RÉSUMÉ
Objective To study the neurotoxicity of homocysteine (HCY) on routine hippocampal neuronal HT22 cells and investigate the mechanisms. Methods Differentiated HT22 cells were treated with different concentrations of HCY (0, 0.5, 1.0, 1.5, 2.0, and 2.5 mmol/L) in the presence or absence of NMDA antagonists MK801 and memantine. The cell viability was tested using MTS cytotoxicity assay. Hoechst 33342 and PI staining were used to observe the morphological changes of the cells. Results HCY induced concentration-dependent toxicity in HT22 cells with the 50% effective concentration (EC50>) of about 1.25 mmol/L. Administration of MKS01 and memantine significantly increased the cell viability, which reached the highest level after treatment with MKS01 and memantine at the concentration of 10 μmol/L (P<0.05). Hoechst 33342 and PI staining revealed obvious cell apoptosis at low HCY concentrations (1.0 mmol/L), while cell necrosis was obvious at a higher concentration (2.0 mmol/L). Conclusion HCY induced obvious concentration-dependent neurotoxicity in HT22 cells largely through the activation of NMDA receptors, and the interaction between HCY and the NMDA receptors may provides an important pathway for research of neuronal cell loss.