Maternal immune mechanisms and offspring neurodevelopment

Adversity during pregnancy, including sickness and stress, causes inflammation in mothers and their unborn babies. Scientific evidence over the last several decades has shown that inflammation during pregnancy may promote risk for psychological disorders, including autism spectrum disorder and attention deficit hyperactivity disorder, in children. What remains unclear, however, is precisely why this risk is increased and what might be done to prevent it. To develop treatment and prevention targets, it is important to understand the molecular and cellular changes that occur in mothers and babies (particularly in the brain) during inflammation.

The studies outlined in this dissertation used multiple pro-inflammatory manipulations in pregnant mice to determine the aspects of offspring neurodevelopment that were most impacted by maternal inflammation and what factors mediated those impacts. Two specific pro-inflammatory proteins (IL-6 and IL-17) drove some but not all changes in the fetal brain that occur with maternal inflammation during pregnancy. In another study of a broader form of inflammation, a mouse version of preeclampsia, a dangerous condition of pregnancy, resulted in offspring brain growth and behavior changes. These changes were likely not caused by a few specific factors, but rather by complex changes in maternal and placental physiology and by multiple molecular pathways.

These findings demonstrate that, while single proteins can drive some particular impacts of maternal inflammation on the fetal brain, complex inflammatory physiology impacts offspring neurodevelopment and behavior. Determining the more nuanced aspects of these complex inflammatory changes is required for the development of improved treatments and prevention strategies.