Asthma drug helps sleep-deprived mice regain lost memories

Students may stay up all night preparing for exams. However, studies show that lack of sleep is bad for memory. Robert Jabekes, a neuroscientist at the University of Groningen, has found that what you learn from lack of sleep isn’t necessarily lost, it’s just harder to remember. Working with his team, he used an optogenetic approach and the human-approved asthma drug roflumilast to re-access this ‘hidden knowledge’ after days of sleep-deprived study. These findings were published Dec. 27 in the journal Current Biology.

Jabekes, associate professor of neuroscience of memory and sleep at the University of Groningen in the Netherlands, and his team have extensively studied how sleep deprivation affects memory processes. The focus of the episode was finding ways to support the memory process,” says Havekes. In his latest study, however, his team investigated whether memory loss as a result of sleep deprivation was a direct result of information loss or simply caused by difficulties in retrieving information. “Sleep deprivation undermines memory processes, but every student knows that an answer missed during an exam can appear hours later. In that case, the information is actually It was stored in the brain, but it was difficult to obtain.

To address this issue, Havekes and his team used an optogenetic approach. Using a genetic approach, we selectively produced a light-sensitive protein (channelrhodopsin) in neurons that are activated during learning experiences. This made it possible to recall specific experiences by shining a light on these cells. “In our study of sleep deprivation, we applied this approach to neurons in the hippocampus, a region of the brain where spatial information and factual knowledge are stored,” says Havekes.

First, genetically engineered mice were given a spatial learning task that required learning the location of individual objects, a process that relies heavily on neurons in the hippocampus. The mouse had to perform the same task a few days later, but this time he had one object moved to a new location. Mice that were sleep deprived hours before the first session failed to detect this spatial change. This suggests that the object’s original position cannot be remembered. “But when we reactivated the hippocampal neurons that originally stored this information with light, and then challenged them again, they were able to remember where they came from,” Havekes says. say. “This indicates that information was stored in the hippocampus during sleep deprivation, but could not be retrieved without stimulation.”

Molecular pathways initiated during reactivation are also targets of the drug roflumilast, used by patients with asthma or COPD. Havekes: “Just before the second test, when we gave the sleep-deprived trained mice roflumilast, they remembered exactly as they did with direct stimulation of the neurons.” Clinically approved for use in humans and known to enter the brain, these findings raise the question of whether they can be applied to regain access to ‘lost’ memories in humans. It paves the way for testing.

The discovery that there is more information in the brain than we previously expected and that these ‘hidden’ memories can be accessed again opens up all sorts of exciting possibilities, at least in mice. “The use of roflumilast may stimulate age-related memory impairment and memory accessibility in patients with early Alzheimer’s disease,” said Havekes. “And we may be able to reactivate certain memories and make them permanently available, as we have successfully done in mice.” This information may be reintegrated more tightly in the brain if the subject’s neurons are stimulated with a drug when they are ill. “For now, of course, this is all speculation, but time will tell.”

At this time, Havekes is not directly involved in such research in humans. “My interest is in unraveling the molecular mechanisms underlying all these processes,” he explains. “What makes memories accessible or inaccessible? How does roflumilast restore access to these ‘hidden’ memories? and get many new problems for free.

reference: Borcius YG, Heckmann PRA, Palaciani C, et al. Restoring memory of object locations after sleep-deprivation-induced amnesia. current life2022. doi: 10.1016/j.cub.2022.12.006

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