Pyruvate and lactate protect striatal neurons against N‐methyl‐d‐aspartate‐induced neurotoxicity

European Journal of Neuroscience - Tập 11 Số 9 - Trang 3215-3224 - 1999
M. Maus1, Philippe Marin2, Maurice Israël3, J. Głowiński2, Joël Prémont2
1INSERM U114, College de France, Paris.
2Chaire de Neuropharmacologie, INSERM U114, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
3CNRS UPR 9040, Laboratoire de Neurobiologie Cellulaire et Moléculaire, 1, Avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France

Tóm tắt

AbstractA sustained release of glutamate contributes to neuronal loss during cerebral ischaemia. Using cultured mouse striatal neurons, we observed that glucose deprivation, which occurs in this pathological process, enhanced the N‐Methyl‐d‐aspartate (NMDA)‐ or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)‐induced neurotoxicity. The end products of glycolysis, lactate and pyruvate, strongly protected neurons from these neurotoxic effects. The neuroprotective effect of pyruvate (which is more prominent in the absence of glucose) was not related to its ability to react with H2O2 by a decarboxylation process. Pyruvate and l‐lactate strongly counteracted the deep decrease in the neuronal ATP content induced by NMDA, indicating that they might protect striatal neurons by rescuing cellular energy charge. Addition of MK‐801 after the NMDA withdrawal completely protected neurons, suggesting that NMDA neurotoxicity resulted from a delayed NMDA receptor activation probably linked to a delayed release of an endogenous agonist in the extracellular medium. The strong accumulation of extracellular glutamate which was found in both sham and NMDA‐treated cultures was markedly decreased by pyruvate. Thus, pyruvate might also exert its protecting activity by decreasing the delayed accumulation of glutamate which seemed to be neurotoxic only after a preexposure of neurons to NMDA.

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European Journal of Neuroscience

Tập 11 Số 9

3215-3224

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