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How do we remember memories we have forgotten ?: The Asahi Shimbun

Japanese scientists improved long-term memory in subjects by activating histamine in the brain, finding that could help unveil the mechanism of remembering, as well as develop drugs to treat Alzheimer's disease.

The study by a research team, comprising scientists from Hokkaido University and the University of Tokyo, was published in Biological Psychiatry, the journal of the Society of Psychiatry Biology, on Jan. 8

Over time, memories slowly fade and are eventually forgotten. However, traces of them are believed to remain in the brain.

Histamine, a substance released in allergic reactions, is also involved in learning and memories as well as sleep and wakefulness.

As anti-histamine drugs reduce the performance of remembering, it is believed that if the central nervous system that releases and receives histamine, which functions as neurotransmitters in the brain, can be activated enough, memories can be recovered.

The study team thus investigated how the histamine-boosting drug affected memory performance in mice and humans through experiments.

In the experiments with mice, the scientists placed two identical objects in a box with a mouse, and then replaced one of them with a different object.

Rodents have a habit of taking interest, through touch and smell, in new objects, meaning that if they still remember the objects in the box, they will prefer the newly placed one.

In an initial training session, the mice preferred the new item, but after more than three days, they were unable to distinguish between the two.

However, after being administered the drug that boosts histamine in the nervous system, the mice approached the new object even one month after the initial training sessions, meaning that the drug enabled the mice to remember the difference between them.

The study team identified that the brain's perirhinal cortex, which functions when recognizing and memorizing objects, was activated in mice while releasing histamine, showing that the histamine-boosting drug improved long-term memory.

Based on the results of the study of experiments with mice, the team investigated whether the same type of drug could promote memory recovery in humans.

The experimental design was a randomized double-blind, placebo-controlled crossover trial with 38 subjects.

The team asked the male and female participants to take histamine-activating drugs and tested them on their memory of images they had seen a week before.

Those who had taken the histamine-boosting drug were able to remember the images much more easily, with a success rate several percentage points higher than those in the group that had not taken the drugs.

The rate of correct answers especially improved for questions at a higher level of difficulty.

The effect of the drug differed depending on the research participants as well as the difficulty level of the question in the experiment, the team said.

"Although the study results do not immediately apply to memory retrieval in humans, it could lead to the development of a drug treatment for Alzheimer's disease and other conditions," said Hiroshi Nomura, a pharmacy lecturer at Hokkaido University and a member of the team .

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