Fig. 7
Depletion of microglia using PLX5622 reduces the presence of small plaques but exacerbates the paired-pulse ratio effects of App knock-in mice. Red and blue timelines indicate the PLX5622 feeding regimen for App knock-in mice and age-matched wild types. The first age indicates the start of treatment, the second the age animals were killed for experimentation. A&F) Fluorescent micrographs of AppNL-G-F (A) and AppNL-F (F) CA1 region of the hippocampus following labelling of Aβ with LCOs and fluorescent immunohistological staining for IBA1 and CD68. Stratum oriens (SO), stratum pyramidale (SP), stratum radiatum (SR) and stratum lacunosum moleculare (SLM) are indicated in the no-drug AppNL-G-F condition (for further orientation, the stratum moleculare (SM), stratum granulosum (SG) and hilus (H) within the dentate gyrus are also shown). Scale bar in NL-G-F 1200 mg/kg PLX image is 200 μm. B&G) Densities determined as cells that were IBA1+ microglia. Two-way ANOVA revealed significant main effects of drug (AppNL-G-F p < 0·0001; AppNL-F p < 0·0001). C&H) Densities of IBA1+ microglia that were also CD68+ in the CA1 region of AppNL-G-F (C) or AppNL-F mice. Data are presented as total density (i) and proportion of IBA1+ microglia (ii). Sample sizes (animals) for panels B and C are indicated within the bars of panel B; and for panels G and H are indicated in panel G. In panels B,C,G&H, Sidak corrected simple comparisons within drug are indicated by * versus control (0 mg PLX5622/kg food) and † versus 300 mg/kg; † p < 0·05; ** p < 0·01; *** p < 0·001; ****/†††† p < 0·0001. D&I) Plaque size histograms. Dunnett’s post hoc test for within plaque size bin comparisons to 0 mg/kg PLX5622 are indicated by *** p < 0·001 and **** p < 0·0001. Sample sizes (animals) are indicated within the parentheses in the legends. E&J) Paired-pulse ratios from PLX5622-treated. In wild type (Ei and Ji) and AppNL-G-F (Eii) or AppNL-F (Jii) mice. Sample sizes are indicated in the legend. For simplicity in panels E&J, only Sequential Sidak comparisons within drug dose versus control at the 25 ms inter-stimulus interval are indicated * p < 0·05; **** p < 0·0001; see main text for further details. Data in panels B-E and G-J plotted as mean ± SEM