Figure 6.

Aβ (1 μm) increases p38 MAPK/JNK phosphorylation in cortical slices. A, The plot represents averaged phospho-p38 MAPK levels measured using ELISA and expressed as unit/total content of p38 MAPK protein. Tissue levels of phospho-p38 MAPK after slices perfusion with 1 μm Aβ(1-42) were significantly higher with respect to control vehicle-treated slices (*p < 0.05 vs control vehicle) both before and after LFS. Selective deficiency of RAGE signaling in microglia (DNMSR) and complete inactivation of RAGE with anti-RAGE IgG did not modify basal level of phospho-p38 MAPK (p > 0.05 vs control vehicle). Blockade of RAGE was able to prevent Aβ-induced increase of phospho-p38 MAPK (p < 0.05 vs slices treated with Aβ alone), even if the increase induced by LFS was still present. p38 MAPK activation by Aβ was also significantly reduced in slices treated with IL-1Ra (p < 0.05 vs Aβ alone) and in slices treated with the JNK inhibitor SP600125 (p < 0.05 vs Aβ alone). B, The plot represents averaged phospho-JNK levels measured using ELISA and expressed as unit/total content of JNK protein. Elevated phospho-JNK levels were increased by 1 μm Aβ treatment (*p < 0.05 vs control vehicle) but not by LFS. Deficiency of RAGE signaling in microglia (DNMSR) and complete inactivation of RAGE with anti-RAGE IgG did not modify basal level of phospho-JNK both before and after LFS (p > 0.05 vs control vehicle). Blockade of RAGE was able to prevent Aβ-induced increase of phospho-JNK (p < 0.05 vs slices treated with Aβ alone). Phospho-JNK level after 1 μm Aβ treatment was also significantly reduced in slices treated with IL-1Ra (p < 0.05 vs Aβ alone). C, The plot represents average IL-1β levels (in picograms per milliliter) in EC slices; IL-1β level was significantly increased in cortical slices exposed to 1 μm Aβ for 10 min, whereas inhibition of JNK (SP600125) but not of p38 MAPK (SB203580) prevented Aβ effect and IL-1β levels were comparable with control values (p > 0.05 vs control). Error bars indicate SEM.