PrP^Sc synaptotoxicity is reversible by a p38 MAPK inhibitor.

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