Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Recently, pathological prion protein PrP Sc , the putative key constituent of infectious agents causing transmissible spongiform encephalopathies (TSEs), was found in muscles of rodents experimentally infected with scrapie and in patients with Creutzfeldt-Jakob disease (CJD).For the assessment of risk scenarios originating from these findings (e.g., alimentary transmission of pathogens associated with bovine spongiform encephalopathy [BSE] and chronic wasting disease [CWD] via tainted beef and game or iatrogenic dissemination of CJD agent through contaminated surgical instruments) more detailed information about the time course of PrP Sc accumulation in muscles at preclinical and clinical stages of incubation is needed.Here we show that PrP Sc in muscles of hamsters fed with scrapie can be detected prior to the onset of clinical symptoms, but that the bulk of PrP Sc was deposited late in clinical disease.Additionally, regarding the question of how muscles become invaded, we report on the intramuscular location of PrP Sc and substantial indications for centrifugal spread of infection from spinal motor neurons to myofibers.Our findings in a well-established animal model for TSEs contribute to a better assessment of the risks for public health emanating from "Prions in skeletal muscle" and provide new insights into the pathophysiological spread of TSE agents through the body.Nonstandard abbreviations used: bovine spongiform encephalopathy (BSE); chronic wasting disease (CWD); Creutzfeldt-Jakob disease (CJD); immunohistochemistry (IHC); intracerebral lethal doses (LD50ic); musculus (M.); paraffinembedded tissue blot (PET blot); prion protein (PrP); transmissible spongiform encephalopathies (TSEs); variant Creutzfeldt-Jakob disease (vCJD).