Increased ferric iron content and iron-induced oxidative stress in the brains of scrapie-infected mice

Scrapie is a transmissible neurodegenerative disease of sheep and goats. Th e neuropathological changes include vacuolation, astrocytosis, the developm ent of amyloid plaques in some instances, and neuronal loss. The mechanisms involved in neuronal cell death in scrapie are not known. Recently, we rep orted the presence of oxidative stress in the brains of scrapie-infected an imals and suggested that this is the main mechanism that induces neuronal c ell loss. It is known that oxidative stress induced by free radicals is ass ociated with iron accumulation; this association led to an examination of t he levels of iron (total iron, Fe2+ and Fe3+) in the brains of control and scrapie-infected mice by biochemical methods. In the scrapie-infected group , both the level of total iron and the Fe3+ level were significantly increa sed in cerebral cortex, striatum, and brainstem as compared to the values i n the control group. A shift in the ratio of Fe2+/Fe3+ was observed in the same regions of infected mice. Additionally, in this scrapie model, we conf irmed the presence of oxidative stress, as evidenced by the increase of fre e malondialdehyde. These results suggest that iron metabolism is changed an d that iron-induced oxidative stress partly contributes to neurodegeneratio n in scrapie infection. (C) 2000 Elsevier Science B.V. All rights reserved.