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NEUROLOGY 1998;50:2
© 1998 American Academy of Neurology

Changes in the localization of brain prion proteins during scrapie infection

S. J. DeArmond, MD, PhD, W. C. Mobley, MD, PhD, D. L. DeMott, BA, R. A. Barry, PhD, J. H. Beckstead, MD and S. B. Prusiner, MD

From the Departments of Pathology (Neuropathology Unit) (Dr. DeArmond, Ms. DeMott, and Dr. Beckstead), Neurology (Drs. DeArmond, Mobley, and Prusiner), Pediatrics (Dr. Mobley), and Biochemistry and Biophysics (Dr. Prusiner), University of California, San Francisco, CA; and Immunology Research(Dr. Barry), Veterans Administration Medical Center, Portland, OR.

Address correspondence and reprint requests to Dr. DeArmond, Department of Pathology, Box 0506, University of California, San Francisco, CA 94143.

Abstract.

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.

Footnotes

Supported by research grants from the John Douglas French Foundation for Alzheimer's Disease and the National Institutes of Health (NS22786, AG02132 and NS14069), as well as by gifts from R.J. Reynolds Industries, Inc., Sherman Fairchild Foundation, and Joseph and Stephanie Koret Foundation

Received December 29, 1986. Accepted for publication in final form May 15, 1987.






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