Posts Tagged ‘sleep’

Laura Lewis and her team of researchers have been putting in late nights in their Boston University lab. Lewis ran tests until around 3:00 in the morning, then ended up sleeping in the next day. It was like she had jet lag, she says, without changing time zones. It’s not that Lewis doesn’t appreciate the merits of a good night’s sleep. She does. But when you’re trying to map what’s happening in a slumbering human’s brain, you end up making some sacrifices. “It’s this great irony of sleep research,” she says. “You’re constrained by when people sleep.”

Her results, published last week in the journal Science, show how our bodies clear toxins out of our brains while we sleep and could open new avenues for treating and preventing neurodegenerative diseases like Alzheimer’s.

When we sleep our brains travel through several phases, from a light slumber to a deep sleep that feels like we’ve fallen unconscious, to rapid eye movement (REM) sleep, when we’re more likely to have dreams. Lewis’ work looks at non-REM sleep, that deep phase which generally happens earlier in the night and which has already been associated with memory retention. One important 2013 study on mice showed that while the rodents slept, toxins like beta amyloid, which can contribute to Alzheimer’s disease, got swept away.

Lewis was curious how those toxins were cleared out and why that process only happened during sleep. She suspected that cerebrospinal fluid, a clear, water-like liquid that flows around the brain, might be involved. But she wasn’t sure what was unique about sleep. So her lab designed a study that measured several different variables at the same time.

Study participants had to lie down and fall asleep inside an MRI machine. To get realistic sleep cycles, the researchers had to run the tests at midnight, and they even asked subjects to stay up late the night before so people would be primed to drift off once the test began.

Lewis outfitted the participants with an EEG cap so she could look at the electrical currents flowing through their brains. Those currents showed her which stage of sleep the person was in. Meanwhile, the MRI measured the blood oxygen levels in their brains and showed how much cerebrospinal fluid was flowing in and out of the brain. “We had a sense each of these metrics was important, but how they change during sleep and how they relate to each other during sleep was uncharted territory for us,” she says.

What she discovered was that during non-REM sleep, large, slow waves of cerebrospinal fluid were washing over the brain. The EEG readings helped show why. During non-REM sleep, neurons start to synchronize, turning on and off at the same time. “First you would see this electrical wave where all the neurons would go quiet,” says Lewis. Because the neurons had all momentarily stopped firing, they didn’t need as much oxygen. That meant less blood would flow to the brain. But Lewis’s team also observed that cerebrospinal fluid would then rush in, filling in the space left behind.

“It’s a fantastic paper,” says Maiken Nedergaard, a neuroscientist at the University of Rochester who led the 2013 study that first described how sleep can clear out toxins in mice. “I don’t think anybody in their wildest fantasy has really shown that the brain’s electrical activity is moving fluid. So that’s really exciting.”

One big contribution of the paper is it helps show that the systems Nedergaard has been studying in mice are present and hugely important for humans too. “It’s telling you sleep is not just to relax,” says Nedergaard. “Sleep is actually a very distinct function.” Neurons don’t all turn off at the same time when we’re awake. So brain blood levels don’t drop enough to allow substantial waves of cerebrospinal fluid to circulate around the brain and clear out all the metabolic byproducts that accumulate, like beta amyloid.

The study also could have clinical applications for treating Alzheimer’s. Recent attempts at developing medications have targeted beta amyloid. But drugs that looked promising at first all failed once they got into clinical trials. “This opens a new avenue,” says Nedergaard. Instead of trying to act on one particular molecule, new interventions might instead focus on increasing the amount of cerebrospinal fluid that washes over the brain.

That would help clear out beta amyloid but also could help with other molecules like tau, a protein that gets tangled in Alzheimer’s patients’ brains and harms the connections between neurons. Finding a way to clear out all of that garbage could be much more powerful than just focusing on one piece of the problem. “Aging is not just about one molecule,” says Nedergaard. “Everything fails.”

These discoveries bring along their own set of questions. Lewis didn’t study what happens during other stages of sleep, and she only looked at healthy young adults. But the methods she used were entirely noninvasive—or as noninvasive as having people sleep in an MRI while hooked up to lots of machines can be. She didn’t even inject any dye. That will make it easier to start studying older participants who may be developing neurodegenerative diseases.

https://www.wired.com/story/scientists-now-know-how-sleep-cleans-toxins-from-the-brain/?bxid=5c48e315fc942d0477abe04c&cndid=50678559&esrc=sign-up-page&source=EDT_WIR_NEWSLETTER_0_DAILY_ZZ&utm_brand=wired&utm_campaign=aud-dev&utm_mailing=WIR_Daily_110119&utm_medium=email&utm_source=nl&utm_term=list1_p4


Brain tissue from deceased patients with Alzheimer’s has more tau protein buildup (brown spots) and fewer neurons (red spots) as compared to healthy brain tissue.

By Yasemin Saplakoglu

Alzheimer’s disease might be attacking the brain cells responsible for keeping people awake, resulting in daytime napping, according to a new study.

Excessive daytime napping might thus be considered an early symptom of Alzheimer’s disease, according to a statement from the University of California, San Francisco (UCSF).

Some previous studies suggested that such sleepiness in patients with Alzheimer’s results directly from poor nighttime sleep due to the disease, while others have suggested that sleep problems might cause the disease to progress. The new study suggests a more direct biological pathway between Alzheimer’s disease and daytime sleepiness.

In the current study, researchers studied the brains of 13 people who’d had Alzheimer’s and died, as well as the brains from seven people who had not had the disease. The researchers specifically examined three parts of the brain that are involved in keeping us awake: the locus coeruleus, the lateral hypothalamic area and the tuberomammillary nucleus. These three parts of the brain work together in a network to keep us awake during the day.

The researchers compared the number of neurons, or brain cells, in these regions in the healthy and diseased brains. They also measured the level of a telltale sign of Alzheimer’s: tau proteins. These proteins build up in the brains of patients with Alzheimer’s and are thought to slowly destroy brain cells and the connections between them.

The brains from patients who had Alzheimer’s in this study had significant levels of tau tangles in these three brain regions, compared to the brains from people without the disease. What’s more, in these three brain regions, people with Alzheimer’s had lost up to 75% of their neurons.

“It’s remarkable because it’s not just a single brain nucleus that’s degenerating, but the whole wakefulness-promoting network,” lead author Jun Oh, a research associate at UCSF, said in the statement. “This means that the brain has no way to compensate, because all of these functionally related cell types are being destroyed at the same time.”

The researchers also compared the brains from people with Alzheimer’s with tissue samples from seven people who had two other forms of dementia caused by the accumulation of tau: progressive supranuclear palsy and corticobasal disease. Results showed that despite the buildup of tau, these brains did not show damage to the neurons that promote wakefulness.

“It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease,” Oh said in the statement. “Understanding why this is the case is something we need to follow up in future research.”

Though amyloid proteins, and the plaques that they form, have been the major target in several clinical trials of potential Alzheimer’s treatments, increasing evidence suggests that tau proteins play a more direct role in promoting symptoms of the disease, according to the statement.

The new findings suggest that “we need to be much more focused on understanding the early stages of tau accumulation in these brain areas in our ongoing search for Alzheimer’s treatments,” senior author Dr. Lea Grinberg, an associate professor of neurology and pathology at the UCSF Memory and Aging Center, said in the statement.

The findings were published Monday (Aug. 12) in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

https://www.livescience.com/alzheimers-attacks-wakefulness-neurons.html?utm_source=notification

by Ed Cara

People who only occasionally fall down an internet rabbit hole on their smartphones late at night might be able to rest easier—at least according to the results of a new study in mice. Researchers found that short bursts of light exposure at night won’t necessarily disrupt your internal clock, including sleep habits.

The researchers used mice to study the circadian rhythm. In both mice and humans, the circadian rhythm is primarily controlled by the brain’s suprachiasmatic nucleus (SCN), a tiny region found in the hypothalamus. One crucial aspect of the SCN involves regulating our sleep/wake, or light/dark, cycle. It’s long been thought that any kind of light exposure our eyes take in affects the SCN, and thus, can affect our sleep.

“Light information comes into the SCN, and that’s what synchronizes all of the body’s clocks to the light/dark cycle,” said lead author Tiffany Schmidt, a neurogeneticist at Northwestern, in a release from the university. “This one master pacemaker makes sure everything is in sync.”

Schmidt and her team wanted to test this long-held theory that the SCN responds to any light exposure. So they bred mice that had light-sensitive nerve cells in the retina that were only capable of communicating with the SCN. Then they exposed these mice to light for short periods of time.

Because mice, unlike people, are nocturnal, the light should have made them want to fall asleep. But they instead just carried out on with their day, sleeping and waking as normal. Their body temperature, which fluctuates predictably before, during, and after sleep, also followed the same pattern seen in mice with normal circadian rhythms.

What this could mean, according to the authors, is that our brains respond to acute light—meaning brief exposures to light—through a different neural pathway than what’s used for long periods of light exposure, a pathway that doesn’t involve the SCN.

“If these two effects—acute and long-term light exposure—were driven through the same pathway, then every minor light exposure would run the risk of completely shifting our body’s circadian rhythms,” Schmidt said.

The findings will be published this week in the journal eLife.

Mice and their brains aren’t a perfect proxy for people, obviously. And even if the same general principle does apply to us, Schmidt and her team say there’s no clear lead on where these other pathways could exist in the brain. And there’s undoubtedly a point where being exposed to light late at night too long or too often can start to affect our internal clock—even if where that point lies is still a mystery right now. There needs to be a lot much research studying these questions and others.

What is clear, the authors cautioned, is that chronic nighttime light exposure, and the disruptions to our sleep it can cause, can be very bad for health. In other words, don’t use this study as an excuse to start regularly binge-watching Netflix till 4 a.m.

“Light at the wrong time of day is now recognized as a carcinogen,” Schmidt said. “We want people to feel alert while they are exposed to light without getting the health risks that are associated with shifted circadian rhythms, such as diabetes, depression and even cancer.”

https://gizmodo.com/checking-your-phone-at-night-wont-necessarily-throw-off-1836603924

Birds do it, bees do it, even educated fleas do it: No, they don’t fall in love, they sleep. However, exactly why all animals with a nervous system evolved to sleep has been a longstanding scientific mystery. Slumber certainly feels great, but it doesn’t exactly make sense — why should we spend a third of our lives passed out?

In a study published Tuesday in Nature Communications, scientists say they’ve figured out why on the cellular level. The core cellular function of sleep, they explain, is to combat the neuronal DNA damage that accumulates during waking hours. Sleep allows neurons to perform the efficient DNA maintenance that’s essential to a healthy life: Scientists already know that less sleep means greater vulnerability to anxiety, frustration, and ill health, but now they’re closer to understanding exactly why that’s the case.

“We’ve found a causal link between sleep, chromosome dynamics, neuronal activity, and DNA damage and repair with direct physiological relevance to the entire organism,” study lead Lior Appelbaum, Ph.D., said Tuesday. “Sleep gives an opportunity to reduce DNA damage accumulated in the brain during wakefulness.”

Applebaum and his team examined how sleep is linked to nuclear maintenance by examining one of the most frequently used model organisms for genetic and developmental studies: the zebrafish. These transparent zebrafish were genetically engineered so that the chromosomes in their neurons carried colorful chemical tags. While the fish were awake and asleep, the scientists observed the movement of DNA and nuclear proteins inside the fish with a high-resolution microscope, which can be seen in the video above.

They witnessed that when the fish were awake, the chromosomes were relatively inactive, and broken strands of DNA accumulated in the neurons. However, when the fish were asleep the chromosomes became more active, and the DNA damage that had accumulated began to be repaired. Subsequent analysis confirmed that in order to perform nuclear maintenance, single neurons need an animal to go to sleep.

The accumulation of DNA damage, says Appelbaum, is the “price of wakefulness.” During wakefulness, chromosomes are less active, leaving them vulnerable to DNA damage caused by radiation, oxidative stress, and neuronal activity. Sleep kickstarts chromosomal activity and synchronizes nuclear maintenance within individual neurons, allowing the brain to be repaired while it’s not being used to the extent that it is during the day.

“It’s like potholes in the road,” Applebaum says. “Roads accumulate wear and tear, especially during daytime rush hours, and it is most convenient and efficient to fix them at night, when there is light traffic.”

Anecdotally, we know that a good night’s sleep can be restorative. Now it appears that it’s quantifiably restorative for the brain as well, allowing it to naturally mend the damage of the day.

Abstract:

Sleep is essential to all animals with a nervous system. Nevertheless, the core cellular function of sleep is unknown, and there is no conserved molecular marker to define sleep across phylogeny. Time-lapse imaging of chromosomal markers in single cells of live zebrafish revealed that sleep increases chromosome dynamics in individual neurons but not in two other cell types. Manipulation of sleep, chromosome dynamics, neuronal activity, and DNA double-strand breaks (DSBs) showed that chromosome dynamics are low and the number of DSBs accumulates during wakefulness. In turn, sleep increases chromosome dynamics, which are necessary to reduce the amount of DSBs. These results establish chromosome dynamics as a potential marker to define single sleeping cells, and propose that the restorative function of sleep is nuclear maintenance.

mice-x

by SUKANYA CHARUCHANDRA

The protein Bmal1, which helps regulate the body’s internal clock, is found in especially high levels in the brain and in skeletal muscles. Mice completely deficient in Bmal1 were known to suffer from sleep impairments, but the specifics at play weren’t clear. At the University of California, Los Angeles, Ketema Paul and colleagues looked to these mice for clues about the role Bmal1 plays in sleep regulation.

MUSCLE PLAY
When Paul’s team restored levels of the Bmal1 protein in the mice’s brains, their ability to rebound from a night of bad sleep remained poor. However, turning on production in skeletal muscles alone enabled mice to sleep longer and more deeply to recover after sleep loss.

SWEET DREAMS
For decades, scientists have thought sleep was controlled purely by the brain. But the new study indicates the ability to catch up on one’s sleep after a bout of sleeplessness is locked away in skeletal muscles, not the brain—at least for mice. “I think it’s a real paradigm shift for how we think about sleep,” says John Hogenesch, a chronobiologist at Cincinnati Children’s Hospital Medical Center who discovered the Bmal1 gene but was not involved in this study.

TARGET LOCKED
Paul’s group also found that having too much of the Bmal1 protein in their muscles not only made mice vigilant but also invulnerable to the effects of sleep loss, so that they remained alert even when sleep-deprived and slept fewer hours to regain lost sleep. “To me, that presents a potential target where you could treat sleep disorders,” says Paul, noting that an inability to recover from sleep loss can make us more susceptible to diseases.

The paper
J.C. Ehlen et al., “Bmal1 function in skeletal muscle regulates sleep,” eLife, 6:e26557, 2017.

https://www.the-scientist.com/the-literature/muscles-hold-a-key-to-sleep-recovery-64685?utm_campaign=TS_DAILY%20NEWSLETTER_2018&utm_source=hs_email&utm_medium=email&utm_content=66141129&_hsenc=p2ANqtz–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129

he number of people sleeping in McDonald’s outlets has increased six-fold over the past five years, a trend partly driven by rising rents and substandard housing that makes life especially unbearable in the city’s baking weather, a study has found.

The survey, organised by Junior Chamber International’s Tai Ping Shan branch and conducted in June by volunteers, found 334 people had slept in a McDonald’s outlet nightly over at least the past three months. Of the 110 branches that operate 24 hours in the city, 84 had seen overnight sleepers.

This is a six-fold increase from a similar study in 2013, which found only 57 such people, popularly dubbed McRefugees or McSleepers.

A branch in Tsuen Wan hosted more than 30 sleepers, the highest among all branches, according to the latest study.

Researchers were able to interview 53 McRefugees aged between 19 and 79 in depth, and found 57 per cent of them had a job and 71 per cent of them had flats that they rented or owned, contrary to the common belief that these people tended to be jobless and homeless.

Saving on air conditioning costs, as well as comfort and security, topped a list of reasons given by these interviewees, followed by high rents, conflict with family members, the ability to develop social relations at the chain and substandard housing.

Other reasons included saving on transport costs and time to work, and seeking temporary shelter while waiting for low-rent public housing.

“Family is the basic unit in a society,” Tai Ping Shan publication commission chairwoman Jennifer Hung Sin-yu said. “Even one person who has a home but cannot return is too many. This phenomenon is worth our attention.”

Hung said the reasons given by interviewees showed that unaffordable housing had forced the poor into inferior living conditions such as subdivided flats, which subsequently drove them into McDonald’s for comfort and security.

One McRefugee renting a subdivided flat in To Kwa Wan, Hung said, told volunteers that her landlord charged her HK$16 for a unit of electricity, compared to about HK$1.10 charged by the city’s two main power suppliers.

Hung said the woman’s flat did not have any windows, which made the city’s humid and hot summer even more unbearable without air conditioning.

“She told us sometimes she couldn’t even feel the flow of the air,” Hung said.

Hong Kong is consistently ranked the world’s least affordable property market. As of the end of March, there were 270,000 applicants on the waiting list for public rental housing; the average waiting time for families or single elderly applicants was five years and one month.

Subdivided housing is the main option for these families while they wait, but it is affordable only because of the small sizes – often around 100 sq ft – of these units, which entail fire risks, poor ventilation and poor hygiene.

Besides inadequate housing, family problems are another main issue, Hung said.

One of the cases, a 19-year-old referred to in the study as Ah Lung, was a construction worker who ate, played mobile phone games and slept at a McDonald’s branch in Mong Kok. He did not want to go home due to a bad relationship with his parents, while his income enabled him to live away from home.

A 60-year-old woman was observed by volunteers as “without the unique characteristics of street sleepers”. She was well dressed, with her diamond wedding ring still on her finger. She also had a flat in the New Territories, but had nobody to share the home with her.

She and her late husband did not have any children and she felt lonely in her home and eating by herself, which was why she spent most of her time at the fast-food chain, where there were many people coming and going.

Project consultant Lee Ho-ey said the government should allocate more resources to non-governmental organisations to reach out to McRefugees, providing them with counselling and help.

https://www.scmp.com/news/hong-kong/community/article/2158365/number-people-sleeping-hong-kong-mcdonalds-branches

Thanks to Kebmodee for bringing this to the It’s Interesting community.

By Hilary Hurd Anyaso

Leading theories propose that sleep presents an opportune time for important, new memories to become stabilized. And it’s long been known which brain waves are produced during sleep. But in a new study, researchers set out to better understand the brain mechanisms that secure memory storage.

The team from Northwestern and Princeton universities set out to find more direct and precisely timed evidence for the involvement of one particular sleep wave — known as the “sleep spindle.”

In the study, sleep spindles, described as bursts of brain activity typically lasting around one second, were linked to memory reactivation. The paper, “Sleep spindle refractoriness segregates periods of memory reactivation,” published today in the journal Current Biology.

“The most novel aspect of our study is that we found these spindles occur rhythmically — about every three to six seconds — and this rhythm is related to memory,” said James W. Antony, first author of the study and a postdoctoral fellow in Princeton’s Computational Memory Lab.

Three experiments explored how recent memories are reactivated during sleep. While volunteers took an afternoon nap, sound cues were surreptitiously played. Each was linked to a specific memory. The researchers’ final experiment showed that if cues were presented at opportune times such that spindles could follow them, the linked memories were more likely to be retained. If they were presented when a spindle was unlikely to follow, the linked memories were more likely to be forgotten.

“One particularly remarkable aspect of the study was that we were able to monitor spindles moment by moment while people slept,” said Ken A. Paller, senior author of the study and professor of psychology at Northwestern’s Weinberg College of Arts and Sciences. “Therefore, we could know when the brain was most ready for us to prompt memory reactivation.”
If the researchers reminded people of a recently learned fact, a spindle would likely be evident in the cerebral cortex, and memory for that information would be improved, added Paller, also director of Northwestern’s Cognitive Neuroscience Program.

“In memory research, we know it’s important to segregate experiences while you’re awake so that everything doesn’t just blend together,” said Antony, who worked in Paller’s lab at Northwestern as a doctoral student. “If that happens, you may have difficulty retrieving information because so many things will come to mind at once. We believe the spindle rhythmicity shown here might play a role in segregating successive memory reactivations from each other, preventing overlap that might cause later interference between memories.”

Ultimately, the researchers’ goal is to understand how sleep affects memory under natural conditions and how aging or disease can impact these functions.

“With that goal in mind, we’ve helped elucidate the importance of sleep spindles more generally,” Antony said.

Paller said they are on the trail of the physiology of memory reactivation.

“Future work will be needed to see how spindles fit together with other aspects of the physiology of memory and will involve other types of memory testing and other species,” Paller said.

In addition to Antony and Paller, co-authors are Luis Piloto, Margaret Wang, Paula Pacheco and Kenneth A. Norman, all of Princeton.

https://news.northwestern.edu/stories/2018/may/bursts-of-brain-activity-linked-to-memory-reactivation/