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Journal of Toxicology
Volume 2011, Article ID 543512, 14 pages
http://dx.doi.org/10.1155/2011/543512
Research Article

Domoic Acid-Induced Neurotoxicity Is Mainly Mediated by the AMPA/KA Receptor: Comparison between Immature and Mature Primary Cultures of Neurons and Glial Cells from Rat Cerebellum

1Environmental Health Science, School of Public Health, The Johns Hopkins University, Baltimore, MD 21205-2103, USA
2Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, 615 N Wolfe Street, W7032 Baltimore, MD 21205, USA
3In-Vitro Methods Unit, Institute for Health and Consumer Protection, European Commission Joint Research Centre, 21020 Ispra (VA), Italy

Received 14 July 2011; Accepted 24 August 2011

Academic Editor: Lucio Guido Costa

Copyright © 2011 Helena T. Hogberg and Anna K. Bal-Price. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Domoic acid (DomA) is a naturally occurring shellfish toxin that can induce brain damage in mammalians. Neonates have shown increased sensitivity to DomA-induced toxicity, and prenatal exposure has been associated with e.g. decreased brain GABA levels, and increased glutamate levels. Here, we evaluated DomA-induced toxicity in immature and mature primary cultures of neurons and glial cells from rat cerebellum by measuring the mRNA levels of selected genes. Moreover, we assessed if the induced toxicity was mediated by the activation of the AMPA/KA and/or the NMDA receptor. The expression of all studied neuronal markers was affected after DomA exposure in both immature and mature cultures. However, the mature cultures seemed to be more sensitive to the treatment, as the effects were observed at lower concentrations and at earlier time points than for the immature cultures. The DomA effects were completely prevented by the antagonist of the AMPA/KA receptor (NBQX), while the antagonist of the NMDA receptor (APV) partly blocked the DomA-induced effects. Interestingly, the DomA-induced effect was also partly prevented by the neurotransmitter GABA. DomA exposure also affected the mRNA levels of the astrocytic markers in mature cultures. These DomA-induced effects were reduced by the addition of NBQX, APV, and GABA.