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Keywords:

  • hippocampus;
  • ketamine;
  • miR-34c;
  • neurotoxicity

Abstract

Ketamine is a commonly used pediatric anesthetic, but it might affect development, or even induce neurotoxicity in the neonatal brain. We have used an in vivo neonatal mouse model to induce ketamine-related neurotoxicity in the hippocampus, and found that miR-34c, a microRNA associated with pathogenesis of Alzheimer's disease, was significantly upregulated during ketamine-induced hippocampal neurodegeneration. Functional assay of silencing miR-34c demonstrated that downregulation of miR-34c activated PKC-ERK pathway, upregulated anti-apoptotic protein BCL2, and ameliorated ketamine-induced apoptosis in the hippocampus. Cognitive examination with the Morris water maze test showed that ketamine-induced memory impairment was significantly improved by miR-34c downregulation. Thus, miR-34c is important in regulating ketamine-induced neurotoxicity in hippocampus.