(ORDO NEWS) — Biologists have identified several steps in the signaling pathway that regulates the depth and duration of sleep at the level of individual neurons. Experiments on mice have shown that sleep can be controlled by changing the activity of a single enzyme.
Sleep has been of concern to scientists since ancient times. They are still trying to figure out what it is for, how it works, how it is regulated and how it affects the condition of humans and animals.
In the new work, a team from the University of Tsukuba explored these processes at the level of individual genes and the proteins that regulate their activity.
This made it possible to find several key links in the chain of reactions that control the duration and depth of sleep.
The group of Professor Hiromasy Funato (Hiromasa Funato) studied the effect of various mutations on the nature of sleep in experimental mice.
The work showed that mutations leading to a decrease in the activity of the enzyme histone deacetylase 4 (HDAC4) caused animals to sleep longer and deeper than mice with normal HDAC4.
This protein is involved in the regulation of many genes, including, apparently, those that trigger intracellular mechanisms associated with sleep in neurons.
A decrease in HDAC4 activity can be caused by the addition of a phosphorus group ( phosphorylation ).
With this chemical modification, HDAC4 molecules are removed from the cell nucleus and do not significantly reduce the activity of its genes.
This was confirmed by additional experiments. In them, scientists have modified the protein so as to impede its phosphorylation, or blocked the work of another enzyme, SIK3, which carries out such a reaction. Mice with similar changes actually slept less than usual.
And vice versa, with an artificial increase in HDAC4 phosphorylation, sleep lengthened, became deeper and more restful.
Scientists have identified the next step in this chain. Protein LKB1, which, in turn, regulates the work of SIK3, also influenced the nature of sleep in experimental animals.
“Our work shows that there is a signaling pathway from LKB1 through SIK3 and then to HDAC4 in brain cells,” says Prof. Funato.
“This pathway ultimately leads to HDAC4 phosphorylation, which enhances sleep. Most likely, due to the fact that this protein affects the work of the corresponding genes.
By artificially changing the amounts of SIK3 and HDAC4 in different brain cells, biologists have shown that the activity of these proteins in the cerebral cortex determines the depth of sleep, and in the hypothalamus, its duration.
Apparently, these enzymes affect excitatory neurons: by acting on the corresponding genes, they suppress their activity during sleep.
Perhaps if scientists can better understand how this signaling pathway works, we will get completely new and more effective drugs to combat sleep disorders.
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