Laboratory mice infected with the agent of scrapie, a brain-wasting disease of sheep, has shown high levels of the scrapie agent in their heart several hundred days after being infected in the brain, indicating that heart infection might be a new aspect of this disease.

The study is published in the journal Science.

Scrapie belongs to a group of diseases called prion diseases, also known as transmissible spongiform encephalopathies, or TSEs, because of the sponge-like holes created in the brain. In addition to scrapie in sheep, prion diseases include Creutzfeldt-Jacob disease in humans, mad cow disease in cattle and chronic wasting disease in deer and elk. The cause of prion diseases, still under debate, may be abnormal aggregated forms of prion protein.

The research has provided cardiologists an animal model in which to study heart amyloidosis, a family of heart diseases that affect humans, says Bruce Chesebro, senior author of the paper. Amyloidoses involve waxy protein deposits that stiffen the heart, limit its pumping ability and typically lead to fatal heart stoppage.

" Although several types of protein are known to form heart amyloid, this is the first time prion protein amyloid has been found in heart muscle and also found to cause heart malfunction," says Bruce Chesebro, senior author of the paper.

Last year, Chesebro's research group from Hamilton, collaborated with Michael Oldstone, and other researchers at The Scripps Research Institute in La Jolla, and learned that scrapie-infected mice engineered without an "anchor" between the membrane of cells and the prion protein regularly lived for more than 600 days, ultimately dying of old age. Wild mice infected with scrapie typically die after about 150 days.

In this earlier research, signs of prion protein amyloid were most prominent near blood vessels in the mouse brain. In the newly reported study, researchers at Scripps found similar amyloid in heart muscle. They then secured the help of Kirk Knowlton, at the University of California - San Diego, who investigated the effect of prion protein amyloid on mouse heart function, discovering that it decreased the heart's ability to pump blood.

Unusually high levels of scrapie infectivity were also found in the blood of the same mice used in the heart study. In the future, this finding could help scientists develop a blood-based diagnostic test to identify brain-wasting diseases and possibly lead to a way to filter or chemically treat blood to remove any infectious prion disease agents, says Chesebro.

Source: National Institutes of Health, 2006


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