PROTECTION BY PYRUVATE AND MALATE AGAINST GLUTAMATE-MEDIATED NEUROTOXICITY

PYRUVATE and malate (P/M) increase the contribution of mitochondria to neuronal calcium homeostasis. We have now found that cortical neurona l cultures utilize pyruvate preferentially over glucose. The supply of pyruvate and malate protects hippocampal and cortical neurons against delayed cell death occurring 24 h after glutamate exposure. High [Ca2 +](i) levels attained during and after glutamate exposure were reduced when neurons were incubated in the presence of P/M. At the single cel l level, this was reflected in a decrease in the number of neurons tha t respond to glutamate with high rises in [Ca2+](i) The results sugges t that the ability to prevent large increases in [Ca2+](i) may underli e the beneficial effects of pyruvate and malate during glutamate excit otoxicity. (C) 1998 Rapid Science Ltd.