اثر حفاظتي آگونيست گيرنده كانابينوييدي (WIN55,212-2) در سميت ناشي از پاروكسان در سلول هاي PC12 و تداخل گيرنده N-methy-D-aspartate با اين اثر

The Neuroprotective Effect of Cannabinoid Receptor Agonist (WIN55,212-2) in Paraoxon Induced Neurotoxicity in PC 12 Cells and N-methyl-D-aspartate Receptor Interaction

Objective: 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. Materials and Methods: In this study PC12 cells were maintained in Dulbeccoʹs modified eagleʹs medium (DMEM+F12) culture medium supplemented with 10% fetal bovine serum. The cells were treated with paraoxon (200 }jM) in the presence or absence of WIN55,212-2 (0.1 pM), NMDA receptor agonist NMDA (100 mM), cannabinoid receptor antagonist AM251 and NMDA receptor antagonist MK801 (1 |jM) at 15 minutes intervals. After 48 hours of exposure, cellular viability and protein expression of the CB1 receptor were evaluated in PC12 cells. Results: Following the exposure of PC12 cells to paraoxon (200 |jM), 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 |jM) and NMDA (100 jjM) prior to paraoxon exposure significantly elevated cell survival and protein level of the CB1 receptor (p<0.01). Also, AM251 (1 jjM) 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 pM) did inhibit cell survival and protein expression of the CB1 receptor increase induced by NMDA(p<0.001). Conclusion: 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