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After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE),
the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the
autonomic ...nervous system. However, the timeline of this progression has thus far remained widely
undetermined. Previous studies were focused on later time points after oral exposure of animals
that were already 4 to 6 months old when challenged. In contrast, in this present study, we have
orally inoculated 4 to 6 weeks old unweaned calves with high doses of BSE to identify any possible
BSE infectivity and/or PrPBSE in peripheral nervous tissues during the first eight months postinoculation
(mpi). For the detection of BSE infectivity, we used a bovine PrP transgenic mouse
bioassay, while PrPBSE depositions were analyzed by immunohistochemistry (IHC) and by protein
misfolding cyclic amplification (PMCA). We were able to show that as early as 8 mpi the thoracic
spinal cord as well as the parasympathetic nodal ganglion of these animals contained PrPBSE and
BSE infectivity. This shows that the centripetal prion spread starts early after challenge at least in this
age group, which represents an essential piece of information for the risk assessments for food, feed,
and pharmaceutical products produced from young calves.
