Posts tagged brain
Articles and news from the latest research reports.
Making Sense out of the Biological Matrix of Bipolar Disorder
ScienceDaily (Aug. 20, 2012) — The more that we understand the brain, the more complex it becomes. The same can be said about the genetics and neurobiology of psychiatric disorders. For “Mendelian” disorders, like Huntington disease, mutation of a single gene predictably produces a single clinical disorder, following relatively simple genetic principals. Compared to Mendelian disorders, understanding bipolar disorder has been extremely challenging. Its biology is not well understood and its genetics are complex.
In a new paper, Dr. Inti Pedroso and colleagues utilize an integrative approach to probe the biology of bipolar disorder. They combined the results of three genome-wide association studies, which examined the association of common gene variants with bipolar disorder throughout the genome, and a study of gene expression patterns in post-mortem brain tissue from people who had been diagnosed with bipolar disorder. The findings were analyzed within the context of how brain proteins relate to each other based on the Human Protein Reference Database protein-protein interaction network.
"None of our research approaches provides us with sufficient information, by itself, to understand the neurobiology of psychiatric disorders. This innovative paper wrestles with this challenge in a creative way that helps us to move forward in thinking about the neurobiology of bipolar disorder," commented Dr. John Krystal, Editor of Biological Psychiatry.
Dr. Pedroso explained, “We combined information about genetic variation from thousands of cases and controls with brain gene expression data and information from protein databases to identify networks of genes and proteins in the brain that are key in the development of bipolar disorder.”
The analysis resulted in the ability to define risk gene variants that were deemed functional, by virtue of the association with changes in gene expression levels, and to group these functional gene variants in biologically meaningful pathways.
The results implicated genes involved in several neural signaling pathways, including the Notch and Wnt signaling pathways. These pathways are key processes in neurotransmission and brain development and these findings indicate they are also likely to be involved in causing this severe disorder. The authors noted that three features stand out among these genes: i) they localized to the human postsynaptic density, which is crucial for neuronal function; ii) their mouse knockouts present altered behavioral phenotypes; and iii) some are known targets of the pharmacological treatments for bipolar disorder.
Dr. Gerome Breen, senior author on the study and Senior Lecturer at King’s College London Institute of Psychiatry, said, “Our study provides some of the first evidence to show the biochemical and developmental processes involved in causing risk for developing this life-long and costly illness. We have highlighted potential new avenues for new drug treatments and intervention.”
Source: Science Daily
A technique called high-definition fiber tractography (HDFT) provides a powerful new tool for tracing the course of nerve fiber connections within the brain — with the potential to improve the accuracy of neurosurgical planning and to advance scientific understanding of the brain’s structural and functional networks, reports a paper in the August issue of Neurosurgery, official journal of the Congress of Neurological Surgeons.
Amputation disrupts not only the peripheral nervous system but also central structures of the brain. While the brain is able to adapt and compensate for injury in certain conditions, in amputees the traumatic event prevents adaptive cortical changes. A group of scientists reports adaptive plastic changes in an amputee’s brain following implantation of multielectrode arrays inside peripheral nerves.
"We found that a neurally-interfaced hand prosthesis re-established communication between the central and peripheral nervous systems, not only restructuring the areas directly responsible for motor control but also their functional balance within the bi-hemispheric system necessary for motor control," says lead investigator Camillo Porcaro, PhD, of the Institute of Neuroscience, Newcastle University, Medical School, Newcastle upon Tyne, UK and the Institute of Cognitive Sciences and Technologies (ISTC) — National Research Council (CNR).
Deep Brain Stimulation to Treat Obesity?
ScienceDaily (Aug. 20, 2012) — Scientific advances in understanding the “addiction circuitry” of the brain may lead to effective treatment for obesity using deep brain stimulation (DBS), according to a review article in the August issue of Neurosurgery, official journal of the Congress of Neurological Surgeons.
Electrical brain stimulation targeting the “dysregulated reward circuitry” could make DBS — already an accepted treatment for Parkinson’s disease — a new option for the difficult-to-treat problem of obesity. Dr. Alexander Taghva of Ohio State University and University of Southern California was lead author of the new review.
New Insights into ‘Reward Circuitry’
Obesity is a major public health problem that is notoriously difficult to treat. Although various approaches can promote weight loss, patients typically gain weight soon after the end of treatment. Drug options have shown limited success, with several products removed from the market because of serious adverse effects. Bariatric surgery is effective in many cases of obesity but has a significant failure rate and is associated with side effects.
Drug treatments for obesity have targeted the homeostatic (self-regulating) mechanism regulating appetite and body weight. The homeostatic mechanism is thought to involve the “feeding center” in the hypothalamus, which produces hormones (such as leptin and insulin) that affect feeding behavior.
Initial experiments exploring DBS as a treatment for obesity have targeted the hypothalamus. However — as with drug options focusing on the homeostatic mechanisms — success has been limited.
Possible Role of DBS for Obesity
More recent studies have explored a different mechanism: specifically, the “reward circuitry,” of the brain. Research has suggested that obesity is associated with a “relative imbalance” of the reward circuitry. Studies show that obese subjects — like those with addictive behaviors — are more impulsive and less able to delay gratification. The reward circuitry is intimately interconnected with the homeostatic mechanisms.
Together, these studies raise the possibility of new DBS approaches to the treatment of obesity. In DBS, a small electrode is surgically placed in a precise location in the brain. A mild electrical current is delivered to stimulate that area of the brain, with the goal of interrupting abnormal activity. Deep brain stimulation has become a standard and effective treatment for movement disorders such as Parkinson’s disease.
Just as stimulation of the brain areas responsible for abnormal movement helps “turn off” tremors in patients with Parkinson’s disease, stimulation of the areas involved in dysregulated reward circuitry might be able to “turn off” abnormal feeding behaviors in obese patients. The authors outline evidence implicating several different brain areas involved in the brain’s reward circuitry — particularly the “frontostriatal circuitry” — which could be useful targets for DBS.
Previous reports in individual patients have suggested that DBS performed for other reasons — particularly severe obsessive-compulsive disorder — have unexpectedly had unpredicted beneficial effects on addictive behaviors like smoking and overeating. Dr. Taghva and colleagues hope their review will open the way to further exploration of DBS as part of new and effective strategies for the treatment of obesity, perhaps in combination with therapies targeting the homeostatic mechanism.
Source: Science Daily
Stroke disrupts how brain controls muscle synergies
The simple act of picking up a pencil requires the coordination of dozens of muscles: The eyes and head must turn toward the object as the hand reaches forward and the fingers grasp it. To make this job more manageable, the brain’s motor cortex has implemented a system of shortcuts. Instead of controlling each muscle independently, the cortex is believed to activate muscles in groups, known as “muscle synergies.” These synergies can be combined in different ways to achieve a wide range of movements.
This graphic shows the brain, with the motor cortex highlighted in yellow.
Graphic: Christine Daniloff
A new study from MIT, Harvard Medical School and the San Camillo Hospital in Venice finds that after a stroke, these muscle synergies are activated in altered ways. Furthermore, those disruptions follow specific patterns depending on the severity of the stroke and the amount of time that has passed since the stroke.
The findings, published this week in the Proceedings of the National Academy of Sciences, could lead to improved rehabilitation for stroke patients, as well as a better understanding of how the motor cortex coordinates movements, says Emilio Bizzi, an Institute Professor at MIT and senior author of the paper.
“The cortex is responsible for motor learning and for controlling movement, so we want to understand what’s going on there,” says Bizzi, who is a member of the McGovern Institute for Brain Research at MIT. “How does the cortex translate an idea to move into a series of commands to accomplish a task?”
Have you ever wondered why you can remember things from long ago as if they happened yesterday, yet sometimes can’t recall what you ate for dinner last night? According to a new study led by psychologists at the University of Toronto, it’s because how much something means to you actually influences how you see it as well as how vividly you can recall it later.
"We’ve discovered that we see things that are emotionally arousing with greater clarity than those that are more mundane," says Rebecca Todd, a postdoctoral fellow in U of T’s Department of Psychology and lead author of the study published recently in the Journal of Neuroscience. "Whether they’re positive — for example, a first kiss, the birth of a child, winning an award — or negative, such as traumatic events, breakups, or a painful and humiliating childhood moment that we all carry with us, the effect is the same."
"What’s more, we found that how vividly we perceive something in the first place predicts how vividly we will remember it later on," says Todd. "We call this ‘emotionally enhanced vividness’ and it is like the flash of a flashbub that illuminates an event as it’s captured for memory."
All vertebrates’ eyes emerge from a single group of cells, called the eye field, located in the middle of the brain. The eye field cells evaginate to form two optic vesicles, which eventually give rise to two retinas, one on either side of the brain.
Eyes Emerge
Top image: In a ~5 somites embryo, eye field cells are stained red, and forebrain cells are outlined in green (upper left). A few hours later, in a ~10 somites embryo, the eye field (green) separates into two optic vesicles. At the same embryonic stage, the dorsal telencephalon, which sits atop the evaginating eyes, is labeled blue (bottom left). In both of these images, a midline positioned cross outlines the apical surface of the optic vesicles and the ventricular space. The animation follows the development of this same surface as the eyes emerge from the brain.
Sunrise in the Eye
Bottom image: Once the basic shape of the eye is specified, cells within the optic cup differentiate, populating the retina with neurons that sense light and refine the visual information before it is transmitted to the brain. In fish and amphibia, retinal stem cells are maintained throughout the animal’s lifetime in a stem cell niche located adjacent to the lens (yellow). Here in situ hybridization of a zebrafish eye (from a ~ 3-day-old larva) reveals gene expression patterns that distinguish retinal stem cells (red) from the cells that are becoming neurons (purple). By comparing gene expression patterns within the retinal stem cell niche in normal and mutant eyes, we gain insight into how stem cells turn into neurons.
(Source: cell.com)
Microbes manipulate your mind
Gut bacteria may influence thoughts and behaviour
The human gut contains a diverse community of bacteria that colonize the large intestine in the days following birth and vastly outnumber our own cells. These so-called gut microbiota constitute a virtual organ within an organ, and influence many bodily functions. Among other things, they aid in the uptake and metabolism of nutrients, modulate the inflammatory response to infection, and protect the gut from other, harmful micro-organisms. A study by researchers at McMaster University in Hamilton, Ontario now suggests that gut bacteria may also influence behaviour and cognitive processes such as memory by exerting an effect on gene activity during brain development.
Image: Brian Stauffer
Jane Foster and her colleagues compared the performance of germ-free mice, which lack gut bacteria, with normal animals on the elevated plus maze, which is used to test anxiety-like behaviours. This consists of a plus-shaped apparatus with two open and two closed arms, with an open roof and raised up off the floor. Ordinarily, mice will avoid open spaces to minimize the risk of being seen by predators, and spend far more time in the closed than in the open arms when placed in the elevated plus maze.
This is exactly what the researchers found when they placed the normal mice into the apparatus. The animals spent far more time in the closed arms of the maze and rarely ventured into the open ones. The germ-free mice, on the other hand, behaved quite differently – they entered the open arms more often, and continued to explore them throughout the duration of the test, spending significantly more time there than in the closed arms.
(Source: Guardian)
Scientists have demonstrated an automated system that uses artificial intelligence and cutting-edge image processing to rapidly examine large numbers of individual Caenorhabditis elegans, a species of nematode widely used in biological research. Beyond replacing existing manual examination steps using microfluidics and automated hardware, the system’s ability to detect subtle differences from worm-to-worm – without human intervention – can identify genetic mutations that might not have been detected otherwise.
By allowing thousands of worms to be examined autonomously in a fraction of the time required for conventional manual screening, the technique could change the way that high throughput genetic screening is carried out using C. elegans.
Hang Lu’s research team is studying genes that affect the formation and development of synapses in the worms, work that could have implications for understanding human brain development. The researchers use a model in which synapses of specific neurons are labeled by a fluorescent protein. Their research involves creating mutations in the genomes of thousands of worms and examining the resulting changes in the synapses. Mutant worms identified in this way are studied further to help understand what genes may have caused the changes in the synapses.
Gypsy study unravels a novel ataxia gene
17 August 2012
A WA study of an isolated population of Eastern European Gypsies known as “Bowlmakers” has unlocked clues about a serious developmental disease - congenital cerebellar ataxia.
Professor Luba Kalaydjieva and Dr Dimitar Azmanov, from The University of Western Australia, say the discovery of an important genetic mutation is likely to inspire other scientific work around the world.
The result of their research for the UWA-affiliated Western Australian Institute for Medical Research (WAIMR) was published online today in the prestigious American Journal of Human Genetics.
It involved working collaboratively with other Australian and European researchers to discover mutations within a gene which has never before been linked to this form of heredity ataxia in humans.
Ataxias are a large group of neurodegenerative disorders that affect the ability to maintain balance, and learn and maintain motor skills. While many genes have already been implicated in hereditary ataxias, understanding their molecular basis is far from complete. New knowledge will help the understanding of normal brain development and function, and the mechanisms of degeneration.
"Gypsies are a founder population," Professor Kalaydjieva said. "They are derived from a small number of ancestors and have remained relatively isolated from surrounding populations. The Bowlmakers - known for their wooden handicrafts such as bowls and spoons - were an ideal group to study because they are a younger sub-isolate, showing limited genetic diversity.
"We studied a novel form of ataxia in 3 families in this ethnic group. Clinical and brain-imaging investigations were done in Bulgaria, in collaboration with radiologists from Sir Charles Gairdner Hospital and Princess Margaret Hospital, and were followed-up by genetic studies at WAIMR and the Walter and Eliza Hall Institute (WEHI), Melbourne.
"Signs of ataxia were detected in early infancy when motor skills like crawling and rolling over did not develop. The affected individuals presented with global developmental delay, ataxia and intellectual deficit. MRI scans showed signs of degeneration of the cerebellum, which is part of the brain controlling motor and learning skills. Overall, the life expectancy is not decreased but the quality of life is severely affected.
"The parents of the affected individuals did not present with any clinical symptoms of the ataxia, suggesting recessive inheritance," Dr Azmanov said. "Our genetic studies showed unique changes in the gene encoding metabotropic glutamate receptor 1 (GRM1), which is important for the normal development of the cerbellar cortex. The mutations inherited by all affected individuals from their unaffected carrier parents dramatically altered the structure of the GRM1 receptor.”
Professor Kalaydjieva said the exact pathogenetic mechanisms leading to the clinical manifestations and cerebellar degeneration are yet to be explained and that this opens novel research avenues for the wider scientific community. ”It also remains to be seen if other ataxia patients around the world carry mutations in GRM1,” she said.