Prion proteins (PrP) were localized in the brains of normal and
scrapie-infected hamsters by immunohistochemistry and Western blotting. PrP
monoclonal antibodies and monospecific anti-
PrP peptide sera, which react with both the cellular (PrPC) and
scrapie (PrPSc)
isoforms of the
prion protein, were used to locate PrP in tissue sections. In normal hamsters, PrPC was located primarily in nerve cell bodies throughout the CNS; whereas, in the terminal stages of
scrapie, PrP immunoreactivity was shifted to the neuropil and was absent from most nerve cell bodies.
Prion proteins were not uniformly dispersed throughout the gray matter of
scrapie-infected hamster brains; rather, they were concentrated in those regions that exhibited spongiform degeneration and reactive
astrogliosis. Since earlier studies showed that the level of PrPC remains constant during
scrapie infection as measured in whole brain homogenates and no
antibodies are presently available that can distinguish PrPC from PrPSc, we analyzed individual brain regions by Western blotting. Analysis of
proteinase K-digested homogenates of dissected brain regions showed that most of the regional changes in PrP immunoreactivity that are seen during
scrapie infection are due to the accumulation of PrPSc. These observations indicate that the tissue pathology of
scrapie can be directly correlated with the accumulation of PrPSc in the neuropil, and they suggest that the synthesis and distribution of the
prion protein has a central role in the pathogenesis of this disorder.