The role of miR-124 in modulating hippocampal neurotoxicity induced by ketamine anesthesia. (4th March 2015)

• Record Type: Journal Article
• Authors: Xu, Haiyang; Zhang, Jingjing; Zhou, Wei; Feng, Yazhen; Teng, Shiyong; Song, Xuesong
• Is Part Of: International journal of neuroscience. Volume 125:Number 3(2015:Mar.)
• Page Start: 213
• Page End: 220
• Publication Date: 2015-03-04
• Subjects: Nervous system -- Periodicals; 612.805
• DOI: 10.3109/00207454.2014.919915
• Languages: English
• ISSNs: 0020-7454

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Purpose</italic>: Ketamine is widely used in pediatric anesthesia. Recent studies have demonstrated that excessive application of ketamine leads 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. <italic>Methods</italic>: Real-time quantitative PCR (RT-PCR) was used to examine the effect of high-dosage ketamine on the expression of miR-124 in murine hippocampus <italic>in vitro</italic>. Downregulation of hippocampal miR-124 was achieved by lentivirual transfection, and its effects on protecting ketamine-induced hippocampal neurodegeneration were examined both <italic>in vitro</italic> and <italic>in vivo</italic>. <italic>Results</italic>: Hippocampal miR-124 was upregulated by ketamine treatment. Knocking down miR-124 <italic>in vitro</italic> reduced ketamine-induced apoptosis in hippocampal CA1 neurons, upregulated AMPA receptors phosphorylation and activated the protein kinase C/extracellular signal-regulated kinases (PKC/ERK) pathway. In the <italic>in vivo</italic> Morris water maze test, following ketamine-induced hippocampal neurodegeneration, mice subjected to hippocampal miR-124 inhibition showed improved memory performance. <italic>Conclusions</italic>: 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 overanesthetizing-related neurotoxicity.</p> </abstract>