Neural Tube Defects, Folic Acid and Methylation

Abstract

Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

Role of folic acid in the prevention of fetal nervous system diseases

“…Анализируя различные этиологические факторы пороков развития у плода, мож-но выделить генетические и негенетические причинные факторы (например, нутритивный статус или ожирение у матери) [19][20][21].…”

“…С другой стороны, по данным проведенных за последние десятилетия исследо-ваний [24], отмечено, что развитие ДНТ связано с авита-минозом, а экзогенное или периконцепционное посту-пление ФК в организм будущей матери способствует сни-жению риска ДНТ у плода. Необходимо отметить, что не только дефицит фолатов в организме беременной являет-ся фактором риска развития ДНТ, но и особенность тече-ния всего процесса метилирования влияет на формирова-ние ДНТ [20,25]. В ряде исследований [26] сообщается о профилактике ДНТ и коррекции дефектов биосинтеза при поступлении экзогенной ФК и тимидина у гомози-готных эмбрионов мыши splotch (Pax3).…”

A Randomized, Placebo-Controlled Trial in Women of Childbearing Age to Assess the Effect of Folic Acid and Methyl-Tetrahydrofolate on Erythrocyte Folate Levels

“…The efficacy of periconceptional folic acid supplementation in reducing the risk of NTDs is well established [8], although it might be less efficacious in women with genetic variants of methyl-tetrahydrofolate reductase (MTHFR), an enzyme required to transform folic acid into its active form MTHF [9][10][11]. Those women may particularly benefit from supplemental MTHF as this bypasses the metabolic activation.…”

Quantitative studies of Co(II)-thymoquinone complex using cyclic voltammetry

“…Some of them are pernicious anaemia, nervous disorders, paralysis [3][4][5][6] , thyroid stimulation and polycythemia. 7 Co(II) forms numerous complexes, out of which its octahedral and tetrahedral complexes are most common but it forms five-coordinate and square planer complexes also.…”