Background: Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. Results: In the clinical stage of the disease, we detected 105 genes that were differentially expressed (≥2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. Conclusions: The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.
Experimental transmission of the bovine spongiform encephalopathy (BSE) agent has been successfully reported in pigs inoculated via three simultaneous distinct routes (intracerebral, intraperitoneal and intravenous). Sheep derived BSE (Sh-BSE) is transmitted more efficiently than the original cattle-BSE isolate in a transgenic mouse model expressing porcine prion protein. However, the neuropathology and distribution of Sh-BSE in pigs as natural hosts, and susceptibility to this agent, is unknown. In the present study, seven pigs were intracerebrally inoculated with Sh-BSE prions. One pig was euthanized for analysis in the preclinical disease stage. The remaining six pigs developed neurological signs and histopathology revealed severe spongiform changes accompanied by astrogliosis and microgliosis throughout the central nervous system. Intracellular and neuropil-associated pathological prion protein (PrPSc) deposition was consistently observed in different brain sections and corroborated by Western blot. PrPSc was detected by immunohistochemistry and enzyme immunoassay in the following tissues in at least one animal: lymphoid tissues, peripheral nerves, gastrointestinal tract, skeletal muscle, adrenal gland and pancreas. PrPSc deposition was revealed by immunohistochemistry alone in the retina, optic nerve and kidney. These results demonstrate the efficient transmission of Sh-BSE in pigs and show for the first time that in this species propagation of bovine PrPSc in a wide range of peripheral tissues is possible. These results provide important insight into the distribution and detection of prions in non-ruminant animals.
Lower airway diseases are a major health concern in sheep, often presenting with overlapping clinical signs that hinder accurate diagnosis. This study evaluated the diagnostic value of computed tomography (CT) in 58 adult sheep examined in northeastern Spain between 2017 and 2024. All animals underwent full clinical examination, CT under general anaesthesia, and post-mortem investigation. CT identified 82 pulmonary lesions, including interstitial pneumonia, respiratory complex, gangrenous pneumonia, caseous lymphadenitis, parasitic pneumonia, pulmonary adenocarcinoma, and pulmonary hydatidosis. Tissue density measurements provided additional information regarding disease stage and severity. The level of agreement between CT findings and definitive diagnoses consistently exceeded that of clinical evaluation, reaching almost perfect concordance for several conditions. Moreover, CT revealed concomitant respiratory pathologies within the same animal, many of which were not detected by conventional diagnostic methods. Although thorough individual clinical examination remains essential for the correct interpretation of imaging findings and the accurate diagnosis of respiratory disorders in the field, these results demonstrate that CT provides superior diagnostic accuracy compared with standard approaches and yields valuable insights for both clinical practice and research. Despite its practical limitations, CT could represent a major advance in improving health, welfare, and productivity in sheep farming.
Enzootic nasal adenocarcinoma is a contagious neoplasm of goats for which early antemortem diagnosis remains challenging under field conditions. This study evaluated the diagnostic accuracy of infrared nasal thermography for detecting the disease using histopathology as the reference standard. Eighty-six goats from a dairy herd with confirmed enzootic nasal adenocarcinoma were examined by infrared thermography one day prior to slaughter under standardized environmental conditions. Thermal images of the ethmoidal region were qualitatively assessed for asymmetry or focal hyperthermia. Following slaughter, all heads underwent systematic necropsy and bilateral histopathological examination. Twenty-three goats (26.7%) were histologically confirmed as positive with confirmation by RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) from tissue samples. Infrared thermography showed a sensitivity of 82.6% and a specificity of 90.5%, with an overall diagnostic accuracy of 88.4%. Positive and negative predictive values were 76.0% and 93.4%, respectively. Agreement between thermography and histopathology was substantial (Cohen’s κ = 0.711; p < 0.001). Although thermography did not achieve the specificity of macroscopic post-mortem examination, its non-invasive and rapid nature supports its potential as a preliminary complementary antemortem screening approach, although its applicability at herd level requires validation in broader and more representative populations.