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首页> 外文OA文献 >Circuit-specific alterations of N-methyl-D-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys.
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Circuit-specific alterations of N-methyl-D-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys.

机译：老年猴齿状回中N-甲基-D-天冬氨酸受体亚基1的电路特异性改变。

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Age-associated memory impairment occurs frequently in primates. Based on the established importance of both the perforant path and N-methyl-D-aspartate (NMDA) receptors in memory formation, we investigated the glutamate receptor distribution and immunofluorescence intensity within the dentate gyrus of juvenile, adult, and aged macaque monkeys with the combined use of subunit-specific antibodies and quantitative confocal laser scanning microscopy. Here we demonstrate that aged monkeys, compared to adult monkeys, exhibit a 30.6% decrease in the ratio of NMDA receptor subunit 1 (NMDAR1) immunofluorescence intensity within the distal dendrites of the dentate gyrus granule cells, which receive the perforant path input from the entorhinal cortex, relative to the proximal dendrites, which receive an intrinsic excitatory input from the dentate hilus. The intradendritic alteration in NMDAR1 immunofluorescence occurs without a similar alteration of non-NMDA receptor subunits. Further analyses using synaptophysin as a reflection of total synaptic density and microtubule-associated protein 2 as a dendritic structural marker demonstrated no significant difference in staining intensity or area across the molecular layer in aged animals compared to the younger animals. These findings suggest that, in aged monkeys, a circuit-specific alteration in the intradendritic concentration of NMDAR1 occurs without concomitant gross structural changes in dendritic morphology or a significant change in the total synaptic density across the molecular layer. This alteration in the NMDA receptor-mediated input to the hippocampus from the entorhinal cortex may represent a molecular/cellular substrate for age-associated memory impairments.
机译：与年龄相关的记忆障碍经常发生在灵长类动物中。基于既定的穿孔途径和N-甲基-D-天冬氨酸（NMDA）受体在记忆形成中的重要性，我们调查了幼年，成年和成年猕猴的齿状回中谷氨酸受体的分布和免疫荧光强度。结合使用亚单位特异性抗体和定量共聚焦激光扫描显微镜。在这里，我们证明，与成年猴子相比，成年猴子的齿状回颗粒细胞远端树突中NMDA受体亚基1（NMDAR1）免疫荧光强度的比率降低了30.6％，它们从内嗅途径输入穿孔路径相对于近端树突的皮质，其从齿状齿接收固有的兴奋性输入。 NMDAR1免疫荧光中的树突状细胞内发生改变而没有非NMDA受体亚基的类似改变。与幼年动物相比，使用突触前体素反映总突触密度和微管相关蛋白2作为树突结构标记的进一步分析表明，老年动物的整个分子层的染色强度或面积没有显着差异。这些发现表明，在成年猴子中，树突状细胞内NMDAR1浓度发生了电路特异性变化，而树突状形态没有伴随的总体结构变化或整个分子层中总突触密度的显着变化。从内嗅皮质向海马的NMDA受体介导的输入中的这种改变可能代表了与年龄相关的记忆障碍的分子/细胞底物。

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