Molecular and Cellular Biology Program & Dept. of Biomedical Science, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Behav Brain Res. 2011 Sep 12;222(1):122-33. doi: 10.1016/j.bbr.2011.03.045. Epub 2011 Apr 2.
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.
与不同 NMDA 受体亚单位的 mRNA 和蛋白表达变化相关的与年龄相关的记忆衰退。NMDA 受体 GluN1 亚单位似乎是受体功能所必需和充分的。有证据表明，一些亚单位剪接形式的 mRNA 表达受老年和/或老年小鼠行为测试经验的影响。本研究探讨了在衰老过程中大脑前额叶/额叶中不同 GluN1 亚单位异构体的行为测试经验与蛋白表达之间的关系。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的表现均下降。观察到 GluN1 C 末端盒 C2 和 C2'，但不是 C1 或 N1 盒，的蛋白表达随年龄的增加而下降，无论经验如何。在中年动物中，GluN1 亚单位和 C2'盒蛋白的高表达与初始搜索时的良好参考记忆有关。GluN1 亚单位含有 C1 盒和整个 GluN1 亚单位的蛋白表达较高的老年动物在探针试验的最后阶段更接近先前平台的位置。然而，在这一阶段，C1 盒高表达的老年小鼠并没有表现出准确的搜索。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，不同剪接盒的 GluN1 亚单位的表达受衰老影响存在异质性。这也表明，在中年时，GluN1 亚单位可能对良好的参考记忆最重要，但这种关系可能无法维持到老年。
