Figure 2
Selective loss of activity-dependent genes in postmortem human brain. (A–H) The RNAseq-derived gene expression coverage from four fresh human cortex tissues (EP158FP2, EP158FP4, EP168SF10 and EP168FP57) are shown in blue and compared to healthy postmortem cortex samples (SRR1747164, SRR1747173, SRR1747186 and SRR1747190) shown in red. While housekeeping genes including GAPDH, HMBS, SDHA and UBC appear relatively unaffected, the activity-dependent genes SOCS3, SPP1, ZFP36 and THBS1 showed a significant reduction in exon-specific transcript levels in postmortem samples (p < 0.05). For each gene, the y-axis is the same for each sample with the scale in the upper left corner. (I) We cross-referenced 2000 of the most downregulated genes in postmortem samples compared to fresh samples and ordered them based on their fold change (expression of the gene in fresh tissue/expression of the gene in postmortem sample) into four groups of 500 genes each. For each group, we computed the enrichment in activity-dependent genes. The hypergeometric analysis of the distribution of activity-dependent genes shows their expression is significantly reduced, more than four times what is expected by chance in the 500 most downregulated genes of the postmortem samples, E Enrichment, hP hypergeometric p-value. (J) A PCA of the 500 activity-dependent genes with the greatest decrease in expression in the postmortem samples highly separated all the fresh tissues samples from the postmortem samples, independent of the degree of epileptic activity. Each dot corresponds to a given sample, the barycenters are represented by triangles and the ellipses show the 80% confidence interval for the position of the barycenter. L158, L168, H158, H168 correspond to the four fresh samples from patient EP158 and EP168, ‘L’ corresponds to low activity brain regions and ‘H’ corresponds to the high activity brain regions.
