First motion MRI of unborn twins
If you want to get a sense of what it might be like to share a womb with a sibling, this video may give you a glimpse. For the first time, unborn twins have been captured using cinematic MRI, a technique that images slices of the body several times to create a video with astonishing detail.
According to Marisa Taylor-Clarke of Imperial College London, who recorded the images, this is “raw” footage, unlike typical videos of the womb, which require computer processing afterwards. She uses the technique to study twin-to-twin transfusion syndrome, a potentially fatal condition where one twin’s growth is stunted when its sibling receives more of the blood supply.
Filed under MRI sibling rivalry womb twins science
Gene-swap therapy eases rare brain disease
A new therapy that uses a virus to switch genes in the brain may help extend the lives of children with a rare and fatal neurodegenerative disorder. The results of the clinical trial, which began in 2001, show that the gene therapy cocktail conveyed into the brain by a molecular special delivery vehicle holds promise for children with Canavan disease.
As reported in Science Translational Medicine, the treatment uses a virus (adeno-associated virus, or AAV) as a “viral vector” meticulously tailored to enter the brain and safely switch good genes for bad.
“This was the first AAV-based gene therapy produced by a US academic institution to be approved for neurological use by the FDA,” says R. Jude Samulski, professor of pharmacology and director of the University of North Carolina Gene Therapy Center.
“It’s also the first vector produced by the university’s Gene Therapy Center Vector Core facility to go into patients.”
Children with Canavan disease have mutations in the ASPA gene that normally codes for an enzyme that helps the brain degrade N-acetyl-aspartate (NAA). The unregulated buildup of NAA is toxic to the brain’s gray matter, the protective myelin sheath surrounding nerve cells.
As the myelin deteriorates and neurons become unable to communicate, the child’s head size increases (macrocephaly), there are problems with movement, such as an inability to crawl, seizures occur, vision becomes impaired, and the children often die by age three. Fewer than 1,000 children in the US have the disorder.
Filed under canavan disease neurodegenerative diseases gene therapy
How can the immune system be reprogrammed once it goes on the attack against its own body? EPFL scientists retrained T-cells involved in type I diabetes, a common autoimmune disease. Using a modified protein, they precisely targeted the white blood cells (T-lymphocytes, or T-cells) that were attacking pancreatic cells and causing the disease. When tested on laboratory mice, the therapy eliminated all signs of the pathology. This same method could be a very promising avenue for treating multiple sclerosis as well. The scientists have just launched a start-up company, Anokion SA, on the Lausanne campus, and are planning to conduct clinical trials within the next two years. Their discovery has been published in the journal PNAS (Proceedings of the National Academy of Science).
To retrain the rebellious white blood cells, the researchers began with a relatively simple observation: every day, thousands of our cells die. Each time a cell bites the dust, it sends out a message to the immune system. If the death is caused by trauma, such as an inflammation, the message tends to stimulate white blood cells to become aggressive. But if the cell dies a programmed death at the end of its natural life cycle, it sends out a soothing signal.
In the human body there is a type of cell that dies off en masse, on the order of 200 billion per day – red blood cells. Each of these programmed deaths sends a soothing message to the immune system. The scientists took advantage of this situation, and attached the pancreatic protein targeted by T-cells in type I diabetes to red blood cells.
"Our idea was that by associating the protein under attack to a soothing event, like the programmed death of red blood cells, we would reduce the intensity of the immune response," explains Jeffrey Hubbell, co-author of the study. To do this, the researchers had to do some clever bioengineering and equip the protein with a tiny, molecular scale hook, that is able to attach itself to a red blood cell. Billions of these were manufactured and then simply injected into the body.
Complete eradication of diabetes symptoms
As these billions of red blood cells died their programmed death, they released two signals: the artificially attached pancreatic protein, and the soothing signal. The association of these two elements, like Pavlov’s dog, who associates the ringing of a bell with a good or bad outcome, essentially retrained the T lymphocytes to stop attacking the pancreatic cells. “It was a total success. We were able to eliminate the immune response in type I diabetes in mice,” explains Hubbell.
Minimizing risks and side effects
Co-author Stephan Kontos adds that the great advantage of this approach is its extreme precision. “Our method carries very little risk and shouldn’t introduce significant side effects, in the sense that we are not targeting the entire immune system, but just the specific kind of T-cells involved in the disease.”
The scientists are planning to conduct clinical trials in 2014, at the earliest. To demonstrate the potential of their method, they plan to first test applications that would counteract the immune response to a drug known for its effectiveness against gout. “We chose to begin with this application before we tackled diabetes or multiple sclerosis, since we knew and were in control of all the parameters,” explains Hubbell.
Currently, the researchers are also testing the potential of this method in treating multiple sclerosis. In this disease, T-cells destroy myelin cells, which form a protective sheath around nerve fibers. They are also studying the potential of their method with another kind of white blood cell, B-lymphocytes, that are involved in many other autoimmune diseases.
(Source: eurekalert.org)
Filed under white blood cells immune system type I diabetes science
Brain displays an intrinsic mechanism for fighting infection
White blood cells have long reigned as the heroes of the immune system. When an infection strikes, the cells, produced in bone marrow, race through the blood to fight off the pathogen. But new research is emerging that individual organs can also play a role in immune system defense, essentially being their own hero. In a study examining a rare and deadly brain infection, scientists at The Rockefeller University have found that the brain cells of healthy people likely produce their own immune system molecules, demonstrating an “intrinsic immunity” that is crucial for stopping an infection.
Shen-Ying Zhang, a clinical scholar in the St. Giles Laboratory of Human Genetics of Infectious Diseases, has been studying children with Herpes simplex encephalitis, a life-threatening brain infection from the herpes virus, HSV-1, that can cause significant brain damage. The scientists already knew from previous work that children with this encephalitis have a genetic defect that impairs the function of an immune system receptor — toll-like receptor 3 (TLR3) — in the brain. For this study they wanted to see how the defect in TLR3 was hampering the brain’s ability to fight the herpes infection.
When TLR3 detects a pathogen it triggers an immune response causing the release of proteins called interferons to sound the alarm and “interfere” with the pathogen’s replication. It’s most commonly associated with white blood cells, found throughout the body, but here the researchers were examining the receptor’s presence on neurons and other brain cells.
“One interesting thing about these patients is that they didn’t have any of the other, more common herpes symptoms. They didn’t have an infection on their skin or their mouths, just in their brains. We therefore hypothesized that the TLR3 response must be specifically responsible for keeping the herpes virus from infecting the brain and not necessary in other parts of the body,” says Zhang.
The lab, headed by Jean-Laurent Casanova, collaborated with scientists at Harvard Medical School and Memorial Sloan-Kettering Cancer Institute to create induced pluripotent stem cells. Made from the patients’ own tissue, the stem cells were developed into central nervous system cells that carried the patients’ genetic defects. Zhang exposed the cells to HSV-1 and to synthetic double-stranded RNA, which mimics a byproduct of the virus that spurs the toll-like receptors into action. By measuring levels of interferon, Zhang showed that the patients’ TLR3 response was indeed faulty; their cells weren’t making these important immune system proteins, leaving them unable to fight off the infection.
Zhang also exposed the patients’ blood cells to the virus and found that the TLR3 defect was not an issue there as it was in the brain — interferons were released by other means.
Because the toll-like receptors on neurons proved to be vital in preventing the encephalitis infection, the researchers concluded that brain cells use it as an in-house mechanism to fight infection, rather than relying on white blood cells. When its function was impaired, patients couldn’t get better.
“This is evidence of an intrinsic immunity, a newly-discovered function of the immune system,” says Zhang. “It’s likely that other organs also have their own specific tools for fighting infection.”
The researchers are putting together a pilot study to test an interferon-based treatment in patients with the encephalitis, believing it will help speed recovery and increase the survival rate when used alongside antiviral drugs. They’ll also explore whether the brain displays an intrinsic immunity to other types of viral infection.
Filed under brain brain infection white blood cells immune system encephalitis neuroscience science
Scientists Map Initial Anti-Aging Formula
A new study indicates that scientists have found a new way of delaying the aging process in mice, and they hope to replicate the finding in people.
The scientists published their findings in the journal Cell Metabolism. The research was built upon an earlier study that shed light on progeria, a rare genetic disease that prematurely ages one in four million babies.
A mutation was found in the Lamin A protein, which lines the nucleus in human cells, disrupting the repair process and accelerating aging. They also found that normal and healthy Lamin A binds to and activates the gene SIRT1, which has been long associated with longevity. If scientists can develop drugs that mimic Lamin A or increase the binding between Lamin A and SIRT1, this may lead to anti-aging drugs.
The team also examined if the binding efficiency was boosted with resveratrol, a compound found in the skin of red grapes. Mice fed with concentrated resveratrol fared significantly better than healthy mice that weren’t given it and the onset of aging was delayed and the life expectancy was extended. Mice with progeria lived 30% longer when fed with resveratrol compared with progerial mice not given the compound.
Filed under aging progeria genetic diseases mutation proteins resveratrol science
Why overlearned sequences are special: distinct neural networks for ordinal sequences
Several observations suggest that overlearned ordinal categories (e.g., letters, numbers, weekdays, months) are processed differently than non-ordinal categories in the brain. In synesthesia, for example, anomalous perceptual experiences are most often triggered by members of ordinal categories (Rich et al., 2005; Eagleman, 2009). In semantic dementia (SD), the processing of ordinal stimuli appears to be preserved relative to non-ordinal ones (Cappelletti et al., 2001). Moreover, ordinal stimuli often map onto unconscious spatial representations, as observed in the SNARC effect (Dehaene et al., 1993; Fias, 1996). At present, little is known about the neural representation of ordinal categories. Using functional neuroimaging, we show that words in ordinal categories are processed in a fronto-temporo-parietal network biased toward the right hemisphere. This differs from words in non-ordinal categories (such as names of furniture, animals, cars, and fruit), which show an expected bias toward the left hemisphere. Further, we find that increased predictability of stimulus order correlates with smaller regions of BOLD activation, a phenomenon we term prediction suppression. Our results provide new insights into the processing of ordinal stimuli, and suggest a new anatomical framework for understanding the patterns seen in synesthesia, unconscious spatial representation, and SD.
Filed under brain brain activity ordinal sequences predictability semantic dementia neuroscience science
New Research Shows Music Improves Health and Disease
Music has been incorporated into medical practice since before the ancient Greeks. However, though practitioners have been convinced of music’s health benefits for thousands of years, there had been little peer-reviewed research to back them up. But recent studies are providing an empirical backbone for the anecdotal evidence. A 2012 scientific review, published in the journal Nutrition, collects information from a number of studies to support music’s influence on the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS) and the immune system. These results support the experiences of complementary practitioners, who have long used music to help heal.
“As an integrative physician and traditional Chinese medicine practitioner, the healing power of music has always been an important part of my practice and family life,” says integrative medicine pioneer Isaac Eliaz, M.D. “Harmony and tempo help synchronize the rhythms of the natural world with the music of the heart – each person’s individual energetic pattern, expressed in their pulse.”
Proven Medicine
The review highlighted a number of studies that confirm music’s healing potential. For example, music reduces levels of serum cortisol in the blood. An important player in the HPA axis, cortisol increases metabolic activity, suppresses the immune system and has been associated with both anxiety and depression. A number of studies have shown that exposing post-operative patients to music dramatically lowers their cortisol levels, enhancing their ability to heal.
Other studies in the review measured music’s impact on congestive heart failure, premature infants, immunity, digestive function and pain perception. In particular, music’s effects on the limbic and hypothalamic systems reduced the incidence of heart failure. Other studies showed that surgical patients required less sedation and post-operative pain medication.
“These results only confirm what I have observed for many years in my practice,” says Dr. Eliaz. “Music produces quantifiable healing. For example, my daughter Amity, a professional musician, regularly plays her songs for chronically ill patients who express how uplifting her music is. These performances do more than encourage good feelings, they help the body heal on a molecular level.”
Powerful Impact
Perhaps the most interesting aspect of music’s healing properties is how widespread they are. For example, music also aided recovery time following strenuous exercise. Other studies showed that fast-paced music can increase resting metabolism, which may prove helpful for people trying to lose weight.
“Modern science has just begun to scratch the surface of music and sound in terms of healing potential,” says Dr. Eliaz. “However, traditional medical systems from around the world have long revered the beneficial vibrations of music, harmony and rhythm for health and vitality. The effects are instant and tangible, but they are also powerful and long lasting.”
Filed under diseases healing health medicine music
Decision to give a group effort in the brain
A monkey would probably never agree that it is better to give than to receive, but they do apparently get some reward from giving to another monkey.
During a task in which rhesus macaques had control over whether they or another monkey would receive a squirt of fruit juice, three distinct areas of the brain were found to be involved in weighing benefits to oneself against benefits to the other, according to new research by Duke University researchers.
The team used sensitive electrodes to detect the activity of individual neurons as the animals weighed different scenarios, such as whether to reward themselves, the other monkey or nobody at all. Three areas of the brain were seen to weigh the problem differently depending on the social context of the reward. The research appears Dec. 24 in the journal Nature Neuroscience.
Using a computer screen to allocate juice rewards, the monkeys preferred to reward themselves first and foremost. But they also chose to reward the other monkey when it was either that or nothing for either of them. They also were more likely to give the reward to a monkey they knew over one they didn’t, preferred to give to lower status than higher status monkeys, and had almost no interest in giving the juice to an inanimate object.
Calculating the social aspects of the reward system seems to be a combination of action by two centers involved in calculating all sorts of rewards and a third center that adds the social dimension, according to lead researcher Michael Platt, director of the Duke Institute for Brain Sciences and the Center for Cognitive Neuroscience.
The orbital frontal cortex, right above the eyes, was activated when calculating rewards to the self. The anterior cingulate sulcus in the middle of the top of the brain seemed to calculate giving up a reward. But both centers appear “divorced from social context,” Platt said. A third area, the anterior cingulate gyrus (ACCg), seemed to “care a lot about what happened to the other monkey,” Platt said.
Based on results of various combinations of the reward-giving scenario the monkeys were put through, it would appear that neurons in the ACCg encode both the giving and receiving of rewards, and do so in a remarkably similar way.
The use of single-neuron electrodes to measure the activity of brain areas gives a much more precise picture than brain imaging, Platt said. Even the best imaging available now is “a six-second snapshot of tens of thousands of neurons,” which are typically operating in milliseconds.
What the team has seen happening is consistent with other studies of damaged ACCg regions in which animals lost their typical hesitation about retrieving food when facing social choices. This same region of the brain is active in people when they empathize with someone else.
"Many neurons in the anterior cingulate gyrus (ACCg) respond both when monkeys choose a drink for themselves and when they choose to give a drink to another monkey," Platt said. "One might view these as sort of mirror neurons for the reward system." The region is active as an animal merely watches another animal receiving a reward without having one themselves.
The research is another piece of the puzzle as neuroscientists search for the roots of charity and social behavior in our species and others. There have been two schools of thought about how the social reward system is set up, Platt said. One holds that there is generic circuitry for rewards that has been adapted to our social behavior because it helped humans and other social animals like monkeys thrive. Another school holds that social behavior is so important to humans and other highly social animals like monkeys that there may be some special circuits for it, Platt said.
This finding, in macaques that have only a very distant common ancestor with us and are “not a particularly prosocial animal,” suggests that “this specialized social circuitry evolved a long time ago presumably to support cooperative behavior,” Platt said.
(Photo: EPA)
Filed under brain orbital frontal cortex reward system primates social behavior neuroscience science
Autistic-like behaviors can be partially remedied by normalizing excessive levels of protein synthesis in the brain, a team of researchers has found in a study of laboratory mice. The findings, which appear in the latest issue of Nature, provide a pathway to the creation of pharmaceuticals aimed at treating autism spectrum disorders (ASD) that are associated with diminished social interaction skills, impaired communication ability, and repetitive behaviors.
"The creation of a drug to address ASD will be difficult, but these findings offer a potential route to get there," said Eric Klann, a professor at NYU’s Center for Neural Science and the study’s senior author. "We have not only confirmed a common link for several such disorders, but also have raised the exciting possibility that the behavioral afflictions of those individuals with ASD can be addressed."
The study’s other co-authors included researchers from the University of California, San Francisco (UCSF) and three French institutions: Aix-Marseille Universite’; Institut National de la Santé et de la Recherche Médicale (INSERM); and Le Centre National de la Recherche Scientifique (CNRS).
The researchers focused on the EIF4E gene, whose mutation is associated with autism. The mutation causing autism was proposed to increase levels of the eIF4E, the protein product of EIF4E, and lead to exaggerated protein synthesis. Excessive eIF4E signaling and exaggerated protein synthesis also may play a role in a range of neurological disorders, including fragile X syndrome (FXS).
In their experiments, the researchers examined mice with increased levels of eIF4E. They found that these mice had exaggerated levels of protein synthesis in the brain and exhibited behaviors similar to those found in autistic individuals—repetitive behaviors, such as repeatedly burying marbles, diminished social interaction (the study monitored interactions with other mice), and behavioral inflexibility (the afflicted mice were unable to navigate mazes that had been slightly altered from ones they had previously solved). The researchers also found altered communication between neurons in brain regions linked to the abnormal behaviors.
To remedy to these autistic-like behaviors, the researchers then tested a drug, 4EGI-1, which diminishes protein synthesis induced by the increased levels of eIF4E. Through this drug, they hypothesized that they could return the afflicted mice’s protein production to normal levels, and, with it, reverse autistic-like behaviors.
The subsequent experiments confirmed their hypotheses. The mice were less likely to engage in repetitive behaviors, more likely to interact with other mice, and were successful in navigating mazes that differed from those they previously solved, thereby showing enhanced behavioral flexibility. Additional investigation revealed that these changes were likely due to a reduction in protein production—the levels of newly synthesized proteins in the brains of these mice were similar to those of normal mice.
"These findings highlight an invaluable mouse model for autism in which many drugs that target eIF4E can be tested," added co-author Davide Ruggero, an associate professor at UCSF’s School of Medicine and Department of Urology. "These include novel compounds that we are developing to target eIF4E hyperactivation in cancer that may also be potentially therapeutic for autistic patients."
(Source: eurekalert.org)
Filed under autism ASD fragile x syndrome protein synthesis neuroscience science
The Top 5 Neuroscience Breakthroughs of 2012
More than any year before, 2012 was the year neuroscience exploded into pop culture. From mind-controlled robot hands to cyborg animals to TV specials to triumphant books, brain breakthroughs were tearing up the airwaves and the internets. From all the thrilling neurological adventures we covered over the past year, we’ve collected five stories we want to make absolutely sure you didn’t miss.
A Roadmap of Brain Wiring
Neuroscientists like to compare the task of unraveling the brain’s connections to the frustration of untangling the cords beneath your computer desk – except that in the brain, there are hundreds of millions of cords, and at least one hundred trillion plugs. Even with our most advanced computers, some researchers were despairing of ever seeing a complete connectivity map of the human brain in our lifetimes. But thanks to a team led by Van Wedeen at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, 2012 gave us an unexpectedly clear glimpse of our brains’ large-scale wiring patterns. As it turns out, the overall pattern isn’t so much a tangle as a fabric – an intricate, multi-layered grid of cross-hatched neural highways. What’s more, it looks like our brains share this grid pattern with many other species. We’re still a long way from decoding how most of this wiring functions, but this is a big step in the right direction.
Laser-Controlled Desire
Scientists have been stimulating rats’ pleasure centers since the 1950s – but 2012 saw the widespread adoption of a new brain-stimulation method that makes all those wires and incisions look positively crude. Researchers in the blossoming field of optogenetics develop delicate devices that control the firing of targeted groups of neurons – using only light itself. By hooking rats up to a tiny fiber-optic cable and firing lasers directly into their brains, a team led by Garret D. Stuber at the University of North Carolina at Chapel Hill School of Medicine were able to isolate specific neurochemical shifts that cause rats to feel pleasure or anxiety – and switch between them at will. This method isn’t only more precise than electrical stimulation – it’s also much less damaging to the animals.
Programmable Brain Cells
Pluripotent stem cell research took off like a rocket in 2012. After discovering that skin cells can be genetically reprogrammed into stem cells, which can in turn be reprogrammed into just about any cell in the human body, a team led by Sheng Ding at UCSF managed to engineer a working network of newborn neurons from a harvest of old skin cells. In other words, the team didn’t just convert skin cells into stem cells, then into neurons – they actually kept the batch of neurons alive and functional long enough to self-organize into a primitive neural network. In the near future, it’s likely that we’ll be treating many kinds of brain injuries by growing brand-new neurons from other kinds of cells in a patient’s own body. This is already close on the horizon for liver and heart cells – but the thought of being able to technologically shape the re-growth of a damaged brain is even more exciting.
Memories on Disc
We’ve talked a lot about how easily our brains can modify and rewrite our long-term memories of facts and scenarios. In 2012, though, researchers went Full Mad Scientist with the implications of this knowledge, and blew some mouse minds in the process. One team, led by Mark Mayford of the Scripps Research Institute, took advantage of some recently invented technology that enables scientists to record and store a mouse’s memory of a familiar place on a microchip. Mayford’s team figured out how to turn specific mouse memories on and off with the flick of a switch – but they were just getting warmed up. The researchers then proceeded to record a memory in one mouse’s brain, transfer it into another mouse’s nervous system, and activate it in conjunction with one of the second mouse’s own memories. The result was a bizarre “hybrid memory” – familiarity with a place the mouse had never visited. Well, not in the flesh, anyway.
Videos of Thoughts
Our most exciting neuroscience discovery of 2012 is also one of the most controversial. A team of researchers from the Gallant lab at UC Berkeley discovered a way to reconstruct videos of entire scenes from neural activity in a person’s visual cortex. Those on the cautionary side emphasize that activity in the visual cortex is fairly easy to decode (relatively speaking, of course) and that we’re still a long, long way from decoding videos of imaginary voyages or emotional palettes. In fact, from one perspective, this isn’t much different from converting one file format into another. On the other hand, though, these videos offer the first hints of the technological reality our children may inhabit: A world where the boundaries between the objective external world and our individual subjective experiences are gradually blurred and broken down. When it comes to transforming our relationship with our own consciousness – and those of the people around us – it doesn’t get much more profound than that.
Filed under brain breakthroughs neuroscience 2012 neuroscience science
