Role of miR-34c in ketamine-induced neurotoxicity in neonatal mice hippocampus
Role of miR-34c in ketamine-induced neurotoxicity in neonatal mice hippocampus
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DOI：
10.1002/cbin.10349
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发表时间：
2015-02-01
影响因子：
3.9
通讯作者：
Zhang, Yongqiang
中科院分区：
文献类型：
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作者：
Cao, Shu-e;Tian, Jianmin;Zhang, Yongqiang
氯胺酮是一种常用的儿科麻醉剂，但它可能影响发育，甚至在新生儿大脑中诱发神经毒性。我们使用了一种体内新生小鼠模型在海马体中诱发与氯胺酮相关的神经毒性，并发现与阿尔茨海默病发病机制相关的微小RNA——miR - 34c在氯胺酮诱导的海马体神经变性过程中显著上调。对miR - 34c进行沉默的功能测定表明，miR - 34c的下调激活了PKC - ERK通路，上调了抗凋亡蛋白BCL2，并改善了氯胺酮诱导的海马体凋亡。通过莫里斯水迷宫测试进行的认知检查显示，miR - 34c的下调显著改善了氯胺酮诱导的记忆损伤。因此，miR - 34c在调节氯胺酮诱导的海马体神经毒性方面具有重要作用。
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.