Mol Neurobiol:低叶酸饮食和轻度MTHFR缺乏导致脑衰老的早期表现

2019-07-15 sunshine 译 MedSci原创

叶酸是甲基化反应,核苷酸和神经递质合成以及维持高半胱氨酸处于无毒性水平所需的重要的B族维生素。其代谢与胆碱,乙酰胆碱和膜磷脂的前体紧密相关。叶酸代谢中的低叶酸摄入和遗传变异,例如亚甲基四氢叶酸还原酶(MTHFR)677 C> T多态性,可影响脑功能并增加认知衰退和晚发性阿尔茨海默病的发病风险。本研究旨在评估小鼠模型中叶酸代谢的遗传和营养紊乱对认知衰退和脑生化特征的影响,及其潜在的相互作用。将

叶酸是甲基化反应,核苷酸和神经递质合成以及维持高半胱氨酸处于无毒性水平所需的重要的B族维生素。其代谢与胆碱,乙酰胆碱和膜磷脂的前体紧密相关。叶酸代谢中的低叶酸摄入和遗传变异,例如亚甲基四氢叶酸还原酶(MTHFR)677 C> T多态性,可影响脑功能并增加认知衰退和晚发性阿尔茨海默病的发病风险。本研究旨在评估小鼠模型中叶酸代谢的遗传和营养紊乱对认知衰退和脑生化特征的影响,及其潜在的相互作用。

将野生型和Mthfr +/-小鼠(MTHFR 677 C> T多态性的模型)从断奶开始喂以对照或叶酸缺乏的饮食,直至8和10月龄。结果研究人员发现,新物体识别程序中小鼠出现短期记忆障碍,突触标记物和表观遗传酶的转录水平改变,以及由于皮质或海马中的Mthfr +/-基因型导致的胆碱代谢受损。此外,研究人员还检测到由于叶酸缺乏的饮食,Presenillin-1,神经营养因子,单碳代谢和表观遗传酶的mRNA水平的变化,以及S-腺苷甲硫氨酸和乙酰胆碱水平的降低。

这些发现进一步深入了解了遗传和饮食叶酸代谢紊乱增加认知衰退风险的机制,并表明这些机制是不同的。

原始出处:

Bahous RH, Cosín-Tomás M, et al., Early Manifestations of Brain Aging in Mice Due to Low Dietary Folate and Mild MTHFR Deficiency. Mol Neurobiol. 2019 Jun;56(6):4175-4191. doi: 10.1007/s12035-018-1375-3. Epub 2018 Oct 4.

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