Modeling the epigenesis of the cerebral cortex: an In Vitro study of nurture on the nature and epigenetics of cerebral cortical development : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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College Station, Tex. :
Texas A&M University System Health Science Center,
2006.
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| Subjects: |
| Abstract: | ABSTRACTS: During the brain growth spurt, the ventricular neuroepithelium exhibits significant mitotic activity and gives rise to early differentiating neurons. These proto-neurons leave the ventricular zone to populate the cortical plate or the more superficial subventricular zone, where they may continue to proliferate before migrating into the developing cortical plate. The cortical plate is populated in an 'inside-out' gradient, by successive waves of migrating neurons from the ventricular and sub-ventricular zones, giving rise to the mature lamination pattern of the adult cerebral cortex. One advantage of in vitro models is that they provide a simplistic environment by which to examine the underlying molecular actions of biological processes. In vitro models can also be used to examine the molecular actions of environmental influences on epigenetics. In the following chapters of my dissertation, I describe the experimental models used that I used for exploring the underlying molecular mechanisms of neuronal progentior proliferation, neuronal migration, neuronal differentiation and survival. In chapter II, I describe the experiments that I performed to identify a cohort of neuronal-differentiation associated genes using microarray analysis. In chapter III, I describe a cell culture model that was derived from embryonic murine neurosphere culture to model neuroblasts differentiation. These neurospheres were differentiated by the step-wise removal of the mitogenic factors EGF, LIF and bFGF, and by the simultaneous addition of laminin. In chapter III and IV, I describe the application of this in vitro model in an effort to understand the molecular actions of alcohol exposure during neuronal differentiation and to examine the effects of alcohol exposure on cytokine secretion. Collectively, these data demonstrate that alcohol exposure during cerebral cortical progenitor proliferation can affect subsequent neuronal differentiation. Alcohol pre-exposure prolonged the proliferation potential of differentiated cells, induced aneuploidy, increased migration and neurite outgrowth, increased apoptosis of differentiated cells, disrupted the expression of cell growth and neuronal differentiation associated gene, and increased the secretion of chemotatic cytokines rather than inflammatory cytokines. In summary, this data suggest ethanol-induced changes are likely to have long term consequences on the organization of the neuronal and vascular compartments of the brain. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy August 2006." Approved as to style and content by: Rajesh C. Miranda, Wei-Jung A. Chen, C. Jane Welsh, Reza Forough, John B. Geldard. |
| Physical Description: | xiv, 189 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references. |