Synucleinopathies encompass several neurodegenerative diseases, which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit of alpha-synuclein aggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson's disease and dementia with Lewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated with alpha-synuclein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark of multiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neurodegeneration.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 primates. After a 2-year in vivo phase, extensive histochemical and biochemical analyses were performed on the whole brain.We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendrocytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neuroinflammation and alpha-synuclein pathology were also observed. These results show that the alpha-synuclein species in multiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human primates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy and gliosis.The present data pave the way for using this experimental model for MSA research and therapeutic development.

Brain injections of glial cytoplasmic inclusions induce a multiple system atrophy-like pathology

Morari, Michele;
2022

Abstract

Synucleinopathies encompass several neurodegenerative diseases, which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit of alpha-synuclein aggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson's disease and dementia with Lewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated with alpha-synuclein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark of multiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neurodegeneration.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 primates. After a 2-year in vivo phase, extensive histochemical and biochemical analyses were performed on the whole brain.We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendrocytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neuroinflammation and alpha-synuclein pathology were also observed. These results show that the alpha-synuclein species in multiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human primates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy and gliosis.The present data pave the way for using this experimental model for MSA research and therapeutic development.
2022
Teil, Margaux; Dovero, Sandra; Bourdenx, Mathieu; Arotcarena, Marie-Laure; Camus, Sandrine; Porras, Gregory; Thiolat, Marie-Laure; Trigo-Damas, Ines; Perier, Celine; Estrada, Cristina; Garcia-Carrillo, Nuria; Morari, Michele; Meissner, Wassilios G; Herrero, María Trinidad; Vila, Miquel; Obeso, Jose A; Bezard, Erwan; Dehay, Benjamin
File in questo prodotto:
File Dimensione Formato  
GCI_paper-Brain-v4_MM.pdf

solo gestori archivio

Descrizione: articolo principale
Tipologia: Pre-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 425.14 kB
Formato Adobe PDF
425.14 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
awab374.pdf

accesso aperto

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 2.51 MB
Formato Adobe PDF
2.51 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2485539
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 12
social impact