Posts tagged science
Articles and news from the latest research reports.
BPA May Affect the Developing Brain by Disrupting Gene Regulation
Environmental exposure to bisphenol A (BPA), a widespread chemical found in plastics and resins, may suppress a gene vital to nerve cell function and to the development of the central nervous system, according to a study led by researchers at Duke Medicine.
The researchers published their findings - which were observed in cortical neurons of mice, rats and humans - in the journal Proceedings of the National Academy of Sciences on Feb. 25, 2013.
"Our study found that BPA may impair the development of the central nervous system, and raises the question as to whether exposure could predispose animals and humans to neurodevelopmental disorders," said lead author Wolfgang Liedtke, M.D., PhD, associate professor of medicine/neurology and neurobiology at Duke.
BPA, a molecule that mimics estrogen and interferes with the body’s endocrine system, can be found in a wide variety of manufactured products, including thermal printer paper, some plastic water bottles and the lining of metal cans. The chemical can be ingested if it seeps into the contents of food and beverage containers.
Research in animals has raised concerns that exposure to BPA may cause health problems such as behavioral issues, endocrine and reproductive disorders, obesity, cancer and immune system disorders. Some studies suggest that infants and young children may be the most vulnerable to the effects of BPA, which led the U.S. Food and Drug Administration to ban the use of the chemical in baby bottles and cups in July 2012.
While BPA has been shown to affect the developing nervous system, little is understood as to how this occurs. The research team developed a series of experiments in rodent and human nerve cells to learn how BPA induces changes that disrupt gene regulation.
During early development of neurons, high levels of chloride are present in the cells. These levels drop as neurons mature, thanks to a chloride transporter protein called KCC2, which churns chloride ions out of the cells. If the level of chloride within neurons remains elevated, it can damage neural circuits and compromise a developing nerve cell’s ability to migrate to its proper position in the brain.
Exposing neurons to minute amounts of BPA alters the chloride levels inside the cells by somehow shutting down the Kcc2 gene, which makes the KCC2 protein, thereby delaying the removal of chloride from neurons.
MECP2, another protein important for normal brain function, was found to be a possible culprit behind this change. When exposed to BPA, MECP2 is more abundant and binds to the Kcc2 gene at a higher rate, which might help to shut it down. This could contribute to problems in the developing brain due to a delay in chloride being removed.
These findings raise the question of whether BPA could contribute to neurodevelopmental disorders such as Rett syndrome, a severe autism spectrum disorder that is only found in girls and is characterized by mutations in the gene that produces MECP2.
While both male and female neurons were affected by BPA in the studies, female neurons were more susceptible to the chemical’s toxicity. Further research will dig deeper into the sex-specific effects of BPA exposure and whether certain sex hormone receptors are involved in BPA’s effect on KCC2.
"Our findings improve our understanding of how environmental exposure to BPA can affect the regulation of the Kcc2 gene. However, we expect future studies to focus on what targets aside from Kcc2 are affected by BPA," Liedtke said. "This is a chapter in an ongoing story."
Study finds higher levels of several toxic metals in children with autism
In a recently published study in the journal Biological Trace Element Research, Arizona State University researchers report that children with autism had higher levels of several toxic metals in their blood and urine compared to typical children. The study involved 55 children with autism ages 5–16 years compared to 44 controls of similar age and gender.
The autism group had significantly higher levels of lead in their red blood cells (+41 percent) and significantly higher urinary levels of lead (+74 percent), thallium (+77 percent), tin (+115 percent), and tungsten (+44 percent). Lead, thallium, tin, and tungsten are toxic metals that can impair brain development and function, and also interfere with the normal functioning of other body organs and systems.
A statistical analysis was conducted to determine if the levels of toxic metals were associated with autism severity, using three different scales of autism severity. It was found that 38-47 percent of the variation of autism severity was associated with the level of several toxic metals, with cadmium and mercury being the most strongly associated.
In the paper about the study, the authors state “We hypothesize that reducing early exposure to toxic metals may help ameliorate symptoms of autism, and treatment to remove toxic metals may reduce symptoms of autism; these hypotheses need further exploration, as there is a growing body of research to support it.”
The study was led by James Adams, a President’s Professor in the School for Engineering of Matter, Transport and Energy, one of ASU’s Ira A. Fulton Schools of Engineering. He directs the ASU Autism/Asperger’s Research Program.
Adams previously published a study on the use of DMSA, an FDA-approved medication for removing toxic metals. The open-label study found that DMSA was generally safe and effective at removing some toxic metals. It also found that DMSA therapy improved some symptoms of autism. The biggest improvement was for children with the highest levels of toxic metals in their urine.
Overall, children with autism have higher average levels of several toxic metals, and levels of several toxic metals are strongly associated with variations in the severity of autism for all three of the autism severity scales investigated.
(Source: fullcircle.asu.edu)
Ultrasound reveals autism risk at birth
Low-birth-weight babies with a particular brain abnormality are at greater risk for autism, according to a new study that could provide doctors a signpost for early detection of the still poorly understood disorder.
Led by Michigan State University, the study found that low-birth-weight newborns were seven times more likely to be diagnosed with autism later in life if an ultrasound taken just after birth showed they had enlarged ventricles, cavities in the brain that store spinal fluid. The results appear in the Journal of Pediatrics.
“For many years there’s been a lot of controversy about whether vaccinations or environmental factors influence the development of autism, and there’s always the question of at what age a child begins to develop the disorder,” said lead author Tammy Movsas, clinical assistant professor of pediatrics at MSU and medical director of the Midland County Department of Public Health.
“What this study shows us is that an ultrasound scan within the first few days of life may already be able to detect brain abnormalities that indicate a higher risk of developing autism.”
Movsas and colleagues reached that conclusion by analyzing data from a cohort of 1,105 low-birth-weight infants born in the mid-1980s. The babies had cranial ultrasounds just after birth so the researchers could look for relationships between brain abnormalities in infancy and health disorders that showed up later. Participants also were screened for autism when they were 16 years old, and a subset of them had a more rigorous test at 21, which turned up 14 positive diagnoses.
Ventricular enlargement is found more often in premature babies and may indicate loss of a type of brain tissue called white matter.
“This study suggests further research is needed to better understand what it is about loss of white matter that interferes with the neurological processes that determine autism,” said co-author Nigel Paneth, an MSU epidemiologist who helped organize the cohort. “This is an important clue to the underlying brain issues in autism.”
Prior studies have shown an increased rate of autism in low-birth-weight and premature babies, and earlier research by Movsas and Paneth found a modest increase in symptoms among autistic children born early or late.
Scientists Find Way to Image Brain Waste Removal Process Which May Lead to Alzheimer’s Diagnostic
A novel way to image the entire brain’s glymphatic pathway, a dynamic process that clears waste and solutes from the brain that otherwise might build-up and contribute to the development of Alzheimer’s disease, may provide the basis for a new strategy to evaluate disease susceptibility, according to a research paper published online in The Journal of Clinical Investigation. Through contrast enhanced magnetic resonance imaging (MRI) and other tools, a Stony Brook University-led research team successfully mapped this brain-wide pathway and identified key anatomical clearance routes of brain waste.
In their article titled “Brain-wide pathway for waste clearance captured by contrast enhanced MRI,” Principal Investigator Helene Benveniste, MD, PhD, a Professor in the Departments of Anesthesiology and Radiology at Stony Brook University School of Medicine, and colleagues built upon a previous finding by Jeffrey Iliff, PhD, and Maiken Nedergaard, MD, PhD, from University of Rochester that initially discovered and defined the glymphatic pathway, where cerebral spinal fluid (CSF) filters through the brain and exchanges with interstitial fluid (ISF) to clear waste, similar to the way lymphatic vessels clear waste from other organs of the body. Despite the discovery of the glymphatic pathway, researchers could not visualize the brain wide flow of this pathway with previous imaging techniques.
“Our experiments showed proof of concept that the glymphatic pathway function can be measured using a simple and clinically relevant imaging technique,” said Dr. Benveniste. “This technique provides a three-dimensional view of the glymphatic pathway that captures movement of waste and solutes in real time. This will help us to define the role of the pathway in clearing matter such as amyloid beta and tau proteins, which affect brain processes if they build up.”
Dr. Benveniste said that the pathology of certain neurological conditions is associated with the accumulation of these proteins and other large extracellular aggregates. In particular, she explained that plaque deposits of these proteins are implicated in the development of Alzheimer’s disease, as well as chronic traumatic encephalopathy that occurs after repetitive mild traumatic brain injuries.
Scientists find genes linked to human neurological disorders in sea lamprey genome
Scientists at the Marine Biological Laboratory (MBL) have identified several genes linked to human neurological disorders, including Alzheimer’s disease, Parkinson’s disease and spinal cord injury, in the sea lamprey, a vertebrate fish whose whole-genome sequence is reported this week in the journal Nature Genetics.
"This means that we can use the sea lamprey as a powerful model to drive forward our molecular understanding of human neurodegenerative disease and neurological disorders," says Jennifer Morgan of the MBL’s Eugene Bell Center for Regenerative Biology and Tissue Engineering. The ultimate goals are to determine what goes wrong with neurons after injury and during disease, and to determine how to correct these deficits in order to restore normal nervous system functions.
Unlike humans, the lamprey has an extraordinary capacity to regenerate its nervous system. If a lamprey’s spinal cord is severed, it can regenerate the damaged nerve cells and be swimming again in 10-12 weeks.
Morgan and her collaborators at MBL, Ona Bloom and Joseph Buxbaum, have been studying the lamprey’s recovery from spinal cord injury since 2009. The lamprey has large, identified neurons in its brain and spinal cord, making it an excellent model to study regeneration at the single cell-level. Now, the lamprey’s genomic information gives them a whole new “toolkit” for understanding its regenerative mechanisms, and for comparing aspects of its physiology, such as inflammation response, to that of humans.
The lamprey genome project was accomplished by a consortium of 59 researchers led by Weiming Li of Michigan State University and Jeramiah Smith of the University of Kentucky. The MBL scientists’ contribution focused on neural aspects of the genome, including one of the project’s most intriguing findings.
Lampreys, in contrast to humans, don’t have myelin, an insulating sheath around neurons that allows faster conduction of nerve impulses. Yet the consortium found genes expressed in the lamprey that are normally expressed in myelin. In humans, myelin-associated molecules inhibit nerves from regenerating if damaged. “A lot of the focus of the spinal cord injury field is on neutralizing those inhibitory molecules,” Morgan says.
"So there is an interesting conundrum," Morgan says. "What are these myelin-associated genes doing in an animal that doesn’t have myelin, and yet is good at regeneration? It opens up a new and interesting set of questions, " she says. Addressing them could bring insight to why humans lost the capacity for neural regeneration long ago, and how this might be restored.
At present, Morgan and her collaborators are focused on analyzing which genes are expressed and when, after spinal cord injury and regeneration. The whole-genome sequence gives them an invaluable reference for their work.
Ability of brain to protect itself from damage revealed
(Image: Matthias Kulka / Corbis)
The origin of an innate ability the brain has to protect itself from damage that occurs in stroke has been explained for the first time.
The Oxford University researchers hope that harnessing this inbuilt biological mechanism, identified in rats, could help in treating stroke and preventing other neurodegenerative diseases in the future.
'We have shown for the first time that the brain has mechanisms that it can use to protect itself and keep brain cells alive,' says Professor Alastair Buchan, Head of the Medical Sciences Division and Dean of the Medical School at Oxford University, who led the work.
The researchers report their findings in the journal Nature Medicine and were funded by the UK Medical Research Council and National Institute for Health Research.
Stroke is the third most common cause of death in the UK. Every year around 150,000 people in the UK have a stroke.
It occurs when the blood supply to part of the brain is cut off. When this happens, brain cells are deprived of the oxygen and nutrients they need to function properly, and they begin to die.
'Time is brain, and the clock has started immediately after the onset of a stroke. Cells will start to die somewhere from minutes to at most 1 or 2 hours after the stroke,' says Professor Buchan.
This explains why treatment for stroke is so dependent on speed. The faster someone can reach hospital, be scanned and have drugs administered to dissolve any blood clot and get the blood flow re-started, the less damage to brain cells there will be.
It has also motivated a so-far unsuccessful search for ‘neuroprotectants’: drugs that can buy time and help the brain cells, or neurons, cope with damage and recover afterwards.
The Oxford University research group have now identified the first example of the brain having its own built-in form of neuroprotection, so-called ‘endogenous neuroprotection’.
They did this by going back to an observation first made over 85 years ago. It has been known since 1926 that neurons in one area of the hippocampus, the part of the brain that controls memory, are able to survive being starved of oxygen, while others in a different area of the hippocampus die. But what protected that one set of cells from damage had remained a puzzle until now.
'Previous studies have focused on understanding how cells die after being depleted of oxygen and glucose. We considered a more direct approach by investigating the endogenous mechanisms that have evolved to make these cells in the hippocampus resistant,' explains first author Dr Michalis Papadakis, Scientific Director of the Laboratory of Cerebral Ischaemia at Oxford University.
Working in rats, the researchers found that production of a specific protein called hamartin allowed the cells to survive being starved of oxygen and glucose, as would happen after a stroke.
They showed that the neurons die in the other part of the hippocampus because of a lack of the hamartin response.
The team was then able to show that stimulating production of hamartin offered greater protection for the neurons.
Professor Buchan says: ‘This is causally related to cell survival. If we block hamartin, the neurons die when blood flow is stopped. If we put hamartin back, the cells survive once more.’
Finally, the researchers were able to identify the biological pathway through which hamartin acts to enable the nerve cells to cope with damage when starved of energy and oxygen.
The group points out that knowing the natural biological mechanism that leads to neuroprotection opens up the possibility of developing drugs that mimic hamartin’s effect.
Professor Buchan says: ‘There is a great deal of work ahead if this is to be translated into the clinic, but we now have a neuroprotective strategy for the first time. Our next steps will be to see if we can find small molecule drug candidates that mimic what hamartin does and keep brain cells alive.
'While we are focussing on stroke, neuroprotective drugs may also be of interest in other conditions that see early death of brain cells including Alzheimer's and motor neurone disease,' he suggests.
(Source: eurekalert.org)
How electrodes in the brain block obsessive behaviour
Deep brain stimulation helps some people with obsessive-compulsive disorder (OCD), but no one was quite sure why it is effective. A new study offers an explanation: the stimulation has surprisingly pervasive effects, fixing abnormal signalling between different parts of the brain.
A small number of people with difficult-to-treat OCD have had electrodes permanently implanted deep within their brain. Stimulating these electrodes reduces their symptoms.
To work out why stimulation has this effect, Damiaan Denys and Martijn Figee at the Academic Medical Center in Amsterdam, the Netherlands, and colleagues recorded neural activity in people with electrodes implanted into a part of the brain called the nucleus accumbens. This region is vital for conveying motivational and emotional information to the frontal cortex to guide decisions on what actions to take next. In some people with OCD, feedback loops between the two get jammed, leading them to do the same task repeatedly to reduce anxiety.
The researchers took fMRI scans as participants rested. In 13 people with OCD and implanted electrodes, there was continuous and excessive exchange of signals between the nucleus accumbens and the frontal cortex that was not seen in 11 control subjects. When the electrodes were activated, though, the neural activity of both brain regions in the people with OCD became virtually identical to that in the controls.
The researchers also used EEGs to monitor electrical activity in the brain as the 13 people with OCD viewed images linked with their obsessions, such as cleaning toilets. This time, the team observed excessive activity in the frontal cortex – and again, this activity disappeared when the electrodes were activated.
"The most striking thing is that stimulation doesn’t just affect the nucleus accumbens, but the whole network linked up with the cortex," says Figee.
The study suggests that the electrodes do more than normalise brain activity at the site where they are implanted, as had been assumed. Rather, they appear to repair entire brain circuits that had been faulty. “It resets and normalises these circuits,” says Figee.
Thomas Schlaepfer at the University of Bonn, Germany, points out that such work may allow researchers to use deep brain stimulation to learn about the causes of OCD as they treat it. “It will serve as a research platform informing us about the underlying neurobiology of such disorders,” he says.
(Image courtesy: Michael S. Okun)
Insects inspiring new technology
Scientists from the University of Lincoln and Newcastle University have created a computerised system which allows for autonomous navigation of mobile robots based on the locust’s unique visual system.
The work could provide the blueprint for the development of highly accurate vehicle collision sensors, surveillance technology and even aid video game programming according to the research published today.
Locusts have a distinctive way of processing information through electrical and chemical signals, giving them an extremely fast and accurate warning system for impending collisions.
The insect has incredibly powerful data processing systems built into its biology, which can in theory be recreated in robotics.
Inspired by the visual processing power built into these insects’ biology, Professor Shigang Yue from the University of Lincoln’s School of Computer Science and Dr Claire Rind from Newcastle University’s Institute of Neuroscience created the computerised system.
Their findings are published in the International Journal of Advanced Mechatronic Systems.
The research started by understanding the anatomy, responses and development of the circuits in the locust brain that allow it to detect approaching objects and avoid them when in flight or on the ground.
A visually stimulated motor control (VSMC) system was then created which consists of two movement detector types and a simple motor command generator. Each detector processes images and extracts relevant visual clues which are then converted into motor commands.
Prof Yue said: “We were inspired by the way the locusts’ visual system works when interacting with the outside world and the potential to simulate such complex systems in software and hardware for various applications. We created a system inspired by the locusts’ motion sensitive interneuron – the lobula giant movement detector. This system was then used in a robot to enable it to explore paths or interact with objects, effectively using visual input only.”
Funded by the European Union’s Seventh Framework Programme (FP7), the research was carried out as part of a collaborative project with the University of Hamburg in Germany and Tsinghua University and Xi’an Jiaotong University, China.
Students invited to take cocaine for London university’s research
King’s College London has sent an email to hundreds of undergraduates inviting them to “take part in a clinical study involving nasal administration of cocaine”.
Students who use drugs recreationally will not be allowed to participate, nor those studying medicine or dentistry. Those who are accepted will be given “reasonable financial compensation” for the time and expenses incurred. The email explains the study will mean that: “After cocaine administration, repeated biological samples (blood, urine, hair, sweat, oral fluid) will be taken to compare and investigate how cocaine and its metabolites are spread through the human body.”
Participants will not be able to cut or dye their hair for 120 days during the study follow-up period as scientists investigate a wide range of physical effects on the body.
The project, which has been approved by London Westminster Research Ethics Committee, will be supervised by the clinical toxicology department at St Thomas’ Hospital.
A spokesman for King’s said: “This is an important scientific study to investigate how cocaine and its metabolites are spread through the human body.
“All the relevant ethical approvals were received for this study. The study will be conducted under the highest level of medical supervision in a dedicated clinical research suite. Further information about the NHS ethical approval process, which was followed, is available on our website.”
The email has already attracted online comments and jokes from students. The university has a reputation for research into the use and effects of illegal drugs, including studies into the genetic causes of addiction and papers on whether certain substances should be legalised.
An estimated 700,000 people in Britain took cocaine last year, making it the second most popular drug after cannabis.
Scientists behind groundbreaking research that enabled rats with severed spines to run again after two weeks have outlined their plans for human trials.
The technology brings fresh hope to sufferers of spinal cord injuries, and the team say they hope the first humans could be implanted with the technology within months.
Using a cocktail of drugs and electrical impulses, researchers hope to begin testing the project to ‘regrow’ nerves linking the spinal cord to the brain in five patients in a Swiss clinic.
Last June in the journal Science, Grégoire Courtine, of the École Polytechnique Fédérale de Lausanne (EPFL), reported that rats in his lab are not only voluntarily initiating a walking gait, but they were sprinting, climbing up stairs, and avoiding obstacles after a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical and chemical stimulation.
At the 2013 Annual Meeting of the American Association for the Advancement of Science (AAAS) in Boston, Courtine revealed the next step for the research.
He has since repeated the study in rats with bruised spines, which more closely resembles human trauma patients, and after a few weeks they could walk with no assistance.
He now believes that the technique could help people who have been immobile for up to two years.
Although full human trials are still a few years off, he plans to attempt electrical stimulation on five patients who have limited leg movement in the coming months.
‘We know that spinal cord stimulation is safe, we know that training is good, so we want to start the first trial in people who can move their legs but cannot walk independently.
'So we will implant five patients, we have a new technology which allows us to stimulate the spinal cord of humans just like we do in the rats.’
Once they have refined the technique, they hope to fully rehabilitate patients with moderately damaged spines, while others would regain some movement.
‘We already have preliminary data from the rats with these clinically relevant lesions is that a number of them would recover at the end of the training and could walk without any help. It depends on the severity of the damage,’ he said.
‘But if you talk to the patient and you tell them at least you could use it at home to cook, to watch TV and have normal activity, they say their life would be so different. So it is less ambitious, but we are talking about improving the quality of life, allowing people to stand and take a few steps at home with a walker.’