A new study suggests that changes in an overactive immune system can contribute to autism-like behaviors in mice.
The study from the California Institute of Technology (Caltech) also found that, in some cases, this activation can be related to what a developing fetus experiences in the womb.
“We have long suspected that the immune system plays a role in the development of autism spectrum disorder,” said Dr. Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences at Caltech, who led the work.
“In our studies of a mouse model based on an environmental risk factor for autism, we find that the immune system of the mother is a key factor in the eventual abnormal behaviors in the offspring.”
The first step was establishing a mouse model that tied the autism-related behaviors to immune changes, he said.
Several large studies — including one that involved tracking the medical history of every person born in Denmark between 1980 and 2005 — found a correlation between viral infection during the first trimester of a mother’s pregnancy and a higher risk for autism in her child. As part of the new study, researchers injected pregnant mouse mothers with a viral mimic that triggered the same type of immune response a viral infection would.
“In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring,” said Elaine Hsiao, a graduate student in Patterson’s lab and lead author of the paper.
The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorder, including repetitive or stereotyped behaviors, decreased social interactions, and impaired communication.
In mice, this translates to such behaviors as compulsively burying marbles placed in their cage, excessively self-grooming, choosing to spend time alone or with a toy rather than interacting with a new mouse, or vocalizing ultrasonically less often or in an altered way compared to typical mice.
Next, the researchers studied the immune system of the offspring of mothers that had been infected and found that they displayed a number of immune changes.
Some of those changes parallel those seen in people with autism, including decreased levels of regulatory T cells, which play a role in suppressing the immune response, the researchers said.
Taken together, the observed alterations add up to an immune system in overdrive, which promotes inflammation.
“Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers,” Hsiao said. “This tells us that a prenatal challenge can result in long-term consequences for health and development.”
The researchers were then able to test whether the offspring’s immune problems contribute to their autism-related behaviors. In a test of this hypothesis, the researchers gave the affected mice a bone-marrow transplant from typical mice.
The normal stem cells in the transplanted bone marrow not only replenished the immune system of the mice, but altered their autism-like behavior, the researchers report.
The researchers note that because the work was conducted in mice, the results cannot be readily extrapolated to humans, and they do not suggest that bone-marrow transplants should be considered as a treatment for autism.
They also have yet to establish whether it was the infusion of stem cells or the bone-marrow transplant procedure itself — complete with irradiation — that corrected the behaviors.
However, the results do suggest that immune irregularities in children could be an important target for innovative immune manipulations in addressing the behaviors associated with autism, said Patterson. By correcting these immune problems, it might be possible to ameliorate some of the classic developmental delays seen in autism, he noted.
The results appear in a paper in the Proceedings of the National Academy of Sciences (PNAS).