Fig. 3: Human wild-type Aβ exacerbates the formation of OC+ clusters in the hippocampus of hAβ-KI mice.
a Representative images for astrocytes and OC+ cluster in WT (a1–a3) and homozygous hAβ-KI (a4–a6) mice across their lifespans (individual clusters highlighted by white arrowheads). Confocal images showed the association of the astrocytes with OC+ granules (a4b–a6b) in hAβ-KI mice. b Quantification of the number of OC+ clusters/hippocampal section at each age in homozygous hAβ-KI (green) and WT (blue) mice (WT 2 mo = 16, 6 mo = 6; 10 mo = 6; 15 mo = 6; 18 mo = 5; 22 mo = 10; hAβ-KI 2 mo = 9; 6 mo = 6; 10 mo = 6, unpaired, two-tailed t-test, *p = 0.0411; 14 mo = 6, unpaired, two-tailed t-test, **p = 0.0070; 18 mo = 7; 22 mo = 11, unpaired, two-tailed t-test, **p = 0.0022). c Schematic representation of OC+ clusters of granules distribution in the brain of hAβ-KI mice (light brown = Anterior Olfactory Nucleus, brown = Olfactory Tubercle, blue = Piriform Cortex, yellow = Cortical Amygdala, green = Piriform Amygdalar Cortex, gray = CA1 and orange = Cochlear nucleus). Graphic adapted from Image 26, 47, 73, 81 and 110 of the Allen Mouse Brain Atlas. Copyright 2004, Allen Institute for Brain Science. Available from https://mouse.brain-map.org/static/atlas63. d Immunostaining for astrocytes (GFAP, red channel) and protofibrils (OC, green channel) shows their accumulation in the piriform cortex, lining the cortical edge in hAβ-KI (d1) and WT (d2) mice. e Experimental design in which hAβ-KI homozygous; UBC-CREERT2 hemizygous mice are treated with tamoxifen or vehicle for 6 months (green box = exon 14, red triangle = loxP sequence, yellow and blue box = UBC-Cre-ERT2). Mice were sacrificed at 8-month of age. f Immunostaining for astrocytes (GFAP, red) and protofibrils (OC, green) in the hippocampus of either vehicle or tamoxifen-treated hAβ-KI homozygous; UBC-CREERT2 hemizygous mice. g Quantification of OC+ granular clusters in vehicle (blue) and Tamoxifen (brown) treated hAβ-KI homozygous; UBC-CREERT2 hemizygous mice (Vehicle n = 7, Tamoxifen n = 8; unpaired, two-tailed t-test, *p = 0.0160). Data are presented as mean values ± SEM. Scale bar: 300 μm (a1–a6 and f1–f2) and 200 μm (d1–d2).
