Histopathological and molecular changes produced by hippocampal microinjection of domoic acid
Abstract
The phytoplankton-derived neurotoxin, domoic acid (DOM), frequently causes poisoning of marine animals and poses an increasing threat to public health through contamination of seafood. In this study, we used stereotactic microinjection technique to administer varying amounts of DOM into the hippocampal CA1 region in order to examine potential histopathological changes after injection of sub-lethal concentrations to CA1 pyramidal neurons. Gross anatomical abnormalities in CA1 were observed at above 10 microM DOM (3 pmol in 0.3 microl saline). At 1mM concentration, DOM produces both ipsilateral and contralateral neuronal cell death in CA1, CA3 as well as dentate gyrus subfields. Animal behavioral changes after microinjection were similar to those observed by previous studies through systemic DOM injection. Neuronal degeneration was paralleled by reduced glutamate receptor (NR1, GluR1 and GluR6/7) immunolabeling throughout the whole hippocampal formation. Pre-injection of the AMPA/KA receptor antagonist NBQX (10 microM, 0.3 microl) blocked 1mM DOM-induced neuronal degeneration as well as behavioral symptoms. At concentrations lower than 10 microM, no histopathological changes were observed microscopically, nor were the levels of i...Continue Reading
References
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation
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