The role of miR-124 in modulating hippocampal neurotoxicity induced by ketamine anesthesia.
OBJECTIVE
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.


METHODS
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 in vitro. Downregulation 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 the protein kinase C/extracellular signal-regulated kinases (PKC/ERK) pathway. In the in vivo Morris water maze test, following ketamine-induced hippocampal neurodegeneration, mice subjected to 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 overanesthetizing-related neurotoxicity.
Departments of Anesthesiology,1.
Haiyang
H
Xu
Jingjing
J
Zhang
Wei
W
Zhou
Yazhen
Y
Feng
Shiyong
S
Teng
Xuesong
X
Song
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D007649:Ketamine / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D009924:Organ Culture Techniques; D018091:Receptors, AMPA / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000187:drug effects
D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D009498:Neurotoxins; D016376:Oligonucleotides, Antisense; D018091:Receptors, AMPA; D007649:Ketamine
anesthesia; hippocampus; miR-124; neurodegeneration