Chapter Seven - Effects of Ethanol Exposure on Nervous System Development in Zebrafish

Abstract

Alcohol (ethanol) is a teratogen that adversely affects nervous system development in a wide range of animal species. In humans numerous congenital abnormalities arise as a result of fetal alcohol exposure, leading to a spectrum of disorders referred to as fetal alcohol spectrum disorder (FASD). These abnormalities include craniofacial defects as well as neurological defects that affect a variety of behaviors. These human FASD phenotypes are reproduced in the rodent central nervous system (CNS) following prenatal ethanol exposure. While the study of ethanol effects on zebrafish development has been more limited, several studies have shown that different strains of zebrafish exhibit differential susceptibility to ethanol-induced cyclopia, as well as behavioral deficits. Molecular mechanisms underlying the effects of ethanol on CNS development also appear to be shared between rodent and zebrafish. Thus, zebrafish appear to recapitulate the observed effects of ethanol on human and mouse CNS development, indicating that zebrafish can serve as a complimentary developmental model system to study the molecular basis of FASD. Recent studies examining the effect of ethanol exposure on zebrafish nervous system development are reviewed, with an emphasis on attempts to elucidate possible molecular pathways that may be impacted by developmental ethanol exposure. Recent work from our laboratories supports a role for perturbed extracellular matrix function in the pathology of ethanol exposure during zebrafish CNS development. The use of the zebrafish model to assess the effects of ethanol exposure on adult nervous system function as manifested by changes in zebrafish behavior is also discussed.