Neurotoxicity of early life exposure to contaminants isolated

Neurotoxicity of early life exposure to contaminants isolated
from Onondaga Lake bed sediment
Katharine Lewisa, John Hassettb, Frank Middletonc, and James Hewetta.
Syracuse University, Department of Biology
College of Environmental Science and Forestry, Department of Chemistry
Upstate Medical University, Department of Neuroscience and Physiology
Chemical manufacturing processes during the industrial era in Central NY severely polluted the
lakebed sediment of Onondaga Lake. Chemical analyses of the heavily contaminated
sediments led to the identification of structurally-related pollutants, termed PTE and PXE, that
possess the core carbon backbone structure of the organochloride pesticide,
dichlorodiphenyltrichloroethane (DDT). In addition to its notorious effects on reproductive
capacity, early life exposure to DDT has been linked to developmental toxicity, particularly to the
nervous system, raising the possibility that these Onondaga Lake sediment contaminants
(OLSC) may possess similar toxic potential. Developmental alterations may include alterations
in postnatal gene expression patterns in the brain with consequent persistent behavioral
modifications. Two separate approaches were undertaken in this Hill Collaboration project to
test these hypotheses. Studies by the Lewis laboratory exposed zebrafish embryos to the
OLSCs. The results demonstrated that OLSCs are highly toxic to developing embryos, causing
massive heart edema and lethality, indicating that OLSCs are teratogenic to fish. Interestingly,
OLSCs were found to be much more potent than DDT in this animal model. Furthermore, both
acute and chronic treatment with OLSCs caused an increase in the incidence of experimentallyinduced convulsions, indicating that these pollutants cause changes in zebrafish nervous
system function as well. In a second series of studies by the Hewett laboratory, mice were
exposed to PTE over the course of gestation. In agreement with studies in zebrafish, results
from these studies demonstrated that offspring of exposed pregnant female mice exhibited an
enhanced sensitivity to experimentally-induced convulsive seizures during adulthood. Because
seizures are the defining characteristic of epilepsy, these results raise concern that early life
exposure to OLSCs could be an environmental risk factor for epilepsy development in exposed
individuals. Finally, gene expression analyses have detected changes in both fish and mice
exposed to OLSCs. The relevance of these changes to the toxic effects of OLSCs is an ongoing
investigation of this Hill Collaboration project. It is possible that such analyses could lead to the
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