Prenatal maternal immune activation triggers lasting cell-specific transcriptomic dysregulation in the amygdala of primate offspring.

Prenatal exposure to a heightened maternal immune response, such as that triggered by viral infection in the mother, can alter fetal brain development and increase risk of neurodevelopmental disorders in offspring, including autism (ASD) and schizophrenia. However, the cellular and molecular mechanisms linking early inflammatory signals to long-term changes in brain function remain unclear. While rodent models of maternal immune activation (MIA) display brain and behavioral disruptions, their translational relevance to humans is limited. To address this gap, we utilized a nonhuman primate (NHP) MIA model to examine how transient maternal immune responses in early gestation alter gene expression in the amygdala-a brain region essential for socioemotional behavior and implicated many neurodevelopmental disorders. Pregnant macaques were administered the viral mimic Poly(I:C) during the late first trimester, and amygdala samples were collected from 4-year-old male offspring for single-nucleus RNA sequencing (>71,000 nuclei). We identified 2768 unique differentially expressed genes (DEGs), concentrated in excitatory and inhibitory neurons of the lateral nucleus and microglia of the central nucleus. These DEGs converge on synaptic structure, neurotransmission, and neuroimmune signaling-core processes in circuit assembly and behavioral regulation. MIA-associated DEGs significantly overlap with high-confidence ASD- and psychosis-risk gene sets, directly linking prenatal immune events to human disease pathways. This study provides the first region- and cell-type-specific evidence in a primate model that transient prenatal maternal immune responses lead to lasting transcriptomic dysregulation. These findings reveal how early immune insults may alter neurodevelopment and offer a translational framework for identifying molecular targets for early intervention.