Could This Gene Cure Sleep Disorders?
New research on mice at UCLA could hold a key for humans with sleep disorders.
Sleep is having its day. While we’ve long known that how we spend our nighttime hours is important, why that should be so eluded researchers for some time. The more sleep is studied, however, the more we realize how essential it is for proper cognitive and physical functioning.
Yet so many distractions keep us from enjoying a proper night’s rest: the blue hue of cell phones, binge watching, chronic anxiety, poor nutrition, parenting, overnight shifts. The cost of lost sleep is steep, increasing your risk for heart problems, infectious diseases, diabetes, and stroke.
Up until now, the most common treatment for insomnia has been sleeping pills, which come with a steep price tag, including impaired cognition, stomach problems, burning sensations in your body’s extremities, and daytime drowsiness, all for mere minutes of extra sleep each evening.
Sleeping pills slow down your nervous system by interacting with specific brain receptors. Specifically, benzodiazepines increase the effects of gamma-Aminobutyric acid (GABA), which causes a system-wide reduction in neuronal activity in your nervous system. As with similar but slower-acting nonbenzodiazepines, these pills are not prescribed for long-term use.
Interestingly, treating sleep disorders by targeting the brain may have been misguided, or so claims a new study on mice published in eLife. Researchers at UCLA targeted the Bmal1 gene—a “master gene” discovered in 1997, it has long been known to effect circadian rhythms—in both the brain and muscles of mice. What they found surprised them.
According to the team, led by senior author Ketema Paul, this study provides the first evidence that a gene in muscles can send signals to the brain that it’s ready to sleep. Only the opposite had been assumed. Paul had his crew repeat the experiment numerous times to ensure their findings were correct.
Paul’s team turned Bmal1 off throughout the brain and body of the mice, which means they would not be able to recover from sleep deprivation. Then they turned it back on, one group in the brain, another in the body. The body group rebounded while the brain group did not. Paul states,
We show that not only is Bmal1 responsible for the ability to recover from sleep loss, but also that Bmal1 expression in the skeletal muscle is responsible for that process. When we increased Bmal1 in the skeletal muscle, the mice were able to tolerate more sleep loss. That suggests the skeletal muscle is directly communicating with the brain.
When the gene was removed from muscles, the mice were much sleepier. Paul believes this oversight in sleep research is in part due to the focus on targeting the brain. If the evidence bears out in humans, Paul envisions a pill that boosts levels of Bmal1 in muscles, perhaps even targeting the specific gene that communicates with the brain.
Though an early state for this research, it’s an exciting one for poor sleepers. Until then, plenty of breathing exercises and regenerative techniques are available to help insomniacs calm their nervous systems in the late hours, without the need for sleeping pills. Side effects of increased Bmal1 will also have to be considered, though at the moment, this is a promising start.
Derek is the author of Whole Motion: Training Your Brain and Body For Optimal Health. Based in Los Angeles he is working on a new book about spiritual consumerism. Stay in touch on Facebook and Twitter.
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A new method promises to capture an elusive dark world particle.
- Scientists working on the Large Hadron Collider (LHC) devised a method for trapping dark matter particles.
- Dark matter is estimated to take up 26.8% of all matter in the Universe.
- The researchers will be able to try their approach in 2021, when the LHC goes back online.
Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.
- Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
- They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
- The research raises many ethical questions and puts to the test our current understanding of death.
The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?
But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.
What's dead may never die, it seems
The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.
BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.
The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.
As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.
The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.
"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.
An ethical gray matter
Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.
The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.
Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.
Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?
"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."
One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.
The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.
"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.
It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.
Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?
The dilemma is unprecedented.
Setting new boundaries
Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."
She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.
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