Changes in expression of splice cassettes of NMDA receptor GluN1 subunits within the frontal lobe and memory in mice during aging.
Changes in expression of splice cassettes of NMDA receptor GluN1 subunits within the frontal lobe and memory in mice during aging.
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DOI：
10.1016/j.bbr.2011.03.045
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发表时间：
2011-09-12
影响因子：
2.7
通讯作者：
Magnusson, Kathy R.
中科院分区：
文献类型：
--
作者：
Das, Siba R.;Magnusson, Kathy R.
关键词：
年龄相关的记忆力下降与不同 NMDA 受体亚基 mRNA 和蛋白质表达的变化有关。 NMDA 受体 GluN1 亚基对于受体功能来说似乎是必要且充分的。有证据表明，某些亚基剪接形式的 mRNA 表达受到衰老和/或老年小鼠行为测试经历的影响。本研究探讨了衰老过程中行为测试经历与大脑前额叶/额叶皮层不同 GluN1 亚基异构体的蛋白质表达之间的关系。具有行为测试经验的老年 C57BL/6 小鼠在空间工作和参考记忆任务中表现出下降。无论经验如何，GluN1 C 末端盒 C2 和 C2'（而非 C1 或 N1 盒）的蛋白质表达随着年龄的增长而下降。在中年动物中，GluN1 亚基和 C2' 盒蛋白的较高表达与初始搜索时良好的参考记忆相关。含有 C1 盒的 GluN1 亚基蛋白表达较高的老年动物和整个 GluN1 亚基群体在探针试验的最后阶段表现出更接近以前的平台位置。然而，C1盒高表达的老年小鼠在此阶段并未表现出准确的搜索。 C1盒蛋白表达较低的老年小鼠更接近年轻和中年小鼠的表现。这些结果表明，衰老对含有不同剪接盒的 GluN1 亚基表达的影响存在异质性。它还表明，GluN1 亚基可能对于中年时期的良好参考记忆最为重要，但这种关系可能不会维持到老年。
Age-related decline in memory has been associated with changes in mRNA and protein expression of different NMDA receptor subunits. The NMDA receptor GluN1 subunit appears to be necessary and sufficient for receptor function. There is evidence that the mRNA expressions of some splice forms of the subunit are influenced by aging and/or behavioral testing experience in old mice. The present study explored the relationships between behavioral testing experience and protein expression of different GluN1 subunit isoforms in the prefrontal/frontal cortex of the brain during aging. Aged C57BL/6 mice with behavioral testing experience showed declines in performance in both spatial working and reference memory tasks. Protein expression of GluN1 C-terminal cassettes C2 and C2′, but not the C1 or N1 cassettes, was observed to decline with increasing age, regardless of experience. In middle-age animals, higher expressions of the GluN1 subunit and C2′ cassette proteins were associated with good reference memory on initial search. Aged animals with a higher protein expression of GluN1 subunits containing C1 cassettes and the whole population of GluN1 subunits exhibited a closer proximity to the former platform location within the final phase of probe trials. However, the old mice with high expression of the C1 cassette did not show an accurate search during this phase. The old mice with lower expression of the C1 cassette protein more closely mimicked the performances of the young and middle-aged mice. These results indicate that there was heterogeneity in the effect of aging on the expression of the GluN1 subunits containing different splice cassettes. It also suggests that the GluN1 subunit might be most important for good reference memory during middle age, but this relationship may not be maintained into old age.
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影响因子：
1.9
作者：
GALLAGHER, M;BURWELL, RD;BURCHINAL, M
通讯作者：
BURCHINAL, M
影响因子：
2.9
作者：
Das, Siba R.;Magnusson, Kathy R.
通讯作者：
Magnusson, Kathy R.
影响因子：
4.2
作者：
BARNES, CA
通讯作者：
BARNES, CA
影响因子：
1.8
作者：
DEAN, RL;SCOZZAFAVA, J;BARTUS, RT
通讯作者：
BARTUS, RT
DOI：
10.1073/pnas.90.14.6731
发表时间：
1993-07-15
影响因子：
11.1
作者：
DURAND, GM;BENNETT, MVL;ZUKIN, RS
通讯作者：
ZUKIN, RS