Inositol, neural tube closure and the prevention of neural tube defects.
Inositol, neural tube closure and the prevention of neural tube defects.
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DOI：
10.1002/bdra.23533
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发表时间：
2017-01-30
影响因子：
2.1
通讯作者：
Copp AJ
中科院分区：
文献类型：
--
作者：
Greene ND;Leung KY;Copp AJ
神经管缺陷（NTDs），如无脑畸形和脊柱裂的易感性受到遗传和环境因素，包括母亲营养的影响。孕妇围受孕期补充叶酸可显著降低NTD影响妊娠的风险，但不能预防所有NTD，并且“叶酸无反应”NTD仍会发生。同样，在NTD的小鼠模型中，一些对叶酸有反应，而另一些则没有。在营养因素中，肌醇缺乏导致小鼠的颅NTD，而补充肌醇防止卷曲尾（Grhl 3亚型）小鼠、高血糖症或诱导的糖尿病的啮齿动物模型以及叶酸缺乏诱导的NTD模型中的脊髓和颅NTD。NTD也发生在缺乏某些肌醇激酶表达的小鼠中。含肌醇的磷脂（磷酸肌醇）和可溶性肌醇磷酸盐介导一系列功能，包括细胞内信号传导、与细胞骨架蛋白的相互作用以及在运输和细胞分裂中调节膜特性。 肌醇已在人类中进行了一系列条件的试验，并且似乎可安全用于人类妊娠。在意大利和英国的试点研究中，妇女在一次或多次受NTD影响的怀孕后，孕前服用肌醇和叶酸。在英国的非随机队列和随机双盲研究中，迄今为止报告的52例妊娠中未观察到复发性NTD。需要进行更大规模的充分试验来确定补充肌醇和叶酸是否比单独服用叶酸更有效地预防NTD。出生缺陷研究109：68-80，2017年。© 2016作者出生缺陷研究出版的威利期刊，公司.
Susceptibility to neural tube defects (NTDs), such as anencephaly and spina bifida is influenced by genetic and environmental factors including maternal nutrition. Maternal periconceptional supplementation with folic acid significantly reduces the risk of an NTD‐affected pregnancy, but does not prevent all NTDs, and “folic acid non‐responsive” NTDs continue to occur. Similarly, among mouse models of NTDs, some are responsive to folic acid but others are not. Among nutritional factors, inositol deficiency causes cranial NTDs in mice while supplemental inositol prevents spinal and cranial NTDs in the curly tail (Grhl3 hypomorph) mouse, rodent models of hyperglycemia or induced diabetes, and in a folate‐deficiency induced NTD model. NTDs also occur in mice lacking expression of certain inositol kinases. Inositol‐containing phospholipids (phosphoinositides) and soluble inositol phosphates mediate a range of functions, including intracellular signaling, interaction with cytoskeletal proteins, and regulation of membrane identity in trafficking and cell division. Myo‐inositol has been trialed in humans for a range of conditions and appears safe for use in human pregnancy. In pilot studies in Italy and the United Kingdom, women took inositol together with folic acid preconceptionally, after one or more previous NTD‐affected pregnancies. In nonrandomized cohorts and a randomized double‐blind study in the United Kingdom, no recurrent NTDs were observed among 52 pregnancies reported to date. Larger‐scale fully powered trials are needed to determine whether supplementation with inositol and folic acid would more effectively prevent NTDs than folic acid alone. Birth Defects Research 109:68–80, 2017. © 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.