Posts tagged neuroscience
Articles and news from the latest research reports.
Scientists identify new Huntington disease pathway
An international group of researchers has identified a major new pathway thought to be involved in the development of Huntington disease. The findings, published in the Proceedings of the National Academy of Sciences journal, could eventually lead to new treatments for the disease, which currently has no cure.
Scientists at the BC Cancer Agency Research Centre and the Centre for Molecular Medicine and Therapeutics in Vancouver, Canada, and the MRC Toxicology Unit in Leicester, UK, studied mice and human tissue and found that the HACE1 gene is essential for mopping up toxic molecules during periods of oxidative stress, where harmful ‘reactive oxygen species’ build up in the cell.
Oxidative stress is thought to be involved in the development of a number of diseases including cancer and neurodegenerative disorders like Alzheimer’s and Parkinson’s disease. Therefore finding out how this process occurs in the body is important for understanding the course of disease.
The body has evolved highly effective defence mechanisms that sense and respond to oxidative stress to protect the cells from damage. One of these protective mechanisms is controlled by a molecule called NRF2 which springs into action and switches on the production of proteins and enzymes that detoxify the cell.
In this study, scientists found that the HACE1 also plays a vital role in this detoxification process, by activating NRF2. The authors believe that this mechanism goes wrong in Huntington’s disease, leading to gradual destruction of nerve cells in the brain.
Lead author Dr Barak Rotblat, of the MRC Toxicology Unit, said:
“One of the early observations was that enhanced HACE1 expression rescued cells from mutant Huntingtin (the mutant protein that is responsible for Huntington disease) toxicity. We knew then that we had to figure out how HACE1 can protect these cells.
“Our evidence points towards a previously unknown role of HACE1 in Huntington disease and possibly other forms of neurodegeneration. It’s very early days, but if we were able to find a way to boost this pathway, we might be able to develop a treatment that halts, or even reverses progression of Huntington disease.”
HACE1 is already known to play a protective role against tumour formation, but its role in neurodegeneration has not been investigated before.
Dr Poul Sorensen, the senior author of the work from the BC Cancer Agency Research Centre and a Professor at the University of British Columbia, said:
“This is a glowing example of how work in one field, namely childhood cancers, where we first identified the HACE1 gene, has applications to a completely different disease, Huntington disease”.
In this study, researchers looked at mice with and without the HACE1 gene and found that those without the gene had more oxidative stress in the brain, and their response to this was impaired. Depleting HACE1 in cells also resulted in reduced NRF2 activity, leading to lower tolerance against oxidative stress triggers.
The scientists also looked at human brain samples from Huntington disease patients and found a striking reduction of HACE1 levels in the striatum – the area of the brain where the disease develops and is most damaged.
Finally, they looked at HACE1 in a cellular model of Huntington disease. They found that upping expression of the gene in nerve precursor cells protected them against oxidative stress.
(Source: mrc.ac.uk)
The brains of jazz musicians engrossed in spontaneous, improvisational musical conversation showed robust activation of brain areas traditionally associated with spoken language and syntax, which are used to interpret the structure of phrases and sentences. But this musical conversation shut down brain areas linked to semantics - those that process the meaning of spoken language, according to results of a study by Johns Hopkins researchers.
The study used functional magnetic resonance imaging (fMRI) to track the brain activity of jazz musicians in the act of “trading fours,” a process in which musicians participate in spontaneous back and forth instrumental exchanges, usually four bars in duration. The musicians introduce new melodies in response to each other’s musical ideas, elaborating and modifying them over the course of a performance.
The results of the study suggest that the brain regions that process syntax aren’t limited to spoken language, according to Charles Limb, M.D., an associate professor in the Department of Otolaryngology-Head and Neck Surgery at the Johns Hopkins University School of Medicine. Rather, he says, the brain uses the syntactic areas to process communication in general, whether through language or through music.
Limb, who is himself a musician and holds a faculty appointment at the Peabody Conservatory, says the work sheds important new light on the complex relationship between music and language.
"Until now, studies of how the brain processes auditory communication between two individuals have been done only in the context of spoken language," says Limb, the senior author of a report on the work that appears online Feb. 19 in the journal PLOS ONE. “But looking at jazz lets us investigate the neurological basis of interactive, musical communication as it occurs outside of spoken language.
"We’ve shown in this study that there is a fundamental difference between how meaning is processed by the brain for music and language. Specifically, it’s syntactic and not semantic processing that is key to this type of musical communication. Meanwhile, conventional notions of semantics may not apply to musical processing by the brain."
To study the response of the brain to improvisational musical conversation between musicians, the Johns Hopkins researchers recruited 11 men aged 25 to 56 who were highly proficient in jazz piano performance. During each 10-minute session of trading fours, one musician lay on his back inside the MRI machine with a plastic piano keyboard resting on his lap while his legs were elevated with a cushion. A pair of mirrors was placed so the musician could look directly up while in the MRI machine and see the placement of his fingers on the keyboard. The keyboard was specially constructed so it did not have metal parts that would be attracted to the large magnet in the fMRI.
The improvisation between the musicians activated areas of the brain linked to syntactic processing for language, called the inferior frontal gyrus and posterior superior temporal gyrus. In contrast, the musical exchange deactivated brain structures involved in semantic processing, called the angular gyrus and supramarginal gyrus.
"When two jazz musicians seem lost in thought while trading fours, they aren’t simply waiting for their turn to play," Limb says. "Instead, they are using the syntactic areas of their brain to process what they are hearing so they can respond by playing a new series of notes that hasn’t previously been composed or practiced."
Study uncovers surprising differences in brain activity of alcohol-dependent women
A new Indiana University study that examines the brain activity of alcohol-dependent women compared to women who were not addicted found stark and surprising differences, leading to intriguing questions about brain network functions of addicted women as they make risky decisions about when and what to drink.
The study used functional magnetic resonance imaging, or fMRI, to study differences between patterns of brain network activation in the two groups of women. The findings indicate that the anterior insular region of the brain may be implicated in the process, suggesting a possible new target of treatment for alcohol-dependent women.
"We see that the network dynamics of alcohol-dependent women may be really different from that of healthy controls in a drinking-related task," said Lindsay Arcurio, a graduate student in the Department of Psychological and Brain Sciences. "We have evidence to suggest alcohol-dependent women have trouble switching between networks of the brain."
The research is part of a larger new effort to understand the differences between men and women with respect to alcohol. Arcurio said most of the research on alcohol dependence has been conducted with men or groups of men and women. Yet several factors make looking at women “really important.”
One such factor is that the physiological effects of drinking alcohol, which include liver damage, heart disease or breast cancer, set in much earlier in women than in men. For this reason, the suggested limit on the number of drinks per week that women can safely consume is eight, whereas for men, it is 14. Secondly, binge-drinking in women is on the rise. One in five adolescent girls is binge-drinking three times a month. In women between the ages of 18 and 54, that number is one in eight.
A ‘sledgehammer’ approach to defining differences in brain network activation
Research on decision-making mechanisms in alcohol-dependent individuals typically involves a general risk-taking situation in which money or points are at stake. In this study, participants were placed in the fMRI brain scanner and asked to consider low-risk and high-risk situations specifically related to alcohol — what the researchers describe as “ecological” tasks. Participants were then asked to make decisions regarding control stimuli — food as well as a presumably neutral stimuli, a stapler — to observe whether risky behavior was greater with respect to drinking than with these other items. The same picture cues were used to present high-risk and low-risk scenarios, and these two extremes were as follows:
For the low-risk situation, participants were told: Imagine you are at a bar. You are offered a drink, already paid for, with two shots of alcohol, and you have a safe ride home. For the high-risk, they were told: You are at a bar and are offered a drink already paid for, with six shots of alcohol, but you do not have a safe ride home.
The reason for such an extreme contrast between the two situations, Arcurio said, is that “as one of the first ecological tasks used in the scanner, we wanted to take a sledgehammer approach to really find the differences between cases that are definitely high-risk and those that are definitely low-risk.”
The findings, however, reflect an equally sharp contrast in differences between the brain network activation in alcohol-dependent women versus the controls.
For the control group, high-risk decisions to drink led to the deactivation of regions associated with “approach behavior,” deciding to take the drink in a risky situation. Conversely, women in the control group activate regions associated with the default mode network, a region traditionally thought to involve resting-state behavior or inactive or relaxed mental state, but which some now speculate plays a role in conceptualizing one’s future.
"It gets really interesting," Arcurio said, "comparing this pattern of activation to those in alcohol-dependent women, who behaviorally say they’re more likely to take the high-risk drink compared to the controls. They don’t deactivate anything. In contrast to the controls, alcohol-dependent women activate all three regions in question. They activate regions associated with reward (which release dopamine). They also activate frontal control regions involved in cognitive control and regions associated with the default mode network, involved in resting-state behavior. They are activating everything."
The investigators infer from these findings that alcohol-dependent women have trouble switching between networks. Being unable to activate one region and deactivate another in response to an alcohol-related situation means they are unable to use one strategy over another.
Furthermore, Arcurio said, “a lot of evidence suggests that switching between networks is influenced by the anterior insular and anterior cingulate regions of the brain, and we did find major differences in the insula between the alcohol-dependent women and controls. We’re thinking the issue is pinpointed to that region.”
The researchers are now running analyses to test the hypothesis that the insula helps in this process, which could offer new possibilities for intervention, with both behavioral therapy and medication.
The research is part of a whole research program, both planned and in the works, to further explore the questions about risky decision-making in alcohol-dependent women: studies of adolescent drinking, risky sexual behavior in alcohol-dependent women, the interaction of visual networks with decision-making networks, as well as the way music (or auditory networks) interacts with decision-making mechanisms in alcohol-dependent women. In the latter experiment, college-age participants choose a song that they associate with drinking and one with quiet reflection.
"There’s a lot of Miley Cyrus in the first category," Arcurio said.
(Source: news.indiana.edu)
To answer the seemingly simple question “Have I been here before?” we must use our memories of previous experiences to determine if our current location is familiar or novel. In a new study published in the Journal of Neuroscience researchers from the RIKEN Brain Science Institute have identified a region of the hippocampus, called CA2, which is sensitive to even small changes in a familiar context. The results provide the first clue to the contributions of CA2 to memory and may help shed light on why this area is often found to be abnormal in the schizophrenic brain.
Change comes in many flavors; if we move to a new country, city or house it is easy to recognize the novelty of the environment, but if we come home to find the furniture rearranged or a new piece of art on the wall, this recognition may be much slower. Scientists believe this is because memory formation requires comparing current information with previous experience and the larger the overlap, the more difficult the distinction. It has long been known that the hippocampus is a region of the brain crucial for this type of memory, however the identification of neurons responsible for this comparison has remained elusive.
In this study Marie Wintzer, Roman Boehringer, Denis Polygalov and Thomas McHugh used genetically modified mice and advanced cell imaging techniques to demonstrate that while the entire hippocampus is capable of detecting large changes in context, the small and often overlooked CA2 region is exquisitely sensitive to small changes.
Mice were familiarized with one context and then placed either in a much different context or back in the original with small alterations, such as several new small objects. By detecting the expression of activity induced genes Wintzer and colleagues were able to demonstrate that just a few new objects in the otherwise unchanged context completely altered the pattern of active cells specifically in CA2. Mice that had been genetically engineered to lack this CA2 response explored the new context much less than their normal siblings.
“CA2 has often been overlooked or simply grouped together with its more prominent neighbors, but these data suggest it’s unique and important for recognizing and reacting to changes in our environments” explains Dr. McHugh, the leader of the study.
Compared to rodents, human CA2 is proportionally larger, but still as mysterious. One intriguing finding has been that early in the onset of schizophrenia and bipolar disorder there is a loss of inhibitory neurons specifically in CA2. In addition to the memory problems that accompany these diseases, patients often exhibit a hyper-sensitivity to changes in environment and routine. This study suggests there may be a functional relationship between this sensitivity and CA2 dysfunction, hinting at a new circuit to target in our attempts to understand the function of both the normal and diseased brain.
Molecular biology mystery unravelled
The nature of the machinery responsible for the entry of proteins into cell membranes has been unravelled by scientists, who hope the breakthrough could ultimately be exploited for the design of new anti-bacterial drugs.
Groups of researchers from the University of Bristol and the European Molecular Biology Laboratory (EMBL) used new genetic engineering technologies to reconstruct and isolate the cell’s protein trafficking machinery. Its analysis has shed new light on a process which had previously been a mystery for molecular biologists.
The findings, published this week in the Proceedings of the National Academy of Sciences (PNAS), could also have applications for synthetic biology - an emerging field of science and technology, for the development of novel membrane proteins with useful activities.
Proteins are the building blocks of all life and are essential for the growth of cells and tissue repair. The proteins in the membrane typically help the cell interact with its environment and conserve energy.
Researchers were able to identify the ‘holo-translocon’ as the machinery which inserts proteins into the membrane. It is a large membrane protein complex and is uniquely capable of both protein-secretion and membrane-insertion.
Professor Ian Collinson, from the School of Biochemistry at Bristol University, said: “These findings are important as they address outstanding questions in one of the central pillars of biology, a process essential in every cell in every organism. Having unravelled how this vital holo-translocon works, we’re now in a position to look at its components to see if they can help in the design or screening for new anti-bacterial drugs.”
Why does the brain remember dreams?
Some people recall a dream every morning, whereas others rarely recall one. A team led by Perrine Ruby, an Inserm Research Fellow at the Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1), has studied the brain activity of these two types of dreamers in order to understand the differences between them. In a study published in the journal Neuropsychopharmacology, the researchers show that the temporo-parietal junction, an information-processing hub in the brain, is more active in high dream recallers. Increased activity in this brain region might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, thereby facilitating the encoding of dreams in memory.
The reason for dreaming is still a mystery for the researchers who study the difference between “high dream recallers,” who recall dreams regularly, and “low dream recallers,” who recall dreams rarely. In January 2013 (work published in the journal Cerebral Cortex), the team led by Perrine Ruby, Inserm researcher at the Lyon Neuroscience Research Center, made the following two observations: “high dream recallers” have twice as many time of wakefulness during sleep as “low dream recallers” and their brains are more reactive to auditory stimuli during sleep and wakefulness. This increased brain reactivity may promote awakenings during the night, and may thus facilitate memorisation of dreams during brief periods of wakefulness.
In this new study, the research team sought to identify which areas of the brain differentiate high and low dream recallers. They used Positron Emission Tomography (PET) to measure the spontaneous brain activity of 41 volunteers during wakefulness and sleep. The volunteers were classified into 2 groups: 21 “high dream recallers” who recalled dreams 5.2 mornings per week in average, and 20 “low dream recallers,” who reported 2 dreams per month in average. High dream recallers, both while awake and while asleep, showed stronger spontaneous brain activity in the medial prefrontal cortex (mPFC) and in the temporo-parietal junction (TPJ), an area of the brain involved in attention orienting toward external stimuli.
Scientists discover hormone released after exercise can ‘predict’ biological age
Scientists from Aston University have discovered a potential molecular link between Irisin, a recently identified hormone released from muscle after bouts of exercise, and the ageing process.
Irisin, which is naturally present in humans, is capable of reprograming the body’s fat cells to burn energy instead of storing it. This increases the metabolic rate and is thought to have potential anti-obesity effects which in turn could help with conditions such as type-2 diabetes.
The research team led by Dr James Brown have proven a significant link exists between Irisin levels in the blood and a biological marker of ageing called telomere length. Telomeres are small regions found at the end of chromosomes that shorten as cells within the body replicate. Short telomere length has been linked to many age-related diseases including cancer, heart disease and Alzheimer’s disease.
Using a population of healthy, non-obese individuals, the team has shown those individuals who had higher levels of Irisin were found to have longer telomeres. The finding provides a potential molecular link between keeping active and healthy ageing with those having higher Irisin levels more ‘biological young’ than those with lower levels of the hormone.
Dr James Brown from Aston’s Research Centre for Healthy Ageing, said; “Exercise is known to have wide ranging benefits, from cardiovascular protection to weight loss. Recent research has suggested that exercise can protect people from both physical and mental decline with ageing. Our latest findings now provide a potential molecular link between keeping active and a healthy ageing process.”
The Aston Research Centre for Healthy Ageing takes a multidisciplinary approach to successful ageing by asking how technological, therapeutic and psychosocial strategies can be employed to understand and arrest age-related decline and degeneration.
How Well Do Football Helmets Protect Players from Concussions?
A new study finds that football helmets currently used on the field may do little to protect against hits to the side of the head, or rotational force, an often dangerous source of brain injury and encephalopathy. The study released today will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.
"Protection against concussion and complications of brain injury is especially important for young players, including elementary and middle school, high school and college athletes, whose still-developing brains are more susceptible to the lasting effects of trauma," said study co- author Frank Conidi, MD, DO, MS, director of the Florida Center for Headache and Sports Neurology and Assistant Clinical Professor of Neurology at Florida State University College of Medicine in Port Saint Lucie, Fla. Conidi is also the vice chair of the American Academy of Neurology’s Sports Neurology Section.
For the study, researchers modified the standard drop test system, approved by the National Operating Committee on Standards for Athletic Equipment, that tests impacts and helmet safety. The researchers used a crash test dummy head and neck to simulate impact. Sensors were also placed in the dummy’s head to measure linear and rotational responses to repeated 12 mile-per-hour impacts. The scientists conducted 330 tests to measure how well 10 popular football helmet designs protected against traumatic brain injury, including: Adams a2000, Rawlings Quantum, Riddell 360, Riddell Revolution, Riddell Revolution Speed, Riddell VSR4, Schutt Air Advantage, Schutt DNA Pro+, Xenith X1 and Xenith X2.
The study found that football helmets on average reduced the risk of traumatic brain injury by only 20 percent compared to not wearing a helmet. Of the 10 helmet brands tested, the Adams a2000 provided the best protection against concussion and the Schutt Air Advantage the worst. Overall, the Riddell 360 provided the most protection against closed head injury and the Adams a2000 the least, despite rating the best against concussion.
"Alarmingly, those that offered the least protection are among the most popular on the field," said Conidi. "Biomechanics researchers have long understood that rotational forces, not linear forces, are responsible for serious brain damage including concussion, brain injury complications and brain bleeds. Yet generations of football and other sports participants have been under the assumption that their brains are protected by their investment in headwear protection."
The study found that football helmets provided protection from linear impacts, or those leading to bruising and skull fracture. Compared to tests using dummies with no helmets, leading football helmets reduced the risk of skull fracture by 60 to 70 percent and reduced the risk of focal brain tissue bruising by 70 to 80 percent.
The study was supported by BRAINS, Inc., a research and development company based in San Antonio, Fla., focused on biomechanics of traumatic brain injury.
Learning to see better in life and baseball
With a little practice on a computer or iPad—25 minutes a day, 4 days a week, for 2 months—our brains can learn to see better, according to a study of University of California, Riverside baseball players reported in the Cell Press journal Current Biology on February 17. The new evidence also shows that a visual training program can sometimes make the difference between winning and losing.
The study is the first, as far as the researchers know, to show that perceptual learning can produce improvements in vision in normally seeing individuals.
"The demonstration that seven players reached 20/7.5 acuity—the ability to read text at three times the distance of a normal observer—is dramatic and required players to stand forty feet back from the eye chart in order to get a measurement of their vision," says Aaron Seitz of the University of California, Riverside. For reference, 20/20 is considered normal visual acuity.
In the training game, the players’ task was to find and select visual patterns modeled after stimuli to which neurons in the early visual cortex of the brain respond best, Seitz explains. As game play commenced, those patterns were made dimmer and dimmer, exercising the players’ vision as they searched.
"The goal of the program is to train the brain to better respond to the inputs that it gets from the eye," Seitz says. "As with most other aspects of our function, our potential is greater than our normative level of performance. When we go to the gym and exercise, we are able to increase our physical fitness; it’s the same thing with the brain. By exercising our mental processes we can promote our mental fitness."
After the 2 month training period, players reported “seeing the ball much better,” “greater peripheral vision,” “easy to see further,” “able to distinguish lower-contrasting things,” “eyes feel stronger, they don’t get tired as much,” and so on.
The players also showed greater-than-expected improvements in their game. They were less likely to strike out and got more runs. The researchers estimate that those gains in batting statistics may have given the team an additional four or five wins in the 2013 season.
The researchers are now extending their work to include different groups, including members of the Los Angeles and Riverside Police Departments and people with low vision due to cataracts, macular degeneration, or amblyopia. They will also apply the same principles to other aspects of cognition, including memory and attention.
It all comes down to one thing: “Understanding the rules of brain plasticity unlocks great potential for improvement of health and wellbeing,” Seitz says.
Environmentally sensitive cells with a Hulk-like rage
Human exposure to urban air pollution may trigger toxic responses in brain cells and impact neurodegenerative disease pathways
From diesel exhaust to gaseous pollutants and suspended particulate matter, such as dust, smoke and fumes, air pollution from transportation, industry and energy generation has taken a toll on the environment and human health.
While the adverse effects of air pollution on the cardiovascular and respiratory systems have been well documented, little is known about how the associated toxins may impact the brain and the central nervous system. In recent years, experts have reported a marked rise in the prevalence of stroke, autism and cognitive decline in the elderly.
Researchers such as Michelle Block, Ph.D., associate professor in the Department of Anatomy and Neurobiology in the Virginia Commonwealth University School of Medicine, are now on a mission to define the impact of air pollution on the brain and central nervous system.
Through basic science, Block and her team are working to understand the underlying molecular mechanisms in hopes of developing an intervention that can protect human health.
Recent scientific reports suggest air pollution exposure and the activation of a specific group of cells found in the brain being studied in Block’s laboratory may play a role in the increased incidence of central nervous system diseases and neurological conditions. They have observed that these factors may also impact the neurodegenerative disease process.
Last week, Block, presented her team’s significant research findings to peers from across the country during a symposium she co-organized at the 2014 annual meeting of the American Association for the Advancement of Science, held in Chicago, from Feb. 13 to 17.
“Angry” cells, toxic responses
Block’s research examines microglia, a group of resident immune cells found in the brain and spinal cord, which can display a kind of dual personality – one good, and the other bad if agitated.
Under normal conditions, microglia primarily serve as the defenders of the central nervous system. They bring balance to the system. They destroy infectious agents, engulf various unwanted cellular and foreign materials and promote regrowth of damaged neural tissue.
But microglia can be dangerous when they are exceptionally “angry” and are known to leave behind significant bystander damage to neighboring cells. This adverse behavior may lead to the development of any number of neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, or Gulf War Illness.
In some ways, microglia are similar to misunderstood superhero The Incredible Hulk. Despite having a decent-sized heart and extraordinary abilities to help save the day, nobody wants to stir his rage and anger.
Block’s laboratory specializes in understanding the cellular and molecular machinery responsible for essentially fueling microglia “anger” – why they become chronically and excessively activated to drive damage in the brain.
“Our goal is to define how microglia detect and respond to air pollution, reveal when this microglial response may actually be damaging the brain, identify potential markers of ongoing silent neuropathology and ultimately use the mechanistic information we acquire as a tool to halt the induced or augmented neuropathology,” Block said.
In several peer-reviewed, published reports, Block and her colleagues have demonstrated that exposure to a diverse source of urban air pollution can trigger toxic microglial responses and impact neurodegenerative disease pathways.
“Given the prevalence of human exposure to urban air pollution above safety regulations, it is critical to understand the underlying mechanisms through which air pollution affects the brain,” Block said. “We hope to find an opportunity to intervene and protect human central nervous system health.”
According to Block, her team’s work shows that many components of urban air pollution, including the particle components of air pollution, also called particulate matter, and gases, such as ground level ozone, activate microglia.
Some of the problems with this cell type come in when the same molecular tools used by microglia internalize (eat) and clean up toxic stimuli and accidentally trigger the switch to an excessive, angry activation state. The work she presented reveals how air pollution does this, essentially leaving microglia with much more than a mouthful. Her lab has discovered that the MAC1 pattern recognition receptor may be a common mechanism through which microglia detect and ultimately misinterpret different forms of air pollution as an invading pathogen to result in excessive production of reactive oxygen species and consequent damage to neighboring brain cells.
Further, ongoing research in Block’s lab aims to define where damage to the lungs through inhaled toxicants produces injury signals in the circulation that are not only detected by microglia in the brain, but are responsible for shifting microglia to a deleterious phenotype impacting central nervous system health. She refers to this as a “Lung-Brain Axis.”