Maternal Stress and Maternal Microbiome Manipulations Remodel Offspring Medial Prefrontal Cortex in a Sex‐Dependent Manner

Maternal stress and disruptions of the maternal microbiome during development can have profound organizational effects on the brain and behavior of offspring. We have previously demonstrated that these manipulations have marked, sex-dependent effects on aggressive behavior in Siberian hamsters, Phodopus sungorus. Given that the prelimbic cortex is sensitive to stress and may play a role in modulating social behaviors, here we investigated how maternal stress and disruption of the microbiome during pregnancy may affect the development of the prelimbic cortex in offspring. Pregnant hamsters were exposed to either a broad-spectrum antibiotic, social stress, combined treatments, or no manipulation (i.e., control). Adult offspring (PND 107-115) were euthanized, brains were stained using Golgi histology, and apical and basilar dendritic lengths of pyramidal cells in the prelimbic cortex were quantified. Our data indicate that maternal stress and microbiome manipulation have a sex-dependent effect on offspring dendritic morphology. Maternal stress increased apical dendritic length in female but not male offspring relative to controls. However, the combination of maternal stress and maternal antibiotics ameliorated the effect of stress alone. Thus, maternal stress and disruption of the microbiome interact to produce lasting changes in the prefrontal cortex of female offspring. Such changes may contribute to the behavioral effects of these manipulations.