Aggressive Brain Tumors Can Originate From a Range of Nervous System Cells
Scientists have long believed that glioblastoma multiforme (GBM), the most aggressive type of primary brain tumor, begins in glial cells that make up supportive tissue in the brain or in neural stem cells. In a paper published October 18 in Science, however, researchers at the Salk Institute for Biological Studies have found that the tumors can originate from other types of differentiated cells in the nervous system, including cortical neurons.
GBM is one of the most devastating brain tumors that can affect humans. Despite progress in genetic analysis and classification, the prognosis of these tumors remains poor, with most patients dying within one to two years of diagnosis. The Salk researcher’s findings offer an explanation for the recurrence of GBM following treatment and suggest potential new targets to treat these deadly brain tumors.
"One of the reasons for the lack of clinical advances in GBMs has been the insufficient understanding of the underlying mechanisms by which these tumors originate and progress," says Inder Verma, a professor in Salk’s Laboratory of Genetics and the Irwin and Joan Jacobs Chair in Exemplary Life Science.
To better understand this process, Verma’s team harnessed the power of modified viruses, called lentiviruses, to disable powerful tumor suppressor genes that regulate the growth of cells and inhibit the development of tumors. With these tumor suppressors deactivated, cancerous cells are given free rein to grow out of control.
Filed under brain tumors nervous system glial cells lentiviruses neuroscience science
2012 Photomicrography Competition
1st Place: Dr. Jennifer L. Peters & Dr. Michael R. Taylor (St. Jude Children’s Research Hospital, Memphis, Tennessee, USA)
Subject Matter: The blood-brain barrier in a live zebrafish embryo (20x)
Technique: Confocal
Dr. Jennifer Peters’ and Dr. Michael Taylor’s winning image of the blood-brain barrier in a live zebrafish embryo perfectly demonstrates the intersection of art and science that drives the Nikon Small World Competition.
The blood-brain barrier plays a critical role in neurological function and disease. Drs. Peters and Taylor, developed a transgenic zebrafish to visualize the development of this structure in a live specimen. By doing so, this model proves that not only can we image the blood-brain barrier, but we can also genetically and chemically dissect the signaling pathways that modulate the blood-brain barrier function and development.
To achieve this image, Peters and Taylor used a maximum intensity projection of a series of images acquired in the z plane. The images were first pseudo-colored with a rainbow palette based on depth so that the coloring scheme would be both visually appealing and provide spatial information. In doing so, Peters and Taylor captured an image that Peters says“not only captures the beauty of nature, but is also topical and biomedically relevant.”
Both Peters and Taylor have more than ten years of imaging experience. Peters is an imaging scientist in the St. Jude Children’s Research Hospital’s Light Microscopy Core Facility and Taylor is an Assistant Member in the Department of Chemical Biology and Therapeutics at St. Jude Children’s Research.
See the 2012 winners
Filed under Nikon Small World Nikon 2012 photography science competition photomicrography
New imaging techniques are mapping the locations of our aesthetic response
In Michelangelo’s Expulsion from Paradise, a fresco panel on the ceiling of the Sistine Chapel, the fallen-from-grace Adam wards off a sword-wielding angel, his eyes averted from the blade and his wrist bent back defensively. It is a gesture both wretched and beautiful. But what is it that triggers the viewer’s aesthetic response—the sense that we’re right there with him, fending off blows?
Recently, neuroscientists and an art historian asked ten subjects to examine the wrist detail from the painting, and—using a technique called transcranial magnetic stimulation (TMS)—monitored what happened in their brains. The researchers found that the image excited areas in the primary motor cortex that controlled the observers’ own wrists.
“Just the sight of the raised wrist causes an activation of the muscle,” reports David Freedberg, the Columbia University art history professor involved in the study. This connection explains why, for instance, viewers of Degas’ ballerinas sometimes report that they experience the sensation of dancing—the brain mirrors actions depicted on the canvas.
Freedberg’s study is part of the new but growing field of neuroaesthetics, which explores how the brain processes a work of art. The discipline emerged 12 years ago with publication of British neuroscientist Semir Zeki’s book, Inner Vision: An Exploration of Art and the Brain. Today, related studies depend on increasingly sophisticated brain-imaging techniques, including TMS and functional magnetic resonance imaging (fMRI), which maps blood flow and oxygenation in the brain. Scientists might monitor an observer’s reaction to a classical sculpture, then warp the sculpture’s body proportions and observe how the viewer’s response changes. Or they might probe what occurs when the brain contemplates a Chinese landscape painting versus an image of a simple, repetitive task.
Ulrich Kirk, a neuroscientist at the Virginia Tech Carilion Research Institute, is also interested in artworks’ contexts. Would a viewer respond the same way to a masterpiece enshrined in the Louvre if he beheld the same work displayed in a less exalted setting, such as a garage sale? In one experiment, Kirk showed subjects a series ofimages—some, he explained, were fine artwork; others were created by Photoshop. In reality, none were Photoshop-generated; Kirk found that different areas of viewers’ brains fired up when he declared an image to be “art.”
Kirk also hopes one day to plumb the brains of artists themselves. “You might be able to image creativity as it happens, by putting known artists in the fMRI,” he says.
Others, neuroscientists included, worry that neuroscience offers a reductionist perspective. Vilayanur Ramachandran, a neuroscientist at the University of California at San Diego, says that neuroaesthetics undoubtedly “enriches our understanding of human aesthetic experience.” However, he adds, “We have barely scratched the surface…the quintessence of art, and of genius, still eludes us—and may elude us forever.”
(Source: smithsonianmag.com)
Filed under art brain neuroimaging neuroscience psychology TMS fMRI science neuroaesthetics
About face: Study shows long-ignored segments of DNA play role in coordinating early stages of face development
The human face is a fantastically intricate thing. The billions of people on the planet have faces that are individually recognizable because each has subtle differences in its folds and curves. How is the face put together during development so that, out of billions of people, no two faces are exactly the same?
School of Medicine researcher Joanna Wysocka, PhD, and her colleagues have discovered key genetic elements that guide the earliest stages of the process.
Their research, published in the Sept. 13 issue of Cell Stem Cell, provides a resource for others studying facial development and could give insights to the cause of some facial birth defects. Because there is not enough genetic information in the body to define exactly where each cell will go, development of the face proceeds much like origami: genes provide instructions for folding, crimping, and movement of cells. As with origami, following a sequence of simple instructions can result in a complex, intricate object.
Wysocka focused on the first critical fold in the process of making an embryo, when the whole of the embryo is a flat sheet of cells that creases and closes over on itself to make a tube. Much of the tube eventually becomes the foundation of the brain and the spinal column, but one end sets the stage for the formation of the head and face. This process is driven by a small population of remarkable cells called neural crest cells.
"We were interested in identifying the portions of the human genome that are responsible for the behavior of the neural crest," Wysocka said.
What they discovered is that the modification of a collection of DNA sequences called “enhancers” can dial up or down the activity of the genes governing which cells eventually become the face. It’s almost as if they have discovered how the instructions for a piece of origami can be modified — slightly change how a fold is made and you may end up with something very different looking.
Filed under facial development genetics genomics neural crest cells DNA sequence neuroscience science
How fear skews our spatial perception
That snake heading towards you may be further away than it appears. Fear can skew our perception of approaching objects, causing us to underestimate the distance of a threatening one, finds a study published in Current Biology.
“Our results show that emotion and perception are not fully dissociable in the mind,” says Emory psychologist Stella Lourenco, co-author of the study. “Fear can alter even basic aspects of how we perceive the world around us. This has clear implications for understanding clinical phobias.”
Lourenco conducted the research with Matthew Longo, a psychologist at Birkbeck, University of London.
People generally have a well-developed sense for when objects heading towards them will make contact, including a split-second cushion for dodging or blocking the object, if necessary. The researchers set up an experiment to test the effect of fear on the accuracy of that skill.
Filed under emotion fear perception spatial perception neuroscience psychology science
New Dementia Diagnostic Exams and Gene Findings Bode Well for Treatment
The number of people affected by dementias continues to climb as baby boomers age, increasing the urgency to identify ways to prevent, diagnose and treat these neurodegenerative brain disorders.
Today it is possible to diagnose dementias more accurately than ever before, thanks to improvements in behavioral assessment tools, imaging techniques, gene testing and data collection and analysis, according to Bruce L. Miller, MD, a behavioral neurologist and professor of neurology at UCSF.
Miller, who came to UCSF in 1998 and directs the UCSF Memory and Aging Center, described recent advances during the lecture he gave at UCSF Mission Bay on Oct. 15 as part of receiving the Academic Senate’s 12th Annual Faculty Research Lectureship in Clinical Science.
The ability to diagnose different types of dementias accurately and to distinguish among the biological factors that cause them will become increasingly important as treatments become more promising and better targeted, Miller said.
Despite continued improvements in the tools available to physicians for diagnosing dementias, a common neurodegenerative disease known as frontotemporal dementia (FTD) remains understudied and is very often misdiagnosed, Miller said. For reasons that are in part historical, FTD still is thought of as a rare disease, a misconception that greatly contributes to its being underdiagnosed, he said. While Alzheimer’s disease is the most common dementia overall, among the population aged 65 and younger, FTD is just as common, according to Miller.
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Filed under brain neurodegenerative diseases dementia memory neuroscience science
Analysis of specific biomarkers in a cerebrospinal fluid sample can differentiate patients with Alzheimer’s disease from those with other types of dementia. The method, which is being studied by researchers at Sahlgrenska Academy, may eventually permit earlier detection of Alzheimer’s disease.
Due to the similarity of the symptoms, differentiating patients with Alzheimer’s from those with other types of dementia – or patients with Parkinson disease from those with other motor disorders – is often difficult.
Making a proper diagnosis is essential if proper treatment and medication are to commence at an early stage. A research team at Sahlgrenska Academy, University of Gothenburg, is developing a new method to differentiate patients with Alzheimer’s disease or Parkinson disease by analyzing a cerebrospinal fluid sample.
The study, led by Professor Kaj Blennow and conducted among 450 patients at Skåne University Hospital and Sahlgrenska University Hospital, involved testing five proteins that serve as biomarkers for the two diseases.
“Previous studies have shown that Alzheimer’s disease is associated with biochemical changes in specific proteins of the brain,” says Annika Öhrfelt, a researcher at Sahlgrenska Academy. “This study has found that the inclusion of a new protein can differentiate patients with Alzheimer’s disease from those with Lewy body dementia, Parkinson disease dementia and other types of dementia.”
Similarly, the biomarkers can differentiate patients with Parkinson disease from those with atypical Parkinsonian disorders.
“Additional studies are needed before the biomarkers can be used in clinical practice during the early stages of disease,” says Öhrfelt, “but these results represent an important step along the way.”
(Source: alphagalileo.org)
Filed under biomarkers cerebrospinal fluid alzheimer alzheimer's disease neuroscience science
Researchers at Washington University School of Medicine in St. Louis have found a key difference in the brains of people with Alzheimer’s disease and those who are cognitively normal but still have brain plaques that characterize this type of dementia.
“There is a very interesting group of people whose thinking and memory are normal, even late in life, yet their brains are full of amyloid beta plaques that appear to be identical to what’s seen in Alzheimer’s disease,” says David L. Brody, MD, PhD, associate professor of neurology. “How this can occur is a tantalizing clinical question. It makes it clear that we don’t understand exactly what causes dementia.”
Hard plaques made of a protein called amyloid beta are always present in the brain of a person diagnosed with Alzheimer’s disease, according to Brody. But the simple presence of plaques does not always result in impaired thinking and memory. In other words, the plaques are necessary – but not sufficient – to cause Alzheimer’s dementia.
The new study, available online in Annals of Neurology, still implicates amyloid beta in causing Alzheimer’s dementia, but not necessarily in the form of plaques. Instead, smaller molecules of amyloid beta dissolved in the brain fluid appear more closely correlated with whether a person develops symptoms of dementia. Called amyloid beta “oligomers,” they contain more than a single molecule of amyloid beta but not so many that they form a plaque.
Oligomers floating in brain fluid have long been suspected to have a role in Alzheimer’s disease. But they are difficult to measure. Most methods only detect their presence or absence, or very large quantities. Brody and his colleagues developed a sensitive method to count even small numbers of oligomers in brain fluid and used it to compare amounts in their samples.
The researchers examined samples of brain tissue and fluid from 33 deceased elderly subjects (ages 74 to 107). Ten subjects were normal – no plaques and no dementia. Fourteen had plaques, but no dementia. And nine had a diagnosis of Alzheimer’s disease – both plaques and dementia.
They found that cognitively normal patients with plaques and Alzheimer’s patients both had the same amount of plaque, but the Alzheimer’s patients had much higher oligomer levels.
But even oligomer levels did not completely distinguish the two groups. For example, some people with plaques but without dementia still had oligomers, even in similar quantity to some patients with Alzheimer’s disease. Where the two groups differed completely, according to Brody and his colleagues, was the ratio of oligomers to plaques. They measured more oligomers per plaque in patients with dementia, and fewer oligomers per plaque in the samples from cognitively normal people.
In people with plaques but no dementia, Brody speculates that the plaques could serve as a buffer, binding with free oligomers and keeping them tied down. And in dementia, perhaps the plaques have exceeded their capacity to capture the oligomers, leaving them free to float in the brain’s fluid, where they can damage or interfere with neurons.
Brody cautions that, due to the difficulty in getting samples, oligomer levels have never been measured in living people. Therefore, it’s possible these floating clumps of amyloid beta only form after death. Even so, he says, there is still a clear difference between the two groups.
“The plaques and oligomers appear to be in some kind of equilibrium,” Brody says. “What happens to shift the relationship between the oligomers and plaques? Like much Alzheimer’s research, this study raises more questions than it answers. But it’s an important next piece of the puzzle.”
(Source: news.wustl.edu)
Filed under brain alzheimer alzheimer's disease dementia brain plaques amyloid beta neuroscience science
A circuit diagram of the mouse brain
What happens in the brain when we see, hear, think and remember? To be able to answer questions like this, neuroscientists need information about how the millions of neurons in the brain are connected to each other. Scientists at the Max Planck Institute for Medical Research in Heidelberg have taken a crucial step towards obtaining a complete circuit diagram of the brain of the mouse, a key model organism for the neurosciences. The research group working with Winfried Denk has developed a method for preparing the whole mouse brain for a special microscopy process. With this, the resolution at which the brain tissue can be examined is so high that the fine extensions of almost every single neuron are visible.
Filed under brain neuron electron microscopy circuit diagram neuroscience science
Raw Food Not Enough to Feed Big Brains
Eating a raw food diet is a recipe for disaster if you’re trying to boost your species’ brainpower. That’s because humans would have to spend more than 9 hours a day eating to get enough energy from unprocessed raw food alone to support our large brains, according to a new study that calculates the energetic costs of growing a bigger brain or body in primates. But our ancestors managed to get enough energy to grow brains that have three times as many neurons as those in apes such as gorillas, chimpanzees, and orangutans. How did they do it? They got cooking, according to a study published online today in the Proceedings of the National Academy of Sciences.
"If you eat only raw food, there are not enough hours in the day to get enough calories to build such a large brain," says Suzana Herculano-Houzel, a neuroscientist at the Federal University of Rio de Janeiro in Brazil who is co-author of the report. "We can afford more neurons, thanks to cooking."
Humans have more brain neurons than any other primate—about 86 billion, on average, compared with about 33 billion neurons in gorillas and 28 billion in chimpanzees. While these extra neurons endow us with many benefits, they come at a price—our brains consume 20% of our body’s energy when resting, compared with 9% in other primates. So a long-standing riddle has been where did our ancestors get that extra energy to expand their minds as they evolved from animals with brains and bodies the size of chimpanzees?
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Filed under brain brain size cooking food evolution neuroscience science
