Fig. 6: Alpha-1 adrenergic signaling regulates Tauopathy.
A Schematics showing the rationale of Phenylephrine (Adra1 agonist) and Prazosin (Adra1 antagonist) treatment in WT and CgA-KO hippocampal OTSC to access the Tau aggregation ex-vivo (Created in BioRender84). B Representative WB showing p-Tau, total tau and actin (loading control) from OTSC lysates upon different treatment. WT hippocampus OTSC treated with DMSO (n = 3) and PR (Prazosin) (n = 3). CgA-KO hippocampus OTSC treated with PBS (n = 3) and PE (Phenylephrine) (n = 3). C Representative IF images showing MC1+ misfolded Tau species in WT hippocampus OTSC treated with PR (n = 6) and DMSO (n = 6) control. Scale bar = 200 μm. D Representative IF images showing MC1+ misfolded Tau species in CgA-KO hippocampus OTSC treated with PBS (n = 6) and PE (n = 6). Scale bar = 200 μm. E Western Blot of cortex RIPA lysate of Prazosin (PR) treated (n = 5) and Vehicle (Veh.) treated (n = 5) PS19 mice showing levels of pTau, Tau and actin. F, G Densitometric quantification of p-Tau in PR (n = 5) and veh. (n = 5) treated mice. P-value in F and G was calculated using Unpaired two-tailed T-test with Welch’s correction ((F) t = 3.757, df = 4.267, (G) t = 2.924, df = 4.577). H Representative IHC image of MC1 staining in PR and veh. treated mice. Scale bar = 50 µm. Data are presented as mean values +/− SEM. Source data are provided as a Source Data file.
