“This shows how complex the sleep machinery is” — ScienceDaily

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Researchers from the University of Copenhagen and the University of Aalborg present a new study showing that a small molecule in brain cells affects the level of hypocretin, which is responsible for making us feel awake during the day and tired during the day. night. People with a genetic variation of this molecule have a higher risk of suffering from daytime sleepiness.

When brain specialist Birgitte Kornum from the Department of Neuroscience recently arrived in Rome for one of the largest sleep conferences in the world, she was completely taken aback. There were pharmaceutical companies everywhere — with stands, information materials and campaigns.

They all wanted to treat daytime sleepiness or turn off the brain at night. And many of them have focused on hypocretin, which is a protein found in brain cells that has recently attracted a lot of attention in sleep research.

Indeed, hypocretin is suspected to play a role in both insomnia, which is a decreased ability to fall asleep at night, and in narcolepsy, which is a decreased ability to stay awake for the day. People with insomnia may have too much hypocretin in the brain, while people with narcolepsy have too little. Researchers also suspect hypocretin may play a role in depression, ADHD, and other mental disorders.

Much is already known about the hypocretin system in the brain. There’s even a new drug for insomnia that counteracts the effect of hypocretin, last introduced in Canada in 2018. According to Birgitte Kornum, however, the problem is that we know very little about how hypocretin works. Hypocretin is regulated inside cells.

Therefore, Associate Professor Birgitte Kornum and her colleagues set out to shed some light on the matter in a new study, which was recently published in the reputable journal PNAS. The study combines tests on mice, zebrafish and human cells, and the researchers cooperated with their neighbors at the Department of Cellular and Molecular Medicine at the University of Copenhagen, among others.

MicroRNA associated with sleep regulation

The research team spent several years studying one of the cellular mechanisms that affect hypocretin levels. Here they focused on a small molecule called microRNA-137 (miR-137).

“We found that miR-137 helps regulate hypocretin. To have normal sleep, you need to have the right amount of hypocretin in the brain at the right time, and miR-137 helps with that. Although MiR-137 is also found in other parts of the body, it is particularly pronounced in the brain,” Birgitte Kornum says of the new study, which she led with Assistant Professor Anja Holm of Aalborg University.

The microRNA regulates various cellular processes, including hypocretin levels. Therefore, there is considerable interest in research on microRNAs, as they could be targeted to regulate these processes.

Previously, scientists knew very little about the role played by miR-137 in the brain, but now Birgitte Kornum’s research team has demonstrated that it is associated with the regulation of hypocretin and therefore with sleep.

“This is the first time that a microRNA has been linked to sleep regulation. Building on the UK Biobank, we discovered genetic mutations in miR-137 that cause daytime sleepiness. The study demonstrates this link in mice and zebrafish, and we are able to prove the link to hypocretin Our discovery shows how complex the sleep machinery is Imagine inheriting a variant of miR-137 that exposes you to a higher risk of feeling drowsy during the day,” says Birgitte Kornum.

Hypocretin affects sleep phases

Hypocretin, which has caught the attention of pharmaceutical companies, also affects sleep phase order.

Our sleep is generally divided into four stages. The steps follow a specific order, and this order is vital for the quality of our sleep.

“Narcolepsy patients with low levels of hypocretin experience confused sleep stages. We know this from tests in mice showing that hypocretin affects the order of these stages,” says Anja Holm from the Aalborg University, who is the first author of the study and who did the testing. with Birgitte Kornum.

Existing research suggests that to solve the problem, we need to gain more knowledge about the regulation of hypocretin. And here, the Danish researchers point to a different, but equally important piece of the puzzle, namely the immune system.

“Most people know that when you are sick, you often feel tired. And when you have a fever and the immune system is working hard, you often suffer from poor sleep. So we know something is going on. at the level of hypocretin when the body is fighting against a viral infection, for example, and we try to understand this process”, explains Birgitte Kornum.

“In the study, we show that one of the immune system’s emitting substances, IL-13, has a special effect on hypocretin. We can say that when we add IL-13, it affects miR-137 and therefore also the level of hypocretin in the body. We still don’t know why, but we are currently doing some tests that might give us an answer.”

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