Posts tagged science
Articles and news from the latest research reports.
Male and female brains aren’t equal when it comes to fat
Researchers have found that male and female brains respond in remarkably different ways to high-fat meals. Those differences in the brain lead to greater inflammation and increased health risks in males that indulge on fatty foods in comparison to females, a new study in mice shows. The findings reported in the Cell Press journal Cell Reports on October 16th may help to explain observed differences in obesity outcomes between women and men – premenopausal women carrying extra weight fare better than men do – and suggest that dietary advice should be made more sex-specific.
"Our findings, for the first time, suggest that males and females respond to high-fat diets differently," said Deborah Clegg of the Cedar-Sinai Diabetes And Obesity Research Institute in Los Angeles. "The data would suggest that is probably ‘ok’ for females to occasionally have a high-fat meal, where it is not recommended for males.
"The way we treat patients and provide dietary and nutritional advice should be altered. We might be less concerned about an occasional hamburger for women, but for men, we might more strongly encourage avoidance, especially if they have pre-existing diseases such as heart disease or type 2 diabetes."
Earlier data from Clegg’s team and others had suggested that inflammation in the brain is tied to overeating, blood sugar imbalances, and increased inflammation in other parts of the body, including fat tissue. Those effects can be triggered, in males in particular, by short-term exposure to a high-fat diet.
The researchers say they were initially shocked to discover that male and female brains differ in their fatty acid composition. When they manipulated male mouse brains to have the fatty acid profile of females, they found that those animals were protected from the ill effects of a diet high in fat.
When males with average male brains entered an inflammatory state after eating diets high in fat, they also suffered from reduced cardiac function in a way that female animals in the study did not. Those sex differences in the brain’s response to fat are related to differences between females and males in estrogen and estrogen receptor status.
Clegg says her team is now working out a strategy to confirm whether the findings in mice apply to people too. If they do, there will be some very immediate practical implications for what men and women should put on their plates.
"We have always had ‘one size fits all’ with respect to our nutritional information and our pharmaceutical approach," Clegg said. "Our data begin to suggest that sex should be factored in, and men should be more closely monitored for fat intake and inflammation than women."
(Image: Shutterstock)
Are Male Brains Wired to Ignore Food for Sex?
Choosing between two good things can be tough. When animals must decide between feeding and mating, it can get even trickier. In a discovery that might ring true even for some humans, researchers have shown that male brains – at least in nematodes – will suppress the ability to locate food in order to instead focus on finding a mate.
(Image caption: C. elegans male (top) and hermaphrodite (bottom))
The results, which appear today in the journal Current Biology, may point to how subtle changes in the brain’s circuitry dictate differences in behavior between males and females.
“While we know that human behavior is influenced by numerous factors, including cultural and social norms, these findings point to basic biological mechanisms that may not only help explain some differences in behavior between males and females, but why different sexes may be more susceptible to certain neurological disorders,” said Douglas Portman, Ph.D., an associate professor in the Department of Biomedical Genetics and Center for Neural Development and Disease at the University of Rochester and lead author of the study.
The findings were made in experiments involving C. elegans, a microscopic roundworm that has long been used by researchers to understand fundamental mechanisms in biology. Many of the discoveries made using C. elegans apply throughout the animal kingdom and this research has led to a broader understanding of human biology. In fact, three Nobel Prizes in medicine and chemistry have been awarded for discoveries involving C. elegans.
C. elegans is particularly useful in the study of the nervous system and scientists understand in great detail the development, function, and multiple connections of its entire neural network.
The study published today focuses on the activity of a single pair of neurons found in C. elegans – called AWA – that control smell. Smell, along with taste and touch, are critical sensory factors that dictate how C. elegans understands and navigates its environment, including finding food, avoiding danger, and locating a mate.
There are two sexes of C. elegans, males and hermaphrodites. Though the hermaphrodites are able to self-fertilize, they are also mating partners for males, and are considered to be modified females.
It has been previously observed that males and hermaphrodites act differently when exposed to food. If placed at a food source, the hermaphrodites tend to stay there. Males, however, will leave food source and “wander” – scientist believe they do this because they are in search of a mate.
The Rochester researchers discovered that the sensory mechanisms – called chemoreceptors – of the AWA neurons were regulated by the sexual identity of these cells, which, in turn, controls the expression of a receptor called ODR-10. These receptors bind to a chemical scent that is given off by food and other substances.
In hermaphrodites, more of the ODR-10 receptors are produced, making the worms more sensitive – and thereby attracted – to the presence of food. In males, fewer of these receptors are active, essentially suppressing their ability – and perhaps desire – to find food. However, when males were deprived of food, they produced dramatically higher levels of this receptor, allowing them to temporarily focus on finding food.
To confirm the role of these genetic differences between the sexes on behavior, the researchers designed a series of experiments in which they observed the activity of C. elegans when placed in a petri-dish and confronted with the option to either feed or go in search of a mate. The hermaphrodites were place in the center of the dish at a food source and, as expected, they stayed put.
The males were placed in their own individual food sources at the periphery of the dish. As a further obstacle between the males and their potential mates, an additional ring of food surrounded the hermaphrodites in the center of the dish. The males in the experiment consisted of two categories, one group with a normal genetic profile and another group that had been engineered by the researchers to overexpress the ODR-10 receptor, essentially making them more sensitive to the smell of food.
The researchers found that the normal worms left their food source and eventually made their way to the center of the dish where they mated with the hermaphrodites. The genetically engineered males were less successful at finding a mate, presumably because they were more interested in feeding. By examining the genetic profile of the resulting offspring, the scientists observed that the normal males out-produced the genetically engineered males by 10 to one.
In separate experiments, the researchers were also able to modify the behavior of the hermaphrodites by suppressing the ODR-10 receptors, causing them to act like males and abandon their food source.
“These findings show that by tuning the properties of a single cell, we can change behavior,” said Portman. “This adds to a growing body of evidence that sex-specific regulation of gene expression may play an important role in neural plasticity and, consequently, influence differences in behaviors – and in disease susceptibility – between the sexes.”
(Source: urmc.rochester.edu)
(Image caption: The complex shape of individual oligodendrocytes (OLs) and myelin in adult mice injected with tamoxifen. Credit: Sarah Jolly)
Myelin vital for learning new practical skills
New evidence of myelin’s essential role in learning and retaining new practical skills, such as playing a musical instrument, has been uncovered by UCL research. Myelin is a fatty substance that insulates the brain’s wiring and is a major constituent of ‘white matter’. It is produced by the brain and spinal cord into early adulthood as it is needed for many developmental processes, and although earlier studies of human white matter hinted at its involvement in skill learning, this is the first time it has been confirmed experimentally.
The study in mice, published in Science today, shows that new myelin must be made each time a skill is learned later in life and the structure of the brain’s white matter changes during new practical activities by increasing the number of myelin-producing cells. Furthermore, the team say once a new skill has been learnt, it is retained even after myelin production stops. These discoveries could prove important in finding ways to stimulate and improve learning, and in understanding myelin’s involvement in other brain processes, such as in cognition.
For a child to learn to walk or an adult to master a new skill such as juggling, new brain circuit activity is needed and new connections are made across large distances and at high speeds between different parts of the brain and spinal cord. For this, electrical signals fire between neurons connected by “axons” – thread-like extensions of their outer surfaces which can be viewed as the ‘wire’ in the electric circuit. When new signals fire repeatedly along axons, the connections between the neurons strengthen, making them easier to fire in the same pattern in future. Neighbouring myelin-producing cells called oligodendrocytes (OLs) recognise the repeating signal and wrap myelin around the active circuit wiring. It is this activity-driven insulation that the team identified as essential for learning.
The team demonstrated that young adult mice need to make myelin to learn new motor skills but that new myelin does not need to be produced to recall and perform a pre-learned skill. They tested the ability of mice to learn to run on a complex wheel with irregularly spaced rungs. The study looked at thirty-six normal mice and thirty-two mice with a drug-controlled genetic switch to prevent new OLs and myelin from being made. They found the mice that were prevented from producing new myelin could not master the complex wheel, whereas those that could produce myelin did learn, with differences between the two groups’ abilities seen after only two hours of practice.
A second experiment looked at mice that were first allowed to learn to run on the complex wheel before being treated with the drug to prevent further myelin production. When the mice were later re-introduced to the complex wheel, they were immediately able to run at top speed without having to spend time re-learning. This shows that the inability to make new myelin did not affect the mouse’s running ability and that new myelin is not required to remember and perform a skill once learned; it is required only during the initial learning phase.
Lead researcher, Professor Bill Richardson, Director of the UCL Wolfson Institute for Biomedical Research, said: “From earlier studies of human white matter using advanced MRI technology, we thought OLs and myelin might be involved in some way in skill learning, so we decided to attack this idea experimentally. We were surprised how quickly we saw differences in the ability of mice from each group to learn how to run on complex wheel, which shows just how fast the brain can respond to wrap newly-activated circuits in myelin and how this improves learning. This rapid response suggests that a number of alternative axon pathways might already exist in the brain that could be used to drive a particular sequence of movements, but it quickly works out which of those circuits is most efficient and both selects and protects its chosen route with myelin.
“We think these findings are really exciting as they open up opportunities to investigate the role of OLs and myelin in other brain processes, such as cognitive activities (like navigating through a maze), to see if the requirement for new myelin is general or specific to motor activity. I’m keen to find out the precise sequence of changes to OLs and myelin during learning and whether these changes are needed more in some parts of the brain than others, which might shed light on some of the mysteries still surrounding how the brain adapts and learns throughout life.”
Scientists find ‘hidden brain signatures’ of consciousness in vegetative state patients
There has been a great deal of interest recently in how much patients in a vegetative state following severe brain injury are aware of their surroundings. Although unable to move and respond, some of these patients are able to carry out tasks such as imagining playing a game of tennis. Using a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, researchers have previously been able to record activity in the pre-motor cortex, the part of the brain which deals with movement, in apparently unconscious patients asked to imagine playing tennis.
Now, a team of researchers led by scientists at the University of Cambridge and the MRC Cognition and Brain Sciences Unit, Cambridge, have used high-density electroencephalographs (EEG) and a branch of mathematics known as ‘graph theory’ to study networks of activity in the brains of 32 patients diagnosed as vegetative and minimally conscious and compare them to healthy adults. The findings of the research are published today in the journal PLOS Computational Biology. The study was funded mainly by the Wellcome Trust, the National Institute of Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC).
The researchers showed that the rich and diversely connected networks that support awareness in the healthy brain are typically – but importantly, not always – impaired in patients in a vegetative state. Some vegetative patients had well-preserved brain networks that look similar to those of healthy adults – these patients were those who had shown signs of hidden awareness by following commands such as imagining playing tennis.
Dr Srivas Chennu from the Department of Clinical Neurosciences at the University of Cambridge says: “Understanding how consciousness arises from the interactions between networks of brain regions is an elusive but fascinating scientific question. But for patients diagnosed as vegetative and minimally conscious, and their families, this is far more than just an academic question – it takes on a very real significance. Our research could improve clinical assessment and help identify patients who might be covertly aware despite being uncommunicative.”
The findings could help researchers develop a relatively simple way of identifying which patients might be aware whilst in a vegetative state. Unlike the ‘tennis test’, which can be a difficult task for patients and requires expensive and often unavailable fMRI scanners, this new technique uses EEG and could therefore be administered at a patient’s bedside. However, the tennis test is stronger evidence that the patient is indeed conscious, to the extent that they can follow commands using their thoughts. The researchers believe that a combination of such tests could help improve accuracy in the prognosis for a patient.
Dr Tristan Bekinschtein from the MRC Cognition and Brain Sciences Unit and the Department of Psychology, University of Cambridge, adds: “Although there are limitations to how predictive our test would be used in isolation, combined with other tests it could help in the clinical assessment of patients. If a patient’s ‘awareness’ networks are intact, then we know that they are likely to be aware of what is going on around them. But unfortunately, they also suggest that vegetative patients with severely impaired networks at rest are unlikely to show any signs of consciousness.”
The Neuroscience of Holding It
Wherever you are right now: squeeze your glutes. Feel that? You just also contracted your pelvic floor too, whether you wanted to or not.
Scientists studying the source of chronic abdominal and pelvic floor pain found an unexpected connection in the brain between the pelvic floor – the muscle responsible for, among other things, keeping you from peeing your pants – and various muscles throughout the body. They’ve found some evidence for a link as far away as the toes (try tapping a toe and see if you feel the clench), but the strongest link so far is with the glutes.
“We knew that pelvic floor muscles contract involuntarily in healthy people to make sure they don’t accidently urinate, but we didn’t know what part of the nervous system was doing this,” said Jason Kutch, corresponding author on a study about the research and an assistant professor in the Division of Biokinesiology & Physical Therapy at the USC Ostrow School of Dentistry. “Now we know that there are specific brain regions controlling involuntary pelvic floor contraction.”
Kutch collaborated with colleagues at USC Ostrow, the Keck School of Medicine of USC, and Loma Linda University on the research. Their findings were published on October 8 in the Journal of Neuroscience.
The team used electromyographic recordings – which measure the activation of muscle tissue – to show that pelvic floor activation occurred in conjunction with the activation of certain muscles (like the glutes), but not others (like fingers).
They then used functional magnetic image resonance (fMRI) imaging to show that a specific part of the brain (the medial wall of the precentral gyrus – a part of the primary motor cortex) activates both when the pelvic floor contracts and when the glutes are squeezed – but not when fingers move.
“We hope that this vein of research will help us to find the causes of chronic pelvic floor pain, which disproportionately affect women, and may even yield information that could help people struggling with incontinence,” Kutch said.
Broadly, the finding speaks to the interconnected nature of our bodies and brains, and all of the hard work going on in the pelvic floor muscles – without us even know it.
Discovery of a new mechanism that can lead to blindness
An important scientific breakthrough by a team of IRCM researchers led by Michel Cayouette, PhD, is being published today by The Journal of Neuroscience. The Montréal scientists discovered that a protein found in the retina plays an essential role in the function and survival of light-sensing cells that are required for vision. These findings could have a significant impact on our understanding of retinal degenerative diseases that cause blindness.
The researchers studied a process called compartmentalization, which establishes and maintains different compartments within a cell, each containing a specific set of proteins. This process is crucial for neurons (nerve cells) to function properly.
“Compartments within a cell are much like different parts of a car,” explains Vasanth Ramamurthy, PhD, first author of the study. “In the same way that gas must be in the fuel tank in order to power the car’s engine, proteins need to be in a specific compartment to properly exercise their functions.”
A good example of compartmentalization is observed in a specialized type of light-sensing neurons found in the retina, the photoreceptors, which are made up of different compartments containing specific proteins essential for vision.
“We wanted to understand how compartmentalization is achieved within photoreceptor cells,” says Dr. Cayouette, Director of the Cellular Neurobiology research unit at the IRCM. “Our work identified a new mechanism that explains this process. More specifically, we found that a protein called Numb functions like a traffic controller to direct proteins to the appropriate compartments.”
“We demonstrated that in the absence of Numb, photoreceptors are unable to send a molecule essential for vision to the correct compartment, which causes the cells to progressively degenerate and ultimately die,” adds Dr. Ramamurthy, who carried out the project in Dr. Cayouette’s laboratory in collaboration with Christine Jolicoeur, research assistant. “This is important because the death of photoreceptor cells is known to cause retinal degenerative diseases in humans that lead to blindness. Our work therefore provides a new piece of the puzzle to help us better understand how and why the cells die.”
“We believe our results could eventually have a substantial impact on the development of treatments for retinal degenerative diseases, like retinitis pigmentosa and Leber’s congenital amaurosis, by providing novel drug targets to prevent photoreceptor degeneration,” concludes Dr. Cayouette.
According to the Foundation Fighting Blindness Canada, millions of people in North America live with varying degrees of irreversible vision loss because they have an untreatable, degenerative eye disorder that affects the retina. Research aiming to better understand what causes vision loss could lead to preserving and restoring sight.
(Source: ircm.qc.ca)
New lead for potential Parkinson’s treatment: Effects of high-risk Parkinson’s mutation are reversible
Mutations in a gene called LRRK2 carry a well-established risk for Parkinson’s disease, however the basis for this link is unclear.
(Image caption: A microscope image of a cultured cell)
The team, led by Parkinson’s UK funded researchers Dr Kurt De Vos from the Department of Neuroscience and Dr Alex Whitworth from the Department of Biomedical Sciences, found that certain drugs could fully restore movement problems observed in fruit flies carrying the LRRK2 Roc-COR Parkinson’s mutation.
These drugs, deacetylase inhibitors, target the transport system and reverse the defects caused by the faulty LRRK2 within nerve cells. The study is published in Nature Communications.
Dr De Vos, a Lecturer in Translational Neuroscience at the world-leading Sheffield Institute for Translational Neuroscience (SITraN), said: “Our study provides compelling evidence that there is a direct link between defective transport within nerve cells and movement problems caused by the LRRK2 Parkinson’s mutation in flies.”
Co-investigator Dr Alex Whitworth explained: “We could also show that these neuronal transport defects caused by the LRRK2 mutation are reversible.
“By targeting the transport system with drugs, we could not only prevent movement problems, but also fully restore movement abilities in fruit flies who already showed impaired movement marked by a significant decrease in both climbing and flight ability.”
The LRRK2 gene produces a protein that affects many processes in the cell. It is known to bind to the microtubules, the cells’ transport tracks. A defect in this transport system has been suggested to contribute to Parkinson’s disease. The researchers have investigated this link and have now found the evidence that certain LRRK2 mutations affect transport in nerve cells which leads to movement problems observed in the fruit fly (Drosophila).
The team then used several approaches to show that preventing the association of the mutant LRRK2 protein with the microtubule transport system rescues the transport defects in nerve cells, as well as the movement deficits in fruit flies.
Dr De Vos added: “We successfully used drugs called deacetylase inhibitors to increase the acetylated form of α-tubulin within microtubules which does not associate with the mutant LRRK2 protein. We found that increasing microtubule acetylation had a direct impact on cellular axonal transport.
“These are very promising results which point to a potential Parkinson’s therapy. However, further studies are needed to confirm that this rescue effect also applies in humans.“
Dr Beckie Port, Research Communications Officer at Parkinson’s UK, which helped to fund the study, said: “This research gives hope that, for people with a particular mutation in their genes, it may one day be possible to intervene and stop the progression of Parkinson’s.
“The study has only been carried out in fruit flies, so much more research is needed before we know if these findings could lead to new treatment approaches for people with Parkinson’s.”
(Source: sheffield.ac.uk)
Chemical Derived from Broccoli Sprouts Shows Promise in Treating Autism
Results of a small clinical trial suggest that a chemical derived from broccoli sprouts — and best known for claims that it can help prevent certain cancers — may ease classic behavioral symptoms in those with autism spectrum disorders (ASDs).
The study, a joint effort by scientists at MassGeneral Hospital for Children and the Johns Hopkins University School of Medicine, involved 40 teenage boys and young men, ages 13 to 27, with moderate to severe autism.
In a report published online in the journal Proceedings of the National Academy of Sciences during the week of Oct. 13, the researchers say that many of those who received a daily dose of the chemical sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared to those who received a placebo.
“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” says Paul Talalay, M.D., professor of pharmacology and molecular sciences, who has researched these vegetable compounds for the past 25 years.
“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” says co-investigator Andrew Zimmerman, M.D., now a professor of pediatric neurology at UMass Memorial Medical Center.
Institutional Rearing May Increase Risk for Attention-Deficit Disorder by Altering Cortical Development
Over the past decades, we have seen numerous tragic examples where the failure of institutions to meet the needs of infants for social contact and stimulation has led to the failure of these infants to thrive.
Infancy and childhood are critical life periods that shape the development of the cortex. A generation of research suggests that enriched environments, full of interesting stimuli to explore, promote cortical development and cognitive function. In contrast, deprivation and stress may compromise cortical development and attenuate some cognitive functions.
Young children who are raised in environments of psychosocial neglect, such as those who grow up in institutions for orphaned or abandoned children, are at markedly elevated risk for developing a wide range of mental health problems, including attention-deficit/hyperactivity disorder (ADHD).
Now, new data from the Bucharest Early Intervention Project (BEIP), published in the current issue of Biological Psychiatry, suggests that this type of deprived early environment is associated with drastic changes in brain development in children.
BEIP is a longitudinal study that has followed a sample of children raised from early infancy in institutions in Romania. The authors of the current report used data from 58 of those children and compared it with 22 typically-reared children from the same community. All children underwent a structural imaging scan and were assessed for symptoms of ADHD.
The researchers discovered that children raised in institutional settings exhibited widespread reductions in cortical thickness in multiple brain regions including the prefrontal, parietal, and temporal cortices relative to children raised in families in the community.
The data also revealed that the reduced cortical thickness in several of those same brain regions was associated with greater ADHD symptoms of inattention and impulsivity.
This is consistent with previous research that has implicated those brain regions in regulating attention, memory, and other vital cognitive processes.
"Perhaps most importantly, the new findings indicate that the high rates of ADHD among children raised in these deprived environments are explained, in part, by these atypical patterns of brain development," explained first author Dr. Katie McLaughlin, Assistant Professor at the University of Washington.
"These disturbing data provide a mechanism that links institutional rearing to compromised cortical development," said Dr. John Krystal, Editor of Biological Psychiatry. “They suggest that society may have to choose between investing in enriching institutional environments and enhancing the capacity of these institutions to offer mental health support on the one hand and bearing the cost of ADHD and its impact on social and vocational productivity on the other.”
McLaughlin agrees and added, “The early caregiving environment has lasting effects on brain development in children. Identifying strategies for mitigating these effects is critical for improving mental health and educational outcomes among children raised in deprived environments.”
(Source: elsevier.com)
Neurons are electrically charged cells, located in the nervous system, that interpret and transmit information using electrical and chemical signals. Now, researchers at the University of Missouri have determined that individual neurons can react differently to electrical signals at the molecular level and in different ways—even among neurons of the same type. This variability may be important in discovering underlying problems associated with brain disorders and neural diseases such as epilepsy.
“Genetic mutations found in neurological disorders create imbalances in the inward and outward flow of electrical current through cells,” said David Schulz, associate professor in the Division of Biological Sciences in the College of Arts and Science and a researcher in the Interdisciplinary Neuroscience Program at MU. “Often, neurons react to electrical signals, or voltage, and compensate by altering their own electrical outputs. The variability in these imbalances, even among multiple cells of the same kind within the brain, is one of the major problems scientists face when trying to design therapeutics for disorders like epilepsy. Seizures in individuals can be caused by different imbalances—therefore getting to the root of how neurons act individually makes our studies important.”
Schulz and his team previously proved that two identical neurons can reach the same electrical activity in different ways. In his new study, Schulz hypothesized that neurons might use the cell’s genetic code, or its messenger RNA (mRNA), to “fine tune” the production of proteins, helping individual cells react accordingly.
Using clusters of neurons obtained from Jonah crabs, Schulz and his team experimentally altered electrical input and output in the neurons and measured the messenger RNA (mRNA) levels found within the cells. Invertebrates like crabs are useful in neuroscience research because their neurons are simple enough to observe and study, but advanced enough that they can be “scaled up” to apply to higher organisms, Schulz said.
They found that when normal patterns of stimulation were maintained, cells engaged the correct ratios of mRNA to produce the proteins needed to help keep electrical impulses in order; however, when normal patterns of activity were not maintained, this fundamentally changed the cells at the molecular level.
“We were the first to show that the correct ratios of mRNAs are actively maintained by the actual activity or voltage of the cell, and not chemical feedback,” Schulz said. “These results represent a novel aspect of regulation that might be useful for developing therapeutics for neuronal disorders later.”
Schulz’ study, “Activity-dependent feedback regulates correlated ion channel mRNA levels in single identified motor neurons,” was published in the August 18th edition of Current Biology.