Folic acid supplementation changes the fate of neural progenitors in mouse embryos of hyperglycemic and diabetic pregnancy.
Folic acid supplementation changes the fate of neural progenitors in mouse embryos of hyperglycemic and diabetic pregnancy.
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DOI：
10.1016/j.jnutbio.2012.09.004
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发表时间：
2013-07
期刊：
影响因子：
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通讯作者：
Qiuhuan Yuan;Shidou Zhao;Shangming Liu;Yanmin Zhang;Jie Fu;Fu‐wu Wang;Qian Liu;E. Ling;A. Hao-A.
中科院分区：
文献类型：
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作者：
Qiuhuan Yuan;Shidou Zhao;Shangming Liu;Yanmin Zhang;Jie Fu;Fu‐wu Wang;Qian Liu;E. Ling;A. Hao-A.
叶酸已被证明可以降低正常和高血糖条件下神经管缺陷（NTD）的发生率，但叶酸对中枢神经系统发育的影响尚未完全了解。本研究旨在探讨叶酸，特别是高剂量叶酸对高血糖和糖尿病小鼠胚胎神经前体细胞特性的影响。高血糖和糖尿病妊娠小鼠从胚胎第0.5天（E0.5）开始给予3 mg/kg或15 mg/kg叶酸，并在E11.5、E13.5或E18.5处死。统计E13.5时NTD的发生率。采用BrdU掺入法、TUNEL法、免疫荧光法、Western blot和实时逆转录聚合酶链反应检测神经前体细胞的增殖、凋亡、分化和神经元迁移。正常和高剂量叶酸均能降低高血糖和糖尿病小鼠胚胎神经管缺陷的发生率，促进神经上皮细胞增殖，减少神经上皮细胞凋亡。重要的是，叶酸，特别是在高剂量，可能会影响神经前体细胞在高血糖和糖尿病妊娠胚胎的过早分化。这可能是由于一些基本螺旋环螺旋转录因子的信使RNA表达水平的变化。此外，叶酸可能参与调节高血糖和糖尿病妊娠胚胎神经元迁移。这些研究结果表明，围受孕期补充叶酸，特别是在高剂量，可能是一把双刃剑，因为它可能会导致不良后果，影响神经元和神经胶质细胞的分化在高血糖和糖尿病妊娠。
Folic acid has been shown to decrease the incidence of neural tube defects (NTDs) in normal and hyperglycemic conditions, but the influence of folic acid on the development of central nervous system is not fully understood. Here, we aimed to explore the effects of folic acid, especially high dose of folic acid, on the characteristics of neural progenitors in embryos of hyperglycemic and diabetic mouse. Hyperglycemic and diabetic pregnant mice were given 3 mg/kg or 15 mg/kg folic acid from embryonic day 0.5 (E0.5) and were euthanased on E11.5, E13.5 or E18.5. The incidence of NTDs at E13.5 was counted. The proliferation, apoptosis and differentiation of neural progenitors and neuronal migration were determined using BrdU incorporation assay, TUNEL assay, immunofluorescence, Western blot and real-time reverse transcriptase polymerase chain reaction. Both normal and high doses of folic acid decreased the incidence of NTDs, promoted proliferation and reduced apoptosis of neuroepithelial cells in embryos of hyperglycemic and diabetic mice. Importantly, folic acid, especially at high dose, might affect the premature differentiation of neural progenitors in embryos of hyperglycemic and diabetic pregnancy. This may be attributed to changes of messenger RNA expression levels of some basic–helix–loop–helix transcription factors. In addition, folic acid might be involved in regulating neuronal migration in embryos of hyperglycemic and diabetic pregnancy. These findings suggest that periconceptional supplementation of folic acid, especially at high dose, may be a double-edged sword because it may result in undesirable outcomes affecting both the neuronal and glial differentiation in hyperglycemic and diabetic pregnancy.