Posts tagged sleep
Articles and news from the latest research reports.
A new study in a mutant fruitfly called sleepless (sss) confirmed that the enzyme GABA transaminase, which is the target of some epilepsy drugs, contributes to sleep loss. The findings, published online in Molecular Psychiatry, were led by Amita Sehgal, PhD, head of the Chronobiology Program at the University of Pennsylvania’s Perelman School of Medicine. The findings shed light on mechanisms that may be shared between sleep disruption and some neurological disorders. A better understanding of this connection could enable treatments that target both types of symptoms and perhaps provide better therapeutic efficacy.
“Epilepsy is essentially an increase-in-firing disorder of the brain and maybe a decrease in activity of the neurotransmitter GABA, too,” says Sehgal, who is also a professor of Neuroscience and an investigator with the Howard Hughes Medical Institute (HHMI). “This connects our work to drugs that inhibit GABA transaminase. Changes in GABA transaminase activity are implicated in epilepsy and some other psychiatric disorders, which may account for some of the associated sleep problems.”
The team looked at the proteomics of the sss mutant brain – a large-scale study of the structure and function of related proteins — and found that GABA transaminase is increased in the sss brain compared to controls. This enzyme breaks down GABA, so GABA is decreased in the sss brain. Because GABA promotes sleep, there is a decrease in sleep in the sss mutant fly, as the name implies.
The relationship between the SSS protein and GABA is not fully understood. The SSS protein controls neural activity, and its absence results in increased neural firing, which likely uses up a lot of energy, says Sehgal. GABA transaminase works in the mitochondria, the energy-production organelle in the glial cells of the brain, which provide fuel for neurons. The large energy demand created by the increased neural firing in sss brains probably alters mitochondrial metabolism, including GABA transaminase function in glia.
In the sss mutant fly, there is a stream of connections that leads to its signature loss of sleep: The sss mutant has increased neuron firing caused by downregulation of a potassium channel protein called Shaker. Recently, the Sehgal lab showed that SSS also affects activity of acetylcholine receptors. Both of these actions may directly cause an inability to sleep. In addition, increased energy demands on glia, which increase GABA transaminase and decrease GABA, may further contribute to sleep loss. On the other hand, if GABA is increased, then sleep is increased, as in flies that lack GABA transaminase.
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.
Researchers Identify Gene That Helps Fruit Flies Go to Sleep
A novel protein may explain how biological clocks regulate human sleep cycles
In a series of experiments sparked by fruit flies that couldn’t sleep, Johns Hopkins researchers say they have identified a mutant gene — dubbed “Wide Awake” — that sabotages how the biological clock sets the timing for sleep. The finding also led them to the protein made by a normal copy of the gene that promotes sleep early in the night and properly regulates sleep cycles.
Because genes and the proteins they code for are often highly conserved across species, the researchers suspect their discoveries — boosted by preliminary studies in mice — could lead to new treatments for people whose insomnia or off-hours work schedules keep them awake long after their heads hit the pillow.
“We know that the timing of sleep is regulated by the body’s internal biological clock, but just how this occurs has been a mystery,” says study leader Mark N. Wu, M.D., Ph.D., an assistant professor of neurology, medicine, genetic medicine and neuroscience at the Johns Hopkins University School of Medicine. “We have now found the first protein ever identified that translates timing information from the body’s circadian clock and uses it to regulate sleep.”
A report on the work was published online March 13 in the journal Neuron.
In their hunt for the molecular roots of sleep regulation, Wu and his colleagues studied thousands of fruit fly colonies, each with a different set of genetic mutations, and analyzed their sleep patterns. They found that one group of flies, with a mutation in the gene they would later call Wide Awake (or Wake for short), had trouble falling asleep at night, a malady that looked a lot like sleep-onset insomnia in humans. The investigators say Wake appears to be the messenger from the circadian clock to the brain, telling it that it’s time to shut down and sleep.
After isolating the gene, Wu’s team determined that when working properly, Wake helps shut down clock neurons of the brain that control arousal by making them more responsive to signals from the inhibitory neurotransmitter called GABA. Wake does this specifically in the early evening, thus promoting sleep at the right time. Levels of Wake cycle during the day, peaking near dusk in good sleepers.
Flies with a mutated Wake gene that couldn’t get to sleep were not getting enough GABA signal to quiet their arousal circuits at night, keeping the flies agitated.
The researchers found the same gene in every animal they studied: humans, mice, rabbits, chickens, even worms.
Importantly, when Wu’s team looked to see where Wake was located in the mouse brain, they found that it was expressed in the suprachiasmatic nucleus (SCN), the master clock in mammals. Wu says the fact that the Wake protein was expressed in high concentrations in the SCN of mice is significant.
“Sometimes we discover things in flies that have no direct relevance in higher order animals,” Wu says. “In this case, because we found the protein in a location where it likely plays a role in circadian rhythms and sleep, we are encouraged that this protein may do the same thing in mice and people.”
The hope is that someday, by manipulating Wake, possibly with a medication, shift workers, military personnel and sleep-onset insomniacs could sleep better.
“This novel pathway may be a place where we can intervene,” Wu says.
(Source: hopkinsmedicine.org)
Plumes in the sleeping avian brain
When we drift into deep slow-wave sleep (SWS), waves of neuronal activity wash across our neocortex. Birds also engage in SWS, but they lack this particular brain structure. Researchers from the Max Planck Institute for Ornithology in Seewiesen, Germany together with colleagues from the Netherlands and Australia have gained deeper insight into the sleeping avian brain. They found complex 3D plumes of brain activity propagating through the brain that clearly differed from the two-dimensional activity found in mammals. These findings show that the layered neuronal organization of the neocortex is not required for waves to propagate, and raise the intriguing possibility that the 3D plumes of activity perform computations not found in mammals.
Mammals, including humans, depend upon the processing power of the neocortex to solve complex cognitive tasks. This part of the brain also plays an important role in sleep. During SWS, slow neuronal oscillations propagate across the neocortex as a traveling wave, much like sports fans performing the wave in a stadium. It is thought that this wave might be involved in coordinating the processing of information in distant brain regions. Birds have mammalian-like cognitive abilities, but yet different neuronal organization. They lack the elegant layered arrangement of neurons characteristic of the neocortex. Instead, homologous neurons are packaged in unlayered, seemingly poorly structured nuclear masses of neurons.
Researchers from the Max Planck Institute for Ornithology in Seewiesen together with colleagues from the Netherlands and Australia now investigated in female zebra finches how brain activity changed over space and time during sleep. “When we first looked at the recordings, it appeared that the slow waves were occurring simultaneously in all recording sites. However, when we visualized the data as a movie and slowed it down, a fascinating picture emerged!” says Gabriël Beckers from Utrecht University, who developed the high-resolution recording method at the Max Planck Institute for Ornithology in Seewiesen. The waves were moving across the two-dimensional recording array as rapidly changing arcs of activity. Rotating the orientation of the array by 90 degrees revealed similar patterns, and thereby established the 3D nature of the plumes propagating through the brain. The researchers found similar patterns in distant brain regions involved in processing different types of information, suggesting that this type of activity is a general feature of the sleeping avian brain.
In addition to revealing how neurons in the avian brain behave during sleep, this research also adds to our understanding of the sleeping neocortex. “Our findings demonstrate that the traveling nature of slow waves is not dependent upon the layered organization of neurons found in the neocortex, and is unlikely to be involved in functions unique to this pattern of neuronal organization,” says Niels Rattenborg, head of the Avian Sleep Group in Seewiesen. “In this respect, research on birds refines our understanding of what is and is not special about the neocortex.” Finally, the researchers wonder whether the 3D geometry of wave propagation in the avian brain reflects computational properties not found in the neocortex. While this idea is clearly speculative, the authors note that during the course of evolution, birds replaced the three-layered cortex present in their reptilian ancestors with nuclear brain structures. “Presumably, there are benefits to the seemingly disorganized, nuclear arrangement of neurons in the avian brain that we are far from understanding. Whether this relates to what we have observed in the sleeping bird brain is a wide open question,” says Rattenborg.
Researchers Identify Brain Differences Linked to Insomnia
Johns Hopkins researchers report that people with chronic insomnia show more plasticity and activity than good sleepers in the part of the brain that controls movement.
"Insomnia is not a nighttime disorder," says study leader Rachel E. Salas, M.D., an assistant professor of neurology at the Johns Hopkins University School of Medicine. "It’s a 24-hour brain condition, like a light switch that is always on. Our research adds information about differences in the brain associated with it."
Salas and her team, reporting in the March issue of the journal Sleep, found that the motor cortex in those with chronic insomnia was more adaptable to change - more plastic - than in a group of good sleepers. They also found more “excitability” among neurons in the same region of the brain among those with chronic insomnia, adding evidence to the notion that insomniacs are in a constant state of heightened information processing that may interfere with sleep.
Researchers say they hope their study opens the door to better diagnosis and treatment of the most common and often intractable sleep disorder that affects an estimated 15 percent of the United States population.
To conduct the study, Salas and her colleagues from the Department of Psychiatry and Behavioral Sciences and the Department of Physical Medicine and Rehabilitation used transcranial magnetic stimulation (TMS), which painlessly and noninvasively delivers electromagnetic currents to precise locations in the brain and can temporarily and safely disrupt the function of the targeted area. TMS is approved by the U.S. Food and Drug Administration to treat some patients with depression by stimulating nerve cells in the region of the brain involved in mood control.
The study included 28 adult participants - 18 who suffered from insomnia for a year or more and 10 considered good sleepers with no reports of trouble sleeping. Each participant was outfitted with electrodes on their dominant thumb as well as an accelerometer to measure the speed and direction of the thumb.
The researchers then gave each subject 65 electrical pulses using TMS, stimulating areas of the motor cortex and watching for involuntary thumb movements linked to the stimulation. Subsequently, the researchers trained each participant for 30 minutes, teaching them to move their thumb in the opposite direction of the original involuntary movement. They then introduced the electrical pulses once again.
The idea was to measure the extent to which participants’ brains could learn to move their thumbs involuntarily in the newly trained direction. The more the thumb was able to move in the new direction, the more likely their motor cortexes could be identified as more plastic.
Because lack of sleep at night has been linked to decreased memory and concentration during the day, Salas and her colleagues suspected that the brains of good sleepers could be more easily retrained. The results, however, were the opposite. The researchers found much more plasticity in the brains of those with chronic insomnia.
Salas says the origins of increased plasticity in insomniacs are unclear, and it is not known whether the increase is the cause of insomnia. It is also unknown whether this increased plasticity is beneficial, the source of the problem or part of a compensatory mechanism to address the consequences of sleep deprivation associated with chronic insomnia. Patients with chronic phantom pain after limb amputation and with dystonia, a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements, also have increased brain plasticity in the motor cortex, but to detrimental effect.
Salas says it is possible that the dysregulation of arousal described in chronic insomnia - increased metabolism, increased cortisol levels, constant worrying - might be linked to increased plasticity in some way. Diagnosing insomnia is solely based on what the patient reports to the provider; there is no objective test. Neither is there a single treatment that works for all people with insomnia. Treatment can be a hit or miss in many patients, Salas says.
She says this study shows that TMS may be able to play a role in diagnosing insomnia, and more importantly, she says, potentially prove to be a treatment for insomnia, perhaps through reducing excitability.
(Source: hopkinsmedicine.org)
Scientists wake up to causes of sleep disruption in Alzheimer’s disease
Being awake at night and dozing during the day can be a distressing early symptom of Alzheimer’s disease, but how the disease disrupts our biological clocks to cause these symptoms has remained elusive.
Now, scientists from Cambridge have discovered that in fruit flies with Alzheimer’s the biological clock is still ticking but has become uncoupled from the sleep-wake cycle it usually regulates. The findings – published in Disease Models & Mechanisms – could help develop more effective ways to improve sleep patterns in people with the disease.
People with Alzheimer’s often have poor biological rhythms, something that is a burden for both patients and their carers. Periods of sleep become shorter and more fragmented, resulting in periods of wakefulness at night and snoozing during the day. They can also become restless and agitated in the late afternoon and early evening, something known as ‘sundowning’.
Biological clocks go hand in hand with life, and are found in everything from single celled organisms to fruit flies and humans. They are vital because they allow organisms to synchronise their biology to the day-night changes in their environments.
Until now, however, it has been unclear how Alzheimer’s disrupts the biological clock. According to Dr Damian Crowther of Cambridge’s Department of Genetics, one of the study’s authors: “We wanted to know whether people with Alzheimer’s disease have a poor behavioural rhythm because they have a clock that’s stopped ticking or they have stopped responding to the clock.”
The team worked with fruit flies – a key species for studying Alzheimer’s. Evidence suggests that the A-beta peptide, a protein, is behind at least the initial stages of the disease in humans. This has been replicated in fruit flies by introducing the human gene that produces this peptide.
Taking a group of healthy flies and a group with this feature of Alzheimer’s, the researchers studied sleep-wake patterns in the flies, and how well their biological clocks were working.
They measured sleep-wake patterns by fitting a small infrared beam, similar to movement sensors in burglar alarms, to the glass tubes housing the flies. When the flies were awake and moving, they broke the beam and these breaks in the beam were counted and recorded.
To study the flies’ biological clocks, the researchers attached the protein luciferase – an enzyme that emits light – to one of the proteins that forms part of the biological clock. Levels of the protein rise and fall during the night and day, and the glowing protein provided a way of tracing the flies’ internal clock.
"This lets us see the brain glowing brighter at night and less during the day, and that’s the biological clock shown as a glowing brain. It’s beautiful to be able to study first hand in the same organism the molecular working of the clock and the corresponding behaviours," Dr Crowther said.
They found that healthy flies were active during the day and slept at night, whereas those with Alzheimer’s sleep and wake randomly. Crucially, however, the diurnal patterns of the luciferase-tagged protein were the same in both healthy and diseased flies, showing that the biological clock still ticks in flies with Alzheimer’s.
"Until now, the prevailing view was that Alzheimer’s destroyed the biological clock," said Crowther.
"What we have shown in flies with Alzheimer’s is that the clock is still ticking but is being ignored by other parts of the brain and body that govern behaviour. If we can understand this, it could help us develop new therapies to tackle sleep disturbances in people with Alzheimer’s."
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, who helped to fund the study, said: “Understanding the biology behind distressing symptoms like sleep problems is important to guide the development of new approaches to manage or treat them. This study sheds more light on the how features of Alzheimer’s can affect the molecular mechanisms controlling sleep-wake cycles in flies.
"We hope these results can guide further studies in people to ensure that progress is made for the half a million people in the UK with the disease."
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)
Scientists identify the switch that says it’s time to sleep
The switch works by regulating the activity of a handful of sleep-promoting nerve cells, or neurons, in the brain. The neurons fire when we’re tired and need sleep, and dampen down when we’re fully rested.
‘When you’re tired, these neurons in the brain shout loud and they send you to sleep,’ says Professor Gero Miesenböck of Oxford University, in whose laboratory the new research was performed.
Although the research was carried out in fruit flies, or Drosophila, the scientists say the sleep mechanism is likely to be relevant to humans.
Dr Jeffrey Donlea, one of the lead authors of the study, explains: ‘There is a similar group of neurons in a region of the human brain. These neurons are also electrically active during sleep and, like the flies’ cells, are the targets of general anaesthetics that put us to sleep. It’s therefore likely that a molecular mechanism similar to the one we have discovered in flies also operates in humans.’
The researchers say that pinpointing the sleep switch might help us identify new targets for novel drugs – potentially to improve treatments for sleep disorders.
But there is much still to find out, and further research could give insight into the big unanswered question of why we need to sleep at all, they say.
‘The big question now is to figure out what internal signal the sleep switch responds to,’ says Dr Diogo Pimentel of Oxford University, the other lead author of the study. ‘What do these sleep-promoting cells monitor while we are awake?
‘If we knew what happens in the brain during waking that requires sleep to reset, we might get closer to solving the mystery of why all animals need to sleep.’
The findings are reported in the journal Neuron. The work of the Centre for Neural Circuits and Behaviour is funded by the Wellcome Trust and the Gatsby Charitable Foundation. This study was also supported by the UK Medical Research Council, the US National Institutes of Health, and the Human Frontier Science Program.
The body uses two mechanisms to regulate sleep. One is the body clock, which attunes humans and animals to the 24 hour cycle of day and night. The other mechanism is the sleep ‘homeostat’: a device in the brain that keeps track of your waking hours and puts you to sleep when you need to reset. This mechanism represents an internal nodding off point that is separate from external factors. When it is turned off or out of use, sleep deficits build up.
What makes us go to sleep at night is probably a combination of the two mechanisms,’ says Professor Miesenböck. ‘The body clock says it’s the right time, and the sleep switch has built up pressure during a long waking day.’
The work in fruit flies allowed the critical part of the sleep switch to be discovered. ‘We discovered mutant flies that couldn’t catch up on their lost sleep after they had been kept awake all night,’ says Dr Jeffrey Donlea.
Flies stop moving when they go to sleep and require more disturbance to get them up. Sleep-deprived flies are prone to nodding off and are cognitively impaired – they have severe learning and memory deficits, much as sleep loss in humans leads to problems.
Professor Miesenböck says: ‘The sleep homeostat is similar to the thermostat in your home. A thermostat measures temperature and switches on the heating if it’s too cold. The sleep homeostat measures how long a fly has been awake and switches on a small group of specialized cells in the brain if necessary. It’s the electrical output of these nerve cells that puts the fly to sleep.’
In the mutant flies, the researchers were able to show a key molecular component of the electrical activity switch is broken and the sleep-inducing neurons are always off, causing insomnia.
(Source: ox.ac.uk)
Why does the brain remember dreams?
Some people recall a dream every morning, whereas others rarely recall one. A team led by Perrine Ruby, an Inserm Research Fellow at the Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1), has studied the brain activity of these two types of dreamers in order to understand the differences between them. In a study published in the journal Neuropsychopharmacology, the researchers show that the temporo-parietal junction, an information-processing hub in the brain, is more active in high dream recallers. Increased activity in this brain region might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, thereby facilitating the encoding of dreams in memory.
The reason for dreaming is still a mystery for the researchers who study the difference between “high dream recallers,” who recall dreams regularly, and “low dream recallers,” who recall dreams rarely. In January 2013 (work published in the journal Cerebral Cortex), the team led by Perrine Ruby, Inserm researcher at the Lyon Neuroscience Research Center, made the following two observations: “high dream recallers” have twice as many time of wakefulness during sleep as “low dream recallers” and their brains are more reactive to auditory stimuli during sleep and wakefulness. This increased brain reactivity may promote awakenings during the night, and may thus facilitate memorisation of dreams during brief periods of wakefulness.
In this new study, the research team sought to identify which areas of the brain differentiate high and low dream recallers. They used Positron Emission Tomography (PET) to measure the spontaneous brain activity of 41 volunteers during wakefulness and sleep. The volunteers were classified into 2 groups: 21 “high dream recallers” who recalled dreams 5.2 mornings per week in average, and 20 “low dream recallers,” who reported 2 dreams per month in average. High dream recallers, both while awake and while asleep, showed stronger spontaneous brain activity in the medial prefrontal cortex (mPFC) and in the temporo-parietal junction (TPJ), an area of the brain involved in attention orienting toward external stimuli.
Tired all the time: Could undiagnosed sleep problems be making MS patients’ fatigue worse?
People with multiple sclerosis (MS) might assume that the fatigue they often feel just comes with the territory of their chronic neurological condition.
But a new University of Michigan study suggests that a large proportion of MS patients may have an undiagnosed sleep disorder that is also known to cause fatigue. And that disorder – obstructive sleep apnea – is a treatable condition.
In the latest issue of the Journal of Clinical Sleep Medicine, researchers from the U-M Health System’s Sleep Disorders Center report the results of a study involving 195 patients of the U-M Multiple Sclerosis Center.
In all, 56 percent of the MS patients were found to be at increased risk for obstructive sleep apnea, based on a method of screening for the condition known as the STOP-Bang questionnaire. But most had never received a formal diagnosis of sleep apnea, and less than half of those who had been told they had sleep apnea were using the standard treatment for it.
The authors also found that patients who were more fatigued were more likely to also be at elevated risk for sleep apnea – even after taking into account other factors that might have contributed to feelings of fatigue, such as age, gender, body mass index (BMI), sleep duration, depression, and other nighttime symptoms.
The research is based on patients’ answers from a sleep questionnaire designed by the authors, and four validated instruments designed to assess daytime sleepiness, fatigue severity, insomnia severity and obstructive sleep apnea risk. Medical records also were accessed with patients’ permission, to examine clinical characteristics that may predict fatigue or obstructive sleep apnea risk.
“We were particularly surprised by the difference between the proportion of patients who carried an established diagnosis of obstructive sleep apnea – 21 percent — and the proportion at risk for obstructive sleep apnea based on their STOP-Bang scores, which was 56 percent,” says the study’s lead author, Tiffany Braley, M.D., M.S. “These findings suggest that OSA may be a highly prevalent and yet under-recognized contributor to fatigue in persons with MS.”
Braley, an assistant professor of Neurology and multiple sclerosis specialist at the U-M Medical School, conducted the study in collaboration with professors Ronald Chervin, M.D., M.S., and Benjamin Segal, M.D. Chervin is the Director of U-M Sleep Disorders Center, and Segal directs the U-M MS Center.
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that causes inflammation and damage of the brain and spinal cord. In addition to neurological disability, MS patients suffer from a number of chronic symptoms, the most common of which is fatigue. Fatigue is also one of the most disabling symptoms experienced by MS patients.
Braley cautions that the design of this new study does not allow for demonstration of cause and effect – that is, the researchers can’t prove based on survey results that the patients felt more fatigued because they had a high score on a sleep apnea risk survey. But, she says, “the findings should prompt doctors who treat MS patients to consider sleep apnea as a possible contributor to their patients’ fatigue, and recommend appropriate testing and treatment.”
The standard treatment for obstructive sleep apnea, called continuous positive airway pressure, or CPAP, involves a machine and mask device that applies a stream of air to the upper airway to keep it open during sleep.
The patients in the study had an average age of 47 and had lived with MS for an average of 10 years. Two-thirds were female, consistent with the prevalence of MS in the U.S., and two-thirds were taking a medication to treat their MS. Three-quarters had the relapsing-remitting form of the disease.