Figure 3.

ISRIB confers neuroprotection in prion-diseased mice, via a mechanism independent of prion replication. (a) Representative images of hematoxylin and eosin-stained hippocampal sections from uninfected control (left hand panels) and prion-infected mice treated with vehicle (central panels) or ISRIB (right hand panels). Vehicle-treated mice show extensive neuronal loss in the CA1-3 region, with associated spongiosis, while ISRIB treatment prevents neurodegeneration and reduces spongiosis. Scale bar, top row 400 μm, bottom row 50 μm). (b) ISRIB treatment does not affect the levels of total PrP and PrP^Sc. Total PrP and PrP^Sc levels, detected with and without proteinase K (PK) digestion, were equivalent in prion-infected mice treated with vehicle or ISRIB. Representative immunoblots of three independent hippocampal lysate samples for total PrP and PrP^Sc after PK (50 μg/ml) digestion. Control samples are from mice inoculated with normal brain homogenate