Grantee Research Project Results
2004 Progress Report: Regulation of Embryonic Neuronal Development by Chemical Mixtures from Brick, NJ
EPA Grant Number: R829359Title: Regulation of Embryonic Neuronal Development by Chemical Mixtures from Brick, NJ
Investigators: Reinisch, Carol L. , Cox, Rachel L. , Kreiling, Jill
Institution: Marine Biological Laboratory
EPA Project Officer: Hahn, Intaek
Project Period: July 1, 2001 through June 30, 2004 (Extended to September 23, 2006)
Project Period Covered by this Report: July 1, 2003 through June 30, 2004
Project Amount: $749,333
RFA: Complex Chemical Mixtures (2000) RFA Text | Recipients Lists
Research Category: Hazardous Waste/Remediation , Safer Chemicals , Land and Waste Management
Objective:
The objective of this research project is to use marine embryos as a model to assess the neurological effects of environmental contaminants that were found in Brick, New Jersey. Our interests lie in identification of exposure-induced changes occurring at the molecular level during development of the nervous system. Specifically, we analyze altered expression patterns of various proteins and their corresponding transcripts, including transcription factors (p53 and its family members) and kinases.
Initially, we used surf clam (Spisula solidissima) embryos, a unique model well-suited for this study by virtue of a highly synchronized and rapidly developing nervous system. Using bromoform, chloroform, and tetrachloroethyelene (BCE), a ternary mixture of contaminants, we tested the hypothesis that BCE exposure specifically alters neural signaling pathways during development in Spisula.
Progress Summary:
Our results (in press, 2005) showed that BCE exposure increases expression of RII, a developmentally expressed isoform of the regulatory subunit of protein kinase A (PKA). Specifically, BCE exposure induces both a global, as well as a localized increase in RII, at the site of innervation for the primordial gill and ciliated velar epithelium. A resultant enhanced ciliary activity in the velum causes increased larval swimming speed. A critical point to emphasize is that these effects occur only with the ternary mixture; each component, tested individually or in pairs, has no significant effect on RII levels or ciliary activity.
The results documented in Spisula demonstrate the selectivity of the Brick, New Jersey contaminants for specific targets in the developing embryo. PKA is part of a ubiquitous signaling pathway known to be involved in learning and memory across species. These results imply that chronic exposure to the BCE contaminants in drinking water could alter normal neuronal development during embryonic development in humans.
These observations laid the foundation for our current research in another aquatic species, Danio rerio (zebrafish). The prevalence of PKA in neural tissue, as well as the highly conserved nature of the protein across species, indicates the relevance of this pathway to comparative toxicogenomic analysis. Following the Spisula model, we extended our experimental program to zebrafish, a species for which the entire genome is accessible.
Future Activities:
Our preliminary studies using the anti-mytilus RII antibody in zebrafish show a more intense staining of neural cell bodies localized to the region of the developing spinal chord in BCE-exposed versus normal embryos. These results demonstrate that exposure to BCE specifically targets a neural pathway by causing a localized increase in RII production during development. We are confirming our earlier results in Spisula. The direct effect of environmental contamination on neural development can be repeated in zebrafish, a vertebrate species.
Further analysis of the BCE-induced RII enhancement requires production of molecular probes based on sequences of genes involved in these signaling pathways. This will be facilitated by our shift to zebrafish, a model well established for its utility in high-throughput genetic screens to determine chemical exposure sensitivity.
Our comparative studies clearly demonstrate molecular changes induced by embryonic exposure to environmental contaminants. Using zebrafish, we will continue to define how these changes specifically impact the development of the vertebrate nervous system.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 2 publications | 1 publications in selected types | All 1 journal articles |
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Cox RL, Stephens RE, Reinisch CL. p63/73 homologues in surf clam: novel signaling motifs and implications for control of expression. Gene 2003;320:49-58. |
R829359 (2003) R829359 (2004) |
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Supplemental Keywords:
Spisula solidissima , surf clam, environmental toxicants, p63/73 gene, chemical exposures, protein kinase A, RII, ecology and ecosystems, chemical kinetics, genotoxicity, embryonic neuronal development,, RFA, Scientific Discipline, Geographic Area, Waste, Hazardous, Fate & Transport, State, chemical mixtures, Environmental Chemistry, Hazardous Waste, Ecology and Ecosystems, environmental transport and fate, hazardous organic substances, bioavailability, contaminated sediments, analytical models, fate and transport , biodegradation, complex mixtures, fate and transport, effects assessment, embryonic neuronal development, PCE, chemical kinetics, contaminant transport models, genotoxicity, contaminated soils, hazardous chemicalsProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.