1. Violent sleep patterns, stress hormones change after a violent crime in the neighborhood

    August 14, 2017 by Ashley

    From the Society for Research in Child Development press release:

    Almost 1.2 million violent crimes — homicide, sexual assault, assault, and robbery — were committed in the United States in 2015, according to the U.S. Department of Justice. A new study has found that violent crime changes youth’s sleep patterns the night immediately following the crime and changes patterns of the stress hormone cortisol the following day. Both may then disrupt academic performance in students.

    The study was conducted by researchers at Northwestern University, New York University, and DePaul University. It appears in the journal Child Development.

    “Past research has found a link between violent crimes and performance on tests, but researchers haven’t been able to say why crime affects academic performance,” explains Jennifer A. Heissel, a PhD graduate in human development and sociology at Northwestern University, who led the study. “Both sleep and cortisol are connected to the ability to learn and perform academic tasks; our study identifies a pathway by which violent crime may get under the skin to affect academic performance.” The study did so by examining the causal pathways involved with sleep and the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress.

    Researchers tracked the sleep and stress hormones of 82 youth (ages 11 to 18) in a large Midwestern city who attended public schools that were racially, ethnically, and socioeconomically diverse. The students filled out daily diaries over four days, wore activity-tracking watches that measured sleep, and had their saliva tested three times a day to check for cortisol. Researchers also collected information on all the violent crimes reported to the police in the city during the study, including which youth had a violent crime occur in his or her neighborhood.

    For each youth, researchers compared the students’ sleep on the nights following a violent crime to their sleep on nights when there were no violent crimes committed nearby. They also compared students’ stress hormones (cortisol) on days following a violent crime to their stress hormones on days when there were no violent crimes committed nearby.

    Among the findings: Youth went to sleep later on nights when a violent crime occurred near their home, often resulting in fewer total hours of sleep. In addition, the increase in youth’s cortisol levels the morning after a crime occurred nearby the day before was larger than on mornings following no crime the previous day, a pattern that previous research suggests might reflect the body’s anticipation of more stress the day following a crime. The changes in sleep and cortisol were largest when the crime committed the previous day was homicide, moderate for assault and sexual assault, and nonexistent for robbery.

    “The results of our research have several implications for policy,” suggests Emma Adam, professor of human development and social policy at Northwestern University, who also conducted the study. “They provide a link between violent crime and several mechanisms known to affect cognitive performance. They also may help explain why some low-income youth living in high-risk neighborhoods sleep less than higher-income youth. And they suggest that although programs to reduce violent crime may be the best policy solution, schools could also provide students with programs or methods to cope with their response to stressful events like nearby violent crimes.”


  2. Sleep disorders may increase cognitive problems particularly in those at risk for Alzheimer’s

    August 8, 2017 by Ashley

    From the American Thoracic Society press release:

    People who carry a genetic susceptibility to Alzheimer’s disease appear to be at greater risk of diminished cognition from sleep-disordered breathing than those without the susceptibility, according to new research published online, ahead of print in the Annals of the American Thoracic Society.

    In “Greater Cognitive Deficits with Sleep-Disordered Breathing among Individuals with Genetic Susceptibility to Alzheimer’s Disease: The Multi-Ethnic Study of Atherosclerosis,” researchers report that study participants carrying the apolipoprotein ?-4 (APOE-?4) allele showed greater cognitive deficits with the various indices of sleep-disordered breathing compared to those without the allele.

    APOE is a major cholesterol carrier that supports injury repair in the brain. Other studies have shown that those carrying the alternate form of the gene, ?4 allele, are at increased risk of Alzheimer’s disease. Estimates are that 20 percent of the population carries the ?4 allele.

    “Previous studies have shown inconsistent findings between sleep-disordered breathing and cognition, which may be due to the different tests used,” said lead study author Dayna A. Johnson, PhD, MPH, MS, MSW, instructor of medicine at Brigham and Women’s Hospital and Harvard Medical School.

    Dr. Johnson and colleagues investigated the association in a diverse sample using several indicators of sleep-disordered breathing and cognition. They also evaluated whether the presence of the APOE-?4 allele, which is known to increase risk of Alzheimer’s disease, influenced the link between sleep-disordered breathing and cognition.

    The authors analyzed data from 1,752 participants (average age 68) in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent an in-home polysomnography (sleep) study, completed standardized sleep questions, and a battery of tests to measure their cognition. The authors defined sleep-disordered breathing as an apnea-hypopnea index (AHI), which measures the number of stopped or shallow breaths per hour, as AHI > 15, and sleep apnea syndrome as AHI > 5 (below 5 is normal) plus self-reported sleepiness (based on a standardized scale).

    The study found:

    • Increased overnight hypoxemia (oxygen saturation below 90 percent) or increased daytime sleepiness was associated with poorer attention and memory.
    • More daytime sleepiness was also associated with slower cognitive processing speed.
    • Sleep apnea syndrome was associated with poorer attention and processing speed.
    • These associations were strongest in APOE-?4 carriers.

    The researchers adjusted for race, age, body mass index, education level, smoking status, hypertension, diabetes, benzodiazepine use, and depressive symptoms.

    Dr. Johnson said that, overall, the effects of the various sleep factors they measured on cognition were small, but in the range previously reported for several other lifestyle and health risk factors for dementia. Screening and treating sleep-disordered breathing, she added, may help reduce a person’s risk of dementia, especially if that individual carries APOE-?4.

    “Our study provides further evidence that sleep-disordered breathing negatively affects attention, processing speed and memory, which are robust predictors of cognitive decline,” said senior study author Susan Redline, MD, MPH, Peter C. Farrell Professor of Sleep Medicine, Harvard Medical School.

    “Given the lack of effective treatment for Alzheimer’s disease, our results support the potential for sleep-disordered breathing screening and treatment as part of a strategy to reduce dementia risk.”

    Find the report online at: http://www.thoracic.org/about/newsroom/press-releases/resources/sleep-disordered-breathing-ad-cognition.pdf


  3. Purpose in life by day linked to better sleep at night

    July 28, 2017 by Ashley

    From the Northwestern University press release:

    Having a good reason to get out of bed in the morning means you are more likely to sleep better at night with less sleep apnea and restless leg syndrome, reports a new Northwestern Medicine and Rush University Medical Center study based on older adults.

    This is the first study to show having a purpose in life specifically results in fewer sleep disturbances and improved sleep quality and over a long period of time. Previous research showed having a purpose in life generally improves overall sleep when measured at a single point in time.

    Although the participants in the study were older, researchers said the findings are likely applicable to the broader public.

    “Helping people cultivate a purpose in life could be an effective drug-free strategy to improve sleep quality, particularly for a population that is facing more insomnia,” said senior author Jason Ong, an associate professor of neurology at Northwestern University Feinberg School of Medicine. “Purpose in life is something that can be cultivated and enhanced through mindfulness therapies.”

    The paper will be published in the journal Sleep Science and Practice.

    Individuals have more sleep disturbances and insomnia as they get older. Clinicians prefer to use non-drug interventions to improve patients’ sleep, a practice now recommended by the American College of Physicians as a first line treatment for insomnia, Ong said.

    The next step in the research should be to study the use of mindfulness-based therapies to target purpose in life and resulting sleep quality, said Arlener Turner, the study’s first author and a former postdoctoral fellow in neurology at Feinberg.

    The 823 participants — non-demented individuals 60 to 100 years old with an average age of 79 — were from two cohorts at Rush University Medical Center. More than half were African American and 77 percent were female.

    People who felt their lives had meaning were 63 percent less likely to have sleep apnea and 52 percent less likely to have restless leg syndrome. They also had moderately better sleep quality, a global measure of sleep disturbance.

    For the study, participants answered a 10-question survey on purpose in life and a 32-question survey on sleep. For the purpose in life survey, they were asked to rate their response to such statements as, “I feel good when I think of what I’ve done in the past and what I hope to do in the future.”

    The next step in the research should be to study the use of mindfulness-based therapies to target purpose in life and resulting sleep quality, Turner said.

    Poor sleep quality is related to having trouble falling asleep, staying asleep and feeling sleepy during the day. Sleep apnea is a common disorder that increases with age in which a person has shallow breathing or pauses in breathing during sleep several times per hour. This disruption often makes a person feel unrefreshed upon waking up and excessively sleepy during the day.

    Restless leg syndrome causes uncomfortable sensations in the legs and an irresistible urge to move them. Symptoms commonly occur in the late afternoon or evening hours and are often most severe at night when a person is resting, such as sitting or lying in bed.


  4. Controlling memory by triggering specific brain waves during sleep

    July 25, 2017 by Ashley

    From the Institute for Basic Science press release:

    Have you ever tried to recall something just before going to sleep and then wake up with the memory fresh in your mind? While we absorb so much information during the day consciously or unconsciously, it is during shut eye that a lot of facts are dispatched to be filed away or fall into oblivion. A good quality sleep is the best way to feel mentally refreshed and memorize new information, but how is the brain working while we sleep? Could we improve such process to remember more, or maybe even use it to forget unwanted memories?

    Scientists at the Center for Cognition and Sociality, within the Institute for Basic Science (IBS), enhanced or reduced mouse memorization skills by modulating specific synchronized brain waves during deep sleep. This is the first study to show that manipulating sleep spindle oscillations at the right timing affects memory. The full description of the mouse experiments, conducted in collaboration with the University of Tüebingen, is published in the journal Neuron.

    The research team concentrated on a non-REM deep sleep phase that generally happens throughout the night, in alternation with the REM phase. It is called slow-wave sleep and it seems to be involved with memory formation, rather than dreaming.

    During slow-wave sleep, groups of neurons firing at the same time generate brain waves with triple rhythms: slow oscillations, spindles, and ripples. Slow oscillations originate from neurons in the cerebral cortex. Spindles come from a structure of the brain called thalamic reticular nucleus and spike around 7-15 per second. Finally, ripples are sharp and quick bursts of electrical energy, produced within the hippocampus, a brain component with an important role in spatial memory.

    “Often during the night a regular pattern is manifested, where a slow oscillation from the cortex is immediately followed by a thalamic spindle and while this happens, a hippocampal ripple appears in parallel. We believe that the correct timing of these three rhythms acts like a communication channel between different parts of the brains that facilitates memory consolidation,” explains Charles-Francois V. Latchoumane, first co-author of the study.

    The researchers focused on spindles because it was shown that the number of spindles is connected with memorization. It has been shown that the number of spindles increases following a day stuffed with learning and declines in the elderly, and in patients with schizophrenia. This is the first study to show that artificial thalamic spindles affect memory, if administered in sync with slow oscillations.

    In the experiment, mice were put in a special cage and given a mild electric shock after hearing a tonal noise. The day after, their memory was tested, by checking their fear reaction in response to either the same noise or the same cage. Latchoumane explains that this could be simplified and compared to the experience of hearing a fire alarm in a certain location, like a cafe. The incident would be followed by either another visit to the same cafe or the sound of the fire alarm in another cafe on the following day.

    At nighttime between the two days, scientists introduced artificial thalamic spindles in some of the mice using a light-based technique called optogenetics. The mice were divided into three groups. The first group received the light input just after the slow oscillations, so their spindle could form a triple rhythm (in phase): slow oscillation-spindle-ripples. In the second group the light stimulations were applied later “out of sync.” The third group was used as a control and did not receive any light stimulation.

    The day after, mice were placed in the same location and their movement was recorded. The mice of the first group were frozen in fear 40% of the time, even in absence of the noise. On the contrary, mice in the second and third groups only froze up to 20%. Instead, when the mice heard the same tone in a different location, remembered the tone and froze in fear up to 40% of the time, independently from the group they belonged to. The hippocampus is involved in spatial memories which might explain the difference.

    The opposite was also true: it was possible to make mice forget. By reducing the number of overnight spindles, the researchers could reduce the memory recall.

    The research team thinks that the thalamus is the coordinator of long-term memory consolidation, the process where recently acquired information is transferred from the hippocampus to the cortex to be filed away as long-term memory. The hippocampus is like a hub, where a lot of information comes in and has to be redirected to the correct destination within the brain, especially to the cortex. This study shows that the thalamus seems to mediate the information exchange between hippocampus and cortex. “We think that memorization during deep sleep has to do with time coordination. If the hippocampus tries to exchange information when the cortex neurons are not ready to receive it, the information could be wasted,” describes Latchoumane. “Slow oscillations might be the signal used by the cortex to flag that it is ready to accept information. Then, the thalamus would alert the hippocampus via the spindles.”

    It is possible to foresee that patients with memory deficiencies could benefit from translation of this research into humans. However, several points need to be clarified: can we manipulate single memories independently? Is the REM phase influencing the outcome? How is stored memory retrieved? While waiting for the next research outcomes on the science of sleep, sweet dreams… and sweet memories too.


  5. Sleep problems may be early sign of Alzheimer’s

    July 24, 2017 by Ashley

    From the American Academy of Neurology press release:

    Poor sleep may be a sign that people who are otherwise healthy may be more at risk of developing Alzheimer’s disease later in life than people who do not have sleep problems, according to a study published in the July 5, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers have found a link between sleep disturbances and biological markers for Alzheimer’s disease found in the spinal fluid.

    “Previous evidence has shown that sleep may influence the development or progression of Alzheimer’s disease in various ways,” said study author Barbara B. Bendlin, PhD, of the University of Wisconsin-Madison. “For example, disrupted sleep or lack of sleep may lead to amyloid plaque buildup because the brain’s clearance system kicks into action during sleep. Our study looked not only for amyloid but for other biological markers in the spinal fluid as well.”

    Amyloid is a protein that can fold and form into plaques. Tau is a protein that forms into tangles. These plaques and tangles are found in the brains of people with Alzheimer’s disease.

    For the study, researchers recruited 101 people with an average age of 63 who had normal thinking and memory skills but who were considered at risk of developing Alzheimer’s, either having a parent with the disease or being a carrier of a gene that increases the risk for Alzheimer’s disease called apolipoprotein E or APOE. Participants were surveyed about sleep quality. They also provided spinal fluid samples that were tested for biological markers of Alzheimer’s disease.

    Researchers found that people who reported worse sleep quality, more sleep problems and daytime sleepiness had more biological markers for Alzheimer’s disease in their spinal fluid than people who did not have sleep problems. Those biological markers included signs of amyloid, tau and brain cell damage and inflammation.

    “It’s important to identify modifiable risk factors for Alzheimer’s given that estimates suggest that delaying the onset of Alzheimer’s disease in people by a mere five years could reduce the number of cases we see in the next 30 years by 5.7 million and save $367 billion in health care spending,” said Bendlin.

    While some of these relationships were strong when looking at everyone as a group, not everyone with sleep problems has abnormalities in their spinal fluid. For example, there was no link between biological markers in the spinal fluid and obstructive sleep apnea.

    The results remained the same when researchers adjusted for other factors such as use of medications for sleep problems, amount of education, depression symptoms or body mass index.

    “It’s still unclear if sleep may affect the development of the disease or if the disease affects the quality of sleep,” said Bendlin. “More research is needed to further define the relationship between sleep and these biomarkers.”

    Bendlin added, “There are already many effective ways to improve sleep. It may be possible that early intervention for people at risk of Alzheimer’s disease may prevent or delay the onset of the disease.”

    One limitation of the study was that sleep problems were self-reported. Monitoring of sleep patterns by health professionals may be beneficial in future studies.


  6. Study examines link between sleep disruptions and Alzheimer’s

    July 23, 2017 by Ashley

    From the Washington University in St. Louis press release:

    A good night’s sleep refreshes body and mind, but a poor night’s sleep can do just the opposite. A study from Washington University School of Medicine in St. Louis, Radboud University Medical Centre in the Netherlands, and Stanford University has shown that disrupting just one night of sleep in healthy, middle-aged adults causes an increase in amyloid beta, a brain protein associated with Alzheimer’s disease. And a week of tossing and turning leads to an increase in another brain protein, tau, which has been linked to brain damage in Alzheimer’s and other neurological diseases.

    “We showed that poor sleep is associated with higher levels of two Alzheimer’s-associated proteins,” said David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor, head of the Department of Neurology and the study’s senior author. “We think that perhaps chronic poor sleep during middle age may increase the risk of Alzheimer’s later in life.”

    These findings, published July 10 in the journal Brain, may help explain why poor sleep has been associated with the development of dementias such as Alzheimer’s.

    More than 5 million Americans are living with Alzheimer’s disease, which is characterized by gradual memory loss and cognitive decline. The brains of people with Alzheimer’s are dotted with plaques of amyloid beta protein and tangles of tau protein, which together cause brain tissue to atrophy and die. There are no therapies that have been proven to prevent, slow or reverse the course of the disease.

    Previous studies by Holtzman, co-first author Yo-El Ju, MD, an assistant professor of neurology, and others have shown that poor sleep increases the risk of cognitive problems. People with sleep apnea, for example, a condition in which people repeatedly stop breathing at night, are at risk for developing mild cognitive impairment an average of 10 years earlier than people without the sleep disorder. Mild cognitive impairment is an early warning sign for Alzheimer’s disease.

    But it wasn’t clear how poor sleep damages the brain. To find out, the researchers — Holtzman; Ju; co-first author and graduate student Sharon Ooms of Radboud; Jurgen Claassen, MD, PhD, of Radboud; Emmanuel Mignot, MD, PhD, of Stanford; and colleagues — studied 17 healthy adults ages 35 to 65 with no sleep problems or cognitive impairments. Each participant wore an activity monitor on the wrist for up to two weeks that measured how much time they spent sleeping each night.

    After five or more successive nights of wearing the monitor, each participant came to the School of Medicine to spend a night in a specially designed sleep room. The room is dark, soundproof, climate-controlled and just big enough for one; a perfect place for sleeping, even as the participants wore headphones over the ears and electrodes on the scalp to monitor brain waves.

    Half the participants were randomly assigned to have their sleep disrupted during the night they spent in the sleep room. Every time their brain signals settled into the slow-wave pattern characteristic of deep, dreamless sleep, the researchers sent a series of beeps through the headphones, gradually getting louder, until the participants’ slow-wave patterns dissipated and they entered shallower sleep.

    The next morning, the participants who had been beeped out of slow-wave sleep reported feeling tired and unrefreshed, even though they had slept just as long as usual and rarely recalled being awakened during the night. Each underwent a spinal tap so the researchers could measure the levels of amyloid beta and tau in the fluid surrounding the brain and spinal cord.

    A month or more later, the process was repeated, except that those who had their sleep disrupted the first time were allowed to sleep through the night undisturbed, and those who had slept uninterrupted the first time were disturbed by beeps when they began to enter slow-wave sleep.

    The researchers compared each participant’s amyloid beta and tau levels after the disrupted night to the levels after the uninterrupted night, and found a 10 percent increase in amyloid beta levels after a single night of interrupted sleep, but no corresponding increase in tau levels. However, participants whose activity monitors showed they had slept poorly at home for the week before the spinal tap showed a spike in levels of tau.

    “We were not surprised to find that tau levels didn’t budge after just one night of disrupted sleep while amyloid levels did, because amyloid levels normally change more quickly than tau levels,” Ju said. “But we could see, when the participants had several bad nights in a row at home, that their tau levels had risen.”

    Slow-wave sleep is the deep sleep that people need to wake up feeling rested. Sleep apnea disrupts slow-wave sleep, so people with the disorder often wake up feeling unrefreshed, even after a full eight hours of shut-eye.

    Slow-wave sleep is also the time when neurons rest and the brain clears away the molecular byproducts of mental activity that accumulate during the day, when the brain is busily thinking and working.

    Ju thinks it is unlikely that a single night or even a week of poor sleep, miserable though it may be, has much effect on overall risk of developing Alzheimer’s disease. Amyloid beta and tau levels probably go back down the next time the person has a good night’s sleep, she said.

    “The main concern is people who have chronic sleep problems,” Ju said. “I think that may lead to chronically elevated amyloid levels, which animal studies have shown lead to increased risk of amyloid plaques and Alzheimer’s.”

    Ju emphasized that her study was not designed to determine whether sleeping more or sleeping better reduce risk of Alzheimer’s but, she said, neither can hurt.

    “Many, many Americans are chronically sleep-deprived, and it negatively affects their health in many ways,” Ju said. “At this point, we can’t say whether improving sleep will reduce your risk of developing Alzheimer’s. All we can really say is that bad sleep increases levels of some proteins that are associated with Alzheimer’s disease. But a good night’s sleep is something you want to be striving for anyway.”


  7. Sleep problems may be early sign of Alzheimer’s

    July 22, 2017 by Ashley

    From the American Academy of Neurology press release:

    Poor sleep may be a sign that people who are otherwise healthy may be more at risk of developing Alzheimer’s disease later in life than people who do not have sleep problems, according to a study published in the July 5, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers have found a link between sleep disturbances and biological markers for Alzheimer’s disease found in the spinal fluid.

    “Previous evidence has shown that sleep may influence the development or progression of Alzheimer’s disease in various ways,” said study author Barbara B. Bendlin, PhD, of the University of Wisconsin-Madison. “For example, disrupted sleep or lack of sleep may lead to amyloid plaque buildup because the brain’s clearance system kicks into action during sleep. Our study looked not only for amyloid but for other biological markers in the spinal fluid as well.”

    Amyloid is a protein that can fold and form into plaques. Tau is a protein that forms into tangles. These plaques and tangles are found in the brains of people with Alzheimer’s disease.

    For the study, researchers recruited 101 people with an average age of 63 who had normal thinking and memory skills but who were considered at risk of developing Alzheimer’s, either having a parent with the disease or being a carrier of a gene that increases the risk for Alzheimer’s disease called apolipoprotein E or APOE. Participants were surveyed about sleep quality. They also provided spinal fluid samples that were tested for biological markers of Alzheimer’s disease.

    Researchers found that people who reported worse sleep quality, more sleep problems and daytime sleepiness had more biological markers for Alzheimer’s disease in their spinal fluid than people who did not have sleep problems. Those biological markers included signs of amyloid, tau and brain cell damage and inflammation.

    “It’s important to identify modifiable risk factors for Alzheimer’s given that estimates suggest that delaying the onset of Alzheimer’s disease in people by a mere five years could reduce the number of cases we see in the next 30 years by 5.7 million and save $367 billion in health care spending,” said Bendlin.

    While some of these relationships were strong when looking at everyone as a group, not everyone with sleep problems has abnormalities in their spinal fluid. For example, there was no link between biological markers in the spinal fluid and obstructive sleep apnea.

    The results remained the same when researchers adjusted for other factors such as use of medications for sleep problems, amount of education, depression symptoms or body mass index.

    “It’s still unclear if sleep may affect the development of the disease or if the disease affects the quality of sleep,” said Bendlin. “More research is needed to further define the relationship between sleep and these biomarkers.”

    Bendlin added, “There are already many effective ways to improve sleep. It may be possible that early intervention for people at risk of Alzheimer’s disease may prevent or delay the onset of the disease.”

    One limitation of the study was that sleep problems were self-reported. Monitoring of sleep patterns by health professionals may be beneficial in future studies.


  8. Study examines the secret connection between anxiety, sleep

    July 17, 2017 by Ashley

    From the University of Tsukuba press release:

    You may have experienced sleepless nights when you were anxious, stressed or too excited. Such emotions are well-known to affect wakefulness and can even cause insomnia, though the underlying mechanisms in our brain have still been unclear. Scientists in the Sleep Institute in Japan spotted neurons that play crucial roles in connecting emotions and sleep, shedding light on the future discovery of drug targets for anxiety disorder and/or sleep disorders.

    Encountering predators, adapting to a novel environment or expecting a reward ? these stressful or emotionally-salient situations require animals to shift their behavior to a vigilant state, altering their physiological conditions through modulation of autonomic and endocrine functions.

    The bed nucleus of the stria terminalis (BNST) is a part of the extended amygdala, which is generally considered as a key player in stress response, fear and anxiety. Through projections to various brain regions including relay nuclei of the autonomic nervous system, hypothalamic regions and the central nucleus of the amygdala, the BNST controls endocrine and autonomic reactions in response to emotionally-salient stimuli, along with behavioral expression of anxiety and fear.

    A group of researchers led by Takeshi Sakurai, Vice Director of the International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, found that acute optogenetic excitation of GABAergic neurons in BNST during non-rapid eye movement (NREM) sleep in mice resulted in immediate transition to a wakefulness state without the function of orexins, highly important neuropeptides for maintaining wakefulness. Notably, stimulation of the same neurons during REM sleep did not show any effects on sleep/wakefulness states.

    Prolonged excitation of GABAergic neurons in BNST by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, and it was abolished by administering a dual orexin receptor blocker (antagonist) DORA 22 in advance, meaning that orexins are involved in this phenomenon.

    “Our study revealed a role of the BNST GABAergic system in sleep/wakefulness control, especially in shifting animals’ behavioral states from NREM sleep to wakefulness. It also provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation, which will hopefully lead to the first step to develop remedies for sleep disorders,” Sakurai says.


  9. Why social isolation can bring a greater risk of illness

    July 14, 2017 by Ashley

    From the University of Pennsylvania School of Medicine press release:

    Social isolation has been linked to a wide range of health problems, as well as a shorter lifespan in humans and other animals. In fact, during a U.S. Senate hearing on aging issues this spring, a representative for the Gerontological Society of America urged lawmakers to support programs that help older adults stay connected to their communities, stating that social isolation is a “silent killer that places people at higher risk for a variety of poor health outcomes.”

    Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have found a possible explanation for this association. The team observed that in the fruit fly Drosophila melanogaster, social isolation leads to sleep loss, which in turn leads to cellular stress and the activation of a defense mechanism called the unfolded protein response (UPR). Their findings are published online in the journal SLEEP this month. The UPR is found in virtually all animal species. Although its short-term activation helps protect cells from stress, chronic activation can harm cells. Long-term, harmful activation of the UPR is suspected as a contributor to the aging process and to specific age-related diseases such as Alzheimer’s and diabetes.

    Studies also have shown that social isolation is a growing problem in developed countries. In the United States, for example, about half of people older than 85 live alone, and decreased mobility or ability to drive may cut opportunities for other socialization.

    “A lot of elderly people live alone, and so we suspect that stresses from the combination of aging and social isolation creates a double-whammy at the cellular and molecular level,” said senior author Nirinjini Naidoo, PhD, a research associate professor of Sleep Medicine. “If you have an age-related disruption of the UPR response, compounded by sleep disturbances, and then you add social isolation, that may be a very unhealthy cocktail.”

    This line of research stemmed from a surprise finding by the new study’s first author, Marishka K. Brown, PhD, who was then a postdoctoral researcher at Penn. She is now Program Director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute (NHLBI). While evaluating the effects of aging on the UPR in fruit flies, she noticed that molecular markers of UPR activation were at higher levels in flies kept singly in vials, compared to same-aged flies kept in groups.

    “Ultimately, she realized that keeping animals isolated induces a cellular stress response and a higher level of UPR activation,” Naidoo said. Markers of UPR activation include the protein BiP, a molecular “chaperone” that helps ensure proper protein folding within cells. Proteins, after being synthesized as simple chains of amino acids, are meant to fold into functional shapes, which are often highly complex. This delicate process is easily disturbed when cells are under stress and can lead to the harmful, runaway clumping of unfolded or misfolded proteins.

    As its name suggests, the UPR is supposed to protect against this cellular catastrophe. But when it fails to work efficiently to restore proper protein-folding conditions, and stays activated, it can trigger harmful inflammation, suppress normal, healthy cellular activity, and ultimately force the death of the cell. Scientists have found evidence that this inefficient, chronic response becomes more likely with aging. “When animals get older, you start to see a more maladaptive UPR,” Naidoo said.

    Why does social isolation trigger the UPR? Naidoo and others have shown in prior studies that sleep loss induces the UPR in multiple animal species. Other studies have shown that social isolation induces sleep loss, again in multiple species, including humans. When Brown forced the isolated flies to sleep more, for example by giving them the sleep drug Ambien (zolpidem), their levels of UPR markers dropped to those seen in grouped flies. Conversely, when she caused sleep loss in otherwise healthy grouped flies, their levels of UPR markers rose towards the levels seen in socially isolated flies.

    “When you keep animals isolated, it basically induces a disturbance of sleep, which then gives rise to a cellular stress that in turn triggers the UPR,” Naidoo said.

    Naidoo and her colleagues are continuing to study the connections among aging, sleep loss, the UPR, and age-related diseases such as Alzheimer’s. “Aging itself seems to make the UPR more defective, but we suspect this is worsened by the fact that aging also tends to cause more fragmented sleep,” Naidoo said.


  10. Lack of sleep fuels harmful inflammatory response to marital stress

    by Ashley

    From the Ohio State University Wexner Medical Center press release:

    A lack of sleep doesn’t just leave you cranky and spoiling for a fight. Researchers at The Ohio State University Institute for Behavioral Medicine Research say it also puts you at risk for stress-related inflammation.

    This type of inflammation is associated with higher risk of cardiovascular disease, diabetes, arthritis and other diseases.

    “We know sleep problems are also linked with inflammation and many of the same chronic illnesses. So we were interested to see how sleep related to inflammation among married couples, and whether one partner’s sleep affected the other’s inflammation,” said Stephanie Wilson, lead researcher on the study.

    Results of the study were published in the journal Psychoneuroendocrinology.

    The research team recruited 43 couples who completed two study visits. Each time, the couples provided blood samples and said how many hours they had slept the previous two nights. Then researchers had the couples try to resolve a topic that sparks conflict in their marriage. Blood samples were taken again following the discussion.

    “We found that people who slept less in the past few nights didn’t wake up with higher inflammation, but they had a greater inflammatory response to the conflict. So that tells us less sleep increased vulnerability to a stressor,” Wilson said.

    If both partners got less than seven hours of sleep the previous two nights, the couple was more likely to argue or become hostile. For every hour of sleep lost, the researchers noted that levels of two known inflammatory markers rose 6 percent. Couples who used unhealthy tactics in their disagreement had an even greater inflammatory response — about a 10 percent increase with each hour of less sleep.

    “Any increase isn’t good, but a protracted increase that isn’t being addressed is where it can become a problem,” Wilson said. “What’s concerning is both a lack of sleep and marital conflict are common in daily life. About half of our study couples had slept less than the recommended seven hours in recent nights.”

    That’s higher than the current national average. The CDC reports 35 percent of Americans get less than seven hours of sleep per night.

    “Part of the issue in a marriage is that sleep patterns often track together. If one person is restless, or has chronic problems, that can impact the other’s sleep. If these problems persist over time, you can get this nasty reverberation within the couple,” said Janice Kiecolt-Glaser, senior author and director of the Institute for Behavioral Medicine Research.

    Researchers were encouraged to see that there was a protective effect if one of the partners was well-rested, or discussed conflict in a healthy way. They tended to neutralize the disagreement that might be stirred by the sleep-deprived partner.

    “We would tell people that it’s important to find good ways to process the relationship and resolve conflict — and get some sleep,” Kiecolt-Glaser said.