DNA Topoisomerase Top3β Is Impacted by Early Life Stress in the Developing Female and Male Rat Brain

Brain, behavior, and physiological changes associated with predator stress–An animal model for trauma exposure in adult and neonatal rats

“…Consistently, other labs have reported increased neuronal activation in the amygdala within 2 h of predator odor exposure (POE) cessation (Wiedenmayer and Barr, 2001a;Moriceau et al, 2004). In males (but not females) we find decreases in DNA-remodeling enzymes related to genomic integrity (Cuarenta et al, 2023) and increases in retrotransposon translation and insertion, resulting in increased gene copy number (Cuarenta et al, 2020)-the latter being an interesting contrast to work showing suppression of retrotransposon activity by maternal care (Bedrosian et al, 2018). These effects were present in multiple brain regions, including the PFC, amygdala, and hippocampus.…”

“…Both males and females show increased insertion of Line1 retrotransposon into the genome; this insertion negatively predicts levels of juvenile social play (Cuarenta et al, 2021). Further, males and females exhibit decreased expression of DNA topoisomerase Top3β in the PFC, perhaps indicating decreased resiliency to further genomic insults (Cuarenta et al, 2023). Collectively this work suggests that neonatal exposure to POE, even at a developmental time point when defensive behaviors may not yet be evident, causes lasting effects on a variety of behaviors via reorganization of the genome at several levels, including DNA (Kigar et al, 2017;Cuarenta et al, 2020Cuarenta et al, , 2021Cuarenta et al, , 2023, RNA (Kigar et al, 2017;Chang et al, 2019;Cuarenta et al, 2020Cuarenta et al, , 2021Cuarenta et al, , 2023, chromatin (Kigar et al, 2017), and retrotransposon expression (Cuarenta et al, 2020(Cuarenta et al, , 2021.…”