Brain structure generates pockets of sleep within the brain

 

MIT neuroscientists have discovered a brain circuit that can trigger small regions of the brain to fall asleep or become less alert, while the rest of the brain remains awake. Credit: Illustration by Jose-Luis Olivares/MIT Sleep is usually considered an all-or-nothing state: The brain is either entirely awake or entirely asleep. However, MIT neuroscientists have discovered a brain circuit that can trigger small regions of the brain to fall asleep or become less alert, while the rest of the brain remains awake. This circuit originates in a brain structure known as the thalamic reticular nucleus (TRN), which relays signals to the thalamus and then the brain's cortex, inducing pockets of the slow, oscillating brain waves characteristic of deep sleep. Slow oscillations also occur during coma and general anesthesia, and are associated with decreased arousal. With enough TRN activity, these waves can take over the entire brain. The researchers believe the TRN may help the brain consolidate new memories by coordinating slow waves between different parts of the brain, allowing them to share information more easily. "During sleep, maybe specific brain regions have slow waves at the same time because they need to exchange information with each other, whereas other ones don't," says Laura Lewis, a research affiliate in MIT's Department of Brain and Cognitive Sciences and one of the lead authors of the new study, which appears in the journal eLife. The TRN may also be responsible for what happens in the brain when sleep-deprived people experience brief sensations of "zoning out" while struggling to stay awake, the researchers say. The paper's other first author is Jakob Voigts, an MIT graduate student in brain and cognitive sciences. Senior authors are Emery Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at MIT and an anesthesiologist at Massachusetts General Hospital, and Michael Halassa, an assistant professor at New York University. Other authors are MIT research affiliate Francisco Flores and Matthew Wilson, the Sherman Fairchild Professor in Neurobiology and a member of MIT's Picower Institute for Learning and Memory. Local control Until now, most sleep research has focused on global control of sleep, which occurs when the entire brain is awash in slow waves -- oscillations of brain activity created when sets of neurons are silenced for brief periods. However, recent studies have shown that sleep-deprived animals can exhibit slow waves in parts of their brain while they are still awake, suggesting that the brain can also control alertness at a local level. The MIT team began its investigation of local control of alertness or drowsiness with the TRN because its physical location makes it perfectly positioned to play a role in sleep, Lewis says. The TRN surrounds the thalamus like a shell and can act as a gatekeeper for sensory information entering the thalamus, which then sends information to the cortex for further processing. Using optogenetics, a technique that allows scientists to stimulate or silence neurons with light, the researchers found that if they weakly stimulated the TRN in awake mice, slow waves appeared in a small part of the cortex. With more stimulation, the entire cortex showed slow waves. "We also found that when you induce these slow waves across the cortex, animals start to behaviorally act like they're drowsy. They'll stop moving around, their muscle tone will go down," Lewis says. The researchers believe the TRN fine-tunes the brain's control over local brain regions, enhancing or reducing slow waves in certain regions so those areas can communicate with each other, or inducing some areas to become less alert when the brain is very drowsy. This may explain what happens in humans when they are sleep-deprived and momentarily zone out without really falling asleep. "I'm inclined to think that happens because the brain begins to transition into sleep, and some local brain regions become drowsy even if you force yourself to stay awake," Lewis says. Natural sleep and general anesthesia Understanding how the brain controls arousal could help researchers design new sleep and anesthetic drugs that create a state more similar to natural sleep. Stimulating the TRN can induce deep, non-REM-like sleep states, and previous research by Brown and colleagues uncovered a circuit that turns on REM sleep. Brown adds, "The TRN is rich in synapses -- connections in the brain -- that release the inhibitory neurotransmitter GABA. Therefore, the TRN is almost certainly a site of action of many anesthetic drugs, given that a large classes of them act at these synapses and produce slow waves as one of their characteristic features." Previous work by Lewis and colleagues has shown that unlike the slow waves of sleep, the slow waves under general anesthesia are not coordinated, suggesting a mechanism for why these drugs impair information exchange in the brain and produce unconsciousness.   http://www.sciencedaily.com/releases/2015/10/151013182735.htm

A New Way to Fight Aging in the Brain

 

For the first time, scientists can take skin cells from people of various ages and transform them into brain cells reflecting the ages of their donors. By Faye Flam on October 9, 2015 Why It Matters Aging is the number-one risk factor for Alzheimer’s and Parkinson’s diseases. Studying how living human brain cells age could speed the development of treatments for disease and cognitive decline. Scientists created these aging human brain cells not from old brains but from the skin cells of older people. Our brain cells change with age: various genes become more or less active, the membrane that holds the nucleus together starts to degenerate, and molecules that in young cells are neatly compartmentalized become scattered and disorganized. Now scientists have found a way to transform ordinary skin cells into living cultures of aging human neurons—test beds for ways we might reverse these effects of time. In the past, scientists have created neurons in a dish using stem-cell technology, but those efforts produced the equivalent of embryonic neurons. Jerome Mertens of the Salk Institute for Biological Studies and his colleagues took skin cells from donors of different ages and transformed them into neurons that retained the effects of aging. This technique opens up new avenues for studying aging, age-associated diseases, and the possibility that drugs might stave off what was once inevitable. “These results are obviously going to have an impact,” says John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania, who was not part of the study. The results will not only advance research into aging, he says, but could aid in the continued quest to create new cells to repair or replace damaged organs. Gearhart says that the new findings address a major problem in his field. There are several ways to force cells to switch from one type to another, but scientists haven’t been sure how the neurons made from a skin cell differ from the neurons that develop normally in people’s brains. The earliest method for reprogramming cells set the aging clock back to zero, he says, because the skin cells first had to be turned into a type of stem cell similar to those in early embryos. Mertens and his colleagues tried a newer technique, first developed at Stanford University, in which a series of biochemical tweaks switched skin cells directly into brain cells. What nobody knew, says Mertens, was how the cells created by this more direct route differed from the ones that had been first returned to an embryonic state. Were they making baby neurons or ones that reflected the ages of the donors? To find out, he and his colleagues collected skin cells from 19 people of different ages from infancy to 89, turned them directly into brain cells, and compared them with cells obtained from autopsies of people at different ages. They found that the transformed neurons carried certain telltale signs of aging in proportion to the age of the donors. Indeed, he says, they found that skin cells from older people could be turned into the equivalent of neurons from older people. They published their results in the latest issue of the journal Cell Stem Cell. The older neurons show different patterns of gene activation, says Martens. Age also disrupts what’s called compartmentalization—the ordered way in which some proteins stay confined to the nucleus of cells and others to the surrounding cytoplasm. Martens says the membrane separating the nucleus from the rest of the cell starts to fail, so as our cells age, more proteins end up in the wrong place. He’s eager to understand how this process affects the way our brains age and our susceptibility to diseases such as ALS and Alzheimer’s. The cell-transforming technique might also be expanded to produce three-dimensional structures called organoids, he says, which can be used as models of human organs.   http://www.technologyreview.com/news/542336/a-new-way-to-fight-aging-in-the-brain/

Viral and parasitic diseases are not only worth killing off, they are also increasingly vulnerable

 

Oct 10th 2015 | From the print edition TO EXTERMINATE a living species by accident is normally frowned on. To do so deliberately might thus seem an extraordinary sin. But if that species isPlasmodium falciparum, the sin may be excused. This parasitic organism causes the most deadly form of malaria. Together with four cousins, it is responsible for about 450,000 deaths a year, and the ruination of the lives of millions more people who survive the initial crisis of disease. Besides the direct suffering this causes, the lost human potential is enormous. The Gates Foundation, an American charity, reckons that eradicating malaria would bring the world $2 trillion of benefits by 2040.   Malaria is one of the worst examples of the damage that transmissible diseases can wreak. But it is not alone. AIDS carries off fit, young adults by the millions and tuberculosis by the hundreds of thousands. Measles, whooping cough and diarrhoea together kill over 1m children a year. Parasitic worms and mosquito-borne viruses like dengue, though they take relatively few lives, debilitate many. Campaigns have brought the toll down heroically. As recently as 2000, malaria killed around 850,000 people a year; likewise, since 2000 deaths from measles have fallen by 75%, to around 150,000. These successes are to be celebrated, but an even greater prize exists: to go beyond controlling infections and infestations and instead to eradicate some of them completely, by exterminating the pathogens and parasites that cause them. That has been accomplished a couple of times in the past, for smallpox (a human disease) and rinderpest (a cattle disease similar to measles). The end is reckoned to be close for polio (a virus that once killed and crippled millions) and dracunculiasis (a parasitic worm). But more must follow. Swat teams Some diseases are not suitable for eradication because the organisms that cause them hang around in the environment, or have other animal hosts. Others, such as tuberculosis, can infect people “silently”, without causing symptoms, so are invisible to doctors. But sometimes the culprit is a poverty of ambition. A list of five plausible targets—measles, mumps, rubella, filariasis and pork tapeworm—has hardly changed since the early 1990s, yet measles, mumps and rubella are all the subjects of intensive vaccination campaigns that could easily be converted into ones of eradication. And even though Swaziland is poised to become the first malaria-free country in sub-Saharan Africa (see article), only a few dare to make explicit the goal of ridding the planet of the disease. Hepatitis C should be made a target, too. It kills half a million a year, and affects rich and poor countries alike, yet new drugs against it are almost 100% effective and there are no silent carriers. Eradicating these seven diseases—the five, plus malaria and hepatitis C—would save a yearly total of 1.2m lives. It would transform countless more. People argue that the cost of chasing down the last few cases of a disease is not worth it. If the mass-vaccination campaigns under way can lower the incidence of measles, mumps, rubella and so on in poor countries to something close to rich-world levels, the argument goes, that is surely good enough. Well, it isn’t. A disease can bounce back. That is what malaria did in the 1960s, when political attention waned, and the parasites that cause it evolved resistance to drugs and the mosquitoes that spread it evolved resistance to insecticides. Three big improvements underpin the argument for throwing eradication’s net more widely. The first is better communications. The technology for locating and monitoring cases of disease in poor countries, even when few and far between, has improved immeasurably in the past two decades with the spread of mobile phones and the internet, and the expansion of road networks. The second is better medical technology. The reason filariasis is on the “possibles” list, for example, is the invention of ivermectin, a drug that kills the worm which causes it. The inventors of this drug won half of this year’s Nobel prize for medicine (see article). The other half was won by the woman who came up with an answer to drug resistance in malaria—a medicine called artemisinin, which has been crucial to the success of the recent push against the disease. (This time, alert to the risk of resistance, doctors have formulated it with other drugs to create combination therapies that natural selection finds hard to get around.) Even better technology is in the pipeline. In the case of mosquito-borne illnesses such as malaria and dengue, genetic engineering promises ways of making the insects resistant to the pathogens that they pass on to people, of crashing the mosquito population, and even of attacking insects and pathogens with genetically modified fungi and bacteria. Genetic engineering also promises a wide range of new vaccines. The third reason for seeking eradication is a change in political attitudes. The emergence of AIDS, in particular, made governments everywhere sit up and take notice. Last year’s west African outbreak of Ebola only reinforced the message. Political attention leads to better medical infrastructure. To deal with AIDS, new networks of clinics were created and staffed with trained personnel. These can serve as the backbone of the campaigns that would be the starting-point for many extermination programmes. The Dalek doctrine The list of candidates for such programmes should be extended as and when circumstances change. The biggest prize might be AIDS itself. Smallpox, the first target for eradication, was picked in part because the virus that caused it had only humans as hosts and could not survive independently for more than a few hours. It had, in other words, no hiding place. Both of these are true of HIV, the AIDS-causing virus. What is missing is the third ingredient for smallpox: a reliable vaccine. Throughout history, humans and disease have waged a deadly and never-ending war. Today the casualties are chiefly the world’s poorest people. But victory against some of the worst killers is at last within grasp. Seize it. From the print edition: Leaders   http://www.economist.com/news/leaders/21672213-viral-and-parasitic-diseases-are-not-only-worth-killing-they-are-also-increasingly?fsrc=scn%2Fesp%2FFB

China's middle class overtakes US as largest in the world

 

World's second largest economy has seen its middle class grow to 109 million Luxury homes in Shanghai By Agency 7:37AM BST 14 Oct 2015 Comments China's middle class has overtaken the United States to become the largest in the world according to a comprehensive new report on the distribution of global wealth. Despite fears of a global growth slowdown in the emerging world, Asia is set to be the scene for the greatest expansion of the world's middle class, said Credit Suisse, in its annual wealth report. • How the world's up and coming rich spend their money The Swiss bank said with 109 million adults "this year, the Chinese middle class for the first time outnumbered" that in the United States at 92 million. While the number of middle class worldwide grew last year at a slower pace than the wealthy, it "will continue to expand in emerging economies overall, with a lion's share of that growth to occur in Asia," said Credit Suisse chief executive Tidjane Thiam. Number of middle-class adults (million), 2015, by region and country "As a result, we will see changing consumption patterns as well as societal changes as, historically, the middle class has acted as an agent of stability and prosperity," he added. The report said size and wealth of the middle class was a key factor in economic development, and the middle class was often at the heart of political movements and new consumption trends. China now accounts for a fifth of the world population, while holding nearly 10pc of the global wealth. The report used a floor for the middle class as having wealth double the annual medium income for their country. While wealth may still be mostly concentrated in Europe and the United States, Mr Thiam said "the growth of wealth in emerging markets has been most impressive, including a fivefold rise in China since the beginning of the century." Overall, the report found that global wealth fell by nearly 5pc in the year to mid-2015 to $250 trillion due a strengthening of the US dollar in which income is compared. However if currency effects are stripped out, wealth continued to expand at the trend rate since the beginning of the century. The report also found the number of millionaires is forecast to increase 46pc to 49.3 million over the next five years, with Malaysia more than doubling the number of affluent individuals with $1 million.   http://www.telegraph.co.uk/finance/china-business/11929794/Chinas-middle-class-overtakes-US-as-largest-in-the-world.html?utm_source=dlvr.it&utm_medium=twitter