Quali-quantitative evaluation of ileal peyer's patches innervation in scrapie-free or scrapie-affected sarda breed ovines

Although Peyer's patches (PPs) and the enteric nervous system (ENS) play a key role in early sheep scrapie pathogenesis, little is known on the kinetics of ENS plexuses colonization. This study was aimed at quali-quantitatively evaluating ileal PP innervation in 29 Sarda breed ovines (12 scrapie-free, 2 months-old lambs, 4 ARQ/ARQ, 4 ARR/ARQ and 4 ARR/ARR, respectively; 12 scrapie-free, 2-4 years-old sheep, 3 ARQ/ARQ, 7 ARR/ARQ and 2 ARR/ARR, respectively; 5 ARQ/ARQ scrapie-affected sheep)

Indagini istologiche, immunoistochimiche e immunobiochimiche in capre clinicamente sane provenienti da un focolaio di scrapie

Nel corso del 2003, nell’ambito del piano di sorveglianza passiva sulle Encefalopatie Spongiformi Trasmissibili (TSEs), per la prima volta in Sardegna, è stata diagnosticata istologicamente ed immunoistochimicamente la scrapie in una capra. Il soggetto proveniva da un gregge nel quale da 2 anni si manifestava una patologia polimorfa caratterizzata talvolta da sintomi neurologici e da una mortalità intorno al 20%. Sulla base della legge attualmente in vigore in Italia si è proceduto all’abbattimento di tutte le capre presenti in allevamento (n = 93). Durante l’abbattimento venivano prelevati da ciascun capo obex, linfonodi retrofaringei e tonsille. L’esame istologico dell’obex non evidenziava quadri lesivi di tipo spongiforme mentre l’esame immunoistochimico del tessuto nervoso e linfatico evidenziava la presenza di cinque soggetti nello stato pre-clinico della malattia

LTalpha and LTbeta gene expression in organs of sheep showing different lymphoproliferative changes induced by maedi-visna virus

In lung and mammary gland of sheep, Maedi-Visna virus (MVV) causes lymphoproliferative inflammation often with follicular structures (lymphofollicular inflammation). The aim of this work was to define whether Limphotoxin α and β (LTα, LTβ) play a role in the formation of these peculiar lesions in sheep experimentally infected with MVV

Additional polymorphisms of the <i>PRNP</i> gene significantly decrease the susceptibility to scrapie of ARQ/ARQ sheep

The aim of this work was to investigate the risk of scrapie of the ARQ/ARQ genotype carrying at least one point mutation at codons 112, 137, 141, 142, 154 and 176 in comparison with the ARQ/ARQ without any point mutations

Intraepithelial and Interstitial Deposition of Pathological Prion Protein in Kidneys of Scrapie-Affected Sheep

Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE). The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrPSc. We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrPSc from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla) and occasional interstitial (papilla) deposition of PrPSc in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrPSc. PrPSc was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrPSc in kidney varied from approximately 27% (subclinical) to 73.6% (clinical) in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrPSc. Here we demonstrate unexpectedly frequent deposition of high levels of PrPSc in ovine kidneys of various flocks. Renal deposition of PrPSc is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep

A Survey of <i>Taenia multiceps coenurosis</i> in Sardinian sheep

A survey was carried out to assess the occurrence of Coenurus cerebralis infection in Sardinian sheep. A prevalence of 0.35% was observed when 566 regularly slaughtered sheep were examined. However, in 120 sheep with suspected symptoms of coenurosis examined from November 2001 to October 2002, a total of 299 cerebral coenurosis lesions were observed with an incidence of 1% per year. Lesions were classified as migratory, cystic and secondary. Most migratory lesions were found in sheep aged 3–6 months. Cavitary lesions containing cysts in different developing stages were found with high incidence per year in sheep aged 7–12 months. Secondary lesions due to the development of Coenurus were most frequent in sheep aged 19–36 months. Most sheep were found infected in spring and in early summer, between March and June. Most lesions were located in the cortex. The mean number of protoscolices per cyst was 149 (range 10–370)

Glioblastoma with oligodendroglioma component in a ewe

Herein we describe a glioblastoma partially occupying the telencephalic portion of the left cerebral hemisphere of a Sardinian (syn. Sarda) breed ewe. Microscopically, the mass consisted of a pleomorphic spindle-shaped cell component organized as bundles and numerous small areas of round cells displaying an oligodendroglioma-like aspect. A high number of mitotic figures, large areas of necrosis surrounded by pseudopalisading glial cells, and multiple foci of dystrophic mineralization were also observed. The neoplasm was highly vascularized with glomerular vascular proliferation. Immunohistochemically, neoplastic cells proved to be strongly positive for nestin, vimentin, and olig-2, whereas they were invariably negative for synaptophysin. Few neoplastic cells and reactive astrocytes, mainly located at the edge of necrotic foci, proved to be positive for glial fibrillary acidic protein, whereas glomerular vascular proliferation was clearly positive for factor VIII and vascular endothelial growth factor. Gene sequencing analysis demonstrated homozygous p53 tumor suppressor gene (TP53) point mutations in the DNA-binding domain located in exon 8. The presence of round cells immunoreactive for olig-2 demonstrated that this tumor is a glioblastoma with oligodendroglioma component. Our pathologic, immunohistochemical, and molecular findings largely overlap those previously reported in humans and dogs

A lympho-follicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep.

In sheep scrapie, pathological prion protein (PrP(Sc)) deposition occurs in the lymphoreticular and central nervous systems. We investigated PrP(Sc) distribution in scrapie-affected sheep showing simultaneous evidence of chronic lymphofollicular, lymphoproliferative/non-lymphofollicular, and/or granulomatous inflammations in their mammary gland, lung, and ileum. To do this, PrP(Sc) detection was carried out via immunohistochemistry and Western Blotting techniques, as well as through inflammatory cell immunophenotyping. Expression studies of gene coding for biological factors modulating the host's inflammatory response were also carried out. We demonstrated that ectopic PrP(Sc) deposition occurs exclusively in the context of lymphofollicular inflammatory sites, inside newly formed and well-organized lymphoid follicles harboring follicular dendritic cells. On the contrary, no PrP(Sc) deposition was detected in granulomas, even when they were closely located to newly formed lymphoid follicles. A significantly more consistent expression of lymphotoxin α and β mRNA was detected in lymphofollicular inflammation compared to the other two types, with lymphotoxin α and β signaling new lymphoid follicles' formation and, likely, the occurrence of ectopic PrP(Sc) deposition inside them. Our findings suggest that, in sheep co-affected by scrapie and chronic inflammatory conditions, only newly formed lymphoid follicles provide a suitable micro-environment that supports the scrapie agent's replication in inflammatory sites, with an increased risk of prion shedding through body secretions/excretions