In an effort to better understand the biological processes influencing the organization of our co-expressed gene networks in NAc, we performed GSEA, utilizing a well-curated collection of gene sets ascertained from both physiological and pathological cellular states and functions. This analysis revealed that neuron-specific modules were downregulated for gene sets enriched with: 1) brain related functions such as neuronal signaling, neurotransmission, long-term potentiation, and constitutive cell maintenance, 2) growth functions such as glucose metabolism, oxidative phosphorylation, mitochondrial function, and MAPK signaling, and 3) involvement in the etiology of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s. In support of our findings, alcohol has been shown to modulate MAPK signaling cascades depending on cell type, brain region, and ethanol treatment paradigm [13, 64, 65]. However, our results contrast those of an earlier study assessing gene expression in the PFC, VTA and NAc of chronic alcoholics [8]. The authors reported that genes involved in oxidative phosphorylation and energy production were only differentially expressed in PFC, whereas we observed these functional pathways to be differentially expressed in the NAc. Potential reasons for this discrepancy could be either the small sample size of the previous study or technical, platform-dependent differences.
