Cargando…

Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling

In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during brain pathology remains unknown. Here we study the nanoscale organization of pathological ECS in adult...

Descripción completa

Detalles Bibliográficos
Autores principales: Soria, Federico N., Paviolo, Chiara, Doudnikoff, Evelyne, Arotcarena, Marie-Laure, Lee, Antony, Danné, Noémie, Mandal, Amit Kumar, Gosset, Philippe, Dehay, Benjamin, Groc, Laurent, Cognet, Laurent, Bezard, Erwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351768/
https://www.ncbi.nlm.nih.gov/pubmed/32651387
http://dx.doi.org/10.1038/s41467-020-17328-9
_version_ 1783557510008930304
author Soria, Federico N.
Paviolo, Chiara
Doudnikoff, Evelyne
Arotcarena, Marie-Laure
Lee, Antony
Danné, Noémie
Mandal, Amit Kumar
Gosset, Philippe
Dehay, Benjamin
Groc, Laurent
Cognet, Laurent
Bezard, Erwan
author_facet Soria, Federico N.
Paviolo, Chiara
Doudnikoff, Evelyne
Arotcarena, Marie-Laure
Lee, Antony
Danné, Noémie
Mandal, Amit Kumar
Gosset, Philippe
Dehay, Benjamin
Groc, Laurent
Cognet, Laurent
Bezard, Erwan
author_sort Soria, Federico N.
collection PubMed
description In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during brain pathology remains unknown. Here we study the nanoscale organization of pathological ECS in adult mice under degenerative conditions. Using electron microscopy in cryofixed tissue and single nanotube tracking in live brain slices combined with super-resolution imaging analysis, we find enlarged ECS dimensions and increased nanoscale diffusion after α-synuclein-induced neurodegeneration. These animals display a degraded hyaluronan matrix in areas close to reactive microglia. Furthermore, experimental hyaluronan depletion in vivo reduces dopaminergic cell loss and α-synuclein load, induces microgliosis and increases ECS diffusivity, highlighting hyaluronan as diffusional barrier and local tissue organizer. These findings demonstrate the interplay of ECS, extracellular matrix and glia in pathology, unraveling ECS features relevant for the α-synuclein propagation hypothesis and suggesting matrix manipulation as a disease-modifying strategy.
format Online
Article
Text
id pubmed-7351768
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-73517682020-07-16 Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling Soria, Federico N. Paviolo, Chiara Doudnikoff, Evelyne Arotcarena, Marie-Laure Lee, Antony Danné, Noémie Mandal, Amit Kumar Gosset, Philippe Dehay, Benjamin Groc, Laurent Cognet, Laurent Bezard, Erwan Nat Commun Article In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during brain pathology remains unknown. Here we study the nanoscale organization of pathological ECS in adult mice under degenerative conditions. Using electron microscopy in cryofixed tissue and single nanotube tracking in live brain slices combined with super-resolution imaging analysis, we find enlarged ECS dimensions and increased nanoscale diffusion after α-synuclein-induced neurodegeneration. These animals display a degraded hyaluronan matrix in areas close to reactive microglia. Furthermore, experimental hyaluronan depletion in vivo reduces dopaminergic cell loss and α-synuclein load, induces microgliosis and increases ECS diffusivity, highlighting hyaluronan as diffusional barrier and local tissue organizer. These findings demonstrate the interplay of ECS, extracellular matrix and glia in pathology, unraveling ECS features relevant for the α-synuclein propagation hypothesis and suggesting matrix manipulation as a disease-modifying strategy. Nature Publishing Group UK 2020-07-10 /pmc/articles/PMC7351768/ /pubmed/32651387 http://dx.doi.org/10.1038/s41467-020-17328-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Soria, Federico N.
Paviolo, Chiara
Doudnikoff, Evelyne
Arotcarena, Marie-Laure
Lee, Antony
Danné, Noémie
Mandal, Amit Kumar
Gosset, Philippe
Dehay, Benjamin
Groc, Laurent
Cognet, Laurent
Bezard, Erwan
Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
title Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
title_full Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
title_fullStr Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
title_full_unstemmed Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
title_short Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
title_sort synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351768/
https://www.ncbi.nlm.nih.gov/pubmed/32651387
http://dx.doi.org/10.1038/s41467-020-17328-9
work_keys_str_mv AT soriafedericon synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT paviolochiara synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT doudnikoffevelyne synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT arotcarenamarielaure synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT leeantony synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT dannenoemie synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT mandalamitkumar synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT gossetphilippe synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT dehaybenjamin synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT groclaurent synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT cognetlaurent synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling
AT bezarderwan synucleinopathyaltersnanoscaleorganizationanddiffusioninthebrainextracellularspacethroughhyaluronanremodeling