Similar to the expression patterns of genes modulated by nicotine, the overrepresented GO categories were region specific. This indicates the differential responses of these regions to nicotine treatment. Despite these differences, the GO categories related to the mitochondrion were enriched in all six brain regions. In the amygdala, hippocampus, PFC, and VTA, the GSEA scores (Table 2) for mitochondria-related GO categories all were positive, indicating that nicotine exposure preferentially upregulated the expression of a subset of genes, the leading-edge subset (Subramanian et al. 2005), whereas in the NA and striatum, the GSEA scores for mitochondria-related GO categories were all negative, indicating the genes of leading-edge subset were suppressed by nicotine. Specifically, in each brain region, the mitochondrial electron transport system or part of it (such as complex I or ATP synthase) were among the enriched GO categories detected by GSEA.
