Medical researchers from Sophia University in Japan have conducted a study shedding light on the potential mechanisms behind melatonin-induced memory enhancement. Melatonin and its derivatives have previously shown memory-improving effects in animal models. The researchers, including Dr. Masahiro Sano and Dr. Hikaru Iwashita, investigated the effects of melatonin, its derivative N1-acetyl-5-methoxyquinuramine (AMK), and another compound ramelteon on memory formation. They focused on phosphorylation, the addition of phosphate groups to proteins, in five proteins known to be involved in memory formation.
The researchers administered melatonin, ramelteon, or AMK at a dose of 1 mg/kg to male mice. They evaluated long-term memory formation through a task called the novel object recognition task (NORT). In this task, mice were familiarized with an experimental arena and then exposed to two identical objects. Later, one familiar object was replaced with a new one, and the time spent exploring each object was measured.
Regarding the premise of the study, lead author Professor Atsuhiko Chiba from the Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, stated, “Our study aimed to investigate the effects of melatonin, ramelteon, and N1-acetyl-5-methoxyquinuramine on the relative phosphorylation levels of memory-related proteins in order to explore candidate signaling pathways associated with the receptor- and nonreceptor-mediated memory-enhancing effects of melatonin.”
Results showed that melatonin, ramelteon, and AMK administration improved long-term memory formation in male mice. The researchers focused on phosphorylation changes in key proteins in the hippocampus (associated with learning and memory) and the perirhinal cortex (PRC), another memory-related region.
Ramelteon and AMK treatment increased the phosphorylation of ERK and CREB in the hippocampus. However, they decreased the phosphorylation of CaMKII. In the PRC, both ramelteon and AMK increased ERK phosphorylation, and ramelteon specifically increased CaMKIIβ phosphorylation. The researchers noted that in the hippocampus/PRC, ramelteon and AMK did not affect CaMKIV phosphorylation.
These findings offer insights into the potential mechanisms by which melatonin and its derivatives might enhance memory formation. However, the study focused solely on male mice to avoid data variability caused by the reproductive cycles of female mammals. Further research may be needed to fully understand the implications of these findings and to explore potential gender differences in these effects.
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Talking about the study’s results, Prof. Chiba concluded, “Our findings suggest that melatonin is involved in promoting the formation of long-term object recognition memory by modulating the phosphorylation levels of memory-related proteins such as ERK, CaMKIIs, and CREB in both receptor-mediated and nonreceptor-mediated signalling pathways.”
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