Fig. 8: Astrocytic Nrf2 does not alter APP processing but boosts autophagy. | Nature Communications

Fig. 8: Astrocytic Nrf2 does not alter APP processing but boosts autophagy.

From: Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology

Fig. 8

A Western analysis of BACE1 expression. F (1,8) = 0.99, p = 0.35 (APP/PS1 effect-cortex); F (1,8)=0.38, p = 0.55 (GFAP-Nrf2 effect-cortex); F (1,8) = 2.24, p = 0.17 (APP/PS1 effect-hippocampus); F (1,8) = 0.43, p = 0.53 (GFAP-Nrf2 effect- hippocampus); Mean ± SEM shown here and throughout this figure. B Western analysis of 99 and 83 amino acid C-terminal fragments of APP (antibody C1/6.1) in the cortex (left) and hippocampus (right). Cortex: two-way ANOVA F (3, 16) = 53.98, p = 12.4E−08 (main genotype effect). #p = 2.1E−07, 3.6E−06, 1.7E−05, 3.8E−05 (Bonferroni’s post-hoc test, n = 3); ns p values: 0.14, >0.99. Hippocampus: two-way ANOVA F (3, 16) = 77.88, p = 9.2E−10 (main genotype effect). #p = 9.2E−06, 9.8E−04, 8.6E−06, 8.3E−05 (vs. WT, Bonferroni’s post-hoc test, n = 3); ns p values: 0.46, >0.99. C Analysis of p62 in biochemical fractions. For each fraction a two-way ANOVA was performed, showing a main effect of the APP/PS1 genotype: (Triton: F (1, 8) = 346.3, p = 9.8E−07; SDS: F (1, 8) =109.4, p = 3.1E−08; urea: F (1, 8) = 45.1, p = 0.0002), and interaction of GFAP-Nrf2 and APP/PS1 status (Triton: F (1, 8) = 31.5, p = 0.0005; SDS: F (1, 8) =13.2, p = 0.0066; urea: F (1, 8) = 12.55, p = 0.0076). #p = 2.7E−07, 3.2E−05, 1.7E−05, 0.0026, 0.0002 (effect of APP/PS1, Bonferroni’s post-hoc test). *p = 0.020, 0.0002, 4.2E−06 (effect of GFAP-Nrf2, Bonferroni’s post-hoc test). N = 3 animals/genotype. D Immunofluorescence staining of cortical sections for Iba1 (red) and amyloid (green, 6E10 antibody). Arrows indicate Iba1 immunofluorescent cells; arrowheads show 6E10 staining in plaques and neurons. Scale bar: 10 μm. E, F Western analysis of Iba1 expression. Two-way ANOVA for Iba1: F (1, 8) = 7.1, p = 0.029 (APP/PS1 effect); F (1, 8) = 23.2, p = 0.0013 (GFAP-Nrf2 effect). *p values: 0.014, 0.0018 (Bonferroni’s post-hoc test, n = 3). G Immunofluorescence staining of cortical sections for Gfap (red) and amyloid (green, 6E10 antibody). Arrows indicate Gfap-positive cells; arrowheads show 6E10 staining in plaques and neurons. Scale bar: 10 μm. H Western analysis of Gfap expression; quantitation in Fig. 8F. Two-way ANOVA for Gfap: F (1, 8) = 23.5, p = 0.0013 (APP/PS1 effect); F (1, 8) = 25.7, p = 0.0010 (GFAP-Nrf2 effect). *p values: 0.014, 0.0006 (Bonferroni’s post-hoc test, n = 3).

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