Astrocytosis and amyloid deposition in scrapie-infected hamsters

In scrapie infection, prion protein (PrP^Sc) is localized in areas where there is neurodegeneration and astrocytosis. It is thought that PrP^Sc is toxic to neurons and trophic for astrocytes. In our study, paraffin sections from scrapie infected (263K and 139H) and control hamsters were examined with histological and immunocytochemical staining. We found that PrP^Sc was present in the ependymal cells of both 263K- and 139H-infected hamsters. In 139H-infected hamsters, PrP^Sc was found in the cytoplasm of neurons in cerebral cortex and in hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. In contrast, neuronal cytoplasm and nuclei, were positive for PrP^Sc in most areas such as cortex, hippocampus, and thalamus in 263K-infected hamsters. Many aggregations of PrP^Sc could be seen in the cortex, hippocampus, substantia nigra and around the Pia mater, corpus callosum, fimbria, ventricles, and blood vessels in sections from 139H- and/or 263K-positive animals. Furthermore, PrP^Sc was also co-localized with glial fibrillary acidic protein (GFAP) in many reactive astrocytes (approximately 90%) in certain areas such as the hippocampus in 263K-infected hamsters, but not 139H-infected hamsters. The patterns of astrocytosis and PrP^Sc formation were different between 139H- and 263K-infected hamsters, which may be used for a diagnosis purpose. Our results suggest a hypothesis that multiple cell-types are capable of PrP^Sc production. Our results also confirm that reactive astrocytes can produce and/or accumulate PrP^Sc during some scrapie strain infections. The findings suggest a `snowball effect', that is: astrocytosis might play an important role in amyloidosis, while amyloidosis may induce further astrocytosis at least in 263K-infected hamsters.