Intrahippocampal kainic acid reduces glutamine synthetase

Kainic acid was injected into the hippocampus of rats and glutamine synthetase was measured to determine whether astrocytes are involved in the early effects of this neurotoxic agent. Glutamine synthetase was reduced by 38%, 24 h after the stereotaxic application of 4 nmol of kainic acid to this region. The reduction in glutamine synthetase by kainic acid was not due to direct inhibition of the brain enzyme. This effect also was not due to seizure activity since rats peripherally injected with a convulsant dose of kainic acid were found to have normal hippocampal glutamine-synthetase activity. Exposure of astrocyte cultures to kainic acid for 24 h produced no evidence of gliotoxicity and no change in glutamine synthetase activity. The effect of intrahippocampal kainic acid on glutamine synthetase appears to be indirect, most likely produced secondarily to its neuronal effects. Several studies have shown that endogenous glutamate is involved in kainate neurotoxicity. A reduction in glutamine synthetase by kainic acid may impair the capacity for astrocytes to metabolize glutamate. Such an impairment could contribute to the glutamate-mediated cell death following kainic acid exposure.