PrPSᶜ spreading patterns in the brain of sheep linked to different prion types

• Published in: Veterinary research (Paris) 2011-02, Vol.42 (1), p.32-32, Article 32
• Main Authors: Wemheuer, Wiebke M, Benestad, Sylvie L, Wrede, Arne, Wemheuer, Wilhelm E, Brenig, Bertram, Bratberg, Bjørn, Schulz-Schaeffer, Walter J
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western - methods; Blotting, Western - veterinary; bovine spongiform encephalopathy; Brain - pathology; brain stem; cerebellum; cortex; ganglia; Germany; Immunoassay - methods; Immunoassay - veterinary; immunohistochemistry; Immunohistochemistry - veterinary; Lymph Nodes - pathology; Norway; Palatine Tonsil - pathology; Paraffin Embedding - methods; Paraffin Embedding - veterinary; pathogens; prions; PrPSc Proteins - genetics; PrPSc Proteins - metabolism; scrapie; Scrapie - metabolism; Scrapie - pathology; Sensitivity and Specificity; Sheep; spinal cord; Spinal Cord - pathology; thalamus
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/1297-9716-42-32

Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (BSE) and Creutzfeldt-Jakob disease in humans. According to the prion hypothesis, the pathological isoform (PrPSᶜ) of the cellular prion protein (PrPᶜ) comprises the essential, if not exclusive, component of the transmissible agent. Currently, two types of scrapie disease are known - classical and atypical/Nor98 scrapie. In the present study we examine 24 cases of classical and 25 cases of atypical/Nor98 scrapie with the sensitive PET blot method and validate the results with conventional immunohistochemistry. The sequential detection of PrPSᶜ aggregates in the CNS of classical scrapie sheep implies that after neuroinvasion a spread from spinal cord and obex to the cerebellum, diencephalon and frontal cortex via the rostral brainstem takes place. We categorize the spread of PrPSᶜ into four stages: the CNS entry stage, the brainstem stage, the cruciate sulcus stage and finally the basal ganglia stage. Such a sequential development of PrPSᶜ was not detectable upon analysis of the present atypical/Nor98 scrapie cases. PrPSᶜ distribution in one case of atypical/Nor98 scrapie in a presumably early disease phase suggests that the spread of PrPSᶜ aggregates starts in the di- or telencephalon. In addition to the spontaneous generation of PrPSᶜ, an uptake of the infectious agent into the brain, that bypasses the brainstem and starts its accumulation in the thalamus, needs to be taken into consideration for atypical/Nor98 scrapie.