Evaluation of neurodegeneration in scrapie-infected animals by selective methods that detect cellular degeneration

Scrapie is a fatal neurodegenerative disease of sheep and goats. The precis e details of neuronal and neurite degeneration in scrapie-infected animals remain unknown. Using specific silver staining methods, we compared the neu rodegeneration caused by treatment of rats with kainic acid (KA) or ibogain e (IBO) to the neuropathology observed in mice infected with the C602 strai n of scrapie. As reported previously, KA resulted in extensive silver label ing of neurons, especially in the cortex, putamen and hippocampus. IBO silv er labeling was observed only in small clusters of Purkinje neurons in the paravermal region of the cerebellum. However, in scrapie-infected mice, a f ew silver stained neurons (differing from the dark degenerating neurons obs erved following neurotoxic exposure) were found in layer II of cortex, cing ulate cortex, zona incerta, thalamus and hypothalamus. Some silver grains w ere observed in glial-like cells, especially those in the paraventricular r egion. Degenerating axons were positive for silver staining and were found in the cortex, cingulate cortex, corpus callosum, habenulae, septum, fornix , thalamus, caudate putamen and a few in fasciculus retroflexus and substan tia nigra. Our results suggest that the limbic system is one of the importa nt loci for the neurodegenerative effect of at least some scrapie strains. (C) 2001 Elsevier Science B.V. All rights reserved.