Yu Zhang1, Lulu Yan2, Yan Cao3, Gaoyin Kong4, Chunshui Lin5. 1. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha 410002, China. 2. Department of Anesthesiology, Hunan Children's Hospital, Changsha 410007, China. 3. Department of Emergency, Hunan Provincial People's Hospital, Changsha 410002, China. 4. Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha 410002, China. 5. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: chengwei.song@aol.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: BDNF-AS downregulation rescued local anesthetic-induce neurotoxicity in DRG neurons, probably through the activation of neurotrophin TrkB signaling pathway.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: BDNF-AS downregulation rescued local anesthetic-induce neurotoxicity in DRG neurons, probably through the activation of neurotrophin TrkB signaling pathway.