Secrets Of A Good Night Sleep

Study Discovers Secrets Of A Good Night’s Sleep

A good night’s sleep can be beneficial to both the mind and the body. But what determines how much sleep we require, and what causes us to sleep more deeply? Researchers from the University of Tsukuba have discovered a signalling pathway within brain cells that controls the length and depth of sleep in a new study.

“We examined genetic mutations in mice and how these affect their patterns of sleep,” says senior author of the study, Professor Hiromasa Funato. “We identified a mutation that led to the mice sleeping much longer and more deeply 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 greatly affected by the attachment of phosphate molecules in a process known as phosphorylation. When this occurs, HDAC4 tends to move away from the cell nucleus, and the suppression of certain proteins is reduced. The researchers were interested in whether this phosphorylation of HDAC4 would affect sleep.

“We focused on a protein called salt-inducible kinase 3, otherwise known as SIK3, which phosphorylates HDAC4,” says Professor Funato. “We previously found that this protein has strong effects on sleep.” The team found that when there was a lack of SIK3 or when HDAC4 was modified to prevent phosphorylation, the mice slept less. In contrast, when the mice had a more active version of SIK3, which increased the phosphorylation of HDAC4, they slept a lot more. They also identified a further protein, LKB1, which phosphorylates SIK3, and has similar sleep-suppressing effects when deficient.

“Our findings indicate that there is a signaling pathway within brain cells from LKB1 to SIK3 and then to HDAC4,” says study co-senior author, Professor Masashi Yanagisawa. “This pathway leads to the phosphorylation of HDAC4, which promotes sleep, most probably 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 involved altering the amounts of SIK3 and HDAC4 in different cell types and brain regions. The results indicated that signaling within the cells of the cortex regulates the depth of sleep while signaling within the hypothalamus regulates the amount of deep sleep. For both brain regions, the excitatory neurons, which can activate other neurons, were identified as playing a key role.

These results provide an important insight into how sleep is regulated, which could potentially lead to a greater understanding of sleep disorders as well as the development of new treatments. (ANI)

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Why Warm Milk Makes You Sleepy, Study Explains

According to time-honoured advice, drinking a glass of warm milk at bedtime will encourage a good night’s rest. Here’s why.

Milk’s sleep-enhancing properties are commonly ascribed to tryptophan, but scientists have also discovered a mixture of milk peptides, called casein tryptic hydrolysate (CTH), that relieves stress and enhances sleep.

Now, researchers reporting in the American Chemical Society’s Journal of Agricultural and Food Chemistry have identified specific peptides in CTH that might someday be used in new, natural sleep remedies.

According to the US Centers for Disease Control and Prevention, one-third of U.S. adults don’t get enough sleep. Sedatives, such as benzodiazepines and zolpidem, are commonly prescribed for insomnia, but they can cause side effects, and people can become addicted to them. Many sedatives work by activating the GABA receptor, a protein in the brain that suppresses nerve signaling.

Scientists have also discovered several natural peptides, or small pieces of proteins, that bind the GABA receptor and have anti-anxiety and sleep-enhancing effects. For example, treating a protein in cow’s milk, called casein, with the digestive enzyme trypsin produces the mixture of sleep-enhancing peptides known as CTH.

Within this mixture, a specific peptide known as a-casozepine (a-CZP) has been identified that could be responsible for some of these effects. Lin Zheng, Mouming Zhao and colleagues wondered if they could find other, perhaps more powerful, sleep-enhancing peptides in CTH.

The researchers first compared the effects of CTH and a-CZP in mouse sleep tests, finding that CTH showed better sleep-enhancing properties than a-CZP alone. This result suggested that other sleep-promoting peptides besides a-CZP exist in CTH.

The team then used mass spectrometry to identify bioactive peptides released from CTH during simulated gastric digestion, and they virtually screened these peptides for binding to the GABA receptor and for the ability to cross the blood-brain barrier.

When the strongest candidates were tested in mice, the best one (called YPVEPF) increased the number of mice that fell asleep quickly by about 25 per cent and the sleep duration by more than 400 per cent compared to a control group. In addition to this promising peptide, others in CTH should be explored that might enhance sleep through other pathways, the researchers say.

The authors acknowledge funding from the National Natural Science Foundation of China, the Guangdong Provincial Key R and D Program, the Shandong Provincial Key R and D Program, and the Specific Fund Program for Basic and Applied Basic Research of Guangdong Province. (ANI)