Domoic acid-induced neuronal degeneration in the primate forebrain revealed by degeneration specific histochemistry

Abstract

Domoic acid is a potent excitotoxin produced by diatoms which is subsequently passed along the marine food chain. Its chemical structure and toxicological properties are similar to kainic acid. Like kainic acid, exposure results in extensive hippocampal degeneration. The effect of domoic acid on other primate brain structures, however, is less resolved. In an attempt to clarify this issue, the present study applied a degeneration specific histochemical technique (de Olmos' cupric-silver method) to reveal degeneration within the brains of domoic acid-dosed cynomolgus monkeys. Degenerating neuronal cell bodies and terminals were found not only within the hippocampus, but also within a number of other ‘limbic’ structures including the entorhinal cortex, the subiculum, the piriform cortex, the lateral septum, and the dorsal lateral nucleus of the thalamus. Although the hippocampus is a component of the original limbic circuit of Papez, other components such as the mammillary bodies, the anterior nucleus of the thalamus and the cingulate cortex contained no degeneration, while a number of more recently documented efferent targets of the hippocampal formation revealed extensive degeneration. The pattern of degeneration generally correlated with those regions containing high densities of kainate receptors.