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Enteroglial and neuronal involvement without apparent neuron loss in ileal enteric nervous system plexuses from scrapie-affected sheep

¹ Department of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
² Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy
³ Department of Veterinary Morphophysiology and Animal Productions, Faculty of Veterinary Medicine, University of Bologna, Ozzano Emilia (Bologna), Italy
⁴ Department of Veterinary Public Health and Animal Pathology, Division of Veterinary Pathology, Faculty of Veterinary Medicine, University of Bologna, Ozzano Emilia (Bologna), Italy
⁵ Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Viterbo, Italy
⁶ Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy
⁷ Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland

Correspondence
Giovanni Di Guardo
gdiguardo{at}unite.it

The enteric nervous system (ENS) probably plays a dominant role in sheep scrapie pathogenesis, but little is known about the cell types involved. We investigated the ileal myenteric and submucosal plexuses of four naturally and four orally experimentally scrapie-affected ARQ/ARQ Sarda sheep, as well as those of 12 healthy-control Sarda sheep carrying different PrP genotypes. All scrapie-affected animals, euthanized at clinical-disease end stage, showed PrPd deposition within enteric glial cells (EGCs) and calbindin-immunoreactive (CALB-IR) and neuronal nitric oxide synthase (nNOS)-IR neurons. Whole-mount investigations revealed no significant differences between the densities of total, CALB-IR and nNOS-IR neurons in scrapie-affected versus healthy sheep, irrespective of PrP genotype. Our results suggest that EGCs and CALB-IR and nNOS-IR neurons are probably involved in the pathogenesis of natural and oral experimental sheep scrapie. Furthermore, the infectious agent may be less pathogenic towards ENS neurons than it is towards central nervous system neurons.

A supplementary table showing tissue antigens and details of the monoclonal and polyclonal antibodies utilized in the study is available with the online version of this paper.