Altered dendritic morphology in dorsolateral prefrontal cortex of nonhuman primates prenatally exposed to maternal immune activation

Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development.

Automated summary

Women who contract an infection during pregnancy, either viral or bacterial, are at a higher risk of having a child with a neurodevelopmental or psychiatric disorder. Maternal immune response plays a crucial role in mediating the effects of maternal infection, as evidenced by previous studies on animal models. This study focuses on the impact of maternal immune activation during the first or second trimester on neuronal morphology in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of male rhesus monkeys. The findings reveal that offspring exposed to maternal immune activation exhibit increased dendritic branching in DLPFC pyramidal cells, particularly in the infra- and supragranular layers, and a decreased diameter of apical dendrites in the infragranular layer of DLPFC, independent of trimester exposure. However, no noticeable alterations in hippocampal neuronal morphology were observed. These results highlight the long-term consequences of maternal immune challenge on dendritic structure in a brain region crucial for socioemotional and cognitive development.