Fig. 4

Am580 reduces microglial toxicity. The effect of Am580 on naïve or LPS-stimulated CD11b + microglia isolated from 7-month-5xFAD transgenic mice was examined. A–D Data from a representative experiment. Am580 significantly inhibited the expression levels of iNOS (A) and TNFα (B) RNA in microglia stimulated by LPS. Am580 had no significant effect on the expression of Il-1b (C) and had a suppressor effect on Il-10 expression (D). Activation of microglia with Zymosan caused increase in iNOS, TNFα and Il-1b expression, which were effectively attenuated by pre-exposure to Am580 (E–G). Am580 was given continuously in an ICV delivery, using mini-osmotic pumps for 4 weeks in 7-month-old 5xFAD mice (n = 4). H, I Representative images of the cortex stained for Iba1 + microglia. Am580 treated mice had significant decrease in the fraction on iNOS + toxic microglia without affecting the total number of Iba1 + cells (J–K, n = 4). Error bars-SD. P values by students unpaired T test in J and one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test in A–D #P = 0.06, *P < 0.05, **P < 0.01. E–G show representative data.