Melatonin, a hormone that regulates sleep-wake cycles, may hold the key to enhancing memory and potentially treating age-related memory impairment, according to recent research conducted by medical researchers from Sophia University in Japan. The study investigated the effects of melatonin and its derivatives on the phosphorylation levels of key memory proteins in male mice, revealing intricate mechanisms through which melatonin enhances memory.
Multiple studies have already shown the memory-enhancing effects of melatonin and its derivatives in animal models. Forming both short- and long-term memories requires the phosphorylation of specific memory-related proteins, but until now, the molecular mechanisms underlying melatonin-induced memory enhancement have remained unknown.
The researchers focused on three compounds: melatonin, a hormone secreted by the pineal gland in the brain; N1-acetyl-5-methoxyquinuramine (AMK), a biological metabolite of melatonin; and ramelteon, a drug that activates the melatonin receptor. They examined the effects of these compounds on memory formation and the phosphorylation of five key memory-related proteins.
The team conducted experiments on male mice, administering melatonin, ramelteon, or AMK at a dose of 1 mg/kg. The results showed that all three compounds facilitated the formation of long-term memory.
The researchers then examined the effects of ramelteon and AMK on the phosphorylation of memory-related proteins in the hippocampus and perirhinal cortex of the male mouse brain. They found that treatment with these compounds increased the phosphorylation of the extracellular signal-regulated kinase (ERK) and the cAMP-response element binding protein (CREB) in the hippocampus, which is the brain’s learning and memory center. However, phosphorylation levels of calcium/calmodulin-dependent kinase IIα (CaMKIIα) and CaMKIIβ were decreased in the same region. In the perirhinal cortex, both compounds increased ERK phosphorylation, while ramelteon specifically increased CaMKIIβ phosphorylation.
Lead author Professor Atsuhiko Chiba explained that these findings suggest melatonin promotes the formation of long-term object recognition memory by modulating the phosphorylation levels of memory-related proteins such as ERK, CaMKIIs, and CREB through both receptor- and non-receptor-mediated signaling pathways.
The implications of this study for humans are significant. The researchers believe that these findings could contribute to the development of new drugs that improve memory function in individuals with age-related memory impairment, with potentially fewer side effects. With a global society that is steadily aging, this research represents a remarkable breakthrough in the quest for treatments for memory-related conditions.
In conclusion, the study conducted by researchers from Sophia University sheds light on the intricate mechanisms through which melatonin enhances memory. By identifying the effects of melatonin and its derivatives on the phosphorylation of memory-related proteins, the study highlights potential pathways for improving memory function and treating age-related memory impairments. This discovery brings hope to a society grappling with the challenges of an aging population and paves the way for further research and the development of novel treatments.
