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首页> 外文期刊>Journal of Neuroscience Methods >A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease.
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A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease.

机译：一种在神经退行性疾病小鼠模型中同时进行双侧脑部输注的新技术。

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A common problem faced by researchers using transgenic models to study disease is the phenotypic variability that exists within a group or colony of animals. Significant pathological analyses thus often require large numbers of mice to perform. Many lines of transgenic mice harboring the gene for human amyloid precursor protein (APP) with different mutations causing familial Alzheimer's disease have been developed over the past decade to study plaque deposition and other aspects of AD. However, variations in size, density, plaque number, and total amyloid load between animals of the same age and genotype have been identified by our lab and others. Therefore, to study the effects of compounds on amyloid pathology, it was imperative to develop a technique that would allow each brain hemisphere to receive different infusions. We have developed catheters that facilitate simultaneous bilateral infusion in mouse brains, thereby using the contralateral hemisphere of the same animal as an internal control while studying, for example, the effect of compounds on amyloid plaques, a pathological hallmark of the progression of Alzheimer's disease (AD). Several molecules have been identified within the plaques including the major component, the Abeta peptide, and two inflammation-related proteins, apolipoprotein E (apoE) and the serine protease inhibitor alpha-1-antichymotrypsin (ACT). In these experiments, ACT was infused unilaterally over a period of 28 days into the parenchyma and lateral ventricles of PS/APP mice and observed to associate with amyloid plaques, with minimal mortality. Utilizing the ACT/Abeta interaction, details of this procedure are discussed here in detail.
机译：研究人员使用转基因模型研究疾病时面临的一个普遍问题是动物群或动物群中存在的表型变异性。因此，重要的病理分析通常需要大量的小鼠才能进行。在过去十年中，已经开发出许多带有人类淀粉样蛋白前体蛋白（APP）基因的转基因小鼠品系，这些基因具有导致家族性阿尔茨海默氏病的不同突变，以研究斑块沉积和AD的其他方面。但是，我们的实验室和其他实验室已经确定了相同年龄和基因型的动物在大小，密度，菌斑数量和总淀粉样蛋白负荷方面的差异。因此，要研究化合物对淀粉样蛋白病理学的影响，必须开发一种技术，使每个大脑半球接受不同的输注。我们已经开发了有助于同时向小鼠大脑进行双侧输注的导管，从而在研究例如化合物对淀粉样蛋白斑的影响（这是阿尔茨海默氏病进展的病理学标志（）时）使用同一只动物的对侧半球作为内部对照。广告）。斑块中已鉴定出几种分子，包括主要成分Abeta肽和两种炎症相关蛋白，载脂蛋白E（apoE）和丝氨酸蛋白酶抑制剂α-1-抗胰凝乳蛋白酶（ACT）。在这些实验中，在28天的时间内将ACT单侧注入PS / APP小鼠的实质和侧脑室，并观察到与淀粉样斑块相关，死亡率最低。利用ACT / Abeta交互作用，此处将详细讨论此过程的细节。

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