Fig. 5: CgA deletion induces reprogramming of adrenergic receptor expression in Tauopathy mice brain.

A Heatmap representation of normalized read Z-scores of shared upregulated or downregulated genes in WT (n = 5) and CgA-KO/PS19 (n = 6) relative to PS19 (n = 6) (log2 fold-change > 0.5, p value < 0.01) from 9-month-old mice cortices. Adra gene family showing significant expression changes are highlighted. B Z-score of hierarchical clusters I of WT, PS19 and CgA-KO/PS19. P-value was calculated using One-way Anova (F_{2, 1248} = 163.9, P < 0.0001) Sidak’s multiple comparison test. C Z-score of hierarchical clusters II of WT, PS19 and CgA-KO/PS19. P-value was calculated using One-way Anova (F_{2, 876} = 45.91, P < 0.0001) Sidak’s multiple comparison test. D Venn diagram showing number of upregulated genes as compared in two groups (WT/PS19 and CgA-KO/PS19). Expression of 417 genes overlaps in PS19 vs. WT and PS19 vs. CgA-KO/PS19. E Gene ontology analysis for pathways enriched in shared genes in (D). Number of genes involved in each pathway are shown in the bar. F Venn diagram showing number of downregulated genes as compared in two groups (WT/PS19 and CgA-KO/PS19). Expression of 293 genes overlaps in PS19 vs. WT and PS19 vs. CgA-KO/PS19. G Gene ontology analysis for pathways enriched in shared genes in (E) Number of genes involved in each pathway are shown in the bar. H Representative WB showing Adra1b, Adra2b and Adrb2 protein levels in three mouse groups, WT (n = 4), PS19 (n = 4) and CgA-KO/PS19 (n = 4). Also shown are the levels of p-Tau (S202/T205), total PS19, CgA and tubulin (loading control). I Quantitation showing relative levels of Adra1b in (H). WT (n = 4), PS19 (n = 4) and CgA-KO/PS19 (n = 4). P-value was calculated using One-way Anova (F_{2, 9} = 0.07055, P = 0.0004) Sidak’s multiple comparison test. J Quantitation showing relative levels of Adra2b in (H). WT (n = 4), PS19 (n = 4) and CgA-KO/PS19 (n = 4). P-value was calculated using One-way Anova (F_{2, 9} = 0.8729, P = 0.0004) Sidak’s multiple comparison test. K Representative IF images of Adra1b, NeuN and DAPI in the hippocampus slices of PS19, CgA-KO/PS19 and WT mice. Scale bar = 200 μm. L Image (J) Quantitation of IF images as in (H) showing relative levels of Adra1b in PS19 (n = 5) and CgA-KO/PS19 (n = 5). P-value was calculated using (Unpaired two-tailed T-test with Welch’s correction, t = 2.649, df = 4.293). M Pearson correlation between Adra1b area fraction and the hippocampus volumes of PS19 (red dots) and CgA-KO/PS19 (blue dots) mice. Data are presented as mean values +/− SEM. Source data are provided as a Source Data file.