Impaired learning and memory in Pitx3 deficient aphakia mice:: A genetic model for striatum-dependent cognitive symptoms in Parkinson's disease
Impaired learning and memory in Pitx3 deficient aphakia mice:: A genetic model for striatum-dependent cognitive symptoms in Parkinson's disease
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DOI：
10.1016/j.nbd.2008.05.017
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发表时间：
2008-09-01
影响因子：
6.1
通讯作者：
Kim, Kwang-Soo
中科院分区：
文献类型：
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作者：
Ardayfio, Paul;Moon, JiSook;Kim, Kwang-Soo
帕金森氏病(PD)和亨廷顿病等基底节疾病通常被认为主要是运动障碍：然而，这些疾病的认知症状，如执行功能障碍、学习、记忆和注意力障碍是突出的，往往比标志性的运动症状更致残。在帕金森病的临床前研究中，帕金森病的认知特征往往被忽视，这可能是由于缺乏可用的动物模型来研究它们。无晶状体小鼠缺乏转录因子Pitx3，建立了帕金森病选择性黑质纹状体DA丢失的模型。在这里，我们报告了无晶状体小鼠在纹状体依赖的认知任务中受到损害，包括旋转学习、T迷宫和抑制性回避任务，但不包括纹状体非依赖的食物偏好社会传递任务。这些结果表明，帕金森病的一些神经精神症状与疾病的病理生理学有关，而不是与疾病负担或用于治疗帕金森病的药物相关的压力。此外，无晶状体小鼠可作为帕金森病非运动性症状的新模型。(C)2008 Elsevier Inc.保留所有权利。
Disorders of the basal ganglia such as Parkinson's disease (PD) and Huntington's disease are commonly thought of primarily as motor disorders: however, the cognitive symptoms of these diseases such as executive dysfunction, learning, memory and attention deficits are prominent and often more disabling than the hallmark motor symptoms. Cognitive features of PD are often neglected in preclinical studies of PD, likely due to the lack of available animal models to study them. Aphakia mice, which are deficient in the transcription factor Pitx3, model the selective nigrostriatal DA loss in PD. Here we report that aphakia mice are impaired in striatum-dependent cognitive tasks including rotarod learning, T-maze and inhibitory avoidance tasks, but not the striatum-independent social transmission of food preference task. These results suggest that some neuropsychiatric symptoms in PD are related to the pathophysiology of the disease rather than stress associated with disease burden, or medications used to treat PD. Furthermore aphakia mice may be used as a novel model of non-motor symptoms in PD. (C) 2008 Elsevier Inc. All rights reserved.