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Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection
Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion-affected brains is neuroinflammation, histopathologically characterized by reactive gliosis surrounding prion deposition. The cause and effect of these cel...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378504/ https://www.ncbi.nlm.nih.gov/pubmed/37508542 http://dx.doi.org/10.3390/cells12141878 |
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author | Kang, Sang-Gyun Kim, Chiye Aiken, Judd McKenzie, Debbie |
author_facet | Kang, Sang-Gyun Kim, Chiye Aiken, Judd McKenzie, Debbie |
author_sort | Kang, Sang-Gyun |
collection | PubMed |
description | Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion-affected brains is neuroinflammation, histopathologically characterized by reactive gliosis surrounding prion deposition. The cause and effect of these cellular responses are still unclear. Here we investigate the impact of innate immune responses on prion replication using in vitro cell culture models. Hamster-adapted transmissible mink encephalopathy prions, hyper (HY) and drowsy (DY) strains, were assayed for accumulation of pathogenic prion protein (PrP(Sc)) in primary glial cultures derived from 8-day-old hamster pups. The kinetics of PrP(Sc) accumulation largely depended on prion strain and brain regions from where glial cells originated. Glial cells derived from the cerebellum were susceptible to HY, but resistant to DY strain as determined by western blot analysis, immunocytochemistry, and animal bioassay. Glial cells from the cerebral cortex were, however, refractory to both strains. PrP(Sc) accumulation was affected by innate immune modulators. Priming glial cells with lipopolysaccharide decreased prion replication, whereas pre-treatment with dexamethasone, inhibiting innate immunity, increased susceptibility to DY infection. Our results suggest that neuroinflammation resulting from prion infection is a response to resolve and/or prevent prion propagation in the brain. It implies a therapeutic potential of innate immune modulation in the early stages of prion disease. |
format | Online Article Text |
id | pubmed-10378504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103785042023-07-29 Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection Kang, Sang-Gyun Kim, Chiye Aiken, Judd McKenzie, Debbie Cells Article Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion-affected brains is neuroinflammation, histopathologically characterized by reactive gliosis surrounding prion deposition. The cause and effect of these cellular responses are still unclear. Here we investigate the impact of innate immune responses on prion replication using in vitro cell culture models. Hamster-adapted transmissible mink encephalopathy prions, hyper (HY) and drowsy (DY) strains, were assayed for accumulation of pathogenic prion protein (PrP(Sc)) in primary glial cultures derived from 8-day-old hamster pups. The kinetics of PrP(Sc) accumulation largely depended on prion strain and brain regions from where glial cells originated. Glial cells derived from the cerebellum were susceptible to HY, but resistant to DY strain as determined by western blot analysis, immunocytochemistry, and animal bioassay. Glial cells from the cerebral cortex were, however, refractory to both strains. PrP(Sc) accumulation was affected by innate immune modulators. Priming glial cells with lipopolysaccharide decreased prion replication, whereas pre-treatment with dexamethasone, inhibiting innate immunity, increased susceptibility to DY infection. Our results suggest that neuroinflammation resulting from prion infection is a response to resolve and/or prevent prion propagation in the brain. It implies a therapeutic potential of innate immune modulation in the early stages of prion disease. MDPI 2023-07-18 /pmc/articles/PMC10378504/ /pubmed/37508542 http://dx.doi.org/10.3390/cells12141878 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kang, Sang-Gyun Kim, Chiye Aiken, Judd McKenzie, Debbie Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection |
title | Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection |
title_full | Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection |
title_fullStr | Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection |
title_full_unstemmed | Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection |
title_short | Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection |
title_sort | innate immune status of glia modulates prion propagation in early stage of infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378504/ https://www.ncbi.nlm.nih.gov/pubmed/37508542 http://dx.doi.org/10.3390/cells12141878 |
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