Fig. 4

SEMA4D antibody treatment inhibits reactive astrocytes and restores neuronal and cognitive deficits in CVN mouse model of AD. CVN and WT mice were treated in vivo with anti-SEMA4D “aS4D” or mouse IgG1 isotype control antibody “CTRL”. a CA1 hippocampal region of CVN and wild type mice were stained GFAP and b fractal dimension analysis and c GS expression in GFAP+ cells demonstrates significant changes in brains of CVN mice compared to wild type, which is restored following treatment with anti-SEMA4D antibody. d The hippocampal region was stained with anti-somatostatin antibody or anti-Neuropeptide-Y (NPY) to identify specific subsets of inhibitory neurons. No effects on excitatory synapses were observed in diseased mice (as determined by Synaptophysin and VGLUT-1 staining). Percentages were quantified for all animals (n = 9–13/group) and normalized to total area scanned; group mean + SEM are shown. For b–d, group differences and statistical significance were determined using Kruskal–Wallis H test and subsequent pairwise comparisons were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. e Latency was assessed in Radial Arm Water Maze at week 36. Group means of all animals + SEM for each trial block is shown. Statistical significance was determined by 2way mixed ANOVA with repeated measures