Folate, Homocysteine and the Cardiac Neural Crest

Rosenquist, Thomas H.

doi:10.1002/dvdy.23922

Cited by 40 publications

(31 citation statements)

References 254 publications

(344 reference statements)

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“…Many teratogens have significant effects on the early development of the cardiovascular system. These include environmental toxins and medications, many which affect neural crest cells (Grimes et al, and reviewed in van Gelder et al, ; Rosenquist, ). Two important classes of teratogenic mechanisms discussed by van Gelder et al (), “folate antagonism” and “neural crest disruption” may be at work in inducing CHDs.…”

Section: Teratogens Disturb Neural Crest Cellsmentioning

confidence: 99%

“…Too low or too high levels of retinoic acid (RA) signaling are known to cause cardiac and other effects very similar to those observed after neural crest ablation (Sinning, ; Zile, ; Pan and Baker, ). Lithium, elevated homocysteine, and ethanol may work through a common pathway, the one carbon cycle, that is rescued by folate and other compounds (Linask and Laties, ; Han et al, ; Linask and Huhta, and reviewed in van Gelder et al, ; Rosenquist, ). This link to a common pathway suggests that an understanding of how one teratogen causes defects may elucidate a general mechanism that might be activated by other teratogens.…”

Section: Teratogens Disturb Neural Crest Cellsmentioning

confidence: 99%

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Connecting teratogen‐induced congenital heart defects to neural crest cells and their effect on cardiac function

Karunamuni

et al. 2014

Birth Defects Research Pt C

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Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies.

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Section: Teratogens Disturb Neural Crest Cellsmentioning

confidence: 99%

Section: Teratogens Disturb Neural Crest Cellsmentioning

confidence: 99%

Connecting teratogen‐induced congenital heart defects to neural crest cells and their effect on cardiac function

Karunamuni

et al. 2014

Birth Defects Research Pt C

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“…Folate provides methyl groups for DNA methylation (Fox, & Stover, 2008) and is shown to be critical for the formation of craniofacial structures (Jiang, Bush, & Lidral, 2006;Rosenquist, 2013). The folate level and provided methyl group are influenced by the key enzyme encoded by methyltetrahydrofolate reductase (MTHFR) gene (van der Put et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

LINE‐1 methylation in cleft lip tissues: Influence of infant MTHFR c.677C>T genotype

et al. 2019

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Objective To investigate the influence of MTHFR c.677C>T genotype on LINE‐1 methylation in lateral and medial tissues from cleft lip (CL). Methods Forty‐five consecutive non‐syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study. Genomic DNA was extracted from tissues at both sides of cleft lip, and LINE‐1 methylation was detected by bisulfite conversion and pyrosequencing. MTHFR c.677C>T genotyping was carried out using the TaqMan genotyping assay. Results LINE‐1 methylation level was significantly higher on medial side of cleft lip compared with lateral side (p = 0.001). This difference was not significantly influenced by the case's sex or cleft type. However, MTHFR c.677C>T genotyping revealed that the difference in LINE‐1 methylation across cleft lip was restricted to carriers of C allele of MTHFR c.677C>T and was not apparent in TT homozygous cases (p = 0.027). Conclusion This integrated analysis supports the previous finding of differences in DNA methylation across the two sides of cleft lip and further suggests a possible role of MTHFR c.677C>T genotype in establishing this difference.

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“…Methylation from folates also occurs in a cycle that generates methionine. Within this cycle, methyl groups can also be removed from methionine leading to homocysteine, a nonprotein amino acid that, if accumulating at high serum levels, can lead to vascular inflammation and ischemic injury, and can also be teratogenic during embryonic development [reviewed by Rosenquist, 2013]. This cycle requires folate to provide methyl groups.…”

Section: Introductionmentioning

confidence: 99%

Influence of Folic Acid on Neural Connectivity during Dorsal Root Ganglion Neurogenesis

Wiens

DeWitt

Kosar

et al. 2016

Cells Tissues Organs

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The vitamin folic acid (FA) is essential for DNA synthesis, repair and methylation, and for methionine synthesis. Although it is necessary for neural development, recent studies suggest a possible link between excess maternal supplemental FA intake and adverse interferences with single-carbon metabolism and neural development. Insufficient FA early in brain development can lead to failure of the neural tube closure, but the consequences of too much intake have not been fully investigated. Plasma FA concentrations can increase greatly with dietary supplementation. To model the development of neural connectivity, we cultured dorsal root ganglia (DRGs) taken from 8-day-old chick embryos in a range of pteroylmonoglutamate (PteGlu, synthetic supplemental FA) concentrations. DRGs were cultured for 36 h, fixed and immunostained to reveal the locations of neural networks with synaptic vesicles. We found a concentration-dependent relationship with significant reduction in neurite length in PteGlu concentrations from 0.25 to 20 μM. The average total of stained synaptic areas surrounding each cultured DRG was significantly reduced as well. To further characterize the effects, we carried out time-lapse imaging of growth cones at terminals of extending neurites. We found that PteGlu reduced the area-changing activity of the growth cone, hindering its exploratory capabilities, along with a tendency to inhibit overall advancement, thus altering the ability to extend and form synapses. Our results show that PteGlu at 250 nM and higher reduces neurite extension and synapse formation in a dose-dependent manner during neurogenesis, and that its effect is mediated through inhibition of growth cone motility.

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Folate, Homocysteine and the Cardiac Neural Crest

Cited by 40 publications

References 254 publications

Connecting teratogen‐induced congenital heart defects to neural crest cells and their effect on cardiac function

Connecting teratogen‐induced congenital heart defects to neural crest cells and their effect on cardiac function

LINE‐1 methylation in cleft lip tissues: Influence of infant MTHFR c.677C>T genotype

Influence of Folic Acid on Neural Connectivity during Dorsal Root Ganglion Neurogenesis

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