Collections > Electronic Theses and Dissertations > Exploring a fish model of developmental neurotoxicity using the Japanese medaka fish (Oryzias latipes)

Ethanol exposure induces profound disruptions in developing organisms, but the period(s) of maximal susceptibility for these effects are not clearly defined. The overall hypothesis of this dissertation was that the timing of developmental ethanol exposure would influence manifestations of ethanol toxicity in medaka. Hatching success and morphometric measures of medaka growth and development were used to assess the dose-response for developmental ethanol toxicity. Specifically, medaka embryos were exposed to a range of sublethal ethanol concentrations (0.1, 0.5, to 1.0 % about equal to 17.2, 86, or 172 mM) during early, middle or late development in order to address temporal variations in sensitivity. Ethanol-induced decreases in total body length were found to be most severe with increasing ethanol concentrations that occurred either early or late in embryonic development, whereas head width was consistently decreased at all ethanol concentrations, regardless of developmental timing. These effects were accompanied by dose-related decreases in hatching success which were more pronounced with ethanol exposures that occurred early in development. Subsequent analyses of time-dependent changes in brain growth and caspase-3/7 activation were used to address the neurodevelopmental consequences of ethanol exposure. In these studies, medaka embryos were exposed to 1% ethanol during early, middle or late development and evaluated for treatment-related changes in brain volume and caspase-3/7 activation on day 9 postfertilization. Interestingly, the pattern of sensitivity observed for ethanol-induced decreases in total brain volume was similar to that seen with ethanol-induced decreases in somatic growth; embryos treated either early or late in development were most severely affected. Treatment-related decreases in caspase-3/7 activity were independent of developmental timing. In general, these data show that the sensitivity to developmental ethanol exposure varies according to both the timing of exposure and the endpoint used to assess toxicity.