N-Acetylaspartate monomethyl ester increases N-acetylaspartate concentration in cultured rat hippocampal slices: Effects on excitotoxicity and levels of amino acids and chloride

N-acetylaspartate (NAA) was discovered in mammalian brain 50 years ago but its functions remain debated. One reason for the relatively slow progress of NAA research is the paucity of tools to specifically modify NAA concentrations. In this work we evaluated the use of the monomethyl ester of NAA (NAA MME) to increase the relatively low level of NAA in cultured hippocampal slices. When slices were treated with 30 mM NAA MME for 3 days the NAA concentration increased from 31.6 to 185.3 nmol/mg protein. Incubation with NAA alone increased the NAA concentration non-significantly to 65.6 nmol/mg protein. NAA MME treatment increased NAA in neurons and the increase was non-toxic as determined by the low uptake of propidium iodide, a dye that only enters damaged cells. NMDA-mediated excitotoxicity which is initiated by influx of Ca2+ was unaltered by increased NAA levels indicating poor intracellular Ca2+-chelation by NAA.