Home > Publications Database > Oral and intravenous transmission of α-synuclein fibrils to mice. > print

001     141488
005     20240323120019.0
024 7 _ |a 10.1007/s00401-019-02037-5
|2 doi
024 7 _ |a pmid:31230104
|2 pmid
024 7 _ |a pmc:PMC6778172
|2 pmc
024 7 _ |a 0001-6322
|2 ISSN
024 7 _ |a 1432-0533
|2 ISSN
024 7 _ |a altmetric:62634082
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037 _ _ |a DZNE-2020-07812
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Lohmann, Stephanie
|0 P:(DE-2719)2812190
|b 0
|e First author
|u dzne
245 _ _ |a Oral and intravenous transmission of α-synuclein fibrils to mice.
260 _ _ |a Heidelberg
|c 2019
|b Springer
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-06-22
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-10-01
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1711118793_19998
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Parkinson's disease and related disorders are neuropathologically characterized by cellular deposits of misfolded and aggregated α-synuclein in the CNS. Disease-associated α-synuclein adopts a conformation that causes it to form oligomers and fibrils, which have reduced solubility, become hyperphosphorylated, and contribute to the spatiotemporal spreading of pathology in the CNS. The infectious properties of disease-associated α-synuclein, e.g., by which peripheral route and with which efficiency it can be transmitted, are not fully understood. Here, we investigated the potential of α-synuclein fibrils to induce neurological disease in TgM83+/- mice expressing the A53T mutant of human α-synuclein after oral or intravenous challenge and compared it to intraperitoneal and intracerebral challenge. Oral challenge with 50 µg of α-synuclein fibrils caused neurological disease in two out of eight mice in 220 days and 350 days, and challenge with 500 µg in four out of eight mice in 384 ± 131 days, respectively. Intravenous challenge with 50 µg of α-synuclein fibrils led to disease in 208 ± 20 days in 10 out of 10 mice and was in duration comparable to intraperitoneal challenge with 50 µg of α-synuclein fibrils, which caused disease in 10 out of 10 mice in 202 ± 35 days. Ten out of 10 mice that were each intracerebrally challenged with 10 µg or 50 µg of α-synuclein fibrils developed disease in 156 ± 20 days and 133 ± 4 days, respectively. The CNS of diseased mice displayed aggregates of sarkosyl-insoluble and phosphorylated α-synuclein, which colocalized with ubiquitin and p62 and were accompanied by gliosis indicative of neuroinflammation. In contrast, none of the control mice that were challenged with bovine serum albumin via the same routes developed any neurological disease or neuropathology. These findings are important, because they show that α-synuclein fibrils can neuroinvade the CNS after a single oral or intravenous challenge and cause neuropathology and disease.
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542 _ _ |i 2019-06-22
|2 Crossref
|u https://creativecommons.org/licenses/by/4.0
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 2 |a Administration, Intravenous
|2 MeSH
650 _ 2 |a Administration, Oral
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Brain: drug effects
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Phosphorylation
|2 MeSH
650 _ 2 |a Synucleinopathies: chemically induced
|2 MeSH
650 _ 2 |a Synucleinopathies: pathology
|2 MeSH
650 _ 2 |a alpha-Synuclein: administration & dosage
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
700 1 _ |a Bernis, Maria E
|0 P:(DE-2719)2810557
|b 1
|u dzne
700 1 _ |a Babila, Julius Tachu
|0 P:(DE-2719)2810720
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700 1 _ |a Ziemski, Alexandra
|b 3
700 1 _ |a Grigoletto, Jessica
|0 P:(DE-2719)2812381
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700 1 _ |a Tamgüney, Gültekin
|0 P:(DE-2719)2810376
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773 1 8 |a 10.1007/s00401-019-02037-5
|b : Springer Science and Business Media LLC, 2019-06-22
|n 4
|p 515-533
|3 journal-article
|2 Crossref
|t Acta Neuropathologica
|v 138
|y 2019
|x 0001-6322
773 _ _ |a 10.1007/s00401-019-02037-5
|g Vol. 138, no. 4, p. 515 - 533
|0 PERI:(DE-600)1458410-4
|n 4
|q 138:4<515 - 533
|p 515-533
|t Acta neuropathologica
|v 138
|y 2019
|x 0001-6322
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/141488/files/DZNE-2020-07812.pdf
856 4 _ |y OpenAccess
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856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778172
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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913 1 _ |a DE-HGF
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999 C 5 |9 -- missing cx lookup --
|a 10.1002/mds.25421
|2 Crossref
|o 10.1002/mds.25421
999 C 5 |9 -- missing cx lookup --
|a 10.1128/jvi.02095-16
|2 Crossref
|o 10.1128/jvi.02095-16
999 C 5 |9 -- missing cx lookup --
|a 10.1128/jvi.00586-18
|2 Crossref
|o 10.1128/jvi.00586-18
999 C 5 |9 -- missing cx lookup --
|a 10.1099/0022-1317-78-5-1187
|2 Crossref
|o 10.1099/0022-1317-78-5-1187
999 C 5 |9 -- missing cx lookup --
|a 10.1128/JVI.77.1.583-591.2003
|2 Crossref
|o 10.1128/JVI.77.1.583-591.2003
999 C 5 |9 -- missing cx lookup --
|a 10.1099/0022-1317-79-3-601
|2 Crossref
|o 10.1099/0022-1317-79-3-601
999 C 5 |9 -- missing cx lookup --
|a 10.1186/s40478-015-0254-7
|2 Crossref
|o 10.1186/s40478-015-0254-7
999 C 5 |9 -- missing cx lookup --
|a 10.1016/S0197-4580(02)00065-9
|2 Crossref
|o 10.1016/S0197-4580(02)00065-9
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00702-002-0808-2
|2 Crossref
|o 10.1007/s00702-002-0808-2
999 C 5 |9 -- missing cx lookup --
|a 10.1128/JVI.01399-16
|2 Crossref
|o 10.1128/JVI.01399-16
999 C 5 |9 -- missing cx lookup --
|a 10.1126/science.1195227
|2 Crossref
|o 10.1126/science.1195227
999 C 5 |9 -- missing cx lookup --
|a 10.1016/S0140-6736(04)17103-1
|2 Crossref
|o 10.1016/S0140-6736(04)17103-1
999 C 5 |9 -- missing cx lookup --
|a 10.1101/cshperspect.a006833
|2 Crossref
|o 10.1101/cshperspect.a006833
999 C 5 |9 -- missing cx lookup --
|a 10.1016/S0140-6736(06)68930-7
|2 Crossref
|o 10.1016/S0140-6736(06)68930-7
999 C 5 |y 1964
|2 Crossref
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|o RM Dougherty Animal virus titration techniques 1964
999 C 5 |9 -- missing cx lookup --
|a 10.1126/science.142303
|2 Crossref
|o 10.1126/science.142303
999 C 5 |9 -- missing cx lookup --
|a 10.1016/S0896-6273(02)00682-7
|2 Crossref
|o 10.1016/S0896-6273(02)00682-7
999 C 5 |9 -- missing cx lookup --
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|2 Crossref
|o 10.1111/j.1749-6632.2009.04365.x
999 C 5 |9 -- missing cx lookup --
|a 10.1111/j.1365-2990.2007.00874.x
|2 Crossref
|o 10.1111/j.1365-2990.2007.00874.x
999 C 5 |9 -- missing cx lookup --
|a 10.1111/j.1423-0410.2006.00833.x
|2 Crossref
|o 10.1111/j.1423-0410.2006.00833.x
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|a 10.1038/38925
|2 Crossref
|o 10.1038/38925
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|2 Crossref
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|a 10.1007/s00401-014-1343-6
|2 Crossref
|o 10.1007/s00401-014-1343-6
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|a 10.1126/science.404706
|2 Crossref
|o 10.1126/science.404706
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|2 Crossref
|o 10.1016/0021-9975(78)90059-2
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|2 Crossref
|o 10.1038/ng0298-106
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|2 Crossref
|o 10.1097/00001756-200107200-00009
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|a 10.1002/ana.23894
|2 Crossref
|o 10.1002/ana.23894
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|2 Crossref
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|o 10.1126/science.1227157
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|2 Crossref
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|o 10.1038/nmeth.2019
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|2 Crossref
|o 10.1073/pnas.95.11.6469
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|2 Crossref
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|a 10.1002/ana.24648
|2 Crossref
|o 10.1002/ana.24648
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