Persistent transcriptomic alterations in medial prefrontal cortex after prenatal exposure to maternal inflammation

Infection during pregnancy is strongly implicated as an environmental risk factor for autism spectrum disorder (ASD), with activation of the maternal immune system (MIA) identified in the causative pathway. Maternal exposure to viral and bacterial mimics at midgestation leads to the development of core ASD behaviors in rodent offspring. However, the fundamental pathogenic mechanisms coupling MIA to persistent changes in brain function and behavior are incompletely understood.The medial prefrontal cortex (mPFC) is a major locus of pathology in ASD and highly associated with behaviors dysregulated by MIA. Transcriptomic profiling of the mPFC from adult MIA and control offspring provides insight into molecular pathways persistently disrupted by prenatal exposure to maternal inflammation. Pregnant dams received a single intraperitoneal injection of saline (control) or the viral mimic polyinosinic:polycytidylic acid (poly(I:C)) to induce MIA at embryonic day 12.5 (E12.5). Brains were removed from saline and poly(I:C) offspring at 4 months of age and medial prefrontal cortices were dissected for RNA extraction (Stanford TASC) and hybridization onto Affymetrix Clariom S Mouse microarrays (Stanford PAN facility).