[Effects of peroxisome proliferator-activated receptors γ on the expression of insulin receptor substrate-4 gene in rat cortical neurons and mouse brain].

ABSTRACT

OBJECTIVE: To investigate the effect of peroxisome proliferator-activated receptors γ (PPARγ) on insulin receptor substrate-4 (IRS-4) gene expression in the brain. METHODS: Primarily cultured cortical neurons from E17-18 Sprague Dawley rats, after 1 week of plating, were exposed to 10 µmol/L PPARγ agonist rosiglitazone for 0, 1, 4 or 24 h. Adult C57BL/6J mice or conditional brain PPARγ knock-out mice (B-PPARγ-KO, BKO) received an intraperitoneal injection of rosiglitazone in 10% DMSO at 12 mg/kg or injection of the same volume of saline containing 10% DMSO. The effect of rosiglitazone on the survival of the neurons was examined by MTT assay. The expression of IRS-4 mRNA was analyzed by real-time quantitative PCR. RESULTS: The survival of the cortical neurons showed no significant difference between the agonist groups and the control group. The expression of IRS-4 mRNA was significantly up-regulated in the cortical tissues and neurons of the agonist groups compared with the control groups (P<0.05), but in BKO mice without treatment, IRS-4 mRNA expression was significantly down-regulated (P<0.05). CONCLUSION: PPARγ can enhance the expression of IRS-4 mRNA in the brain.