INSOMNIA: Discovery of a new sleep molecule

INSOMNIA: Discovery of a new sleep molecule

That’s the thought of lead author and brain scientist Dr. Birgitte Kornum from the Department of Neuroscience at the University of Copenhagen. The researcher points out that hypocretin is suspected of playing a role both in insomnia and in narcolepsy, characterized by a reduction or even suppression of the ability to stay awake during the day. People with insomnia might show excessively high levels of hypocretin in the brain, while people with narcolepsy might have insufficient levels. Scientists also suggest the protein may be involved in depression, ADHD and other mental disorders.

Better understand the hypocretin system in the brain

The study, conducted in vitro and in vivo, combined tests on mice, zebrafish and human cells to better understand the action of hypocretin. While there is already a new drug for insomnia that counteracts the effect of hypocretin, the process by which hypocretin is regulated inside brain cells and produces its effects remains poorly understood. While the team had already been working for several years on one of the cellular mechanisms that affect hypocretin levels, they focused on a small molecule called microRNA-137 (miR-137).

miR-137, a hypocretin regulator: to have normal sleep, it is necessary to have normal levels of hypocretin in the brain at the right time, and miR-137 contributes to this. Although MiR-137 is also present in other parts of the body, it is particularly pronounced in the brain. MicroRNA regulates various cellular processes, beyond hypocretin levels, which is why there is considerable research interest in microRNAs. Research confirms that miR-137 is significantly associated with the regulation of hypocretin and therefore with sleep.

miR-137, a sleep regulator: Based on the UK Biobank, researchers show that certain genetic mutations in miR-137 cause daytime sleepiness. The study demonstrates this link in both mice and zebrafish.

miR-137 and hypocretin affect sleep phases: while our sleep is structured in 4 stages which follow a precise order, that this order is vital for the quality of sleep, people who have low levels of hypocretin experience disordered stages of sleep: tests carried out on mice show that hypocretin affects the order of these different stages.

Finally, while diseases or infections are associated with sleep disturbance, it is likely that a process is triggered at the level of hypocretin, when the body tries to defend itself; the team is currently working to understand this process but has revealed that certain immune system emitting substances, including IL-13, exert a particular effect on hypocretin: in vitro, on brain cell lines, the addition of IL -13 affects miR-137 and therefore also the level of hypocretin.

“We are currently carrying out tests which could perhaps give us the answer”.

However, research already suggests hypocretin and miR-137 as potential new therapeutic targets for fighting insomnia.

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