Biochemical changes in animal models of fetal alcohol spectrum disorder
Fetal alcohol spectrum disorder (FASD) is a completely preventable disease, that has profound effects on life-long health and function of the affected individual. Prevalence estimates of FASD in the United States indicate 33.5 per 1,000 live births are affected with this disorder (Roozen, 2016). FASD is caused by maternal ethanol intake during pregnancy. However, recommendations of the amounts of alcohol safe to drink during pregnancy are not established. Further, we lack a comprehensive understanding of the biochemical pathways modified in prenatal ethanol exposure. Biomarkers are also lacking. Our results demonstrate the vast array of biochemical pathways modified in the chronic ethanol exposure zebrafish model of FASD. Many of these pathways agree with existing literature, but the comprehensive nature of this study expands upon several of them, and links branches that were previously considered in isolation as mediators of FASD. In addition, examination of the non-polar excised embryonic mouse demonstrates a significant difference between a single binge dose of ethanol and a two binge doses. Similar metabolites to the zebrafish are identified in this model, though the degree and direction of change is not always consistent. These findings suggest that more ethanol does not necessarily result in an amplified, same-direction response, and that longer duration exposures do not always change metabolites the same way binge exposures do. In addition, a novel application of the probabilistic principal component and covariate analysis (PPCCA) is used to examine latent variables suggested by the combined models. Lastly, we review biomarkers suggested from the mouse and zebrafish model metabolomes, the PPCCA, and Ingenuity Pathway Analysis. We consider these biomarkers with a morphometric analysis of the zebrafish, where few significant differences are noted. Together, these observations suggest that in spite of a lack of morphologic changes, biochemistry of the prenatally exposed individual is significantly changed.
Brown, Purdue University.
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