AUTHOR=Wang Rui , Wang Wei , Xu Jingjing , Liu Dexiang , Jiang Hong , Pan Fang TITLE=Dynamic Effects of Early Adolescent Stress on Depressive-Like Behaviors and Expression of Cytokines and JMJD3 in the Prefrontal Cortex and Hippocampus of Rats JOURNAL=Frontiers in Psychiatry VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00471 DOI=10.3389/fpsyt.2018.00471 ISSN=1664-0640 ABSTRACT=Abstract Aims: Expression of inflammatory cytokines in the brain has been reported to be involved in the pathogenesis of and susceptibility to depression. Jumonji domain containing-3 (Jmjd3), which is a histone H3 lysine 27 (H3K27) demethylase and can regulate microglial activation, has been regarded as a crucial element in the expression of inflammatory cytokines. Furthermore, recent studies highlighted the fact that lipopolysaccharides induce depressive-like behaviors and higher Jmjd3 expression and lower H3K27me3 expression in the brain. However, whether Jmjd3 mediating inflammatory cytokine was involved in the susceptibility to depression caused by early life stress remained elusive. Methods: Rats exposed to chronic unpredictable mild stress (CUMS) in adolescence were used in order to detect dynamic alterations in depressive-like behaviors and expression of cytokines, Jmjd3, and H3K27me3 in the prefrontal cortex and hippocampus. Moreover, minocycline, an inhibitor of microglial activation, was employed to observe the protective effects. Results: Our results showed that CUMS during the adolescent period induced depressive-like behaviors, over-expression of cytokines, and increased Jmjd3 and decreased H3K27me3 expression in the prefrontal cortex and hippocampus of both adolescent and adult rats. However, minocycline relieved all the alterations. Conclusion: The study revealed that JMJD3 might be involved in the susceptibility to depressive-like behaviors by modulating H3K27me3 and pro-inflammatory cytokine expression in the prefrontal cortex and hippocampus of rats that had been stressed during early adolescence.