Neuroscience
Month
August 26, 2012
Vitamin B12 is essential to human health. However, some people have inherited conditions that leave them unable to process vitamin B12. As a result they are prone to serious health problems, including developmental delay, psychosis, stroke and dementia. An international research team recently discovered a new genetic disease related to vitamin B12 deficiency by identifying a gene that is vital to the transport of vitamin into the cells of the body. This discovery will help doctors better diagnose this rare genetic disorder and open the door to new treatments. The findings are published in the journal Nature Genetics.
"We found that a second transport protein was involved in the uptake of the vitamin into the cells, thus providing evidence of another cause of hereditary vitamin B12 deficiency", said Dr. David Rosenblatt, one of the study’s co-authors, scientist in medical genetics and genomics at the Research Institute of the McGill University Health Centre (RI MUHC) and Dodd Q. Chu and Family Chair in Medical Genetics and the Chair of the Department of Human Genetics at McGill University. "It is also the first description of a new genetic disease associated with how vitamin B12 is handled by the body".
These results build on previous research by the same team from the RI MUHC and McGill University, with their colleagues in Switzerland, Germany and the United States. In previous work, the researchers discovered that vitamin B12 enters our cells with help from of a specific transport protein. In this study, they were working independently with two patients showing symptoms of the cblF gene defect of vitamin B12 metabolism but without an actual defect in this gene. Their work led to the discovery of a new gene, ABCD4, associated with the transport of B12 and responsible for a new disease called cblJ combined homocystinuria and methylmalonic aciduria (cblJ-Hcy-MMA).
Using next generation sequencing of the patients’ genetic information, the scientists identified two mutations in the same ABCD4 gene, in both patients. “We were also able to compensate for the genetic mutation by adding an intact ABCD4 protein to the patients’ cells, thus allowing the vitamin to be properly integrated into the cells,” explained Dr. Matthias Baumgartner, senior author of the study and a Professor of metabolic diseases at Zurich’s University Children’s Hospital.
Vitamin B12, or cobalamin, is essential for healthy functioning of the human nervous system and red blood cell synthesis. Unable to produce the vitamin itself, the human body has to obtain it from animal-based foods such as milk products, eggs, red meat, chicken, fish, and shellfish – or vitamin supplements. Vitamin B12 is not found in vegetables.
"This discovery will lead to the early diagnosis of this serious genetic disorder and has given us new paths to explore treatment options. It also helps explain how vitamin B12 functions in the body, even for those without the disorder," said Dr. Rosenblatt who is the director of one of only two referral laboratories in the world for patients suspected of having this genetic inability to absorb vitamin B12. Dr. Rosenblatt points out that the study of patients with rare diseases is essential to the advancement of our knowledge of human biology.
Source: medicalxpress.com
26 August 2012 by Mo Costandi
Subjects trained to sniff pleasant smells while asleep retain the conditioning when they wake up.
It sounds like every student’s dream: research published today in Nature Neuroscience shows that we can learn entirely new information while we snooze.
TIPS/Photoshot
Anat Arzi of the Weizmann Institute of Science in Rehovot, Israel, and her colleagues used a simple form of learning called classical conditioning to teach 55 healthy participants to associate odours with sounds as they slept.
They repeatedly exposed the sleeping participants to pleasant odours, such as deodorant and shampoo, and unpleasant odours such as rotting fish and meat, and played a specific sound to accompany each scent.
It is well known that sleep has an important role in strengthening existing memories, and this conditioning was already known to alter sniffing behaviour in people who are awake. The subjects sniff strongly when they hear a tone associated with a pleasant smell, but only weakly in response to a tone associated with an unpleasant one.
But the latest research shows that the sleep conditioning persists even after they wake up, causing them to sniff strongly or weakly on hearing the relevant tone — even if there was no odour. The participants were completely unaware that they had learned the relationship between smells and sounds. The effect was seen regardless of when the conditioning was done during the sleep cycle. However, the sniffing responses were slightly more pronounced in those participants who learned the association during the rapid eye movement (REM) stage, which typically occurs during the second half of a night’s sleep.
Pillow power
Arzi thinks that we could probably learn more complex information while we sleep. “This does not imply that you can place your homework under the pillow and know it in the morning,” she says. “There will be clear limits on what we can learn in sleep, but I speculate that they will be beyond what we have demonstrated.”
In 2009, Tristan Bekinschtein, a neuroscientist at the UK Medical Research Council’s Cognition and Brain Sciences Unit in Cambridge, and his colleagues reported that some patients who are minimally conscious or in a vegetative state can be classically conditioned to blink in response to air puffed into their eyes. Conditioned responses such as these could eventually help clinicians to diagnose these neurological conditions, and to predict which patients might subsequently recover. “It remains to be seen if the neural networks involved in sleep learning are similar to the ones recruited during wakefulness,” says Bekinschtein.
The findings by Arzi and her colleagues might also be useful for these purposes, and could lead to ‘sleep therapies’ that help to alter behaviour in conditions such as phobia.
“We are now trying to implement helpful behavioural modification through sleep-learning,” says Arzi. “We also want to investigate the brain mechanisms involved, and the type of learning we use in other states of altered consciousness, such as vegetative state and coma.”
Source: Nature
The nervous system is a complex collection of nerves and specialized cells known as neurons that transmit signals between different parts of the body. Vertebrates — animals with backbones and spinal columns — have central and peripheral nervous systems.
The central nervous system is made up of the brain, spinal cord and retina. The peripheral nervous system consists of sensory neurons, ganglia (clusters of neurons) and nerves that connect to one another and to the central nervous system.
Credit: iDesign, Shutterstock
Description of the nervous system
The nervous system is essentially the body’s electrical wiring. It is composed of nerves, which are cylindrical bundles of fibers that start at the brain and central cord and branch out to every other part of the body.
Neurons send signals to other cells through thin fibers called axons, which cause chemicals known as neurotransmitters to be released at junctions called synapses. A synapse gives a command to the cell and the entire communication process typically takes only a fraction of a millisecond.
Sensory neurons react to physical stimuli such as light, sound and touch and send feedback to the central nervous system about the body’s surrounding environment. Motor neurons, located in the central nervous system or in peripheral ganglia, transmit signals to activate the muscles or glands.
Glial cells, derived from the Greek word for “glue,” support the neurons and hold them in place. Glial cells also feed nutrients to neurons, destroy pathogens, remove dead neurons and act as traffic cops by directing the axons of neurons to their targets. Specific types of glial cells (oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system) generate layers of a fatty substance called myelin that wraps around axons and provides electrical insulation to enable them to rapidly and efficiently transmit signals.
24 August 2012 by Michael Marshall
THE latest twist in the origin-of-life tale is double helical. Chemists are close to demonstrating that the building blocks of DNA can form spontaneously from chemicals thought to be present on the primordial Earth. If they succeed, their work would suggest that DNA could have predated the birth of life.
Lurking at the dawn of time (Image: Snorri Gunnarsson/Flickr/Getty)
DNA is essential to almost all life on Earth, yet most biologists think that life began with RNA. Just like DNA, it stores genetic information. What’s more, RNA can fold into complex shapes that can clamp onto other molecules and speed up chemical reactions, just like a protein, and it is structurally simpler than DNA, so might be easier to make.
After decades of trying, in 2009 researchers finally managed to generate RNA using chemicals that probably existed on the early Earth. Matthew Powner, now at University College London, and his colleagues synthesised two of the four nucleotides that make up RNA. Their achievement suggested that RNA may have formed spontaneously - powerful support for the idea that life began in an “RNA world”.
August 24th, 2012
Researchers from the Laboratory of astrocyte biology and CNS regeneration headed by Prof. Milos Pekny just published a research article in a prestigious journal Stem Cells on the molecular mechanism that controls generation of new neurons in the brain.
Astrocytes are cells that have many functions in the central nervous system, such as the control of neuronal synapses, blood flow, or the brain’s response to neurotrauma or stroke.
Reduces brain tissue damage
Prof. Pekny’s laboratory together with collaborators have earlier demonstrated that astrocytes reduce the brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.
Generation of new neurons
In their current study, the Sahlgrenska Academy researchers show how astrocytes control the generation of new neurons in the brain. An important contribution to this project came from Åbo Academy, one of Sahlgrenska’s traditional collaborative partners.
“In the brain, astrocytes control how many new neurons are formed from neural stem cells and survive to integrate into the existing neuronal networks. Astrocytes do this by secreting specific molecules but also by much less understood direct cell-cell interactions with stem cells”, says Prof. Milos Pekny.
Image shows GFAP stained cortex from a TgAPP mouse showing activated astrocytes from a different study.
Important regulator
“Astrocytes are in physical contact with neural stem cells and we have shown that they signal through the Notch pathway to stem cells to keep the birth rate of new neurons low. We have also shown that the intermediate filament system of astrocytes is an important regulator of this process. It seems that astrocyte intermediate filaments can be used as a target to increase the birthrate of new neurons.”
Target for future therapies
“We are starting to understand some of the cellular and molecular mechanisms behind the control of neurogenesis. Neurogenesis is one of the components of brain plasticity, which plays a role in the learning process as well as in the recovery after brain injury or stroke. This work helps us to understand how plasticity and regenerative response can be therapeutically promoted in the future”, says Prof. Milos Pekny.
Source: Neuroscience News
The researchers from Lancaster University have found that those with the degenerative brain disease have difficulty with one particular test. They also found that the inability to carry out the tests in those who had already been diagnosed with Alzheimer’s was linked to lower memory function.
Photo: ALAMY
Dr Trevor Crawford said the latest results were potentially exciting. They showed, for the first time, a physical connection with the memory impairment that so often is the first noticeable symptom in Alzheimer’s.
Dr Crawford, of the department of Psychology and the Centre for Ageing Research, Lancaster University, said: “The diagnosis of Alzheimer’s disease is currently heavily dependent on the results of a series of lengthy neuropsychological tests.
"However, patients with a dementia often find that these tests are difficult to complete due to a lack of clear understanding and lapse in their attention or motivation.
"Over the last 10 years, researchers in laboratories around the world have been working on an alternative approach based on the brain’s control of the movements of the eye as a tool for investigating cognitive abilities, such as attention, cognitive inhibition and memory."
During the study, 18 patients with Alzheimer’s disease, 25 patients with Parkinson’s disease, 17 healthy young people and 18 healthy older people were asked to follow the movements of light on a computer monitor. In some instances they were asked to look away from the light. Detailed eye–tracking measurements showed stark contrasts in results.
Patients with Alzheimer’s made errors on the task when they were asked to look away from the light. They were unable correct those errors, despite being able to respond normally when they were asked to look towards the light.
These uncorrected errors were 10 times more frequent in the Alzheimers’ patients than the control groups. Researchers also measured memory function among those Alzheimer’s patients who found the test difficult and were able to show a clear correlation with lower memory function. Dr Crawford added: “The light tracking test could play a vital role in the diagnosis of Alzheimer’s.”
August 24, 2012 By Barbara Bronson Gray
(HealthDay)—Whether it’s an email from an unknown gentleman on another continent pleading for money or a financial scammer selling a promising penny stock, the young and old tend to be more easily duped than middle-aged people.
Changes in this region could explain why seniors, children are less doubting.
Now, researchers have pinpointed the area of the brain responsible for this gullibility and have theorized why it makes children, teens and seniors less likely to doubt.
The ventromedial area of the prefrontal cortex of the brain—a softball-sized lobe in the front of your head, just above your eyes—appears to be responsible for allowing you to pause after hearing or reading something and consider whether it’s true, according to a study published recently in the journal Frontiers in Neuroscience.
ScienceDaily (Aug. 23, 2012) — We use language every day to express our emotions, but can this language actually affect what and how we feel? Two new studies from Psychological Science, a journal of the Association for Psychological Science, explore the ways in which the interaction between language and emotion influences our well-being.
Putting Feelings into Words Can Help Us Cope with Scary Situations
Katharina Kircanski and colleagues at the University of California, Los Angeles investigated whether verbalizing a current emotional experience, even when that experience is negative, might be an effective method for treating for people with spider phobias. In an exposure therapy study, participants were split into different experimental groups and they were instructed to approach a spider over several consecutive days.
One group was told to put their feelings into words by describing their negative emotions about approaching the spider. Another group was asked to ‘reappraise’ the situation by describing the spider using emotionally neutral words. A third group was told to talk about an unrelated topic (things in their home) and a fourth group received no intervention. Participants who put their negative feelings into words were most effective at lowering their levels of physiological arousal. They were also slightly more willing to approach the spider. The findings suggest that talking about your feelings — even if they’re negative — may help you to cope with a scary situation.
Unlocking Past Emotion: The Verbs We Use Can Affect Mood and Happiness
Our memory for events is influenced by the language we use. When we talk about a past occurrence, we can describe it as ongoing (I was running) or already completed (I ran). To investigate whether using these different wordings might affect our mood and overall happiness, Will Hart of the University of Alabama conducted four experiments in which participants either recalled or experienced a positive, negative, or neutral event. They found that people who described a positive event with words that suggested it was ongoing felt more positive. And when they described a negative event in the same way, they felt more negative.
The authors conclude that one potential way to improve mood could be to talk about negative past events as something that already happened as opposed to something that was happening.
Source: Science Daily
ScienceDaily (Aug. 23, 2012) — Scientists at the University of Houston (UH) have discovered what may possibly be a key ingredient in the fight against Parkinson’s disease.
Affecting more than 500,000 people in the U.S., Parkinson’s disease is a degenerative disorder of the central nervous system marked by a loss of certain nerve cells in the brain, causing a lack of dopamine. These dopamine-producing neurons are in a section of the midbrain that regulates body control and movement. In a study recently published in the Proceedings of the National Academy of Sciences (PNAS), researchers from the UH Center for Nuclear Receptors and Cell Signaling (CNRCS) demonstrated that the nuclear receptor liver X receptor beta (LXRbeta) may play a role in the prevention and treatment of this progressive neurodegenerative disease.
"LXRbeta performs an important function in the development of the central nervous system, and our work indicates that the presence of LXRbeta promotes the survival of dopaminergic neurons, which are the main source of dopamine in the central nervous system," said CNRCS director and professor Jan-Åke Gustafsson, whose lab discovered LXRbeta in 1995. "The receptor continues to show promise as a potential therapeutic target for this disease, as well as other neurological disorders."
To better understand the relationship between LXRbeta and Parkinson’s disease, the team worked with a potent neurotoxin, called MPTP, a contaminant found in street drugs that caused Parkinson’s in people who consumed these drugs. In lab settings, MPTP is used in murine models to simulate the disease and to study its pathology and possible treatments.
The researchers found that the absence of LXRbeta increased the harmful effects of MPTP on dopamine-producing neurons. Additionally, they found that using a drug that activates LXRbeta receptors prevented the destructive effects of MPTP and, therefore, may offer protection against the neurodegeneration of the midbrain.
"LXRbeta is not expressed in the dopamine-producing neurons, but instead in the microglia surrounding the neurons," Gustafsson said. "Microglia are the police of the brain, keeping things in order. In Parkinson’s disease the microglia are overactive and begin to destroy the healthy neurons in the neighborhood of those neurons damaged by MPTP. LXRbeta calms down the microglia and prevents collateral damage. Thus, we have discovered a novel therapeutic target for treatment of Parkinson’s disease."
Source: Science Daily
Better diagnosis and treatment of a crippling inherited nerve disorder may be just around the corner thanks to an international team that spanned Asia, Europe and the United States. The team had been hunting DNA strands for the cause of the inherited nerve disorder known as spinocerebellar ataxia, or SCA. The disease causes progressive loss of balance, muscle control and ability to walk. Thanks to their diligence and detective work they have discovered the disease gene in a region of chromosome 1 where another group from the Netherlands had previously shown linkage with a form of SCA called SCA19, and the Taiwanese group on the new paper had shown similar linkage in a family for a form of the disease that was then called SCA22. The international team, from France, Japan, Taiwan and the USA have published their discovery in the Annals of Neurology. The Dutch group has also published results in the same issue of the journal.
Their paper reveals that mutations in the gene KCND3 were found in six families in Asia, Europe and the United States that have been haunted by SCA. Their results will allow for a better understanding of why nerves in the brain’s movement-controlling centre die, and how new DNA mapping techniques can find the causes of other diseases that run in families.
Margit Burmeister, Ph.D., a geneticist at University of Michigan Health System (U-M), helped lead the work and stressed that the gene could not have been found without a great deal of DNA detective work and the cooperation of the families who volunteered to let researchers map all the DNA of multiple members of their family tree. ‘We combined traditional genetic linkage analysis in families with inherited diseases with whole exome sequencing of an individual’s DNA, allowing us to narrow down and ultimately identify the mutation,’ she says. ‘This new type of approach has already resulted in many new gene identifications, and will bring in many more.’
The gene is very important as it manages the production of a protein that allows nerve cells to ‘talk’ to one another through the flow of potassium. Pinpointing its role as a cause of ataxia will now allow more people with ataxia to learn the exact cause of their disease, give a very specific target for new treatments, and perhaps allow the families to stop the disease from affecting future generations.
U-M neurologist Vikram Shakkottai, M.D., Ph.D., an ataxia specialist and co-author on the paper, also notes that the new genetic information will help patients find out the specific cause of their disease. He and his colleagues are already working to find drugs that might alter potassium flow, and provide a treatment for a group of diseases that currently are only treated with supportive care such as physical activity and balance training as patients deteriorate. ‘Many of the families who come to our clinic for treatment don’t have a recognised genetic mutation, so it’s important to find new genetic mutations to explain their symptoms,’ says Shakkottai. ‘But at the same time, this research is helping us understand a common mechanism of nerve cell dysfunction in progressive and non-progressive disease.’
Their findings however are not restricted to just ataxia. The researchers were also able to show that when KCND3 is mutated, it causes poor communication between nerve cells in the cerebellum as well as the death of those cells. This discovery could aid research on other neurological disorders involving balance and movement.
The Dutch team, that also published its findings about KCND3 at the same time, studied families in the Netherlands and found that mutations on the gene are responsible for SCA19, the cause of which had up until now been a mystery. ‘In other words, mutations in this gene are not uncommon and present all over the world,’ says Burmeister. ‘This means that in the future, this gene should be tested for mutations as part of a clinical genetic test panel for patients with ataxia symptoms. Because a generation can be skipped, it may even be relevant in some sporadic cases - those where the patient isn’t aware of any other family members with a similar disease.’
Source: Cordis News
Helium reveals gibbon’s soprano skill
Apes are unlikely to become virtuosos at the opera house, but gibbons have naturally mastered some of the vocal techniques that human sopranos rely on, scientists in Japan report.
The research shows that, like humans, gibbons use a ‘source–filter’ mode of sound generation. The sound originates from the creatures’ vocal folds as a mixture of different harmonics, which are multiples of the frequency at which the vocal folds vibrate. The resonant frequencies of the vocal tract then determine which of these harmonics are projected. By altering the position of the mouth, lips and teeth, humans vary these resonant frequencies to make the different sounds required for speech.
The gibbon’s melodious calling bears many similarities to the techniques of human singers. Like professional sopranos, gibbons tune the resonant frequency of their vocal tract to the pitch frequency generated by the vocal folds to amplify the sound. Acoustic physicist Joe Wolfe of the University of New South Wales in Sydney, Australia, says that this type of “resonance tuning” is something that comes fairly easily to human singers and is key to their ability to project their voice over a loud orchestra.
22 August 2012
Scientists have found a switch in the brain which may explain why smoking cannabis causes psychosis and addiction in more than one-in-ten users.
The team, at Aberdeen University found a genetic difference in the switch, probably inherited from early humans who smoked the drug in prehistoric times. The difference may also explain why some people could be more susceptible to conditions such as obesity.
The researchers, at the university’s Kosterlitz Centre for Therapeutics, studied genetic differences around a gene called ‘CNR1’, which produces what are known as cannabinoid receptors in the brain which control parts of the brain involved in memory, mood, appetite and pain.
Cannabinoid receptors activate these areas of the brain when they are triggered by naturally-occurring chemicals in the body known as endocannabinoids. Chemicals found in the cannabis and ‘skunk’ mimic the action of endocannabinoids. It is known that cannabis has pain-relieving and anti-inflammatory properties which can help treat diseases such as multiple sclerosis and arthritis.
However, developing drugs from cannabis to treat these conditions is hampered by the fact that such drugs will have psychoactive side effects - and smoked cannabis can cause addiction and psychosis in up to 12 per cent of users.
Dr Alasdair MacKenzie, who led the research, said:
We looked at one specific genetic difference in CNR1 because we know it is linked to obesity and addiction. What we found was a mutation that caused a change in the genetic switch for the gene itself - a switch that is very ancient and has remained relatively unchanged in over three hundred million years of evolution, since before the time of the dinosaurs.
These genetic ‘switches’ regulate the gene itself, ensuring that it is turned on or off in the right place at the right time and in the right amount. It is normally thought that mutations cause disease by reducing the function of the gene, or the switch that controls it. In this case however, the mutation actually increased the activity of the switch in parts of the brain that control appetite and pain, and also, and most especially, in the part of the brain called the hippocampus, which is affected in psychosis.
He added: We know that this overactive switch is relatively rare in Europeans, but is quite common in African populations. But we were all once African, so something must have decreased it in our early ancestors who left Africa and migrated through Central Asia towards Europe and the north. One possibility we are keen to explore is that once in Central Asia these early migrants came into contact with the cannabis plant, which we know was endemic across that area at that time.
It is possible that the side effects of taking cannabis were such that people with the mutation were not so effective in producing and raising children. Therefore, over the generations the numbers of people with the mutation decreased.
This work is at a very early stage however, and there are likely to be more exciting discoveries - not only on how these differences came about, but also about the role of this genetic switch in health and disease.
Co-researcher Dr Scott Davidson said: Further analysis of this mutation will help us to understand many of the side effects which are associated with cannabis use such as addiction and psychosis.
Professor Ruth Ross, head of the Kosterlitz Centre, an internationally recognised expert in cannabis pharmacology, said: Previously in drug research, attempts to detect the causes of adverse drug reactions have focused on the genes themselves.
Our study is one of the first to explore the possibility that changes in gene switches are involved in causing side effects to drugs. We believe this approach will be crucially important in the future development of more effective personalised medicine, with fewer side effects.
One question that is intriguing the research team is why this overactive genetic switch evolved in the first place.
A collaborative research effort by scientists at the University of North Carolina School of Medicine, Duke University, and University College of London in the UK, sheds new light on alcohol-related birth defects.
The project, led by Kathleen K. Sulik, PhD, a professor in the Department of Cell and Developmental Biology and the Bowles Center for Alcohol Studies at UNC, could help enhance how doctors diagnose birth defects caused by alcohol exposure in the womb. The findings also illustrate how the precise timing of that exposure could determine the specific kinds of defects.
“We now know that maternal alcohol use is the leading known and preventable cause of birth defects and mental disability in the United States,” Sulik said. “Alcohol’s effects can cause a range of cognitive, developmental and behavioral problems that typically become evident during childhood, and last a lifetime.”
Fetal alcohol syndrome (FAS) is at the severe end of fetal alcohol spectrum disorders (FASD). First described in 1972, FAS is recognized by a specific pattern of facial features: small eyelid openings, a smooth ridge on the upper lip (absence of a central groove, or philtrum), and a thin upper lip border.
In its full-blown state, FAS affects roughly 1 in 750 live births in the U.S. And while clinicians typically look for those classical facial features in making a diagnosis, within the broader classification of FASD “adverse outcomes vary considerably and most individuals don’t exhibit the facial characteristics that currently define FAS,” said the study’s lead author Robert J. Lipinski, PhD, a postdoctoral scientist in Sulik’s lab. “This study could expand the base of diagnostic criteria used by clinicians who suspect problems caused by maternal alcohol use.”
In their animal-based studies, the Sulik lab team has collaborated with co-author G. Allan Johnson, PhD and his group at Duke University’s Center for In Vivo Microscopy. Johnson, professor of radiology and physics, has developed new imaging tools with spatial resolution up to a million times higher than clinical magnetic resonance imaging (MRI). These include small bore tools suitable for imaging fetal mice that are only 15 mm long.
To quantify facial shape from MRI data, the study team turned to co-author Peter Hammond, a professor of computational biology at UCL’s Institute of Child Health, in London. Hammond invented powerful new techniques for 3D shape analysis that have already proven successful in objectively defining facial shape changes in humans.
In the study, described in the August 22, 2012 issue of the online journal PLOS ONE, Lipinski and Sulik treated one group of mice with alcohol on their seventh day of pregnancy, a time corresponding to the third week of pregnancy in humans. A second group of mice was treated just 36 hours later, approximating the fourth week of human pregnancy. The amount of alcohol given was large, “high doses that most women wouldn’t achieve unless they were alcoholic and had a tolerance for alcohol,” Sulik said.
Near the end of pregnancy, the fetuses were then imaged at Duke University. These 3D data sets showed individual brain regions, as well as accurate and detailed facial surfaces, from which Hammond and research assistant and co-author Michael Suttie performed shape analyses.
The team found that the earlier alcohol exposure time elicited the classic FAS facial features, including characteristic abnormalities of the upper lip and eyes. What they observed in fetuses exposed just 36 hours later, however, was a surprise. These mice exhibited unique and in some cases opposing facial patterns, such as shortened upper lip, a present philtrum, and the brain, instead of appearing too narrow in the front, appeared wide.
“Overall, the results of our studies show that alcohol can cause more than one pattern of birth defects, and that the type and extent of brain abnormalities—which are the most devastating manifestation of prenatal alcohol exposure—in some cases may be predicted by specific facial features,” Sulik said. “And, importantly, alcohol can cause tremendously devastating and permanent damage at a time in development when most women don’t recognize that they’re pregnant.”
Source: Newswise
August 22, 2012
Animals that literally have holes in their brains can go on to behave as normal adults if they’ve had the benefit of a little cognitive training in adolescence. That’s according to new work in the August 23 Neuron, a Cell Press publication, featuring an animal model of schizophrenia, where rats with particular neonatal brain injuries develop schizophrenia-like symptoms.
"The brain can be loaded with all sorts of problems," said André Fenton of New York University. "What this work shows is that experience can overcome those disabilities."
Fenton’s team made the discovery completely by accident. His team was interested in what Fenton considers a core problem in schizophrenia: the inability to sift through confusing or conflicting information and focus on what’s relevant.
"As you walk through the world, you might be focused on a phone conversation, but there are also kids in the park and cars and other distractions," he explained. "These information streams are all competing for our brain to process them. That’s a really challenging situation for someone with schizophrenia."
Fenton and his colleagues developed a laboratory test of cognitive control needed for that kind of focus. In the test, rats had to learn to avoid a foot shock while they were presented with conflicting information. Normal rats can manage that task quickly. Rats with brain lesions can also manage this task, but only up until they become young adults—the equivalent of an 18- or 20-year-old person—when signs of schizophrenia typically set in.
While that was good to see, Fenton says, it wasn’t really all that surprising. But then some unexpected circumstances in the lab led them to test animals with adolescent experience in the cognitive control test again, once they had grown into adults.
These rats should have shown cognitive control deficits, similar to those that had not received prior cognitive training, or so the researchers thought. Instead, they were just fine. Their schizophrenic symptoms had somehow been averted.
Fenton believes their early training for focus forged some critical neural connections, allowing the animals to compensate for the injury still present in their brains in adulthood. Not only were the animals’ behaviors normalized with training, but the patterns of activity in their brains were also.
The finding is consistent with the notion that mental disorders are the consequence of problems in brain development that might have gotten started years before. They raise the optimistic hope that the right kinds of experiences at the right time could change the future by enabling people to better manage their diseases and better function in society. Adolescence, when the brain undergoes significant change and maturation, might be a prime time for such training.
"You may have a damaged brain, but the consequences of that damage might be overcome without changing the damage itself," Fenton says. "You could target schizophrenia, but other disorders aren’t very different," take autism or depression, for example.
And really, in this world of infinite distraction, couldn’t we all use a little more cognitive control?
Source: medicalxpress.com
22 August 2012 by Ewen Callaway
Genome study may explain links between paternal age and conditions such as autism.
Older fathers’ sperm have more mutations — as do their children.
V. Peñafiel/Flickr/GETTY
In the 1930s, the pioneering geneticist J. B. S. Haldane noticed a peculiar inheritance pattern in families with long histories of haemophilia. The faulty mutation responsible for the blood-clotting disorder tended to arise on the X chromosomes that fathers passed to their daughters, rather than on those that mothers passed down. Haldane subsequently proposed that children inherit more mutations from their fathers than their mothers, although he acknowledged that “it is difficult to see how this could be proved or disproved for many years to come”.
22 August 2012 by Kai Kupferschmidt
In June of last year, a 43-year old woman was admitted to the Clinical Center of the National Institutes of Health in Bethesda, Maryland, for a lung disease. Doctors knew she was carrying a highly resistant form of a deadly bacterium known as Klebsiella pneumoniae—although it didn’t make her sick—and they placed her in isolation. When the woman was discharged, no one else appeared to have become infected. A few weeks later, however, another patient was found to be carrying the bacterium, and over the next 3 months, 12 more intensive care patients contracted it. Six died as a direct result of the infection.
Doctors could not make sense of the outbreak with the usual methods: A survey of bed locations showed that the first patient had had no direct contact with any of the others and, in theory, Klebsiella might have been introduced into the hospital multiple times. So physicians turned to the bacterium’s genome for answers. The approach, known as genomic epidemiology, helped them track the path of the microbe, contain the disease, and save lives, according to a new study.
Tracking a killer. Full-genome sequencing revealed the movements of Klebsiella (shown) within one hospital. Credit: Image courtesy of Adrian Zelazny
Genomic epidemiology makes use of the fact that when bacteria divide, they accumulate mutations. As a result, the bacterial genome differs slightly—often by just one or two letters of genetic code, or base pairs—from one patient to the next. By fully sequencing the genomes of patients’ bacteria and finding these minute differences, researchers can track microbial movements with unprecedented precision. The technique has already been used to reconstruct the spread of methicillin-resistant Staphylococcus aureus (MRSA) around the world and to pinpoint the origin of a cholera outbreak in Haiti.
It also helped the doctors at the hospital in Bethesda. Comparing the genomes from all patients showed that the female patient admitted in June had indeed initiated the outbreak; the researchers showed that the bacteria had been transmitted from her to other patients three times independently. Apparently, transmission occurred in ways the researchers didn’t understand, says Tara Palmore, an infectious disease physician at the hospital. “When we realized there was more than met the eye, we started testing everyone in the hospital,” she says. That helped identify four more infected patients outside the intensive care unit, the scientists report online today in Science Translational Medicine. They were quickly isolated, which Palmore believes prevented further spread.
Just how the microbes were transmitted is still unclear. Palmore assumes that the bacteria mainly traveled on the hands of doctors. But the clinic had stationed a person outside the isolation rooms to make sure everyone who entered followed a hygiene regimen 24/7. That suggests that bacteria might have established colonies on surfaces or medical equipment and spread that way as well. “The conventional wisdom is that Klebsiellas do not really survive in the environment, but we found them in six sink drains and a ventilator,” Palmore says.
"This small study demonstrates the potential power of whole genome sequencing for outbreak investigation and surveillance," says Sharon Peacock, a microbiologist at the University of Cambridge in the United Kingdom who was not involved in the work. And infectious disease specialist Dag Harmsen of the University Clinic of Münster in Germany says it is "further proof that the time is ripe for using genomic sequencing of pathogens in a hospital setting." The paper also highlights the dangers of resistant Gram-negative bacteria like Klebsiella p., he adds. In many patients, the bacteria were not susceptible to any available antibiotic; not even to colistin, an old compound used only when all else fails. “This is even more dramatic than MRSA, because you have nothing left to treat the patients with,” Harmsen says. Since the outbreak, every patient at the hospital is checked for such dangerous pathogens; one more resistant Klebsiella case—although a different strain—has been found so far.
Genomic epidemiology could make it easier for hospitals to deal with similar outbreaks, Palmore says. “A lot of academic centers have the ability to do this now,” she says. The cost is becoming less of an issue; during last year’s outbreak, scientists still paid about $2000 per genome sequenced; now that would be closer to $500. But Peacock cautions that it still takes bioinformatics specialists several weeks to interpret the data. “This technology will not be applicable to routine clinical practice until automated interpretation tools become available.”
ScienceDaily (Aug. 22, 2012) — A low dose of the sedative clonazepam alleviated autistic-like behavior in mice with a mutation that causes Dravet syndrome in humans, University of Washington researchers have shown.
(Credit: © Vasiliy Koval / Fotolia)
Dravet syndrome is an infant seizure disorder accompanied by developmental delays and behavioral symptoms that include autistic features. It usually originates spontaneously from a gene mutation in an affected child not found in either parent.
Studies of mice with a similar gene mutation are revealing the overly excited brain circuits behind the autistic traits and cognitive impairments common in this condition. The research report appears in the Aug. 23 issue of Nature. Dr William Catterall, professor and chair of pharmacology at the UW, is the senior author.
Dravet syndrome mutations cause loss-of-function of the human gene called SCN1A. People or mice with two copies of the mutation do not survive infancy; one copy results in major disability and sometimes early death. The mutation causes malformation in one type of sodium ion channels, the tiny pores in nerve cells that produce electrical signals by gating the flow of sodium ions.
The Catteralll lab is studying these defective ion channels and their repercussion on cell-to-cell signaling in the brain. They also are documenting the behavior of mice with this mutation, compared to their unaffected peers. Their findings may help explain how the sporadic gene mutations that cause Dravet syndrome lead to its symptoms of cognitive deficit and autistic behaviors.
Scientists at Georgia State University have found that the ability to hear is lessened when, as a result of injury, a region of the brain responsible for processing sounds receives both visual and auditory inputs.
Yu-Ting Mao, a former graduate student under Sarah L. Pallas, professor of neuroscience, explored how the brain’s ability to change, or neuroplasticity, affected the brain’s ability to process sounds when both visual and auditory information is sent to the auditory thalamus.
The study was published in the Journal of Neuroscience.
The auditory thalamus is the region of the brain responsible for carrying sound information to the auditory cortex, where sound is processed in detail.
When a person or animal loses input from one of the senses, such as hearing, the region of the brain that processes that information does not become inactive, but instead gets rewired with input from other sensory systems.
In the case of this study, early brain injury resulted in visual inputs into the auditory thalamus, which altered how the auditory cortex processes sounds.
The cortical “map” for discriminating different sound frequencies was significantly disrupted, she explained.
“One of the possible reasons the sound frequency map is so disrupted is that visual responsive neurons are sprinkled here and there, and we also have a lot of single neurons that respond to both light and sound,” Pallas said. “So those strange neurons sprinkled there probably keeps the map from forming properly.”
Mao also discovered reduced sensitivity and slower responses of neurons in the auditory cortex to sound.
Finally, the neurons in the auditory cortex were less sharply tuned to different frequencies of sound.
“Generally, individual neurons will be pretty sensitive to one sound frequency that we call their ‘best frequency,’” Pallas said. “We found that they would respond to a broader range of frequencies after the rewiring with visual inputs.”
While Pallas’ research seeks to create a basic understanding of brain development, knowledge gained from her lab’s studies may help to give persons who are deaf, blind, or have suffered brain injuries ways to keep visual and auditory functions from being compromised.
“Usually we think of plasticity as a good thing, but in this case, it’s a bad thing,” she said. “We would like to limit the plasticity so that we can keep the function that’s supposed to be there.”
Source: Georgia State University