Pregnancy: overactive immune system linked to offspring brain damage

Pregnancy: overactive immune system linked to offspring brain damage

In a mouse study, researchers found that fetal mice who were exposed in the womb to a maternal immune system in overdrive - due to an infection or other illness - displayed lasting signs of brain damage into adulthood. And the investigators believe their findings could be relevant to human neurologic diseases, such as schizophrenia and autism.

Results of the study, conducted by researchers from Johns Hopkins Medicine in Baltimore, MD, are published in the journal Brain, Behavior and Immunity.

They note that the hippocampus, which is the part of the brain responsible for memory and spatial navigation, was smaller in the males who were exposed to the ramped-up maternal immune system.

Additionally, the males had fewer nerve cells in their brains, and the investigators found a type of immune cell that should not be present in their brains.

To create the effects of maternal infection or inflammation in mice, the researchers injected the wombs of one group of pregnant mice with lipopolysaccharide (LPS), which is a toxin that produces inflammatory effects similar to E. coli bacteria.

Fetal mice - particularly males - who were exposed to inflammation in the womb showed poor motor skills and behavioral issues.

The team notes that inflammation in pregnant women between weeks 18 and 32 of their pregnancy has previously been linked to preterm birth and imbalanced immune cells in the brains of their children. Sometimes, it even results in nerve cell death in those children's brains.

In the study, researchers injected the wombs of a control group of mice with a saline solution and waited to see what happened in the brains of the offspring from both groups over the long term.

The investigators observed that just after birth, the LPS group had poor motor skills and behavioral issues, such as hyperactivity.

Then, at 60 days post-weaning - which is the equivalent of adulthood in mice - the mice from the LPS group could walk well but still showed hyperactivity. The researchers say this suggests their motor problems had resolved but their behavioral problems had not.

Dr. Irina Burd, assistant professor of gynecology/obstetrics and neurology at Johns Hopkins, says that the sex-specific differences, including the smaller hippocampus, were also found in adulthood.

Dr. Burd adds:

Our research suggests that in mice, males may be more vulnerable to the effects of maternal inflammation than females, and the impact may be life long.

Now we wonder if this could explain why more males have diseases such as autism and schizophrenia, which appear to have neurobiological causes."

She suggests that chronic inflammation might be a mechanism behind keeping the hippocampus small because it inhibits brain development.

However, why males and females respond differently to inflammation in the womb remains a mystery for now. Burd notes that solving this mystery could provide knowledge necessary for developing interventions and new drug therapies. recently reported on a study that suggested small fetal size in pregnancy could indicate future heart problems in offspring.

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