A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease
A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease
复制标题
DOI：
10.1016/j.jneumeth.2009.08.021
复制
发表时间：
2009-11-15
影响因子：
3
通讯作者：
Potter, Huntington
中科院分区：
文献类型：
--
作者：
Bennett, Steven P.;Boyd, Tim D.;Potter, Huntington
使用转基因模型研究疾病的研究人员面临的一个常见问题是动物群体或群体内存在的表型变异性。因此，重要的病理学分析通常需要大量的小鼠来执行。在过去的十年中，已经开发了许多转基因小鼠品系，这些转基因小鼠含有导致家族性阿尔茨海默病的不同突变的人类淀粉样前体蛋白（APP）基因，用于研究斑块沉积和AD的其他方面。然而，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之间在大小、密度、斑块数量和总淀粉样蛋白负荷方面的差异。因此，为了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。我们已经开发了导管，促进小鼠大脑中的同时双侧输注，从而使用同一动物的对侧半球作为内部对照，同时研究，例如，化合物对淀粉样蛋白斑块的影响，淀粉样蛋白斑块是阿尔茨海默病（AD）进展的病理标志。在斑块中已经鉴定出几种分子，包括主要成分A β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，ACT在28天内单侧输注到PS/APP小鼠的实质和侧脑室中，并观察到与淀粉样蛋白斑块相关，死亡率最低。利用ACT/A β相互作用，在此详细讨论该过程的细节。(C)2009爱思唯尔有限公司版权所有。
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 A beta 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/A beta interaction, details of this procedure are discussed here in detail. (C) 2009 Elsevier B.V. All rights reserved.