Tag Archives: #sleep

Neuroscience

Brain Cortex May Regulate the Need For Sleep (Neuroscience)

Leave a comment

Why we sleep, and the processes behind sleep, are amongst the most interesting questions in modern neuroscience. 

Researchers at the University of Oxford have now uncovered a new target for sleep investigations within the mammalian brain – the cerebral cortex. The paper was published today in Nature Neuroscience.

The cerebral cortex makes up about 80% of the brain’s volume and is responsible for many complex phenomena, including perception, thought, language, attention and memory. While activity in the cortex is normally used in sleep studies to record sleep/awake patterns, the latest study from Oxford has found that processes within the cortex itself may actually be responsible for sleep control, such as how long to sleep for and how deeply to sleep.

The study monitored brain activity in laboratory mice, which have fundamental brain similarities to humans in terms of anatomy and sleep mechanisms. Neurons in two areas of the cortex – neocortical layer 5 and a part of the hippocampus – were ‘silenced’ in the mice’s brains. When the neurons in these areas of the brain were deactivated, the lab mice suddenly stayed awake for at least three hours longer every day. To put this into perspective, an average mouse lives for approximately two years, which means they gained three full months of ‘awake’ time in over their lifespans. In human terms, this would equate to about 10 years.

Though the mice were awake longer, their need for deep sleep did not appear to be affected. Normally, when mice (and humans) stay awake longer than usual and get more tired, we sleep more deeply to compensate. This study in lab mice found that they did not sleep any more deeply than usual. Their body clock did not appear to be affected at all by the extra waking hours in their days.

Dr Lukas Krone of the Department of Physiology, Anatomy and Genetics, University of Oxford, and lead author on the study, said, ‘Our finding that the cortex is part of the sleep-regulating system opens new perspectives for sleep medicine. It might be possible to use already-established non-invasive brain stimulation techniques to alter cortical activity and thereby moderate sleep for therapeutic purpose, such as for the treatment of sleep disorders.’

Professor Vladyslav Vyazovskiy, Head of Sleep, Brain and Behaviour Laboratory in the Department of Physiology, Anatomy and Genetics and a member of Sleep and Circadian Neuroscience Institute (SCNi), a co-corresponding author on the paper, said, ‘The cortex is a highly complex structure, both anatomically and functionally, and is therefore difficult to study; and this is why we think its role in sleep control was previously overlooked. The effects on sleep of cortical silencing offers a novel and fresh perspective on the mechanisms of sleep control, and has the strong potential to transform the field of sleep neurobiology.’

Professor Zoltán Molnár, Head of Cerebral Cortical Development and Evolution Laboratory in the Department of Physiology, Anatomy and Genetics and co-corresponding author on the paper said, ‘Much effort and funding over the last decades has been spent on clarifying the role of subcortical structures in sleep regulation and the cerebral cortex was not the focus of attention. When we first performed our ‘silencing’ study on different cortical projection neurons, I expected such phenotype from another neuronal population and not from layer 5 and hippocampus. For me, the discovery of its effect on the mice’s sleep was a great surprise.’

While this study is an important first step, more work needs to be done. ‘We hope that many other research groups will now be investigating how exactly the cortex contributes to sleep regulations,’ said Dr Krone. ‘A multidisciplinary approach will help us to fully understand the cellular mechanisms and neuronal circuits through which the cortex regulates sleep.’

Featured image credit: Shutterstock

Reference: Lukas B. Krone et al, A role for the cortex in sleep–wake regulation, Nature Neuroscience (2021). DOI: 10.1038/s41593-021-00894-6

Provided by University of Oxford

Psychiatry

Want To Reduce Your Depression Risk? Wake Up An Hour Earlier (Psychiatry)

1 Comment

Waking up just one hour earlier could reduce a person’s risk of major depression by 23%, suggests a sweeping new genetic study published May 26 in the journal JAMA Psychiatry.

The study of 840,000 people, by researchers at University of Colorado Boulder and the Broad Institute of MIT and Harvard, represents some of the strongest evidence yet that chronotype—a person’s propensity to sleep at a certain time —influences depression risk.

It’s also among the first studies to quantify just how much, or little, change is required to influence mental health.

As people emerge, post-pandemic, from working and attending school remotely— a trend that has led many to shift to a later sleep schedule—the findings have important implications.

“We have known for some time that there is a relationship between sleep timing and mood, but a question we often hear from clinicians is: How much earlier do we need to shift people to see a benefit?” said senior author Celine Vetter, assistant professor of integrative physiology at CU Boulder. “We found that even one-hour earlier sleep timing is associated with significantly lower risk of depression.”

Previous observational studies have shown that night owls are as much as twice as likely to suffer from depression as early risers, regardless of how long they sleep. But because mood disorders themselves can disrupt sleep patterns, researchers have had a hard time deciphering what causes what.

Other studies have had small sample sizes, relied on questionnaires from a single time point, or didn’t account for environmental factors which can influence both sleep timing and mood, potentially confounding results.

In 2018, Vetter published a large, long term study of 32,000 nurses showing that “early risers” were up to 27% less likely to develop depression over the course of four years, but that begged the question: What does it mean to be an early riser?

How your genes influence when you wake up

To get a clearer sense of whether shifting sleep time earlier is truly protective, and how much shift is required, lead author Iyas Daghlas turned to data from the DNA testing company 23 and Me and the biomedical database UK Biobank. Daghlas then used a method called “Mendelian randomization” that leverages genetic associations to help decipher cause and effect.

“Our genetics are set at birth so some of the biases that affect other kinds of epidemiological research tend not to affect genetic studies,” said Daghlas, who graduated in May from Harvard Medical School.

More than 340 common genetic variants, including variants in the so-called “clock gene” PER2, are known to influence a person’s chronotype, and genetics collectively explains 12-42% of our sleep timing preference.

The researchers assessed deidentified genetic data on these variants from up to 850,000 individuals, including data from 85,000 who had worn wearable sleep trackers for 7 days and 250,000 who had filled out sleep-preference questionnaires. This gave them a more granular picture, down to the hour, of how variants in genes influence when we sleep and wake up.

In the largest of these samples, about a third of surveyed subjects self-identified as morning larks, 9% were night owls and the rest were in the middle. Overall, the average sleep mid-point was 3 a.m., meaning they went to bed at 11 p.m. and got up at 6 a.m.

With this information in hand, the researchers turned to a different sample which included genetic information along with anonymized medical and prescription records and surveys about diagnoses of major depressive disorder.

Using novel statistical techniques, they asked: Do those with genetic variants which predispose them to be early risers also have lower risk of depression?

The answer is a firm yes.

Each one-hour earlier sleep midpoint (halfway between bedtime and wake time) corresponded with a 23% lower risk of major depressive disorder.

Put another way, if someone who normally goes to bed at 1 a.m. goes to bed at midnight instead and sleeps the same duration, they could cut their risk by 23%; if they go to bed at 11 p.m., they could cut it by about 40%.

It’s unclear from the study whether those who are already early risers could benefit from getting up even earlier. But for those in the intermediate range or evening range, shifting to an earlier bedtime would likely be helpful.

Light days, dark nights key

What could explain this effect?

Some research suggests that getting greater light exposure during the day, which early-risers tend to get, results in a cascade of hormonal impacts that can influence mood.

Others note that having a biological clock, or circadian rhythm, that trends differently than most peoples’ can in itself be depressing.

“We live in a society that is designed for morning people, and evening people often feel as if they are in a constant state of misalignment with that societal clock,” said Daghlas.

He stresses that a large randomized clinical trial is necessary to determine definitively whether going to bed early can reduce depression. “But this study definitely shifts the weight of evidence toward supporting a causal effect of sleep timing on depression.”

For those wanting to shift themselves to an earlier sleep schedule, Vetter offers this advice:

“Keep your days bright and your nights dark,” she says. “Have your morning coffee on the porch. Walk or ride your bike to work if you can, and dim those electronics in the evening.”

Reference: Daghlas I, Lane JM, Saxena R, Vetter C. Genetically Proxied Diurnal Preference, Sleep Timing, and Risk of Major Depressive Disorder. JAMA Psychiatry. 2021 May 26. doi: 10.1001/jamapsychiatry.2021.0959. Epub ahead of print. PMID: 34037671.

Provided by University of Colorado Boulder

Medicine

Does Listening To Calming Music At Bedtime Actually Help You Sleep? (Medicine)

Leave a comment

Geriatrics Society Research Summary

A new study published in the Journal of the American Geriatrics Society has found that listening to music can help older adults sleep better.

Researchers from the National Cheng Kung University Hospital in Taiwan combined the results of past studies to understand the effect that listening to music can have on the quality of older adults’ sleep. Their work suggests that:

  • Older adults (ages 60 and up) living at home sleep better when they listen to music for 30 minutes to one hour at bedtime.
  • Calm music improves older adults’ sleep quality better than rhythmic music does.
  • Older adults should listen to music for more than four weeks to see the most benefit from listening to music.

Why Older Adults Have Trouble Getting a Good Night’s Sleep

As we age, our sleep cycles change and make a good night’s sleep harder to achieve. What does it really mean to get a good night’s sleep? If you wake up rested and ready to start your day, you probably slept deeply the night before. But if you’re tired during the day, need coffee to keep you going, or wake up several times during the night, you may not be getting the deep sleep you need. [1] According to the National Institute on Aging, older adults need seven to nine hours of sleep each night.[2]

But studies have shown that 40 to 70 percent of older adults have sleep problems and over 40 percent have insomnia, meaning they wake up often during the night or too early in the morning.  Sleep problems can make you feel irritable and depressed, can cause memory problems, and can even lead to falls or accidents.

How the Researchers Studied the Effect of Music on Older Adults’ Quality of Sleep

For their study, the researchers searched for past studies that tested the effect of listening to music on older adults with sleep problems who live at home. They looked at five studies with 288 participants. Half of these people listened to music; the other half got the usual or no treatment for their sleep problems. People who were treated with music listened to either calming or rhythmic music for 30 minutes to one hour, over a period ranging from two days to three months.  (Calming music has slow tempo of 60 to 80 beats per minute and a smooth melody, while rhythmic music is faster and louder.) All participants answered questions about how well they thought they were sleeping. Each participant ended up with a score between 0 and 21 for the quality of their sleep.

The researchers looked at the difference in average scores for:

  • people who listened to music compared to people who did not listen to music;
  • people who listened to calm music compared to people who listened to rhythmic music;
  • and people who listened to music for less than four weeks compared to people who listened to music for more than four weeks.

What the Researchers Learned

Listening to calming music at bedtime improved sleep quality in older adults, and calming music was much better at improving sleep quality than rhythmic music. The researchers said that calming music may improve sleep by slowing your heart rate and breathing, and lowering your blood pressure.[3] This, in turn helps lower your levels of stress and anxiety.

Researchers also learned that listening to music for longer than four weeks is better at improving sleep quality than listening to music for a shorter length of time.

Limits of the Study

  • Researchers only looked at studies published in English and Chinese, meaning they may have missed studies in other languages on the effect of listening to music on sleep in older adults.
  • Results may not apply to older adults with Alzheimer’s disease or Parkinson’s disease.
  • In the studies researchers used, people who listened to music received more attention from researchers than did people who got standard or no treatment for their sleep problems. This means that sleep improvements in the music therapy group could be due to that extra attention.
  • Since the different studies used different kinds of music, researchers could not single out which type of calming music improved sleep the most.
  • All of the people in the study had similar kinds of sleep problems. This means listening to music may not help people with other kinds of sleep problems.

What this Study Means for You

If you’re having trouble sleeping, listening to music can be a safe, effective, and easy way to help you fall and stay asleep. It may also reduce your need for medication to help you sleep.

This summary is from “Effect of music therapy on improving sleep quality in older adults: A systematic review and meta-analysis.” It appears online ahead of print in the Journal of the American Geriatrics Society. The study authors are Chia-Te Chen, NP, MS; Yen-Chin Chen, RN, PhD; Heng-Hsin Tung RN, FNP, PhD; Ching-Ju, Fang, MLIS; Jiun-Ling Wang, MD; Nai-Ying Ko RN, PhD; and Ying-Ju Chang, RN, PhD.

[1] https://www.sleepfoundation.org/how-sleep-works/what-makes-good-night-sleep

[2] https://www.nia.nih.gov/health/good-nights-sleep

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011183/

[4] https://sixtyandme.com/aging/fall-prevention-guide/

Reference: Chen, C‐T, Tung, H‐H, Fang, C‐J, et al. Effect of music therapy on improving sleep quality in older adults: A systematic review and meta‐analysis. J Am Geriatr Soc. 2021; 1– 8. https://doi.org/10.1111/jgs.17149

Provided by American Geriatrics Society

Medicine

Music Improves Older Adults’ Sleep Quality (Medicine)

Leave a comment

Listening to music before going to be can improve sleep quality among older adults, according to an analysis of all relevant published clinical trials.

In the analysis, which is published in the Journal of the American Geriatrics Society, five randomized trials met the investigators’ criteria. Older adults who listened to music experienced significantly better sleep quality than those who did not listen to music. Also, older adults who listened to sedative music experienced a greater improvement in sleep quality than those who listened to more rhythmic music. Furthermore, listening to music for longer than four weeks was especially effective at improving sleep quality. 

“Music intervention is an effective strategy and is easy to administer by a caregiver or healthcare worker,” the authors wrote. “Music therapy might be the first line of therapy to recommend in older adults with sleep disturbances, which would reduce the need for dependence on sedatives and sleeping medication.”

Read the American Geriatrics Society’s Health in Aging blog summary of this article here.

Additional Information

Link to Study: https://onlinelibrary.wiley.com/doi/10.1111/jgs.17149

Provided by Wiley

About Journal

The Journal of the American Geriatrics Society (JAGS) is the go-to journal for clinical aging research. We provide a diverse, interprofessional community of healthcare professionals with the latest insights on geriatrics education, clinical practice, and public policy—all supporting the high-quality, person-centered care essential to our well-being as we age. Since the publication of our first edition in 1953, JAGS has remained one of the oldest and most impactful journals dedicated exclusively to gerontology and geriatrics.

About Wiley

Wiley drives the world forward with research and education. Through publishing, platforms and services, we help students, researchers, universities, and corporations to achieve their goals in an ever-changing world. For more than 200 years, we have delivered consistent performance to all of our stakeholders. The Company’s website can be accessed at www.wiley.com.

Medicine

A Good Night’s Sleep Could Do Wonders for Your Sex Life (Medicine)

Leave a comment

New study suggests that poor sleep quality, not duration, can lead to female sexual dysfunction

The importance of getting a good night’s sleep cannot be overstated. Lack of sleep can lead to a number of health problems and affect a woman’s overall quality of life. A new study suggests that insufficient quality sleep also may lead to problems in the bedroom in the form of female sexual dysfunction. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Both sleep and sexual function problems are common in women during midlife. More than 26% of midlife women experience significant sleep symptoms that meet the criteria for insomnia, and sleep problems are reported by nearly half of women during the menopause transition. Up to 43% of women report sexual problems during this same period in their lives.

Multiple studies have been conducted to determine whether there is any association between sleep and sexual function problems. However, most of the previous studies did not consistently evaluate sexual dysfunction with validated tools, nor did they define sexual dysfunction by the presence of sex problems associated with distress.

In this study involving more than 3,400 women (mean age, 53 y), researchers evaluated potential associations between sleep quality and duration and sexual function using validated tools after accounting for factors that may influence both outcomes. They concluded that poor sleep quality, but not sleep duration, was associated with greater odds of female sexual dysfunction. Good sleep quality, in contrast, was linked with sexual activity.

Understanding this association is valuable as clinicians seek to identify potential treatment options for women affected by sleep and sexual problems. Both of these common midlife issues have been determined to adversely affect a woman’s quality of life.

Results are published in the article “Associations of sleep and female sexual function: good sleep quality matters.”

“This study highlights an association between poor sleep quality and sexual dysfunction. These are two common issues for midlife women and asking about and addressing each may contribute to improved quality of life,” says Dr. Stephanie Faubion, NAMS medical director and senior author of the study.

For more information about menopause and healthy aging, visit http://www.menopause.org.

Founded in 1989, The North American Menopause Society (NAMS) is North America’s leading nonprofit organization dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field–including clinical and basic science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and education–makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit http://www.menopause.org.

ORIGINAL SOURCE

https://www.menopause.org/docs/default-source/press-release/sleep-and-sexual-function-association-4-21-21.pdf

Provided by Menopause

Neuroscience

Healthy Sleep May Rely on Long-Overlooked Brain Cells (Neuroscience)

Leave a comment

Cells Called Astrocytes Can Independently Promote Longer or Deeper Sleep in Mice, a New Study Shows

For something we spend one-third of our lives doing, we still understand remarkably little about how sleep works – for example, why can some people sleep deeply through any disturbance, while others regularly toss and turn for hours each night? And why do we all seem to need a different amount of sleep to feel rested?

For decades, scientists have looked to the behavior of the brain’s neurons to understand the nature of slumber. Now, though, researchers at UC San Francisco have confirmed that a different, long under-studied type of brain cell – astrocytes, named for their star-like shape – can influence how long and how deeply animals sleep. The findings could open new avenues for exploring sleep disorder therapies and help scientists better understand brain diseases linked to sleep disturbances, like Alzheimer’s and other dementias, the authors say.   

“This is the first example where someone did an acute and fast manipulation of astrocytes and showed that it was able to actually affect sleep,” said Trisha Vaidyanathan, the study’s first author and a neuroscience graduate student at UCSF. “That positions astrocytes as an active player in sleep. It’s really exciting.”  

When we’re awake, our brains are a Babel of disjointed neuronal voices chattering amongst themselves to allow us to work through life’s daily tasks. But when we sleep, the voices of signaling neurons meld into a unified chorus of bursts, which neuroscientists call slow-wave activity. Recent research had suggested that astrocytes, not just neurons, may help trigger this switch. 

Comprising an estimated 25 percent to 30 percent of brain cells, astrocytes are a type of so-called glial cell that blanket the brain with countless bushy tendrils. This coverage allows each individual astrocyte to listen in on tens of thousands of synapses, the sites of communication between neurons. The plentiful cells connect to each other through specialized channels, which researchers think may allow astrocytes located across the brain to function as one unified network. The hyperconnected and ubiquitous astrocytes might be able to drive synchronized signaling in neurons, as suggested by the new study, published March 17, 2021, in eLife.  

“This could give us new insights not only into sleep but into diseases in which sleep dysregulation is a symptom,” said study senior author Kira Poskanzer, PhD, an assistant professor in the UCSF Department of Biochemistry and Biophysics. “Maybe some diseases are affecting astrocytes in a way we hadn’t thought about before.” 

Poskanzer and her team tracked changes in slow-wave activity in the brains of mice while manipulating astrocytes using a drug that can switch the cells on in genetically engineered animals. Slow-wave activity can be represented in much the same way as vibrations from an earthquake are scratched out on a seismograph. When the brain’s awake, the resulting traces are typically a dense scribble of short and jerky motions. But when slow-wave activity kicks in during certain stages of sleep, the signal slows, lazily looping up and down to create a trace with deep valleys and high peaks. The researchers found that firing up astrocytes led to more slow-wave activity – and thus sleep – in the mice. 

But the team wanted to examine astrocytes’ role in finer detail, asking how these cells exert their influence and what aspects of sleep they manage.  

In addition to the specialized junctions that join neighboring astrocytes, these cells are studded with a variety of receptor molecules that allow them to respond to signals coming from neurons and other types of cells around them. In the study the team hijacked two of these molecules – called the Gi and Gq receptors – and found that they each appeared to control a distinct aspect of sleep. Activating Gq receptors made animals sleep longer, but not more deeply, according to slow-wave measurements, while engaging Gi receptors put into a much deeper slumber without affecting sleep duration.

“Depth and duration are aspects of sleep that often get glossed over and lumped together even in neuroscience,” said Vaidyanathan. “But picking apart these different aspects and how they’re regulated is going to be important down the line for creating more specific sleep treatments.” 

The team also found that astrocyte activity has long reach across the brain: triggering astrocytes in one part of the cortex could affect neuronal behavior at a distant point. The researchers are eager to look further into the extent of this influence and to continue to study how different astrocytic receptors work together to impact sleep, Poskanzer says.  

“What have people been missing because they’re ignoring this group of cells?”  she wondered. “The questions that haven’t been answered thus far in sleep neurobiology – maybe they haven’t been answered because we haven’t been looking in the right places.”  

Authors: Kira Poskanzer is the senior and corresponding author, and Trisha Vaidyanathan is the study’s first author. Other authors were Max Collard, Sae Yokoyama and Michael E. Reitman, all of UCSF.

Study title and doi: Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways DOI: 10.7554/eLife.63329 link: https://elifesciences.org/articles/63329

Funding: The research was supported by the National Institutes of Health (R01NS099254, R01MH121446, R21DA048497), the National Science Foundation (CAREER 1942360), and the UCSF Genentech Fellowship.  

Featured image: UCSF researchers have found that astrocytes impact the length and depth of sleep in mice – a finding that could open new avenues of studying sleep in humans. Image by Poskanzer lab

Provided by UCSF

Biology

How Bacteria Sleep through Antibiotic Attacks? (Biology)

Leave a comment

Bacteria can survive antibiotic treatment even without antibiotic resistance by slowing down their metabolism and going into a type of deep sleep. A research team reveals the changes bacteria undergo to reach this “persister” state. Annelies Zinkernagel, an infectiologist at UZH, is main author of the publication in the scientific journal PNAS.

Resistant bacteria evade the effects of antibiotics by becoming less susceptible, for example by breaking the drugs down. But some bacteria have another survival strategy: they withstand treatment by going into a sleep-like state that enables them to tolerate antibiotics. Once therapy is complete, the bacteria wake up and re-establish the infection. This “persister” state can result in recurrent and difficult-to-treat infections.

A research team from several swiss universities has now gained new insights into this bacterial strategy that could lead to new and effective treatments. Last author of the publication in the journal PNAS* is Annelies Zinkernagel, Professor of infectious diseases at the University of Zurich and University Hospital Zurich.

The research team worked with the bacterium Staphylococcus aureus, which is found on the skin of many people and often causes invasive and difficult-to-treat infections. The researchers took bacteria from an infected patient and cultivated them in Petri dishes. Certain bacterial colonies turned out to be smaller than others. “This tells us that the sample contains persistent bacteria,” says Annelies Zinkernagel. “Unlike other bacteria, persistent bacteria must first ‘awaken’, leading to delayed growth in the nutrient medium.”

Detection and analysis of persistent bacteria in a patient sample are particularly interesting because most of the previous studies on persistent bacteria used bacteria that were cultivated over a prolonged period of time in the laboratory and not taken directly from a patient.

Annelies Zinkernagel was able to show that bacteria can slow down their metabolism under certain situations. (Image: Nicolas Zonvi)

To determine the conditions under which bacteria become persistent, the researchers carried out various stress tests. Stress factors include the presence of human immune cells, antibiotics or an acidic environment, as occurs with abscesses. The researchers discovered that the more extreme the stress conditions, the higher the percentage of persistent bacteria.

Slowed metabolism

Using bacteria recently isolated from patients, the researchers also analysed how persistence mechanisms work. To do this, they looked at the entire set of bacterial proteins, known as the proteome. Their analysis showed that comprehensive molecular reprogramming had taken place and slowed metabolism down in persisters.

However, it did not come to a complete standstill, but the bacteria rather entered a kind of deep sleep. In this way, the bacteria increased their chances of survival in a hostile environment. The researchers also observed that as soon as the environment becomes more hospitable, the persistent bacteria reverse these changes and again become infectious.

“The idea that bacteria do not halt their metabolism but slow it down and change it is not entirely new. However, it is still controversial,” says Zinkernagel. “Our study confirms this idea with great precision.” The current study looked primarily at persistent bacteria. “Previous experiments were based on mixed populations, and the results may thus have been biased by the other bacteria, which are usually in the majority.”

New treatments on the horizon

A better understanding of these mechanisms will contribute to developing new treatments against persistent bacteria. The researchers also showed that vitamin A derivatives that target the cell membrane exhibit promising potential for combating less metabolically active bacteria. Alternatively, says Zinkernagel, “if we succeed in reactivating the growth of these bacteria, they would probably no longer be able to evade the antibiotics.”

The fight against persistent bacteria is also important in the fight against resistance, because recurrent infections must be treated with antibiotics over an extended period. This constant exposure increases the risk of developing antibiotic resistance. The research work was supported by the Swiss National Science Foundation and the clinical research priority programme CRPP – BacVivo – Precision medicine for bacterial infections as well as by the Uniscentia Foundation.

Featured image: Stained staphylococci, imaged through a scanning electron microscope. The bacteria colonise the skin and are usually harmless, but they can also cause serious infections. (Image: istock/Dr Microbe)

Reference: M. Huemer, S.M. Shambat et. al: Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success. PNAS (2021)

Provided by University of Zurich

Biology

Gene Regulator Pumps Iron To Control Sleep, Inflammation and More, Study Finds (Biology)

Leave a comment

A key process in cells that affects immunity and circadian rhythms is illuminated in detail for the first time.

Scientists at Scripps Research have clarified the molecular workings of an important signaling mechanism involved in a host of biological processes including immunity, cholesterol metabolism, and circadian rhythms.

The discovery, reported January 27 in the journal Science Advances, is a significant advance in basic cell biology, and opens up the possibility of designing drug molecules that target this mechanism to treat diseases.

The signaling mechanism illuminated in the study includes an iron-containing molecule called heme, and two molecular switches called REV-ERBα and REV-ERBβ, which work deep within cells to control the activities of large groups of genes. The scientists resolved a long-running conundrum in the field by showing in detail how heme triggers the activation of these switches.

“The REV-ERB receptors are critical regulators of many biological processes and knowing at last how heme interacts with them enables us to start thinking about the design of drugs to target that interaction, potentially to treat sleep disorders, diabetes, atherosclerosis, autoimmune diseases, perhaps even cancers,” says study senior author Douglas Kojetin, PhD, associate professor in the Department of Integrative Structural and Computational Biology at Scripps Research’s Florida campus.

Douglas Kojetin, PhD, associate professor in the Department of Integrative Structural and Computational Biology, collaborated with first author Sarah Mosure on a study of heme’s role in bringing together nuclear receptors involved in sleep and other processes. © SCRIPPS

Scientists have known since 2007 that REV-ERB receptors can be activated by heme, a distinctively four-cornered, red-tinted molecule that contains an iron atom and—though it has many functions in mammals—is best known for its oxygen-carrying role in red blood cells.

Knowing the molecular details of how heme switches on the REV-ERBs would, in principle, enable researchers to engineer drugs to enhance or disrupt the interaction. But those molecular details have been elusive. To work properly, the REV-ERBs have to bind to another protein called NCoR, and experiments to illuminate how heme helps the REV-ERBs hook up with NCoR have yielded conflicting results. In particular, tests using fluorescent tags on the molecules have suggested confusingly that heme prevents the REV-ERBs from coupling to NCoR.

In the new study, Kojetin and colleagues, including first author Sarah Mosure, a PhD candidate in the Kojetin lab who performed most of the experiments, found a flaw in the standard fluorescence-based tests that had caused so much confusion: Heme’s unusual optical properties result in a big distortion of the fluorescence readout and essentially a false picture of heme’s effects. Using two alternative, non-fluorescence-based methods, Mosure showed that heme does in fact help bring REV-ERB and NCoR together.

The team also used X-ray crystallography to reveal at atomic scale how heme and NCoR bind to a REV-ERB receptor.

The experiments used REV-ERBβ, but the researchers expect essentially the same results for the sister receptor REV-ERBα.

“We were able in this study to make sense of more than a decade’s contradictory experiments, by demonstrating the detailed structural basis for this three-way interaction,” Mosure says.

The results mean that the Kojetin lab and other investigators can start designing molecules to interrupt or otherwise alter heme-based activation of the REV-ERBs, to aid the study of this process and its role in disease, and pave the way for future drugs that target it.

Based on the success of this research so far, Mosure has been awarded a two-year predoctoral fellowship from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to study the heme-REV-ERB role in inflammatory disorders.

“Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ” was co-authored by Sarah Mosure, Timothy Strutzenberg, Jinsai Shang, Paola Munoz-Tello, Laura Solt, Patrick Griffin, and Douglas Kojetin.

Funding was provided by the National Institutes of Health (R01GM114420, F31GM126842, R01AI116885, and R01CA241816) and a Richard and Helen DeVos graduate fellowship award.

Featured image: The three-dimensional structure of REV-ERB-beta protein (yellow) bound to heme (red ball and sticks) and NCoR (blue) reveals the molecular basis for a three-way interaction that affects transcription of genes involved in sleep, immunity, and more. Visualizing the complex enables scientists to design potential medicines to affect the interaction.

Provided by SCRIPPS

Biology

On Nights Before a Full Moon, People Go to Bed Later And Sleep Less, Study Shows (Biology)

Leave a comment

For centuries, humans have blamed the moon for our moods, accidents and even natural disasters. But new research indicates that our planet’s celestial companion impacts something else entirely — our sleep.

In a paper published Jan. 27 in Science Advances, scientists at the University of Washington, the National University of Quilmes in Argentina and Yale University report that sleep cycles in people oscillate during the 29.5-day lunar cycle: In the days leading up to a full moon, people go to sleep later in the evening and sleep for shorter periods of time. The research team, led by UW professor of biology Horacio de la Iglesia, observed these variations in both the time of sleep onset and the duration of sleep in urban and rural settings — from Indigenous communities in northern Argentina to college students in Seattle, a city of more than 750,000. They saw the oscillations regardless of an individual’s access to electricity, though the variations are less pronounced in individuals living in urban environments.

The pattern’s ubiquity may indicate that our natural circadian rhythms are somehow synchronized with — or entrained to — the phases of the lunar cycle.

“We see a clear lunar modulation of sleep, with sleep decreasing and a later onset of sleep in the days preceding a full moon,” said de la Iglesia. “And although the effect is more robust in communities without access to electricity, the effect is present in communities with electricity, including undergraduates at the University of Washington.”

Using wrist monitors, the team tracked sleep patterns among 98 individuals living in three Toba-Qom Indigenous communities in the Argentine province of Formosa. The communities differed in their access to electricity during the study period: One rural community had no electricity access, a second rural community had only limited access to electricity — such as a single source of artificial light in dwellings — while a third community was located in an urban setting and had full access to electricity. For nearly three-quarters of the Toba-Qom participants, researchers collected sleep data for one to two whole lunar cycles.

Past studies by de la Iglesia’s team and other research groups have shown that access to electricity impacts sleep, which the researchers also saw in their study: Toba-Qom in the urban community went to bed later and slept less than rural participants with limited or no access to electricity.

But study participants in all three communities also showed the same sleep oscillations as the moon progressed through its 29.5-day cycle. Depending on the community, the total amount of sleep varied across the lunar cycle by an average of 46 to 58 minutes, and bedtimes seesawed by around 30 minutes. For all three communities, on average, people had the latest bedtimes and the shortest amount of sleep in the nights three to five days leading up to a full moon.

When they discovered this pattern among the Toba-Qom participants, the team analyzed sleep-monitor data from 464 Seattle-area college students that had been collected for a separate study. They found the same oscillations.

The team confirmed that the evenings leading up to the full moon — when participants slept the least and went to bed the latest — have more natural light available after dusk: The waxing moon is increasingly brighter as it progresses toward a full moon, and generally rises in the late afternoon or early evening, placing it high in the sky during the evening after sunset. The latter half of the full moon phase and waning moons also give off significant light, but in the middle of the night, since the moon rises so late in the evening at those points in the lunar cycle.

“We hypothesize that the patterns we observed are an innate adaptation that allowed our ancestors to take advantage of this natural source of evening light that occurred at a specific time during the lunar cycle,” said lead author Leandro Casiraghi, a UW postdoctoral researcher in the Department of Biology.

Whether the moon affects our sleep has been a controversial issue among scientists. Some studies hint at lunar effects only to be contradicted by others. De la Iglesia and Casiraghi believe this study showed a clear pattern in part because the team employed wrist monitors to collect sleep data, as opposed to user-reported sleep diaries or other methods. More importantly, they tracked individuals across lunar cycles, which helped filter out some of the “noise” in data caused by individual variations in sleep patterns and major differences in sleep patterns between people with and without access to electricity.

These lunar effects may also explain why access to electricity causes such pronounced changes to our sleep patterns, de la Iglesia added.

Credit: Rebecca Gourley/University of Washington

“In general, artificial light disrupts our innate circadian clocks in specific ways: It makes us go to sleep later in the evening; it makes us sleep less. But generally we don’t use artificial light to ‘advance’ the morning, at least not willingly. Those are the same patterns we observed here with the phases of the moon,” said de la Iglesia.

“At certain times of the month, the moon is a significant source of light in the evenings, and that would have been clearly evident to our ancestors thousands of years ago,” said Casiraghi.

The team also found a second, “semilunar” oscillation of sleep patterns in the Toba-Qom communities, which seemed to modulate the main lunar rhythm with a 15-day cycle around the new and full moon phases. This semilunar effect was smaller and only noticeable in the two rural Toba-Qom communities. Future studies would have to confirm this semilunar effect, which may suggest that these lunar rhythms are due to effects other than from light, such as the moon’s maximal gravitational “tug” on the Earth at the new and full moons, according to Casiraghi.

Regardless, the lunar effect the team discovered will impact sleep research moving forward, the researchers said.

“In general, there has been a lot of suspicion on the idea that the phases of the moon could affect a behavior such as sleep — even though in urban settings with high amounts of light pollution, you may not know what the moon phase is unless you go outside or look out the window,” said Casiraghi. “Future research should focus on how: Is it acting through our innate circadian clock? Or other signals that affect the timing of sleep? There is a lot to understand about this effect.”

Reference: “Moonstruck sleep: Synchronization of human sleep with the moon cycle under field conditions” by Casiraghi L, Spiousas I, Dunster GP, McGlothlen K, Fernández-Duque E, Valeggia C and de la Iglesia HO. Science Advances: Jan. 27, 2021.
Manuscript number: sciadv.abe0465.

Provided by University of Washington