Fetal alcohol spectrum disorders: alteration of neuronal morphology by ethanol, choline and tissue plasminogen activator Public Deposited

Fetal Alcohol Spectrum Disorders (FASD), which results from gestational ethanol (a short-chain primary alcohol) exposure, is the most common form of preventable intellectual disability. Individuals with FASD have a variety of Central Nervous System dysfunctions, including impulsivity, difficulties with abstract thinking, problems with memory, and learning disabilities. FASD is highly prevalent throughout the world; in the United States alone, it is estimated that 24-48 in 1,000 individuals have FASD. While the mechanisms underlying the response of the developing brain to gestational ethanol exposure are not fully understood, a potential mechanism is tissue plasminogen activator (tPA), which is upregulated by ethanol, both in vivo and in vitro. There is also a potential treatment for FASD, choline, which has been shown to ameliorate some of the effects of prenatal ethanol exposure. Furthermore, some of the effects of ethanol on tPA, and the capacity for choline to be a treatment, may be mediated by astrocytes, which have been shown to influence neurons and neuronal morphology. Therefore, the experiments in this dissertation examined the hypothesis that gestational ethanol exposure alters neuronal morphology, and that this alteration is, in part, due to astrocyte-mediated increases in tPA caused by ethanol. These experiments also examined the secondary hypothesis that astrocytes can mediate a rescue effect of choline on neuronal morphology alterations induced by ethanol. To test the main hypothesis, experiments examined in vitro astrocytic modulation of neurite outgrowth following treatment of astrocytes with ethanol, choline or tPA. Other experiments analyzed the effects of ethanol and choline in vivo, to examine alterations of hippocampal pyramidal CA1 neuronal morphology induced by these treatments (see Fig. 1.1 for mechanisms of choline and Fig. 1.2 for mechanisms of tPA).

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  • 0000-0002-4288-9886
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  • goeke.calla.2019.pdf
  • 10.6083/x346d472h
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  • 2019
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  • Goeke, C. M. "Fetal alcohol spectrum disorders: alteration of neuronal morphology by ethanol, choline and tissue plasminogen activator" (2019). OHSU Digital Collections. goeke.calla.2019.pdf
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