Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-D-aspartate receptor and spatial memory in aged mice
Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-D-aspartate receptor and spatial memory in aged mice
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DOI：
10.1016/j.brainres.2008.02.046
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发表时间：
2008-05-01
期刊：
影响因子：
2.9
通讯作者：
Magnusson, Kathy R.
中科院分区：
文献类型：
--
作者：
Das, Siba R.;Magnusson, Kathy R.
在小鼠和大鼠中已经观察到NMDA受体zeta 1（NR 1）亚基的一些剪接形式的蛋白质和mRNA表达的与NMDA相关的变化。本研究的目的是确定是否个别剪接形式的1亚基的NMDA受体在前额叶/额叶皮层区域有助于记忆缺陷在老化过程中，是否在学习任务的经验可以影响剪接形式的表达。通过原位杂交检测4种剪接形式（zeta 1-1、zeta 1-3、zeta 1-a和zeta 1-B）和所有已知剪接形式（zeta 1-pan）的mRNA表达。尽管zeta 1-pan mRNA的总体表达并没有受到衰老的显著影响，但在几个脑区，C-末端剪接形式zeta 1-1（+C1和+ C2盒）和zeta 1-3（+ C1和+C2 '）的mRNA在衰老过程中表现出显著的下降。这表明这些剪接形式比整个亚基更受衰老的影响。相对于年轻组，有行为经验的老年小鼠中zeta 1-a（-N1盒）剪接形式的表达增加。在眶皮层zeta 1-a剪接形式的mRNA表达水平较高的老年小鼠在工作记忆任务中表现最好，但在线索联想学习任务中表现最差。这些结果表明，在衰老过程中，1剪接形式表达和记忆任务的表现之间存在复杂的相互作用。(C)2008 Elsevier B. V.保留所有权利。
Age-related changes in the protein and mRNA expression of some of the splice forms of the zeta 1 (NR1) subunit of the NMDA receptor have been seen in mice and rats. The present study was designed to determine whether individual splice forms of the 1 subunit of the NMDA receptor within prefrontal/frontal cortical regions contribute to memory deficits during aging and whether experience in learning tasks can influence the expression of the splice forms. mRNA expression of 4 splice forms (zeta 1-1, zeta 1-3, zeta 1-a and zeta 1-b) and mRNA for all known splice forms (zeta 1-pan) were examined by in situ hybridization. mRNA for C-terminal splice forms, zeta 1-1 (+ C1 and + C2 cassettes) and zeta 1-3 (+ C1 and + C2') showed significant declines during aging in several brain regions even though overall zeta 1-pan mRNA expression was not significantly affected by aging. This suggests that these splice forms are more influenced by aging than the subunit as a whole. There was an increase in the expression of zeta 1-a (-N1 cassette) splice form in the behaviorally-experienced old mice relative to the younger groups. Old mice with high levels of mRNA expression for the zeta 1-a splice form in orbital cortex showed the best performances in the working memory task, but the poorest performances in the cued, associative learning task. These results suggest that there is a complex interaction between 1 splice form expression and performance of memory tasks during aging. (C) 2008 Elsevier B.V. All rights reserved.