CircDYM ameliorates CUMS mice depressive-like behavior and inhibits hippocampal neurons injury via miR-497a-5p/NR3C1 axis.

ABSTRACT

BACKGROUND: Depression is an important mental disease that threatens human physical and mental health. Circular RNA (circRNA) has been confirmed to be involved in the regulation of depression progression, but the role and mechanism of circDYM in depression progression need to be further explored. METHODS: Chronic unpredictable mild stress (CUMS) mice model was constructed to assess mice depressive-like behavior using novelty-suppressed feeding test, sucrose preference test, social interaction test, and forced swimming test. The expression of circDYM, microRNA (miR)-497a-5p and glucocorticoid receptor (NR3C1) was measured by quantitative real-time PCR. The protein levels of NR3C1 and apoptosis markers were analyzed by western blot analysis. Hippocampal neurons viability, apoptosis and inflammation were detected by cell counting kit 8 assay, flow cytometry and ELISA assay. Furthermore, RNA interaction was confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. RESULTS: Our study showed that circDYM and NR3C1 were downregulated and miR-497a-5p was upregulated in the hippocampus tissues of CUMS mice. Overexpressed circDYM alleviated CUMS mice depressive-like behavior and repressed hippocampal neurons injury. In terms of mechanism, circDYM could upregulate NR3C1 by sponging miR-497a-5p. MiR-497a-5p overexpression reversed the regulation of circDYM on CUMS mice depressive-like behavior and hippocampal neurons injury. In addition, the function of miR-497a-5p overexpression on CUMS mice depressive-like behavior and hippocampal neurons injury also could be reversed by overexpressing NR3C1. CONCLUSION: In summary, our study confirmed that circDYM could relieve the depressive-like behavior in CUMS mice and hippocampal neurons injury through miR-497a-5p/NR3C1 pathway. These data confirmed that circDYM had an anti-depressive function, which might be a potential target for depression treatment.