Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.
Department of Social Medicine and Health Administration, School of Public Health, Tianjin Medical University, Tianjin, China.
Cereb Cortex. 2019 Jul 22;29(8):3390-3397. doi: 10.1093/cercor/bhy207.
Maternal folic acid supplementation during pregnancy is associated with improved cognitive performances in offspring. However, the effect of supplementation on offspring's neurogenesis and synaptogenesis is unknown, and whether supplementation should be continued throughout pregnancy is controversial. In present study, 3 groups of female rats were fed a folate-normal diet, folate-deficient diet, or folate-supplemented diet from 1 week before mating until the end of pregnancy. A fourth group fed folate-normal diet from 1 week before mating until mating, then fed folate-supplemented diet for 10 consecutive days, then fed folate-normal diet until the end of pregnancy. Offspring were sacrificed on postnatal day 0 for measurement of neurogenesis and synaptogenesis by immunofluorescence and western blot. Additionally neural stem cells (NSCs) were cultured from offspring's hippocampus for immunocytochemical measurement of their rates of proliferation and neuronal differentiation. The results demonstrated that maternal folic acid supplementation stimulated hippocampal neurogenesis by increasing proliferation and neuronal differentiation of NSCs, and also enhanced synaptogenesis in cerebral cortex of neonatal offspring. Hippocampal neurogenesis was stimulated more when supplementation was continued throughout pregnancy instead of being limited to the periconceptional period. In conclusion, maternal folic acid supplementation, especially if continued throughout pregnancy, improves neurogenesis and synaptogenesis in neonatal offspring.
孕期母体补充叶酸可改善后代的认知表现。然而，补充剂对后代神经发生和突触发生的影响尚不清楚，且补充剂是否应在整个孕期持续补充存在争议。在本研究中，3 组雌性大鼠从交配前 1 周开始分别喂食叶酸正常饮食、叶酸缺乏饮食或叶酸补充饮食，直至妊娠结束。第四组大鼠从交配前 1 周开始喂食叶酸正常饮食，然后连续 10 天喂食叶酸补充饮食，然后喂食叶酸正常饮食直至妊娠结束。产后第 0 天处死后代，通过免疫荧光和 Western blot 测量神经发生和突触发生。此外，还从后代海马中培养神经干细胞（NSCs），通过免疫细胞化学测量其增殖和神经元分化率来测量其增殖和神经元分化率。结果表明，母体叶酸补充通过增加 NSCs 的增殖和神经元分化来刺激海马神经发生，并增强新生后代大脑皮质中的突触发生。当补充剂持续整个孕期而不是仅在围孕期时，会更刺激海马神经发生。总之，母体叶酸补充，尤其是持续整个孕期补充，可改善新生后代的神经发生和突触发生。
