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【文献解读】 2019年8月美国亚利桑那州立大学研究团队在期刊《Aging Cell》中发表文章，探究终生有规律的补充胆碱是否能减轻阿尔兹海默症患者（AD）病理和相关的空间参考记忆缺陷。结果表明，终身服用额外的胆碱对患者AD病理和相关的认知缺陷有显著的益处，胆碱改善了空间参考记忆，降低了β-淀粉样蛋白（A-β）负担。  该团队在试验中以雌性小鼠为模式生物，雌性APP/PS1和野生型(NonTg)小鼠被随机分配接受不同浓度的氯化胆碱对照饮食(CTL)，高浓度摄入组是低浓度摄入组的4.5倍。用抗小胶质细胞标志物IBA1和溶酶体标志物CD68的抗体对组织进行双重染色。发现了显著的基因型主效应，APP/PS1小鼠的激活的小胶质细胞与总小胶质细胞的比率显著低于非Tg小鼠，胆碱组的CD68/IBA1共定位明显低于CTL组。结果表明，终生补充胆碱降低了激活的小胶质细胞的水平，从而减轻了与AD样病理相关的脑部炎症的有害影响。然后用抗α7烟碱型乙酰胆碱受体（α7nAchR）和IBA1的抗体对组织进行了双重染色定量分析显示显著的基因型主效应，APP/ps 1小鼠的α7nAchRs表达量显著低于非Tg小鼠，还发现APP/PS1CH 小鼠的α7nAchR/IBA1结合强度显著低于CTL7nAchR/IBA1结合强度(p<0.001)。这些结果表明，终生补充胆碱可降低小胶质细胞内α7nAchR的表达，这可能与小胶质细胞活化程度降低有关。  注：(a-b)APP/PS1CTL和CH 小鼠海马区A-β-42斑块的显微照片；(C-e)APP/PS1小鼠海马区Aβ42斑块的数量 结果证实，终生补充胆碱的饮食方案可以减轻雌性APP/PS1小鼠的病理负担和相关的认知缺陷。这些结果强调了外源膳食胆碱在一生中的重要作用，并证明了CH 作为一种健康大脑老化策略的潜力。 【文献节选】 Alzheimer's disease (AD), the most prevalent neurodegenerative dis‐ order worldwide, is clinically characterized by impairments in cog‐ nition, memory, and intellectual disabilities (LaFerla & Oddo, 2005). The neuropathological hallmarks of the AD brain are extracellular plaques composed predominately of the amyloid‐β (Aβ) peptide, in‐ traneuronal tangles of hyperphosphorylated tau, and synaptic and neuronal loss (LaFerla & Oddo, 2005). Additionally, brain inflamma‐ tion plays a significant role in neurodegeneration (Akiyama et al., 2000; Heppner, Ransohoff, & Becher, 2015; Holmes, Cunningham, Zotova, Culliford, & Perry, 2011; Schwab, Klegeris, & McGeer, 2010). Over the next few decades, there will be a dramatic increase in the prevalence of AD due to the advancing age of the global population; to this end, it is estimated that by the year 2050, there will be 14 mil‐ lion affected by this disorder in the United States alone (Alzheimer's Association, 2019). This is alarming given that no effective treatment options are available to prevent, treat, or manage AD. 更多前沿医学研究请点击↓ |
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