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

hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorSORIA, Federico
hal.structure.identifierLaboratoire Photonique, Numérique et Nanosciences [LP2N]
dc.contributor.authorPAVIOLO, Chiara
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorDOUDNIKOFF, Evelyne
dc.contributor.authorAROTCARENA, Marie-Laure
hal.structure.identifierLaboratoire Photonique, Numérique et Nanosciences [LP2N]
dc.contributor.authorLEE, Antony
hal.structure.identifierLaboratoire Photonique, Numérique et Nanosciences [LP2N]
dc.contributor.authorDANNÉ, Noémie
hal.structure.identifierLaboratoire Photonique, Numérique et Nanosciences [LP2N]
dc.contributor.authorMANDAL, Amit Kumar
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorGOSSET, Philippe
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorDEHAY, Benjamin
hal.structure.identifierInterdisciplinary Institute for Neuroscience / Institut interdisciplinaire de neurosciences [Bordeaux] [IINS]
dc.contributor.authorGROC, Laurent
hal.structure.identifierLaboratoire Photonique, Numérique et Nanosciences [LP2N]
dc.contributor.authorCOGNET, Laurent
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorBÉZARD, Erwan
dc.date.accessioned2023-05-12T10:40:44Z
dc.date.available2023-05-12T10:40:44Z
dc.date.issued2020-12
dc.identifier.issn2041-1723
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/181608
dc.description.abstractEnIn 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.
dc.language.isoen
dc.publisherNature Publishing Group
dc.title.enSynucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
dc.typeArticle de revue
dc.identifier.doi10.1038/s41467-020-17328-9
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalNature Communications
bordeaux.page3440
bordeaux.volume11
bordeaux.hal.laboratoriesLaboratoire Photonique, Numérique et Nanosciences (LP2N) - UMR 5298*
bordeaux.issue1
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierinserm-02904850
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//inserm-02904850v1
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