title: Downregulation of miR-210 protected bupivacaine-induced neurotoxicity in dorsal root ganglion.
abstract: 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.
authors.affiliation: College of Clinical Medicine, Jilin University, Changchun, 130021, China.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Basic Medical College, Beihua University, Jilin, 132000, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ni
authors.affiliation: Department of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Wenrui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Endoscopy Center, The First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Clinical Medicine, Jilin University, Changchun, 130021, China. haishan_zhang@aol.com.|Department of Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai St., Changchun, 130033, China. haishan_zhang@aol.com.
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D002045:Bupivacaine
keywords: Anesthesia; Apoptosis; BDNF; Dorsal root ganglion; Neurotoxicity; miRNA