Changes at the molecular level capacitate the plasticity displayed by the brain in response to stress stimuli. Weaning stress can trigger molecular changes that influence the physiology of the offspring. Likewise, maternal immune activation (MIA) during gestation has been associated with behavior disorders and molecular changes in the amygdala of the offspring. This study advances the understanding of the effects of pre- and postnatal stressors in amygdala gene networks. The amygdala transcriptome was profiled on female and male pigs that were either exposed to viral-elicited MIA or not and were weaned or nursed. Overall, 111 genes presented interacting or independent effects of weaning, MIA, or sex (FDR-adjusted P-value <0.05). PIGY upstream reading frame and orthodenticle homeobox 2 are genes associated with MIA-related neurological disorders, and presented significant under-expression in weaned relative to nursed pigs exposed to MIA, with a moderate pattern observed in non-MIA pigs. Enriched among the genes presenting highly over- or under-expression profiles were 24 Kyoto Encyclopedia of Genes and Genomes pathways including inflammation, and neurological disorders. Our results indicate that MIA and sex can modulate the effect of weaning stress on the molecular mechanisms in the developing brain. Our findings can help identify molecular targets to ameliorate the effects of pre- and postnatal stressors on behaviors regulated by the amygdala such as aggression and feeding.
Keywords: RNA-seq; double-hit hypothesis; gestational stress; weaning stress.
© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.