When brain scientist Birgitte Kornum arrived in Rome for one of the world''s largest sleep conferences, she was completely reprimanded. There were pharmaceutical companies everywhere, with stands, information materials, and campaigning.
They all wanted to treat daytime sleepiness or to turn off the brain at night. Several of them focused on hypocretin, a protein found in brain cells, which has recently received some attention.
Hypocretin is believed 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 during the day. Moreover, individuals suffering from insomnia may have too much hypocretin in the brain, while people suffering from narcolepsy have too little. Researchers also suspect hypocretin to play a role in depression, ADHD, and other mental disorders.
The hypocretin system in the brain is already known. There is even a new medication for insomnia that is preventing hypocretin''s effects, which was previously introduced in Canada in 2018. However, the problem is that we know very little about how hypocretin is regulated inside the cells.
In a new study, Associate Professor Birgitte Kornum and her colleagues were able to clarify the subject, which has recently been published in the reputed journalPNAS. The study combines experiments on mice, zebrafish, and human cells, and the researchers collaborated with their neighbours at the Department of Cellular and Molecular Medicine at the University of Copenhagen.
MicroRNA associated with sleep regulation
A team of researchers has spent several years studying one of the cellular processes that affect hypocretin levels. Here they have focused on a small molecule called microRNA-137 (miR-137).
We discovered that miR-137 aids regulate hypocretin. It''s important to have the right amount of hypocretin in the brain at the right time, but miR-137 also helps with that. Birgitte Kornum, the author of the new study, has led with Assistant Professor Anja Holm from Aalborg University.
MicroRNA regulates many cell processes, including hypocretin levels. There is therefore considerable research interest in microRNAs, as they may be targeted in order to regulate such processes.
Previously, the researchers knew very little about the role played by miR-137 in the brain, but now the Birgitte Kornums research team has demonstrated that it is linked to hypocretin regulation and thus with sleep.
This is the first time a microRNA is linked to sleep regulation. We used the UK Biobank to discover some genetic mutations in miR-137, which cause daily sleepiness. This study demonstrates the connection between mice and zebrafish, and we are able to demonstrate the connection with hypocretin. Imagine inheriting a variant of miR-137, which puts you at greater risk of feeling sleepy during the day, according to Birgitte Kornum.
Hypocretin affects sleep stages
Hypocretin, which has sparked attention among pharmaceutical companies, has also a negative impact on the mood of the sleep days.
Our sleep is usually divided into four stages. Each stage follows a specific order, and this is crucial to our sleep''s quality.
Patients with low levels of hypocretin experience muddled sleep stages. We know this from mice testing that demonstrate that hypocretin is infected with these stages, according to Anja Holm, who is the first author of the study and who performed the tests together with Birgitte Kornum.
Existing research suggests that to resolve the problem, we must gain greater knowledge of hypocretin regulation. Here, Danish researchers point to a different, but equally important piece of the puzzle, namely the immune system.
When you are sick, you often feel tired. And when you have a fever and your immune system is hard at work, you often suffer from poor sleep. So we know that something happens to the hypocretin level when the body is trying to combat a virus infection, for example, and we are now trying to understand this process.
We can prove that when we add IL-13, it affects miR-137 and thus the level of hypocretin in the body. We are still doing tests that may be able to provide an answer.