Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.
Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.
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DOI：
10.1016/j.neuroscience.2016.12.041
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发表时间：
2017-03-06
期刊：
影响因子：
3.3
通讯作者：
Magnusson KR
中科院分区：
文献类型：
--
作者：
Márquez Loza A;Elias V;Wong CP;Ho E;Bermudez M;Magnusson KR
与年龄相关的长期和短期记忆下降与N-甲基-D-天冬氨酸(NMDA)受体表达减少有关，这可能与炎症有关。这项研究旨在确定抗炎药布洛芬在衰老过程中对认知功能和NMDA受体表达的影响。雄性C57BL/6小鼠(5、14、20和26个月龄)在试验前分别饲喂布洛芬(375ppm)NIH31饲料或单独饲料6周。用Morris水迷宫进行的行为学测试表明，在空间长期记忆、反转和短期记忆任务中，年龄较大的小鼠表现明显比年轻小鼠差。布洛芬提高了短期记忆任务的整体表现，但这似乎更多地与执行功能的改善有关，而不是记忆。布洛芬诱导的GluN2B亚单位、所有GluN1剪接变体和GluN1-1剪接形式的mRNA密度在所有年龄组均显著降低，在海马区GluN2A、GluN2B和GluN1 C2‘盒的蛋白表达显著降低。布洛芬治疗组小鼠额叶GluN1-3剪接体mRNA和C2‘盒蛋白在各年龄组均显著增加。布洛芬不改变促炎细胞因子IL-1β和肿瘤坏死因子α的表达，但减少了老龄小鼠额叶皮质星形胶质细胞免疫反应染色的面积。执行功能的增强与GluN1-3mRNA的增加和胶质细胞的减少有关。这些发现表明，炎症可能在老年动物执行功能下降中发挥作用，但布洛芬对NMDA受体的其他影响似乎与衰老或炎症无关。
Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-D-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26 months) were fed ibuprofen (375 ppm) in NIH31 diet or diet alone for 6 weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2′ cassettes in the hippocampus. GluN1-3 splice form mRNA and C2′ cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation.