The effects of aging on N-methyl-D-aspartate receptor subunits in the synaptic membrane and relationships to long-term spatial memory.
The effects of aging on N-methyl-D-aspartate receptor subunits in the synaptic membrane and relationships to long-term spatial memory.
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DOI：
10.1016/j.neuroscience.2009.05.018
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发表时间：
2009-09-15
期刊：
影响因子：
3.3
通讯作者：
Magnusson, K. R.
中科院分区：
文献类型：
--
作者：
Zhao, X.;Rosenke, R.;Kronemann, D.;Brim, B.;Das, S. R.;Dunah, A. W.;Magnusson, K. R.
C57 BL/6小鼠大脑皮层和海马中N-甲基-D-天冬氨酸（NMDA）受体NR 2B（小鼠ε2）和NR 1（小鼠ε 1）亚单位的蛋白表达在衰老过程中下降。这项研究旨在确定是否有一个更大的影响老化的亚基表达和长期空间记忆和亚基表达之间的关系比在整个细胞内的突触膜。在Morris水迷宫中测试雄性C57 BL/6 JNIA小鼠（4、11和26月龄）的长期空间记忆。额皮质，包括前额叶区，和海马均质化和分馏成轻和突触体膜馏分。采用蛋白质印迹法分析NMDA受体NR 2B和NR 1亚基的蛋白表达。老年小鼠在空间任务中的表现显着低于其他年龄。在额叶皮层，NR 2B亚基的蛋白质水平表现出更大的下降与老化的突触膜部分比在整个匀浆，而在海马类似的年龄相关的下降，观察到在这两个部分。衰老对NR 1亚基的表达没有显著影响。在中年小鼠组中，突触膜中NR 2B和NR 1亚基的高表达与更好的记忆力相关。然而，在老年小鼠中，这两种亚基的高表达与记忆力下降有关。这些结果表明，老化可能会改变NR 2B亚单位的额叶皮质内的突触膜的本地化。相关性结果表明，NMDA受体的功能，受体亚基的组成，和/或在海马中的受体相互作用的环境是不一样的，在老年动物在年轻的小鼠，这可能有助于在衰老过程中的记忆力下降。
There are declines in the protein expression of the NR2B (mouse ε2) and NR1 (mouse ζ1) subunits of the N-methyl-D-aspartate (NMDA) receptor in the cerebral cortex and hippocampus during aging in C57BL/6 mice. This study was designed to determine if there is a greater effect of aging on subunit expression and a stronger relationship between long-term spatial memory and subunit expression within the synaptic membrane than in the cell as a whole. Male, C57BL/6JNIA mice (4, 11 & 26 months old) were tested for long-term spatial memory in the Morris water maze. Frontal cortex, including prefrontal regions, and hippocampus were homogenized and fractionated into light and synaptosomal membrane fractions. Western blots were used to analyze protein expression of NR2B and NR1 subunits of the NMDA receptor. Old mice performed significantly worse than other ages in the spatial task. In the frontal cortex, the protein levels of the NR2B subunit showed a greater decline with aging in the synaptic membrane fraction than in the whole homogenate, while in the hippocampus a similar age-related decline was observed in both fractions. There were no significant effects of aging on the expression of the NR1 subunit. Within the middle-aged mouse group, higher expression of both NR2B and NR1 subunits in the synaptic membrane was associated with better memory. In the aged mice, however, higher expression of both subunits was associated with poorer memory. These results indicate that aging could be altering the localization of the NR2B subunit to the synaptic membrane within the frontal cortex. The correlational results suggest that NMDA receptor functions, receptor subunit composition, and/or the environment in which the receptor interacted in the hippocampus were not the same in the old animals as in younger mice and this may have contributed to memory declines during aging.
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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：
4.8
作者：
Clayton, DA;Grosshans, DR;Browning, MD
通讯作者：
Browning, MD
影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA