Posts tagged science
Articles and news from the latest research reports.
Meat, egg and dairy nutrient essential for brain development
Asparagine, found in foods such as meat, eggs, and dairy products, was until now considered non-essential because it is produced naturally by the body. Researchers at the University of Montreal and its affiliated CHU Sainte-Justine Hospital found that the amino acid is essential for normal brain development. This is not the case for other organs. “The cells of the body can do without it because they use asparagine provided through diet. Asparagine, however, is not well transported to the brain via the blood-brain barrier,” said senior co-author of the study Dr. Jacques Michaud, who found that brain cells depend on the local synthesis of asparagine to function properly. First co-author José-Mario Capo-Chichi and colleague Grant Mitchell also made major contributions to the study.
In April 2009, a Quebec family experienced the worst tragedy for parents: before the age of one, one of their sons died of a rare genetic disease causing congenital microcephaly, intellectual disability, cerebral atrophy, and refractory seizures. The event was even more tragic because it was the third infant to die in this family from the same disease.
This tragedy led Dr. Michaud to discover the genetic abnormality responsible for this developmental disorder. “We are not at the verge of a miracle drug,” Michaud said, “but we at least know where to look.”
The team identified the gene affected by the mutation code for asparagine synthetase, the enzyme responsible for synthesizing the amino acid asparagine. The study is the first to associate a specific genetic variant with a deficiency of this enzyme. “In healthy subjects, it seems that the level of asparagine synthetase in the brain is sufficient to supply neurons,” Michaud said. “In individuals with the disability, the enzyme is not produced in sufficient quantity, and the resulting asparagine depletion affects the proliferation and survival of cells during brain development.”
Potential treatment
Children who are carriers of this mutation suffer, to varying degrees, from a variety of symptoms, including intellectual disability and cerebral atrophy, which can lead to death. The Quebec family lost three infant sons to this disorder. Two of their other children are alive and healthy.
Knowledge about gene mutations can be used to develop treatments. “Our results not only open the door to a better understanding of the disease,” Michaud said, “but they also give us valuable information about the molecular mechanisms involved in brain development, which is important for the development of new treatments.”
For example, asparagine supplement could be given to infants to ensure an adequate level of asparagine in the brain and the latter’s normal development. “The amount of supplementation remains to be determined, as well as its effectiveness,” said the geneticist. “Since these children are already born with neurological abnormalities, it is uncertain whether this supplementation would correct the neurological deficits.”
Creating a pediatric clinical genomics centre
To date, nine children from four different families have been identified as carriers of the mutation: three infants from Quebec, three from a Bengali family living in Toronto, and three Israelis, whose symptoms are less severe.
Dr. Michaud’s team discovered the genetic mutation by comparing the complete DNA of the Quebec family’s children with symptoms of the disease. The researchers then identified children, among other families, who carried the single candidate gene. The gene was revealed only in the affected children, but not in the unaffected children of the families studied.
The discovery comes at a time when CHU Sainte-Justine Mother and Child University Hospital has reached an agreement with Génome Québec to create the first pediatric clinical genomic centre in Canada. “This initiative will transform the quality of care for younger patients to ensure better prevention from childhood,” says Dr. Michaud. “More than 80% of genetic diseases occur in childhood or adolescence. “This new technology will allow us to sequence all the genes in the genome and obtain a genetic portrait of the children more quickly to know which disease they suffer from and to provide treatment, if available, or when it becomes available.”
(Source: nouvelles.umontreal.ca)
Broken cellular ‘clock’ linked to brain damage
A new discovery may help explain the surprisingly strong connections between sleep problems and neurodegenerative conditions such as Alzheimer’s disease. Sleep loss increases the risk of Alzheimer’s disease, and disrupted sleeping patterns are among the first signs of this devastating disorder.
Scientists at Washington University School of Medicine in St. Louis and the University of Pennsylvania have shown that brain cell damage similar to that seen in Alzheimer’s disease and other disorders results when a gene that controls the sleep-wake cycle and other bodily rhythms is disabled.
The researchers found evidence that disabling a circadian clock gene that controls the daily rhythms of many bodily processes blocks a part of the brain’s housekeeping cycle that neutralizes dangerous chemicals known as free radicals.
“Normally in the hours leading up to midday, the brain increases its production of certain antioxidant enzymes, which help clean up free radicals,” said first author Erik Musiek, MD, PhD, assistant professor of neurology at the School of Medicine. “When clock genes are disabled, though, this surge no longer occurs, and the free radicals may linger in the brain and cause more damage.”
Musiek conducted the research in the labs of Garret FitzGerald, MD, chairman of pharmacology at the University of Pennsylvania, and of David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology at Washington University School of Medicine, who are co-senior authors.
The study appears Nov. 25 in The Journal of Clinical Investigation.
Musiek studied mice lacking a master clock gene called Bmal1. Without this gene, activities that normally occur at particular times of day are disrupted.
“For example, mice normally are active at night and asleep during the day, but when Bmal1 is missing, they sleep equally in the day and in the night, with no circadian rhythm,” Musiek said. “They get the same amount of sleep, but it’s spread over the whole day. Rhythms in the way genes are expressed are lost.”
FitzGerald uses mice lacking Bmal1 to study whether clock cells have links to diabetes and heart disease. He has shown that clock genes influence blood pressure, blood sugar and lipid levels.
Several years ago, Musiek, who at the time was a neurology resident at the University of Pennsylvania, and FitzGerald decided to investigate how knocking out Bmal1 affects the brain. Holtzman, who has published pioneering work on sleep and Alzheimer’s disease, encouraged Musiek to continue and expand these studies when he came to Washington University as a postdoctoral fellow.
In the new study, Musiek found that as the mice aged, many of their brain cells became damaged and did not function normally. The patterns of damage were similar to those seen in Alzheimer’s disease and other neurodegenerative disorders.
“Brain cell injury in these mice far exceeded that normally seen in aging mice,” Musiek said. “Many of the injuries appear to be caused by free radicals, which are byproducts of metabolism. If free radicals come into contact with brain cells or other tissue, they can cause damaging chemical reactions.”
This led Musiek to examine the production of key antioxidant enzymes, which usually neutralize and help clear free radicals from the brain, thereby limiting damage. He found levels of several antioxidant proteins peak in the middle of the day in healthy mice. However, this surge is absent in mice lacking Bmal1. Without the surge, free radicals may remain in the brain longer, contributing to the damage Musiek observed.
“We’re trying to identify more specifics about how problems in clock genes contribute to neurodegeneration, both with and without influencing sleep,” Musiek said. “That’s a challenging distinction to make, but it needs to be made because clock genes appear to control many other functions in the brain in addition to sleeping and waking.”
(Source: news.wustl.edu)
Navigational ability is visible in the brain
The brains of people who immediately know their way after travelling along as a passenger are different from the brains of people who always need a GPS system or a map to get from one place to another. This was demonstrated by Joost Wegman, who will defend his thesis at Radboud University Nijmegen, the Netherlands on the 27th of November.
Wegman demonstrates that good navigators store relevant landmarks automatically on their way. Bad navigators on the other hand, often follow a fixed procedure or route (such as: turn left twice, then turn right at the statue).
Anatomical differences
Wegman also found that there are detectable structural differences between the brains of good and bad navigators. ‘These anatomical differences are not huge, but we found them significant enough, because we had a lot of data’, the researcher explains. ‘The difference is in the hippocampus. We saw that good navigators had more so-called gray matter. In the brain’s gray matter information is processed. Bad navigators, on the other hand, have more white matter - which connects gray matter areas with each other - in a brain area called the caudate nucleus. This area stores spatial actions with respect to oneself. For example, to turn right at the record store’, Wegman describes.
Questionnaires
For his research, Wegman combined data from several studies done by the Radboud University research group Neural Correlates of Spatial Memory at the Donders Institute for Brain, Cognition and Behaviour.
Wegman: ‘We always give participants extensive questionnaires in our studies. This allows us to explain possible differences in behaviour afterwards. People generally have a good insight into their ability to find their way, so these questions provide a feasible way to assess these abilities. I have coupled the answers of these questionnaires with the brain scans we have collected over the years, which allowed us to detect these differences’.
Objects in space - the neural basis of landmark-based navigation and individual differences in navigational ability (PhD defence)
Wednesday 27 November 2013, promotors: prof. dr. L.T.W. Verhoeven, prof. dr. P. Hagoort,
copromotor: dr. G. Janzen
The papers to which this article refers are both included in Joost Wegman’s thesis:
1. Wegman, J. & Janzen, G. Neural encoding of objects relevant for navigation and resting state correlations with navigational ability. Journal of Cognitive Neuroscience 23, 3841-3854 (2011).
2. Wegman, J. et al. Gray and white matter correlates of navigational ability in humans. Human Brain Mapping (in press).
A gene mutation for excessive alcohol drinking found
Researchers have discovered a gene that regulates alcohol consumption and when faulty can cause excessive drinking. They have also identified the mechanism underlying this phenomenon.
The study showed that normal mice show no interest in alcohol and drink little or no alcohol when offered a free choice between a bottle of water and a bottle of diluted alcohol.
However, mice with a genetic mutation to the gene Gabrb1 overwhelmingly preferred drinking alcohol over water, choosing to consume almost 85% of their daily fluid as drinks containing alcohol - about the strength of wine.
The consortium of researchers from five UK universities – Newcastle University, Imperial College London, Sussex University, University College London and University of Dundee – and the MRC Mammalian Genetics Unit at Harwell, funded by the Medical Research Council (MRC), Wellcome Trust and ERAB, publish their findings today in Nature Communications.
Dr Quentin Anstee, Consultant Hepatologist at Newcastle University, joint lead author said: “It’s amazing to think that a small change in the code for just one gene can have such profound effects on complex behaviours like alcohol consumption.
“We are continuing our work to establish whether the gene has a similar influence in humans, though we know that in people alcoholism is much more complicated as environmental factors come into play. But there is the real potential for this to guide development of better treatments for alcoholism in the future.”
Identifying the gene for alcohol preference
Working at the MRC Mammalian Genetics Unit, a team led by Professor Howard Thomas from Imperial College London introduced subtle mutations into the genetic code at random throughout the genome and tested mice for alcohol preference. This led the researchers to identify the gene Gabrb1 which changes alcohol preference so strongly that mice carrying either of two single base-pair point mutations in this gene preferred drinking alcohol (10% ethanol v/v - about the strength of wine), over water.
The group showed that mice carrying this mutation were willing to work to obtain the alcohol-containing drink by pushing a lever and, unlike normal mice, continued to do so even over long periods. They would voluntarily consume sufficient alcohol in an hour to become intoxicated and even have difficulty in coordinating their movements.
The cause of the excessive drinking was tracked down to single base-pair point mutations in the gene Gabrb1, which codes for the beta 1 subunit, an important component of the GABAA receptor in the brain. This receptor responds to the brain’s most important inhibitory chemical messenger (GABA) to regulate brain activity. The researchers found that the gene mutation caused the receptor to activate spontaneously even when the usual GABA trigger was not present.
These changes were particularly strong in the region of the brain that controls pleasurable emotions and reward, the nucleus accumbens, as Dr Anstee explains: “The mutation of the beta1 containing receptor is altering its structure and creating spontaneous electrical activity in the brain in this pleasure zone, the nucleus accumbens. As the electrical signal from these receptors increases, so does the desire to drink to such an extent that mice will actually work to get the alcohol, for much longer than we would have expected.”
Professor Howard Thomas said: “We know from previous human studies that the GABA system is involved in controlling alcohol intake. Our studies in mice show that a particular subunit of GABAA receptor has a significant effect and most importantly the existence of these mice has allowed our collaborative group to investigate the mechanism involved. This is important when we come to try to modify this process first in mice and then in man.”
Leading to a treatment for alcohol addiction
Initially funded by the MRC, the 10-year project aimed to find genes affecting alcohol consumption. Professor Hugh Perry, Chair of the MRC’s Neurosciences and Mental Health Board, said: “Alcohol addiction places a huge burden on the individual, their family and wider society. There’s still a great deal we don’t understand about how and why consumption progresses into addiction, but the results of this long-running project suggest that, in some individuals, there may be a genetic component. If further research confirms that a similar mechanism is present in humans, it could help us to identify those most at risk of developing an addiction and ensure they receive the most effective treatment.”
New therapeutic target identified for Huntington’s disease
A new study published 26th November in the open access journal PLOS Biology, identifies a new target in the search for therapeutic interventions for Huntington’s disease – a devastating late-onset neurodegenerative disorder.
The disease is genetic, affecting up to one person in 10,000, and from the age of about 35 leads to increasingly severe problems with movement, mental function, and behavior. Patients usually die within 20 years of onset, and there is to date no treatment that will modify the disease onset or progression.
Huntington’s disease is caused by an unusual type of mutation in a gene that encodes the “huntingtin” protein. These mutations create long stretches of the amino acid glutamine within the protein chain, preventing huntingtin from folding properly and making it more ‘sticky’. This causes huntingtin proteins to self-aggregate in both the nucleus and cytoplasm of cells, disrupting multiple aspects of cellular function and ultimately leading to the progressive death of nerve cells.
Nuclear huntingtin aggregates have been found to interfere with the transcription of many genes, and previous work has shown beneficial effects for Huntington’s disease of inhibiting a family of enzymes that are normally thought to regulate transcription – the histone deacetylases, or HDACs. However, humans have eleven different HDAC enzymes, and it’s been uncertain exactly which HDAC needs to be inhibited to see these benefits.
The new study from Michal Mielcarek, Gillian Bates and colleagues at King’s College London has pinpointed just one of these enzymes as the target – HDAC4 – but with an intriguing twist; everything is happening in the cytoplasm, not the nucleus, and HDAC4’s classic role in transcription has little to do with it.
The researchers noted that the HDAC4 protein naturally contains a region that, like mutant huntingtin, is rich in the amino acid glutamine. They show that HDAC4 can associate directly with huntingtin protein in a manner that depends on the length of the glutamine tracts, but that this association between HDAC4 and huntingtin occurs in the cytoplasm of nerve cells in the mouse brain, and – surprisingly – not in the nucleus, where HDAC4 is known to have its transcriptional role.
Bates and colleagues did their work in an aggressive disease mouse model of Huntington’s disease – the gold standard model for this type of study. They find that halving the levels of HDAC4 in the cells of Huntington’s disease mice can delay the aggregation of huntingtin in the cytoplasm, thereby identifying a new route to modulating the toxicity of mutant huntingtin protein. Crucially, reducing HDAC4 levels can also rescue the overall function of nerve cells and their synapses, with corresponding improvements seen in coordination of movement, neurological performance and lifespan of the mice. In agreement with the cytoplasmic association between HDAC4 and huntingtin, this all happens without any obvious improvement in the defective gene transcription in the nucleus.
There are currently no disease-modifying therapeutics available for Huntington’s disease. It is still very early days and it is important to note that the medical applications of any therapy arising from this study have not been studied in a clinical setting and are far from clear. However, one broad-brush HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) had previously been shown to improve movement defects in preclinical tests in this mouse model. The authors have shown in a related publication that, in addition to inhibiting HDAC enzyme function, SAHA decreases levels of the HDAC4 protein. Therefore it is hoped that the development of HDAC4-targeted compounds may be a promising strategy in improving the lot of Huntington’s disease patients.
(Source: eurekalert.org)
Memories Are ‘Geotagged’ With Spatial Information
Using a video game in which people navigate through a virtual town delivering objects to specific locations, a team of neuroscientists from the University of Pennsylvania and Freiburg University has discovered how brain cells that encode spatial information form “geotags” for specific memories and are activated immediately before those memories are recalled.
Their work shows how spatial information is incorporated into memories and why remembering an experience can quickly bring to mind other events that happened in the same place.
"These findings provide the first direct neural evidence for the idea that the human memory system tags memories with information about where and when they were formed and that the act of recall involves the reinstatement of these tags," said Michael Kahana, professor of psychology in Penn’s School of Arts and Sciences.
The study was led by Kahana and professor Andreas Schulze-Bonhage of Freiberg. Jonathan F. Miller, Alec Solway, Max Merkow and Sean M. Polyn, all members of Kahana’s lab, and Markus Neufang, Armin Brandt, Michael Trippel, Irina Mader and Stefan Hefft, all members of Schulze-Bonhage’s lab, contributed to the study. They also collaborated with Drexel University’s Joshua Jacobs.
Their study was published in the journal Science.
Kahana and his colleagues have long conducted research with epilepsy patients who have electrodes implanted in their brains as part of their treatment. The electrodes directly capture electrical activity from throughout the brain while the patients participate in experiments from their hospital beds.
As with earlier spatial memory experiments conducted by Kahana’s group, this study involved playing a simple video game on a bedside computer. The game in this experiment involved making deliveries to stores in a virtual city. The participants were first given a period where they were allowed to freely explore the city and learn the stores’ locations. When the game began, participants were only instructed where their next stop was, without being told what they were delivering. After they reached their destination, the game would reveal the item that had been delivered, and then give the participant their next stop.
After 13 deliveries, the screen went blank and participants were asked to remember and name as many of the items they had delivered in the order they came to mind.
This allowed the researchers to correlate the neural activation associated with the formation of spatial memories (the locations of the stores) and the recall of episodic memories: (the list of items that had been delivered).
“A challenge in studying memory in naturalistic settings is that we cannot create a realistic experience where the experimenter retains control over and can measure every aspect of what the participant does and sees. Virtual reality solves that problem,” Kahana said. “Having these patients play our games allows us to record every action they take in the game and to measure the responses of neurons both during spatial navigation and then later during verbal recall.”
By asking participants to recall the items they delivered instead of the stores they visited, the researchers could test whether their spatial memory systems were being activated even when episodic memories were being accessed. The map-like nature of the neurons associated with spatial memory made this comparison possible.
"During navigation, neurons in the hippocampus and neighboring regions can often represent the patient’s virtual location within the town, kind of like a brain GPS device," Kahana said. "These so-called ‘place cells’ are perhaps the most striking example of a neuron that encodes an abstract cognitive representation."
Using the brain recordings generated while the participants navigated the city, the researchers were able to develop a neural map that corresponded to the city’s layout. As participants passed by a particular store, the researchers correlated their spatial memory of that location with the pattern of place cell activation recorded. To avoid confounding the episodic memories of the items delivered with the spatial memory of a store’s location, the researchers excluded trips that were directly to or from that store when placing it on the neural map.
With maps of place cell activations in hand, the researchers were able to cross- reference each participant’s spatial memories as they accessed their episodic memories of the delivered items. The researchers found that the neurons associated with a particular region of the map activated immediately before a participant named the item that was delivered to a store in that region.
“This means that if we were given just the place cell activations of a participant,” Kahana said, “we could predict, with better than chance accuracy, the item he or she was recalling. And while we cannot distinguish whether these spatial memories are actually helping the participants access their episodic memories or are just coming along for the ride, we’re seeing that this place cell activation plays a role in the memory retrieval processes.”
Earlier neuroscience research in both human and animal cognition had suggested the hippocampus has two distinct roles: the role of cartographer, tracking
location information for spatial memory, and the role of scribe, recording events for episodic memory. This experiment provides further evidence that these roles are intertwined.
“Our finding that spontaneous recall of a memory activates its neural geotag suggests that spatial and episodic memory functions of the hippocampus are intimately related and may reflect a common functional architecture,” Kahana said.
Eat crow if you think I’m a bird-brain
Scientists have long suspected that corvids – the family of birds including ravens, crows and magpies – are highly intelligent. Now, Tübingen neurobiologists Lena Veit und Professor Andreas Nieder have demonstrated how the brains of crows produce intelligent behavior when the birds have to make strategic decisions. Their results are published in the latest edition of Nature Communications.
Crows are no bird-brains. Behavioral biologists have even called them “feathered primates” because the birds make and use tools, are able to remember large numbers of feeding sites, and plan their social behavior according to what other members of their group do. This high level of intelligence might seem surprising because birds’ brains are constructed in a fundamentally different way from those of mammals, including primates – which are usually used to investigate these behaviors.
The Tübingen researchers are the first to investigate the brain physiology of crows’ intelligent behavior. They trained crows to carry out memory tests on a computer. The crows were shown an image and had to remember it. Shortly afterwards, they had to select one of two test images on a touchscreen with their beaks based on a switching behavioral rules. One of the test images was identical to the first image, the other different. Sometimes the rule of the game was to select the same image, and sometimes it was to select the different one. The crows were able to carry out both tasks and to switch between them as appropriate. That demonstrates a high level of concentration and mental flexibility which few animal species can manage – and which is an effort even for humans.
The crows were quickly able to carry out these tasks even when given new sets of images. The researchers observed neuronal activity in the nidopallium caudolaterale, a brain region associated with the highest levels of cognition in birds. One group of nerve cells responded exclusively when the crows had to choose the same image – while another group of cells always responded when they were operating on the “different image” rule. By observing this cell activity, the researchers were often able to predict which rule the crow was following even before it made its choice.
The study published in Nature Communications provides valuable insights into the parallel evolution of intelligent behavior. “Many functions are realized differently in birds because a long evolutionary history separates us from these direct descendants of the dinosaurs,” says Lena Veit. “This means that bird brains can show us an alternative solution out of how intelligent behavior is produced with a different anatomy.” Crows and primates have different brains, but the cells regulating decision-making are very similar. They represent a general principle which has re-emerged throughout the history of evolution. “Just as we can draw valid conclusions on aerodynamics from a comparison of the very differently constructed wings of birds and bats, here we are able to draw conclusions about how the brain works by investigating the functional similarities and differences of the relevant brain areas in avian and mammalian brains,” says Professor Andreas Nieder.
Researchers Find Gene Responsible For Susceptibility To Panic Disorder
A study published recently in the Journal of Neuroscience points, for the first time, to the gene trkC as a factor in susceptibility to the disease. The researchers define the specific mechanism for the formation of fear memories which will help in the development of new pharmacological and cognitive treatments.
Five out of every 100 people* in Spain suffer from panic disorder, one of the diseases included within the anxiety disorders, and they experience frequent and sudden attacks of fear that may influence their everyday lives, sometimes even rendering them incapable of things like going to the shops, driving the car or holding down a job.
It was known that this disease had a neurobiological and genetic basis and for some time the search had been on to discover which genes were involved in its development, with certain genes being implicated without their physiopathological contribution being understood. Now, for the first time, researchers from the Centre for Genomic Regulation (CRG) have revealed that the gene NTRK3, responsible for encoding a protein essential for the formation of the brain, the survival of neurones and establishing connections between them, is a factor in genetic susceptibility to panic disorder.
"We have observed that deregulation of NTRK3 produces changes in brain development that lead to malfunctions in the fear-related memory system", explains Mara Dierssen, head of the Cellular and Systems Neurobiology group at the CRG. “In particular, this system is more efficient at processessing information to do with fear, the thing that makes a person overestimate the risk in a situation and therefore feel more frightened and, also, that stores that information in a more lasting and consistent manner".
Different regions of the human brain are responsible for processing this feeling, although the hippocampus and amygdala play crucial roles. On the one hand, the hippocampus is responsible for forming memories and processing contextual information, which means that the person may be afraid of being in places where they could suffer a panic attack; and on the other, the amygdala is crucial in converting this information into a physiological fear response.
Although these circuits are activated in everyone in warning situations, what the CRG researchers have discovered is that “in those people who suffer from panic disorder there is overactivation of the hippocampus and altered activation in the amygdala circuitry, resulting in exaggerated formation of fear memories”, explains Davide D’Amico, a PhD student at the CRG, co-author of the work and the article published in the Journal of Neuosciences, together with Dierssen and the researcher Mónica Santos.
They have also found that Tiagabine, a drug that modulates the brain’s fear inhibition system, is able to reverse the formation of panic memories. Although it had already been observed to alleviate certain symptoms in some patients, “we have discovered that it specifically helps restore the fear memory system”, points out Dierssen.
Panic disorder
Panic attacks are a key symptom of panic disorder. They can last several minutes, be sudden and repeated, and the sufferer has a physical reaction similar to the alarm response to real danger, involving palpitations, cold sweats, dizziness, shortness of breath, tingling in the body, nausea and stomach pain. On top of this, they feel continuously anxious when faced with the prospect of suffering another attack.
This study by the CRG researchers reveals that the way in which the memories resulting from a panic attack are stored is what ultimately ends up producing the disorder, which usually appears between 20 and 30 years of age. Although it has a genetic basis, it is also influenced by other environmental factors, such as accumulated stress. This is why the authors of the paper consider elevated environmental stress in Spanish society to have led to an increase in the occurrence of these disorders.
Currently, there is no cure for this disease, which is treated with medicines that block the more serious symptoms, as well as with cognitive therapy, which aims to help the person learn to survive the attacks better. “The problem is that drugs have many side effects and psychotherapy is not really aimed at specific moments in the process of forming and forgetting fear memories. In our work we have defined a specific creation mechanism for these fear memories that could help in the development of new drugs and, also, in identifying the key moments for applying cognitive therapy”, indicates D’Amico.
(Source: alphagalileo.org)
Polymer Foam Expands Potential to Treat Aneurysms
Thirty thousand Americans suffer severe neurological damage or death from brain aneurysms each year and the existing treatments eventually fail in nearly half of patients. Currently, these “bubbles” in the blood vessel are either clamped off, which requires invasive brain surgery, or filled with platinum coils to induce clotting in the aneurysm. Both treatments, although somewhat effective, can have subsequent problems, including inflammation, incomplete healing, and the development of secondary aneurysms adjacent to the initial site. These complications result in approximately 40 percent of patients needing additional treatment to attempt to re-repair the aneurysm.
NIBIB-funded researchers in Texas A&M’s bioengineering department are moving rapidly to provide a better treatment for this serious disorder. The group specializes in using the unique properties of foam shape memory polymers (SMPs) to solve clinical conditions lacking satisfactory treatments.
The group, led by Associate Professor Duncan Maitland, is using SMPs in a pig model of brain aneurysm to develop a minimally-invasive procedure that fills and stabilizes the aneurysm. Because the system induces only minimal inflammation, it successfully allows natural healing of the border between the aneurysm and the blood vessel. As reported in the May 22 issue of the Journal of Biomedical Materials Research, partial healing was observed at 30 days post-procedure and almost complete healing had occurred at 90 days in the pig model.
How it Works
Two of the properties of SMP are critical to the success seen in the animal experiments:
- the foam’s ability to be compressed into a very thin sheath and then induced to expand to 100 times its compressed volume when heated, and
- its rigid, yet porous structure when fully expanded.
The rigid uniform structure of the expanded foam is a significant improvement over the current practice of filling an aneurysm with a platinum coil. Because a coil is threaded into the aneurysm until it fills the space, pressure is exerted on the aneurysm during the process, which can damage the vessel wall. In addition, the platinum coils do not uniformly fill the space, leaving large gaps that can allow shifting of the coils as well as the formation of unstable, large clots. The platinum coil approach can also result in inflammation which destabilizes the aneurysm, resulting in incomplete healing and failure to completely wall-off from the blood vessel.
The minimally-invasive procedure involves inserting the slim, compressed foam into the aneurysm using a microcatheter. The microcatheter is inserted into an artery through a small cut in the groin and then threaded through the blood vessels to the location of the aneurysm in the brain. Once in position, a laser optical fiber heats the foam to induce expansion and complete filling of the fragile pouch of the aneurysm. In contrast to the platinum coils currently in use, the foam exerts a firm, uniform pressure on the walls of the aneurysm, which reduces chances of rupture.
The foam contains tiny compartments that result in the development of a matrix of blood clots that further stabilize the structure. The investigators found that unlike the aneurysms filled with metal coils, the foam structure produced little inflammation and allowed natural healing, defined by the growth of new cells at the border between the foam and the wall of the damaged blood vessel.
Making a Difference through Innovative Technologies
Dr. Maitland describes his work, broadly, as developing technologies to solve clinical problems that lack satisfactory solutions. He has formed a company called Shape Memory Therapeutics to assist with moving the encouraging results obtained with the SMP system from animal models into testing and, potentially, eventual use in humans. Maitland’s desire to make a difference is clear. “There are people walking around with aneurysms that are untreatable. My hope is to develop a game-changing therapy that reduces the risk of aneurysm ruptures, increases patient safety, and has a real impact on human health care.”
With right-handed people, it is positioned in the left side of the brain; left-handed people have it (usually) in the right side: the location of speech production has been known for quite some time. But it is not that simple, states psychologist Gesa Hartwigsen, Professor at Kiel University. In her current scientific publication, published in the magazine Proceedings of the National Academy of Science of the USA (PNAS), she investigates which areas in the brain really are in charge of speech, and how these interact. Her findings are supposed to help patients who have speech production problems or aphasia following a stroke.
Comprehending & Speaking
Gesa Hartwigsen and her team started by analysing speech production. They let healthy right-handed test persons listen to words, which they should then repeat. “These were pseudo words such as `beudo`. In German, they don’t have any associated meaning. Therefore, when hearing and repeating these words, no areas of the brain that had a connection to the meaning of what had been heard were activated”, said Hartwigsen.
The psychologist applies a combination of non-invasive methods (fMRI– functional magnetic resonance imaging and TMS – transcranial magnetic stimulation) to deduce what happens in the brain during the test. “We thus proved that the left hemisphere, as expected, was activated during speech production, while the right hemisphere did not actively contribute to language function”, explains Hartwigsen. This is the regular functionality within a healthy brain. From these results as well as others, scientists had up to now deduced that the right hemisphere did not contribute to speech production in the healthy system and was therefore suppressed.
Interfering & Measuring
With a second test, the Kiel University scientists simulated a dysfunction in the brain comparable to a stroke. A magnetic coil transmits a current pulse that interrupts the function of the area responsible for producing speech (Broca’s Area) in the left hemisphere. This completely harmless method influences the speech production of the volunteers for about 30 to 45 minutes. “During this period, the ability to listen and repeat was tested again. While we observed a suppressed activity in the left hemisphere during repeating, with some test persons taking longer to repeat the pseudo words, we also found unexpected activities in the right hemisphere”, reports Hartwigsen.
The right hemisphere showed increased activity during pseudo word repetition. The more the activity in the right Borca’s Area increased, the faster the volunteers were able to solve their speech tests. The right hemisphere also increased its facilitatory influence on the right hemisphere, a finding that was not observed prior to the TMS-induced lesion. “This reaction lends further support to the notion that the right hemisphere area reacts to the dysfunction of the left hemisphere and tries to compensate for the lesion.” Does the right hemisphere have a supporting influence and does it play an active role in speech production? So far, the common opinion was that it does not.
Result & Outlook
The findings of Gesa Hartwigsen and her team show an interaction of both hemispheres during speech repetition. When the left hemisphere is suppressed for example by a stroke, the right hemisphere could actively facilitate speech production. “By stimulating the right hemisphere, it could be possible to support speech recovery”, speculates the scientist. Here, timing would be very important. “Right after a stroke, we could support the right hemisphere. But when the remaining areas of the left hemisphere are ready to do their work again, it might be more helpful if the right hemisphere was suppressed. During this phase, we could stimulate the left hemisphere instead. The correct timing can therefore be crucial for recovery of speech after a stroke.”
In collaboration with the Department of Neurology at Kiel University, a stroke specialist from Leipzig and doctoral students of Medicine and Psychology, Gesa Hartwigsen has started a follow-up study on the recent publication. “We would like to find out more about the collaboration of the hemispheres and the right timing in helping stroke patients to recover”, says Hartwigsen. Her field of research is fairly new within the cognitive neuroscience. Nevertheless, she is positive that it will offer practical help in the form of concrete therapies within the next ten to fifteen years.