PrP^Sc and Aβ oligomers activate different signaling pathways.

Hippocampal neurons were treated for 24 hrs with vehicle (A), with ADDLs (500 nM) in the absence of inhibitors (B), with ADDLs in the presence of an mGluR5 inhibitor (MPEP, 10 μM) (C), or with ADDLS in the presence of a p38 MAPK inhibitor (SB239063, 10 μM) (D). Another set of cultures was treated for 24 hrs with purified PrPSc in the absence of inhibitor (E) or in the presence of the mGluR5 inhibitor (F). Neurons were then fixed and stained with fluorescent phalloidin. Pooled measurements of dendritic spine number were collected from 15–20 cells from 3 independent experiments (G). ***p<0.001 by Student’s t-test; N.S., not significantly different. Scale bar in panel F = 20 μm (also applicable to panels A-E).