Browsing by Subject "Multiple system atrophy"

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    Brain injections of glial cytoplasmicinclusions induce a multiple systematrophy-like pathology
    (Oxford University Pres, 2022-03-14) Margaux, Teil; 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.; Vila, Miquel; Obeso, Jose A.; Bezard, Erwan; Dehay, Benjamin; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
    Synucleinopathies 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 development