Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783594061062471680
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
work_keys_str_mv AT dimarcovieirabruno extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT radfordrowanaw extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT hayashijunna extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT eatonemmad extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT greenawayben extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT jambasmark extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT petcueugenb extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT chungrogers extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes
AT pountneydeanl extracellularalphasynucleinpromotesaneuroinhibitorysecretoryphenotypeinastrocytes