Glutamate toxicity in neuron-enriched and neuron–astrocyte co-cultures: effect of the glutamate uptake inhibitor ?-trans-pyrrolidine-2,4-dicarboxylate

Amin, N. and Pearce, B.R. (1997) Glutamate toxicity in neuron-enriched and neuron–astrocyte co-cultures: effect of the glutamate uptake inhibitor ?-trans-pyrrolidine-2,4-dicarboxylate. Neurochemistry International, 30 (3). p. 271. 10.1016/S0197-0186(96)00092-7.

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DOI: 10.1016/S0197-0186(96)00092-7

Abstract

Exposure of neuron-enriched cultures of the embryonic rat cerebral cortex to glutamate (Glu) resulted in a concentration-dependent (EC50 = 50 μM) increase in the release of lactate dehydrogenase (LDH) into the bathing medium. Glu-induced neurotoxicity appeared to be mediated predominantly by the activation of N-methyl-D-aspartate receptors because its effects were almost completely reversed by 1 μM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). The potency of Glu was increased by ca eight-fold (EC50 = 6 μM) when neuronal cultures were incubated with Glu in the presence of the uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC). Increased LDH release was also observed when neuron-enriched cultures were exposed to an ineffective concentration of Glu in the presence of increasing concentrations of L-trans-PDC, moreover, the uptake inhibitor itself became neurotoxic at concentrations above 100 μM. Glu also stimulated the release of LDH from neuron-astrocyte co-cultures in a concentration-dependent manner, however, it was found to be less potent (EC50 = 200 μM) in these cultures than it was in the neuron-enriched cultures. Incubation of the co-cultures with Glu in the presence of the uptake inhibitor increased the potency of Glu (EC50 = 100 μM) but to a much lesser extent than that found in neuron-enriched cultures. Cultured astrocytes were found to be resistant to injury by Glu even in the presence of the uptake inhibitor.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3327
Journal or Publication Title:Neurochemistry International
Deposited By:Library Staff
Deposited On:31 May 2012 16:47
Last Modified:31 May 2012 16:47

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