Clinical Neurosciences, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 806, Southampton, SO16 6YD, UK.
Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, Southampton, SO16 6YD, UK.
J Neural Transm (Vienna). 2018 May;125(5):827-846. doi: 10.1007/s00702-017-1729-4. Epub 2017 May 17.
The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment. With respect to Alzheimer's disease (AD), much of the experimental information currently known about this disease has been gathered from studies using mainly mice as models. Therefore, it is notably important to fully characterise the differences between mice and humans regarding important aspects of the disease. It is now widely known that inflammation plays an important role in the development of AD, a role that is not only a response to the surrounding pathological environment, but rather seems to be strongly implicated in the aetiology of the disease as indicated by the genetic studies. This review highlights relevant differences in inflammation and in microglia, the innate immune cell of the brain, between mice and humans regarding genetics and morphology in normal ageing, and the relationship of microglia with AD-like pathology, the inflammatory profile, and cognition. We conclude that some noteworthy differences exist between mice and humans regarding microglial characteristics, in distribution, gene expression, and states of activation. This may have repercussions in the way that transgenic mice respond to, and influence, the AD-like pathology. However, despite these differences, human and mouse microglia also show similarities in morphology and behaviour, such that the mouse is a suitable model for studying the role of microglia, as long as these differences are taken into consideration when delineating new strategies to approach the study of neurodegenerative diseases.
老鼠是生物医学研究中最广泛使用的动物模型之一，因为它特别容易在实验室中处理和繁殖。作为哺乳动物的一员，老鼠在代谢途径、细胞形态和解剖结构等方面与人类有许多共同之处。然而，老鼠和人类之间存在着重要的生物学差异，在解释研究结果时必须考虑这些差异，以便将实验研究的证据正确地转化为对人类疾病预防和/或治疗有用的信息。
就阿尔茨海默病（AD）而言，目前关于这种疾病的大部分实验信息都是通过主要使用老鼠作为模型的研究收集的。因此，充分描述老鼠和人类在疾病的重要方面的差异是非常重要的。现在已经广泛认识到，炎症在 AD 的发展中起着重要作用，这种作用不仅是对周围病理环境的反应，而且似乎强烈地与疾病的病因学有关，这一点从遗传研究中可以看出。
本综述强调了在正常衰老过程中，老鼠和人类之间在炎症和小胶质细胞（大脑的先天免疫细胞）方面的遗传学和形态学方面的相关差异，以及小胶质细胞与 AD 样病理学、炎症特征和认知之间的关系。我们得出结论，在小胶质细胞的特征方面，老鼠和人类之间存在一些值得注意的差异，表现在分布、基因表达和激活状态上。这可能会对转基因老鼠对 AD 样病理学的反应和影响方式产生影响。然而，尽管存在这些差异，人类和老鼠的小胶质细胞在形态和行为上也存在相似之处，因此老鼠是研究小胶质细胞作用的合适模型，只要在制定新的策略来研究神经退行性疾病时考虑到这些差异。
