Researchers at Tokyo Medical and Dental University (TMDU) at Japan Show that melatonin and its metabolites foster the creation of long-term memories and protect against cognitive decline.
Chiba, Japan — Walk the supplement aisle on your local pharmacy and you will find fish oil, ginko, vitamin E, and ginseng, all known as memory boosters which can enable you to avoid cognitive decline. You will also find melatonin, which can be sold primarily from the United States as a sleep supplement. It now seems that melatonin marketers may have to do a rethink. In a new study, researchers headed by Atsuhiko Hattori in Tokyo Medical and Dental University (TMDU) in Japan have shown that melatonin and two of its metabolites assist memories stick around in the mind and may shield mice, and possibly individuals, from cognitive decline.
One of the easiest methods to test memory in mice is to rely on their natural propensity to examine unknown items. Given a choice, they will spend more time checking out unknown objects than familiar ones. The secret is that for something to be recognizable, it needs to be remembered. Like in people, cognitive decline in mice manifests as poor memory, and if tested with this new object recognition task, they behave like both objects are new.
The group of investigators in TMDU were interested about melatonin’s metabolites, the molecules that melatonin is broken down into after going into the body. “We know that melatonin is converted into N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) in the brain,” explains Hattori, “and we suspected that they might promote cognition.” To test their theory, the researchers familiarized mice to objects and gave them doses of melatonin as well as both metabolites 1 hour afterwards. Then they tested their memory the next day. They found that memory improved following treatment, and that AMK was the most effective. All three gathered in the hippocampal region of the brain, a region important for turning experiences into memories.
For young mice, exposure to an object twice in a day is enough for this to be remembered the following day on the new object recognition task. In contrast, elderly mice behave as if both objects are new and unfamiliar, a indication of cognitive decline. But, 1 dose of AMK 15 minutes after a single exposure to a item, and older mice could remember the things around 4 days later.
Last, the researchers discovered that long-term memory formation may not be enhanced following blocking melatonin from being converted to AMK in the brain. “We have shown that melatonin’s metabolite AMK can facilitate memory formation in all ages of mice,” says Hattori. “Its effect on older mice is particularly encouraging and we are hopeful that future studies will show similar effects in older people. If this happens, AMK therapy could eventually be used to reduce the severity of Mild Cognitive Impairment and its potential conversion to Alzheimer’s disease.”
Related Journal Article: https://onlinelibrary.wiley.com/doi/10.1111/jpi.12703