Epigenetic alteration by prenatal alcohol exposure in developing mouse hippocampus and cortex

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dc.contributor.advisorZhou, Feng C.
dc.contributor.authorChen, Yuanyuan
dc.contributor.otherJin, Xiao-Ming
dc.contributor.otherTruitt, William A.
dc.contributor.otherReiter, Jill L.
dc.date.accessioned2015-02-03T18:27:15Z
dc.date.available2015-02-03T18:27:15Z
dc.date.issued2014
dc.degree.date2014en_US
dc.degree.disciplineDepartment of Anatomy & Cell Biologyen
dc.degree.grantorIndiana Universityen_US
dc.degree.levelPh.D.en_US
dc.descriptionIndiana University-Purdue University Indianapolis (IUPUI)en_US
dc.description.abstractFetal alcohol spectrum disorders (FASD) is the leading neurodevelopment deficit in children born to women who drink alcohol during pregnancy. The hippocampus and cortex are among brain regions vulnerable to alcohol-induced neurotoxicity, and are key regions underlying the cognitive impairment, learning and memory deficits shown in FASD individuals. Hippocampal and cortical neuronal differentiation and maturation are highly influenced by both intrinsic transcriptional signaling and extracellular cues. Epigenetic mechanisms, primarily DNA methylation and histone modifications, are hypothesized to be involved in regulating key neural development events, and are subject to alcohol exposure. Alcohol is shown to modify DNA methylation and histone modifications through altering methyl donor metabolisms. Recent studies in our laboratory have shown that alcohol disrupted genome-wide DNA methylation and delayed early embryonic development. However, how alcohol affects DNA methylation in fetal hippocampal and cortical development remains elusive, therefore, will be the theme of this study. We reported that, in a dietary alcohol-intake model of FASD, prenatal alcohol exposure retarded the development of fetal hippocampus and cortex, accompanied by a delayed cellular DNA methylation program. We identified a programed 5-methylcytosine (5mC) and 5-hydroxylmethylcytosine (5hmC) cellular and chromatic re-organization that was associated with neuronal differentiation and maturation spatiotemporally, and this process was hindered by prenatal alcohol exposure. Furthermore, we showed that alcohol disrupted locus-specific DNA methylation on neural specification genes and reduced neurogenic properties of neural stem cells, which might contribute to the aberration in neurogenesis of FASD individuals. The work of this dissertation suggested an important role of DNA methylation in neural development and elucidated a potential epigenetic mechanism in the alcohol teratogenesis.en_US
dc.identifier.urihttps://hdl.handle.net/1805/5810
dc.identifier.urihttp://dx.doi.org/10.7912/C2/2106
dc.language.isoen_USen_US
dc.subjectEpigeneticsen_US
dc.subject.lcshEpigenetics -- Research -- Methodologyen_US
dc.subject.lcshFetal alcohol syndrome -- Pathophysiologyen_US
dc.subject.lcshAlcohol -- Physiological effecten_US
dc.subject.lcshCognition disorders -- Animal modelsen_US
dc.subject.lcshDNA -- Methylation -- Researchen_US
dc.subject.lcshHistones -- Researchen_US
dc.subject.lcshDevelopmental neurobiology -- Animal modelsen_US
dc.subject.lcshHippocampus (Brain) -- Toxicology -- Animal modelsen_US
dc.subject.lcshHippocampus (Brain) -- Pathophysiology -- Animal modelsen_US
dc.subject.lcshNeural stem cellsen_US
dc.subject.lcshDevelopmental geneticsen_US
dc.subject.lcshGenetic transcriptionen_US
dc.titleEpigenetic alteration by prenatal alcohol exposure in developing mouse hippocampus and cortexen_US
dc.typeThesisen
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