Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway.

AIM: To investigate the protective effect of microRNA-34a (miR-34a) on propofol-induced neurotoxicity and cognitive dysfunction.

METHODS: After SH-SY5Y cells were treated with propofol to induce neurotoxicity, microRNA-34a mimics and inhibitors were transfected into the cells. The expression of apoptosis-related genes and the proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Sprague-Dawley (SD) rats received intraperitoneal injections of propofol, and were treated with microRNA-34a mimics and lentivirus-mediated microRNA-34a inhibitors. The Morris water maze (MWM) test was used to detect changes in motor function.

RESULTS: Propofol anesthesia had an adverse effect on cell survival due to the increased expression of apoptosis-related genes such as cleaved caspase-3/8 and Bax, which was accompanied by reduced expression of ERK1/2, pERK1/2, and phosphorylated NF-kappaB p65 both in vivo and in vitro. Unexpectedly, microRNA-34a was upregulated after propofol treatment, and the inhibitors protected the SH-SY5Y cells from propofol-induced apoptosis. The microRNA-34a inhibitor suppressed the apoptosis-induced effects of propofol. This protection may have been partly diminished by PD98059, a MAPK kinase inhibitor. MicroRNA-34a inhibited or reverted the reduced expression of ERK1/2 and upregulated the expression of p-CREB significantly and specifically. Additionally, the microRNA inhibitors improved the learning and memory functions of animals suffering from neurologic impairment due to propofol treatment and reduced cell apoptosis in the hippocampus.

CONCLUSION: microRNA-34a could improve anesthesia-induced cognitive dysfunction by suppressing cell apoptosis and recovering the expression of genes associated with the MAPK/ERK signaling pathway.