Astrocytosis and proliferating cell nuclear antigen expression in brains of scrapie-infected hamsters

Scrapie is a neurodegenerative disease in sheep and goats. Neuropathologica l examination shows astrocytosis. One issue is whether the astrocytosis see n in scrapie is a function of an increase in reactivity of individual cells , or whether there is actual replication of astrocytes. We used double-labe l immunohistochemistry for proliferating cell nuclear antigen (PCNA) and fo r glial fibrillary acidic protein (GFAP) to determine the mitotic state of cells and to confirm their identity as astrocytes. Brain sections from hams ters (strain LVG/LAK) infected with 139H or 263K scrapie isolates were exam ined. GFAP immunostaining was increased in astrocytes in most regions of th e brains of scrapie-infected hamsters. These qualitative observations were confirmed by computerized image analysis quantification. A proportion of th e hypertrophic astrocytes (0.5-10.8%, depending on specific location) were PCNA immunoreactive. The PCNA-immunopositive astrocytes were most frequentl y found in cerebral cortex, corpus callosum, subependymal areas, fimbria, c audate, thalamus, hypothalamus, hippocampus, and dentate gyrus. Our results suggest that the astrocytosis seen in scrapie-infected animals is, at leas t in part, owing to actual replication of astrocytes in these animals. We h ypothesize that the astrocytes may be an important locus for the disease pr ocess.