Skip to main content
Top
Published in: Acta Neuropathologica 5/2017

01-11-2017 | Original Paper

α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading

Authors: Frida Loria, Jessica Y. Vargas, Luc Bousset, Sylvie Syan, Audrey Salles, Ronald Melki, Chiara Zurzolo

Published in: Acta Neuropathologica | Issue 5/2017

Login to get access

Abstract

Recent evidence suggests that disease progression in Parkinson’s disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, α-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar α-syn, suggesting an active role for these cells in clearing α-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up α-syn fibrils from the slices. Altogether our data support a role for astrocytes in trapping and clearing α-syn pathological deposits in PD.
Appendix
Available only for authorised users
Literature
11.
go back to reference Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMed Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMed
12.
go back to reference Braak H, Sastre M, Del Tredici K (2007) Development of alpha-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 114:231–241. doi:10.1007/s00401-007-0244-3 CrossRefPubMed Braak H, Sastre M, Del Tredici K (2007) Development of alpha-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 114:231–241. doi:10.​1007/​s00401-007-0244-3 CrossRefPubMed
29.
go back to reference Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 14:504–506. doi:10.1038/nm1747 CrossRefPubMed Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 14:504–506. doi:10.​1038/​nm1747 CrossRefPubMed
32.
go back to reference Li JY, Englund E, Holton JL et al (2008) Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 14:501–503. doi:10.1038/nm1746 CrossRefPubMed Li JY, Englund E, Holton JL et al (2008) Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 14:501–503. doi:10.​1038/​nm1746 CrossRefPubMed
37.
go back to reference Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8:2804–2815PubMed Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8:2804–2815PubMed
38.
go back to reference Masliah E, Rockenstein E, Veinbergs I et al (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287:1265–1269CrossRefPubMed Masliah E, Rockenstein E, Veinbergs I et al (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287:1265–1269CrossRefPubMed
41.
42.
48.
go back to reference Ridet JL, Sarkis C, Serguera C, Zennou V, Charneau P, Mallet J (2003) Transplantation of human adult astrocytes: efficiency and safety requirements for an autologous gene therapy. J Neurosci Res 72:704–708. doi:10.1002/jnr.10617 CrossRefPubMed Ridet JL, Sarkis C, Serguera C, Zennou V, Charneau P, Mallet J (2003) Transplantation of human adult astrocytes: efficiency and safety requirements for an autologous gene therapy. J Neurosci Res 72:704–708. doi:10.​1002/​jnr.​10617 CrossRefPubMed
49.
go back to reference Sacino AN, Brooks MM, Chakrabarty P et al (2017) Proteolysis of alpha-synuclein fibrils in the lysosomal pathway limits induction of inclusion pathology. J Neurochem 140:662–678. doi:10.1111/jnc.13743 CrossRefPubMed Sacino AN, Brooks MM, Chakrabarty P et al (2017) Proteolysis of alpha-synuclein fibrils in the lysosomal pathway limits induction of inclusion pathology. J Neurochem 140:662–678. doi:10.​1111/​jnc.​13743 CrossRefPubMed
Metadata
Title
α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading
Authors
Frida Loria
Jessica Y. Vargas
Luc Bousset
Sylvie Syan
Audrey Salles
Ronald Melki
Chiara Zurzolo
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 5/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-017-1746-2

Other articles of this Issue 5/2017

Acta Neuropathologica 5/2017 Go to the issue