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-c) activity on cyclooxygenase 2 (COX-2) expression and N-methyl-Daspartic 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-c agonist), GW9662 (PPAR-c antagonist), NS398 (selective COX-2 antagonist) and NS398 þ ROSI groups. Two hours after treatment in each group, cell viability, intracellular Ca 2þ concentrations, PPAR-c 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 lmol/L of NMDA significantly decreased the neuronal cell viability, increased Ca 2þ concentrations, which also increased the COX-2 protein expression and decreased PPAR-c expression in neurons. Compared with the NMDA group, the cell viability was increased, Ca 2þ concentrations and COX-2 protein expression were significantly decreased, PPAR-c expression was significantly increased in the MK-801, ROSI, NS398 and ROSI þ NS398 groups (both P < 0.01). This finding suggested that upregulation of PPAR-c activity can inhibit COX-2 expression, decrease Ca 2þ concentrations in primary cultured cortical neurons, and protect neurons against NMDA-induced excitatory neurotoxicity.

Guggulsterone Mediated JAK/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism

“…PPAR-gamma controls fatty acid synthesis, glucose metabolism, and adipocyte differentiation [ 23 ]. PPAR gamma activation may protect against neurotoxicity [ 24 ], neurodegeneration, drug dependency [ 25 ], and neuroinflammation [ 26 ]. It was also observed that PPAR gamma enhances antioxidant defence, mitochondrial biogenesis, and oxidative phosphorylation [ 27 ].…”