Domoic acid-containing toxic mussels produce neurotoxicity in neuronal cultures through a synergism between excitatory amino acids

Autor: V. Zitko, Jennifer Kispert, M. Teresa Ferna´ndez-Sa´nchez, Angeles Torreblanca, A. Novelli
Rok vydání: 1992
Předmět:
Zdroj: Brain research. 577(1)
ISSN: 0006-8993
Popis: In 1987, an intoxication by cultured mussels produced neurological problems, such as headache, confusion, and loss of memory, particularly severe at times 24 . Neuronal damage was found in the hippocampus and amygdala of four patients 33 . The intoxication was attributed to the presence in mussels of domoic acid 36 , a rare excitatory amino acid 1 acting at the non-NMDA receptor 30 . We now report that a domoic acid-containing mussel extract is more neurotoxic for cultured neurons than purified domoic acid. Moreover, we show that this increase in neurotoxicity is selectively due to domoic acid potentiation of the excitotoxic effect of glutamic acid and aspartic acid present in high concentration in mussel tissue. We also show that subtoxic concentrations of domoic acid are sufficient to potentiate glutamic acid and aspartic acid neurotoxicity, and we present evidence suggesting that the neurotoxic synergism may occur through a reduction of the voltage-dependent Mg 2+ block at the NMDA receptor-associated channel, following activation of non-NMDA receptors by domoic acid. Thus, based on our results, we suggest that the contemporary presence in the brain of concentrations of domoic acid insufficient alone to be toxic, together with excitatory amino acids, of endogenous and eventually of diet-related origin, may have been relevant in the occurence of the neurological problems reported.
Databáze: OpenAIRE