Abstract | INTRODUCTION: RESULTS: Here we show that brain extracts from two patients with MSA and two patients with probable incidental Lewy body disease (iLBD) but not phosphate-buffered saline induce prion-like spreading of pathological alpha-synuclein after intrastriatal injection into mice expressing human wild-type alpha-synuclein. Mice were sacrificed at 3, 6, and 9 months post injection and analyzed neuropathologically and biochemically. Mice injected with brain extracts from patients with MSA or probable iLBD both accumulated intraneuronal inclusion bodies, which stained positive for phosphorylated alpha-synuclein and appeared predominantly within the injected brain hemisphere after 6 months. After 9 months these intraneuronal inclusion bodies had spread to the contralateral hemisphere and more rostral and caudal areas. Biochemical analysis showed that brains of mice injected with brain extracts from patients with MSA and probable iLBD contained hyperphosphorylated alpha-synuclein that also seeded aggregation of recombinant human wild-type alpha-synuclein in a Thioflavin T binding assay. CONCLUSIONS:
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Authors | Maria E Bernis, Julius T Babila, Sara Breid, Katharina Annick Wüsten, Ullrich Wüllner, Gültekin Tamgüney |
Journal | Acta neuropathologica communications
(Acta Neuropathol Commun)
Vol. 3
Pg. 75
(Nov 26 2015)
ISSN: 2051-5960 [Electronic] England |
PMID | 26612754
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Heat-Shock Proteins
- Sequestosome-1 Protein
- Sqstm1 protein, mouse
- Ubiquitin
- alpha-Synuclein
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Topics |
- Adaptor Proteins, Signal Transducing
(metabolism)
- Age Factors
- Animals
- Brain
(metabolism, pathology)
- Female
- Gene Expression Regulation
(genetics)
- Heat-Shock Proteins
(metabolism)
- Humans
- Lewy Body Disease
(pathology)
- Male
- Mice
- Mice, Transgenic
- Multiple System Atrophy
(pathology)
- Mutation
(genetics)
- Phosphorylation
- Sequestosome-1 Protein
- Ubiquitin
(metabolism)
- alpha-Synuclein
(genetics, metabolism)
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