Ethanol's Effect on Stem Cell Subpopulations And The Implications For Cortical Patterning And Development In Fetal Alcohol Syndrome

dc.creatorTingling, Joseph Duane
dc.date.accessioned2015-05-22T22:10:07Z
dc.date.accessioned2017-04-07T20:16:26Z
dc.date.available2015-05-22T22:10:07Z
dc.date.available2017-04-07T20:16:26Z
dc.date.createdAugust 2012
dc.date.issuedAugust 2012
dc.descriptionHead of Department: William Griffith
dc.description.abstractMaternal alcohol consumption during the first and second trimester of pregnancy remains the leading cause of preventable mental retardation in the United States. Fetal Alcohol Syndrome (FAS) is a wide spectrum disease that is characterized by the craniofacial, cognitive and behavioral developmental defects that occur due to fetal alcohol exposure. FAS describes the extreme manifestation of abnormal fetal development within the broad field of Fetal Alcohol Spectrum Disorders (FASD). Previous work done by Santiallno, et al. have demonstrated that fetal alcohol exposure increases cell cycle activity and decreases stem cell diversity in a mouse neurosphere model of FAS. The goal of this dissertation is to present data on a stem cell surface marker that is ethanol sensitive and serves to indentify a neural stem cell (NSC) subpopulation that is reduced with ethanol exposure. The data presented identifies CD24 as a cell surface marker expressed in mouse neurosphere culture that is decreased with ethanol exposure, which marks a migratory population of NSCs. This paper introduces a novel method of determining the effect of ethanol exposure on this NSC subpopulation by using an in-vivo model of cell migration via ultrasound-guided microinjection. This novel method seeks to address the question of whether an initial cellular exposure to alcohol as opposed to an alcohol microenvironment is responsible for the adverse NSC migration and CNS development in children with FASD. Our data shows that CD24+ expressing cells are significantly reduced in numbers with 320mg/dL high ethanol exposure and as such identifies a pool of NSC that is ethanol sensitive. We also found that ethanol treated CD24+ isolated cells have decreased neurite outgrowth as compared to control after retinoic acid treatment for differentiation. We conclude that an initial binge ethanol exposure is sufficient to cause cell autonomous reprogramming in a newly identified ethanol sensitive subpopulation of migratory NSCs and this provides a stem cell hypothesis for the mechanism behind the teratology of FAS.
dc.identifier.urihttp://hdl.handle.net/1969.1/154259
dc.language.isoen_US
dc.subjectMedical Science
dc.titleEthanol's Effect on Stem Cell Subpopulations And The Implications For Cortical Patterning And Development In Fetal Alcohol Syndrome
dc.typeThesis

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