Fig. 5: RS5 treatment reverses stress-induced gene expression changes in the PL. | Nature Communications

Fig. 5: RS5 treatment reverses stress-induced gene expression changes in the PL.

From: Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice

Fig. 5

a–c Experimental design (a). Heatmap showing the expression profiles of genes changed by ≥1.2-fold after CRST (b) and those changed by RS5 treatment in CRST mice (c), and follow-up unbiased alignment with expression levels of the respective genes changed by RS5 (b) and CRST (c), respectively. ↑ and ↓, indicate up- and down-regulation, respectively. d–f Two clusters identified from GO enrichment analysis with weighted K-means clustering of gene expression profiles (d, e). The PPI networks formed by the genes of clusters 5 (orange, 28 genes) and 7 (green, 24 genes) and 16 genes (black) were identified from an extended search of the STRING database at a confidence level of >0.700 (f). g, h Transcript levels of GR(Nr3c1), MR(Nr3c2), Fkbp5, Fkbp4, Hsp90aa1, and Hsp90ab1 (g) and Dusp1, CaMKIIα, ERK1(Mapk3), and ERK2(Mapk1) (h) in the PL of the indicated groups (n = 8–12 per group). i–n Immunofluorescence images showing total GR (red) and Fkbp5 (green) expression in the PL for the indicated groups (i). DAPI, blue. Quantification levels of GR (j), Fkbp5 (k), and DAPI intensity (l) (n = 4–6 animals per group). Two distinct clusters with differential expression of GR and Fkbp5 across individual cells for the indicated groups (m), and the % composition of individual cells of each group in the clusters (n) (n = 248–309 cells from 4–6 animals per group). o–u Experimental design (o). Immunohistochemical images showing siRNA-mediated knockdown of GR expression (p) and GR transcript levels (q) in the PL. Transcript levels of Fkbp5 in the PL (r), and of CRH and AVP in the PVN (s) of mice injected with siRNA-GR in the PL. Immobility time in the TST (t) and FST (u) for the indicated groups (n = 6–8 per group). Data were mean ± SEM. *, the difference compared to control; #, the difference compared to CRST. *, #, p < 0.05; **, ##, p < 0.01 (Two-sided Student’s t-test; one-way ANOVA followed by Newman–Keuls post hoc test). See Supplementary Data 4 for statistical details.

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