Posts tagged science
Articles and news from the latest research reports.
How fat might be controlled through the body clock
Australian researchers have shed more light on an underexplored aspect of the important brain-signaling system that controls appetite, body composition and energy use. Their findings suggest that a specific gene regulating our body clock may play a central role in determining how fat we become.
Evolution has preserved the ‘neuropeptide Y (NPY) system’, as it is known, in most species – indicating its importance – and much of our understanding comes from studying it in mice. There is one important difference, however, between the NPY system in mouse and man.
In man, the neurotransmitter NPY communicates with four well-known ‘cell surface receptors’ in the brain (Y1, Y2, Y4 and Y5), which in turn trigger the system’s effects.
The new study has shown that mice have an additional receptor, Y6, which has profound effects on their body composition. Y6 is produced in a very small region of the brain that regulates the body clock, as well as growth hormone production.
PhD student Ernie Yulyaningsih, Dr Kim Loh, Dr Shu Lin and Professor Herbert Herzog from Sydney’s Garvan Institute of Medical Research, together with Associate Professor Amanda Sainsbury-Salis, now at the University of Sydney, deleted the Y6 gene from mice to understand its effects. Their study showed that mice without the Y6 gene were smaller, and had less lean tissue, than normal mice. On the other hand, as they aged, these ‘knockout mice’ grew fatter than the normal mice, especially when fed a high-fat diet. In that case, they became obese and developed metabolic problems similar to diabetes. These findings are now published online in the prestigious international journal, Cell Metabolism.
While the gene encoding the Y6 receptor is altered in man, Professor Herzog believes it would be unwise to ignore it because the development of anti-obesity drugs relies heavily on mouse studies.
“It is now clear to us that signaling through the Y6 receptor system is critical for the ways in which energy is used at different times of the day,” said Professor Herbert Herzog.
“Our work shows that Pancreatic Polypeptide has a very high affinity for Y6 in mice. It’s a satiety signal, and probably controls the circadian aspect of food intake – because the same amount of calories eaten at different times of the day has different effects on body weight.”
“The Y6 gene is highly expressed in a part of the brain called the ‘hypothalamic suprachiasmatic nucleus’, which is known to control the body’s circadian rhythm and may also critically modulate metabolic processes in response to food. The gene stimulates higher levels of certain peptides, including vasoactive intestinal peptide (VIP) – which controls growth hormone release.”
“While it is not clear whether the Y6 receptor is fully active in humans, Pancreatic Polypeptide is highly expressed – even more so than in mice – and it’s possible that another receptor to which the peptide has high affinity, such as Y4, could have taken over this function.”
Associate Professor Amanda Sainsbury-Salis expressed surprise at the impact of the Y6 gene deletion on mice, commenting “I find it amazing that one gene, which is expressed in the small part of the brain that controls the body clock, has such a profound impact on how much fat is stored on the body, and how much lean tissue is maintained.”
“Importantly, we use mice as models of human beings in research, and so when looking for anti-obesity drugs, we need to fully understand the function of the NPY system in this animal model to understand how similar circuits in humans connect with the body clock.”
(Source: garvan.org.au)
Neuroscience Study Uncovers New Player in Obesity
A new neuroscience study sheds light on the biological underpinnings of obesity. The in vivo study, published in the January 8 issue of The Journal of Neuroscience, reveals how a protein in the brain helps regulate food intake and body weight. The findings reveal a potential new avenue for the treatment of obesity and may help explain why medications that are prescribed for epilepsy and other conditions that interfere with this protein, such as gabapentin and pregabalin, can cause weight gain.
The protein – alpha2/delta-1 – has not been linked previously to obesity. A team led by Maribel Rios, Ph.D., associate professor in the department of neuroscience at Tufts University School of Medicine, discovered that alpha2/delta-1 facilitates the function of another protein called brain-derived neurotrophic factor (BDNF). A previous study by Rios determined that BDNF plays a critical role in appetite suppression, while the current study identifies a central mechanism mediating the inhibitory effects of BDNF on overeating.
“We know that low levels of the BDNF protein in the brain lead to overeating and dramatic obesity in mice. Deficiencies in BDNF have also been linked to obesity in humans. Now, we have discovered that the alpha2/delta-1 protein is necessary for normal BDNF function, giving us a potential new target for novel obesity treatments,” said Rios, also a member of the cellular and molecular physiology and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.
Rios and colleagues discovered that low levels of BDNF were associated with decreased function of alpha2/delta-1 in the hypothalamus, a brain region that is critical to the regulation of food intake and weight. When the team inhibited the alpha2/delta-1 protein in normal mice, mice ate significantly more food and gained weight. Conversely, when the team corrected the alpha 2/delta-1 deficiency in mice with reduced BDNF levels, overeating and weight gain were mitigated. In addition, blood sugar levels (related to diabetes in humans) were normalized.
“We blocked activity of the alpha2/delta-1 protein in mice using gabapentin. These mice ate 39 percent more food, and as a consequence gained substantially more weight than control mice over a seven-day period,” said first author Joshua Cordeira, Ph.D., a graduate of the neuroscience program at the Sackler School and member of Rios’s lab. This study is related to his Ph.D. thesis.
“When we re-introduced alpha2/delta-1 in obese mice lacking BDNF in the brain, we saw a 15-20 percent reduction in food intake and a significant reduction in weight gain. Importantly, metabolic disturbances associated with obesity, including hyperglycemia and deficient glucose metabolism, were greatly reduced by restoring the function of alpha2/delta-1,” added Rios.
Some individuals who take gabapentin and pregabalin report weight gain. Both gabapentin and pregabalin are anticonvulsants, also used to treat nerve pain from, for example, shingles or diabetes. The findings from the Rios lab suggest that these drugs might contribute to weight gain by interfering with alpha2/delta-1 in the hypothalamus. This new understanding of alpha2/delta-1’s role in appetite may allow researchers to develop complementary treatments that can prevent weight gain for patients taking these medications.
“We now know that alpha2/delta-1 plays a critical role in healthy BDNF function. The finding improves our understanding of the intricate neuroscience involved in appetite control. The next phase of our research will be to unravel the mechanisms mediating the satiety effects of alpha2/delta-1 in the hypothalamus,” said Rios.
This latest finding builds on Rios’s previous studies of BDNF and its role in regulating body weight. Earlier work by Rios established BDNF as an essential component of the neural circuits governing body weight in adult mice. Rios also determined that BDNF expression in two regions of the brain is required to suppress appetite.
Gel reduced daily tremors in Parkinson’s disease
An experimental treatment for Parkinson’s disease reduced by nearly two hours on average the period each day when medication failed to control patients’ slowness and shaking, according to results from a double-blind, phase III clinical trial published in December 2013, in Lancet Neurology.
The study compared AbbVie’s levodopa-carbidopa intestinal gel against the same medication in pill form in patients with advanced disease.
The University of Alabama at Birmingham was among the sites for the study, with David G. Standaert, M.D., Ph.D., chair of the UAB Department of Neurology, an author. Led by the Mount Sinai School of Medicine, preliminary results from the study were first presented at the annual meeting of the American Academy of Neurology in April 2012.
Parkinson’s disease results from the loss of brain cells that make dopamine, which helps to control movement. As dopamine levels fall, patients experience tremors, muscle stiffness and loss of balance. A commonly prescribed treatment, the levodopa-carbidopa combination works as the body converts levodopa into dopamine and carbidopa escorts levodopa to the right part of the brain. The problem is that patients face hours of uncontrolled slowness, freezing and tremors each day — called “off-time” — as the treatment gets into place or wears off.
One reason for the break in treatment coverage is that it comes in a pill, and pills sit in the stomach for up to six hours waiting for it to empty into the small intestine. It is only there that levodopa encounters the proteins capable of transporting it into the bloodstream en route to the brain. Thus, researchers envisioned a system that steadily delivers levodopa gel directly into the small intestine through a surgically placed tube, and with the help of a pump worn on the belt.
“The results are very exciting, considering that other recently approved drugs on the market reduce off-time by, at most, just over an hour,” said Standaert. “In the study, the gel treatment helped patients who had run out of alternatives with current medications. We believe it may be an important new option for patients with severe Parkinson’s, with benefits comparable to more invasive techniques like deep brain stimulation.”
Patients using the gel system saw an average reduction in daily off-time of 1.91 hours, and an increase in “on-time” without troublesome dyskinesia of 1.86 hours compared with the pill form. Nearly all subjects experienced at least one side effect, although most were short-lived and moderate.
(Source: uab.edu)
Tiny Proteins Have Outsized Influence On Nerve Health
Mutations in small proteins that help convey electrical signals throughout the body may have a surprisingly large effect on health, according to results of a new Johns Hopkins study published in Proceedings of the National Academy of Sciences in December using spider, scorpion and sea anemone venom.
The tiny conduits carrying those electrical signals are sodium channels that are vital to our well-being—they trigger action potentials, or spurts of electrical energy that course from body to brain to deliver messages that invoke feelings like pain or temperature sensitivity. When such channels go awry, they contribute to a slew of diseases, one of which is epilepsy.
In the new research, Frank Bosmans, Ph.D., an assistant professor of physiology at the Johns Hopkins University School of Medicine, has found that auxiliary “helper” proteins that interact with sodium channels also play a crucial role. And that, he says, could affect drug development for epilepsy, neurological diseases, muscular disorders and pain syndromes.
“Nobody had thought these tiny molecules that don’t even form the main sodium channel were capable of changing the response of the channel to certain compounds,” Bosmans says. “But in what we consider a new concept, these auxiliary subunits can be considered as drug targets.”
Over the past few decades, there have been hints that these auxiliary proteins were influencing sodium channels, but few analyzed the problem very closely. John Gilchrist, a graduate student in Bosmans’ lab, began evaluating each of the four proteins, one at a time.
Gilchrist engineered frog eggs that made sodium channels and exposed them to the toxins released by tarantulas, scorpions, wasps and sea anemones, an extension of Bosmans’ earlier doctoral research studying the effect of animal venoms on sodium channels. He found that one auxiliary protein in particular, beta4, altered the whole sodium channel system. When exposed to tarantula venom, for instance, tissue in the presence of beta4 showed decreased sensitivity in the sodium channels, meaning that the protein changed the way the nerve fired. This denotes that if a human got bit by a tarantula in a region where beta4 was active, the whole experience might be just a little less painful, says Bosmans.
To figure out what was going on in the altered channels, Bosmans needed to know what the protein looked like, he says. He contacted Filip Van Petegem, a crystallographer at the University of British Columbia in Vancouver, Canada. Van Petegem was able to map the 3-D structure of beta4 down to 1.7 angstroms, the highest possible resolution. Crystal structure in hand, Bosmans could now mutate beta4 and watch what happened.
Purely by chance, Van Petegem had already started that mutation process. To diagram the crystal, Van Petegem had been forced to substitute one protein for another due to quirks in the test system. Bosmans found that the tiny mutation thwarted beta4’s interaction with the sodium channel system.
That finding promptly overturned conventional wisdom into how these proteins behave, Bosmans says.
Back in 1998, Bosmans says, physicians determined that a mutation in the beta1 protein seemed to be triggering a case of epilepsy. Epilepsy has hundreds of causes. It was known at the time that a chemical bridge within the sodium channel held the beta proteins together. If that bridge, known as a disulfide bond, is broken, the proteins fall apart. The physicians theorized that the mutation they found must have destroyed the bridge along with their accompanying proteins. That broken bridge theory has remained dominant ever since.
But when Bosmans introduced that same mutation in beta4, the structure stayed intact. The changes he saw were much more subtle. The position of the protein Van Petegem had mutated changed slightly so that it was farther away from the channel. And only when that mutated crystal was exposed to a toxin did beta4 lose its ability to communicate with the sodium channel.
Bosmans says that even with evidence of the auxiliary proteins’ importance mounting, such as in the epilepsy study, drug developers have continued to ignore the proteins rather than treatment opportunities. Most efforts to develop new drugs to treat epilepsy still focus exclusively on modifying the sodium channels, which don’t need the beta proteins to operate. But Bosmans believes this is only part of the story.
His new finding suggests that such an approach is shortsighted, because mutations in these beta proteins may very well be causing the disease at hand. Drugs that target the beta proteins have the potential to deliver a much more focused treatment, he says.
"That’s one of the new concepts that we’re trying to launch—keep an eye on these little guy proteins, because they are important. If they have a mutation in them, they can cause a disease,” Bosmans says.
Babbling babies – responding to one-on-one ‘baby talk’ – master more words
Common advice to new parents is that the more words babies hear the faster their vocabulary grows. Now new findings show that what spurs early language development isn’t so much the quantity of words as the style of speech and social context in which speech occurs.
Researchers at the University of Washington and University of Connecticut examined thousands of 30-second snippets of verbal exchanges between parents and babies. They measured parents’ use of a regular speaking voice versus an exaggerated, animated baby talk style, and whether speech occurred one-on-one between parent and child or in group settings.
“What our analysis shows is that the prevalence of baby talk in one-on-one conversations with children is linked to better language development, both concurrent and future,” said Patricia Kuhl, co-author and co-director of UW’s Institute for Learning & Brain Sciences.
The more parents exaggerated vowels – for example “How are youuuuu?” – and raised the pitch of their voices, the more the 1-year olds babbled, which is a forerunner of word production. Baby talk was most effective when a parent spoke with a child individually, without other adults or children around.
(Listen to a mother use baby talk with her child)
“The fact that the infant’s babbling itself plays a role in future language development shows how important the interchange between parent and child is,” Kuhl said.
The findings will be published in an upcoming issue of the journal Developmental Science.
Twenty-six babies about 1 year of age wore vests containing audio recorders that collected sounds from the children’s auditory environment for eight hours a day for four days. The researchers used LENA (“language environment analysis”) software to examine 4,075 30-second intervals of recorded speech. Within those segments, the researchers identified who was talking in each segment, how many people were there, whether baby talk – also known as “parentese” – or regular voice was used, and other variables.
When the babies were 2 years old, parents filled out a questionnaire measuring how many words their children knew. Infants who had heard more baby talk knew more words. In the study, 2-year olds in families who spoke the most baby talk in a one-on-one social context knew 433 words, on average, compared with the 169 words recognized by 2-year olds in families who used the least babytalk in one-on-one situations.
The relationship between baby talk and language development persisted across socioeconomic status and despite there only being 26 families in the study.
“Some parents produce baby talk naturally and they don’t realize they’re benefiting their children,” said first author Nairán Ramírez-Esparza, an assistant psychology professor at the University of Connecticut. “Some families are more quiet, not talking all the time. But it helps to make an effort to talk more.”
Previous studies have focused on the amount of language babies hear, without considering the social context. The new study shows that quality, not quantity, is what matters.
“What this study is adding is that how you talk to children matters. Parentese is much better at developing language than regular speech, and even better if it occurs in a one-on-one interaction,” Ramirez-Esparza said.
Parents can use baby talk when going about everyday activities, saying things like, “Where are your shoooes?,” “Let’s change your diiiiaper,” and “Oh, this tastes goooood!,” emphasizing important words and speaking slowly using a happy tone of voice.
“It’s not just talk, talk, talk at the child,” said Kuhl. “It’s more important to work toward interaction and engagement around language. You want to engage the infant and get the baby to babble back. The more you get that serve and volley going, the more language advances.”
Bee dance points the way
QBI scientists at The University of Queensland have found that honeybees use the pattern of polarised light in the sky invisible to humans to direct one another to a honey source.
The study, conducted in Professor Mandyam Srinivasan’s laboratory at the Queensland Brain Institute, a member of the Australian Research Council Centre of Excellence in Vision Science (ACEVS), demonstrated that bees navigate to and from honey sources by reading the pattern of polarised light in the sky.
“The bees tell each other where the nectar is by converting their polarised ‘light map’ into dance movements,” Professor Srinivasan said.
“The more we find out how honeybees make their way around the landscape, the more awed we feel at the elegant way they solve very complicated problems of navigation that would floor most people – and then communicate them to other bees,” he said.
The discovery shines new light on the astonishing navigational and communication skills of an insect with a brain the size of a pinhead.
The researchers allowed bees to fly down a tunnel to a sugar source, shining only polarised light from above, either aligned with the tunnel or at right angles to the tunnel.
They then filmed what the bees ‘told’ their peers, by waggling their bodies when they got back to the hive.
“It is well known that bees steer by the sun, adjusting their compass as it moves across the sky, and then convert that information into instructions for other bees by waggling their body to signal the direction of the honey,” Professor Srinivasan said.
“Other laboratories have shown from studying their eyes that bees can see a pattern of polarised light in the sky even when the sun isn’t shining: the big question was could they translate the navigational information it provides into their waggle dance.”
The researchers conclude that even when the sun is not shining, bees can tell one another where to find food by reading and dancing to their polarised sky map.
In addition to revealing how bees perform their remarkable tasks, Professor Srinivasan says it also adds to our understanding of some of the most basic machinery of the brain itself.
Professor Srinivasan’s team conjectures that flight under polarised illumination activates discrete populations of cells in the insect’s brain.
When the polarised light was aligned with the tunnel, one pair of ‘place cells’ – neurons important for spatial navigation – became activated, whereas when the light was oriented across the tunnel a different pair of place cells was activated.
The researchers suggest that depending on which set of cells is activated, the bee can work out if the food source lies in a direction toward or opposite the direction of the sun, or in a direction ninety degrees to the left or right of it.
(Source: qbi.uq.edu.au)
Epilepsy drug turns out to help adults acquire perfect pitch and learn language like kids
A team of researchers from across the globe believe they have discovered a means of re-opening “critical periods” in brain development, allowing adults to acquire abilities — such as perfect pitch or fluency in language — that could previously only be acquired early in life.
According to the study in Frontiers in Systems Neuroscience, the mood-stabilizing drug valproate allows the adult brain to absorb new information as effortlessly as it did during critical windows in childhood.
A critical period is “a fixed window of time, usually early in an organism’s lifespan, during which experience has lasting effects on the development of brain function and behavior.” They are, for example, what allows children to enter into language without any formal training in grammar or vocabulary.
The researchers postulated that because such periods close when enzymes “impose ‘brakes’ on neuroplasticity,” a drug that blocks the productions of those enzymes might be able to “reopen critical-period neuroplasticity.”
Higher vitamin D levels in pregnancy could help babies become stronger
Children are likely to have stronger muscles if their mothers had a higher level of vitamin D in their body during pregnancy, according to new research from the Medical Research Council Lifecourse Epidemiology Unit (MRC LEU) at the University of Southampton.
Low vitamin D status has been linked to reduced muscle strength in adults and children, but little is known about how variation in a mother’s status during pregnancy affects her child.
Low vitamin D concentrations are common among young women in the UK, and although women are recommended to take an additional 10μg/day of vitamin D in pregnancy, supplementation is often not taken up.
In the research, published in the January edition of the Journal of Clinical Endocrinology and Metabolism, vitamin D levels were measured in 678 mothers in the later stages of pregnancy.
When the children were four years old, grip strength and muscle mass were measured. Results showed that the higher the levels of vitamin D in the mother, the higher the grip strength of the child, with an additional, but less pronounced association between mother’s vitamin D and child’s muscle mass.
Lead researcher Dr Nicholas Harvey, Senior Lecturer at the MRC LEU at the University of Southampton, comments: “These associations between maternal vitamin D and offspring muscle strength may well have consequences for later health; muscle strength peaks in young adulthood before declining in older age and low grip strength in adulthood has been associated with poor health outcomes including diabetes, falls and fractures. It is likely that the greater muscle strength observed at four years of age in children born to mothers with higher vitamin D levels will track into adulthood, and so potentially help to reduce the burden of illness associated with loss of muscle mass in old age.”
The 678 women who took part in the study are part of the Southampton Women’s Survey, one of the largest and best characterised such studies globally.
Professor Cyrus Cooper, Professor of Rheumatology and Director of the MRC LEU at the University of Southampton, who oversaw this work, added: “This study forms part of a larger programme of research at the MRC Lifecourse Epidemiology Unit and University of Southampton in which we are seeking to understand how factors such as diet and lifestyle in the mother during pregnancy influence a child’s body composition and bone development. This work should help us to design interventions aimed at optimising body composition in childhood and later adulthood and thus improve the health of future generations.”
(Source: southampton.ac.uk)
Your gut’s what you eat, too
As the saying goes, you are what you eat. But new evidence suggests that the same may also be true for the microbes in your gut.
A Harvard study shows that, in as little as a day, diet can alter the population of microbes in the gut — particularly those that tolerate bile — as well as the types of genes expressed by gut bacteria.
“What we are really excited about is we and others have shown in animal models that diet can rapidly have major effects on the microbes that are in the gut,” said Peter Turnbaugh, a Bauer Fellow at the Center for Systems Biology in the Faculty of Arts and Sciences. He is senior author of the paper, which appeared in Dec. 11 edition of the journal Nature.
“But it still wasn’t clear how fast the microbes in the human gut respond to changes in diet, and to what degree those changes would be similar in different people. This study is really the first time we’ve seen that, over the course of days, a new diet can reshape the microbial community, and that those changes are consistent and reversible.”
Mind-controlled prostheses offer hope for disabled
The first kick of the 2014 FIFA World Cup may be delivered in Sao Paulo next June by a Brazilian who is paralyzed from the waist down. If all goes according to plan, the teenager will walk onto the field, cock back a foot and swing at the soccer ball, using a mechanical exoskeleton controlled by the teen’s brain.
Motorized metal braces tested on monkeys will support and bend the kicker’s legs. The braces will be stabilized by gyroscopes and powered by a battery carried by the kicker in a backpack. German-made sensors will relay a feeling of pressure when each foot touches the ground. And months of training on a virtual-reality simulator will have prepared the teenager — selected from a pool of 10 candidates — to do all this using a device that translates thoughts into actions.
“We want to galvanize people’s imaginations,” says Miguel Nicolelis, the Brazilian neuroscientist at Duke University who is leading the Walk Again Project’s efforts to create the robotic suit. “With enough political will and investment, we could make wheelchairs obsolete.”
Mind-controlled leg armor may sound more like the movie “Iron Man” than modern medicine. But after decades of testing on rats and monkeys, neuroprosthetics are finally beginning to show promise for people. Devices plugged directly into the brain seem capable of restoring some self-reliance to stroke victims, car crash survivors, injured soldiers and others hampered by incapacitated or missing limbs.