Virdi Sapna, Jadavji Nafisa M
Biomedical Sciences Program, Midwestern University, Glendale, AZ 85308, USA.
College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA.
Metabolites. 2022 Sep 16;12(9):876. doi: 10.3390/metabo12090876.
Folate is vital for biological processes within the body, including DNA synthesis, DNA repair, and methylation reactions that metabolize homocysteine. The role of folate is particularly important in pregnancy, where there is rapid cellular and tissue growth. Maternal folate deficiencies secondary to inadequate dietary supplementation are known to produce defects in the neural tube and spinal cord, yet the exact mechanism of folate in neurodevelopment is unknown. The consequences of maternal folate deficiency on offspring brain development and function beyond gestation are not well defined. The objective of this review is to investigate the role of folate deficiency in offspring neurodevelopment, and the complications that arise post-gestation. This was accomplished through a comprehensive review of the data presented in both clinical and preclinical studies. Evidence supports that folate deficiency is associated with altered offspring neurodevelopment, including smaller total brain volume, altered cortical thickness and cerebral white matter, altered neurogenesis, and neuronal apoptosis. Some of these changes have been associated with altered brain function in offspring with memory, motor function, language skills, and psychological issues. This review of literature also presents potential mechanisms of folate deficiency in neurodevelopment with altered metabolism, neuroinflammation, epigenetic modification through DNA methylation, and a genetic deficiency in one-carbon metabolism.
叶酸对于体内的生物过程至关重要,包括DNA合成、DNA修复以及代谢同型半胱氨酸的甲基化反应。叶酸的作用在孕期尤为重要,因为此时细胞和组织生长迅速。已知因膳食补充不足导致的母体叶酸缺乏会产生神经管和脊髓缺陷,但叶酸在神经发育中的具体机制尚不清楚。母体叶酸缺乏对后代出生后大脑发育和功能的影响尚不明确。本综述的目的是研究叶酸缺乏在后代神经发育中的作用以及出生后出现的并发症。这是通过对临床和临床前研究中呈现的数据进行全面综述来完成的。有证据支持叶酸缺乏与后代神经发育改变有关,包括全脑体积减小、皮质厚度和脑白质改变、神经发生改变以及神经元凋亡。其中一些变化与后代在记忆、运动功能、语言技能和心理问题方面的脑功能改变有关。本综述还介绍了叶酸缺乏在神经发育中的潜在机制,包括代谢改变、神经炎症、通过DNA甲基化的表观遗传修饰以及一碳代谢的遗传缺陷。