Anatomical and functional phenotyping of mice models of Alzheimer's disease by MR microscopy
Anatomical and functional phenotyping of mice models of Alzheimer's disease by MR microscopy
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DOI：
10.1196/annals.1379.006
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Hof, Patrick R.
中科院分区：
文献类型：
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作者：
Benveniste, Helene;Ma, Yu;Hof, Patrick R.
阿尔茨海默病 (AD) 转基因小鼠模型的种类繁多，反映出对影响 AD 病理学的特定基因的探索以及创建临床相关动物模型的动力。理想的 AD 小鼠模型必须表现出标志性 AD 病理学，例如淀粉样斑块、神经原纤维缠结、反应性神经胶质增生、营养不良的神经突、神经元和突触损失以及脑萎缩，同时行为上模仿人类观察到的认知衰退。磁共振 (MR) 显微镜 (MRM) 可以检测淀粉样斑块负荷、脑萎缩的发展和急性神经变性。将介绍并讨论 AD 病理学的 MRM 示例。使用转基因 AD 小鼠模型进行的临床前研究滞后的是大脑的功能表型分析。换句话说，将特定基因型与潜在的异常大脑激活模式相关联的能力。这种信息的缺乏是由于在小鼠中进行功能性 MRI (fMRI) 所涉及的技术挑战造成的，包括麻醉剂的影响和缺乏相关的“认知”范式。使用外部刺激作为啮齿动物大脑激活触发器的经典功能磁共振成像的另一种方法是直接通过电或药理刺激区域，同时使用例如锰增强磁共振成像（MEMRI）技术局部跟踪啮齿动物激活的互连区域。最后，转基因小鼠模型、MRM 和未来的 AD 研究将通过在其他非 AD 转基因小鼠模型中筛选 AD 样病理的能力得到加强。例如，分子生物学家可能会关注转基因小鼠模型中的心脏或肺部病理学，并作为偶然发现发现行为 AD 表型。我们将展示具有行为缺陷的转基因小鼠模型中大脑和心脏表型的 MRM 数据。
The wide variety of transgenic mouse models of Alzheimer's disease (AD) reflects the search for specific genes that influence AD pathology and the drive to create a clinically relevant animal model. An ideal AD mouse model must display hallmark AD pathology such as amyloid plaques, neurofibrillary tangles, reactive gliosis, dystrophic neurites, neuron and synapse loss, and brain atrophy and in parallel behaviorally mimic the cognitive decline observed in humans. Magnetic resonance (MR) microscopy (MRM) can detect amyloid plaque load, development of brain atrophy, and acute neurodegeneration. MRM examples of AD pathology will be presented and discussed. What has lagged behind in preclinical research using transgenic AD mouse models is functional phenotyping of the brain; in other words, the ability to correlate a specific genotype with potential aberrant brain activation patterns. This lack of information is caused by the technical challenges involved in performing functional MRI (fMRI) in mice including the effects of anesthetic agents and the lack of relevant '' cognitive '' paradigms. An alternative approach to classical fMRI using external stimuli as triggers of brain activation in rodents is to electrically or pharmacologically stimulate regions directly while simultaneously locally tracking the activated interconnected regions of rodents using, for example, the manganese-enhanced MRI (MEMRI) technique. Finally, transgenic mouse models, MRM, and future AD research would be strengthened by the ability to screen for AD-like pathology in other non-AD transgenic mouse models. For example, molecular biologists may focus on cardiac or pulmonary pathologies in transgenic mice models and as an incidental finding discover behavioral AD phenotypes. We will present MRM data of brain and cardiac phenotyping in transgenic mouse models with behavioral deficits.