Researchers have prevented mouse pups from developing the autism-like behaviors that commonly appear after simulating an infection in pregnant female mice. They did so by blocking an inflammation-producing immune signal – interleukin-17a (IL-17a).
The report appears today in the journal Science.
A growing body of research – much of it with animals – has suggested that inflammation during pregnancy can affect early brain development in ways that predispose to autism. Inflammation is commonly associated with infections. But it can also result from inflammatory conditions such as diabetes.
The new study still represents a very early stage in research on inflammation during pregnancy and autism. But it goes a step further than past studies to hint at a possible way to protect healthy prenatal brain development in the presence of inflammation.
“This is an elegant study that continues to drive home the message that the immune system plays an important role in the development of symptoms linked to autism,” comments Dan Smith, Autism Speaks vice president for innovative technology. “It adds to an existing body of genetic and biochemical evidence suggesting that specific immune system components change the developing brain in ways that may cause behavioral changes.”
The study was led by researchers at New York University Langone Medical Center, Massachusetts Institute of Technology, University of Massachusetts Medical School and University of Colorado-Boulder.
In the first part of their study, the authors demonstrated that immune responses similar to those triggered by viral infections in pregnant mice changed the brain development of their pups and caused behaviors resembling autism symptoms. These included social avoidance, abnormal communication and repetitive behaviors.
Their further analysis suggested the involvement of immune cells producing the inflammatory chemical IL-17a.
They then showed that blocking the production and action of IL-17a in the womb (using antibodies) prevented both abnormal brain development and autism-like behaviors in the mouse pups.
“To our knowledge, this is the first study to identify a specific population of immune cells that may have a direct role in causing behaviors linked to autism,” says immunologist and co-author Dan Littman, of NYU Langone. “With these study results, Th17 cells, as well as specific proteins they produce, become candidate therapeutic targets.” Littman notes that the immune reactions in the study are caused by viral infections in the mother and have “nothing whatsoever to do with vaccines.”
“We don't yet know just how relevant this mouse model is to people,” cautions developmental pediatrician Paul Wang, Autism Speaks senior vice president and head of medical research, “as autism has many different causes. At the same time, this study shows that researchers are not just asking what causes autism. They’re also asking whether those causes can be modified, or even blocked, giving us hope that the most damaging effects of autism might be ameliorated.”
The study was co-funded by the Simons Foundation Autism Research Initiative, the National Research Foundation of Korea, the Smith Family Foundation, Alzheimer’s Association, National Institutes of Health and the Howard Hughes Medical Institute.
