The effects of low dose lead exposure on the gabaergic system in the developing zebrafish

Sara Elizabeth Wirbisky, Purdue University

Abstract

Lead (Pb) is a physiologically non-essential toxic heavy metal. Its use in industrial applications is widespread and has resulted in an increase in human exposure. Over the previous six decades, due to an increase in adverse health effects in humans, federal regulations concerning industrial and environmental Pb levels have become more stringent leading to a reduction in human exposure. Despite the advances in our knowledge of Pb induced neurotoxicity, the specific molecular pathways underlying neurological disorders are still unclear. The studies in this thesis were designed to test the hypothesis that exposure to environmental levels of lead will alter gene expression in the GABAergic system during its excitatory period leading to a correlating change in GABA levels throughout embryogenesis. Zebrafish embryos were treated with 10, 50, or 100 ppb Pb in aquaria water or a control treatment shortly after fertilization through 72 hours post fertilization. A dose-response was generated between Pb exposure and tissue up-take in zebrafish larvae. Genetic analysis showed that developmental Pb exposure caused both an increase and a decrease in mRNA expression of seven genes (gad2, gad1b, gabra1, gabbr1a, gat-1, gat-3, vgat) throughout the GABAergic pathway at varying developmental time points. GABA levels were analyzed and revealed dose and time point alterations. These data provide a framework for further analysis of the effects of Pb on the GABAergic system not only for developmental toxicity, but also for the lasting neurotoxic effects that extend into adulthood.

Degree

M.S.

Advisors

Freeman, Purdue University.

Subject Area

Toxicology|Surgery

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