Comparative analyses of the in vivo induction and transmission of α-synuclein pathology in transgenic mice by MSA brain lysate and recombinant α-synuclein fibrils
Comparative analyses of the in vivo induction and transmission of α-synuclein pathology in transgenic mice by MSA brain lysate and recombinant α-synuclein fibrils
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MSA 脑裂解物和重组 α-突触核蛋白原纤维在转基因小鼠体内诱导和传播 α-突触核蛋白病理学的比较分析
DOI：
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发表时间：
2019
影响因子：
7.1
通讯作者：
B. Giasson
中科院分区：
文献类型：
--
作者：
Jess;J. Trejo;Cara J. Riffe;Yona Levites;A. Sacino;D. Borchelt;Anthony Y. Yachnis;B. Giasson
α-突触核蛋白（αS）是定义称为突触核蛋白病的神经退行性疾病的几种类型的脑病理性包涵体的主要组分。中枢神经系统（CNS）接种研究使用体外聚合的αS原纤维或体内衍生的含有αS聚集体的裂解物诱导动物疾病模型中αS包涵体病理学的进行性扩散，支持αS介导的进行性神经变性可通过朊病毒样机制发生的观点。我们之前已经证明，在表达野生型人αS的半合子M20+/−转基因小鼠中以及在较小程度上在非转基因小鼠中，用预先形成的αS原纤维接种新生儿脑可导致CNS αS病理的浓度依赖性进行性诱导。最近使用多系统萎缩（MSA）患者的脑裂解物（以少突胶质细胞中的αS包涵体病理为特征）进行的研究表明，这些裂解物可能是诱导具有朊病毒样菌株特异性的αS病理的唯一有效物质。我们在此证明，在研究设计的时间范围内，在表达A53 T人αS的转基因小鼠（M83系）中，新生儿脑接种后，MSA患者（而非对照个体）的脑裂解物可诱导αS病理学，但在表达野生型人αS的转基因小鼠（M20系）或非转基因小鼠中则不诱导。此外，我们发现MSA脑裂解物诱导的病理学的神经解剖学和免疫组织化学性质与半合子M83+/−转基因小鼠中新生儿脑注射预先形成的人αS原纤维所产生的病理学性质非常相似。总的来说，这些发现强化了M83小鼠模型的内在特征优于MSA αS种子的任何推定朊病毒样菌株特性（可诱导病理学）的观点。
α-synuclein (αS) is the major component of several types of brain pathological inclusions that define neurodegenerative diseases termed synucleinopathies. Central nervous system (CNS) inoculation studies using either in vitro polymerized αS fibrils or in vivo derived lysates containing αS aggregates to induce the progressive spread of αS inclusion pathology in animal disease models have supported the notion that αS mediated progressive neurodegeneration can occur by a prion-like mechanism. We have previously shown that neonatal brain inoculation with preformed αS fibrils in hemizygous M20+/− transgenic mice expressing wild type human αS and to a lesser extent in non-transgenic mice can result in a concentration-dependent progressive induction of CNS αS pathology. Recent studies using brain lysates from patients with multiple system atrophy (MSA), characterized by αS inclusion pathology in oligodendrocytes, indicate that these may be uniquely potent at inducing αS pathology with prion-like strain specificity. We demonstrate here that brain lysates from MSA patients, but not control individuals, can induce αS pathology following neonatal brain inoculation in transgenic mice expressing A53T human αS (M83 line), but not in transgenic expressing wild type human αS (M20 line) or non-transgenic mice within the timeframe of the study design. Further, we show that neuroanatomical and immunohistochemical properties of the pathology induced by MSA brain lysates is very similar to what is produced by the neonatal brain injection of preformed human αS fibrils in hemizygous M83+/− transgenic mice. Collectively, these findings reinforce the idea that the intrinsic traits of the M83 mouse model dominates over any putative prion-like strain properties of MSA αS seeds that can induce pathology.
DOI：
10.1016/s0165-3806(96)00210-6
发表时间：
1997-03
期刊：
Brain research. Developmental brain research
影响因子：
--
作者：
G. Withers;J. George;G. Banker;D. F. Clayton
通讯作者：
G. Withers;J. George;G. Banker;D. F. Clayton
DOI：
10.1016/j.bbadis.2008.09.013
发表时间：
2009-07
影响因子：
6.2
作者：
Waxman, Elisa A.;Giasson, Benoit I.
通讯作者：
Giasson, Benoit I.
影响因子：
3.5
作者：
Kuo, Yien-Ming;Li, Zhishan;Nussbaum, Robert L.
通讯作者：
Nussbaum, Robert L.