Extracellular alpha-synuclein promotes a neuroinhibitory secretory phenotype in astrocytes

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*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)
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Abstract

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.

Original languageEnglish
Article number183
Pages (from-to)1-14
Number of pages14
JournalLife
Volume10
Issue number9
DOIs
Publication statusPublished - 8 Sep 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Astrocytes
  • Astrogliosis
  • DLB
  • MSA
  • Munc18

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