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Mechanism of Compound Neurotoxicity Identified

Last Updated: April 15, 2009.

Polychlorinated biphenyls may act through ryanodine receptors, which are calcium ion channels, to mediate their neurotoxic effects, according to several new studies.

WEDNESDAY, April 15 (HealthDay News) -- Polychlorinated biphenyls (PCBs) may act through ryanodine receptors, which are calcium ion channels, to mediate their neurotoxic effects, according to several new studies.

In the study published online March 13 in Toxicology and Applied Pharmacology, Kyung Ho Kim and colleagues from the University of California-Davis, examined the effect of two environmental PCBs on synaptic transmission in rat hippocampal slices. The researchers found that the compounds were able to alter neurotransmission by altering the balance between inhibitory and excitatory circuits within the hippocampus, where hippocampal excitotoxicity was at least partially mediated via ryanodine receptors.

In the study in the April issue of PLoS Biology, Montserrat Samso, Ph.D., from Harvard Medical School in Boston, and colleagues solved the three-dimensional structure of ryanodine receptor type 1 in the closed and open states. They showed that the structures contained two sets of bundles that could explain how the channel could increase in size in the open state to allow calcium ions to flow through. In the third study in the March issue of Environmental Health Perspectives, Dongren Yang, Ph.D., from Oregon Health & Science University in Portland, and colleagues showed that exposure of weanling rats to PCBs led to subtle deficits in spatial learning and memory and interference with normal patterns of dendritic growth and plasticity, possibly through changes in ryanodine receptors.

"With these studies we have now shown, from the whole animal level to the molecular level, how PCBs alter the development and excitability of brain cells. And that could explain why PCBs are associated with higher rates of neurodevelopmental and behavioral disorders," said Isaac N. Pessah, co-author of all three studies, in a prepared statement.

Abstract-Kim
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