Figure 5. Environmental enrichment largely prevented age-SNCA-dependent disturbances and activated topologically relevant genes in the SNCA interactome with respect to both disturbance modes. (A) DEGs identified in response to EE for 12-month-old TG animals compared to 2162 age-SNCA-regulated DEGs (see Fig. 3B). (B) Distribution of 265 overlapping DEGs (see A) with respect to their cluster/class assignments (see Fig 3C). (C) Gene expression modulation of 265 DEGs overlapping with class 2 or 3 (254 total) that significantly responded to the EE in TG animals. Expression medoids and standard deviation as well as cluster cardinalities shown. (D) Interaction network of DEGs attributed to the most significantly overrepresented pathway per cluster in class 2 and 3 (see Fig. 3E) and their relations to DEGs identified in TG12EE/TG12SE. Node colour indicates expression change of a gene in TG12SE/WT12SE and TG12EE/WT12SE. Node stroke reflects origin of a DEG, and node size its topological relevance in the network. Edges according to IPA knowledgebase (see Methods for details). (E) Characterisations of network genes (see D) with respect to their topological relevance and class 2 / 3 neighbourhood ratio. Node colour indicates relative compensation of gene expression change observed in TG animals through provision of EE. DEGs not significantly responding to the EE in TG animals shown in dark purple.