GSE108452
Transgenerational inheritance of chronic adolescent stress: Effects of stress response and the amygdala transcriptome
Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To begin to unravel the molecular mechanisms underlying these long-term effects, we determined if stress administered to males during adolescence (F0) altered anxiety behaviors and gene expression profiles in the amygdala – a critical region in the control of emotional states – of their progeny in two generations (F1, F2). Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for two-weeks during adolescence and were used to produce two generations of offspring. Male and female F1 and F2 animals were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. In behaviorally naïve mice (n = 5), mRNA from the amygdala was sequenced to determine the total transcriptomes and pathway analysis was employed to identify differentially expressed genes of functional interest.  RNA-Seq analysis of the amygdala from F1 and F2 male offspring identified genes with altered expression in mice derived from fathers exposed to CUS. Among the differentially expressed pathway was 'notch signaling', which was significantly altered in F2 males. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.  Overall design: Amygdala of F1 or F2 mice from stress or no stress lineage. All conditions have 5 biological replicates