Vitamin dificiencies and neural tube defects.

Smithells, R. W.; Sheppard, Sheila; Schorah, C. J.

doi:10.1136/adc.51.12.944

Cited by 529 publications

(255 citation statements)

References 30 publications

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“…Elevated tHcy represents a major risk factor of cardiovascular and cerebrovascular diseases (Homocysteine Studies Collaboration 2002). Moreover, lower serum folate and higher plasma tHcy may also be causes of neural tube defects (NTDs) (Smithells et al 1976; Daly et al 1995), cognitive dysfunction (Seshadri et al 2002), and depression (Bottiglieri 2005). …”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms and folate status

Hiraoka

Kagawa

2017

Congenital Anomalies

136

102

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Moderate hyperhomocysteinemia‐induced low folate status is an independent risk factor for cardiovascular disease, dementia, and depression. Folate is an essential cofactor in the one‐carbon metabolism pathway and is necessary in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. In the folate cycle and homocysteine metabolism, folate, vitamin B12, vitamin B6, and vitamin B2 are important cofactors. Many enzymes are involved in folate transport and uptake, the folate pathway, and homocysteine (Hcy) metabolism, and various polymorphisms have been documented in these enzymes. Serum folate and total Hcy (tHcy) levels are influenced by folate intake and genetic polymorphisms in 5,10‐methylenetertahydrofolate reductase (MTHFR) such as C677T. The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, with a frequency of approximately 15% in Japanese populations. Individuals with the TT genotype have significantly higher tHcy levels and lower folate levels in serum than those with the CT and TT genotypes. However, administration of folic acid has been shown to eliminate these differences. Moreover, data have suggested that interventions based on genotype may be effective for motivating individuals to change their lifestyle and improve their nutrition status. Accordingly, in this review, we discuss the effects of MTHFR C677T polymorphisms on serum tHcy and folate levels with folic acid intervention and evaluate approaches for overcoming folic acid deficiency and related symptoms.

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Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms and folate status

Hiraoka

Kagawa

2017

Congenital Anomalies

136

102

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“…In humans, NTD susceptibility shows complex inheritance with both environmental and genetic contributions. One of the most notable environmental factors is perinatal folic acid intake (Smithells et al, 1976;Blom, 2009). In mice, however, most NTDs are due to single gene defects (Harris and Juriloff, 2007).…”

Section: Introductionmentioning

confidence: 99%

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

Dawe

Kooistra

Fairbridge

et al. 2011

Developmental Dynamics

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The loss of Cecr2, which encodes a chromatin remodeling protein, has been associated with the neural tube defect (NTD) exencephaly and open eyelids in mice. Here, we show that two independent mutations of Cecr2 are also associated with specific inner ear defects. Homozygous mutant 18.5 days post coitus (dpc) fetuses exhibited smaller cochleae as well as rotational defects of sensory cells and extra cell rows in the inner ear reminiscent of planar cell polarity (PCP) mutants. Cecr2 was expressed in the neuroepithelium, head mesenchyme, and the cochlear floor. Although limited genetic interaction for NTDs was seen with Vangl2, a microarray analysis of PCP genes did not reveal a direct connection to this pathway. The mechanism of Cecr2 action in neurogenesis and inner ear development is likely complex.

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“…Low blood folate levels in pregnant women are correlated with higher risk of NTDs in their offspring (Detrait et al, 2005;Smithells et al, 1976) and periconceptional supplementation of folate decreases the recurrence and occurrence of NTDs (MRC Vitamin Study Research Group, 1991).…”

Section: Introductionmentioning

confidence: 99%

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

2017

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Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRα) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs.

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Vitamin dificiencies and neural tube defects.

Cited by 529 publications

References 30 publications

Genetic polymorphisms and folate status

Genetic polymorphisms and folate status

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

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