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Validation of behavioral phenotypes in the BACHD rat model.
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2020-06-20 , DOI: 10.1016/j.bbr.2020.112783
Arianna Novati 1 , Giuseppe Manfré 2 , Stefanie Flunkert 3 , Johanneke E Van der Harst 4 , Judith R Homberg 5 , Robert Wronski 3 , Huu Phuc Nguyen 6
Affiliation  

Huntington disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion in the HTT gene. Various HD animal models have been generated to mimic the motor, cognitive and neuropsychiatric disturbances that affect HD patients. Reproducing disease phenotypes within these models is essential to identify reliable readouts for therapy studies. We validated behavioral phenotypes shown earlier by other research groups in the BACHD rat model, using both previously applied and novel tests for motor, cognitive and anxiety-like behaviors. We first confirmed known BACHD rats’ phenotypes in rotarod, open field (OF) and elevated plus maze (EPM) tests. We then assessed the reproducibility of key phenotypes in the model using new tests: cliff hanging, passive avoidance (PA), Morris water maze (MWM), light dark box and light spot tests. We confirmed impaired motor coordination in the rotarod test and reduced activity in the OF. In line with earlier results in BACHD rats using different tests, we showed impaired reversal learning in MWM and decreased anxiety-like behavior with the light spot test supporting the validity of BACHD rats as a model of HD. Results in the EPM, light dark box, cliff hanging and PA tests did not confirm earlier findings. This may depend on phenotype inconsistencies or rather be related to differences in environmental variables, test typology, experimental settings, animal age and chosen behavioral parameters.



中文翻译:

BACHD 大鼠模型中行为表型的验证。

亨廷顿病 (HD) 是一种由HTT 中多聚谷氨酰胺扩张引起的神经退行性疾病基因。已经生成了各种 HD 动物模型来模拟影响 HD 患者的运动、认知和神经精神障碍。在这些模型中重现疾病表型对于确定治疗研究的可靠读数至关重要。我们使用先前应用的和新的运动、认知和焦虑样行为测试,验证了其他研究小组之前在 BACHD 大鼠模型中显示的行为表型。我们首先在旋转棒、开放场 (OF) 和高架十字迷宫 (EPM) 测试中确认了已知的 BACHD 大鼠的表型。然后,我们使用新测试评估了模型中关键表型的可重复性:悬崖悬挂、被动回避 (PA)、莫里斯水迷宫 (MWM)、浅暗箱和亮点测试。我们在旋转棒测试中证实了运动协调受损和 OF 活动减少。与使用不同测试的 BACHD 大鼠的早期结果一致,我们在 MWM 中显示出受损的逆转学习和减少的焦虑样行为,光斑测试支持 BACHD 大鼠作为 HD 模型的有效性。EPM、浅暗盒、悬崖悬挂和 PA 测试的结果并未证实早期的发现。这可能取决于表型不一致,或者与环境变量、测试类型、实验设置、动物年龄和所选行为参数的差异有关。

更新日期:2020-07-08
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