Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice

Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100083, China.
British Journal Of Nutrition (Impact Factor: 3.45). 04/2008; 99(3):455-61. DOI: 10.1017/S0007114507812074
Source: PubMed


Maternal alcohol consumption during pregnancy can induce central nervous system abnormalities in the fetus, and folic acid supplementation can reverse some of the effects. The objective of the present study was to investigate prenatal alcohol exposure-induced fetal brain proteome alteration and the protective effect of folic acid using proteomic techniques. Alcohol (5.0 g/kg) was given intragastrically from gestational day (GD) 6 to 15, with or without 60.0 mg folic acid/kg given intragastrically during GD 1-16 to pregnant Balb/c mice. The control group received distilled water only. Results of litter evaluation on GD 18 showed that supplementation of folic acid reversed the prevalence of microcephaly induced by alcohol. Proteomic analysis indicated that, under the dosage of the present investigation, folic acid mainly reversed the alcohol-altered proteins involved in energy production, signal pathways and protein translation, which are all important for central nervous system development.

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    • "The disturbance of folic acid metabolism causes craniofacial malformation [14,15] and heart defects [16]. Furthermore, studies showed that supplementation of folic acid successfully modulates alcohol-induced gene expression profiles and alleviates the developmental defects [17,18]. However, the exact mechanism underlying on what specific developmental phase folic acid affects remains elusive. "
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    ABSTRACT: Background Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis.ResultsPre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4%¿±¿4.4%, total embryo n¿=¿234), and 1.5% and 2.0% dramatically augment the deformation to 81.2%¿±¿6.5% (n¿=¿205) and 91.6%¿±¿3.0% (n¿=¿235), respectively (P¿<¿0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies.Conclusions Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.
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    • "Rodent studies also demonstrate skeletal anomalies such as " missing, fused, wavy, or bifurcated ribs and asymmetrical, fused, or missing vertebral arches and centra " in the presence of dietary ethanol (Chernoff, 1977; Randall and Taylor, 1979; Schwetz and Staples, 1978 cited in Downing et al., 2011:67). Poor diets (Boehm et al., 1997; Downing and Gilliam, 1999; Downing et al., 2011), including calcium, iron (Ferm and Carpenter, 1967; Ronchetti et al., 2006), and folate deficiencies (Gutierrez et al., 2007; Xu et al., 2008; Yanaguita et al., 2008) can exacerbate epigenetic effects from ethanol. If pregnant/lactating women were consuming leadcontaminated rum at Newton, their fetuses/infants would have been exposed to ethanol and lead. "
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    ABSTRACT: Alcohol Related Birth Defects (ARBD) are yet undocumented among past communities, although alcohol is the leading cause of non-heritable birth defects in the US today. We evaluate potential ARBD at Newton Plantation, Barbados (ca. 1660–1820), where earlier studies suggest frequent, community-wide consumption of lead-tainted rum by enslaved Africans. Skeletons excavated in 1997–1998 (n = 45) were examined for congenital anomalies, using clinical/experimental descriptions to differentially diagnose possible ARBD. Enamel lead data served as a proxy for developmental exposure to tainted rum in a subsample (n = 26). Elevated enamel lead (3.8 μg/g), vertebral synostosis, and micrognathism in one subadult fit expectations for exposure. An adult male with low enamel lead (0.3 μg/g) had congenital anomalies, but not those described with ethanol or lead exposures. Contrary to expectations, we did not identify ARBD in most individuals, including those with isotopic signatures of Barbadian origin who also showed consistently elevated dental lead levels. We discuss how such patterns may have emerged from timing of exposures and colonial medical practices, but underreporting remains a likely concern with ARBD, past and present. Ours is the first attempt to explore developmental signatures of alcohol use archeologically. We report the first possible case of ARBD from a past community.
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    • "Results in our present study confirmed ethanol-induced fetal abnormalities and showed that CNS was the main target of ethanol's developmental toxicity, indicated by failure of neural folds to fuse in the midline in one or more regions of the forebrain, midbrain, and hindbrain as well as microcephaly. This was in accordance with other studies and characteristics of FAS [9–11] and was partly explained by the inhibition of MB cells' proliferation and differentiation of ethanol found in micromass test. Developmental abnormalities of other organs such as heart, visual system, and auditory systems shown in our results were also coincided with previous researches [5, 12]. "
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    ABSTRACT: The objective of this study was to assess whether nucleotides supplementation in vitro could suppress ethanol-induced developmental toxicity in mouse. The models of whole embryo culture (WEC) and midbrain (MB) cell micromass culture were used in this study. In WEC system, exposure to 4.0 mg/mL ethanol for 48 h yielded various developmental malformations of the mice embryos. Nucleotides supplementation (0.16, 0.80, 4.00, 20.00, and 100.00 mg/L) improved the growth parameters to some extent, and the protective effects peaked at 4.00 mg/L. In MB cell micromass culture system, exposure to 4.0 mg/mL ethanol for 5 days resulted in suppression of proliferation and differentiation. Supplementation of nucleotides (0.16, 0.80, 4.00, 20.00, and 100.00 mg/L) showed some protective effects, which peaked at 4.00 mg/L, too. The present research indicated that nucleotides supplementation might be of some benefit in the prevention of ethanol-induced birth defects; however, appropriate dosage requires attention.
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