Maternal genotype influences behavioral development of 3xTg-AD mouse pups

Maternal genotype influences behavioral development of 3xTg-AD mouse pups
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DOI:
10.1016/j.bbr.2013.05.033
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发表时间:
2013-09-01
影响因子:
2.7
通讯作者:
Brown, Richard E.
Brown, Richard E.
中科院分区:
心理学3区
文献类型:
--
作者:
Blaney, Caitlin E.;Gunn, Rhian K.;Brown, Richard E.

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转基因小鼠是研究阿尔茨海默病等神经退行性疾病的重要工具。三重转基因小鼠(3xTg-AD)是阿尔茨海默病的模型,具有年龄相关的淀粉样蛋白β斑块,神经元缠结和细胞死亡以及认知能力下降。由于母体效应可能与幼鼠基因型在确定行为表型方面相互作用,我们使用交叉培养范式来研究母体基因型对3xTg-AD小鼠模型及其野生型对照(B6129 S1 F2)从2至24日龄的行为发育的影响。行为的发展模式受到幼鼠和母体基因型的影响。3xTg-AD小鼠感觉反射延迟,表现出较少的活动和对新物体的适应性较差,但与野生型幼崽相比,表现出运动反射的高级发育。虽然转基因和对照组母亲之间的孕产妇护理水平没有差异,母亲的基因型影响了几个幼犬反射(体重,后肢抓反射,交叉伸肌反射,触须反应,翻正反射的损失)的发展和水平和垂直梁打破在一个开放的领域。这项研究是第一个在阿尔茨海默病小鼠模型中研究神经行为发育和母性行为的研究,并强调了研究早期环境经验以及遗传操作对行为发育的影响的重要性。(C)2013爱思唯尔有限公司版权所有。
Transgenic mice are a valuable tool in the investigation of neurodegenerative disorders such as Alzheimer's disease. The triple transgenic mouse (3xTg-AD) is a model of Alzheimer's disease that possesses age-related amyloid beta plaques, neurofibrillary tangles and cell death as well as cognitive decline. Because maternal effects may interact with pup genotype in determining behavior phenotypes, we used a cross-fostering paradigm to investigate the effects of maternal genotype on behavioral development of the 3xTg-AD mouse model and its wildtype control (B6129S1F2) from 2 to 24 days of age. Developmental patterns of behavior were influenced by both pup and maternal genotype. The 3xTg-AD mice were delayed in sensory reflexes, showed less activity and poorer habituation to a novel object, but showed advanced development of motor reflexes compared to wildtype pups. While there were no differences in levels of maternal care between transgenic and control mothers, maternal genotype affected the development of several pup reflexes (body weight, hindlimb grasp reflex, loss of crossed extensor reflex, vibrissae response, righting reflex) and the number of horizontal and vertical beam breaks in an open field. This study is the first to examine neurobehavioral development and maternal behavior in a mouse model of Alzheimer's disease, and highlights the importance of investigating the consequences of early environmental experience as well as genetic manipulation on behavioral development. (C) 2013 Elsevier B.V. All rights reserved.