How a common sleep supplement could boost memory function

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The potential of melatonin and its derivatives in enhancing memory has been demonstrated in various animal studies.

However, the precise molecular mechanisms orchestrating these beneficial effects have been somewhat elusive until recently.

A groundbreaking study led by researchers from Sophia University, Japan, has offered substantial insights into these mechanisms.


This meticulous study, published in NeuroReport on June 7, 2023, primarily sought to elucidate the effects of melatonin, ramelteon, and N1-acetyl-5-methoxyquinuramine on the relative phosphorylation levels of memory-associated proteins.

The study particularly focused on uncovering the signaling pathways associated with the receptor- and non-receptor-mediated memory-enhancing effects of melatonin.


Male mice were administered melatonin, ramelteon, or AMK, followed by a series of novel object recognition task (NORT) experiments to assess the formation of long-term memory.

This involved familiarization with certain objects and subsequent exposure to new objects, with observations made on the time spent exploring each object.

Following standard protocols, the mice were sacrificed, and effects on phosphorylation of key proteins involved in memory formation were studied in specific brain regions, namely the hippocampus and the perirhinal cortex (PRC).


The administration of melatonin, ramelteon, or AMK facilitated the formation of long-term memory in male mice.

In the hippocampus, ramelteon/AMK significantly increased the phosphorylation of ERK and CREB, whereas CaMKIIα/β phosphorylation was significantly decreased.

In the PRC, ramelteon and AMK significantly increased ERK phosphorylation, and ramelteon significantly increased CaMKIIβ phosphorylation.

Neither ramelteon nor AMK affected the phosphorylation of CaMKIV in the hippocampus/PRC.

Implications and Conclusion:

These findings suggest that melatonin promotes the formation of long-term object recognition memory by modulating the phosphorylation levels of crucial memory-related proteins in both receptor-mediated and non-receptor-mediated signaling pathways.

Professor Atsuhiko Chiba, the lead author, believes that these revelations can pave the way for the development of innovative drugs designed to ameliorate memory functions in individuals experiencing age-related memory impairments, potentially with reduced side effects.

This study serves as a significant milestone in understanding melatonin’s intricate role in memory enhancement, providing a solid foundation for further research and development in the quest for effective memory-enhancing interventions.

If you care about brain health, please read studies about inflammation that may actually slow down cognitive decline in older people, and low vitamin D may speed up cognitive decline.

For more information about brain health, please see recent studies about common exercises that could protect against cognitive decline, and results showing that this MIND diet may protect your cognitive function, and prevent dementia.

The research findings can be found in NeuroReport.

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