MicroRNA-137 and its downstream target LSD1 inversely regulate anesthetics-induced neurotoxicity in dorsal root ganglion neurons

Purpose: Anesthetic reagents, such as bupivacaine (By), induce significant neurotoxicity in dorsal root ganglion neurons (DRGNs). In this study, we investigated the expression, function and cross-association of microRNA-137-3p (miR-137-3p) and lysine (K)-specific demethylase 1A (LSD1) in a murine model of By-induced neural injury in DRGNs. Methods: Murine DRGNs were culture in vitro and treated with By. QPCR was used to evaluate miR-137-3p expression in By-injured DRGNs. MiR-137-3p was genetically downregulated to evaluate its rescuing effect on By-induced DRGN apoptosis and neurite retraction. The association of miR-137-3p on its downstream target, LSD1 coding gene KDM1A, was evaluated by dual-luciferase activity assay and qPCR. In miR-137-3p-down-regulated DRGNs, KDM1A was inhibited to evaluate its involvement in miR-137-3p-mediated modulation on By induced DRGN neurotoxicity. Furthermore, KDM1A expression in By-injured DRGN was evaluated by qPCR, and LSD1 was overexpressed in DRGN to evaluate its direct effect on By-induced neurotoxicity. Results: MiR-137-3p was upregulated in By-injured DRGNs. MIR-137-3p downregulation rescued By-induced DRGN apoptosis and neurite retraction. LSD1 was demonstrated to be downstream to, and inversely modulated by miR-137-3p in DRGN. In By-injured DRGNs, LSD1 downregulation reversed miR-137-3p-downregualtion-induced neural protection. Furthermore, LSD1 upregulation directly rescued By-induced apoptosis and neurite retraction in DRGNs. Conclusions: MiR-137-3p and its downstream target LSD1 are inversely associated to regulate anesthetics-induced neurotoxicity in DRGN. This signaling pathway may be a therapeutic candidate to reduce anesthetics induced neurological damage in human patients.