术后认知功能障碍（POCD）是老年患者的常见全麻并发症，主要表现为记忆缺失，直至痴呆。既往研究表明海马糖原合酶激酶-3β（Glycogen synthase Kinase-3β, GSK-3β）激活导致Aβ诱导的神经毒性及tau蛋白过度磷酸化等阿尔茨海默病（AD）病理特征。此外，我们前期研究发现七氟烷通过激活海马 GSK-3β，进而下调β-catenin表达导致长期记忆缺失。因此，我们假设GSK-3β/β-catenin通路可能同时介导了七氟烷导致的POCD及AD病理变化。本课题拟采用GSK-3β特异性抑制剂或慢病毒转染β-catenin质粒，分别从整体水平、细胞水平以及分子水平上观察七氟醚麻醉下大鼠海马依赖的记忆形成、神经元细胞凋亡、神经突触功能以及不同脑区的Aβ寡聚化及tau蛋白过度磷酸化。探讨七氟烷麻醉导致的POCD是否与AD具有共同的分子机制，为防治POCD及AD提供药物新靶点。

Postoperative Cognitive Dysfunction (POCD) is a common complication of general anesthesia in elderly patients which manifests memory loss or even causes dementia. Researches show that activation of hippocampal Glycogen synthase Kinase-3β (GSK-3β) leads to neurotoxicity and over-phosphorylation of tau protein reproducing hallmark pathologies of Alzheimer`s Disease. Our previous study revealed that sevoflurane down-regulates β-catenin expression through activating GSK-3β and further causes long-term memory loss. Thus, we hypothesize that GSK-3β/β-catenin signaling participates in sevoflurane induced POCD and AD pathology. In this proposal, we are going to modify the activation of GSK-3β/β-catenin signaling in vitro and in vivo via using GSK-3β specific inhibitor(s) and/or overexpressing of β-catenin by lentivirus, and assess the effect of sevoflurane anesthesia on hippocampus-dependent memory formation, neuronal apoptosis, synaptic function, Aβ oligomerization and tau protein over-phosphorylation. Our aim is to identify the mechanism of sevoflurane induced POCD and its common features with AD in order to provide potential drug target for POCD and AD treatment.