Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia
Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia
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DOI：
10.1016/j.neurobiolaging.2013.12.023
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发表时间：
2014-07-01
影响因子：
4.2
通讯作者：
Fryer, John D.
中科院分区：
文献类型：
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作者：
Cook, Casey;Dunmore, Judy H.;Fryer, John D.
17号染色体相关额颞叶痴呆伴帕金森病（FTDP-17）是一种由tau基因（MAPT）突变引起的神经退行性tau病。患有FTDP-17的个体在学习、记忆和语言方面存在缺陷，此外还有个性和行为改变，通常以缺乏社交抑制为特征。一些表达tau突变的转基因小鼠模型已经被广泛地用于记忆或运动障碍的测试，尽管缺乏关于杏仁体依赖行为的报道。为此，我们在行为电池上测试了rTg4510小鼠模型，其中包括杏仁核依赖的探索任务。正如预期的那样，rTg4510小鼠在海马体依赖性学习和记忆测试中表现出严重的损伤，包括情境恐惧条件反射。然而，rTg4510小鼠在野外实验中也表现出异常的高探索性表型，增加了迷宫，光-暗探索和暗示恐惧条件反射，表明杏仁核功能障碍。此外，在rTg4510小鼠和人类FTDP-17患者的杏仁核中都检测到显著的tau负荷，这表明rTg4510小鼠模型再现了FTDP-17特征的杏仁核行为障碍和神经变性。(C) 2014爱思唯尔公司版权所有。
Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17. (C) 2014 Elsevier Inc. All rights reserved.