Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, sala 107, 90050- 170, Porto Alegre, RS, Brazil; Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, 90050- 170, Porto Alegre, RS, Brazil.
Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, 90050- 170, Porto Alegre, RS, Brazil.
J Nutr Biochem. 2018 Oct;60:35-46. doi: 10.1016/j.jnutbio.2018.06.008. Epub 2018 Jul 5.
Folic acid (FA) supplementation (400 μg/day) has been recommended during pregnancy to prevent neural tube defects. However, in some countries, flours are required to be fortified with FA, possibly increasing the levels of this vitamin in pregnant women. Our previous studies have evidenced a dual effect of the FA treatment in a rat model of neonatal hypoxia-ischemia (HI). Aiming to better correlate with humans, this paper evaluated the effects of two different levels of FA supplementation during pregnancy on memory parameters and neuronal survival and plasticity in the hippocampus of rats submitted to the neonatal HI. During pregnancy, female Wistar rats received one of these diets: standard (SD), supplemented with 2 mg/kg of FA or with 20 mg/kg of FA. At the 7 PND, rats suffered the HI procedure. At the 60 PND rats were evaluated in the open field, Morris water maze, novel-object recognition and inhibitory avoidance tasks. Furthermore, neuronal density, synaptophysin densitometry and BDNF concentration were assessed in the hippocampus. Both doses of FA prevented the HI-induced memory impairments. The supplementation reversed the BDNF late increase in the hippocampus of the HI rats, but did not inhibit the neuronal death. In conclusion, FA supplementation during pregnancy prevented memory deficits and BDNF imbalance after neonatal HI. These findings are particularly relevant because neuroprotection was achieved even in the high level of FA supplementation during pregnancy, indicating that this intervention would be considered secure for the offspring development.
叶酸（FA）补充剂（每天 400μg）已被推荐在怀孕期间使用，以预防神经管缺陷。然而，在一些国家，面粉需要添加 FA 进行强化，这可能会增加孕妇体内这种维生素的水平。我们之前的研究在新生大鼠缺氧缺血（HI）模型中证明了 FA 治疗的双重作用。为了更好地与人类相关，本文评估了怀孕期间两种不同水平的 FA 补充对接受新生 HI 的大鼠海马记忆参数、神经元存活和可塑性的影响。在怀孕期间，雌性 Wistar 大鼠接受以下饮食之一：标准（SD）饮食，补充 2mg/kg 的 FA 或 20mg/kg 的 FA。在 7PND 时，大鼠接受 HI 处理。在 60PND 时，大鼠在旷场、Morris 水迷宫、新物体识别和抑制性回避任务中进行评估。此外，还评估了海马中的神经元密度、突触小体密度和 BDNF 浓度。两种剂量的 FA 均可预防 HI 引起的记忆障碍。补充剂逆转了 HI 大鼠海马中 BDNF 的后期增加，但没有抑制神经元死亡。总之，FA 补充剂可预防新生 HI 后记忆缺陷和 BDNF 失衡。这些发现特别重要，因为即使在怀孕期间高剂量的 FA 补充也能实现神经保护，表明这种干预措施对后代的发育是安全的。
