Fig. 7: Complementary approach to identify LpEV-regulated genes in Drd2-KO mice, considering both reversal and nonreversal effects.

a–e, Volcano plots showing LpEV-regulated genes in the dStr (a), NAc (b) and dHP (c) of Drd2-KO mice. Only genes with a fold change greater than 1.2-fold (either upregulated or downregulated) were chosen for further analysis. Genes overlapped with SFARI genes were marked with red for upregulated, blue for downregulated and gray for others. Summary of selecting LpEV-regulated genes in the dStr, NAc and dHP of Drd2-KO mice, and following GO enrichment of selected genes (d). Venn diagrams showing the number of LpEV-regulated genes in each brain region and those overlapped between regions (e). f, g, The interaction networks of genes overlappingly expressed in the dStr, NAc and dHP. Genes (60 genes) commonly upregulated across brain regions in Drd2-KO mice (f) and those (58 genes) commonly downregulated across brain regions in Drd2-KO mice (g) are indicated. Genes overlapped with SAFRI genes are marked with red for unregulated and blue for downregulated, and those overlapped with those RRHO genes (summarized in Fig. 6) are marked with open green boxes. h–o, Heat maps showing expression levels of 60 commonly upregulated in the dStr (h), NAc (j), and dHP (l) and 58 commonly downregulated genes after LpEV treatment in the dStr (i), NAc (k), and dHP (m) of Drd2-KO mice. Note that most genes unbiasedly selected as being up- or downregulated by LpEV in each brain region showed opposite expression patterns in Drd2-KO mice. The number of genes (%) were classified as upregulated (fold change ≥1.1), unchanged or downregulated (fold change ≤−1.1) in each brain region (n and o).