Upregulation of PPAR-gamma activity inhibits cyclooxygenase 2 expression in cortical neurons with N-methyl-d-aspartic acid induced excitatory neurotoxicity

Abstract

This study aimed to investigate the effect of upregulated peroxisome proliferator-activated receptor-gamma (PPAR-γ) activity on cyclooxygenase 2 (COX-2) expression and N-methyl-d-aspartic acid (NMDA)-induced excitatory neurotoxicity in primary cultured cortical neurons. Rat cortical neurons were cultured for 8 days in vitro, and divided into control, NMDA, MK-801 (selective NMDA antagonist), rosiglitazone (ROSI, PPAR-γ agonist), GW9662 (PPAR-γ antagonist), NS398 (selective COX-2 antagonist) and NS398 + ROSI groups. Two hours after treatment in each group, cell viability, intracellular Ca2+ concentrations, PPAR-γ and COX-2 protein expression were detected by CCK-8 assay, flow cytometry and western blot assay, respectively. The results showed that compared with the control group, 100 μmol/L of NMDA significantly decreased the neuronal cell viability, increased Ca2+ concentrations, which also increased the COX-2 protein expression and decreased PPAR-γ expression in neurons. Compared with the NMDA group, the cell viability was increased, Ca2+ concentrations and COX-2 protein expression were significantly decreased, PPAR-γ expression was significantly increased in the MK-801, ROSI, NS398 and ROSI + NS398 groups (both P < 0.01). This finding suggested that upregulation of PPAR-γ activity can inhibit COX-2 expression, decrease Ca2+ concentrations in primary cultured cortical neurons, and protect neurons against NMDA-induced excitatory neurotoxicity.

Keywords

• ppar-γ
• nmda
• excitatory neurotoxicity
• cox-2
• ca2+ concentrations