Posts tagged sleep deprivation
Articles and news from the latest research reports.
Ten-year study highlights sleep deficiency and sleep medication use in astronauts
In an extensive study of sleep monitoring and sleeping pill use in astronauts, researchers from Brigham and Women’s Hospital (BWH) Division of Sleep and Circadian Disorders, Harvard Medical School, and the University of Colorado found that astronauts suffer considerable sleep deficiency in the weeks leading up to and during space flight. The research also highlights widespread use of sleeping medication use among astronauts.
The study, published in The Lancet Neurology on August 8, 2014, recorded more than 4,000 nights of sleep on Earth, and more than 4,200 nights in space using data from 64 astronauts on 80 Shuttle missions and 21 astronauts aboard International Space Station (ISS) missions. The 10-year study is the largest study of sleep during space flight ever conducted. The study concludes that more effective countermeasures to promote sleep during space flight are needed in order to optimize human performance.
"Sleep deficiency is pervasive among crew members," stated Laura K. Barger, PhD, associate physiologist in the BWH Division of Sleep and Circadian Disorders, and lead study author. "It’s clear that more effective measures are needed to promote adequate sleep in crew members, both during training and space flight, as sleep deficiency has been associated with performance decrements in numerous laboratory and field-based studies."
Despite NASA scheduling 8.5 hours of sleep per night for crew members in space flight, the average (mean) duration of sleep during space flight was just under six (5.96) hours on shuttle missions, and just over six hours (6.09) on ISS missions. Twelve percent of sleep episodes on shuttle missions and 24 percent on ISS missions lasted seven hours or more, as compared to 42 percent and 50 percent, respectively, in a post-flight data collection interval when most astronauts slept at home.
Moreover, the results suggest that astronauts’ build-up of sleep deficiency began long before launch, as they averaged less than 6.5 hours sleep per night during the training interval occurring approximately three months prior to space flight.
The research also highlights widespread use of sleeping medications such as zolpidem and zaleplon during space flight. Three-quarters of ISS crew members reported taking sleep medication at some point during their time on the space station, and more than three-quarters (78 percent) of shuttle-mission crew members used medication on more than half (52 percent) of nights in space.
"The ability for a crew member to optimally perform if awakened from sleep by an emergency alarm may be jeopardized by the use of sleep-promoting pharmaceuticals," said Barger. "Routine use of such medications by crew members operating spacecraft are of particular concern, given the U. S. Federal Drug Administration (FDA) warning that patients using sleeping pills should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination, including potential impairment of performance of such activities that may occur the day following ingestion of sedative/hypnotics. This consideration is especially important because all crew members on a given mission may be under the influence of a sleep promoting medication at the same time."
Charles Czeisler, PhD, MD, FRCP, chief, BWH Division of Sleep and Circadian Disorders, and senior study author, adds: “Future exploration spaceflight missions to the moon, Mars or beyond will require development of more effective countermeasures to promote sleep during spaceflight in order to optimize human performance. These measures may include scheduling modifications, strategically timed exposure to specific wavelengths of light, and behavioral strategies to ensure adequate sleep, which is essential for maintaining health, performance and safety.”
(Source: eurekalert.org)
Missing sleep may hurt your memory
Lack of sleep, already considered a public health epidemic, can also lead to errors in memory, finds a new study by researchers at Michigan State University and the University of California, Irvine.
The study, published online in the journal Psychological Science, found participants deprived of a night’s sleep were more likely to flub the details of a simulated burglary they were shown in a series of images.
Distorted memory can have serious consequences in areas such as criminal justice, where eyewitness misidentifications are thought to be the leading cause of wrongful convictions in the United States.
“We found memory distortion is greater after sleep deprivation,” said Kimberly Fenn, MSU associate professor of psychology and co-investigator on the study. “And people are getting less sleep each night than they ever have.”
The Centers for Disease Control and Prevention calls insufficient sleep an epidemic and said it’s linked to vehicle crashes, industrial disasters and chronic diseases such as hypertension and diabetes.
The researchers conducted experiments at MSU and UC-Irvine to gauge the effect of insufficient sleep on memory. The results: Participants who were kept awake for 24 hours – and even those who got five or fewer hours of sleep – were more likely to mix up event details than participants who were well rested.
“People who repeatedly get low amounts of sleep every night could be more prone in the long run to develop these forms of memory distortion,” Fenn said. “It’s not just a full night of sleep deprivation that puts them at risk.”
Sleep deprivation leads to symptoms of schizophrenia
Psychologists at the University of Bonn are amazed by the severe deficits caused by a sleepless night
Twenty-four hours of sleep deprivation can lead to conditions in healthy persons similar to the symptoms of schizophrenia. This discovery was made by an international team of researchers under the guidance of the University of Bonn and King’s College London. The scientists point out that this effect should be investigated more closely in persons who have to work at night. In addition, sleep deprivation may serve as a model system for the development of drugs to treat psychosis. The results have now been published in “The Journal of Neuroscience”.
In psychosis, there is a loss of contact with reality and this is associated with hallucinations and delusions. The chronic form is referred to as schizophrenia, which likewise involves thought disorders and misperceptions. Affected persons report that they hear voices, for example. Psychoses rank among the most severe mental illnesses. An international team of researchers under the guidance of the University of Bonn has now found out that after 24 hours of sleep deprivation in healthy patients, numerous symptoms were noted which are otherwise typically attributed to psychosis or schizophrenia. “It was clear to us that a sleepless night leads to impairment in the ability to concentrate,” says Prof. Dr. Ulrich Ettinger of the Cognitive Psychology Unit in the Department of Psychology at the University of Bonn. “But we were surprised at how pronounced and how wide the spectrum of schizophrenia-like symptoms was.”
The scientists from the University of Bonn, King’s College London (England) as well as the Department of Psychiatry and Psychotherapy of the University of Bonn Hospital examined a total of 24 healthy subjects of both genders aged 18 to 40 in the sleep laboratory of the Department of Psychology. In an initial run, the test subjects were to sleep normally in the laboratory. About one week later, they were kept awake all night with movies, conversation, games and brief walks. On the following morning, subjects were each asked about their thoughts and feelings. In addition, subjects underwent a measurement known as prepulse inhibition.
Unselected information leads to chaos in the brain
"Prepulse inhibition is a standard test to measure the filtering function of the brain,” explains lead author Dr. Nadine Petrovsky from Prof. Ettinger’s team. In the experiment, a loud noise is heard via headphones. As a result, the test subjects experience a startle response, which is recorded with electrodes through the contraction of facial muscles. If a weaker stimulus is emitted beforehand as a “prepulse”, the startle response is lower. “The prepulse inhibition demonstrates an important function of the brain: Filters separate what is important from what is not important and prevent sensory overload,” says Dr. Petrovsky.
In our subjects, this filtering function of the brain was significantly reduced following a sleepless night. “There were pronounced attention deficits, such as what typically occurs in the case of schizophrenia,” reports Prof. Ettinger. “The unselected flood of information led to chaos in the brain.” Following sleep deprivation, the subjects also indicated in questionnaires that they were somewhat more sensitive to light, color or brightness. Accordingly, their sense of time and sense of smell were altered and mental leaps were reported. Many of those who spent the night even had the impression of being able to read thoughts or notice altered body perception. “We did not expect that the symptoms could be so pronounced after one night spent awake,” says the psychologist from the University of Bonn.
Sleep deprivation as a model system for mental illnesses
The scientists see an important potential application for their results in research for drugs to treat psychoses. “In drug development, mental disorders like these have been simulated to date in experiments using certain active substances. However, these convey the symptoms of psychoses in only a very limited manner,” says Prof. Ettinger. Sleep deprivation may be a much better model system because the subjective symptoms and the objectively measured filter disorder are far more akin to mental illnesses. Of course, the sleep deprivation model is not harmful: After a good night’s recovery sleep, the symptoms disappear. There is also a need for research with regard to persons who regularly have to work at night. “Whether the symptoms of sleep deprivation gradually become weaker due to acclimatization has yet to be investigated,” says the psychologist from the University of Bonn.
(Image: Getty)
Study Connects Sleep Deficits Among Young Fruitflies to Disruption in Mating Later in Life
Mom always said you need your sleep, and it turns out, she was right. According to a new study published in Science this week from researchers at the Perelman School of Medicine at the University of Pennsylvania, lack of sleep in young fruit flies profoundly diminishes their ability to do one thing they do really, really well – make more flies.
The study, led by Amita Sehgal PhD, professor of Neuroscience and a Howard Hughes Medical Institute (HHMI) Investigator, links sleep disruption in newborn fruit flies with a critical adult behavior: courtship and mating.
The team, addressed sleep in the very youngest of flies. “These flies sleep considerably more than adults and that behavior repeats across the animal kingdom,” Sehgal says. “Infant humans, rats, and flies, they all sleep a lot.”
Co-author Matthew Kayser, MD, PhD, in the Department of Psychiatry and Center for Sleep and Circadian Neurobiology, whose research centers on the link between sleep disruption and human neuropsychiatric diseases, used the fly – which is far more genetically pliant than mammals — to ask two basic questions: Why do young animals sleep so much? And, what is the implication of altering those patterns?
The team used genetically manipulated flies to show that young flies normally produce relatively little dopamine – a wake-promoting neurotransmitter — in certain neural circuits that feed into the sleep-promoting brain region called the dorsal fan-shaped body (dFSB). Premature activation of those circuits profoundly inhibits the dFSB, reducing sleep.
That answers the first question, Sehgal explains: Young flies make less dopamine, which keeps the dFSB active and sleep levels high. These animals sleep more than adults and are harder to rouse from sleep.
Some clues to the second question – what is the consequence of sleep loss – came from Kayser’s finding that increased dopamine in young flies not only causes sleep loss, but also affects their ability to court when they’re older. “The flies spend less time courting, and those that do usually don’t make it all the way to the end,” Sehgal says.
To address whether sleep loss in young flies affects development of courtship circuits, the team investigated a group of neurons implicated in courtship. One particular subset of those neurons, localized in a specific brain region called VA1v, was smaller in sleep-deprived animals than normal flies, suggesting a possible mechanism for how sleep deprivation can lead to altered courting behavior.
That sleep-deprived flies have altered behavior is not itself a novel finding, Sehgal notes. Earlier studies from her lab and others used mechanical disruption to alter sleep patterns, but in the current study, Sehgal’s team was able to drill down to the specific neural network that is affected. “We identified the circuit that is less active in young flies. If you activate that circuit, you disrupt courtship by impairing the development of a different, courtship-relevant circuit.”
The question now is how these findings relate to human behavior – Kayser’s original question. Though no direct lines can be drawn, the study “does provide the first mechanistic link between sleep in early life and adult behavior,” says Sehgal.
Researchers Show How Lost Sleep Leads to Lost Neurons
Most people appreciate that not getting enough sleep impairs cognitive performance. For the chronically sleep-deprived such as shift workers, students, or truckers, a common strategy is simply to catch up on missed slumber on the weekends. According to common wisdom, catch up sleep repays one’s “sleep debt,” with no lasting effects. But a new Penn Medicine study shows disturbing evidence that chronic sleep loss may be more serious than previously thought and may even lead to irreversible physical damage to and loss of brain cells. The research is published today in The Journal of Neuroscience.
Using a mouse model of chronic sleep loss, Sigrid Veasey, MD, associate professor of Medicine and a member of the Center for Sleep and Circadian Neurobiology at the Perelman School of Medicine and collaborators from Peking University, have determined that extended wakefulness is linked to injury to, and loss of, neurons that are essential for alertness and optimal cognition, the locus coeruleus (LC) neurons.
"In general, we’ve always assumed full recovery of cognition following short- and long-term sleep loss," Veasey says. "But some of the research in humans has shown that attention span and several other aspects of cognition may not normalize even with three days of recovery sleep, raising the question of lasting injury in the brain. We wanted to figure out exactly whether chronic sleep loss injures neurons, whether the injury is reversible, and which neurons are involved."
Mice were examined following periods of normal rest, short wakefulness, or extended wakefulness, modeling a shift worker’s typical sleep pattern. The Veasey lab found that in response to short-term sleep loss, LC neurons upregulate the sirtuin type 3 (SirT3) protein, which is important for mitochondrial energy production and redox responses, and protect the neurons from metabolic injury. SirT3 is essential across short-term sleep loss to maintain metabolic homeostasis, but in extended wakefulness, the SirT3 response is missing. After several days of shift worker sleep patterns, LC neurons in the mice began to display reduced SirT3, increased cell death, and the mice lost 25 percent of these neurons.
"This is the first report that sleep loss can actually result in a loss of neurons," Veasey notes. Particularly intriguing is, that the findings suggest that mitochondria in LC neurons respond to sleep loss and can adapt to short-term sleep loss but not to extended wake. This raises the possibility that somehow increasing SirT3 levels in the mitochondria may help rescue neurons or protect them across chronic or extended sleep loss. The study also demonstrates the importance of sleep for restoring metabolic homeostasis in mitochondria in the LC neurons and possibly other important brain areas, to ensure their optimal functioning during waking hours.
Veasey stresses that more work needs to be done to establish whether a similar phenomenon occurs in humans and to determine what durations of wakefulness place individuals at risk of neural injury. “In light of the role for SirT3 in the adaptive response to sleep loss, the extent of neuronal injury may vary across individuals. Specifically, aging, diabetes, high-fat diet and sedentary lifestyle may all reduce SirT3. If cells in individuals, including neurons, have reduced SirT3 prior to sleep loss, these individuals may be set up for greater risk of injury to their nerve cells.”
The next step will be putting the SirT3 model to the test. “We can now overexpress SirT3 in LC neurons,” explains Veasey. “If we can show that we can protect the cells and wakefulness, then we’re launched in the direction of a promising therapeutic target for millions of shift workers.”
The team also plans to examine shift workers post-mortem for evidence of increased LC neuron loss and signs of neurodegenerative disorders such as Alzheimer’s and Parkinson’s, since some previous mouse models have shown that lesions or injury to LC neurons can accelerate the course of those diseases. While not directly causing theses diseases, “injuring LC neurons due to sleep loss could potentially facilitate or accelerate neurodegeneration in individuals who already have these disorders,” Veasey says.
While more research will be needed to settle these questions, the present study provides another confirmation of a rapidly growing scientific consensus: sleep is more important than was previously believed. In the past, Veasey observes, “No one really thought that the brain could be irreversibly injured from sleep loss.” It’s now clear that it can be.
Study in Fruitflies Strengthens Connection Among Protein Misfolding, Sleep Loss, and Age
Pulling an “all-nighter” before a big test is practically a rite of passage in college. Usually, it’s no problem: You stay up all night, take the test, and then crash, rapidly catching up on lost sleep. But as we age, sleep patterns change, and our ability to recoup lost sleep diminishes.
Researchers at the Perelman School of Medicine, University of Pennsylvania, have been studying the molecular mechanisms underpinning sleep. Now they report that the pathways of aging and sleep intersect at the circuitry of a cellular stress response pathway, and that by tinkering with those connections, it may be possible to alter sleep patterns in the aged for the better – at least in fruit flies.
Nirinjini Naidoo, PhD, associate professor in the Center for Sleep and Circadian Neurobiology and the Division of Sleep Medicine, led the study with postdoctoral fellow Marishka Brown, PhD, which was published online before print in the journal Neurobiology of Aging.
Increasing age is well known to disrupt sleep patterns in all sorts of ways. Elderly people sleep at night less than their younger counterparts and also sleep less well. Older individuals also tend to nap more during the day. Naidoo’s lab previously reported that aging is associated with increasing levels of protein unfolding, a hallmark of cellular stress called the “unfolded protein response.”
Protein misfolding is also a characteristic of several age-related neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, and as it turns out, also associated with sleep deprivation. Naidoo and her team wanted to know if rescuing proper protein folding behavior might counter some of the detrimental sleep patterns in elderly individuals.
Using a video monitoring system to compare the sleep habits of “young” (9–12 days old) and “aged” (8 weeks old) fruit flies, they found that aged flies took longer to recover from sleep deprivation, slept less overall, and had their sleep more frequently interrupted compared to younger control animals. However, adding a molecule that promotes proper protein folding – a molecular “chaperone” called PBA — mitigated many of those effects, effectively giving the flies a more youthful sleep pattern. PBA (sodium 4-phenylbutyrate) is a compound currently used to treat such protein-misfolding-based diseases as Parkinson’s and cystic fibrosis.
The team also asked the converse question: Can protein misfolding induce altered sleep patterns in young animals. Another drug, tunicamycin, induces protein misfolding and stress, and when the team fed it to young flies, their sleep patterns shifted towards those of aged flies, with less sleep overall, more interrupted sleep at night, and longer recovery from sleep deprivation.
Molecular analysis of sleep-deprived and PBA-treated flies suggested that PBA acts through the unfolded protein response. PBA, Naidoo says, had two effects on aged flies: it “consolidated” baseline sleep, increasing the total amount of time slept and shifted recovery sleep, after sleep deprivation, to look more like that of a young fly.
“It rescued the sleep patterns in the older flies,” she explains.
These results, Naidoo says, suggest three key messages. First, sleep loss leads to protein misfolding and cellular stress, and as we age, our ability to recover from that stress decreases. Second, aging and sleep apparently form a kind of negative “chicken-and-egg” feedback loop, in which sleep loss or sleep fragmentation lead to cellular stress, followed by neuronal dysfunction, and finally even poorer-quality sleep.
Sleep recharges neuronal batteries, Naidoo explains, and if a person is forced to stay awake, those batteries run down. Dwindling physiological resources must be devoted to the most critical cell functions, which do not necessarily include protein homeostasis. “Staying awake has a cost, and one of those costs is problems with protein folding.”
Finally, and most importantly, she says these results suggest — assuming they can be replicated in mice and humans – that it may be possible using drugs such as PBA to “fix sleep” in aged or mutant animals.
“People know that sleep deteriorates with aging,” Naidoo says, “But this might be able to be stopped or reversed with molecular chaperones.” Her team is now looking to determine if a similar situation exists in mammals and if better sleep translates into longer lifespan.
(Source: uphs.upenn.edu)
New Sleep Gene, Redeye, Discovered in Fruitflies Promotes the Need to Sleep
All creatures great and small, including fruitflies, need sleep. Researchers have surmised that sleep – in any species — is necessary for repairing proteins, consolidating memories, and removing wastes from cells. But, really, sleep is still a great mystery.
Image caption: An alpha subunit of the nicotinic acetylcholine receptor accounts for the rye mutant phenotype. Expression pattern of redeye (green). Credit: Amita Sehgal and Mi Shi, PhD, Perelman School of Medicine, University of Pennsylvania
The timing of when we sleep versus are awake is controlled by cells in tune with circadian rhythms of light and dark. Most of the molecular components of that internal clock have been worked out. On the other hand, how much we sleep is regulated by another process called sleep homeostasis, however little is known about its molecular basis.
In a study published in eLIFE, Amita Sehgal, PhD, professor of Neuroscience at the Perelman School of Medicine, University of Pennsylvania, and colleagues, report a new protein involved in the homeostatic regulation of sleep in the fruitfly, Drosophila. Sehgal is also an investigator with the Howard Hughes Medical Institute (HHMI).
The researchers conducted a screen of mutant flies to identify short-sleeping individuals and found one, which they dubbed redeye. These mutants show a severe reduction in the amount of time they slumber, sleeping only half as long as normal flies. While the redeye mutants were able to fall asleep, they would wake again in only a few minutes.
The team found that the redeye gene encodes a subunit of the nicotinic acetylcholine receptor. This type of acetylcholine receptor consists of multiple protein subunits, which form an ion channel in the cell membrane, and, as the name implies, also binds to nicotine. Although acetylcholine signaling — and cigarette smoking — typically promote wakefulness, the particular subunit studied in the eLIFE paper is required for sleep in Drosophila.
Levels of the redeye protein in the fly oscillate with the cycles of light and dark and peak at times of daily sleep. Normally, the redeye protein is expressed at times of increasing sleep need in the fly, right around the afternoon siesta and at the time of night-time sleep. From this, the team concluded that the redeye protein promotes sleep and is a marker for sleepiness – suggesting that redeye signals an acute need for sleep, and then helps to maintain sleep once it is underway.
In addition, cycling of the redeye protein is independent of the circadian clock in normal day:night cycles, but depends on the sleep homeostat. The team concluded this because redeye protein levels are upregulated in short-sleeping mutants as well as in wild-type animals following sleep deprivation. And, mutant flies had normal circadian rhythms, suggesting that their sleep problems were the result of disrupted sleep/wake homeostasis.
Ultimately the team wants to use the redeye gene to locate sleep homeostat neurons in the brain. “We propose that the homeostatic drive to sleep increases levels of the redeye protein, which responds to this drive by promoting sleep,” says Sehgal. Identification of molecules that reflect sleep drive could lead to the development of biomarkers for sleep, and may get us closer to revealing the mystery of the sleep homeostat.
(Source: uphs.upenn.edu)
A new study from Uppsala University, Sweden, shows that one night of sleep deprivation increases morning blood concentrations of NSE and S-100B in healthy young men. These molecules are typically found in the brain. Thus, their rise in blood after sleep loss may indicate that a lack of snoozing might be conducive to a loss of brain tissue. The findings are published in the journal SLEEP.
Fifteen normal-weight men participated in the study. In one condition they were sleep-deprived for one night, while in the other condition they slept for approximately 8 hours.
“We observed that a night of total sleep loss was followed by increased blood concentrations of NSE and S-100B. These brain molecules typically rise in blood under conditions of brain damage. Thus, our results indicate that a lack of sleep may promote neurodegenerative processes”, says sleep researcher Christian Benedict at the Department of Neuroscience, Uppsala University, who lead the study.
“In conclusion, the findings of our trial indicate that a good night’s sleep may be critical for maintaining brain health”, says Christian Benedict.
Sleep-Deprived Mice Show Connections Among Lack of Shut-eye, Diabetes, Age
Sleep, or the lack of it, seems to affect just about every aspect of human physiology. Yet, the molecular pathways through which sleep deprivation wreaks its detrimental effects on the body remain poorly understood. Although numerous studies have looked at the consequences of sleep deprivation on the brain, comparatively few have directly tested its effects on peripheral organs.
During sleep deprivation cells upregulate the UPR – the unfolded protein response – a process where misfolded proteins get refolded or degraded.
Five years ago, researchers at the Perelman School of Medicine, University of Pennsylvania, showed that the UPR is an adaptive response to stress induced by sleep deprivation and is impaired in the brains of old mice. Those findings suggested that inadequate sleep in the elderly, who normally experience sleep disturbances, could exacerbate an already-impaired protective response to protein misfolding that happens in aging cells. Protein misfolding and clumping is associated with many diseases such as Alzheimer’s and Parkinson’s, noted Nirinjini Naidoo, Ph.D., research associate professor in the Division of Sleep Medicine in that study.
Naidoo is also senior author of a follow-up study in Aging Cell this month that shows, for the first time, an effect of sleep deprivation on the UPR in peripheral tissue, in this case, the pancreas. They showed that stress in pancreatic cells due to sleep deprivation may contribute to the loss or dysfunction of these cells important to maintaining proper blood sugar levels, and that these functions may be exacerbated by normal aging.
“The combined effect of aging and sleep deprivation resulted in a loss of control of blood sugar reminiscent of pre-diabetes in mice,” says Naidoo. “We hypothesize that older humans might be especially susceptible to the effects of sleep deprivation on the disruption of glucose homeostasis via cell stress.”
Working with Penn colleague Joe Baur, Ph.D., assistant professor of Physiology, Naidoo started a collaboration to look at the relationship of sleep deprivation, the UPR, and metabolic response with age. Other researchers had suggested that the death of beta cells associated with type 2 diabetes may be due to stress in a cell compartment called the endoplasmic reticulum (ER). The UPR is one part of the quality control system in the ER, where some proteins are made.
Knowing this, Naidoo and Baur asked if sleep deprivation (SD) causes ER stress in the pancreas, via an increase in protein misfolding, and in turn, how this relates to aging.
The team examined tissues in mice for cellular stress following acute SD, and they also looked for cellular stress in aging mice. Their results show that both age and SD combine to induce cellular stress in the pancreas.
Older mice fared markedly worse when subjected to sleep deprivation. Pancreas tissue from older mice or from young animals subjected to sleep deprivation exhibited signs of protein misfolding, yet both were able to maintain insulin secretion and control blood sugar levels. Pancreas tissue from acutely sleep-deprived aged animals exhibited a marked increase in CHOP, a protein associated with cell death, suggesting a maladaptive response to cellular stress with age that was amplified by sleep deprivation.
Acute sleep deprivation caused increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in beta cells, since plasma insulin levels were not lower following acute lack of sleep.
Accordingly, young animals subjected to acute sleep deprivation remained tolerant to a glucose challenge. In a chronic sleep deprivation experiment, young mice were sensitized to insulin and had improved control of their blood sugar, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations.
While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, cellular stress in pancreatic tissue suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells, and that these effects may be exacerbated by normal aging, say the researchers.
New biological links between sleep deprivation and the immune system discovered
Population-level studies have indicated that insufficient sleep increases the risk of cardiovascular diseases and type 2 diabetes. These diseases are known to be linked to inflammatory responses in the body.
University of Helsinki researchers have now shown what kinds of biological mechanisms related to sleep loss affect the immune system and trigger an inflammatory response. They identified the genes which are most susceptible to sleep deprivation and examined whether these genes are involved in the regulation of the immune system. The study was published in the journal PLOS ONE on October 23, 2013.
Conducted at the sleep laboratory of the Finnish Institute of Occupational Health, the study restricted the amount of sleep of a group of healthy young men to four hours per night for five days, imitating the schedule of a normal working week. Blood samples were taken before and after the sleep deprivation test. White blood cells were isolated from the samples, and the expression of all genes at the time of the sampling was examined using microarrays. The results were compared with samples from healthy men of comparable age who had been sleeping eight hours per night for the week.
"We compared the gene expression before and after the sleep deprivation period, and focused on the genes whose behaviour was most strongly altered," explains researcher Vilma Aho. "The expression of many genes and gene pathways related to the functions of the immune system was increased during the sleep deprivation. There was an increase in activity of B cells which are responsible for producing antigens that contribute to the body’s defensive reactions, but also to allergic reactions and asthma. This may explain the previous observations of increased asthmatic symptoms in a state of sleep deprivation."
The amount of certain interleukins, or signalling molecules which promote inflammation, increased, as did the amount of associated receptors such as Toll-like receptors (TLR). On the gene level, this was apparent in the higher-than-normal expression of the TLR4 gene after sleep loss. CRP level was also elevated, indicating inflammation.
The researchers also wanted to examine the impact that long-term sleep deprivation could have on the immune system. For this follow-up study, they used material from the national FINRISKI health survey. Participants in this population study underwent blood tests but also answered questions about their health, for example whether they were getting enough sleep.
The researchers compared participants who believed they were sleeping sufficiently with those who felt that they were not sleeping enough. Some of the gene-level changes observed in the experimental working week sleep restriction study were repeated in the population sample. These results may help explain the connection between shorter sleep and the development of inflammatory diseases, such as cardiovascular disease and diabetes, which has been established in epidemiological studies.
"These results corroborate the idea that sleep does not only impact brain function, but also interacts with our immune system and metabolism. Sleep loss causes changes to the system that regulates our immune defence. Some of these changes appear to be long-term, and may contribute to the development of diseases that have been linked to sleep deprivation in epidemiological research,” Aho states.