Fig. 2

Increased susceptibility of 5xFAD brains to the neurotoxic effect of zymosan. a–e Zymosan was delivered ICV continuously for 28 days in wt mice, and cortical neurons were then quantified. Panels a–d show representative images of the cortex stained for Neun+ neurons injected with PBS (a), 15 μg (b), 25 μg (c) or 70 μg (d) zymosan. Quantification indicated a dose-dependent neurotoxic effect of zymosan, inducing neurodegeneration (e). f Twenty-five micrograms zymosan was delivered ICV as single injection, or continuously for 1 week or 28 days in wt and 5xFAD mice. The extent of cortical neuronal loss was dependent on time of exposure. At all durations of exposure, 5xFAD brains exhibited a significantly increased loss of cortical neurons as compared with wt mice. g, h The dynamics of neuronal loss was examined at 3 days, 2 weeks and 28 days after a single ICV injection of zymosan. Panels in g show representative images of the cortex stained for Neun+ neurons in wt and 5xFAD brains at the different time points. Quantification of cortical neuronal density showed that zymosan-induced neuronal death within 3 days after injection (h)