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Small risk: Infections during pregnancy boost autism risk in the child.
Mouse brains exposed to inflammation in the womb become more susceptible to a second challenge, researchers reported today at the 2017 Society for Neuroscience annual meeting in Washington D.C.

When briefly deprived of oxygen, mice exposed to maternal inflammation show higher immune activation and suffer greater brain damage than their unexposed peers.

Studies in people suggest that infections during pregnancy boost autism risk in the child by as much as 37 percent. Mice exposed to inflammation in the womb show autism-like features, such as social deficits and structural changes in the brain.

However, only a small fraction of children exposed to inflammation in utero are diagnosed with autism.

The findings suggest that a second hit can determine which children exposed to maternal inflammation in utero go on to have autism, says Hong-Ru Chen, a postdoctoral fellow in Alex Kuan's lab at Emory University in Atlanta, who presented the findings.

Oxygen supply

The researchers injected pregnant rats with a chemical, polyinosinic-polycytidylic acid, that mimics a viral infection and activates the animals' immune system.

Pups exposed to inflammation in the womb show several markers of inflammation, including clusters of activated microglia, brain cells that are part of the immune system. They also have elevated levels of inflammatory molecules such as interleukins 6 and 17, both of which are implicated in autism.

When the pups were 10 days old, the researchers exposed some of them to a second challenging condition: They briefly deprived the pups of oxygen, long enough that the brain cells went on alarm but before widespread cell death and extensive brain injury occurred.

Although this condition, called hypoxia-ischemia, is a serious problem in infants, the researchers used only a mild version of it to model a 'second hit,' says Kuan, associate professor of pediatrics at Emory University in Atlanta.

A second hit for a baby could be any condition that threatens the health of her brain tissue.

"We don't know what these potential 'second hits' comprise. I think no one knows for sure, but one suspect may be gastrointestinal infection," Kuan says. A study published in October found that treating pregnant mice with an antibiotic lowers the autism risk associated with maternal infection.

Mice that endured both hits show significantly greater inflammatory activity and cell death than those exposed to only inflammation or only a lack of oxygen.

This finding suggests that exposure to maternal inflammation amplifies the response to oxygen challenge, the researchers say.