• Xiu-Li Jiang, Bo-Xiang Du, Jie Chen, Lin Liu, Wei-Bin Shao, and Jie Song.
• Department of Anesthesiology, The Second Affiliated Hospital of Nantong University Nantong 226001, Jiangsu Province, China.
• Int J Clin Exp Patho. 2014 Jan 1;7(10):6760-7.

BackgroundMounting evidence has shown the toxic effects of anesthesia to neonatal hippocampus. We used an in vivo mouse model to explore the role of microRNA 34a (miR-34a) in regulating anesthesia-induced hippocampal neurotoxicity.MethodsOne-month old C57/BL6 mice received daily intraperitoneal injection of anesthesia (ketamine, 50 mg/kg) for 7 days. One day after, apoptosis was evaluated by TUNEL staining in hippocampal CA1 region, and expression level of miR-34a assessed by real-time quantitative PCR (qPCR). Hippocampal miR-34a was then down-regulated through lentivirus mediated cortical injection prior to anesthesia. The effects of inhibiting hippocampal miR-34a on anesthesia-induced hippocampal apoptosis and memory impairment were further investigated by TUNEL staining and Morris water maze (MWM) test. The predicted molecular target of miR-34a, fibroblast growth factor receptor 1 (FGFR1) was down-regulated in hippocampus through siRNA-mediated cortical injection and its effect on hippocampal apoptosis was also examined.ResultsAnesthesia caused severe apoptosis among hippocampal CA1 neurons and upregulated hippocampal miR-34a. On the other hand, lentivirual inhibition of miR-34a protected anesthesia-induced hippocampal apoptosis and memory impairment. Luciferase essay demonstrated FGFR1 was directly regulated by miR-34a in hippocampus. siRNA-induced FGFR1 downregulation further exaggerated anesthesia-induced apoptosis in hippocampus.ConclusionsOverall, we showed that miR-34a negatively modulated anesthesia-induced hippocampal neurotoxicity.

48 keywords...

hide…