MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors

Brain-derived neurotrophic factor (BDNF) and microRNA (miRNA) play crucial roles in the etiology of depression. However, the molecular mechanisms underlying this disease are not fully understood. The primary objective of this study was to investigate the relationship between miR-202-3p and BDNF in a chronic unpredictable mild stress (CUMS) model.

Depression model was established with chronic mild unpredictable mild stimulation (CUMS) combined with solitary feeding. The expression levels of miR-202-3p and BDNF in rat hippocampus were measured by qRT-PCR. The novelty inhibition feeding test (NSFT), sucrose preference test (SPT), and forced swimming test (FST) were used to evaluate the functions of miR-202-3p and BDNF. Target gene prediction and screening and luciferase reporter assay were used to verify the target of miR-202-3p. The expression levels of BNDF, CREB1 and p-CREB1 were detected by Western blot.

Upregulation of miR-202-3p was associated with decreased expression of BDNF in the hippocampus of the CUMS model. Antidepressant was observed when LV-BDNF or LV-si-miR-202-3p was injected into the hippocampus. In addition, in the rat hippocampus and cultured nerve cells, the expression levels of BDNF and cyclic AMP response element binding protein 1 (CREB1), which is a target gene of BDNF, were reduced after LV-miR-202-3p injection. Overexpression of miR-202-3p aggravated depressive behavior and decreased the expression levels of BDNF. Luciferase reporter assay also confirmed that BDNF was a target of miR-202-3p.

Silencing miR-202-3p can reduce the damage to hippocampal nerve in CUMS rats; the mechanism may be related to the upregulation of BNDF expression. miR-202-3p may be an effective target for the treatment of depression.