Neonatal maternal separation stress elicits lasting DNA methylation changes in the hippocampus of stressreactive Wistar Kyoto rats

Early-life stress (ELS) can alter neurodevelopment in variable ways, ranging from producingdeleterious outcomes to stress resilience. While most ELS studies focus on its harmful effects,recent work by our lab and others shows that ELS elicits positive effects in certain individuals.We exposed Wistar-Kyoto (WKY) rats, known for a stress reactive, anxiety-/depression-likephenotype, to maternal separation (MS), a model of ELS. MS exposure elicited anxiolytic andantidepressant behavioral effects as well as improved cardiovascular function in adult WKYoffspring. The present study interrogates an epigenetic mechanism (DNA methylation) that mayconfer the adaptive effects of MS in WKY offspring. MS exposure triggered dramatic DNA hypermethylation specifically inthe hippocampus. This study investigates the hippocampal methylome of MS exposed WKY.