ALPHA-SYNUCLEIN DEFICIENCY IN THE C57BL/6JOIaHsd STRAIN DOES NOT MODIFY DISEASE PROGRESSION IN THE ME7-MODEL OF PRION DISEASE
ALPHA-SYNUCLEIN DEFICIENCY IN THE C57BL/6JOIaHsd STRAIN DOES NOT MODIFY DISEASE PROGRESSION IN THE ME7-MODEL OF PRION DISEASE
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DOI：
10.1016/j.neuroscience.2009.10.047
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发表时间：
2010-02-03
期刊：
影响因子：
3.3
通讯作者：
O'Connor, V.
中科院分区：
文献类型：
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作者：
Asuni, A. A.;Hilton, K.;O'Connor, V.
我们之前详细介绍了如何在C57BL/6J小鼠海马内接种小鼠修饰的痒病（ME7）导致慢性神经变性（Cunningham C, Deacon R, Wells H, Boche D, Waters S, Diniz CP, Scott H, Rawlins JN, Perry VH（2003）欧洲神经科学杂志：2147-2155）。我们对me7模型的描述是基于将这种小鼠改性痒病剂接种到哈伦实验室的C57BL/6J小鼠身上。这种药物在C57BL/6J宿主体内产生一种持续24周的疾病。海马病理表现为进行性错误折叠朊病毒（PrPSc）沉积，星形胶质细胞形成，并导致由神经元死亡之前的早期突触丧失所支持的行为功能障碍。虽然Harlan C57BL/6J被广泛用作野生型小鼠，但它是一种携带α -突触核蛋白自发缺失的亚株，完整描述为C57BL/6JOIaHsd。最近，α -突触核蛋白已被证明可以改善缺乏突触伴侣csp - α的小鼠模型中的突触丢失。这打开了me7模型的一个潜在的混淆，特别是关于支持生理和行为功能障碍的标志性突触丧失。为了研究候选疾病修饰因子的菌株选择性缺失是否会影响ME7的特征病理，我们比较了C57BL/6JOIaHsd （α -synuclein阴性）和Charles Rivers的创始菌株（C57BL/6JCrI， α -synuclein阳性）。当比较来自两个亚菌株的对照动物时，行为发生了微妙的变化，这表明假设这两个菌株的神经生物学特性的研究可能会产生重大后果。然而，没有证据表明α -突触核蛋白的缺失改变了疾病。事实上，在两种遗传背景下，PrPSc的积累、突触丧失和与me7因子相关的行为功能障碍是相同的。我们的数据表明，α -突触核蛋白缺乏不会导致导致朊病毒疾病介导的突触毒性和神经退行性变的室特异性过程。(c) 2010 ibro。Elsevier Ltd.出版。版权所有。
We previously detailed how intrahippocampal inoculation of C57BL/6J mice with murine modified scrapie (ME7) leads to chronic neurodegeneration (Cunningham C, Deacon R, Wells H, Boche D, Waters S, Diniz CP, Scott H, Rawlins JN, Perry VH (2003) Eur J Neurosci 17:2147-2155.). Our characterization of the ME7-model is based on inoculation of this murine modified scrapie agent into C57BL/6J mice from Harlan laboratories. This agent in the C57BL/6J host generates a disease that spans a 24-week time course. The hippocampal pathology shows progressive misfolded prion (PrPSc) deposition, astrogliosis and leads to behavioural dysfunction underpinned by the early synaptic loss that precedes neuronal death. The Harlan C57BL/6J, although widely used as a wild type mouse, are a sub-strain harbouring a spontaneous deletion of alpha-synuclein with the full description C57BL/6JOIaHsd. Recently alpha-synuclein has been shown to ameliorate the synaptic loss in a mouse model lacking the synaptic chaperone CSP-alpha. This opens a potential confound of the ME7-model, particularly with respect to the signature synaptic loss that underpin the physiological and behavioural dysfunction. To investigate if this strain-selective loss of a candidate disease modifier impacts on signature ME7 pathology, we compared cohorts of C57BL/6JOIaHsd (alpha-synuclein negative) with the founder strain from Charles Rivers (C57BL/6JCrI, alpha-synuclein positive). There were subtle changes in behaviour when comparing control animals from the two sub-strains indicating potentially significant consequences for studies assuming neurobiogical identity of both strains. However, there was no evidence that the absence of alpha-synuclein modifies disease. Indeed, accumulation of PrPSc, synaptic loss and the behavioural dysfunction associated with the ME7-agent was the same in both genetic backgrounds. Our data suggest that alpha-synuclein deficiency does not contribute to the compartment specific processes that give rise to prion disease mediated synaptotoxicity and neurodegeneration. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.