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From: TSS ()
Subject: Manganese levels increase in scrapie-infected sheep before clinical symptoms develop
Date: July 2, 2007 at 10:22 am PST

Manganese levels increase in scrapie-infected sheep before clinical symptoms develop

Sheep infected with scrapie and cows infected with BSE have elevated levels of manganese in their blood before clinical symptoms appear, according to new research.

The findings, published in the Journal of Animal Science, also show that scrapie-resistant sheep produce elevated levels of the metal when “challenged” with the disease.

This suggests that elevated manganese levels in the blood and central nervous system are caused by the animal’s initial response to the disease.

The findings raise the possibility of using manganese levels in the blood as a potential diagnostic marker for prion infection. At present, only post-mortem examination of the brain tissue gives a certain diagnosis.

Scrapie, Bovine Spongiform Encephalopathy (BSE) and Creutzfeldt-Jakob Disease (CJD) are neurodegenerative diseases that affect the brain and nervous system of sheep, cows and humans respectively.

They are transmitted by mis-formed prion proteins which cause tiny loss of brain cell in different regions of the brain, leading to impairment of brain function, including memory changes, personality changes and problems with movement that worsen over time.

“Definite diagnosis of prion disease is currently only possible post-mortem," said Professor David Brown from the University of Bath who led the study with colleagues from the universities of Hull and Edinburgh.

“These findings suggest that elevated blood manganese could be used as a robust diagnostic marker for prion infection, even before the onset of apparent clinical disease.

“In practice, however, it would be difficult implement a widespread screening programme, given that the mass spectrometry we use to measure levels is expensive and labour intensive.”

The research builds on the 2002 discovery that mice infected with scrapie have higher levels of manganese. This is the first time that tissue from farm animals infected with prion diseases have been studied in this way.

One of the most interesting findings from this study came from the analysis of blood samples from scrapie-resistant sheep.

When challenged with the disease, these sheep showed similar levels of manganese as non-resistant sheep challenged in the same way.

“Elevated levels of manganese in scrapie-resistant sheep imply that the change in blood manganese is a result of the scrapie challenge and not a consequence of scrapie pathology,” said Professor Brown, from the University of Bath’s Department of Biology & Biochemistry.

“Although these sheep are considered to be resistant to scrapie, they do show some indications that scrapie challenge results in similar metabolic changes as occur in non-resistant sheep.”

Another interesting finding was that although levels of manganese were elevated, there were differences in the blood levels of selenium and molybdenum in experimental and field cases of BSE in cows.

This suggests that the way a cow acquires the disease affects the metabolic processes involved.

“The origin of the increased manganese in the brains and blood of infected animals remains unknown,” said Professor Brown.

“The three possibilities are that there is decreased secretion of manganese from the body, release of manganese from other tissues or increased absorption of manganese from the environment.

“Currently there is insufficient evidence to favour any of these three theories.” -University of Bath

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:

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 PrPSc. 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.


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