阿尔兹海默病（Alzheimer’s disease，AD）是严重损害认知功能的神经退行性疾病，目前缺乏有效治疗措施。我们前期研究发现抗阻运动可显著改善3xTg-AD小鼠的认知功能，减少神经炎症和Aβ蛋白沉积，但其作用机制尚不清楚。既往研究显示AD早期脑内存在氧化应激，可导致线粒体和突触功能损害，是引起AD认知障碍的关键因素。我们的预实验发现抗阻训练可改善AD小鼠海马区线粒体形态和突触可塑性，同时增加抗氧化酶GPX4表达水平，提示抗阻训练具有抗氧化应激作用。有鉴于此，我们假设：抗阻训练可通过增加GPX4活性，减轻线粒体氧化应激，促进线粒新生和功能修复，从而改善AD小鼠的神经突触可塑性和认知障碍。本项目拟采用高尔基染色、透射电镜及条件性基因敲除等方法，利用体外和体内模型阐明GPX4在抗阻训练改善AD认知障碍中的作用，为确立抗阻训练作为AD的非药物治疗措施提供理论依据。

Alzheimer’s disease（AD）is a progressive neurodegenerative disease that induces severe cognitive impairments with limited therapy. Our previous findings have shown that resistance exercise attenuated cognitive impairments, inhibited neuroinflammtion and reduced Aβ accumulation in 3xTg-AD mice. However, the underlying mechanism remains unknown. In early AD brain, oxidative stress was induced and may directly contribute to mitochondrial and synaptic damage, resulting to cognitive impairment. Therefore, oxidative stress plays critical role in the pathogenesis of AD. Our preliminary data suggested that resistance exercise induced beneficial changes in the mitochondrial structure and synaptic plasticity, accompanied with an elevated level of antioxidant enzyme GPX4, implying that resistance exercise might be an anti-oxidative treatment. Therefore, we hypothesis that resistance exercise inhibits oxidative stress via activating GPX4, improves mitochondrial biogenesis and functional recovery, thereby protects synaptic and cognitive function in AD brain. In current study, we will illustrate the role of GPX4 in the beneficial effect of resistance exercise on AD both in vitro and in vivo by using Golgi staining, transmission electron microscopy and conditional genetic knockout mice model. The finding will provide theoretical evidence for applying resistance exercise as a non-pharmacological treatment to AD patients.