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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice
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Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice

机译：抗神经生长因子转基因小鼠老年痴呆样神经变性

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摘要

Neurotrophin nerve growth factor (NGF) has been suggested to be involved in age-related neurodegenerative diseases, but no trans- genic model is currently available to study this concept. We have obtained transgenic mice expressing a neutralizing anti-NGF re- combinant antibody, in which the levels of antibodies are three orders of magnitude higher in adult than in newborn mice [F.R., S. C.. A.C., E. Di Daniel, J. Franzot, S. Gonfloni. G. Rossi, N. B. & A. C. (2000) J. Neurosci, 20, 2589--2601]. In this paper, we analyze the phenotype of aged anti-NGF transgenic mice and demonstrate that these mice acquire an age-dependent neurodegenerative pathol- ogy including amyloid plaques, insoluble and hyperphosphory- lated L and neurofibrillary tangles in cortical and hippocampal neurons. Aged anti-NGF mice also display extensive neuronal loss throughout the cortex. cholinergic deficit in the basal forebrain, and behavioral deficits. The overall picture is strikingly reminiscent of human Alzheimer's disease. Aged anti-NGF mice represent, to our knowledge, the most comprehensive animal model for this severe neurodegenerative disease. Also, these results demonstrate that, in mice, a deficit in the signaling and/or transport of NGF leads to neurodegeneration.
机译：神经营养蛋白神经生长因子（NGF）已被建议参与与年龄有关的神经退行性疾病，但目前尚无转基因模型可用于研究这一概念。我们已经获得了表达中和性抗NGF重组抗体的转基因小鼠，其中成年小鼠的抗体水平比新生小鼠高三个数量级[FR，SC。AC，E. Di Daniel，J. Franzot， S.贡弗洛尼。 G.Rossi，N.B。＆A.C。（2000）J.Neurosci，20，2589--2601]。在本文中，我们分析了老年抗NGF转基因小鼠的表型，并证明这些小鼠获得了年龄依赖性的神经退行性病变，包括淀粉样斑块，不溶性和高磷酸化L以及皮质和海马神经元缠结。老年抗NGF小鼠还在整个皮质中显示出广泛的神经元丢失。基底前脑的胆碱能缺乏症和行为缺陷。总体而言，令人惊讶地让人联想到人类阿尔茨海默氏病。据我们所知，老年抗NGF小鼠代表了这种严重神经退行性疾病的最全面的动物模型。而且，这些结果表明，在小鼠中，NGF的信号传导和/或转运的缺陷导致神经变性。

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