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Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes
Multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are α-synucleinopathies that exhibit widespread astrogliosis as a component of the neuroinflammatory response. Munc18, a protein critical to vesicle exocytosis, was previously found to strongly mark morphologically activated astrocyte...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555668/ https://www.ncbi.nlm.nih.gov/pubmed/32911644 http://dx.doi.org/10.3390/life10090183 |
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author | Di Marco Vieira, Bruno Radford, Rowan A. W. Hayashi, Junna Eaton, Emma D. Greenaway, Ben Jambas, Mark Petcu, Eugen B. Chung, Roger S. Pountney, Dean L. |
author_facet | Di Marco Vieira, Bruno Radford, Rowan A. W. Hayashi, Junna Eaton, Emma D. Greenaway, Ben Jambas, Mark Petcu, Eugen B. Chung, Roger S. Pountney, Dean L. |
author_sort | Di Marco Vieira, Bruno |
collection | PubMed |
description | Multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are α-synucleinopathies that exhibit widespread astrogliosis as a component of the neuroinflammatory response. Munc18, a protein critical to vesicle exocytosis, was previously found to strongly mark morphologically activated astrocytes in brain tissue of MSA patients. Immunofluorescence of MSA, DLB and normal brain tissue sections was combined with cell culture and co-culture experiments to investigate the relationship between extracellular α-synuclein and the transition to a secretory astrocyte phenotype. Increased Munc18-positive vesicles were resolved in activated astrocytes in MSA and DLB tissue compared to controls, and they were also significantly upregulated in the human 1321N1 astrocytoma cell line upon treatment with α-synuclein, with parallel increases in GFAP expression and IL-6 secretion. In co-culture experiments, rat primary astrocytes pretreated with α-synuclein inhibited the growth of neurites of co-cultured primary rat neurons and upregulated chondroitin sulphate proteoglycan. Taken together, these results indicate that the secretory machinery is significantly upregulated in the astrocyte response to extracellular α-synuclein and may participate in the release of neuroinhibitory and proinflammatory factors in α-synucleinopathies. |
format | Online Article Text |
id | pubmed-7555668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75556682020-10-19 Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes Di Marco Vieira, Bruno Radford, Rowan A. W. Hayashi, Junna Eaton, Emma D. Greenaway, Ben Jambas, Mark Petcu, Eugen B. Chung, Roger S. Pountney, Dean L. Life (Basel) Article Multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are α-synucleinopathies that exhibit widespread astrogliosis as a component of the neuroinflammatory response. Munc18, a protein critical to vesicle exocytosis, was previously found to strongly mark morphologically activated astrocytes in brain tissue of MSA patients. Immunofluorescence of MSA, DLB and normal brain tissue sections was combined with cell culture and co-culture experiments to investigate the relationship between extracellular α-synuclein and the transition to a secretory astrocyte phenotype. Increased Munc18-positive vesicles were resolved in activated astrocytes in MSA and DLB tissue compared to controls, and they were also significantly upregulated in the human 1321N1 astrocytoma cell line upon treatment with α-synuclein, with parallel increases in GFAP expression and IL-6 secretion. In co-culture experiments, rat primary astrocytes pretreated with α-synuclein inhibited the growth of neurites of co-cultured primary rat neurons and upregulated chondroitin sulphate proteoglycan. Taken together, these results indicate that the secretory machinery is significantly upregulated in the astrocyte response to extracellular α-synuclein and may participate in the release of neuroinhibitory and proinflammatory factors in α-synucleinopathies. MDPI 2020-09-08 /pmc/articles/PMC7555668/ /pubmed/32911644 http://dx.doi.org/10.3390/life10090183 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Di Marco Vieira, Bruno Radford, Rowan A. W. Hayashi, Junna Eaton, Emma D. Greenaway, Ben Jambas, Mark Petcu, Eugen B. Chung, Roger S. Pountney, Dean L. Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes |
title | Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes |
title_full | Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes |
title_fullStr | Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes |
title_full_unstemmed | Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes |
title_short | Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes |
title_sort | extracellular alpha-synuclein promotes a neuroinhibitory secretory phenotype in astrocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555668/ https://www.ncbi.nlm.nih.gov/pubmed/32911644 http://dx.doi.org/10.3390/life10090183 |
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