MicroRNA-107 regulates anesthesia-induced neural injury in embryonic stem cell derived neurons

Abstract

Ketamine, though widely used in pediatric anesthesia, may induce cortical neurotoxicity in young patients. This study focused on an in vitro model of rat brain embryonic stem cell (ESC)-derived neurons to investigate the effects of microRNA-107 (miR-107) on ketamine-induced neural injury. Rat brain ESCs were proliferated in vitro and differentiated toward neuronal fate. Ketamine induced neural injury in ESC-derived neurons was inspected by TUNEL and neurite growth assays. Ketamine-induce aberrant miR-107 expression was examined by qRT-PCR. MiR-107 was downregulated in ESCs through lentiviral transduction. Its effect on ketamine-induced neural injury in ESC-derived neurons was then examined. Potential downstream target of miR-107, brain derived neurotrophin factor (BDNF), was inspected by dual-luciferase reporter assay and qRT-PCR. BDNF was knocked down, through siRNA transfection, in NSCs to investigate its functional involvement in miR-107 mediated neural protection in ketamine-injured NSC-derived neurons. Ketamine induced apoptosis, neurite degeneration, and upregulated miR-107 in NSC-derived neurons. Lentivirus-mediated miR-107 downregulation attenuated ketamine-induced neural injury. BDNF was proven to be directly and inversely regulated by miR-107 in NSC-derived neurons. SiRNA-mediated BDNF inhibition reversed the protective effect of miR-107 downregulation on ketamine injury in NSC-derived neurons. MiR-107 / BDNF was demonstrated to be an important epigenetic signaling pathway in regulating ketamine-induced neural injury in cortical neurons. © 2018 The Authors. IUBMB Life published by Wiley Periodicals,Inc. on behalf of International Union of Biochemistry and Molecular Biology., 71(1):20–27, 2019.