妊娠中の免疫活性化がエピジェネティックメカニズムを介してシナプスおよび神経発達経路に及ぼす周産期および周産期後の影響

Epidemiological research suggests that maternal immune activation (MIA) during early gestation is a significant risk factor for neurodevelopmental and psychiatric disorders in offspring. Epigenetic factors and chromatin-related phenomena remain highly dynamic throughout prenatal and early postnatal development, offering a substrate through which environmental insults can exert lasting effects on gene regulation. Here, we used a mouse MIA model induced by infection with a mouse-adapted influenza A/WSN/33 (H1N1) virus to investigate the long-term molecular consequences of maternal infection on adult offspring. To separately assess prenatal and postnatal effects of MIA, we cross-fostered half of the pups from each influenza-infected or mock-treated dam at birth. We then profiled histone modifications (H3K27ac, H3K4me3) and transcriptome changes in neuronal nuclei isolated from the frontal cortex of adult offspring. Our results revealed considerable overlap between the prenatal and postnatal effects of MIA on enhancer activity, suggesting a sustained regulatory trajectory across developmental stages. Prenatal MIA was specifically associated with changes in gene regulatory elements related to forebrain and telencephalon development, while postnatal MIA primarily affected pathways involved in axonogenesis and synapse organization. Cross-species enrichment analysis further revealed that MIA-responsive enhancers and promoters are significantly enriched at GWAS loci for neuropsychiatric disorders. Together, these findings support a model in which MIA contributes to disease risk through enduring epigenetic reprogramming of gene regulatory networks in the developing brain.