| First Author | Wu H | Year | 2021 |
| Journal | J Psychiatr Res | Volume | 133 |
| Pages | 142-155 | PubMed ID | 33340793 |
| Mgi Jnum | J:309244 | Mgi Id | MGI:6757642 |
| Doi | 10.1016/j.jpsychires.2020.12.014 | Citation | Wu H, et al. (2021) Effects of chronic stress on depressive-like behaviors and JMJD3 expression in the prefrontal cortex and hippocampus of C57BL/6 and ob/ob mice. J Psychiatr Res 133:142-155 |
| abstractText | BACKGROUND: Depression is a psychiatric disorder which is accompanied by neuroinflammatory responses. Obesity is considered as a low-grade inflammatory state. Studies have found that obese individuals are more likely to suffer from depression, but its possible mechanism has not been specifically illuminated. The Jumonji domain protein 3 (JMJD3) is a specific histone demethylase of trimethylation at lysine 27 of histone-H3 (H3K27me3). Over-expressions of JMJD3 induces the demethylation of H3K27me3 and results in the expression of pro-inflammatory genes, while its upregulation may be limited by adiponectin (APN). However, the role of JMJD3 in susceptibility to neuroinflammation and depression in obesity has not been clarified. METHODS: Chronic unpredictable mild stress (CUMS) was selected to build depression model in C57BL/6 and ob/ob mice. Sucrose preference test, tail suspension test, open field test and Morris water maze test were used to detect depressive-like behaviors and memory impairment. Microglial activation, pro-inflammatory cytokines, APN, NF-kB, JMJD3 and H3K27me3 expressions in the serum, prefrontal cortex (PFC) and hippocampus (HIP) were examined in C57BL/6 and ob/ob mice. Meanwhile, GSK-J4 was used to inhibit JMJD3 expression. RESULTS: CUMS led to depressive-like behaviors and memory impairment, microglial activation, increased expressions of pro-inflammatory cytokines, NF-kappaB and JMJD3, decreased expression of H3K27me3 in the PFC and HIP in C57BL/6 and ob/ob mice. Meanwhile, ob/ob mice showed worse behavioral injury and memory impairment, microglial excessively activation, over-expression of pro-inflammatory cytokines and NF-kB and decreased H3K27me3 levels than C57BL/6 mice. CUMS also decreased the APN levels in the serum and brain tissues in ob/ob mice compared to C57BL/6 mice. But GSK-J4 could relieve these alterations. CONCLUSIONS: JMJD3 might be involved in the susceptibility to depressive-like behaviors and neuroinflammation of obese mice by the demethylation of H3K27me3, and decreased levels of APN could reduce Enhancer of zeste homolog 2 (EZH2) binding with H3K27me3. The role of JMJD3 in severer inflammatory state in the comorbidity of obesity and depression was considered. |
