Metformin exerts antidepressant effects by regulated DNA hydroxymethylation.

We aim to study the antidepressant mechanism of metformin. Tail suspension test and forced swimming test were used to detect the depression-like behavior; the expressions of target protein were examined by western blot; the levels of target genes were tested by quantitative PCR; the content of α-ketoglutarate and 5hmC were detected by ELISA kit. We showed that metformin can improve the depression-like behavior in spatial restraint stress model; then we found that metformin through AMPK/Tet2 pathway increasing the expression of BDNF to antidepression. Our study provided evidences that metformin plays a role of antidepressant effects through the AMPK/Tet2/BDNF pathway.