Mapping PrPSc Propagation in Experimental and Natural Scrapie in Sheep with Different PrP Genotypes

2005 ◽  
Vol 42 (3) ◽  
pp. 258-274 ◽  
Author(s):  
C. Ersdal ◽  
M. J. Ulvund ◽  
A. Espenes ◽  
S. L. Benestad ◽  
P. Sarradin ◽  
...  

Twenty-one orally inoculated and seven naturally infected sheep with scrapie were examined for PrPSc in peripheral tissues and in the central nervous system (CNS), using immunohistochemistry. In the inoculated group, VRQ (valine at codon 136, arginine at codon 154 and glutamine at codon 171)/VRQ sheep generally had a greater accumulation of the pathologic form of prion protein (PrPSc) in peripheral tissues, as compared with VRQ/ARQ (alanine at codon 136, arginine at codon 154, and glutamine at codon 171) animals at corresponding time points after inoculation. PrPSc was not detected in the ileal Peyer's patch, the spleen, the superficial cervical lymph node, and peripheral nervous tissues of several inoculated VRQ/ARQ animals. All inoculated VRQ/VRQ sheep, but only one of eight inoculated VRQ/ARQ animals, were PrPSc-positive in the CNS. Thus, the propagation of PrPSc seemed slower and more limited in VRQ/ARQ animals. Tissue and cellular localization of PrPSc suggested that PrPSc was disseminated through three different routes. PrPSc-positive cells in lymph node sinuses and in lymphatics indicated spreading by lymph. The sequential appearance of PrPSc in the peripheral nervous system and the CNS, with satellite cells as early targets, suggested the periaxonal transportation of PrPSc through supportive cells. Focal areas of vascular amyloid-like PrPSc in the brain of five sheep, suggested the hematogenous dissemination of PrPSc. There was a poor correlation between the amount of PrPSc in the CNS and clinical signs. One subclinically affected sheep showed widespread PrPSc accumulation in the CNS, whereas three sheep had early clinical signs without detectable PrPSc in the CNS. A VV136 (homozygous for valine at codon 136) sheep inoculated with ARQ/ARR (alanine at codon 136, arginine at codon 154, and arginine at codon 171) tissue succumbed to disease, demonstrating successful heterologous transmission. Less susceptible sheep receiving VRQ/VRQ or ARQ/ARR material were PrPSc-negative by immunohistochemistry, enzyme-linked immunosorbent assay, and western blot.

2021 ◽  
Vol 22 (4) ◽  
pp. 1587
Author(s):  
Nuri Song ◽  
Da Yeon Jeong ◽  
Thai Hien Tu ◽  
Byong Seo Park ◽  
Hye Rim Yang ◽  
...  

Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus.


2001 ◽  
Vol 82 (10) ◽  
pp. 2319-2326 ◽  
Author(s):  
J. D. Foster ◽  
D. W. Parnham ◽  
N. Hunter ◽  
M. Bruce

This study has examined the distribution of PrPSc in sheep by immunocytochemistry of tissues recovered from terminally affected animals following their experimental infection by the oral route with BSE. Despite a wide range of incubation period lengths, affected sheep showed a similar distribution of high levels of PrPSc throughout the central nervous system. PrPSc was also found in the lymphoid system, including parts of the digestive tract, and some components of the peripheral nervous system. These abundant PrPSc deposits in sheep in regions outside the central nervous system are in direct contrast with cattle infected with BSE, which show barely detectable levels of PrPSc in peripheral tissues. A number of genetically susceptible, challenged animals appear to have survived.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy M. OʼShea ◽  
Alexander L. Wollenberg ◽  
Jae H. Kim ◽  
Yan Ao ◽  
Timothy J. Deming ◽  
...  

AbstractBiomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.


2018 ◽  
Vol 35 (11) ◽  
pp. 1100-1106
Author(s):  
Alexa Calero ◽  
Hazel Villanueva ◽  
Priyadarshani Giri ◽  
Arthur Tischler ◽  
James Powers ◽  
...  

Objective Prior to maturation of the human sympathetic nervous system, the neonatal adrenal medulla senses and responds to hypoxia. In addition to catecholamine release, the adrenal medulla synthesizes and stores opioid peptides, notably enkephalin (ENK). However, it is not known whether acute hypoxia evokes adrenal ENK production and release, as seen in the central nervous system (CNS). We hypothesize that acute hypoxia stimulates synthesis and release of ENK in chromaffin cells. Study Design Cultures of adrenergic mouse pheochromocytoma cells (MPC) 10/9/96CR were incubated in 10% oxygen (O2) at intervals of up to 60 minutes. ENK content and release were measured by Met-ENK enzyme-linked immunosorbent assay (ELISA). ENK messenger ribonucleic acid (mRNA) was analyzed by quantitative reverse-transcriptase polymerase chain reaction (PCR). Results Incubation of MPC 10/9 cells in 10% O2 evoked rapid release of epinephrine and of Met-ENK which increased approximately twofold in 15 minutes. Reduced [O2] also induced an overall increase (14%) in cellular ENK peptide content within 60 minutes. Acute hypoxia-stimulated release of Met-ENK was accompanied by increased mRNAENK expression in MPC 10/9s, a cell culture model of adrenergic chromaffin cells. Conclusion We speculate that the ability of reduced [O2] to evoke ENK release from chromaffin cells may influence blood pressure regulation and heart contractility, thereby providing an adaptive survival advantage during neonatal asphyxia.


2018 ◽  
Vol 119 (11) ◽  
pp. 1312-1323 ◽  
Author(s):  
Aline Haas de Mello ◽  
Marcela Fornari Uberti ◽  
Bianca Xavier de Farias ◽  
Nathalia Alberti Ribas de Souza ◽  
Gislaine Tezza Rezin

AbstractThe current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).


2011 ◽  
Vol 20 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Elisangela de Oliveira ◽  
Elisa Teruya Oshiro ◽  
Rebeca Vieira Pinto ◽  
Bruna Corrêa de Castro ◽  
Karla Borges Daniel ◽  
...  

Visceral leishmaniasis (VL) is a severe chronic disease caused by Leishmania (Leishmania) infantum chagasi. Better knowledge on the effects caused by this disease can help develop adequate clinical management and treatment. Parasitological and immunohistochemical studies were performed golden hamsters Mesocricetus auratus infected with bone marrow from individuals with VL in the State of Mato Grosso do Sul, central-west Brazil. The effects of parasitism in the spleen, liver, kidneys, lungs, heart and brain of the animals were examined. Eighteen hamsters were inoculated intraperitoneally, and six healthy animals were used as negative controls. The animals were kept in the animal house and checked for clinical signs. Specimens of each organ were examined for the presence of amastigotes. Immunohistochemical technique was performed in all brain specimens and organs negative on the direct examination of parasites. Direct examination of amastigotes was positive in the spleen and liver of all infected animals; 33.3% showed the parasite in the kidneys and lungs, and 16.7% in the heart. Parasitic forms were seen in 83.3% (15/18) of the brain examined. Immunohistochemistry confirmed the results of the direct examination, except in two specimens of lung tissue and in the brain specimens. Other studies are needed to further clarify the effect of the parasite in the central nervous system.


2017 ◽  
Vol 79 (6) ◽  
pp. 970-978 ◽  
Author(s):  
Kazunori KIMITSUKI ◽  
Kentaro YAMADA ◽  
Nozomi SHIWA ◽  
Satoshi INOUE ◽  
Akira NISHIZONO ◽  
...  

2014 ◽  
Vol 20 (30) ◽  
pp. 97-100
Author(s):  
Хетагурова ◽  
Yuliana Khetagurova ◽  
Ревазова ◽  
Asya Revazova ◽  
Бораева ◽  
...  

Despite of significant progress in the development of technologies of clinical monitoring and the fetus and newborn pathology study, perinatal asphyxia or, more accurately – cerebral ischemia (CI) remain serious condition, causing significant mortality and long-term morbidity. Chi-acquired syndrome characterized by clinical and laboratory signs of acute brain injury due to asphyxia (ie, hypoxia, acidosis). The paper reflects the main clinical signs and neurosonographic lesion of the Central nervous system (CNS) in neonatal newborn infants with different gestational age who underwent CI mild to moderate severity.


1970 ◽  
Vol 7 (5) ◽  
pp. 435-447 ◽  
Author(s):  
K. M. Charlton ◽  
K. R. Pierce ◽  
R. W. Storts ◽  
C. H. Bridges

Twenty-two goats were poisoned with daily oral doses of ground coyotillo fruits and were killed at various times after the first day of dosing. The morphologic features and distribution of lesions in the central nervous system were studied by light microscopy. An axonal dystrophy occurred in several of the goats given high daily doses. Swellings occurred along axons of Purkinje cells in the cerebellum and in the white matter of the spinal cord. There was a fairly close correlation between the occurrence of clinical signs suggestive of the neocerebellar syndrome and the occurrence and distribution of lesions in the cerebellum.


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