A good night's sleep can work wonders for both mind and body. But what is it that determines how much we need to sleep, and what can cause us to sleep more deeply?
In a new study, researchers have now provided some answers, revealing a signaling pathway within brain cells that regulates the length and depth of sleep.
"We examined genetic mutations in mice and how these affect their patterns of sleep," says senior author of the study. "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 the senior author. "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. "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.
https://www.nature.com/articles/s41586-022-05450-1
Sleep signaling pathway in brain cells identified!
- 1,034 views
- Added
Latest News
Circadian rhythms can influ…
By newseditor
Posted 27 Apr
With hybrid brains, these m…
By newseditor
Posted 27 Apr
Blocking activation of NF-κ…
By newseditor
Posted 27 Apr
Vitamin D regulates microbi…
By newseditor
Posted 27 Apr
Role of alternative splicin…
By newseditor
Posted 27 Apr
Other Top Stories
Controlling immune-evasive tumors
Read more
CDK drug combinations may work better for breast cancer
Read more
How KRAS regulates sex differences in colon cancer
Read more
Mechanism of protection against breast and ovarian cancer
Read more
Loss of Y chromosome in men enables cancer to grow
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Single dose creatine improv…
By newseditor
Posted 27 Apr
Autonomous circadian rhythm…
By newseditor
Posted 27 Apr
Functional sensory circuits…
By newseditor
Posted 27 Apr
Positive selection CRISPR s…
By newseditor
Posted 27 Apr
Focal clusters of peri-syna…
By newseditor
Posted 27 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar