Fig. 3. Morphological changes associated with glial activation were reduced in 16-month-old APP/PS1;C3 KO mice. Morphological changes associated with glial.

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Fig. 3. Morphological changes associated with glial activation were reduced in 16-month-old APP/PS1;C3 KO mice. Morphological changes associated with glial activation were reduced in 16-month-old APP/PS1;C3 KO mice. (A) Iba-1– and CD68-positive immunostaining showed less activation of microglia and macrophages (that is, smaller cells with thinner processes) and less clustering of GFAP-positive astrocytes in the hippocampal CA3 region of 16-month-old APP/PS1;C3 KO mice compared to APP/PS1 mice. Scale bar, 50 μm. (B to D) Quantification of Iba-1, CD68, and GFAP immunostaining in hippocampal CA3, CA1, and dentate gyrus (DG) showed reduced glial immunoreactivity (IR) in APP/PS1;C3 KO mice compared to APP/PS1 mice (*P < 0.05, **P < 0.01, independent unpaired t tests per region; n = 6 to 8; three equidistant planes, 300 μm apart). (E) High-resolution confocal images of Aβ plaques immunostained with 6E10 antibody show microglia/macrophages (immunoreactive for Iba-1) and phagocytic cells (immunoreactive for CD68) in the hippocampal CA3 region. These findings suggested reduced phagocytosis in APP/PS1;C3 KO mice compared to APP/PS1 mice. Scale bar, 10 μm. DAPI, 4′,6-diamidino-2-phenylindole. (F) Iba-1– and CD68-positive immunofluorescence intensities were lower in APP/PS1;C3 KO mice compared to APP/PS1 mice (**P < 0.01, independent unpaired t tests per marker; n = 5). (G and H) Stereological counts of Iba-1–immunoreactive cells (G) and GFAP-immunoreactive cells (H) counterstained with 3,3′-diaminobenzidine were performed in hippocampal CA3, CA1, and dentate gyrus tissue. The number of Iba-1–positive microglia/macrophages was increased in CA3 and dentate gyrus in APP/PS1 and APP/PS1;C3 KO mice versus WT and C3 KO mice (G). The number of GFAP-positive astrocytes was increased only in the hippocampal CA3 region (H); no differences were observed in glial cell numbers between APP/PS1 and APP/PS1;C3 KO mice (**P < 0.01, one-way ANOVA with Bonferroni post hoc test per region; n = 6 to 8; three equidistant planes, 300 μm apart). Qiaoqiao Shi et al., Sci Transl Med 2017;9:eaaf6295 Published by AAAS