Astaxanthin (Ast) is an effective neuroprotective and antioxidant compound used to treat Alzheimer’s disease (AD); however, the underlying in vivo molecular mechanisms remain unknown. In this study, we report that Ast can activate the mammalian target of rapamycin (mTOR) pathway in the 8-month-old APP/PS1 transgenic mouse model of AD. Our results suggest that Ast could ameliorate the cognitive defects in APP/PS1 mice by activating the mTOR pathway. Moreover, mTOR activation perturbed the mitochondrial dynamics, increased the synaptic plasticity after 21 days of treatment with Ast (10 mg/kg/day), and increased the expression of Aβ-degrading enzymes, mitochondrial fusion, and synapse-associated proteins and decreased the expression of mitochondrial fission proteins. Intraperitoneal injection of the mTOR inhibitor, rapamycin, abolished the effects of Ast. In conclusion, Ast activates the mTOR pathway, which is necessary for mitochondrial dynamics and synaptic plasticity, leading to improved learning and memory. Our results support the use of Ast for the treatment of cognitive deficits.

虾青素 (Ast) 是一种有效的神经保护和抗氧化化合物，用于治疗阿尔茨海默病 (AD)；然而，体内的底层分子机制仍然未知。在这项研究中，我们报告在 8 个月大的 APP/PS1 转基因 AD 小鼠模型中，Ast 可以激活哺乳动物雷帕霉素靶蛋白 (mTOR) 通路。我们的研究结果表明，Ast 可以通过激活 mTOR 通路来改善 APP/PS1 小鼠的认知缺陷。此外，mTOR 激活扰乱线粒体动力学，在用 Ast（10 mg/kg/天）处理 21 天后增加突触可塑性，并增加 Aβ 降解酶、线粒体融合和突触相关蛋白的表达，并降低线粒体裂变蛋白的表达。腹腔注射 mTOR 抑制剂雷帕霉素可消除 Ast 的作用。总之，Ast 激活 mTOR 通路，这是线粒体动力学和突触可塑性所必需的，从而改善学习和记忆。我们的结果支持使用 Ast 治疗认知缺陷。