Fig. 1

Decreased irisin levels and increased microglial senescence in tauopathies. (A-B) Representative western blots (A) and quantifications (B) of irisin, P53, P21, and P16 protein levels in the hippocampus from 9-month-old P301S mice and aged-matched WT mice. N = 5 mice for each group. (C-D) Representative images (C) and statistical quantification (D) of immunofluorescent analysis of Iba1 (green) and β-gal (red) in the hippocampus from 9-month-old P301S mice and aged control WT mice. Paraffin brain sections were immunostained with antibodies against Iba1 and β-gal and counterstained with DAPI to show nuclei (blue). Fluorescence intensity and positive number of Iba1⁺ βgal⁺ cells per mm² were quantified. Scale bar, 20 μm. N = 6 mice for each group. (E-F) qRT-PCR analysis of TΝFα and IL6 mRNA expression in hippocampus from 9-month-old WT mice and P301S mice. N = 5 mice for each group. (G) Representative immunofluorescence images showing endocytosis of tau K18 protein in BV2 cells. BV2 cells were treated with His-tagged K18 protein for 6 h and then stained with anti-His antibody (Red) and anti-Iba1 antibody (Green). Scale bar, 10 μm. (H-I) Representative western blots (H) and quantitative analysis (I) for irisin, P53, P21, and P16 protein levels in control-treated or K18-treated BV2 cells. BV2 cells were subjected to either PBS or K18 fibril treatment for a duration of 72 h to replicate the in vitro milieu of chronic tau stimulation. N = 6 independent experiments for each group. (J-K) Representative images of SA-β-gal staining (J) and quantification of SA-β-gal positive BV2 cells (K). N = 6 independent experiments. (L-M) qRT-PCR analysis of TΝFα and IL6 mRNA expression in control-treated or K18-treated BV2 cells. N = 3 independent experiments. Data were expressed as mean ± standard deviation (SD). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001