The Neuroprotective Effect of Cannabinoid Receptor Agonist (WIN55,212-2) in Paraoxon Induced Neurotoxicity in PC12 Cells and N-methyl-D-aspartate Receptor Interaction

Abstract

Objective: Considering that cannabinoids protect neurons against neurodegeneration, inthis study, the neuroprotective effect of WIN55,212-2 in paraoxon induced neurotoxicity inPC12 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 Dulbecco's modifiedeagle’s medium (DMEM+F12) culture medium supplemented with 10% fetal bovineserum. The cells were treated with paraoxon (200 μM) in the presence or absence ofWIN55,212-2 (0.1 μM), NMDA receptor agonist NMDA (100 μM), cannabinoid receptorantagonist AM251 and NMDA receptor antagonist MK801 (1 μM) at 15 minutes intervals.After 48 hours of exposure, cellular viability and protein expression of the CB1 receptorwere evaluated in PC12 cells.Results: Following the exposure of PC12 cells to paraoxon (200 μM), a reduction in cellsurvival and protein level of the CB1 receptor was observed (p<0.01). Treatment of thecells with WIN55,212-2 (0.1 μM) and NMDA (100 μM) prior to paraoxon exposure significantlyelevated cell survival and protein level of the CB1 receptor (p<0.01). Also, AM251(1μM) did not inhibit the cell survival and protein level of the CB1 receptor increase inducedby WIN55,212-2 (p<0.001). However, MK801 (1 μM) did inhibit cell survival andprotein expression of the CB1 receptor increase induced by NMDA (p<0.001).Conclusion: The results indicate that WIN55,212-2 and NMDA protect PC12 cellsagainst paraoxon induced toxicity. In addition, the neuroprotective effect of WIN55,212-2and NMDA was cannabinoid receptor-independent and NMDA receptor dependent, respectively