Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China.
J Alzheimers Dis. 2019;71(3):825-832. doi: 10.3233/JAD-190596.
Administration of sevoflurane (SEVO) may induce learning and memory deficits, which increases the chances of developing Alzheimer's disease. Here, we studied the effects of SEVO exposure on rats with a focus on the role of insulin-like growth factor (IGF) signaling. SEVO exposure significantly increased neuron cell apoptosis, and caused poor performance of the rats in behavior tests, by suppressing IGF-1 receptor (IGF1R). Bioinformatic analysis predicted microRNA(miR)-223-3p as an IGF1R-binding miRNA, the level of which increased in neurons after exposure to SEVO. In vitro, miR-223-3p suppressed the translation of IGF1R in neural cells. Moreover, transfection with antisense of miR-223-3p significantly attenuated SEVO exposure-induced neuron cell apoptosis. Taken together, these data suggest that SEVO-induced miR-223-3p upregulation suppresses IGF1R to impair IGF signaling, which subsequently leads to learning and memory impairments.
七氟醚(SEVO)的管理可能会导致学习和记忆缺陷,从而增加患阿尔茨海默病的几率。在这里,我们研究了 SEVO 暴露对大鼠的影响,重点关注胰岛素样生长因子(IGF)信号的作用。SEVO 暴露显著增加神经元细胞凋亡,并通过抑制 IGF-1 受体(IGF1R)导致大鼠在行为测试中的表现不佳。生物信息学分析预测 microRNA(miR)-223-3p 是一种 IGF1R 结合 miRNA,其在神经元暴露于 SEVO 后水平增加。在体外,miR-223-3p 抑制神经细胞中 IGF1R 的翻译。此外,转染反义 miR-223-3p 可显著减轻 SEVO 暴露诱导的神经元细胞凋亡。总之,这些数据表明,SEVO 诱导的 miR-223-3p 上调抑制 IGF1R 以损害 IGF 信号,进而导致学习和记忆障碍。