Necroptosis contributes to the NMDA-induced excitotoxicity in rat's cultured cortical neurons

Necroptosis is a newly discovered type of cell death characterized with the combined biochemical and ultrastructural features of necrosis and apoptosis. Nec-1 has been reported to exhibit the selective inhibition for necroptosis, which has now been used as an operational definition of necroptosis. The purpose of this study was to evaluate whether necroptosis is involved in the NMDA-induced excitotoxicity and furthermore whether the elevation of intracellular Ca2+ is involved in the NMDA-induced necroptosis. Our findings showed that Nec-1 (100 μmol/L) inhibited NMDA-induced decrease of cell viability by 26% (p < 0.01), suppressed NMDA-induced decrease of living cells by 23% (p < 0.01) and attenuated NMDA-induced leakage of LDH by 28% (p < 0.01). In addition, Nec-1 also suppressed NMDA-induced elevation of intracellular Ca2+ by 36% (p < 0.05). These findings indicated for the first time that necroptosis contributes to the NMDA-induced excitotoxicity, and the elevation of intracellular Ca2+ may be one of the potential mechanisms underlying NMDA-induced necroptosis. Although necroptosis may be involved in NMDA-induced excitotoxicity, it may just constitute a small contribution.