Silver staining (Campbell-Switzer) of neuronal α-synuclein assemblies induced by multiple system atrophy and Parkinson's disease brain extracts in transgenic mice

被引:32
作者
Lavenir, Isabelle [1 ]
Passarella, Daniela [1 ]
Masuda-Suzukake, Masami [1 ]
Curry, Annabelle [1 ]
Holton, Janice L. [2 ]
Ghetti, Bernardino [3 ]
Goedert, Michel [1 ]
机构
[1] MRC Lab Mol Biol, Cambridge CB2 0QH, England
[2] UCL, Queen Sq Inst Neurol, London WC1N 1PJ, England
[3] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA
基金
英国医学研究理事会;
关键词
alpha-Synuclein; Multiple system atrophy; Parkinson's disease; Seeding; Silver staining; Transgenic; GLIAL CYTOPLASMIC INCLUSIONS; MESSENGER-RNA EXPRESSION; LEWY BODIES; CRYO-EM; TRANSMISSION; OLIGODENDROCYTES; DEMENTIA; PHOSPHORYLATION; DEGENERATION; FILAMENTS;
D O I
10.1186/s40478-019-0804-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Synucleinopathies [Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA)] share filamentous alpha-synuclein assemblies in nerve cells and glial cells. We compared the abilities of brain extracts from MSA and PD patients to induce neuronal alpha-synuclein assembly and neurodegeneration following intracerebral injection in heterozygous mice transgenic for human mutant A53T alpha-synuclein. MSA extracts were more potent than PD extracts in inducing alpha-synuclein assembly and in causing neurodegeneration. MSA assemblies were Campbell-Switzer- and Gallyas-silver-positive, whereas PD assemblies were only Campbell-Switzer-positive, in confirmation of previous findings. However, induced alpha-synuclein inclusions were invariably Campbell-Switzer-positive and Gallyas-negative, irrespective of whether MSA or PD brain extracts were injected. The alpha-synuclein inclusions of non-injected homozygous mice transgenic for A53T alpha-synuclein were also Campbell-Switzer-positive and Gallyas-negative. These findings demonstrate that transgene expression and its intracellular environment dominated over the silver staining properties of the conformers of assembled alpha-synuclein.
引用
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页数:11
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