N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation
N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation
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DOI：
10.1097/wnr.0000000000001893
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发表时间：
2023-03
期刊：
影响因子：
1.7
通讯作者：
Hikaru Iwashita;Masahiro Sano;M. Kawaguchi;A. Chiba
中科院分区：
文献类型：
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作者：
Hikaru Iwashita;Masahiro Sano;M. Kawaguchi;A. Chiba
目的褪黑激素（Melatonin，MEL）具有增强认知功能的作用。最近，我们已经证明，MEL代谢产物N-乙酰基-5-甲氧基犬尿胺（AMK）促进长期物体识别记忆的形成比MEL更有效。在这里，我们研究了1 mg/kg MEL和AMK对物体位置记忆和空间工作记忆的影响。我们还研究了相同剂量的这些药物对海马（HP）、嗅周皮质（PRC）和内侧前额叶皮质（mPFC）中记忆相关蛋白的相对磷酸化/活化水平的影响。方法分别采用物体定位任务和Y迷宫自发交替任务评价物体位置记忆和空间工作记忆。使用蛋白质印迹分析评估记忆相关蛋白的相对磷酸化/活化水平。结果AMK和MEL均能增强物体位置记忆和空间工作记忆。AMK处理后2 h，HP和mPFC中cAMP反应元件结合蛋白（CREB）的磷酸化增加。AMK还增加了细胞外信号调节激酶（ERK）的磷酸化，但减少了Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）在PRC和mPFC处理后30分钟。MEL增加CREB磷酸化的HP治疗后2小时，而没有检测到的变化，在其他蛋白质检查观察。结论与MEL相比，AMK可能通过更显著地改变记忆相关蛋白如ERK、CaMKIIs和CREB在更广泛的脑区（包括HP、mPFC和PRC）的活化，从而发挥更强的记忆增强作用。
Objectives Melatonin (MEL) has been reported to enhance cognitive performance. Recently, we have demonstrated that a MEL metabolite N-acetyl-5-methoxykynuramine (AMK) promoted the formation of long-term object recognition memory more potently than MEL. Here, we examined the effects of 1 mg/kg MEL and AMK on both object location memory and spatial working memory. We also investigated the effects of the same dose of these drugs on relative phosphorylation/activation levels of memory-related proteins in the hippocampus (HP), the perirhinal cortex (PRC) and the medial prefrontal cortex (mPFC). Methods Object location memory and spatial working memory were assessed using the object location task and the Y-maze spontaneous alternation task, respectively. Relative phosphorylation/activation levels of memory-related proteins were assessed using western blot analysis. Results AMK, as well as MEL, enhanced object location memory and spatial working memory. AMK increased the phosphorylation of cAMP-response element-binding protein (CREB) in both the HP and the mPFC 2 h after the treatment. AMK also increased the phosphorylation of extracellular signal-regulated kinases (ERKs) but decreased that of Ca2+/calmodulin-dependent protein kinases II (CaMKIIs) in the PRC and the mPFC 30 min after the treatment. MEL increased CREB phosphorylation in the HP 2 h after the treatment, whereas no detectable changes in the other proteins examined were observed. Conclusion These results suggested the possibility that AMK exerts stronger memory-enhancing effects than MEL by more remarkably altering the activation of memory-related proteins such as ERKs, CaMKIIs and CREB in broader brain regions, including the HP, mPFC and PRC, compared to MEL.