Inositol prevents folate-resistant neural tube defects in the mouse
Inositol prevents folate-resistant neural tube defects in the mouse
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DOI：
10.1038/nm0197-60
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发表时间：
1997-01-01
期刊：
影响因子：
82.9
通讯作者：
Copp, AJ
中科院分区：
文献类型：
--
作者：
Greene, NDE;Copp, AJ
临床试验表明，高达70%的神经管缺陷(NTD)可以通过在怀孕早期补充叶酸来预防，而其余的NTD对叶酸具有抵抗力。在这里，我们展示了第二种维生素，肌醇，能够显著降低卷尾小鼠脊髓NTDS的发生率，卷尾小鼠是一种叶酸抗性NTDS的遗传模型。肌醇通过肌醇/脂循环增加流量，刺激蛋白激酶C活性并上调维甲酸受体β的表达，特别是在胚胎后肠的尾部。这减少了后神经孔关闭的延迟，后神经孔是已知的胚胎缺陷，直接导致卷尾胚胎的脊柱裂。我们的发现揭示了NTD预防的分子途径，并提示叶酸和肌醇联合治疗在克服大多数人类NTDS方面可能有效。
Clinical trials demonstrate that up to 70% of neural tube defects (NTDs) can be prevented by folic acid supplementation in early pregnancy, whereas the remaining NTDs are resistant to folate. Here, we show that a second vitamin, myo-inositol, is capable of significantly reducing the incidence of spinal NTDs in curly tail mice, a genetic model of folate-resistant NTDs. Inositol increases flux through the inositol/lipid cycle, stimulating protein kinase C activity and upregulating expression of retinoic acid receptor beta, specifically in the caudal portion of the embryonic hindgut. This reduces the delay in closure of the posterior neuropore, the embryonic defect that is known to lead directly to spina bifida in curly tail embryos. Our findings reveal a molecular pathway of NTD prevention and suggest the possible efficacy of combined treatment with folate and inositol in overcoming the majority of human NTDs.