Twaroski Danielle, Bosnjak Zeljko J, Bai Xiaowen
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA ; Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Pharm Anal Acta. 2015;6:357. doi: 10.4172/2153-2435.1000357.
Growing evidence demonstrates that prolonged exposure to general anesthetics during brain development induces widespread neuronal cell death followed by long-term memory and learning disabilities in animal models. These studies have raised serious concerns about the safety of anesthetic use in pregnant women and young children. However, the underlying mechanisms of anesthetic-induced neurotoxicity are complex and are not well understood. MicroRNAs are endogenous, small, non-coding RNAs that have been implicated to play important roles in many different disease processes by negatively regulating target gene expression. A possible role for microRNAs in anesthetic-induced developmental neurotoxicity has recently been identified, suggesting that microRNA-based signaling might be a novel target for preventing the neurotoxicity. Here we provide an overview of anesthetic-induced developmental neurotoxicity and focus on the role of microRNAs in the neurotoxicity observed in both human stem cell-derived neuron and animal models. Aberrant expression of some microRNAs has been shown to be involved in anesthetic-induced developmental neurotoxicity, revealing the potential of microRNAs as therapeutic or preventive targets against the toxicity.
越来越多的证据表明,在大脑发育过程中长时间暴露于全身麻醉剂会导致广泛的神经元细胞死亡,随后在动物模型中出现长期记忆和学习障碍。这些研究引发了人们对孕妇和幼儿使用麻醉剂安全性的严重担忧。然而,麻醉剂诱导神经毒性的潜在机制很复杂,尚未得到充分理解。微小RNA是内源性的小非编码RNA,通过负调控靶基因表达在许多不同疾病过程中发挥重要作用。最近已确定微小RNA在麻醉剂诱导的发育性神经毒性中可能发挥作用,这表明基于微小RNA的信号传导可能是预防神经毒性的新靶点。在这里,我们概述了麻醉剂诱导的发育性神经毒性,并重点关注微小RNA在人类干细胞衍生神经元和动物模型中观察到的神经毒性中的作用。一些微小RNA的异常表达已被证明与麻醉剂诱导的发育性神经毒性有关,揭示了微小RNA作为针对该毒性的治疗或预防靶点的潜力。