Results Genome wide gene expression analysis Illumina RatRef 12 selleckbio Expression BeadChip microarrays and GenomeStudio software were used for Inhibitors,Modulators,Libraries genome wide screening. As gene expression changes are generally subtle in the brain, a relatively low fold change cutoff of 1. 2 was used. A statistical significance level of p 0. 05 was used after applying a false discovery rate to correct for multiple testing. Using these criteria, 263 genes were differentially expressed in the ILmPFC from the Inhibitors,Modulators,Libraries stress group compared to controls, with 24 genes having significantly higher expression levels and 239 with significantly lower expression levels. The majority of differentially expressed genes showed a fold change of less than 3, consistent with the notion that brain gene expression changes are generally modest.

Pathways associated with stress induced gene expression change To better interpret the stress induced changes in gene expression in the ILmPFC with regard to potential bio logical function, the list of differentially Inhibitors,Modulators,Libraries expressed genes was subjected to pathways analysis using the Database for Annotation, Visualisation and Integrated Discovery. DAVID analyzes gene lists to statistically determine whether there is enrichment for genes that belong to a priori defined gene sets. Using the Kyoto Encyclopedia of Genes and Genomes defined biological pathways, this analysis found enrichment in the list of genes for 8 pathways. Notably, neu rotrophin signalling was the most significantly enriched pathway in the differentially expressed gene list.

Two other pathways associated with neuroplasticity also had relatively high enrichment scores long term potentiation and erbB signalling. Both of these pathways have been implicated in psychiatric Inhibitors,Modulators,Libraries disorders. Real Inhibitors,Modulators,Libraries time quantitative PCR confirmation of stress induced gene changes In choosing specific genes for RT qPCR confirmation, we used one or more of the following criteria a pres ence in enriched gene lists, as determined by DAVID analysis. b a fold change in either direction of 1. 2, as determined by microarray analysis. c experimental evi dence in the literature supporting Vorinostat an involvement for the gene of interest in stress related mechanisms. For in stance, microarray and pathway analyses showed a down regulation of genes encoding for the neurotrophin receptors Ntrk3 and Ntrk2 and other components of the neurotrophin signalling pathway such as Camk2a, Gsk3B and Braf, in the ILmPFC of rats from the stress group. RT qPCR analysis confirmed that the expression levels of the genes that encode for Braf, Gsk3B, Ntrk2 and Ntrk3 proteins were decreased in the ILmPFC of the stress group, in accordance with microarray results. The decrease in Camk2a gene expression, however, was not confirmed by RT qPCR.