Fig. 4

Metformin inactivates the cGAS-STING signal in senescent astrocytes in vitro and in vivo. A–C Astrocytes were pretreated with metformin at indicated concentrations for 30 min and then stimulated with α-Syn PFF. Representative immunoblots (A) and quantification of relative expression of cGAS (B) and p-STING (C) in astrocytes (Three independent experiments). D–F, Astrocytes were pretreated with metformin (0.2 mM) for 30 min and then stimulated with MPP⁺. Representative immunoblots (D) and quantification of relative expression of cGAS (E) and p-STING (F) in astrocytes (Three independent experiments). G–I, Astrocytes were pretreated with metformin (0.2 mM) and then cultured for 40 days. Representative immunoblots (G) and quantification of relative expression of cGAS (H) and p-STING (I) in astrocytes (Three independent experiments). J–M Representative immunoblots (J) and quantification of relative expression of cGAS (K), p-STING (L) and p16 (M) in the SNpc from MPTP-treated mice (n = 3 animals for each group). N Representative double-immunostaining for cGAS (red) and astrocytic marker GFAP (green) in the SNpc. DAPI stains nucleus (blue). O Quantification of the cGAS level in GFAP⁺ astrocytes from SNpc (n = 6 animals for each group). The data shown are the mean ± SEM. One-way ANOVA with Tukey’s post-hoc tests were used. *p < 0.05, **p < 0.01, ***p < 0.001