Fig. 2: CgA deficiency reduces tauopathy. | Nature Communications

Fig. 2: CgA deficiency reduces tauopathy.

From: Chromogranin A deficiency attenuates tauopathy by altering epinephrine–alpha-adrenergic receptor signaling in PS19 mice

Fig. 2

A Representative Nissl staining of mouse brain section of WT, PS19, CgA-KO and CgA-KO/PS19 littermate mice of 9-10 months of age. Scale bar = 200 μm. B Estimated volume of the hippocampus of 9-10-months-old WT (n = 8), PS19 (n = 6), CgA-KO (n = 6) and CgA-KO/PS19 mice (n = 7). (One-way Anova, Sidak’s Multiple comparison test, F3, 23 = 1.969, P < 0.0001). C WB of cortex RIPA lysates of WT (n = 4), PS19 (n = 5) and CgA-KO/PS19 (n = 5) mice showing levels of pathogenic phosphorylated Tau (pTau), total Tau, PSD95, actin and CgA. D Representative IF images showing the levels of MC1 labeled misfolded Tau species in the Dentate Gyrate (DG) and CA3 region of hippocampus. Scale bar = 100 μm. E ImageJ quantification of MC1+ misfolded Tau species revealed by IF in DG (n = 12) (Unpaired two-tailed t-test with Welch’s correction, t = 3.696, df = 11.71). F ImageJ quantification of MC1+ misfolded Tau species revealed by IF in CA3 (n = 14) (Unpaired two-tailed T-test with Welch’s correction, t = 4.836, df = 17.31). G Fluorescence images of HEK293 cells expressing TauRD-GFP transfected with the brain extracts of PS19 (top) or CgA-KO/PS19 mice. Scale bar = 50 μm. H ImageJ quantification of Misfolded Tau species (FRET+) as shown in G, normalized to DAPI counts (n = 4 per group) (Unpaired two-tailed T-test with Welch’s correction, t = 6.112, df = 4.753). I Schematics describing the Tau fibrils (K18/PL)-induced spreading assay (Created in BioRender83). J Representative IF images using MC1 antibody showing spreading of misfolded Tau species from the site of injection (ipsilateral) to the opposite site (contralateral) of the hippocampus. A zoomed-in view of the aggregate-rich region is shown in each case. Scale bar = 200 μm. K ImageJ quantification of misfolded Tau species as a ratio of MC1+ area in ipsilateral hippocampus relative to the contralateral hippocampus as in (J) (n = 6 mice per group) (Unpaired two-tailed T-test with Welch’s correction, t = 8.814, df = 7.042). Data are presented as mean values +/− SEM. Source data are provided as a Source Data file.

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