摘要
冷漠是阿尔茨海默氏病(AD)患者早期常见的神经精神症状。临床试验里,冷漠与运动减少相关,可以用体动记录仪来监测。三重转基因小鼠AD模型(3xTgAD)已被证明能重现与AD相关的的生化损伤以及许多突触和认知的改变,这项研究里我们发现了这些小鼠还发展了早期持续的冷漠行为,其证据用体动记录仪测量到自发活动量的急剧下降。最近我们确立了这些小鼠也展示了早期的神经内β-分泌酶源的βAPP片段(C99)的积累,而没有β-淀粉样蛋白。有趣的是,我们发现3xTgAD的小鼠冷漠行为与C99的积累和突触的改变短暂性地相关。众所周知,既然动物模型的遗传背景可以强有力地影响行为和诱导转录变化,我们决定明确遗传背景对上述改变的影响。我们将3xTgAD小鼠与C57BL/6小鼠回交,发现遗传背景对C99的积累或突触可塑性的改变没有影响,但明显影响到冷漠行为。
关键词: 冷漠,行为,C99,LTP,免疫组化,三重转基因小鼠,遗传背景。
Current Alzheimer Research
Title:Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice
Volume: 13 Issue: 8
Author(s): R. Pardossi-Piquard, I. Lauritzen, C. Bauer, G. Sacco, P. Robert, F. Checler
Affiliation:
关键词: 冷漠,行为,C99,LTP,免疫组化,三重转基因小鼠,遗传背景。
摘要: Apathy is an early and common neuropsychiatric syndrome in Alzheimer’s disease (AD) patients. In clinical trials, apathy is associated with decreased motor activity that can be monitored by actigraphy. The triple transgenic mouse AD model (3xTgAD) has been shown to recapitulate the biochemical lesions as well as many of the synaptic and cognitive alterations associated with AD. In the present work we found that these mice also develop an early and consistent apathy-like behavior as evidenced by a drastic decrease in spontaneous activity measured by actimetry. We recently established that these mice also display an intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) appearing early, in absence of Aβ. Interestingly, we found that the apathy-like behavior observed in 3xTgAD mice was temporally associated with C99 accumulation and synaptic alterations. Since it is well known that the genetic background can strongly influence behavior and can induce transcriptional variability in animal models, we decided to determine the influence of genetic background on the above-described alterations. We backcrossed 3xTgAD mice to C57BL/6 and found that the genetic background had no influence on either C99 accumulation or synaptic plasticity alterations, but strongly affected the apathy-like behavior.
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Cite this article as:
R. Pardossi-Piquard, I. Lauritzen, C. Bauer, G. Sacco, P. Robert, F. Checler , Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice, Current Alzheimer Research 2016; 13 (8) . https://dx.doi.org/10.2174/1567205013666160404120106
DOI https://dx.doi.org/10.2174/1567205013666160404120106 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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