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Frontiers of Model Animals for Neuroscience: Two Prosperous Aging Model Animals for Promoting Neuroscience Research

机译:神经科学模型动物的前沿:促进神经科学研究的两种繁荣的衰老模型动物

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A model animal showing spontaneous onset is a useful tool for investigating the mechanism of disease. Here, I would like to introduce two aging model animals expected to be useful for neuroscience research: the senescence-accelerated mouse (SAM) and the klotho mouse. The SAM was developed as a mouse showing a senescence-related phenotype such as a short lifespan or rapid advancement of senescence. In particular, SAMP8 and SAMP10 show age-related impairment of learning and memory. SAMP8 has spontaneous spongy degeneration in the brain stem and spinal cord with aging, and immunohistochemical studies reveal excess protein expression of amyloid precursor protein and amyloid β in the brain, indicating that SAMP8 is a model for Alzheimer’s disease. SAMP10 also shows age-related impairment of learning and memory, but it does not seem to correspond to Alzheimer’s disease because senile plaques primarily composed of amyloid β or neurofibrillary tangles primarily composed of phosphorylated tau were not observed. However, severe atrophy in the frontal cortex, entorhinal cortex, amygdala, and nucleus accumbens can be seen in this strain in an age-dependent manner, indicating that SAMP10 is a model for normal aging. The klotho mouse shows a phenotype, regulated by only one gene named α-klotho, similar to human progeria. The α-klotho gene is mainly expressed in the kidney and brain, and oxidative stress is involved in the deterioration of cognitive function of the klotho mouse. These animal models are potentially useful for neuroscience research now and in the near future.
机译:显示自发性的模型动物是研究疾病机理的有用工具。在这里,我想介绍两种预期对神经科学研究有用的衰老模型动物:衰老加速小鼠(SAM)和klotho小鼠。 SAM被开发为显示衰老相关表型(例如寿命短或衰老迅速)的小鼠。特别是,SAMP8和SAMP10显示出与年龄有关的学习和记忆障碍。随着年龄的增长,SAMP8在脑干和脊髓中具有自发性海绵变性,免疫组织化学研究表明,大脑中淀粉样前体蛋白和淀粉样β的蛋白表达过多,这表明SAMP8是阿尔茨海默氏病的模型。 SAMP10还显示出与年龄有关的学习和记忆障碍,但似乎与阿尔茨海默氏病并不对应,因为未观察到主要由淀粉样蛋白β组成的老年斑或主要由磷酸化tau组成的神经原纤维缠结。然而,在该菌株中可以以年龄依赖的方式看到额叶皮质,内嗅皮质,杏仁核和伏隔核的严重萎缩,这表明SAMP10是正常衰老的模型。 klotho小鼠表现出一种表型,仅受一个名为α-klotho的基因调控,与人类早衰类似。 α-klotho基因主要在肾脏和大脑中表达,氧化应激与klotho小鼠的认知功能下降有关。这些动物模型对于现在和不久的将来对神经科学研究都有潜在的帮助。

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