David O.
Carpenter, M.D. Principal Investigator David O.
Carpenter, M.D. Principal Investigator
This project focuses on the mechanisms which may account for altered cognition after exposure to PCBs. The goal of this investigation is to determine whether PCBs alter a variety of neural processes that are known to be important in learning and memory in animal model systems. It is an effort to link behavioral observations in humans and animals exposed to PCBs with neurophysiological observations in animals exposed to PCBs.
Acute and chronic exposures of rats to Aroclor 1248 and four single PCB congeners are being analyzed through a combination of electrophysiologic and flow cytometric techniques. The major hypothesis being tested is that PCBs will reduce or block the process of long-term potentiation (LTP), which is a model system for learning and memory. If PCBs block LTP, the project will attempt to determine the mechanisms of action that are responsible.
Through the use
of electrophysiological recordings, we are studying the synaptic transmission in two
hippocampal circuits, the Schaffer collateral-CA1 pathway and the mossy fiber-CA3 pathway.
This project is also investigating normal transmitter release and post-synaptic responses
in studies of post-tetanic potentiation (PTP), LTP, paired pulse potentiation, and phorbol
ester-induced potentiation. We hypothesize that one of these responses will be selectively
affected, and if so, we will attempt to determine the mechanism.
The effects on responses to specific neurotransmitter receptors, various kinases, and calcium entry and/or release are also being investigated. In order to directly monitor calcium, we will use cerebellar granule neurons studied in a flow cytometer, and determine whether there are direct effects of PCBs on calcium flux. Effects of PCBs on membrane potential change and on generation of free radicals in the cells by different pathways are also monitored. If effects are found, we will determine which congeners are responsible, and whether the effects are mediated via interference with thyroid function, dopamine depletion, or some other mechanism.
PCBs are persistent and the levels that show biological effects are close to what is found in most people. PCBs effect everyone, especially children and the developing fetus, and prenatal exposure is the most statistically significant. This project has shown that acute exposure of rat brain slices to low levels of PCBs block long-term potentiation, which is a model of learning and memory. These effects seem to be selective with blockage occurring with ortho and coplanar PCBs. This project is also working with hypothyroid animals, which show lower IQ. Some PCBs can react with the thyroid, therefore it may be the effects of PCBs on the thyroid that cause lowered IQ. The question is how do PCBs effect long-term potentiation and thyroid function.
Click here to see a list of Publications
We welcome your comments and inquiries regarding this research project.
Please forward comments to:
Dr. David O. Carpenter, University at Albany State of New York, One University Place
Rensselaer,
NY 12144-3456 carpent@cnsvax.albany.edu
518-525-2660, FAX 525-2665
