Neuroprotective Effects of Candesartan in Glutamate-Induced Excitotoxicity

We performed microarray analysis of gene expression in four sets of rat primary neuronal cultures: controls; treated with candesartan at concentrations in the range of blood levels obtained in humans after oral administration [51 (link)]; exposed to excitotoxic glutamate concentrations [25 (link)]; and treated with candesartan before the exposure to glutamate. Excitotoxicity was induced by exposing cultures to 100 μM glutamate (Sigma-Aldrich) and pretreated for 1 h with vehicle (0.1 % saline and 0.1 N Na₂CO₃ at pH 7.4), or the AT1R blocker candesartan (10 μM) (Sigma-Aldrich) dissolved in 0.1 N Na₂CO₃, pH 7.4. After addition of candesartan, the compound was not removed and was present throughout the incubation. candesartan and glutamate concentrations and timing of the experiments were selected on the basis of prior studies demonstrating protection of cultured neurons from inflammation and glutamate-induced injury [25 (link), 27 (link)]. Figure 1 is a flow chart for data analysis.Fig. 1

Flow chart for data analysis. ACE angiotensin converting enzyme, AD Alzheimer’s disease, ANOVA analysis of variance, CGC cerebellar granule cell, ES enrichment score, GSEA gene set enrichment analysis, IFN interferon, IPA ingenuity pathway analysis, KEGG Kyoto encyclopedia of genes and genomes, LPS lipopolysaccharide, pval p value, TGF transforming growth factor, TNF tumor necrosis factor