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...
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MDPI AG
2020-09-01
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| Online Access: | https://www.mdpi.com/2075-1729/10/9/183 |
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| author | Bruno Di Marco Vieira Rowan A. W. Radford Junna Hayashi Emma D. Eaton Ben Greenaway Mark Jambas Eugen B. Petcu Roger S. Chung Dean L. Pountney |
| author_facet | Bruno Di Marco Vieira Rowan A. W. Radford Junna Hayashi Emma D. Eaton Ben Greenaway Mark Jambas Eugen B. Petcu Roger S. Chung Dean L. Pountney |
| author_sort | Bruno Di Marco Vieira |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T16:30:07Z |
| format | Article |
| id | doaj.art-e0b3f8362bed43c2afc12b9eed488836 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T16:30:07Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-e0b3f8362bed43c2afc12b9eed4888362023-11-20T12:55:48ZengMDPI AGLife2075-17292020-09-0110918310.3390/life10090183Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in AstrocytesBruno Di Marco Vieira0Rowan A. W. Radford1Junna Hayashi2Emma D. Eaton3Ben Greenaway4Mark Jambas5Eugen B. Petcu6Roger S. Chung7Dean L. Pountney8School of Medical Science, Griffith University, Gold Coast 4222, AustraliaDepartment of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Sydney 2109, AustraliaSchool of Medical Science, Griffith University, Gold Coast 4222, AustraliaMenzies Research Institute Tasmania, University of Tasmania, Hobart 7000, AustraliaSchool of Medical Science, Griffith University, Gold Coast 4222, AustraliaSchool of Medical Science, Griffith University, Gold Coast 4222, AustraliaSchool of Medicine, Griffith University, Gold Coast 4222, AustraliaDepartment of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Sydney 2109, AustraliaSchool of Medical Science, Griffith University, Gold Coast 4222, AustraliaMultiple 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.https://www.mdpi.com/2075-1729/10/9/183astrocytesastrogliosisMSADLBMunc18 |
| spellingShingle | Bruno Di Marco Vieira Rowan A. W. Radford Junna Hayashi Emma D. Eaton Ben Greenaway Mark Jambas Eugen B. Petcu Roger S. Chung Dean L. Pountney Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes Life astrocytes astrogliosis MSA DLB Munc18 |
| 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 | astrocytes astrogliosis MSA DLB Munc18 |
| url | https://www.mdpi.com/2075-1729/10/9/183 |
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