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

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 atroph...

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Autores principales:	Jennifer A. Macdonald, John L. Chen, Masami Masuda-Suzukake, Manuel Schweighauser, Zane Jaunmuktane, Thomas Warner, Janice L. Holton, Annabelle Grossman, Richard Berks, Isabelle Lavenir, Michel Goedert
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	α-Synuclein Multiple system atrophy Seeded assembly Neurodegeneration Microglia Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/bb04ab8adf9d41ed8dc3cbb1e5c3ee4c
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spelling	oai:doaj.org-article:bb04ab8adf9d41ed8dc3cbb1e5c3ee4c2021-11-28T12:09:14ZAssembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds10.1186/s40478-021-01291-72051-5960https://doaj.org/article/bb04ab8adf9d41ed8dc3cbb1e5c3ee4c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40478-021-01291-7https://doaj.org/toc/2051-5960Abstract 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.Jennifer A. MacdonaldJohn L. ChenMasami Masuda-SuzukakeManuel SchweighauserZane JaunmuktaneThomas WarnerJanice L. HoltonAnnabelle GrossmanRichard BerksIsabelle LavenirMichel GoedertBMCarticleα-SynucleinMultiple system atrophySeeded assemblyNeurodegenerationMicrogliaNeurology. Diseases of the nervous systemRC346-429ENActa Neuropathologica Communications, Vol 9, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	α-Synuclein Multiple system atrophy Seeded assembly Neurodegeneration Microglia Neurology. Diseases of the nervous system RC346-429
spellingShingle	α-Synuclein Multiple system atrophy Seeded assembly Neurodegeneration Microglia Neurology. Diseases of the nervous system RC346-429 Jennifer A. Macdonald John L. Chen Masami Masuda-Suzukake Manuel Schweighauser Zane Jaunmuktane Thomas Warner Janice L. Holton Annabelle Grossman Richard Berks Isabelle Lavenir Michel Goedert Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
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.
format	article
author	Jennifer A. Macdonald John L. Chen Masami Masuda-Suzukake Manuel Schweighauser Zane Jaunmuktane Thomas Warner Janice L. Holton Annabelle Grossman Richard Berks Isabelle Lavenir Michel Goedert
author_facet	Jennifer A. Macdonald John L. Chen Masami Masuda-Suzukake Manuel Schweighauser Zane Jaunmuktane Thomas Warner Janice L. Holton Annabelle Grossman Richard Berks Isabelle Lavenir Michel Goedert
author_sort	Jennifer A. Macdonald
title	Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
title_short	Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
title_full	Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
title_fullStr	Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
title_full_unstemmed	Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
title_sort	assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous m83 mice following the peripheral administration of α-synuclein seeds
publisher	BMC
publishDate	2021
url	https://doaj.org/article/bb04ab8adf9d41ed8dc3cbb1e5c3ee4c
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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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