Advisory Board and had served previously on the Cure Autism Now SAB for 3 years. He also co-chaired the AS/CAN organized workshop on Immunology and Autism held in January of this year.

Read the press release from the California Institute of Technology here.

Read the abstract in the Journal of Neuroscience here.