Morphological changes of glia in prion and a prion-like disorder.

Several neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s are considered to be prion-like disorders in that they are all proteinopathies where in aberrant proteins spread throughout the brain during disease progression, and thus they may share molecular basis and mechanisms of propagation. Therefore, studies elucidating mechanisms of prion propagation may be relevant to other neurodegenerative diseases. While substantial progress has been made, the pathogen- esis of these neurodegenerative diseases is still largely unknown, and as consequence, to date no truly effective treatments that prevent onset or delay progression of these diseases have been identified. In addition to propagation of misfolded proteins, these diseases all induce a host response that includes activation of astrocytes and microglial cells. However, in our opinion, the glial response in each of these diseases has not been well-defined. Since a role for glial response in prion disease has been clearly demonstrated in a previous study concerning Scrapie in sheep, a similar approach to analysis of astrocytic gliosis has been taken here for Creutzfeldt-Jakob (CJD) and Alzheimer’s Diseases (AD). Here, morphological analysis of glial cells in cerebella from CJD and AD patients (as the most common prion and prion-like disorders, respectively) was performed. The results presented in this study support the involvement of glial cells not only in the pathogenesis of CJD, but also of AD. A relationship between intensity and morphology is observed in astroglia from the molecular layer in both pathologies. By contrast, the involvement of microgliosis in AD-affected samples showed a lower relevance from that observed in CJD, since reactive microglia were much more abundant in prion disease. Further analysis of the role of gliosis in CJD and AD, as well as other neurodegenerative diseases, may well advance knowledge of the mechanisms underlying these diseases and may also provide new targets for therapeutic intervention

Morphological changes of glia in prion and a prion-like disorder

Several neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s are considered to be prion-like disorders in that they are all proteinopathies where in aberrant proteins spread throughout the brain during disease progression, and thus they may share molecular basis and mechanisms of propagation. Therefore, studies elucidating mechanisms of prion propagation may be relevant to other neurodegenerative diseases. While substantial progress has been made, the pathogenesis of these neurodegenerative diseases is still largely unknown, and as consequence, to date no truly effective treatments that prevent onset or delay progression of these diseases have been identified. In addition to propagation of misfolded proteins, these diseases all induce a host response that includes activation of astrocytes and microglial cells. However, in our opinion, the glial response in each of these diseases has not been well-defined. Since a role for glial response in prion disease has been clearly demonstrated in a previous study concerning Scrapie in sheep, a similar approach to analysis of astrocytic gliosis has been taken here for Creutzfeldt-Jakob (CJD) and Alzheimer’s Diseases (AD). Here, morphological analysis of glial cells in cerebella from CJD and AD patients (as the most common prion and prion-like disorders, respectively) was performed. The results presented in this study support the involvement of glial cells not only in the pathogenesis of CJD, but also of AD. A relationship between intensity and morphology is observed in astroglia from the molecular layer in both pathologies. By contrast, the involvement of microgliosis in AD-affected samples showed a lower relevance from that observed in CJD, since reactive microglia were much more abundant in prion disease. Further analysis of the role of gliosis in CJD and AD, as well as other neurodegenerative diseases, may well advance knowledge of the mechanisms underlying these diseases and may also provide new targets for therapeutic intervention

First adequately-known quadrupedal sirenian from Eurasia (Eocene, Bay of Biscay, Huesca, northeastern Spain)

Sirenians are the only extant herbivorous mammals fully adapted to an aquatic lifestyle. They originated in Africa during the Paleocene from an undetermined clade of afrotherian mammals, and by the end of the Eocene they were widely distributed across the tropical latitudes. Here we introduce Sobrarbesiren cardieli gen. et sp. nov. It is the first adequately-known quadrupedal sirenian from Eurasia and the oldest record of this clade from western Europe. Fossils have been recovered from the middle Lutetian (SBZ15) site of Castejón de Sobrarbe-41 (Huesca, Spain), and comprise many cranial and postcranial remains, including pelvic girdle and hind limb bones, from at least six sirenian individuals of different ontogenetic stages. Sobrarbesiren shows a suite of characters previously considered synapomorphies of different clades of derived sirenians, such as the presence of the processus retroversus of the squamosal and the pterygoid fossa, combined with ancestral characters such as the presence of an alisphenoid canal, a permanent P5, at least two sacral vertebrae, a primitive pelvis and functional femora and fibulae. Sobrarbesiren is recovered as the sister taxon of Dugongidae and represents a transitional stage of adaptation to aquatic life between the amphibious quadrupedal prorastomids and the aquatic quadrupedal protosirenids

Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scarpie strains within Europe

Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrPd), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, ‘long’ or ‘short’ PrPd profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a ‘CH1641-like’ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the PRNP gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results

Evolución con la edad de los mecanismos de barrera intestinal

Se destetaron 106 gazapos de 20 camadas a los 26 d de edad con un peso de 429 ± 57 g y se sacrificó 1 animal por camada a los 26, 31, 38, 45 y 52 d de edad. La longitud de las vellosidades intestinales y la profundidad de las criptas en el yeyuno se redujeron entre los 26 y los 31 d en un 26 y 9% respectivamente. De los 31 a los 38 días se observó un aumento tanto de la longitud de las vellosidades como de las criptas. A partir de esta edad no se observaron cambios en las vellosidades, que mostraron valores similares a las determinadas en el destete, mientras que las criptas siguieron aumentando ligeramente (9%). El grado de similitud de la microbiota cecal entre animales de la misma edad (que varió entre un 89, 1 y un 95,3%) fue superior al grado de similitud entre animales de diferentes edades (que varió entre un 82,3% y un 92,5%). La variabilidad en la composición de la microbiota fue menor a los 45 y 52 d de edad (mostrando un grado de similitud del 92,5% entre ambas edades) en comparación con la observada entre las primeras edades (26, 31 y 38 d, que varió entre 82,3 y 86,7%). Los menores grados de similitud se observaron entre los animales lactantes y los animales de 31 y 38 d de edad

Use of Placental MSCs and their exosomes as theragnostic agents for cancer treatment and diagnostic.

pre-print39,1 K

Fish oil rich in eicosapentaenoic acid and docosahexaenoic acid in sow diets modifies oxylipins and immune indicators in colostrum and milk

Colostrum and milk are the first nutrient sources for newborn piglets. In addition, n-3 fatty acids (FAs) and their oxygenated derivatives (oxylipins) have the capacity to modulate immune components. The aim of the current study was to include a fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in sow diets to promote an increase of anti-inflammatory molecules in colostrum and milk to benefit piglets. Thirty-six sows were randomly assigned from insemination to the end of lactation to either a control diet with animal fat (15 g/kg in gestation and 30 g/kg in lactation) or an n-3 diet in which animal fat was totally (gestation) or half (lactation) replaced by an equivalent amount of solid fish oil. Performance of sows and piglets was monitored during the study. Colostrum and milk samples were obtained after the birth of the first piglet and at weaning, respectively. From all samples (n = 18 per treatment), FAs were quantified by gas chromatography and immunoglobulins and cytokines by ELISA. Three samples per treatment were randomly selected to analyse oxylipin composition by liquid chromatography-tandem mass spectrometry. In colostrum and in milk, the n-3 FA (P = 0.020 and P < 0.001), particularly EPA (P < 0.001 and P < 0.001) and DHA (P < 0.001 and P < 0.001), and also their oxygenated derivatives were increased in samples from sows fed n-3 diet. Fish oil had no effect on immunoglobulin concentrations, but reduced tumour necrosis factor α (TNFα) (P = 0.011) and a tendency to reduce interleukin 10 (IL10) (P = 0.059) were observed in milk. In conclusion, fish oil in sow diets increased n-3 FA, particularly EPA and DHA, and their oxygenated derivatives in colostrum and milk, reducing TNFα and IL10 in milk.info:eu-repo/semantics/publishedVersio

Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie

Prion diseases are diagnosed in the symptomatic stage, when the neuronal damage is spread throughout the central nervous system (CNS). The assessment of biological features that allow the detection of asymptomatic cases is needed, and, in this context, scrapie, where pre-symptomatic infected animals can be detected through rectal biopsy, becomes a good study model. Neurogranin (Ng) and neurofilament light chain (NfL) are proteins that reflect synaptic and axonal damage and have been studied as cerebrospinal fluid (CSF) biomarkers in different neurodegenerative disorders. In this study, we evaluated Ng and NfL both at the protein and transcript levels in the CNS of preclinical and clinical scrapie-affected sheep compared with healthy controls and assessed their levels in ovine CSF. The correlation between these proteins and the main neuropathological events in prion diseases, PrPSc deposition and spongiosis, was also assessed. The results show a decrease in Ng and NfL at the protein and gene expression levels as the disease progresses, and significant changes between the control and preclinical animals. On the contrary, the CSF levels of NfL increased throughout the progression of the disease. Negative correlations between neuropathological markers of prion disease and the concentration of the studied proteins were also found. Although further research is needed, these results suggest that Ng and NfL could act as biomarkers for neurodegeneration onset and intensity in preclinical cases of scrapie

Recruited macrophages that colonize the post-inflammatory peritoneal niche convert into functionally divergent resident cells

Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment