Xie Youna, Yan Lingli, Zeng Haitao, Chen Weineng, Lu Jia-Hong, Wan Jian-Bo, Su Huanxing, Yao Xiaoli
1Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical, Department and Key Discipline of Neurology, No.58 Zhongshan Road 2, Guangzhou, 510080 China.
2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Chin Med. 2020 Mar 30;15:29. doi: 10.1186/s13020-020-00314-0. eCollection 2020.
Alzheimer's disease (AD) is ranked as the most prevalent neurodegenerative disease. However, the exact molecular mechanisms underlying pathophysiological alterations in AD remain unclear, especially at the prodromal stage. The decreased proteolytic degradation of Aβ, blood-brain barrier (BBB) disruption, and neuroinflammation are considered to play key roles in the course of AD.
Male APPswe/PS1dE9 C57BL/6 J double-transgenic (APP/PS1) mice in the age range from 1 month to 6 months and age-matched wild type mice were used in this study, intending to investigate the expression profiles of Aβ-degrading enzymes for Aβ degradation activities and zonula occludens-1 (zo-1) for BBB integrity at the prodromal stage.
Our results showed that there were no significant genotype-related alterations in mRNA expression levels of 4 well-characterized Aβ-degrading enzymes in APP/PS1 mice within the ages of 6 months. Interestingly, a significant decrease in zo-1 expression was observed in APP/PS1 mice starting from the age of 5 months, suggesting that BBB disrupt occurs at an early stage. Moreover, treatment of fish oil (FO) for 4 weeks remarkably increased zo-1 expression and significantly inhibited the glial activation and NF-κB activation in APP/PS1 mice.
The results of our study suggest that FO supplement could be a potential therapeutic early intervention for AD through protecting the BBB integrity and suppressing glial and NF-κB activation.
阿尔茨海默病（AD）是最常见的神经退行性疾病。然而，AD病理生理改变的确切分子机制仍不清楚，尤其是在疾病前驱期。β淀粉样蛋白（Aβ）的蛋白水解降解减少、血脑屏障（BBB）破坏和神经炎症被认为在AD病程中起关键作用。
本研究使用1至6月龄的雄性APPswe/PS1dE9 C57BL/6 J双转基因（APP/PS1）小鼠和年龄匹配的野生型小鼠，旨在研究疾病前驱期Aβ降解酶的表达谱以了解Aβ降解活性，以及紧密连接蛋白1（zo-1）的表达谱以了解BBB完整性。
我们的结果显示，在6月龄内，APP/PS1小鼠中4种已明确的Aβ降解酶的mRNA表达水平没有显著的基因型相关改变。有趣的是，从5月龄开始，在APP/PS1小鼠中观察到zo-1表达显著下降，这表明BBB破坏在早期就已发生。此外，用鱼油（FO）处理4周可显著增加APP/PS1小鼠的zo-1表达，并显著抑制其神经胶质细胞激活和核因子κB（NF-κB）激活。
我们的研究结果表明，补充FO可能是一种潜在的AD早期治疗干预措施，可通过保护BBB完整性以及抑制神经胶质细胞和NF-κB激活来实现。
