Long noncoding RNA BDNF-AS protects local anesthetic induced neurotoxicity in dorsal root ganglion neurons.

Abstract

Long noncoding RNA (lncRNA) BDNF-AS was recently identified to regulate neurotrophin signaling pathway. In this study, we examined the functional role of BDNF-AS in regulating local anesthetic-induced neurotoxicity in dorsal root ganglion (DRG) neurons. Neonatal mouse DRG neurons were cultured in vitro, and treated with local anesthetic, bupivacaine, to induce neurotoxicity. The corresponding change in BDNF-AS expression level in DRG was probed by qRT-PCR. BDNF-AS was knocked down by siRNA in DRG. The effects of BDNF-AS downregulation on neurite regrowth, neuronal apoptosis and activating TrkB signaling pathway in bupivacaine-injured DRG neurons were probed by neurite outgrowth assay, TUNEL assay and western blot assay, respectively. During the process of bupivacaine-induce neurotoxicity in DRG, BDNF-AS was significantly upregulated in both dosage- and time- dependent manners. In DRG neurons, siRNA-mediated BDNF-AS downregulation promoted neurite outgrowth, reduced neuronal apoptosis, and phosphorylated TrkB signaling pathway after bupivacaine-induce neurotoxicity. BDNF-AS downregulation rescued local anesthetic-induce neurotoxicity in DRG neurons, probably through the activation of neurotrophin TrkB signaling pathway.