en Clinical Neuroscience Clinical Neuroscience Original Original <p align="left" ><p><b><font color="#221e1f" size="2"><font color="#221e1f" size="2">Introduction: </font></font></b></p><p><b><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">The inflammatory response requires a coordinated integration of various signaling pathway including cyclooxygenase (COX). COX catalyzes </font></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">the formation of prostaglandins from arachidonic acid. Among prostaglandins, </font></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">15-Deoxy-D12, 14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of Peroxisome proliferator-activated receptor-gamma (PPAR-γ), has been demonstrated to have anti-inflammatory actions. In this study, we investigated whether 15d-PGJ2 as a PPAR-γ ligand could exert neuroprotective effects in rat pheochromocytoma (PC12) cells in PPAR-γ dependent manner. </font></font></font><b><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"></font></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">In our experiment, using PC12 cells, the levels of NF-κB, Nrf2, γ-glutamylcysteine synthetase (γ-GCS), hemeoxygenase (HO-1) and apoptosis </font></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">factors were determined using Western blot in different groups. Also cell viability </font></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">was determined by the conventional MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) reduction assay and two staining involved Hoechst staining and Acridine Ordange/Ethidiume Bromide staining respectively. </font></font></font><b><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><p align="justify"><font size="4">Results:</font> </p></font></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">Our results show that NS-398, a selective COX-2 inhibitor and 15d-PGJ2, a natural potent ligand of PPAR-γ, were neuroprotective through modulation of at least three different, but related pathways and molecules, including NF-κB and Nrf2 signaling pathway. Our data showed that 15d-PGJ2 and NS-398 induced Nrf2 signaling pathway and its downstream factors such as HO-1 and γ-GCS, while 15d-PGJ2 and NS-398 decreased NF-κB level. Interestingly, the observed protective effects were mediated through PPAR-γ-dependent mechanisms, as they reversed by GW9662, an irreversible antagonist of PPAR-γ receptor. </font></font></font><b><font color="#221e1f" size="2"><font color="#221e1f" size="2"><p><font size="3">Discussion:</font> </p></font></font><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2"><font color="#221e1f" face="Times New Roman,Times New Roman" size="2">Thus we conclude that 15d-PGJ2 as well as NS-398 exert anti cell death effect in a PPAR-γ dependent mechanisms. </font></font></font></b></b></b></b><p></p></p><p align="justify"><font size="3">Methods:</font> </p> Cyclooxygenase,PPAR-γ,PC12,Nrf2,15d-PGJ2,Neuroprotective. 47 55 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1-98&slc_lang=en&sid=1 Shahnaz Babaei Abraki 1370031947532846001406 1370031947532846001406 Yes Parnian Eslami 1370031947532846001407 1370031947532846001407 No Fariba Khodagholi 1370031947532846001408 1370031947532846001408 No