Fig. 1
LD-RT normalizes TSPO-inflammation and decreases sCLU levels in pre-symptomatic TgAD rats. The right hemisphere of 9-month-old TgAD rats was irradiated with 10 Gy (2 Gy in 5 fractions delivered daily). Postmortem analyses were realized 1 month post-treatment. Ex vivo measurement of [125I]-CLINDE, a TSPO specific radiotracer, in the hippocampus (a; two-way ANOVA: F(2,29) = 43.980, P < 0.0001 for group effect), the frontal cortex (b; two-way ANOVA: F(2,29) = 57.90, P < 0.0001 for group effect), the striatum (c; two-way-ANOVA: F(2,27) = 34.79, P < 0.0001 for group effect) or in the rest of the brain (d; two-way ANOVA: F(2,28) = 77.550, P < 0.0001 for group effect). e Quantification of microglial-specific genes by qPCR in the cortex (Two-way ANOVA: F(3,100) = 10.47, P < 0.0001, for group effect). f Quantification of astrocyte-specific genes by qPCR in the cortex (two-way ANOVA: F(3,69) = 7.480, P < 0.001 for group effect). Representing immunoblot (g) and quantification of GFAP (h One-way ANOVA, F(3,19) = 11.72, P < 0.0001), SERPINA3N (i), and STAT3α (j) levels in the Triton-soluble fraction of the frontal cortex. k–m Representing immunoblot and quantification of the different forms of CLUSTERIN (CLU precursor, one-way ANOVA, F(3,19) = 2.933, P = 0.0599; secreted CLU (sCLU, one-way ANOVA, F(3,19) = 13.91, P < 0.0001) and CLUβ chain (Kruskal–Wallis test, P = 0.1337) in the Triton-soluble fraction of the frontal cortex. Western blot data are normalized to GAPDH. Quantification of genes encoding for pro-inflammatory cytokines (o; Two-way ANOVA: F(3,138) = 9.788, P < 0.0001 for group effect; F(3,138) = 6.043, P < 0.001 for gene effect; F(9,138) = 3.748, P < 0.001, group x gene interaction) and anti-inflammatory cytokines (p; Kruskal–Wallis test) by qPCR in the cortex. q–t Pro-inflammatory cytokines levels quantified by ELISA in the hippocampus. Data are normalized to the weight of tissue of the region of interest. Two-way ANOVA: IL-1α: F(2,24) = 3.392, P < 0.05 for group effect; TNFα: F(2,27) = 4.918, P < 0.05 for group effect; MCP-1: F(2,27) = 2.2561, P = 0.0959 for group effect; MCP-3: F(2,27) = 3.988, P < 0.05 for group effect. Main effects or Tukey’s post hoc tests are indicated by *P < 0.05, **P < 0.01, ***P < 0.001. ID: injected dose; L: left hemisphere; R: right hemisphere