Résumé
Considering that cannabinoids protect neurons against neurodegeneration, in this study, the neuroprotective effect of WIN55,212-2 in paraoxon induced neurotoxicity in PC12 cells and the role of the N-methyl-D-aspartate [NMDA] receptor were evaluated. In this study PC12 cells were maintained in Dulbecco's modified eagle's medium [DMEM+F12] culture medium supplemented with 10% fetal bovine serum. The cells were treated with paraoxon [200 micro M] in the presence or absence of WIN55,212-2 [0.1 micro M], NMDA receptor agonist NMDA [100 micro M], cannabinoid receptor antagonist AM251 and NMDA receptor antagonist MK801 [1 micro M] at 15 minutes intervals. After 48 hours of exposure, cellular viability and protein expression of the CB1 receptor were evaluated in PC12 cells. Following the exposure of PC12 cells to paraoxon [200 micro M], a reduction in cell survival and protein level of the CB1 receptor was observed [p<0.01]. Treatment of the cells with WIN55,212-2 [0.1 micro M] and NMDA [100 micro M] prior to paraoxon exposure significantly elevated cell survival and protein level of the CB1 receptor [p<0.01]. Also, AM251 [1 micro M] did not inhibit the cell survival and protein level of the CB1 receptor increase induced by WIN55,212-2 [p<0.001]. However, MK801 [1 micro M] did inhibit cell survival and protein expression of the CB1 receptor increase induced by NMDA [p<0.001]. The results indicate that WIN55,212-2 and NMDA protect PC12 cells against paraoxon induced toxicity. In addition, the neuroprotective effect of WIN55,212-2 and NMDA was cannabinoid receptor-independent and NMDA receptor dependent, respectively