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Elevated manganese levels in blood and central nervous system occur before onset of clinical signs in scrapie and bovine spongiform encephalopathy

S. Hesketh^*, J. Sassoon^*, R. Knight, J. Hopkins and D. R. Brown^*,1

^* Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK; and Department of Chemistry, University of Hull, Hull HU6 7RX, UK; and and Division of Veterinary Biomedical Sciences, University of Edinburgh, Edinburgh, EH9 1QH, UK

¹ Corresponding author: bssdrb{at}bath.ac.uk

Prion diseases, or transmissible spongiform encephalopathies, are neurodegenerative diseases that can only be accurately diagnosed by analysis of central nervous system tissue for the presence of an abnormal isoform of the prion protein known as PrP^Sc. Furthermore, these diseases have long incubation periods during which there are no clear symptoms but where the infectious agent could still be present in the tissues. Therefore, the development of diagnostic assays to detect a surrogate marker for the presence of prion disease is essential. Previous studies on mice experimentally infected with scrapie, an ovine spongiform encephalopathy, suggested that changes in the levels of Mn occur in the blood and brain before the onset of symptoms of the disease. To assess whether these findings have relevance to the animal diseases scrapie and bovine spongiform encephalopathy, tissues from bovine spongiform encephalopathy- and scrapie-infected cattle and sheep were analyzed for their metal content and compared with values for noninfected animals. In field cases and experimentally infected animals, elevated Mn was associated with prion infection. Although some central nervous system regions showed elevated Mn, other regions did not. The most consistent finding was an elevation of Mn in blood. This change was present in experimentally infected animals before the onset of symptoms. In scrapie-infected sheep, elevated Mn levels occurred regardless of the genotype of the sheep and were even detected in scrapie-resistant sheep in which no symptoms of disease were detected. These findings suggest that elevated blood Mn could be a potential diagnostic marker for prion infection even in the absence of apparent clinical disease.

Key Words: scrapie • prion • bovine spongiform encephalopathy • copper • metal

This article has been cited by other articles:

				M. W. Brazier, P. Davies, E. Player, F. Marken, J. H. Viles, and D. R. Brown Manganese Binding to the Prion Protein J. Biol. Chem., May 9, 2008; 283(19): 12831 - 12839. [Abstract] [Full Text] [PDF]