Journal
METABOLITES
Volume 12, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/metabo12090876
Keywords
maternal folate; folic acid; folate deficiency; brain; neurodevelopment
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Funding
- American Heart Association [20AIREA35050015]
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Folate plays a critical role in pregnancy and deficiency can lead to offspring neurodevelopmental defects. This review examines clinical and preclinical studies to explore the impact of folate deficiency on offspring neurodevelopment and brain function.
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.
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