孕期补充胆碱或能帮后代减少阿尔茨海默病风险
  • 阿尔茨海默模型小鼠于孕期和哺乳期补充膳食胆碱,子代(F1)小鼠内部繁殖产生第二代(F2)小鼠,F2小鼠终生和F1小鼠断奶后都不再补充胆碱;
  • 母鼠补充膳食胆碱,减少了F1和F2小鼠的β淀粉样蛋白负荷和小胶质细胞活化,改善了老年F1和F2小鼠的认知缺陷;
  • 伴随着海马组织中27个基因的表达发生显著改变,这些基因的功能主要与炎症、组蛋白修饰和神经元死亡有关;
  • 这种保护性作用与后代小鼠脑中的同型半胱氨酸减少、甲硫氨酸增加相关。
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mildbreeze
同型半胱氨酸(Hcy)是一种神经毒性氨基酸,其水平上升可增加阿尔茨海默(AD)和痴呆风险;而胆碱可帮助将Hcy转化为甲硫氨酸,减少老年认知衰退。Molecular Psychiatry发表的一项最新研究,在AD小鼠模型中证实,母鼠在孕期和哺乳期补充膳食胆碱,可降低其子代和孙代小鼠的AD风险,为防治AD等疾病的营养干预方法提供了新证据。
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Maternal choline supplementation ameliorates Alzheimer’s disease pathology by reducing brain homocysteine levels across multiple generations

母体补充胆碱通过降低多代人的脑同型半胱氨酸水平来改善阿尔茨海默病的病理学

10.1038/s41380-018-0322-z

2019-01-08, Article

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The lack of effective treatments for Alzheimer’s disease (AD) is alarming, considering the number of people currently affected by this disorder and the projected increase over the next few decades. Elevated homocysteine (Hcy) levels double the risk of developing AD. Choline, a primary dietary source of methyl groups, converts Hcy to methionine and reduces age-dependent cognitive decline. Here, we tested the transgenerational benefits of maternal choline supplementation (ChS; 5.0 g/kg choline chloride) in two generations (Gen) of APP/PS1 mice. We first exposed 2.5-month-old mice to the ChS diet and allowed them to breed with each other to generate Gen-1 mice. Gen-1 mice were exposed to the ChS diet only during gestation and lactation; once weaned at postnatal day 21, Gen-1 mice were then kept on the control diet for the remainder of their life. We also bred a subset of Gen-1 mice to each other and obtained Gen-2 mice; these mice were never exposed to ChS. We found that ChS reduced Aβ load and microglia activation, and improved cognitive deficits in old Gen-1 and Gen-2 APP/PS1 mice. Mechanistically, these changes were linked to a reduction in brain Hcy levels in both generations. Further, RNA-Seq data from APP/PS1 hippocampal tissue revealed that ChS significantly changed the expression of 27 genes. These genes were enriched for inflammation, histone modifications, and neuronal death functional classes. Our results are the first to demonstrate a transgenerational benefit of ChS and suggest that modifying the maternal diet with additional choline reduces AD pathology across multiple generations.

First Authors:
Ramon Velazquez

Correspondence Authors:
Salvatore Oddo

All Authors:
Ramon Velazquez,Eric Ferreira,Wendy Winslow,Nikhil Dave,Ignazio S Piras,Marcus Naymik,Matthew J Huentelman,An Tran,Antonella Caccamo,Salvatore Oddo

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