Clemensson Erik Karl Håkan, Clemensson Laura Emily, Riess Olaf, Nguyen Huu Phuc
Institute of Medical Genetics and Applied Genomics, Tuebingen, Germany.
Centre for Rare Diseases, Tuebingen, Germany.
PLoS One. 2017 Jan 3;12(1):e0169051. doi: 10.1371/journal.pone.0169051. eCollection 2017.
The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.
BACHD大鼠是最近开发的亨廷顿病转基因动物模型，亨廷顿病是一种进行性神经退行性疾病，其特征是纹状体神经元大量丧失。认知障碍在患者中很常见，因此在该疾病的动物模型中表征类似的缺陷很有意义。本研究评估了BACHD大鼠在延迟交替和延迟位置匹配测试中的表现，这两项基于斯金纳箱的短期记忆功能测试。转基因大鼠在两项测试中均表现受损，表明在处理测试基本方面存在普遍问题，而短期记忆似乎完好无损。在患有额纹状体损伤的大鼠中也发现了类似的表型，这表明BACHD大鼠可能存在与亨廷顿病相关的神经病理学。进一步分析表明，延迟交替测试中的表现缺陷可能是由于抑制控制受损，这在亨廷顿病患者中也有涉及。该研究最终表明，BACHD大鼠可能患有类似于亨廷顿病患者的神经病理学和认知障碍。
