Scientists have found a sleep switch in the mouse brain


2017-02-17 15:30:12




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Scientists have found a sleep switch in the mouse brain

Biologists have studied sleep for over a hundred years. With time up began to surface interesting details: the sleep deprivation, as we now know, can lead to death. The carotid pressure, the need for sleep increases the longer we are awake. As humans and other mammals, sleep is visible in the readings of brain activity. Gradually a buzzing on the line, the EEG begins to form a series of breaks, the so-called sleep spindles, which are brightly lit monitors sleep laboratories.

But even with all these careful observations of molecular machines behind our night departure from consciousness, remain among the most profound mysteries in modern biology. "At the mechanistic level we do not know what makes us want to sleep," says Amit Segal, chronobiology from the University of Pennsylvania, conducting sleep studies on fruit flies. Biologists were forced to mutate thousands of laboratory organisms, like flies, looking for those those who have abnormalities in the circuits of sleep and studied their genes. Also studied people with sleep disorders. The idea is that if we can determine which genes are broken is what causes people to fall asleep over the table making flies too sleepy to produce offspring, we come closer to understanding why we want to sleep and what is dream at the molecular level.

And now a group of scientists from Japan and Texas, announced the first results of a powerful experiment, which takes the same approach, but involving mice, on an unprecedented scale. For several years scientists have conducted gene mutations thousand mice, plug them into the wave monitor cord and watched them sleep. In a recent article in Nature, scientists have uncovered two genes that may participate in the biological machine sleep. The first was found in mice who had more sleep than usual. Another found in mice that spend less dream sleep (the phase of rapid eye movement, REM). These results put the researchers sleep new goals and contribute to a growing wave of research in identifying the molecular basis of sleep.

The Idea of this experiment appeared in 2007, says Masashi Yanagisawa. At that time, the biologist worked at southwestern medical center the University of Texas. He did a sleep study in ten years before, when together with his colleagues started the hunt for interesting neurotransmitters, by identifying the protein, which was associated with narcolepsy. Patients with narcolepsy can suddenly go into a phase of rapid eye movement (sleep), even if we were laughing or sitting in chat. Studies with the participation of the rodents that lacked this protein, and a colony of narcoleptic dogs at Stanford, as well as human studies soon revealed the role of protein. The so-called orexin helps people stay awake but isn't the whole story. Scientists have discovered the neurons responsible for anxiety and sedation. Yanagisawa was getting more and more wanted to crack the black box of sleep.

Not long ago, biologists began to study thousands of mutant flies in search of genes of sleep. For flies that are in constant motion when awake, scientists define "sleep" as the periods of inactivity. But the gold standard for studying human sleep is electroencephalography, or EEG, allows you to monitor the stage of sleep by measuring brain activity. It would be interesting to try this method with mice, I thought Yanagisawa. Yes, their breeding and maintenance would be more expensive than flies, but they could put implants for monitoring EEG. And mice are evolutionarily closer to humans. Therefore, the scientist has joined forces with Joseph Takanashi of southwestern University, a specialist in deep studies of mice.

They decided that They will be able to create a weekly 30-40 mutant mice, implanted monitors brain activity in their heads and see how long they sleep and how long time spend in each sleep phase. This study generated the same data as the studies on humans. Mice with abnormalities can be identified on the basis of brain activity and then sift through the genomes in search of is responsible for deviation of genes.

The Pilot phase began with several hundred animals. "Each mouse can be a treasure," says Yanagisawa. "You just had to figure out which of them." They pretty soon found the mouse with sleep disorders. And in 2009, Yanagisawa got a huge grant from the government of Japan for sleep study. Grant was so large that allowed him to create a center at the University of Tsukuba in Japan to continue monitoring on a large scale. "Now we do up to 100 mice per week," says Yanagisawa.

In the work of Nature presents the results of a survey of 8000 mice. For many years, as Segal and others, they heard something new about the progress of this group. However, gene names are always kept in strict confidence. Segal recalls a meeting at which a researcher from the laboratory Yanagisawa podrachivaya asked the audience: "Ask what I would like to know?". The crowd roared in response: "What are genes?".

"So I was very pleased to see the work," with a laugh, says Segal, "and finally find out that it was in the genes."

The First gene, which described a team of scientists creates a protein called SIK3. Mouse with a mutant gene SIK3 spend less time in the awake state every day they slept 30% more than other mice. SKI3 is an enzyme that uses cellular batteries — storage molecule of energy called ATP to activate other proteins. When scientists investigated the nature of this mutation, they found that she had removed the switch SIK3. Mutation SIK3 locked in the "on"position.

Another gene found in mice that spent less time in the sleep phase of rapid eye movements, accidentally falling and dropping out of this condition, which usually lasted for a predictable period of time. A mutation in the NALCN protein, which acts as a channel in the cell walls of neurons. This protein allows ions to break through them. Specifically, this mouse mutation could cause neural activity, which is too early withdrawal of the animal from the phase of rapid eye movement.

Identification of genes associated with sleep, will not lead to immediate answers. Sleep is so important for survival that the ancestors of every sleeping creature, which is living today, risk death in order to do it daily. This means that each of us in the body there are many ways to induce sleep. Mechanisms should be plenty to make it difficult to violate the random gene mutation or something else, to exclude the possibility of the whole dream. Mutant fly that is born with a severe pathology of sleep, over generations to produce more and more need for sleep, says Segal. This may present an inconvenience for the scientists, but at the same time indicates the reliability of the sleep mechanism. And most of the genes associated with sleep, which are found in the last ten years, had a lot of appointments. "There is no separate "gene of sleep," says Divya, Sitaraman, sleep researcher from the University of San Diego. "There are genes for basic functions, which can also impact sleep."

In the new work is a great example. SIK3 appeared to be shown not only in the brain. For many years, scientists have found that it is used all over the body. It is associated with metabolic problems that can lead to drowsiness of the body, says Tom Scammell, a physician and researcher of sleep at Harvard medical school. Medical research mice may help to identify whether the drowsiness with the influence SKI3 a dream, or perhaps with damage to the liver or kidneys.

However, as work on animal models continues to reveal more and more associated with sleep genes in humans, this set requires a much more serious approach. Scientists plucked thousands of people depending on the time they sleep, study their genes, to identify in between any connections and patterns. But research does not bring significant results.

While that was revealed not so many associations with genes, says Rick Saxena, a geneticist from Harvard school of medicine. This is due, most likely, with an excess of enforcement mechanisms for sleep — does not exist or is not found specifically expressed genes, the influence of which you can identify against the background.

However, it is absolutely normal for a relatively new area of research. Yes, dreams explore for a long time, but until recently, these studies were very descriptive. Now these studies are more mechanical. Meanwhile, Yanagisawa and his colleagues continue to monitor the sleeping rodents. And believe me, it's very interesting.



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