Browsing by Subject "fetal alcohol spectrum disorder"

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    Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets
    (MDPI, 2013-06-19) Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A.; Biology, School of Science
    Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.
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    Is 5-Hydroxymethylcytosine a Suppressor or Activator in Epigenetic Marks?
    (Office of the Vice Chancellor for Research, 2013-04-05) Watkins, Darryl S.; Chen, Yuanyuan; Zhou, Feng C.
    Alcohol has been observed to have teratogenic effects on humans and mice during different stages of embryonic development. These effects can be condensed under fetal alcohol spectrum disorder (FASD), exhibiting a variety of signs from growth retardations to neurobehavioral aberrations. Despite better understanding of several potential mechanisms, the question of how alcohol, as an environmental factor leads to brain growth delay in FASD remains elusive. DNA methylation is key to development and tissue specification. Studies have suggested that alcohol may alter gene expression by affecting DNA and histone methylation. Previous studies have demonstrated that 5-methylcytosine (5mC), a DNA methylation mark, is associated with histone 3 lysine-9me3, (H3K9me3) to play a role in gene repression. Recently another methylation mark, 5hydroxylmethylcytosine (5hmC), was found to prevail in the nervous system. However, its function has not been clear. Global analysis suggests that it is a transition of demethylation leading to transcription. The study will first identify its association with histone 3 lysine-4me3, (H3K4me3) a transcriptional activator in gene expression, and then study the 5hmC under influence of alcohol exposure. This study will utilize both an in vivo model—the vapor chamber, and an in vitro model—the embryonic culture system to address this question. Embryos were exposed to alcohol (400mg/dL, 88mM) from the beginning of embryonic day (E) 8 for 6hrs, harvested at E10, and processed for immunohistochemistry. Compare the DNA methylation marks, and histone modification marks to see if the spatial and/or temporal distribution has been affected by alcohol exposure. It is expected that in the alcohol-treated embryos, an overall retardation of embryonic growth, delayed neural tube formation, and altered expression of epigenetic markers will be observed. This study could indicate that alcohol, through alteration of DNA and histone methylation is a potential mechanism underpinning brain growth delay in FASD.
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    Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)
    (Wiley, 2017) Muralidharan, Pooja; Connors, Craig; Mohammed, Arooj S.; Sarmah, Swapnalee; Marrs, Kathleen A.; Marrs, James A.; Chism, Grady W.; Biology, School of Science
    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol‐induced developmental defect using zebrafish as a model was determined. Ethanol‐induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol‐induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol‐treated embryos. The mechanism underlying the rescue remains to be determined.