Inhibition of the EphA4-c-Abl pathway decreases the loss of dendritic spines and apoptosis induced by AβOs.

<p>(A) Cultured hippocampal neurons (21 DIV) exposed for 5 hours to 3 μM AβOs with and without STI (5 μM) and (B) KYL (60 μM). The confocal images show F-actin labeled with phalloidin (red) and immunofluorescence labeling for PSD95 (green). Scale bar, 5 μm. Densitometric analysis (A. **p<0.01 for control versus AβOs; *p<0.05 for AβOs versus AβOs + STI. B. ***p<0.001 AβOs versus AβOs + KYL. By one-way ANOVA; n = 15–20 neurites of 3 independent experiments). All graphics show the average values ± standard error. (C) Quantification of dendritic spines in cultures of wild-type (EphA4^+/+, WT) or EphA4 knockout (EphA4^-/-, KO) hippocampal neurons (15 DIV) exposed to AβOs for 5 hours (*p<0.05, ***p<0.001, no significant (NS) by one-way ANOVA; n = 15–20 neurites of 3 independent experiments). (D) Quantification of dendritic spines in neurons transfected with pGFP, sh-EphA4, sh-c-Abl, scramble RNA EphA4 and c-Abl (SC) and treated with AβOs for 5 hours (*p<0.05 for SC versus pGFP+ AβOs; ***p<0.001 for pGFP+ AβOs verus Sh-EphA4+ AβOs or sh-c-Abl+ AβOs **p<0,01). (E) Cell viability assay in primary cultures of hippocampal neurons treated with AβOs and/or 15 or 30 μM KYL peptide for 24 hours (AβOs versus AβOs+ STI and AβOs+ KYL *p<0,05; n = 3). (F) Quantification of apoptotic nuclei in primary cultures of hippocampal neurons treated with AβOs and/or 30 μM KYL for 24 hours.