Browsing by Subject "Neuroepigenetics"

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    DNA Methylation program in normal and alcohol-induced thinning cortex
    (Elsevier, 2017-05) Öztürk, Nail Can; Resendiz, Marisol; Öztürk, Hakan; Zhou, Feng C.; Anatomy and Cell Biology, School of Medicine
    While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7–16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic markers of methylation were assessed using immunohistochemistry, Western blot, and methyl-DNA assays. We report that cortical thickness, neuroepithelial proliferation, and neuronal migration and maturity were found to be deterred by alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program guiding normal embryonic cortical development, was severely affected by in utero alcohol exposure. The intricate relationship between cortical thinning and this DNA methylation program disruption is detailed and illustrated. DNA methylation, dynamic across the multiple cortical layers during the late embryonic stage, is highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with characteristic developmental abnormalities, ranging from structural to molecular. Finally, our findings point to a significant question for future exploration: whether epigenetics guides neurodevelopment or whether developmental conditions dictate epigenetic dynamics in the context of alcohol-induced cortical teratogenesis.
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    Epigenetic regulation of the neural transcriptome and alcohol interference during development
    (Frontiers Media, 2014-08-26) Resendiz, Marisol; Mason, Stephen; Lo, Chiao-Ling; Zhou, Feng C.; Anatomy, Cell Biology and Physiology, School of Medicine
    Alcohol intoxicated cells broadly alter their metabolites - among them methyl and acetic acid can alter the DNA and histone epigenetic codes. Together with the promiscuous effect of alcohol on enzyme activities (including DNA methyltransferases) and the downstream effect on microRNA and transposable elements, alcohol is well placed to affect intrinsic transcriptional programs of developing cells. Considering that the developmental consequences of early alcohol exposure so profoundly affect neural systems, it is not unfounded to reason that alcohol exploits transcriptional regulators to challenge canonical gene expression and in effect, intrinsic developmental pathways to achieve widespread damage in the developing nervous system. To fully evaluate the role of epigenetic regulation in alcohol-related developmental disease, it is important to first gather the targets of epigenetic players in neurodevelopmental models. Here, we attempt to review the cellular and genomic windows of opportunity for alcohol to act on intrinsic neurodevelopmental programs. We also discuss some established targets of fetal alcohol exposure and propose pathways for future study. Overall, this review hopes to illustrate the known epigenetic program and its alterations in normal neural stem cell development and further, aims to depict how alcohol, through neuroepigenetics, may lead to neurodevelopmental deficits observed in fetal alcohol spectrum disorders.