BDNF and major depressive disorder: Huang et al. (2021b) demonstrated that downregulation of miR-139-5p along with upregulation of its target gene PDE4D and downregulation of p-CREB and BDNF after inducing depression-like symptoms in CUMS mice. Such alterations show a bidirectional role for microRNAs in both protection and impairment of the neurogenesis pathways. In addition, Mingardi et al. (2021) found that miR-9-5p expression decreased in the hippocampus of rats subjected to chronic mild stress and primary hippocampal cultures.