‘Short sleep’ gene could protect memory function from sleep deprivation

In a new study, researchers found a gene that’s ever been shown to prevent the memory deficits that normally accompany sleep deprivation.

This gene is the third human genes that promote “natural short sleep”—nightly sleep that lasts just four to six hours but leaves people feeling well-rested.

The researchers believe this latest discovery may one day lead to new therapies that improve sleep and treat sleep disorders.

The research was conducted by a team of UCSF scientists.

The findings were announced just weeks after the same team reported their discovery of the second short sleep gene, an achievement that was a decade in the making.

In the study, the team identified the newest gene in a father-and-son pair who averaged just 5.5 and 4.3 hours of sleep each night, respectively—far less than the eight or more hours that most people need in order to avoid feeling sleep-deprived.

But like other natural short sleepers, the father-son pair don’t seem to experience any of the adverse cognitive or physical effects that generally accompany sleep deprivation.

The team performed gene sequencing on both father and son and zeroed in on a single-letter mutation in a gene called NPSR1, which encodes a signaling protein that sits on the surface of neurons and was previously shown to be involved in regulating sleep.

Like the mutations in the other known short sleep genes, this mutation is exceedingly rare, occurring in fewer than one in 4 million people.

To understand the gene’s function in the brain, the researchers performed a series of experiments on mice that were genetically engineered to carry an identical mutation in the mouse version of NPSR1.

They found NPSR1 is part of a signaling pathway in the brain that promotes wakefulness.

When it’s activated, it switches on other proteins in the same pathway by attaching a chemical modification to them.

They found that mutant NPSR1 activated many more downstream proteins than the non-mutant version.

These results suggest that the version of NPSR1 associated with short sleep is easier to activate, and is also better at switching on other components of this wakefulness-promoting pathway.

The researchers next turned to a memory test.

They found sleep-deprived mice experience memory deficits (just like sleep-deprived humans) and have trouble forming lasting memories.

But carriers of the mutant version of NPSR1 did remember their experience, even after being sleep deprived.

The team says NPSR1 not only promotes short sleep, but it also prevents memory problems that usually result from sleep deprivation.

This is the first gene that anyone’s discovered that exerts a protective effect against one of the many adverse consequences of sleep deprivation.

The lead author of the study is Ying-Hui Fu, Ph.D., a professor of neurology.

The study is published in Science Translational Medicine.

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