First Author | Wang Y | Year | 2016 |
Journal | Exp Brain Res | Volume | 234 |
Issue | 4 | Pages | 1057-65 |
PubMed ID | 26708520 | Mgi Jnum | J:274420 |
Mgi Id | MGI:6295053 | Doi | 10.1007/s00221-015-4513-4 |
Citation | Wang Y, et al. (2016) Downregulation of miR-210 protected bupivacaine-induced neurotoxicity in dorsal root ganglion. Exp Brain Res 234(4):1057-65 |
abstractText | Local anesthetic may cause neurotoxicity in developing neurons. In this study, we examined the molecular mechanisms of microRNA-210 (miR-210) in regulating bupivacaine-induced dorsal root ganglia (DRG) neurotoxicity in vitro. Young mouse (P30) DRG explants were cultured in vitro and treated with 5 mM bupivacaine to induce neurotoxicity. QRT-PCR was used to evaluate the expression profiles of miRNAs within 24 h after bupivacaine treatment. MiR-210 was downregulated in DRG, and its effects on bupivacaine-induced neurotoxicity were evaluated by apoptosis and neurite growth assays, respectively. Putative downstream target of miR-210 in DRG, BDNF, was evaluated by dual-luciferase assay, qRT-PCR, and western blot, respectively. BDNF was then knocked down by siRNA to assess its associated effects in regulating DRG neurotoxicity. Within the initial 24 h after bupivacaine treatment, various patterns of miRNA expression were observed, whereas miR-210 was constantly upregulated. Application of miR-210 inhibitor efficiently downregulated endogenous miR-210, protected apoptosis and neurite retraction in bupivacaine damaged DRG neurons. Using dual-luciferase assay, qRT-PCR, and western blot, BDNF was confirmed to the downstream target of miR-210 in DRG. SiRNA-mediated BDNF downregulation reversed the effect of miR-210 downregulation in DRG neurotoxicity. MiR-210, through the regulation of BDNF, plays important role in anesthetics-induced DRG neurotoxicity. |