Document Type : Original Article
Authors
1
Applied Neurosciences Research Center, Baqiyatallah (a.s.) University of Medical Sciences, Tehran, Iran
2
Physiology and Biophysics Department, Baqiyatallah (a.s.) University of Medical Sciences, Tehran, Iran
3
Molecular Biology Research Center, Baqiyatallah (a.s.) University of Medical Sciences, Tehran, Iran
4
Fertility and Infertility Research Center, Stem Cell Division, Kermanshah University of Medical Sciences, Kermanshah, Iran
Abstract
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 Dulbecco's modified eagle’s medium (DMEM+F12) culture medium supplemented with 10% fetal bovine
serum. The cells were treated with paraoxon (200 μM) in the presence or absence of
WIN55,212-2 (0.1 μM), NMDA receptor agonist NMDA (100 μM), cannabinoid receptor
antagonist 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 receptor
were evaluated in PC12 cells.
Results: Following the exposure of PC12 cells to paraoxon (200 μM), 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 μM) and NMDA (100 μM) prior to paraoxon exposure significantly elevated 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 induced by WIN55,212-2 (p<0.001). However, MK801 (1 μM) 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.
Keywords
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