LncRNA LINC00641 Sponges miR-497-5p to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF

Ketamine, which is widely used in anesthesia, can induce cortical neurotoxicity in patients. This study aims to investigate the effects of long non-coding RNA LINC00641 on the ketamine-induced neural injury.

In this study, rat pheochromocytoma cells (PC12 cells) were used as a cell model and Sprague-Dawley postnatal day 7 rats were used for experiments in vivo. Ketamine-induced aberrant expression levels of LINC00641, miR-497-5p and brain-derived neurotrophic factor (BDNF) were examined by qRT-PCR. The effects of LINC00641 and miR-497-5p on ketamine-induced neural injury were then examined by MTT assays and TUNEL analysis. In addition, the activity of ROS and caspase-3 was measured. The regulatory relationships between LINC00641 and miR-497-5p, miR-497-5p and BDNF were detected by dual-luciferase reporter assay, respectively.

Ketamine induced the apoptosis of PC12 cells, accompanied by down-regulation of LINC00641 and BDNF, and up-regulation of miR-497-5p. LINC00641 overexpression enhanced the resistance to the apoptosis of PC12 cells, while transfection of miR-497-5p had opposite effects. Furthermore, LINC00641 could bind to miR-497-5p and reduce its expression, but indirectly increase the BDNF expression, which was considered as a protective factor in neural injury and activated TrkB/PI3K/Akt pathway.

Collectively, LINC00641/miR-497-5p/BDNF axis was validated to be an important signaling pathway in modulating ketamine-induced neural injury.