Abstract：
Dietary salt is increasingly recognized as an independent risk factor for cognitive impairment. However, the exact mechanisms are not yet fully understood. Mitochondria, which play a crucial role in energy metabolism, are implicated in cognitive function through processes such as mitochondrial dynamics and mitophagy. While mitochondrial dysfunction is acknowledged as a significant determinant of cognitive function, the specific relationship between salt-induced cognitive impairment and mitochondrial health has yet to be fully elucidated. Here, we explored the underlying mechanism of cognitive impairment of mice and N2a cells treated with high-salt focusing on the mitochondrial homeostasis with western blotting, immunofluorescence, electron microscopy, RNA sequencing, and more. We further explored the potential role of SIRT3 in salt-induced mitochondrial dysfunction and synaptic alteration through plasmid transfection and siRNA. High salt diet significantly inhibited mitochondrial fission and blocked mitophagy, leading to dysfunctional mitochondria and impaired synaptic plasticity. Our findings demonstrated that SIRT3 not only promote mitochondrial fission by modulating phosphorylated DRP1, but also rescue mitophagy through promoting PINK1/Parkin-dependent pathway. Overall, our data for the first time indicate that mitochondrial homeostasis imbalance is a driver of impaired synaptic plasticity in a cognitive impairment phenotype that is exacerbated by a long-term high-salt diet, and highlight the protective role of SIRT3 in this process.
摘要：
膳食盐越来越被认为是认知障碍的独立危险因素。然而,确切的机制尚未完全了解。线粒体,在能量代谢中起着至关重要的作用，通过线粒体动力学和线粒体自噬等过程参与认知功能。虽然线粒体功能障碍被认为是认知功能的重要决定因素，盐诱导的认知障碍与线粒体健康之间的具体关系尚未完全阐明.这里,我们探索了小鼠认知障碍的潜在机制和N2a细胞用蛋白质印迹法关注线粒体稳态的高盐处理，免疫荧光，电子显微镜，RNA测序，还有更多.我们通过质粒转染和siRNA进一步探讨了SIRT3在盐诱导的线粒体功能障碍和突触改变中的潜在作用。高盐饮食显著抑制线粒体裂变，阻断线粒体自噬，导致线粒体功能失调和突触可塑性受损。我们的发现表明，SIRT3不仅通过调节磷酸化DRP1促进线粒体裂变，而且还通过促进PINK1/Parkin依赖性途径挽救线粒体自噬。总的来说,我们的数据首次表明，线粒体稳态失衡是认知障碍表型中突触可塑性受损的驱动因素，长期高盐饮食会加剧这种表型。并强调SIRT3在此过程中的保护作用。
