Minding Your PCBs

More Evidence for Learning Effects

For over a decade, in utero and postnatal exposure to polychlorinated biphenyls (PCBs) has been linked with reduced IQ in children, but exactly how the chemicals exert their effects on cognitive functioning remains uncertain. In this issue, Rifat J. Hussain and colleagues from the School of Public Health at the State University of New York at Albany explore PCB-induced changes in electrical activity in the hippocampus, an area of the brain involved in learning and memory [EHP 108:827-831]. Their specific goal is to assess PCBs' effects on long-term potentiation (LTP), a prolonged increase in synaptic responses that is believed to be essential for learning. The motivation for the study rests in part on previous observations that childhood lead exposure and old age, both associated with reduced cognitive functioning, are also associated with reduced LTP.

In the present study, Sprague-Dawley rat pups were exposed to PCB 153, a ubiquitous congener in human tissue and environmental media, by maternal dosing in feed during gestational day 7 through postnatal day 21. Dams were exposed at four dose levels: 0.00, 1.25, 5.00, and 20.00 milligrams per kilogram per day. One male pup from each litter was selected for study, and five animals in total (including one nonexposed control) were selected per dose group.

At the end of the exposure period, the pups' brains were removed and slices of hippocampus prepared. Evaluation of LTP was performed on brain slices from the pups exposed in vivo as well as a separate group of brain slices taken from 30-day-old male pups that received no prior in vivo exposure. These brain slices were perfused in vitro with a solution saturated with PCB 153.

Hussain and colleagues monitored the amplitude of the field excitatory postsynaptic potential (fEPSP), which reflects the intensity of the response of hippocampal neurons to stimulation. Once a stable baseline measure of electrical synaptic activity was obtained, LTP was induced by applying two separate stimulations of 100 hertz for 1 second, 5 seconds apart. LTP was measured as the increase in the amplitude of the fEPSP 60 minutes after this high-frequency stimulation.

Hussain and colleagues found that, while in vivo PCB exposure does not produce any obvious baseline changes in synaptic response prior to stimulation, it reduces the increase in fEPSP after stimulation in a dose-dependent fashion. The results of in vitro exposures are roughly similar: no obvious changes in the prestimulation period, but a degree of poststimulation LTP suppression similar to that observed in the in vivo portion of the study. This somewhat surprising observation that in vivo and in vitro exposures to PCB 153 produce similar effects may indicate that the mechanism of action of PCBs on LTP is more pharmacologic than developmental, but additional study of this observation is necessary.

While Hussain and colleagues acknowledge that PCB-induced changes in behavioral and cognitive function are complex and that the relationship between IQ and LTP is still not proven, their results are significant for at least two reasons. Reduction of LTP is potentially involved in neurobehavioral effects, and this observation provides a model system for further study of the mechanisms of PCB action. Furthermore, PCB 153, a nondioxin-like congener that is one of the most abundant PCBs in humans, has often been considered to be relatively nontoxic. These results show that that is not the case, at least for neurobehavioral effects.

COPYRIGHT 2000 National Institute of Environmental Health Sciences
COPYRIGHT 2004 Gale Group