PMID: 7536810May 1, 1995Paper

Exacerbation of NMDA, AMPA, and L-glutamate excitotoxicity by the succinate dehydrogenase inhibitor malonate

Journal of Neurochemistry
J G Greene, J T Greenamyre

Abstract

We report that a subtoxic dose of the succinate dehydrogenase (SDH) inhibitor malonate greatly enhances the neurotoxicity of three different excitatory amino acid agonists: N-methyl-D-aspartate (NMDA), S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S-AMPA), and L-glutamate. In male Sprague-Dawley rats, intrastriatal stereotaxic injection of malonate alone (0.6 mumol), NMDA alone (15 nmol), S-AMPA alone (1 nmol), or glutamate alone (0.6 mumol) produced negligible toxicity as assessed by measurement of lesion volume. Coinjection of subtoxic malonate with NMDA produced a large lesion (15.2 +/- 1.4 mm3), as did coinjection of malonate with S-AMPA (11.0 +/- 1.0 mm3) or glutamate (12.8 +/- 0.7 mm3). Administration of the noncompetitive NMDA antagonist MK-801 (5 mg/kg i.p.) completely blocked the toxicity of malonate plus NMDA (0.5 +/- 0.3 mm3). This dose of MK-801 had little effect on the lesion produced by malonate plus S-AMPA (9.0 +/- 0.7 mm3), but it attenuated the toxicity of malonate plus glutamate by approximately 40% (7.5 +/- 0.9 mm3). Coinjection of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline (NBQX; 2 nmol) had no effect on malonate plus NMDA or malonate plus glutamate toxicity (12.3...Continue Reading

Citations

Sep 16, 2003·International Journal of Geriatric Psychiatry·Stefan BleichJohannes Kornhuber
Jul 16, 2005·Neurochemical Research·Robson Luiz PuntelJoão Batista Teixeira Rocha
Sep 13, 2018·Metabolites·Massimo S FiandacaHoward J Federoff
Feb 1, 1996·Molecular Neurobiology·F BlandiniJ T Greenamyre
Mar 28, 2008·The European Journal of Neuroscience·Verónica Pérez-De La CruzAbel Santamaría
Oct 30, 2015·Journal of Neuroscience Research·Marc VerleyeRémy Steinschneider
Sep 1, 1996·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·E Gilland, H Hagberg
Jan 14, 1999·Journal of Neurochemistry·M R Sánchez-Carbente, L Massieu
Jun 15, 2014·Cellular and Molecular Neurobiology·Roberto RodriguesGeorge Perry
Jun 22, 2006·Neurotoxicity Research·V Pedersen, W J Schmidt
Oct 26, 2005·The Journal of Biological Chemistry·Alexander PanovJ Timothy Greenamyre
Aug 26, 1998·Biochimica Et Biophysica Acta·D G Nicholls, S L Budd
Aug 18, 2009·Biochimica Et Biophysica Acta·Maria DamianoEmmanuel Brouillet

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