Toxicity of N-acetylaspartylglutamate and its protection by NMDA and non-NMDA receptor antagonists

Abstract

N-Acetylaspartylglutamate (NAAG) is a dipeptide, and has been demonstrated to be a putative neurotransmitter in the brain. We hereby report the toxicity of NAAG in sagittal slices of mouse brain, in vitro, which is prevented by both N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Incubation of mouse brain slices with NAAG resulted in dose-dependent leakage of lactate dehydrogenase (LDH) and potassium from the slices into the medium. Significant leakage of LDH was observed when the slices were incubated with 0.1 pM NAAG. Significant leakage of LDH from the slice was observed only when a very high concentration of L-glutamic acid (10 μM) was added to the incubation medium. Prior incubation with NMDA (MK-801) or non-NMDA (glutamate diethyl ester, (GDEE)) receptor antagonists protected the slices against NAAG-mediated neurotoxicity, indicating the possible involvement of both of these classes of receptors in the toxic action of NAAG.