Novel dose-dependent alterations in excitatory GABA during embryonic development associated with lead (Pb) neurotoxicity

Wirbisky, S.E., Weber, G.J., Lee, J.W., Cannon, J.R., Freeman, J.L.
Toxicology letters   229(1): 1-8 (Journal)
Registered Authors
Freeman, Jennifer
GABA, developmental toxicity, gene expression, lead, neurotoxicity, zebrafish
MeSH Terms
  • Animals
  • Axons/physiology
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Electrochemistry
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/drug effects*
  • Excitatory Postsynaptic Potentials/drug effects
  • GABAergic Neurons/drug effects
  • Lead Poisoning, Nervous System/metabolism*
  • Mass Spectrometry
  • Neurogenesis/drug effects
  • Polymerase Chain Reaction
  • Zebrafish
  • gamma-Aminobutyric Acid/genetics
  • gamma-Aminobutyric Acid/metabolism
  • gamma-Aminobutyric Acid/physiology*
24875535 Full text @ Toxicol. Lett.
Lead (Pb) is a heavy metal that is toxic to numerous physiological processes. Its use in industrial applications is widespread and results in an increased risk of human environmental exposure. The central nervous system (CNS) is most sensitive to Pb exposure during early development due to rapid cell proliferation and migration, axonal growth, and synaptogenesis. One of the key components of CNS development is the Gamma-aminobutyric acid (GABA)-ergic system. GABA is the primary inhibitory neurotransmitter in the adult brain. However, during development GABA acts as an excitatory neurotrophic factor which contributes to these cellular processes. Multiple studies report effects of Pb on GABA in the mature brain; however, little is known regarding the adverse effects of Pb exposure on the GABAergic system during embryonic development. To characterize the effects of Pb on the GABAergic system during development, zebrafish embryos were exposed to 10, 50, or 100 ppb Pb or a control treatment. Tissue up-take, gross morphological alterations, gene expression, and neurotransmitter levels were analyzed. Analysis revealed that alterations in gene expression throughout the GABAergic system and GABA levels were dose and developmental time point specific. These data provide a framework for further analysis of the effects of Pb on the GABAergic system during the excitatory phase and as GABA transitions to an inhibitory neurotransmitter during development.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes