Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment

Guijarro, Isabel M; Garcés, Moisès; Andrés‐Benito, Pol; Marín, Belén; Otero, Alicia; Barrio, Tomás; Carmona, Margarita; Ferrer, Isidró; Badiola, Juan José; Monzón, Marta

doi:10.3390/biom11020204

Cited by 4 publications

(3 citation statements)

References 99 publications

(57 reference statements)

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“…In addition, this enzyme has important functions in the adult brain beyond its role in DNA demethylation, being necessary for a functional axon-myelinic interface and a successful myelin repair [ 65 ] and also critical in the regulation of the neuroinflammation process, associating a downregulation of Tet1 with aberrant activation of inflammatory response pathways [ 66 ]. Interestingly, neuroinflammation is increased during the course of scrapie disease [ 67 , 68 , 69 , 70 ]. In addition, Tet1 knock-out mice show a deficiency in adult neurogenesis, spatial learning, and memory [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues

Hernaiz

Sentre

Betancor

et al. 2023

IJMS

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Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathies or prion diseases, which are caused by an infectious isoform of the innocuous cellular prion protein (PrPC) known as PrPSc. DNA methylation, one of the most studied epigenetic mechanisms, is essential for the proper functioning of the central nervous system. Recent findings point to possible involvement of DNA methylation in the pathogenesis of prion diseases, but there is still a lack of knowledge about the behavior of this epigenetic mechanism in such neurodegenerative disorders. Here, we evaluated by immunohistochemistry the 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in sheep and mouse brain tissues infected with scrapie. Expression analysis of different gene coding for epigenetic regulatory enzymes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, TET1, and TET2) was also carried out. A decrease in 5mC levels was observed in scrapie-affected sheep and mice compared to healthy animals, whereas 5hmC displayed opposite patterns between the two models, demonstrating a decrease in 5hmC in scrapie-infected sheep and an increase in preclinical mice. 5mC correlated with prion-related lesions in mice and sheep, but 5hmC was associated with prion lesions only in sheep. Differences in the expression changes of epigenetic regulatory genes were found between both disease models, being differentially expressed Dnmt3b, Hdac1, and Tet1 in mice and HDAC2 in sheep. Our results support the evidence that DNA methylation in both forms, 5mC and 5hmC, and its associated epigenetic enzymes, take part in the neurodegenerative course of prion diseases.

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Section: Discussionmentioning

confidence: 99%

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues

Hernaiz

Sentre

Betancor

et al. 2023

IJMS

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“…According to the study, Troglitazone (CTD 00002415) weakened prion protein. 81 Based on recent research, curcumin (CTD 00000663) have effects on a variety of neurological disorders including anxiety, depression, Alzheimer’s, Parkinson’s, multiple sclerosis, Huntington’s, and Prions disease. Recent improvements in curcumin (CTD 00000663) formulation’s medicinal effectiveness and the unique delivery techniques used to get over its low bioavailability and toxicity.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder

Mredul

Khan

Rana

et al. 2022

Bioinform Biol Insights

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Prion disorder (PD) is caused by misfolding and the formation of clumps of proteins in the brain, notably Prion proteins resulting in a steady decrease in brain function. Early detection of PD is difficult due to its unpredictable nature, and diagnosis is limited regarding specificity and sensitivity. Considering the uncertainties, the current study used network-based integrative system biology approaches to reveal promising molecular biomarkers and therapeutic targets for PD. In this study, brain transcriptomics gene expression microarray datasets (GSE160208 and GSE124571) of human PD were evaluated and 35 differentially expressed genes (DEGs) were identified. By employing network-based protein–protein interaction (PPI) analysis on these DEGs, 10 central hub proteins, including SPP1, FKBP5, HPRT1, CDKN1A, BAG3, HSPB1, SYK, TNFRSF1A, PTPN6, and CD44, were identified. Employing bioinformatics approaches, a variety of transcription factors (EGR1, SSRP1, POLR2A, TARDP, and NR2F1) and miRNAs (hsa-mir-8485, hsa-mir-148b-3p, hsa-mir-4295, hsa-mir-26b-5p, and hsa-mir-16-5p) were predicted. EGR1 was found as the most imperative transcription factor (TF), and hsa-mir-16-5p and hsa-mir-148b-3p were found as the most crucial miRNAs targeted in PD. Finally, resveratrol and hypochlorous acid were predicted as possible therapeutic drugs for PD. This study could be helpful in better understanding of molecular systems and prospective pharmacological targets for developing effective PD treatments.

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“…Importantly, scaling this assay up from small animals to sheep, researchers were able to demonstrate the ability of the assay to also detect prion protein in CSF in a large animal, which has translated to the development of non-invasive diagnostic screening in humans ( 77 – 79 ). Sheep with naturally occurring scrapie are also being utilized to elucidate the relationship between prion proteins, neuroinflammation, and neurodegeneration, and to trial anti-inflammatory drugs such as glucocorticoids as potential treatments ( 80 – 82 ).…”

Section: Naturally Occurring Sheep Disease Modelsmentioning

confidence: 99%

The Translational Benefits of Sheep as Large Animal Models of Human Neurological Disorders

Murray

Mitchell

2022

Front. Vet. Sci.

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The past two decades have seen a considerable rise in the use of sheep to model human neurological disorders. While each animal model has its merits, sheep have many advantages over small animal models when it comes to studies on the brain. In particular, sheep have brains more comparable in size and structure to the human brain. They also have much longer life spans and are docile animals, making them useful for a wide range of in vivo studies. Sheep are amenable to regular blood and cerebrospinal fluid sampling which aids in biomarker discovery and monitoring of treatment efficacy. Several neurological diseases have been found to occur naturally in sheep, however sheep can also be genetically engineered or experimentally manipulated to recapitulate disease or injury. Many of these types of sheep models are currently being used for pre-clinical therapeutic trials, particularly gene therapy, with studies from several models culminating in potential treatments moving into clinical trials. This review will provide an overview of the benefits of using sheep to model neurological conditions, and highlight naturally occurring and experimentally induced sheep models that have demonstrated translational validity.

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Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment

Cited by 4 publications

References 99 publications

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues

Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder

The Translational Benefits of Sheep as Large Animal Models of Human Neurological Disorders

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