Show simple item record Masuda-Suzukake, Masami Nonaka, Takashi Hosokawa, Masato Kubo, Maki Shimozawa, Aki Akiyama, Haruhiko Hasegawa, Masato 2015-10-08T21:20:10Z 2015-10-08T21:20:10Z 2014-08-06
dc.identifier.citation Acta Neuropathologica Communications. 2014 Aug 06;2(1):88
dc.description.abstract Abstract Background α-Synuclein is the major component of filamentous inclusions that constitute the defining characteristic of Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy, so-called α-synucleinopathies. Recent studies revealed that intracerebral injection of recombinant α-synuclein fibrils into wild-type mouse brains induced prion-like propagation of hyperphosphorylated α-synuclein pathology. However, the propagation mechanisms of α-synuclein have not been fully elucidated. Results In this study, in order to establish where and how α-synuclein pathology propagates, we injected recombinant mouse α-synuclein fibrils into three different brain areas (substantia nigra, striatum, and entorhinal cortex) of wild-type mice and compared the resulting distributions of α-synuclein pathology at 1 month after injection. Distinct patterns of pathology were observed in mice injected at the different sites. Within one month after injection, the pathology had spread to neurons in areas far from the injection sites, especially areas with direct neural connections to the injection sites. Surprisingly, phosphorylated tau and TDP-43 pathologies were also observed in mice injected with α-synuclein fibrils into striatum and entorhinal cortex at one month after injection. Phosphorylated tau and TDP-43 were accumulated in dot-like inclusions, but these were rarely colocalized with α-synuclein pathology. It seems that accumulation of α-synuclein has a synergistic effect on tau and TDP-43 aggregation. Additionally, intracerebral injection with sarkosyl-insoluble fraction prepared from wild-type mice injected synthetic α-synuclein fibrils can also induce phosphorylated α-synuclein pathology in wild-type mice. Conclusions Our data indicate that α-synuclein aggregation spread by prion-like mechanisms through neural networks in mouse brains.
dc.rights info:eu-repo/semantics/openAccess
dc.title Pathological alpha-synuclein propagates through neural networks
dc.type Journal Article
dc.type info:eu-repo/semantics/article
dc.language.rfc3066 en
dc.description.version Peer Reviewed
dc.rights.holder Masami Masuda-Suzukake et al.; licensee BioMed Central Ltd. 2015-09-14T13:39:30Z

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