Morris water maze search strategy analysis in PDAPP mice before and after experimental traumatic brain injury
Morris water maze search strategy analysis in PDAPP mice before and after experimental traumatic brain injury
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DOI：
10.1016/j.expneurol.2005.10.020
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Holtzman, DM
中科院分区：
文献类型：
--
作者：
Brody, DL;Holtzman, DM
创伤性脑损伤（TBI）是认知功能障碍的常见原因，也是阿尔茨海默病（AD）的主要危险因素。PDAPP小鼠是一种过表达与家族性AD有关的突变型人淀粉样前体蛋白（APP）的转基因系，与野生型（WT）同窝仔相比，其在Morris水迷宫中的行为表现明显受损。PDAPP和WT小鼠在实验性TBI后表现进一步恶化。然而，所涉及的认知功能方面还没有得到很好的理解。在这里，我们分析了在中度控制性皮质撞击TBI之前和之后，3-4个月大的PDAPP和WT C57 B16同窝仔在水迷宫中使用的搜索策略。在TBI之前，PDAPP小鼠比WT小鼠使用更少的空间策略和更多的非空间系统策略以及涉及重复循环的策略。通过训练，PDAPP小鼠使用更多的空间策略和更少的重复循环。TBI后，PDAPP小鼠失去了空间策略的使用，更多地依赖于重复循环。WT小鼠中的TBI也减少了它们对空间策略的使用，而是导致了非空间系统策略的转变。我们还分析了小鼠使用每种策略的效率变化，但发现使用哪种策略的差异定量解释了组间表现的大部分差异。这些结果表明，除了对空间学习和记忆的影响之外，次优搜索策略的使用是PDAPP小鼠表现受损和TBI后进一步恶化的基础。人类TBI患者可能具有类似的问题解决策略的不良使用。(c)2005年爱思唯尔公司All rights reserved.
Traumatic brain injury (TBI) is a common cause of cognitive dysfunction and a major risk factor for Alzheimer's disease (AD). PDAPP mice, a transgenic line overexpressing a mutant human amyloid precursor protein (APP) implicated in familial AD, have markedly impaired behavioral performance in the Morris water maze relative to wild-type (WT) littermates. Performance further deteriorates following experimental TBI in both PDAPP and WT mice. However, the aspects of cognitive function involved are not well understood. Here, we have analyzed search strategies used in the water maze by 3-4 month old PDAPP and WT C57B16 littermates both before and after moderate controlled cortical impact TBI. Prior to TBI, PDAPP mice used less spatial strategies and more nonspatial systematic strategies and strategies involving repetitive looping than WT mice. With training, PDAPP mice used more spatial strategies and less repetitive looping. After TBI, PDAPP mice lost use of spatial strategies and relied more on repetitive looping. TBI in WT mice also reduced their use of spatial strategies but instead caused a switch to nonspatial systematic strategies. We also analyzed changes in the efficiency with which mice used each individual strategy, but found that differences in which strategies were used quantitatively accounted for most of the differences in performance between groups. These results demonstrate that suboptimal search strategy use in addition to effects on spatial learning and memory underlies the impaired performance of PDAPP mice and further deterioration following TBI. Human TBI patients may have analogous poor use of problem solving strategies. (c) 2005 Elsevier Inc. All rights reserved.