International Journal of Neuroscience, May 13, 2014.
Xu H, Zhang J, Zhou W, Feng Y, Teng S, Song X.
Abstract
Purpose: Ketamine is widely used in pediatric anesthesia. Recent studies demonstrated that excessive application of ketamine led to cortical neurodegeneration in neonatal brains. The present study aims to characterize the functional role of neuronal microRNA, miR-124 in regulating ketamine-induced neurotoxicity in mouse hippocampus.
Methods: RT-PCR was used to examine the effect of high-dosage ketamine on the expression of miR-124 in murine hippocampus in vitro. Down-regulation of hippocampal miR-124 was achieved by lentivirual transfection and its effects on protecting ketamine-induced hippocampal neurodegeneration were examined both in vitro and in vivo.
Results: Hippocampal miR-124 was upregulated by ketamine treatment. Knocking down miR-124 in vitro reduced ketamine-induced apoptosis in hippocampal CA1 neurons, upregulated AMPA receptors phosphorylation and activated PKC-ERK pathway. In the in vivo Morris water maze test, following ketamine-induced hippocampal neurodegeneration, mice received hippocampal miR-124 inhibition showed improved memory performance.
Conclusions: Our study demonstrated that miR-124 played an important role in regulating ketamine induced hippocampal neurodegeneration. Inhibiting miR-124 may provide a molecular target to improve memory performance in both human and animals suffering from over-anesthetic related neurotoxicity.
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