Age-related alteration of emotional regulation in the BACHD rat model of Huntington disease.,Genes, Brain and Behavior

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Age-related alteration of emotional regulation in the BACHD rat model of Huntington disease.
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2019-12-28 , DOI: 10.1111/gbb.12633
Charlotte Lamirault ₁ , Huu Phuc Nguyen ₂ , Valérie Doyère ₁ , Nicole El Massioui ₁

Affiliation

Huntington's disease (HD) is a genetic neurodegenerative disorder, caused by an expanded CAG repeat in the gene encoding the huntingtin protein. At the premanifest phase, before motor symptoms occur, psychiatric and emotional disorders are observed with high prevalence in HD patients. Agitation, anxiety and irritability are often described but also depression and/or apathy, associated with a lack of emotional control. The aim of the present study was to better circumscribe and understand the emotional symptoms and assess their evolution according to the progression of the disease using a transgenic HD model, BACHD rats, at the age of 4, 12 and 18 months. To achieve this goal, we confronted animals to two types of tests: first, tests assessing anxiety like the light/dark box and the conflict test, which are situations that did not involve an obvious threat and tests assessing the reactivity to a present threat using confrontation with an unknown conspecific (social behavior test) or with an aversive stimulus (fear conditioning test). In all animals, results show an age‐dependent anxiety‐like behavior, particularly marked in situation requiring passive responses (light/dark box and fear conditioning tests). BACHD rats exhibited a more profound alteration than WT animals in these tests from an early stage of the disease whereas, in tasks requiring some kind of motivation (for food or for social contacts), only old BACHD rats showed high anxiety‐like behavior compared to WT, may be partly due to the other symptoms' occurrence at this stage: locomotor difficulties and/or apathy.

中文翻译：

亨廷顿病的BACHD大鼠模型中与年龄相关的情绪调节改变。

亨廷顿舞蹈病（HD）是一种遗传性神经退行性疾病，由亨廷顿蛋白编码基因中CAG重复序列的扩增引起。在预示阶段，在运动症状出现之前，在HD患者中发现精神病和情绪障碍的患病率很高。经常描述躁动，焦虑和烦躁，但也伴有情绪低落的抑郁和/或冷漠。本研究的目的是使用转基因高清模型BACHD大鼠在4、12和18个月大时更好地界定和理解情绪症状，并根据疾病的进展评估其演变。为了实现这一目标，我们将动物面对两种类型的测试：首先，评估焦虑的测试（例如明/暗盒）和冲突测试，那些没有明显威胁的情况，并使用对抗性未知的特定行为（社交行为测试）或厌恶刺激（恐惧条件测试）进行测试以评估对当前威胁的反应性。在所有动物中，结果均显示出与年龄有关的焦虑样行为，特别是在需要被动反应（光/暗盒和恐惧条件测试）的情况下尤为明显。从疾病的早期开始，BACHD大鼠在这些测试中表现出比WT动物更深刻的改变，而在需要某种动机（用于食物或社交活动）的任务中，只有老BACHD大鼠表现出比焦虑动物更高的焦虑样行为。 WT，可能部分是由于在此阶段出现了其他症状：运动困难和/或冷漠。

更新日期：2019-12-28

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