cam.issuedOnline	2021-11-24
dc.contributor.author	Macdonald, Jennifer A
dc.contributor.author	Chen, John L
dc.contributor.author	Masuda-Suzukake, Masami
dc.contributor.author	Schweighauser, Manuel
dc.contributor.author	Jaunmuktane, Zane
dc.contributor.author	Warner, Thomas
dc.contributor.author	Holton, Janice L
dc.contributor.author	Grossman, Annabelle
dc.contributor.author	Berks, Richard
dc.contributor.author	Lavenir, Isabelle
dc.contributor.author	Goedert, Michel
dc.date.accessioned	2021-11-24T16:21:47Z
dc.date.available	2021-11-24T16:21:47Z
dc.date.issued	2021-11-24
dc.date.submitted	2021-09-15
dc.date.updated	2021-11-24T16:21:46Z
dc.description.abstract	Peripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein.
dc.identifier.doi	10.17863/CAM.78474
dc.identifier.eissn	2051-5960
dc.identifier.issn	2051-5960
dc.identifier.other	s40478-021-01291-7
dc.identifier.other	1291
dc.identifier.uri	https://www.repository.cam.ac.uk/handle/1810/331029
dc.language	en
dc.publisher	Springer Science and Business Media LLC
dc.subject	Research
dc.subject	α-Synuclein
dc.subject	Multiple system atrophy
dc.subject	Seeded assembly
dc.subject	Neurodegeneration
dc.subject	Microglia
dc.title	Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds.
dc.type	Article
dcterms.dateAccepted	2021-11-08
prism.issueIdentifier	1
prism.publicationName	Acta Neuropathol Commun
prism.volume	9
pubs.funder-project-id	UK Medical Research Council (MC_U105184291)
rioxxterms.licenseref.uri	http://creativecommons.org/licenses/by/4.0/
rioxxterms.version	VoR
rioxxterms.versionofrecord	10.1186/s40478-021-01291-7

Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds.

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