Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL’s metabolites, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK), in these effects are unknown. The current study directly investigated the acute effects of systemic MEL, AFMK, and AMK on novel object recognition. We also analyzed MEL, AFMK, and AMK levels in hippocampus and temporal lobe containing the perirhinal cortex following systemic MEL and AMK treatment. AMK administered post‐training had a more potent effect on object memory than MEL and AFMK. AMK was also able to rescue age‐associated declines in memory impairments when object memory was tested up to 4 days following training. Results from administering AMK at varying times around the training trial and the metabolism time course in brain tissue suggest that AMK’s memory‐enhancing effects reflect memory consolidation. Furthermore, inhibiting the MEL‐to‐AMK metabolic pathway disrupted object memory at 24 hours post‐training, suggesting that endogenous AMK might play an important role in long‐term memory formation. This is the first study to report that AMK facilitates long‐term object memory performance in mice, and that MEL crosses the blood‐brain barrier and is immediately converted to AMK in brain tissue. Overall, these results support AMK as a potential therapeutic agent to improve or prevent memory decline.

中文翻译：

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褪黑激素代谢物 N1-乙酰基-5-甲氧基犬尿胺促进年轻和衰老小鼠的长期物体记忆

据报道，褪黑激素 (MEL) 可增强认知过程，使其成为认知能力下降的潜在治疗方法。然而，MEL 的代谢物 N1-乙酰基-N2-甲酰基-5-甲氧基犬尿胺 (AFMK) 和 N1-乙酰基-5-甲氧基犬尿胺 (AMK) 在这些作用中的作用尚不清楚。目前的研究直接调查了系统性 MEL、AFMK 和 AMK 对新物体识别的急性影响。我们还分析了全身 MEL 和 AMK 治疗后海马和包含周围皮层的颞叶中的 MEL、AFMK 和 AMK 水平。与 MEL 和 AFMK 相比，AMK 进行训练后对对象记忆的影响更大。当训练后最多 4 天测试对象记忆时，AMK 还能够挽救与年龄相关的记忆障碍下降。在训练试验和脑组织代谢时间过程中的不同时间施用 AMK 的结果表明，AMK 的记忆增强作用反映了记忆巩固。此外，抑制 MEL-to-AMK 代谢途径会在训练后 24 小时破坏物体记忆，表明内源性 AMK 可能在长期记忆形成中发挥重要作用。这是第一项报告 AMK 促进小鼠长期物体记忆性能的研究，并且 MEL 穿过血脑屏障并立即在脑组织中转化为 AMK。总体而言，这些结果支持 AMK 作为改善或预防记忆力下降的潜在治疗剂。抑制 MEL-to-AMK 代谢途径会在训练后 24 小时破坏对象记忆，表明内源性 AMK 可能在长期记忆形成中发挥重要作用。这是第一项报告 AMK 促进小鼠长期物体记忆性能的研究，并且 MEL 穿过血脑屏障并立即在脑组织中转化为 AMK。总体而言，这些结果支持 AMK 作为改善或预防记忆力下降的潜在治疗剂。抑制 MEL-to-AMK 代谢途径会在训练后 24 小时破坏对象记忆，表明内源性 AMK 可能在长期记忆形成中发挥重要作用。这是第一项报告 AMK 促进小鼠长期物体记忆性能的研究，并且 MEL 穿过血脑屏障并立即在脑组织中转化为 AMK。总体而言，这些结果支持 AMK 作为改善或预防记忆力下降的潜在治疗剂。