Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's disease
Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's disease
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DOI：
10.1016/j.brainresbull.2006.02.011
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发表时间：
2006-04-28
影响因子：
3.8
通讯作者：
Dunnett, SB
中科院分区：
文献类型：
--
作者：
Brooks, SP;Betteridgea, H;Dunnett, SB
人们发现患有早期亨廷顿舞蹈症的人在进行超维度转变方面存在特定缺陷。迄今为止，在该疾病的转基因或敲入啮齿动物模型中尚未发现这种缺陷的证据。本文的目的是测试源自 Hdh(CAG(150)) 小鼠品系的纯合敲入小鼠在五种二选一辨别任务（简单、复合、复合反转、维度内移动和维度外移动）中是否受损，以及这些小鼠在第二天回忆这些任务时是否受损。在超维度转换任务中，Hdh(CAG(150)) 纯合子小鼠比小鼠需要更多的试验才能达到标准，并且试验中正确选择的百分比也比动物显着降低。对于回忆任务，在 Hdh(CAG(150)) 纯合小鼠中发现了回忆化合物逆转测试的缺陷，无论是达到标准所需的试验次数还是试验中正确选择的百分比。当通过正确选择的百分比来衡量时，这些动物对维度内转换任务的回忆也受到损害。我们的结果表明，Hdh(CAG(150)) 小鼠不仅在与人类研究一致的外维度转换性能上存在明显缺陷，而且在复合逆转和内维度转换任务的回忆任务上也存在明显缺陷。 (c) 2006 Elsevier Inc. 保留所有权利。
People with early-stage Huntington's disease have been found to have a specific deficit in performing an extra-dimensional shift. To date no evidence of this deficit has been identified in transgenic or knock-in rodent models of the disease. The aim of the present paper then, was to test whether homozygous knock-in mice derived from the Hdh(CAG(150)) mouse line were impaired in any of five 2-choice discrimination tasks (simple, compound, compound reversal, intra-dimensional shift and extra-dimensional shift), and whether these mice were impaired at recalling these tasks on the following day. On the extra-dimensional shift task the Hdh(CAG(150)) homozygous mice required a greater number of trials to reach criteria than mice and the percentage of correct choices within the trials was also significantly reduced compared with the animals. For the recall tasks, a deficit for recalling the compound reversal test was found in the Hdh(CAG(150)) homozygous mice for both number of trials required to reach criteria and percentage of correct choices within the trials. Recall for the intra-dimensional shift task was also impaired in these animals when measured by the percentage of correct choices. Our results demonstrate a pronounced deficit in the Hdh(CAG(150)) mice not only on extra-dimensional shift performance in agreement with human studies, but also on recall tasks for both the compound reversal and the intra-dimensional shift tasks. (c) 2006 Elsevier Inc. All rights reserved.