Investigation of the neuronal death mode induced by glutamate treatment in serum-, antioxidant-free primary cultured cortical neurons

Glutamate, the principal excitatory amino acid neurotransmitter in the central nervous system, is also a potential toxin leading to excitotoxicity when it is over-accumulated in extracellular space. Glutamate excitotoxicity has been implicated in many neurological disorders. To date, the death mode of neurons induced by glutamate remains ambiguous and is widely debated. To further clarify the neuronal death mode after glutamate treatment, we investigated this issue in mouse embryonic cortical neurons that were cultured in a serum-, antioxidant-free condition. Our study shows that exposure to low concentration of glutamate (30 muM) in a delayed time course induces neuronal death in a prevailing form of apoptosis which is accompanied by caspases activation and oligonucleosomal DNA fragmentation. Transient exposure to high concentration of glutamate (300 muM) induces the concurrence of necrosis and apoptosis in individual neurons characterized by necrotic cytoplasm-membrane features and apoptotic nuclear morphology which is not accompanied by caspases activation and oligonucleosomal DNA fragmentation. (C) 2003 Elsevier B.V. All rights reserved.