Laboratory Animal Center, Medical College of Soochow University, 199 Ren'ai Road, Suzhou, China; School of Physical Education, Soochow University, No.50, Donghuan Road, Suzhou, China.
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou, China.
Neurochem Int. 2021 May;145:105010. doi: 10.1016/j.neuint.2021.105010. Epub 2021 Mar 5.
To determine whether voluntary wheel running could improve cognitive function from both the young and middle-aged APP/PS1 mice and the underlying mechanisms involved in. Young (9-weeks old) and middle-aged (24-weeks old) APP/PS1 mice were randomly assigned into control and exercise groups, respectively. Mice from exercise group had free and unlimited access to the running wheel for a total of 16 weeks. Voluntary exercise only improved cognitive function from young but not the middle-aged APP/PS1 mice. This might be owing to that in young APP/PS1 mice voluntary exercise reduced tau phosphorylation via inhibiting p-GSK3β activity, as well as reduced neuro-inflammation and elevated key proteins involved in synaptic plasticity. Additionally, exercise also elevated circulating L-Valine, Glucosamine, Formylanthranilic acid, Myristic acid level and improved gut microbiota profiles (i.e. elevated Oscillibacter, EF097061_g, EU454870_g, EU504554_g, EU505046_g and EF096172_g and reduced Alistipes). Improved circulating metabolites and intestinal microbiome might also contribute to improved learning and memory abilities post exercise. For the middle-aged APP/PS1 mice, exercise reduced ADAM10 and GFAP protein expression in hippocampus, with no notable alterations in circulating metabolites; additionally, mice from exercise group had markedly reduced abundance of the phyla Proteobacteria and Tenericutes, genera Bacteroides and Faecalibacterium, and elevated abundance of the genera Allobaculum. It is suggested that voluntary exercise should be initiated at an early adulthood period rather than at late stage in order to prevent cognitive decline or Alzheimer's disease.
为了确定自愿轮跑是否能改善年轻和中年 APP/PS1 小鼠的认知功能，以及其中涉及的潜在机制。将年轻（9 周龄）和中年（24 周龄）APP/PS1 小鼠随机分为对照组和运动组。运动组的小鼠可以自由且无限地使用跑步轮，总共 16 周。自愿运动仅改善了年轻 APP/PS1 小鼠的认知功能，但对中年 APP/PS1 小鼠没有改善。这可能是因为在年轻的 APP/PS1 小鼠中，自愿运动通过抑制 p-GSK3β 活性降低了 tau 磷酸化，同时还降低了神经炎症并提高了参与突触可塑性的关键蛋白。此外，运动还提高了循环中的 L-缬氨酸、氨基葡萄糖、甲酰基犬尿氨酸、肉豆蔻酸水平，并改善了肠道微生物群谱（即增加了 Oscillibacter、EF097061_g、EU454870_g、EU504554_g、EU505046_g 和 EF096172_g，减少了 Alistipes）。循环代谢物和肠道微生物组的改善也可能有助于运动后学习和记忆能力的提高。对于中年 APP/PS1 小鼠，运动降低了海马体中的 ADAM10 和 GFAP 蛋白表达，但循环代谢物没有明显变化；此外，运动组的小鼠的厚壁菌门和无壁菌门、拟杆菌属和粪杆菌属的丰度明显减少，而 Allobaculum 属的丰度增加。建议为了预防认知能力下降或阿尔茨海默病，应在成年早期开始自愿运动，而不是在晚期。
