Age-related declines in a two-day reference memory task are associated with changes in NMDA receptor subunits in mice.

Age-related declines in a two-day reference memory task are associated with changes in NMDA receptor subunits in mice.
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DOI:
10.1186/1471-2202-8-43
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发表时间:
2007-06-22
期刊:
影响因子:
2.4
通讯作者:
Hammersmark R
Hammersmark R
中科院分区:
医学4区
文献类型:
--
作者:
Magnusson KR;Scruggs B;Zhao X;Hammersmark R

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C57 BL/6小鼠在12天任务中显示了衰老期间NMDA受体表达与空间参考记忆表现之间的关系。本研究旨在确定是否可以用较短的测试方案检测到与年龄相关的缺陷,以及这些缺陷是否与NMDA受体有关。小鼠在Morris水迷宫中在参考记忆任务中训练两天。在参考记忆测试之后或之前进行提示测试。从首先进行参照记忆测试的小鼠的前额叶/额叶皮质和海马体制备粗突触体。用Western blotting分析NMDA受体亚单位和syntaxin蛋白。当在提示测试之前进行参考记忆测试时,年轻小鼠在探测和位置学习方面表现出显着的改善。一个显着的性能下降之间的3个月和26个月的年龄与两天的参考任务,无论是否进行线索测试之前或之后的参考记忆测试。前额叶/额叶皮质中NMDA受体和突触融合蛋白的ε2和ζ1亚基的蛋白表达显着下降。亚基的变化表现出显着的相关性与地方和探测试验性能。无论何时进行线索试验,参考记忆任务的表现都存在与年龄相关的下降,这表明这些缺陷是由于空间参考记忆任务所特有的因素造成的。这些结果还表明,在特定的NMDA受体亚基的前额叶/额叶脑区的突触池中的下降,这些与年龄有关的问题与执行空间参考记忆任务。
C57BL/6 mice show a relationship during aging between NMDA receptor expression and spatial reference memory performance in a 12-day task. The present study was designed to determine if age-related deficits could be detected with a shorter testing protocol and whether these deficits showed a relationship with NMDA receptors. Mice were trained in a reference memory task for two days in a Morris water maze. Cued testing was performed either after or prior to reference memory testing. Crude synaptosomes were prepared from prefrontal/frontal cortex and hippocampus of the mice that underwent reference memory testing first. NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting. Young mice showed significant improvement in probe and place learning when reference memory testing was done prior to cued testing. A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing. There was a significant decline in the protein expression of the ε2 and ζ1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex. The subunit changes showed a significant correlation with both place and probe trial performance. The presence of an age-related decline in performance of the reference memory task regardless of when the cued trials were performed suggests that the deficits were due to factors that were unique to the spatial reference memory task. These results also suggest that declines in specific NMDA receptor subunits in the synaptic pool of prefrontal/frontal brain regions contributed to these age-related problems with performing a spatial reference memory task.
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