Department of Psychology, University of Wisconsin-Madison, United States.
Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, United States.
Brain Res. 2023 Jun 15;1809:148339. doi: 10.1016/j.brainres.2023.148339. Epub 2023 Mar 24.
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, Top3α, and Top3β 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 Top3β 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 Top3β levels, these data suggest that ELS experienced during development may have consequences for genomic structural integrity and increased mental health risk.
DNA 拓扑异构酶对于维持基因组完整性至关重要。DNA 拓扑异构酶通过断裂 DNA 来促进复制和转录，从而缓解 DNA 的超螺旋。拓扑异构酶的异常表达和缺失与精神疾病有关，如精神分裂症和自闭症。我们的研究调查了早期生活应激（ELS）对发育中大鼠大脑中的三种拓扑异构酶（Top1、Top3α 和 Top3β）的影响。新生大鼠在出生后第 1、2 和 3 天接受捕食者气味应激；在第 3 天的最后一次应激后 30 分钟或在青少年期采集脑组织。我们发现，暴露于捕食者气味会导致新生雄性杏仁核和雄性和雌性幼年期前额叶皮层中 Top3β 表达水平降低。这些数据表明，发育中的雄性和雌性对捕食者气味诱导的应激反应不同。由于 ELS 导致 Top3β 水平降低，这些数据表明，发育过程中经历的 ELS 可能对基因组结构完整性和增加的心理健康风险产生影响。
