Fig. 8

Kv1.3 channel blockade promotes Aβ phagocytosis and limits amyloid β burden in 5xFAD mice. a Comparison of ex-vivo phagocytosis of fluorescent Aβ42 fibrils by acutely isolated CNS CD11b⁺ cells from WT (sham-treated or LPS-treated for 4 days) and 5xFAD mice (age 6–8 mo, n = 4 mice/group). Cells were loaded with fluorescent fibrillar Aβ42 in the presence of either sham or ShK-223 (100 nM) for 1 h prior to labeling with anti-CD11b and anti-CD45 antibodies. b Comparison of ex-vivo phagocytic capacity for fluorescent Aβ42 fibrils by acutely isolated CNS CD11b⁺ cells from sham-treated or ShK-223-treated 5xFAD mice (n = 4/group). ShK-223 was administered twice a week (i.p., 100 μg/kg) in this study. c-g In this study of ShK-223 in 5xFAD mice, mice were treated with PBS or ShK-223 (100 μg/kg) between 3 and 6 mo (n = 10 mice/group) and brains were fixed for immunohistochemistry. c Comparison of hippocampal Aβ plaques in PBS-treated (top) and ShK-223-treated (bottom) mice (Right: Higher magnification image). d Quantification of Aβ plaque burden in the hippocampus and frontal cortex. e Comparison of hippocampal (subiculum) Aβ plaque size in PBS- and ShK-223-treated mice. f, g, h Immunofluorescence images showing Iba1 (Green) and Aβ (Blue) immunoreactivities in the hippocampus of PBS- and ShK-223-treated mice. g Quantitative analyses of Iba1 expression (% area) and Aβ plaque burden. h Quantitative analysis of peri-plaque Iba1 immunoreactivity comparing PBS- and ShK-223-treated mice. 5–8 plaques of relatively similar size were selected from each mouse and Iba1⁺ area was normalized to the plaque area and compared across groups. *p < 0.05, **p < 0.01, ***p < 0.005