麻醉药物对脑发育的安全性是医学界关注的焦点之一。临床研究提示婴幼儿接受较长时间手术麻醉是其青少年期学习障碍的独立危险因素。七氟烷是小儿麻醉常用的吸入性全身麻醉药物，我们前期工作显示幼鼠吸入2%七氟烷3h可致海马神经元树突棘形态可塑性发生改变和成年后认知受损。我们同时发现七氟烷可抑制海马神经元兴奋性氨基酸转运体3(EAAT3)的转录、表达及转运谷氨酸(Glu)功能，导致细胞外Glu浓度失衡及树突棘Tau蛋白磷酸化水平增高。结合EAAT3表达量在发育期的阶段性变化和磷酸化Tau对树突棘形态可塑性的作用，我们推测对EAAT3/Glu/Tau磷酸化的调控是七氟烷改变树突棘可塑性的重要机制。本项目拟利用分子生物学技术，从基因-细胞-整体动物水平阐明EAAT3/Glu/Tau磷酸化在七氟烷干扰树突棘发育中的信号转导机制及未成熟脑对麻醉药物易感的分子基础，从而为防治麻醉药物导致的发育期脑损伤提供新思路。

The safety of anesthesia on brain development is one of the focuses of the medical community. It implied that exposure to surgery/anesthesia for a long duration during early development was an independent risk factor for adolescent learning disability by several clinical studies. Sevoflurane is a widely used volatile anesthetic for pediatric anesthesia. In our preliminary work, it was found that exposure to 2% sevoflurane for 3 hours could trigger the changes of morphological plasticity of dendritic spines in immature mouse hippocampus, accompanying with long-term cognitive dysfunction. We also found that sevoflurane could inhibit the transcription, expression and transporting glutamate(Glu) function of excitatory amino acid transporter3 (EAAT3), which induced the imbalance of extracellular Glu concentration and increase of spine Tau phosphorylation level. According to the different level of EAAT3 expression during different developmental stages and the role of Tau phosphorylation in spine plasticity, we hypothesize that regulating EAAT3/Glu/Tau phosphorylation pathway is a crucial mechanism of sevoflurane-induced changes of morphological plasticity of dendritic spines. Therefore, we apply for this project and attempt to explore the role and signal transduction mechanism of EAAT3/Glu/Tau phosphorylation pathway in sevoflurane-induced dysplasia of dendritic spine at gene-cell-animal level, using molecular biology technologies. Also, the question why immature brain is more sensitive to anesthesia-induced neurotoxicity will be answered in molecular level. Results from our study will provide new clues to prevent and treat the injury induced by anesthetics in developing brains.