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处于半自然环境中的转基因阿尔茨海默病小鼠:斑块增多,但日常生活未受影响。

Transgenic Alzheimer mice in a semi-naturalistic environment: more plaques, yet not compromised in daily life.

作者信息

Lewejohann Lars, Reefmann Nadine, Widmann Philipp, Ambrée Oliver, Herring Arne, Keyvani Kathy, Paulus Werner, Sachser Norbert

机构信息

Department of Behavioural Biology, University of Münster, Münster, Germany.

出版信息

Behav Brain Res. 2009 Jul 19;201(1):99-102. doi: 10.1016/j.bbr.2009.01.037. Epub 2009 Feb 6.

DOI:10.1016/j.bbr.2009.01.037
PMID:19428622
Abstract

The behaviour of transgenic animals modelling human diseases such as Alzheimer's disease (AD) is typically characterised in artificial apparatuses rather than labour-intensively observing their spontaneous behaviour in the home environment. Here we report on an in-depth behavioural characterisation of the day-to-day life of a murine model for AD living in a large (6.6 m(2)) semi-naturalistic indoor enclosure. In a genotype-blind investigation, 40 different behavioural patterns of wildtype and transgenic animals were recorded at early ages, before plaques can be found in the brains of the transgenic mice; and later in life, when these mice are known to exhibit AD-like plaques. Basal stress hormone levels (corticosterone) and cerebral amyloid-beta depositions were determined, and compared with individually and group-housed mice from non-enriched standard cages. Semi-naturalistically housed transgenics could not be differentiated from wildtypes by their behavioural profiles nor by basal levels of corticosterone. Surprisingly, the brains of these transgenics revealed an even more pronounced plaque load than controls from standard-housing conditions. Behavioural traits are known to involve gene-environment interactions. Here we show for the first time that despite high beta-amyloid plaque load the day-to-day life of AD mice is not compromised when the genetic predisposition interacts with a generous physically and socially enriched environment.

摘要

诸如阿尔茨海默病(AD)等人类疾病的转基因动物模型的行为,通常是在人工装置中进行表征,而不是通过在家庭环境中进行高强度的自发行为观察。在此,我们报告了对一只生活在大型(6.6平方米)半自然室内围栏中的AD小鼠模型日常生活的深入行为表征。在一项基因类型盲测中,在转基因小鼠大脑中出现斑块之前的早期阶段,以及在这些小鼠已知会出现类AD斑块的生命后期,记录了野生型和转基因动物40种不同的行为模式。测定了基础应激激素水平(皮质酮)和脑淀粉样β蛋白沉积,并与来自非丰富化标准笼舍单独饲养和群居饲养的小鼠进行了比较。半自然饲养的转基因小鼠在行为特征和皮质酮基础水平上与野生型小鼠没有差异。令人惊讶的是,这些转基因小鼠的大脑显示出比标准饲养条件下的对照小鼠更明显的斑块负荷。已知行为特征涉及基因 - 环境相互作用。在此我们首次表明,尽管β淀粉样斑块负荷很高,但当遗传易感性与丰富的物理和社会环境相互作用时,AD小鼠的日常生活并未受到影响。

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