DNA topoisomerase Top3β is impacted by early life stress in the developing female and male rat brain

DNA topoisomerases are essential for preserving genomic integrity. DNA topoisomerases induce breakage of DNA to facilitate replication and transcription by relaxing DNA and relieving supercoiling. Aberrant expression and deletions of topoisomerases are associated with psychiatric disorders such as schizophrenia and autism. Our study investigated the effects of early life stress (ELS) on three topoisomerases, Top1, Top3 alpha, and Top3 beta in the developing rat brain. Newborn rats were exposed to a predator odor stress on postnatal days 1, 2, and 3; brain tissue was collected either 30 min after the last stressor on postnatal day 3 or during the juvenile period. We found that exposure to predator odor resulted in a decrease in Top3 beta expression levels in the neonatal male amygdala and in the juvenile prefrontal cortex of males and females. These data suggest that developing males and females respond differently to predator odor-induced stress. As ELS results in lower Top3 beta levels, these data suggest that ELS experienced during development may have consequences for genomic structural integrity and increased mental health risk.

Automated summary

DNA topoisomerases are important for maintaining genomic integrity by inducing DNA breakage. Our study investigated the effects of early life stress on three topoisomerases in the developing rat brain. We found that exposure to predator odor resulted in a decrease in Top3 beta expression levels, suggesting that early life stress may have consequences for genomic structural integrity and mental health risk.