Fig. 1

The JAK2-STAT3 pathway controls astrocyte reactivity in APP mice. a, Three month-old APP mice were injected in the hippocampus with AAV-GFP or AAV-SOCS3 + AAV-GFP. WT mice were injected with AAV-GFP. All mice were analyzed 6 months later. Another cohort was generated with AAV-JAK2ca used instead of AAV-SOCS3, to enhance astrocyte reactivity. b, Confocal images of astrocytes stained for GFAP (magenta) and STAT3 (cyan). In APP-GFP mice, astrocytes are hypertrophic, overexpress GFAP and show nuclear accumulation of STAT3 (indicating STAT3 activation, arrowhead), compared to WT-GFP mice. SOCS3 significantly reduces GFAP and STAT3 levels, whereas JAK2ca further increases GFAP and STAT3 levels in APP mice. c, d, Quantification of immunoreactivity (IR) for STAT3 (c, N = 4–5/group) and GFAP (d, N = 5–10/group) on immunostainings in b. e, The proportion of GFP⁺ astrocytes co-expressing vimentin is significantly lower in APP-SOCS3 mice and higher in APP-JAK2ca mice, than in control APP-GFP mice. N = 3–7/group. f, g, Western blot of GFAP in WT and APP mice shows the same modulation pattern of GFAP levels by SOCS3 and JAK2ca. GFAP levels were normalized by actin. Representative images and quantification from three independent membranes. N = 5–8/group. h, AAV-SOCS3 is also able to reverse astrocyte reactivity, when injected in the hippocampus of 15 month-old APP mice that already display severe plaque deposition (the hippocampus is outlined). i, GFAP IR quantification from images in h. N = 3/group. c-e, g, ANOVA and Tukey’s test. i, Paired t test. * p < 0.05, ** p < 0.01, *** p < 0.001