miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1.

Exposure to trauma is a potential contributor to anxiety; however, the molecular mechanisms responsible for trauma-induced anxiety require further clarification. In this study, in an aim to explore these mechanisms, we observed the changes in the hypothalamic pituitary adrenal (HPA) axis using a radioimmunoassay and the changes in anxiety-like behavior using the open field test and elevated plus maze test in a rat model following intervention with NBI­27914, a specific corticotropin­releasing hormone receptor 1 (CRHR1) antagonist. CRHR1 was found to be involved in trauma­induced anxiety. We then applied bioinformatic analysis to screen microRNAs (miRNAs or miRs) that target CRHR1, and miR­34b was determined to negatively regulate CRHR1 mRNA in primary hypothalamic neurons. The overexpression of miR­34b in the paraventricular nucleus (PVN) by a miRNA agomir using a drug delivery system decreased the hyperactivity of the HPA axis and anxiety­like behavior. Overall, the involvement of the HPA axis in trauma­induced anxiety was demonstrated, and trauma-induced anxiety was attenuated by decreasing the hyperactivity of the HPA axis via miR­34b by targeting CRHR1.