NEUROCHEMICAL, NEUROBEHAVIORAL AND ENDOCRINE EFFECTS OF DEVELOPMENTAL EXPOSURE OF RATS TO INDIVIDUAL PCB CONGENERS

Richard F. Seegal, Ph.D.
Principal Investigator


PCBs alter the developing brain which may lead to alterations in human cognition. This is a concern for many Akwesasne Mohawk women who had elevated body concentrations of PCBs and whose children were exposed during gestation and through breast feeding. Thus, it is important to understand the mechanism by which PCBs may induce cognitive and physical deficits in these children.

For this purpose, we will determine the neurochemical, neurobehavioral, and endocrine effects of in utero and lactational exposure of the laboratory rat to individual PCB congeners. These congeners were selected because they alter neurochemical and second messenger systems and the development of key endocrine systems including thyroid and estrogens- all of which are important for normal brain development.

During the first year of study, biogenic amine concentrations were measured in brain slices of rats exposed in vitro to each congener to determine which congeners directly affect neurochemical function.

In the remaining years of the study, pregnant rats (dams) will be exposed to these congeners during gestation and lactation. The developing rats will be assayed for PCB induced alterations in endocrine status and these changes will be correlated with neurochemical and neurobehavioral changes. Animals will also be exposed to pharmacological agents during development to determine whether neurochemical and endocrine changes, seen after congener exposure, are due to selective alterations in these specific systems. Finally, the study will determine the effects of developmental exposure to PCBs on cognitive function. These studies, using a number of prototypical PCB congeners, will determine which congeners directly affect neurotransmitter development, indirectly affect endocrine and brain development, and the behavioral consequences of perinatal exposure.

Update: September 1996

This project examined the developmental exposure in rats to congeners 2,4,2'4' and 3,4,3'4, and saw an increase in dopamine levels. These results were unusual since past studies showed a decrease. It is speculated that some type of metabolite may be forming which leads to an increase in dopamine. This project will now study congener 2,6,2'6' which has been determined by Dr. Gierthy to be one of the most estrogenic. This project is also examining the effects of Aroclor 1254 on serum T3 and T4. They originally thought that Aroclor 1254 might be causing hypothyroidism. PTU, a form of hypothyroidism, and PCB exposure lead to a large decrease in T4 and a smaller decrease in T3. However, differences have been found between the two, sometimes even opposite reactions. PTU decreases brain weights and alters cognition, but PCBs do not show any of these effects. These differences may be due to developmental differences. PTU and PCB exposure could have different mechanisms.
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We welcome your comments and inquiries regarding this research project. Please forward comments to: Dr. Richard F. Seegal, Associate Professor, School of Public Health, University at Albany, Wadsworth Center for Labs and Research, Empire State Plaza, Box 509, Albany, NY 12201-0509 seegal@wadsworth.org
TEL:(518) 473-4378 FAX: (518) 486-1505

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