Microsleep: Brain Regions Can Take Short Naps During Wakefulness, Leading to Errors

Microsleep: Brain Regions Can Take Short Naps During Wakefulness, Leading to Errors

  10:28:00 AM    Science Lover

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If you've ever lost your keys or stuck the milk in the cupboard and the cereal in the refrigerator, you may have been the victim of a tired brain region that was taking a quick nap.

A photo of rats with objects introduced into their 
cages to keep them awake. (Credit: Giulio Tononi,
M.D., Ph.D., University of Wisconsin-Madison)

Researchers at the University of Wisconsin-Madison have a new explanation. They've found that some nerve cells in a sleep-deprived yet awake brain can briefly go "off line," into a sleep-like state, while the rest of the brain appears awake.

"Even before you feel fatigued, there are signs in the brain that you should stop certain activities that may require alertness," says Dr. Chiara Cirelli, professor of psychiatry at the School of Medicine and Public Health. "Specific groups of neurons may be falling asleep, with negative consequences on performance."

Until now, scientists thought that sleep deprivation generally affected the entire brain. Electroencephalograms (EEGs) show network brain-wave patterns typical of either being asleep or awake.

"We know that when we are sleepy, we make mistakes, our attention wanders and our vigilance goes down," says Cirelli. "We have seen with EEGs that even while we are awake, we can experience shorts periods of 'micro sleep.' "

Periods of micro sleep were thought to be the most likely cause of people falling asleep at the wheel while driving, Cirelli says.

But the new research found that even before that stage, brains are already showing sleep-like activity that impairs them, she says.

As reported in the current issue of Nature, the researchers inserted probes into specific groups of neurons in the brains of freely-behaving rats. After the rats were kept awake for prolonged periods, the probes showed areas of "local sleep" despite the animals' appearance of being awake and active.

"Even when some neurons went off line, the overall EEG measurements of the brain indicated wakefulness in the rats," Cirelli says.

And there were behavioral consequences to the local sleep episodes.

"When we prolonged the awake period, we saw the rats start to make mistakes," Cirelli says.

When animals were challenged to do a tricky task, such as reaching with one paw to get a sugar pellet, they began to drop the pellets or miss in reaching for them, indicating that a few neurons might have gone off line.

"This activity happened in few cells," Cirelli adds. "For instance, out of 20 neurons we monitored in one experiment, 18 stayed awake. From the other two, there were signs of sleep -- brief periods of activity alternating with periods of silence."

The researchers tested only motor tasks, so they concluded from this study that neurons affected by local sleep are in the motor cortex.

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Antibacterial Soaps: Being Too Clean Can Make People Sick, Study Suggests

Antibacterial Soaps: Being Too Clean Can Make People Sick, Study Suggests

  9:57:00 AM    Science Lover

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Young people who are overexposed to antibacterial soaps containing triclosan may suffer more allergies, and exposure to higher levels of Bisphenol A among adults may negatively influence the immune system, a new University of Michigan School of Public Health study suggests.

Young people who are overexposed to antibacterial 
soaps containing triclosan may suffer more allergies, and 
exposure to higher levels of Bisphenol A among adults 
may negatively influence the immune system, a new 
University of Michigan School of Public Health study 
suggests. (Credit: iStockphoto/Jorge Salcedo)

Triclosan is a chemical compound widely used in products such as antibacterial soaps, toothpaste, pens, diaper bags and medical devices. Bisphenol A (BPA) is found in many plastics and, for example, as a protective lining in food cans. Both of these chemicals are in a class of environmental toxicants called endocrine-disrupting compounds (EDCs), which are believed to negatively impact human health by mimicking or affecting hormones.

Using data from the 2003-2006 National Health and Nutrition Examination Survey, U-M researchers compared urinary BPA and triclosan with cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in a sample of U.S. adults and children over age 6. Allergy and hay fever diagnosis and CMV antibodies were used as two separate markers of immune alterations.

"We found that people over age 18 with higher levels of BPA exposure had higher CMV antibody levels, which suggests their cell-mediated immune system may not be functioning properly," said Erin Rees Clayton, research investigator at the U-M School of Public Health and first author on the paper.

Researchers also found that people age 18 and under with higher levels of triclosan were more likely to report diagnosis of allergies and hay fever.

There is growing concern among the scientific community and consumer groups that these EDCs are dangerous to humans at lower levels than previously thought.

"The triclosan findings in the younger age groups may support the 'hygiene hypothesis,' which maintains living in very clean and hygienic environments may impact our exposure to micro-organisms that are beneficial for development of the immune system," said Allison Aiello, associate professor at the U-M School of Public Health and principal investigator on the study.

As an antimicrobial agent found in many household products, triclosan may play a role in changing the micro-organisms to which we are exposed in such a way that our immune system development in childhood is affected.

"It is possible that a person can be too clean for their own good," said Aiello, who is also a visiting associate professor of epidemiology at Harvard.

Previous animal studies indicate that BPA and triclosan may affect the immune system, but this is the first known study to look at exposure to BPA and triclosan as it relates to human immune function, Aiello said.

One surprise finding is that with BPA exposure, age seems to matter, said Rees Clayton. In people 18 or older, higher amounts of BPA were associated with higher CMV levels, but in people younger than 18 the reverse was true.

"This suggests the timing of the exposure to BPA and perhaps the quantity and length of time we are exposed to BPA may be affecting the immune system response," Rees Clayton said.

This is just the first step, she said, but a very important one. Going forward, researchers would like to study the long-term effects of BPA and triclosan in people to see if they can establish a causal relationship.

One limitation of the study is that it measured disease and exposure simultaneously and thus shows only part of the picture, Aiello said.

"It is possible, for example, that individuals who have an allergy are more hygienic because of their condition, and that the relationship we observed is, therefore, not causal or is an example of reverse causation," Aiello said.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment.

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Genetic Secrets of Human Longevity

Genetic Secrets of Human Longevity

  9:18:00 PM    Science Lover

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While environment and family history are factors in healthy aging, genetic variants play a critical and complex role in conferring exceptional longevity, according to a new study by a team of researchers from the Boston University Schools of Public Health and Medicine and the Boston Medical Center.

While environment and family history are factors in 
healthy aging, genetic variants play a critical 
and complex role in conferring exceptional 
longevity. (Credit: iStockphoto/Catherine Yeulet)

In a study released July 1 online by the journal Science, the research team identified a group of genetic variants that can predict exceptional longevity in humans with 77 percent accuracy -- a breakthrough in understanding the role of genes in determining human lifespan.

Based upon the hypothesis that exceptionally old individuals are carriers of multiple genetic variants that influence their remarkable survival, the team conducted a genome-wide association study of centenarians. Centenarians are a model of healthy aging, as the onset of disability in these individuals is generally delayed until they are well into their mid-nineties.

Researchers led by Paola Sebastiani, PhD, a professor of biostatistics at the BU School of Public Health and Thomas Perls, MD, MPH, associate professor of medicine at the BU School of Medicine and a geriatrician at Boston Medical Center, built a unique genetic model that includes 150 genetic variants, known as single nucleotide polymorphisms (SNPs). They found that these 150 variants could be used to predict if a person survived to very old ages (late 90s and older) with a high rate of accuracy.

In addition, the team's analysis identified 19 genetic clusters or "genetic signatures" of exceptional longevity that characterized 90 percent of the centenarians studied. The different signatures correlated with differences in the prevalence and age-of-onset of diseases such as dementia and hypertension, and may help identify key subgroups of healthy aging, the authors said.

Notably, the team found that 45 percent of the oldest centenarians -- those 110 years and older -- had a genetic signature with the highest proportion of longevity-associated genetic variants.

"These genetic signatures are a new advance towards personalized genomics and predictive medicine, where this analytic method may prove to be generally useful in prevention and screening of numerous diseases, as well as the tailored uses of medications," said Dr. Perls, founder and director of the New England Centenarian Study.

The researchers developed a novel Bayesian statistical approach to analyze genotype data from more than 1,000 centenarians and several control groups, and to identify those SNPs that were most predictive of being centenarians or controls. The team began by using the SNPs that were most likely associated with exceptional longevity, and once the researchers identified 150 SNPs, they found that adding more variants did not further improve the ability to predict whether a person was a centenarian or a control subject.

Dr. Sebastiani noted: "The methodology that we developed can be applied to other complex genetic traits, including Alzheimer's disease, Parkinson's, cardiovascular disease and diabetes. It reinvigorates the potential high utility of collecting and analyzing such data."

Besides looking at which genetic variants were associated with longevity, the authors looked into whether the absence of disease-associated variants also played an important role. They did this by analyzing how many disease-associated variants each centenarian had, compared to each of the controls. Their analysis found little difference between the two groups, suggesting that the presence of genetic variants associated with longevity is of more importance than the absence of disease-associated variants.

If these findings are confirmed, they would suggest that "predicting disease risk using disease-associated variants may be inaccurate and potentially misleading, without more information about other genetic variants that could attenuate such risk" the authors commented.

Overall, the authors said, their preliminary data "suggest that exceptional longevity may be the result of an enrichment of longevity-associated variants that counter the effect of disease-associated variants and contribute to the compression of morbidity and/or disability towards the end of these very long lives." They added that "further investigation is needed to understand how and why these variants collectively predispose for exceptional longevity."

The researchers noted that the 77-percent accuracy rate of predictions "shows that genetic data can indeed predict exceptional longevity without knowledge of any other risk factor."

But they added: "This prediction is not perfect, however, and although it may improve with better knowledge of the variations in the human genome, its limitations confirm that environmental factors (e.g., lifestyle) also contribute in important ways to the ability of humans to survive to very old ages."

Drs. Sebastiani and Perls also cautioned that they developed this genetic risk model as a way to dissect the complex genetic bases of exceptional longevity and to discover the different genetic paths to age 100 and older. An understanding of the implications of this model's use in the general population would be necessary before this test is marketed, they said.

The study was funded by grants from the National Institute of Aging (NIA) and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

"This is a novel approach to studying genetic contributions to exceptional longevity," said Winifred K. Rossi, deputy director of the NIA's Division of Geriatrics and Clinical Gerontology. "It adds to a growing set of analytical tools that aim to identify and understand the complex genetic and environmental factors that lead to healthy long life."

In addition to Perls and Sebastiani, other authors include: Nadia Solovieff and Stephen W. Hartley of the BU School of Public Health Biostatistics Department; Daniel A. Dworkis, Efthymia Melista and Monty Montano of the BU School of Medicine Department of Medicine; Jemma B. Wilk and Richard H. Myers of the BU School of Medicine Department of Neurology; Martin H. Steinberg and Clinton T. Baldwin of the BU School of Medicine Departments of Medicine and Pediatrics and Boston Medical Center; Stacy Anderson of the BU School of Medicine Department of Medicine, Section of Geriatrics, and Boston Medical Center; and Annibale Puca of IRCCS Multimedica, Milano, Italy.

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Cigarettes Harbor Many Pathogenic Bacteria

Cigarettes Harbor Many Pathogenic Bacteria

  12:11:00 AM    Science Lover

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Cigarettes are "widely contaminated" with bacteria, including some known to cause disease in people, concludes a new international study conducted by a University of Maryland environmental health researcher and microbial ecologists at the Ecole Centrale de Lyon in France.

Cigarettes are "widely contaminated" with bacteria, including some known to cause disease in people, concludes a new international study. (Credit: iStockphoto)

 

The research team describes the study as the first to show that "cigarettes themselves could be the direct source of exposure to a wide array of potentially pathogenic microbes among smokers and other people exposed to secondhand smoke." Still, the researchers caution that the public health implications are unclear and urge further research.

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Sleep: Spring Cleaning For The Brain?

Sleep: Spring Cleaning For The Brain?

  11:06:00 AM    Science Lover

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On the left, the brain of the well-rested blue fly has low levels of a synaptic protein called BRP in this 3D view from a confocal mircoscope. On the right, the brain of the sleep-deprived fly glows orange in areas of BRP concentration. (Bruchpilot or BRP is a protein involved in communication between neurons.)In the tired fly, the protein is present at high concentartions in three major areas of the fly's brain that are associated with learning. Sleep reduces the levels of this protein, an indication that synapses get smaller and/or weaker. This process of "downscaling" may be important so the brain is reset to normal levels of synaptic activity and can begin learning again the next day. (Credit: Courtesy of UW Health Public Affairs)

If you've ever been sleep-deprived, you know the feeling that your brain is full of wool.

Now, a study published in the April 3 edition of the journal Science has molecular and structural evidence of that woolly feeling — proteins that build up in the brains of sleep-deprived fruit flies and drop to lower levels in the brains of the well-rested. The proteins are located in the synapses, those specialized parts of neurons that allow brain cells to communicate with other neurons.

Sleep researchers at the University of Wisconsin-Madison School of Medicine and Public Health believe it is more evidence for their theory of "synaptic homeostasis." This is the idea that synapses grow stronger when we're awake as we learn and adapt to an ever-changing the environment, that sleep refreshes the brain by bringing synapses back to a lower level of strength. This is important because larger synapses consume a lot of energy, occupy more space and require more supplies, including the proteins examined in this study.

Sleep — by allowing synaptic downscaling — saves energy, space and material, and clears away unnecessary "noise" from the previous day, the researchers believe. The fresh brain is then ready to learn again in the morning.

The researchers — Giorgio Gilestro, Giulio Tononi and Chiara Cirelli, of the Center for Sleep and Consciousness — found that levels of proteins that carry messages in the synapses (or junctions) between neurons drop by 30 to 40 percent during sleep.

In the Science paper, three-dimensional photos using confocal microscopy show the brains of sleep-deprived flies filled with a synaptic protein called Bruchpilot (BRP), a component of the machinery that allows communication among neurons. In well-rested flies, levels of BRP and four other synaptic proteins drop back to low levels, providing evidence that sleep resets the brain to allow more growth and learning the next day.

"We know that sleep is necessary for our brain to function properly, to learn new things every day, and also, in some cases, to consolidate the memory of what we learned during the day," says Cirelli, associate professor of psychiatry. "During sleep, we think that most, if not all, synapses are downscaled: at the end of sleep, the strongest synapses shrink, while the weakest synapses may even disappear."

The confocal microscope views show this happening in all three major areas of the fruit-fly brain, which are known to be very plastic (involved in learning).

In a paper published last year, Tononi, Cirelli and their co-investigators found similar chemical changes in the synapses of rats' brains. They also showed that rats' brains have a stronger "evoked response" to electrical stimulation after being awake, and a weaker one after sleep. That finding provided more evidence, using electrophysiological rather than molecular techniques, consistent with the idea that synapses grow stronger during the day, then weaker during sleep.

Because sleep performs the same function in the brains of species as diverse as fruit flies and rats, Cirelli says it was likely conserved by evolution because it is so important to an animal's health and survival.

The Wisconsin laboratory has pioneered ways of studying sleep in different species, including fruit flies.

To keep the flies awake, they're put into a "fly agitator" that holds 10 plates, each containing 32 drowsy flies. A robot arm shakes the plates occasionally to keep the flies from dozing.

Flies were deprived of sleep for as long as 24 hours. Researchers then dissected their brains and measured the levels of four pre-synaptic proteins and one post-synaptic protein. All levels rose progressively during periods of wakefulness and fell after sleep. Other experiments confirmed that the changes in protein levels were not caused by exposure to light and darkness or by the stimulation itself, but by sleep and waking. They also used confocal microscopy and an antibody that specifically recognizes BRP to measure the expression of this protein in many fly-brain areas.

Higher levels of these synaptic proteins during waking may be evidence of random experiences that fill the brain every day and need to be dissipated to make room for the learning and memories that are truly significant.

"Much of what we learn in a day, we don't really need to remember," Cirelli says. "If you've used up all the space, you can't learn more before you clean out the junk that is filling up your brain."

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Journal reference:

1. Giorgio F. Gilestro, Giulio Tononi, and Chiara Cirelli. Widespread Changes in Synaptic Markers as a Function of Sleep and Wakefulness in Drosophila. Science, 2009; 324 (5923): 109 DOI: 10.1126/science.1166673

Adapted from materials provided by University of Wisconsin-Madison.

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