A new study has shed light on how Bovine Spongiform Encephalopathy develops in cattle and may help to improve early diagnosis systems, scientists behind the research say.
The study, led by Processor Martin Groschup of the Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institute in Germany, was designed to learn more about the little-understood early incubation period of BSE.
The transmissible disease is caused by the propagation of a misfolded form of protein known as a prion, rather than by a bacterium or virus. The average time from infection to signs of illness is about 60 months.
Previous research has reported that the autonomic nervous system becomes affected by the disease only after the central nervous system has been infected.
To learn more about the pathogenesis (the production and development) of BSE, the researchers orally infected 56 calves aged between four and six months with BSE from infected cattle.
A further 18 calves were inoculated orally with BSE-negative material from calf brainstem as controls.
The study also included samples collected from a calf that had died naturally of BSE. Tissue samples from the gut, the central nervous system and automatic nervous system were collected from animals every four months from 16 to 44 months after infection.
The scientists then examined the samples for the presence of prions by immunohistochemistry.
Samples were also used to infect experimental mice that are highly sensitive to a BSE infection.
In a study published online in the August issue of The American Journal of Pathology, and reported by Science Daily, the researchers said they found that the automatic nervous system can show signs of infection prior to the central nervous system.
"Our results clearly indicate that both pathways are involved in the early pathogenesis of BSE, but not necessarily simultaneously," Dr Groschup said.
A distinct accumulation of the pathological prion protein was observed in the gut in almost all samples.
BSE prions were found in the sympathetic automatic nervous system, located in the thoracic and lumbar spinal cord, starting at 16 months after infection; and in the parasympathetic automatic nervous system, located in the sacral region of the spinal cord and the medulla, from 20 months post infection.
There was little or no sign of infection in the central nervous system in these samples.
The sympathetic part of the automatic nervous system was more widely involved in the early pathogenesis than its parasympathetic counterpart.
More bovines showing clinical symptoms revealed signs of infection in the sympathetic nervous system structures at a higher degree than in the parasympathetic tissue samples. The earliest detection of BSE prions in the brainstem was at 24 months post infection.
However, infection detected in the spinal cord of one animal at 16 months post infection suggests the existence of an additional pathway to the brain.
"The clear involvement of the sympathetic nervous system illustrates that it plays an important role in the pathogenesis of BSE in cattle," notes Dr Groschup.
"Nevertheless, our results also support earlier research that postulated an early parasympathetic route for BSE."
The results, Dr Groschup says, indicate three possible neuronal routes for the ascension of BSE prions to the brain: sympathetic, parasympathetic, and spinal cord projections, in order of importance.
"Our study sheds light on the pathogenesis of BSE in cattle during the early incubation period, with implications for diagnostic strategies and food-safety measures."
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