Pathological alpha-synuclein propagates through neural networks
Identifieur interne : 000794 ( Main/Exploration ); précédent : 000793; suivant : 000795Pathological alpha-synuclein propagates through neural networks
Auteurs : Masami Masuda-Suzukake [Japon] ; Takashi Nonaka [Japon] ; Masato Hosokawa [Japon] ; Maki Kubo [Japon] ; Aki Shimozawa [Japon] ; Haruhiko Akiyama [Japon] ; Masato Hasegawa [Japon]Source :
- Acta Neuropathologica Communications [ 2051-5960 ] ; 2014.
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.
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.
Url:
DOI: 10.1186/s40478-014-0088-8
Affiliations:
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</desc></org></tutelle></tutelles></hal:affiliation><country>Japon</country></affiliation></author><author><name sortKey="Hasegawa, Masato" sort="Hasegawa, Masato" uniqKey="Hasegawa M" first="Masato" last="Hasegawa">Masato Hasegawa</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-268367" status="INCOMING"> <orgName>Department of Neuropathology and Cell Biology</orgName> <desc> <address> <addrLine>Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku 156-0057, Tokyo, Japan</addrLine> <country key="JP"></country> </address> </desc> <listRelation> <relation active="#struct-328915" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-328915" type="direct"><org type="institution" xml:id="struct-328915" status="INCOMING"> <orgName>Tokyo Metropolitan Institute of Medical Science</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Japon</country></affiliation></author></analytic><idno type="DOI">10.1186/s40478-014-0088-8</idno><series><title level="j">Acta Neuropathologica Communications</title><idno type="ISSN">2051-5960</idno><imprint><date type="datePub">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Masuda Suzukake, Masami" sort="Masuda Suzukake, Masami" uniqKey="Masuda Suzukake M" first="Masami" last="Masuda-Suzukake">Masami Masuda-Suzukake</name></noRegion><name sortKey="Akiyama, Haruhiko" sort="Akiyama, Haruhiko" uniqKey="Akiyama H" first="Haruhiko" last="Akiyama">Haruhiko Akiyama</name><name sortKey="Hasegawa, Masato" sort="Hasegawa, Masato" uniqKey="Hasegawa M" first="Masato" last="Hasegawa">Masato Hasegawa</name><name sortKey="Hosokawa, Masato" sort="Hosokawa, Masato" uniqKey="Hosokawa M" first="Masato" last="Hosokawa">Masato Hosokawa</name><name sortKey="Kubo, Maki" sort="Kubo, Maki" uniqKey="Kubo M" first="Maki" last="Kubo">Maki Kubo</name><name sortKey="Nonaka, Takashi" sort="Nonaka, Takashi" uniqKey="Nonaka T" first="Takashi" last="Nonaka">Takashi Nonaka</name><name sortKey="Shimozawa, Aki" sort="Shimozawa, Aki" uniqKey="Shimozawa A" first="Aki" last="Shimozawa">Aki Shimozawa</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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