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Brain injections of glial cytoplasmicinclusions induce a multiple systematrophy-like pathology

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dc.contributor.authorMargaux, Teil
dc.contributor.authorDovero, Sandra
dc.contributor.authorBourdenx, Mathieu
dc.contributor.authorArotcarena, Marie-Laure
dc.contributor.authorCamus, Sandrine
dc.contributor.authorPorras, Gregory
dc.contributor.authorThiolat, Marie-Laure
dc.contributor.authorTrigo-Damas, Ines
dc.contributor.authorPerier, Celine
dc.contributor.authorEstrada, Cristina
dc.contributor.authorGarcia-Carrillo, Nuria
dc.contributor.authorMorari, Michele
dc.contributor.authorMeissner, Wassilios G.
dc.contributor.authorVila, Miquel
dc.contributor.authorObeso, Jose A.
dc.contributor.authorBezard, Erwan
dc.contributor.authorDehay, Benjamin
dc.contributor.authorHerrero Ezquerro, María Trinidad
dc.contributor.departmentAnatomía Humana y Psicobiología
dc.date.accessioned2024-02-10T18:01:16Z
dc.date.available2024-02-10T18:01:16Z
dc.date.issued2022-03-14
dc.description.abstractSynucleinopathies encompass several neurodegenerative diseases, which include Parkinson’s disease, dementiawith Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit ofa-synucleinaggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson’s disease and dementia withLewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated witha-synu-clein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark ofmultiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neu-rodegeneration.To evaluate the possible pathogenic role of glial cytoplasmic inclusions, we inoculated glial cytoplasmic inclusion-containing brain fractions obtained from multiple system atrophy patients into the striatum of non-human pri-mates. After a 2-yearin vivophase, extensive histochemical and biochemical analyses were performed on thewhole brain.We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendro-cytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neu-roinflammation anda-synuclein pathology were also observed. These results show that thea-synuclein species inmultiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human pri-mates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy andgliosis.The present data pave the way for using this experimental model for MSA research and therapeutic developmentes
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dc.format.extent16es
dc.identifier.citationBrain n 145, año 2022
dc.identifier.doihttps://doi.org/10.1093/brain/awab374
dc.identifier.issn1460-2156
dc.identifier.issn0006-8950
dc.identifier.urihttp://hdl.handle.net/10201/139202
dc.languageenges
dc.publisherOxford University Preses
dc.relationThis work was supported by a grant from the Michael J. FoxFoundation(ProjectGrantNo.2013–8499),FundaciondeInvestigacion HM Hospitales (Madrid, Spain), the Fundacio ́nS eneca (Project Grant No: FS19540/PI/14), the TARGET PD ANRgrant and The Simone and Cino Del Duca Prize from FrenchAcademy of Sciences. M.T., M.B. and M.L.A. were supported by aMiniste` re de l’Enseignement Sup erieur et de la Recherche fellow-ship (France). M.B. and M.L.A. were also supported by the FranceParkinson Foundation (France). This study received financial sup-port from the French government in the framework of theUniversity of Bordeaux’s IdEx “Investments for the Future” pro-gram/GPR BRAIN_2030. The sequentiala-synuclein extraction wasperformed in the Biochemistry and Biophysics Platform of theBordeaux Neurocampus at the Bordeaux University funded by theLABEX BRAIN (ANR-10-LABX-43) with the help of Y. Rufin.es
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAlpha-synucleines
dc.subjectMultiple system atrophyes
dc.subjectNon-human primateses
dc.subjectNeurodegenerationes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicinaes
dc.titleBrain injections of glial cytoplasmicinclusions induce a multiple systematrophy-like pathologyes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication9bbe7af5-429b-4029-b621-0399a6838322
relation.isAuthorOfPublication.latestForDiscovery9bbe7af5-429b-4029-b621-0399a6838322
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