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 the process of Jmjd3 mediating inflammatory cytokines was involved in the susceptibility to depression due to 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.
Highlights
Depression, a major psychiatric disorder that affects approximately 16% of the entire population, has the cardinal symptoms of low mood, anhedonia, and cognitive impairment [1]
The results indicated that stress in early adolescence decreased sucrose preference in both adolescent and adult rats, but treatment with minocycline could reverse the decrease in sucrose consumption
These results indicate that stress reduced automatic and exploratory behaviors in both adolescent and adult rats
Summary
Depression, a major psychiatric disorder that affects approximately 16% of the entire population, has the cardinal symptoms of low mood, anhedonia, and cognitive impairment [1]. 50% of the hepatitis C patients receiving interferon-α (IFN-α, a pro-inflammatory cytokine) treatment had depressive symptoms [9, 10]. Our previous studies suggested that both chronic mild stress in rats and the administration of lipopolysaccharides (LPS) in mice induced an increase in pro-inflammatory cytokines in the prefrontal cortex and hippocampus as well as depressive-like behaviors [11, 12]. Those studies suggested that neuroinflammation, overproduction of cytokines, plays a critical role in the etiopathogenesis of depression
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