Departamento de Ciencias Farmacéuticas y de la Alimentación, Facultad de Farmacia, San Pablo CEU University, Madrid, Spain.
Eur J Nutr. 2013 Apr;52(3):1157-67. doi: 10.1007/s00394-012-0426-1. Epub 2012 Jul 26.
Folic acid (FA) is an emerging nutritional factor in the pathogenesis of diverse neurodegenerative disorders by still unknown mechanisms. The hippocampus is altered during the loss of cognitive abilities in humans and selectively affected when homocysteine increases. The aim was to evaluate the potential protective role of folic acid in the maintenance of biochemical markers related to the methionine cycle, as well as the integrity of the hippocampus as part of the brain in aged rats.
Male Sprague-Dawley rats (18 months old) were assigned to four different folic acid groups (0 mg FA/kg diet, deficient; 2 mg FA/kg diet, control; 8 mg FA/kg diet, moderate supplementation; 40 mg FA/kg diet, extra supplementation) for 30 days. We evaluated several parameters related to the methionine cycle. In addition, hippocampus areas were immunostained for specific neuronal markers and astrocytes.
Serum folate levels increased according to FA dietary level (p < 0.01). There was a significant increase in the serum homocysteine concentrations in the folic acid-deficient diet group (p < 0.01). However, brain S-adenosylmethionine and S-adenosylhomocysteine did not differ significantly between the folic acid groups. Consequently, the methylation ratio was also unchanged. The morphometric analysis did not show any differences in the number of neurons and astrocytes between groups, except when comparing the folic acid-deficient diet versus folic acid-supplemented diet in the striatum of the hippocampus.
Clearly, the dietary FA deficiency negatively affects the methionine metabolism biomarkers, while excessive supplementation seems to be unnecessary for optimal maintenance of the methylation cycle and hippocampus integrity.
叶酸（FA）是通过仍未知的机制在多种神经退行性疾病发病机制中出现的新兴营养因素。在人类认知能力丧失期间，海马体发生改变，并且当同型半胱氨酸增加时，海马体受到选择性影响。目的是评估叶酸在维持与蛋氨酸循环相关的生化标志物以及海马体作为大脑一部分的完整性方面的潜在保护作用，因为这是大脑的一部分。
雄性 Sprague-Dawley 大鼠（18 个月大）被分为四个不同的叶酸组（0mg FA/kg 饮食，缺乏；2mg FA/kg 饮食，对照；8mg FA/kg 饮食，中度补充；40mg FA/kg 饮食，额外补充），为期 30 天。我们评估了与蛋氨酸循环相关的几个参数。此外，海马区被用于特定神经元标志物和星形胶质细胞的免疫染色。
血清叶酸水平随 FA 饮食水平的增加而增加（p<0.01）。叶酸缺乏饮食组的血清同型半胱氨酸浓度显著增加（p<0.01）。然而，大脑 S-腺苷甲硫氨酸和 S-腺苷同型半胱氨酸在叶酸组之间没有显著差异。因此，甲基化比率也没有改变。形态计量分析显示，除了在海马体纹状体中比较叶酸缺乏饮食与叶酸补充饮食外，各组之间神经元和星形胶质细胞的数量没有差异。
显然，饮食中 FA 的缺乏会对蛋氨酸代谢生物标志物产生负面影响，而过度补充似乎对于最佳维持甲基化循环和海马体完整性是不必要的。
