Figure 6.

Aβ_1–42 oligomers promote neuronal differentiation of adult hippocampal NPCs via activation of the RAGE/NF-κB axis. A, Representative image of monomeric (mon), oligomeric (olig), and fibrillary (fib) Aβ_1-42 preparations separated onto Tris–tricine gel and revealed by silver staining. B–D, One hundred to 500 nm Aβ_1–42 oligomers significantly increased, compared with vehicle, the percentage of CR⁺ (B), MAP-2⁺/nestin⁺ (C), and MAP-2⁺/nestin⁻ (D) neurons generated in WT NPC cultures. Aβ_1–42 monomers and fibrils had no positive effect on neuronal differentiation of WT NPCs, with 500 nm Aβ_1–42 fibrils significantly reducing the number of MAP-2⁺/nestin⁻ mature neurons in cultures. E, No difference in the number of apoptotic cells in vehicle-treated and monomeric, oligomeric, and fibrillary Aβ_1–42-treated WT NPC cultures. F, No difference in LDH activity released in media was observed between vehicle-treated and 200 nm monomeric, oligomeric, and fibrillary Aβ_1–42-treated WT NPC cultures. G–I, In WT NPCs, the neutralizing anti-RAGE antibody (α-RAGE, 20 μg/ml), SN-50 peptide (10 μg/ml), and JSH-23 (3 μm) prevented the effect of Aβ_1–42 oligomers (200 nm) on CR⁺ (G), MAP-2⁺/nestin⁺ (H), and MAP-2⁺/nestin⁻ (I) neurons. SN-50 alone reduced the percentage of CR⁺ (G) and MAP-2⁺/nestin⁻ (I) cells in WT NPC cultures, whereas SN-50M had no effect alone or in the presence of Aβ_1–42 oligomers. B–I, Data represent the mean ± SEM of n = 3 experiments, run in triplicates. *p < 0.05, **p < 0.01, ***p < 0.001 versus vehicle-treated NPC cultures (Student's t test).