小儿麻醉常用药七氟烷可损害幼年小鼠远期学习记忆功能，其机制尚未阐明。树突棘形成及可塑性变化是学习和记忆功能的关键。Spastin通过剪切细胞骨架调控神经元树突棘形成。 TTLL6通过激发微管多聚谷氨酰化调控Spastin表达。前期研究发现，七氟烷通过增加Tau蛋白磷酸化致幼年小鼠认知功能障碍。预实验进一步发现，七氟烷可使神经元中Tau和TTLL6同时发生树突/胞体易位及Spastin表达增加。由此提出假说：七氟烷通过增加Tau/TTLL6树突易位从而上调Spastin表达，通过剪切细胞骨架造成树突棘重塑，从而影响幼年小鼠远期认知功能。本项目拟应用Tau基因敲除型小鼠和原代海马神经元模型，采用行为学、形态学、电生理学、药理学以及分子生物学等手段，探讨Tau/TTLL6/Spastin信号通路在七氟烷致发育期大脑神经毒性的具体机制，为防治麻醉药致发育大脑认知损伤提供新思路。

Sevoflurane, which commonly used in pediatric anesthesia, can impair long-term learning and memory function of young mice, and its mechanism has not been elucidated. Dendritic spine plasticity plays a key role to learning and memory formation. Spastin regulates neuronal processes and collateral formation by shearing the cytoskeleton. However, TTLL6 can regulate the expression of Spastin by stimulating microtubule polyglutamation. Our previous study found that sevoflurane caused cognitive impairment in young mice by increasing Tau protein phosphorylation. It was further found in pre-experiments that sevoflurane could induce translocation of dendritic cell and enhancement of Spastin expression simultaneously in Tau and TTLL6 in neurons. Thus, the hypothesis is proposed that sevoflurane up-regulates the expression of Spastin by increasing Tau/TTLL6 dendritic translocation and remodels dendritic spine by shearing the cytoskeleton, thereby affecting the long-term cognitive function of young mice. In this study, Tau knock-out mice and primary hippocampal neuron models were applied to explore the specific mechanism of Tau/TTLL6/Spastin signaling pathway in sevoflurane-induced neurotoxicity of developmental brain by means of behavior, electromorphology, electrophysiology, pharmacology and molecular biology, so as to provide new insights for the prevention and treatment of cognitive impairment in the developmental brain caused by anesthetics.