Pulmonary BCG administration induces protection against tuberculosis infection via lung macrophage activation.

Background: Prion diseases are characterized by the accumulation of the pathogenic PrP^Sc 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 PrP^Sc 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.

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrP^C), originating with the pathogenic form (PrP^Sc). Classical scrapie in small ruminants is the paradigm of prion diseases, as it was the first transmissible spongiform encephalopathy (TSE) described and is the most studied. It is necessary to understand the etiological properties, the relevance of the transmission pathways, the infectivity of the tissues, and how we can improve the detection of the prion protein to encourage detection of the disease. The aim of this review is to perform an overview of classical and atypical scrapie disease in sheep and goats, detailing those special issues of the disease, such as genetic factors, diagnostic procedures, and surveillance approaches carried out in the European Union with the objective of controlling the dissemination of scrapie disease.

Background: Neuroinflammation has recently been proposed to be a major component of neurodegenerative diseases. The aim of this study was to determine how the interaction between microglia and astroglia, which are the primary immune cell populations in the brain, and pathological prion protein (PrPsc) could influence the development and propagation of this neurodegenerative disease. Because a relevant role for glial response in prion disease has been clearly demonstrated in our previous studies using the natural animal model, a similar approach has been taken here using the natural human model. Methods: A morphological approach has been developed to analyze cerebellar samples from patients with Creutzfeldt-Jakob disease (CJD) in comparison with healthy control cases. Histopathological lesions were assessed, and PrPsc, glial fibrillary acidic protein (GFAP) and reactive microglia were immunolabelled by specific antibodies. Furthermore, co-location studies using confocal microscopy were performed to determine the possible relationships between both types of glial cells in all samples. Results: The results presented in this study support the involvement of both types of glial cells in CJD. Evidence of increased astrocyte and microglia reactivity can be observed in all CJD cases, and a close relationship between the types of glia is demonstrated by co-location studies. Conclusion: Proteinopathies such as Alzheimer, Parkinson, and Huntington diseases, where aberrant proteins spread throughout the brain during disease progression, may share a molecular basis and mechanisms of propagation. Therefore, studies elucidating the interaction between gliosis and prion propagation may be relevant to these other neurodegenerative diseases and may provide new targets for therapeutic intervention.

The enteric nervous system (ENS) is a fundamental component of the gastrointestinal system, composed of a vast network of neurons and glial cells. It operates autonomously but is interconnected with the central nervous system (CNS) through the vagus nerve. This communication, known as the gut–brain axis, influences the bidirectional communication between the brain and the gut. Background/Objectives: This study aimed to review neurological pathologies related to the ENS. Methods: To this end, a comprehensive literature search was conducted in the “PubMed” database. Articles available in “free format” were selected, applying the filters “Humans” and limiting the search to publications from the last ten years. Results: The ENS has been linked to various neurological diseases, from autism spectrum disorder to Parkinson’s disease including neurological infection with the varicella zoster virus (VZV), even sharing pathologies with the CNS. This finding suggests that the ENS could serve as an early diagnostic marker or therapeutic target for neurological diseases. Gastrointestinal symptoms often precede CNS symptoms, and the ENS’s accessibility aids in diagnosis and treatment. Parkinson’s patients may show intestinal lesions up to twenty years before CNS symptoms, underscoring the potential for early diagnosis. However, challenges include developing standardized diagnostic protocols and the uneven distribution of dopaminergic neurons in the ENS. Continued research is needed to explore the ENS’s potential in improving disease prognosis. Conclusions: The ENS is a promising area for early diagnosis and therapeutic development. Nevertheless, it is essential to continue research in this area, especially to gain a deeper understanding of its organization, function, and regenerative capacity.