Mutation at the neuropeptide S receptor reduced the need for sleep

Mutation at the neuropeptide S receptor reduced the need for sleep
Image by Daniela Dimitrova from Pixabay

Doctors found another mutation that allows its bearer to sleep at 4,3-5,5 hours a day and get enough sleep. Moreover, it seems to protect against memory impairment associated with lack of sleep – at least this is the case in mice. Animals with a mutation that were previously prevented from sleeping better than mice from the control group passed a test that tested the operation of contextual memory.

According to doctors, people from 18 to 65 years old, on average, need to sleep 8-8.5 hours a day. Those who sleep too little or, conversely, too much, are at increased risk of cardiovascular disease. Lack of sleep can lead, inter alia, to a  violation of cognitive functions, the occurrence of depression, and a decrease in immunity.

The duration of sleep depends on circadian rhythms and homeostasis. Genetic factors also affect sleep. Some people sleep 4-6 hours a day all their lives, but they feel good and do not develop disorders and disorders associated with chronic lack of sleep. Ten years ago, neurophysiologists and doctors, led by Ying-Hui Fu from the University of California at San Francisco, found a mutation in the DEC2 gene in a mother and daughter who got enough sleep in six hours. Protein DEC2 regulates the production of the hormone orexin, which supports the state of wakefulness. Recently, the same group of researchers described a mutation in the β1-adrenergic receptor gene. Its carriers got enough sleep, on average, in 5.7 hours.

In a new study, scientists led by Fu described a mutation in the neuropeptide S receptor 1 gene ( NPSR1 ). The neuropeptide S, which the receptor binds to, modulates awakening and falling asleep. Scientists found a mutation (the amino acid tyrosine in the 206 position of the protein chain was replaced by histidine) in a father and son, who needed only 4.3-5.5 hours of sleep for a good rest. Such a replacement is extremely rare, with a probability of 4 × 10 -6, that is, one person out of four million.

To test the effect of the mutation, the authors constructed genetically modified mice carrying the mutant NPSR1 geneMutant animals in comparison with mice from the control group were more active and moved more, both day and night. Studies using electroencephalography and electromyography (recording muscle activity) showed  that animals with a mutation slept day and night on average by 71 minutes less (P <0.0001) than normal mice. Their duration of slow sleep was reduced both day and night, and the time of fast sleep was reduced only in the dark. In mice with a mutation in the NPSR1 gene compared with animals from the control groupthe need for sleep was less (P <0.01), despite the fact that they slept less. They recovered faster after six hours of sleep deprivation. And even after deprivation, their need for sleep was less (P = 0.0013) than in ordinary mice.

Then the researchers decided to find out if the mutation in the NPSR1 gene changes the physiological activity of receptor 1 of neuropeptide S. It is formed in the brain and, in turn, affects the formation of the CREB protein that regulates the transcription of some genes. Conventional and mutant mice were injected with the neuropeptide S in the brain, and then the concentration of the CREB protein was measured in the brain lysate. In mutant mice, it was even higher (P <0.001) than in ordinary animals, so the researchers decided that receptor activity persists even in the presence of a mutation.

Moreover, it turned out that neurons with a mutant NPSR1 protein on their surface are more sensitive to the action of neuropeptide S (P <0.0001) than neurons with a normal protein. Scientists injected a neuropeptide into the brain to activate the NPSR1 receptor protein. And then they monitored the activity of neurons in the central part of the thalamus, where the protein is formed, using calcium imaging. For comparison, they monitored the activity of neurons in the lateral region of the hypothalamus. This part of the brain is also involved in the regulation of sleep, and NPSR1 protein is formed there, but in smaller amounts compared to the thalamus. Nevertheless, the introduction of the neuropeptide S into the hypothalamus included a mutant protein there as well.

Chronic lack of sleep leads to  the emergence of cognitive decline in most people. But carriers of some mutations, allowing them to sleep less, do not suffer from such violations. To find out whether cognitive impairment appears in carriers of mutations in the NPSR1 gene, the authors conducted a test for contextually determined fear in the experimental and control group of mice. This test involves the memory of past events. In rodents, which shortly before participating in the test were not allowed to sleep, the test results were worse than in animals that slept ad libitum. But mice with a mutation in the NPSR1 genepassed the test after 6-hour sleep deprivation no worse than animals from the control group that slept for a sufficient time, and better (P = 0.0179) than normal mice, which were not allowed to sleep before participating in the test.

“The NPSR1 gene not only reduces the duration of sleep, but also prevents memory problems that are usually the result of sleep deprivation,” notes Ying-hui Fu. “This is the first gene found that protects against one of the adverse effects of sleep disturbances.”

SOURCEScience Medicine
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Aakash Molpariya
Aakash started in Nov 2018 as a writer at Revyuh.com. Since joining, as writer, he is mainly responsible for Software, Science, programming, system administration and the Technology ecosystem, but due to his versatility he is used for everything possible. He writes about topics ranging from AI to hardware to games, stands in front of and behind the camera, creates creative product images and much more. He is a trained IT systems engineer and has studied computer science. By the way, he is enthusiastic about his own small projects in game development, hardware-handicraft, digital art, gaming and music. Email: aakash (at) revyuh (dot) com