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斯特拉斯堡遗传性癫痫大鼠(GAERS)的焦虑和运动行为:将 Wistar 大鼠作为第二个对照纳入。

Anxiety and locomotion in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): inclusion of Wistar rats as a second control.

机构信息

Laboratory of Cognitive and Adaptive Neuroscience (LNCA), Faculty of Psychology, UMR 7364, University of Strasbourg - CNRS, Strasbourg, France; Faculty of Medicine, INSERM U 666, University of Strasbourg, Strasbourg, France.

出版信息

Epilepsia. 2014 Sep;55(9):1460-8. doi: 10.1111/epi.12738. Epub 2014 Jul 24.

Abstract

OBJECTIVE

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a genetic model, derived from Wistar rats by selective breeding. In all previous studies, GAERS were compared to their paired selected strain not expressing spike-and-wave discharges (SWDs), namely nonepileptic controls (NECs). Because the occurrence/absence of SWDs is of polygenic origin, some other traits could have been selected along with occurrence/absence of SWDs. Therefore, we explored the importance of using a second control group consisting in Wistar rats, the strain of origin of GAERS, in addition to NECs, on locomotion and anxiety in GAERS.

METHODS

A test battery encompassing home-cage, open-field, beam-walking and elevated plus-maze evaluations was used. In addition, stereologic analyses were performed to assess the volume of thalamus, amygdala, and hippocampus. The occurrence/absence of SWDs was determined in all three strains by electroencephalography (EEG) recording.

RESULTS

When compared to NECs and Wistars, GAERS displayed lower exploratory activity and fastened habituation to novelty. In the plus-maze, scores of GAERS and Wistars were similar, but NECs appeared significantly less anxious (possibly in association with increased amygdala volume); evidence for weaker anxiety in NECs was also found in the open-field evaluation. The volumetric study revealed increased thalamic volume in GAERS compared to both control groups. SWDs were present in all GAERS and in 80% of Wistars.

SIGNIFICANCE

Compared to the original Wistar strain as an additional control group, the selective breeding that generated the GAERS has no incidence on anxiety-related behavior, conversely to the selection of SWD suppression in NECs, in which anxiety is attenuated. These findings point to the importance of using a second control group composed of Wistar rats in studies characterizing the behavioral profile of GAERS. Thereby, possible confusions between occurrence/absence of SWDs and other features that come along with selection and/or differential brain development induced by the genetic mutations are reduced.

摘要

目的

斯特拉斯堡遗传性癫痫大鼠(GAERS)是一种遗传模型,由 Wistar 大鼠通过选择性繁殖衍生而来。在之前的所有研究中,GAERS 均与不表达棘波和尖波放电(SWD)的配对选择株(即非癫痫对照(NECs))进行比较。由于 SWD 的发生/缺失具有多基因遗传基础,因此在选择 SWD 的发生/缺失的同时,可能还选择了其他一些特征。因此,我们探讨了使用第二个对照组(即 GAERS 的原始 Wistar 株)的重要性,该对照组除了 NECs 外,还包括 GAERS 的运动和焦虑。

方法

采用包括笼内、旷场、走棒和高架十字迷宫评估的测试组合。此外,还进行了立体学分析以评估丘脑、杏仁核和海马体的体积。通过脑电图(EEG)记录,在所有三个品系中确定 SWD 的发生/缺失。

结果

与 NECs 和 Wistars 相比,GAERS 的探索性活动较低,对新奇事物的适应较快。在高架十字迷宫中,GAERS 和 Wistars 的评分相似,但 NECs 的焦虑程度明显较低(可能与杏仁核体积增加有关);在旷场评估中也发现了 NECs 焦虑程度较弱的证据。体积研究显示,与两个对照组相比,GAERS 的丘脑体积增加。所有 GAERS 以及 80%的 Wistars 均存在 SWD。

意义

与作为附加对照组的原始 Wistar 株相比,产生 GAERS 的选择性繁殖对与焦虑相关的行为没有影响,而在 NECs 中抑制 SWD 的选择则相反,后者会减轻焦虑。这些发现表明,在研究 GAERS 的行为特征时,使用由 Wistar 大鼠组成的第二个对照组非常重要。这样可以减少由于基因突变引起的选择和/或脑发育差异而导致的 SWD 的发生/缺失与其他特征之间的混淆。

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