School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, PR China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, PR China.
Food Chem Toxicol. 2020 Jul;141:111396. doi: 10.1016/j.fct.2020.111396. Epub 2020 May 14.
In Alzheimer's diseases, beta-amyloid may act as prion-like protein and migrate from the gastrointestinal tract towards the brain. Soy flavonoids have been identified as neuroprotective against cognitive loss in human. Diet with soy flavonoids may be used to slow down the progression of Alzheimer's diseases.
We performed in-vitro tissue culture experiments using myenteric plexus longitudinal muscle layers isolated from the ileum and colon of ICR mice. Beta-amyloid can be taken up into myenteric neurons and induce neuron degeneration, which is protected by flavonoids compounds, including daidzein, genistein, glycitein and luteolin. We also administered oligomeric beta-amyloid (1-42) (total dose: 8 μg) into the gastrointestinal walls of ICR mice and conducted memory tests and gastrointestinal function assessments after 6 and 12 months. Mice treated with beta-amyloid exhibited minor learning deficits in a T-maze memory test at 6 months and significant memory impairment in a novel object recognition task at 12 months. These impairments were prevented by soy flavonoids. Tracking studies performed using fluorescently tagged beta-amyloid found that, beta-amyloid injected at the stomach can aggregate within the layer of myenteric neurons and migrate to the jejunum or via the vagus nerves to the brain after 1 month. Reductions in the gastrointestinal tissue weight and the spontaneous ileal contraction frequency were also observed at 6 and 12 months, respectively.
Our findings indicate that beta-amyloid can migrate from the gastrointestinal tract to the brain to induce cognitive impairments. Furthermore, chronic soy flavonoids in drinking water have protective actions.
在阿尔茨海默病中，β-淀粉样蛋白可能作为朊病毒样蛋白发挥作用，并从胃肠道向大脑迁移。大豆黄酮已被确定为具有人类认知能力丧失的神经保护作用。饮食中添加大豆黄酮可能有助于减缓阿尔茨海默病的进展。
我们使用从 ICR 小鼠回肠和结肠分离的肌间神经丛纵向肌肉层进行了体外组织培养实验。β-淀粉样蛋白可被摄取到肌间神经元中，并诱导神经元变性，而黄酮类化合物（包括大豆苷、染料木黄酮、大豆苷元和木樨草素）可保护神经元免受变性。我们还将寡聚β-淀粉样蛋白（1-42）（总剂量：8μg）注入 ICR 小鼠的胃肠道壁中，并在 6 个月和 12 个月后进行记忆测试和胃肠道功能评估。用β-淀粉样蛋白处理的小鼠在 6 个月时在 T 迷宫记忆测试中表现出轻微的学习缺陷，在 12 个月时在新物体识别任务中表现出明显的记忆障碍。这些损伤可以通过大豆黄酮来预防。使用荧光标记的β-淀粉样蛋白进行的追踪研究发现，注射到胃部的β-淀粉样蛋白可以在肌间神经元层内聚集，并在 1 个月后通过迷走神经迁移到空肠或大脑。在 6 个月和 12 个月时，还分别观察到胃肠道组织重量和自发性回肠收缩频率减少。
我们的研究结果表明，β-淀粉样蛋白可以从胃肠道迁移到大脑，引起认知障碍。此外，长期饮用含大豆黄酮的水具有保护作用。
