"In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring," says Elaine Hsiao, a graduate student in Patterson's lab and lead author of the PNAS paper.
The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorderrepetitive 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 characterized the immune system of the offspring of mothers that had been infected and found that the offspring display 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 key role in suppressing the immune response. Taken together, the observed immune alterations add up to an immune system in overdriveone that promotes inflammation.
"Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers," Hsiao says. "This tells us that a prenatal challenge can result in long-term consequences for health and development."
With the mouse model established, the group was then able to test whether the offspring's immune problems contribute to their autism-related behaviors. In a revealing test of this hypothesis, the researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice. The normal stem cells in the transplanted bone marrow not only replenished the immune system of the host animals but altered their autism-like b
|Contact: Deborah Williams-Hedges|
California Institute of Technology