Scientists uncover secrets of good sleep

A good night’s sleep can do wonders for both the mind and the body. (CREDIT: Creative Commons)

A good night’s sleep can do wonders for both the mind and the body. But what determines how much sleep we need, and what can make us sleep deeper?

In a new study, researchers at the University of Tsukuba have provided some answers by finding a signaling pathway in brain cells that regulates sleep duration and depth.

“We studied genetic mutations in mice and how they affect their sleep patterns,” says senior author of the study, Professor Hiromasa Funato. “We identified a mutation that caused mice to sleep much longer and deeper than usual.” The researchers found that this was caused by low levels of an enzyme called histone deacetylase 4 (HDAC4), which is known to suppress the expression of target genes.

Previous studies on HDAC4 have shown that it is strongly affected by the addition of phosphate molecules in a process known as phosphorylation. When this happens, HDAC4 tends to move away from the cell nucleus and downregulation of certain proteins is reduced. The researchers were interested in whether this HDAC4 phosphorylation would affect sleep.

“We focused on a protein called saline inducible kinase 3, also known as SIK3, which phosphorylates HDAC4,” says Professor Funato. “We have previously found that this protein has a strong effect on sleep.”

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The team found that when SIK3 was deficient, or when HDAC4 was modified to prevent phosphorylation, the mice slept less. In contrast, when mice had a more active version of SIK3, which increased HDAC4 phosphorylation, they slept much more. They also identified another protein, LKB1, that phosphorylates SIK3 and has similar sleep-suppressing effects in deficiency.

“Our results show that there is a signaling pathway from LKB1 to SIK3 and then to HDAC4 in brain cells,” said study co-author Masashi Yanagisawa. “This pathway leads to HDAC4 phosphorylation, which promotes sleep, most likely because it affects the expression of sleep-promoting genes.”

The team carried out further experiments to identify the brain cells in which these pathways regulate sleep. This included changing the amount of SIK3 and HDAC4 in different cell types and brain regions.

Changes in the transcriptome of one nucleus and the molecular pathway associated with the need for sleep. (CREDIT: Nature Communications)

The results showed that signaling in cortical cells regulates the depth of sleep, while signaling in the hypothalamus regulates the duration of deep sleep. For both areas of the brain, excitatory neurons play a key role, which can activate other neurons.

These results provide important insights into how sleep is regulated, potentially leading to a better understanding of sleep disorders as well as the development of new treatments.

Changes in the transcriptome of one nucleus and the molecular pathway associated with the need for sleep. (CREDIT: Nature Communications)

The article “Kinase signaling in excitatory neurons regulates the amount and depth of sleep” was published in Nature.

Tips for Better Sleep

Good sleep habits (sometimes called “sleep hygiene”) can help you get a good night’s sleep.

Some habits that can improve your sleep include:

  • Be consistent. Go to bed at the same time every night and get up at the same time every morning, including on weekends.

  • Make sure your bedroom is quiet, dark, relaxing and at a comfortable temperature.

  • Remove electronic devices from the bedroom, such as televisions, computers, and smartphones.

  • Avoid large meals, caffeine and alcohol before bed.

  • Get some exercise. Physical activity during the day can help you fall asleep more easily at night.

For more information on sleep training, check out the resources here:

This work was supported by the World Premier International Research Center Initiative by MEXT, JSPS KAKENHI, JST CREST, AMED, JSPS DC2, University of Tsukuba Type A Fundamental Research Support Program, World Leading Innovative Science and Technology Research and Development Funding Program (FIRST Program) .

For more science news, visit our New Discoveries section at The bright side of the news.

Note. Materials provided above by the University of Tsukuba. Content can be edited for style and length.

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