MiR-139-5p has an antidepressant-like effect by targeting phosphodiesterase 4D to activate the cAMP/PKA/CREB signaling pathway.

Background: Phosphodiesterase 4D (PDE4D) inhibitor is commonly used to treat depression, but side effects seriously decrease its efficacy. PDE4D was a downstream target mRNA of miR-139-5p. Therefore, we examined the effects of hippocampal miR-139-5p gain- and loss-of-function on depression-like behaviors, the expression level of PDE4D, and hippocampus neurogenesis.