Neurotoxic effect induced by quinolinic acid in dissociated cell culture of mouse hippocampus.

Quinolinic acid (QUIN), an endogenous convulsant that is a product of tryptophan metabolism, is suggested to belong to the pathogenic factors in some neurodegenerative disorders of the central nervous system (CNS). The aim of the present study was to evaluate the effect of QUIN on hippocampal nerve cells in dissociated cell culture at different periods of its development in vitro. The neurodegenerative effect of QUIN in vitro was found 1.5 to 2 hr after exposure to QUIN (500 microM) in differentiated hippocampal culture 20-21 days in vitro (DIV). The cytotoxic action depended on the nature of the interneuronal relations established in culture and on the period of neuronal development in vitro. Neurons in 11-DIV cultures were undamaged even 10 days after exposure to QUIN; nor were the individual, isolated neurons probably not connected synaptically with the other ones in 20-21 DIV cultures. Ultrastructural analysis of 20-21 DIV cultures exposed to QUIN showed acute swelling and destruction of postsynaptic elements and severe degeneration of individual nerve cells located in cellular aggregates, whereas presynaptic axon terminals remained intact. The results emphasize the utility of QUIN as a tool to model degenerative changes of CNS and confirm the participation of mature synaptic junctions in QUIN neurotoxicity.