Fig. 6.

Schematic diagram of the antidepressant-like effect of Rb1 by potentiating synaptic plasticity via the miR-134–mediated BDNF signaling pathway in a mouse model of chronic stress. Long-term chronic and unpredictable mild stress increase the expression of miR-134 in the mouse hippocampus. The highly expressed miR-134 inhibits the activity of BDNF, thereby inhibiting its receptor TrkB and its downstream PI3K–AKT and MAPK–ERK pathways. Inhibition of both pathways reduces the phosphorylation of the Ser9 site of GSK-3β and then promotes the activation of GSK-3β. Activated GSK-3β reduces the stability of β-catenin, alleviates its binding to CREB in the nucleus, and regulates transcription and expression of genes, such as BDNF, PSD-95, GAP-43, and MAP-2. However, Rb1 can inhibit the expression of miR-134 and rescue the negative effects of miR-134 on the BDNF signaling cascade pathway during chronic stress, promoting gene transcription and expression and increasing hippocampal synaptic plasticity. These molecular changes may be the basis for the antidepressant-like effects of Rb1.