Posts tagged brain

ScienceDaily (Apr. 30, 2012) — Researchers studying multiple sclerosis (MS) have long been looking for the specific molecules in the body that cause lesions in myelin, the fatty, insulating cells that sheathe the nerves. Nearly a decade ago, a group at Mayo Clinic found a new enzyme, called Kallikrein 6, that is present in abundance in MS lesions and blood samples and is associated with inflammation and demyelination in other neurodegenerative diseases. In a study published this month in Brain Pathology,the same group found that an antibody that neutralizes Kallikrein 6 is capable of staving off MS in mice.

"We were able to slow the course of disease through early chronic stages, both in the brain and spinal cord," says lead author Isobel Scarisbrick, Ph.D., of the Mayo Clinic Department of Physical Medicine and Rehabilitation.

Researchers looked at mice representing a viral model of MS. The model is based on the theory that infection with viral infection early in life results in an eventual abnormal immune response in the brain and spinal cord. One week after being infected with a virus, the mice showed elevated levels of Kallikrein 6 enzyme in the brain and spinal cord. However, when researchers treated mice to produce an antibody capable of blocking and neutralizing the enzyme, they saw a decrease in diseases effecting the brain and spinal cord, including demyelination. The Kallikrein 6 neutralizing antibody had reduced inflammatory white blood cells and slowed the depletion of myelin basic protein, a key component of the myelin sheath.

The findings in the MS model have implications for other conditions affecting the brain and spinal cord. The group has previously shown that the Kallikrein 6 enzyme, produced by immune cells, is elevated in spinal cord injury, while other studies have shown it to be elevated in animal models of stroke and patients with post-polio syndrome.

"These findings suggest Kallikrein 6 plays a role in the inflammatory and demyelinating processes that accompany many types of neurological conditions," says Dr. Scarisbrick. "In the early chronic stages of some neurological diseases, Kallikrein 6 may represent a good molecule to target with drugs capable of neutralizing its effects."

Source: Science Daily

ScienceDaily (Apr. 30, 2012) — UC Davis researchers have found novel compounds that disrupt the formation of amyloid, the clumps of protein in the brains of people with Alzheimer’s disease believed to be important in causing the disease’s characteristic mental decline. The so-called “spin-labeled fluorene compounds” are an important new target for researchers and physicians focused on diagnosing, treating and studying the disease.

The study was published April 30 in the online journal PLoS ONE.

"We have found these small molecules to have significant beneficial effects on cultured neurons, from protecting against toxic compounds that form in neurons to reducing inflammatory factors," said John C. Voss, professor of biochemistry and molecular medicine at the UC Davis School of Medicine and the principal investigator of the study. "As a result, they have great potential as a therapeutic agent to prevent or delay injury in individuals in the earliest stages of Alzheimer’s disease, before significant damage to the brain occurs."

Amyloid is an accumulation of proteins and peptides that are otherwise found naturally in the body. One component of amyloid − the amyloid beta (Aβ) peptide − is believed to be primarily responsible for destroying neurons in the brain. Fluorene compounds, which are small three-ringed molecules, originally were developed as imaging agents to detect amyloid with PET imaging. In addition to being excellent for detecting amyloid, fluorenes bind and destabilize Aβ peptide and thereby reduce amyloid formation, according to previous findings in mice by Lee-Way Jin, another study author and associate professor in the UC Davis MIND Institute and Department of Medical Pathology and Laboratory Medicine.

The current research studied the effects of fluorene compounds by attaching a special molecule to make their activity evident using electron paramagnetic resonance (EPR) spectroscopy. This technology allows researchers to observe very specific activities of molecules of interest because biological tissues do not emit signals detectable by EPR. Since Voss was interested in the activity of fluorenes, he added a nitroxide “spin label,” a chemical species with a unique signal that can be measured by EPR.

The group found that spin-labeled compounds disrupted Aβ peptide formation even more effectively than did non-labeled fluorenes. In addition, the antioxidant properties of the nitroxide, which scavenge reactive oxygen species known to damage neurons and increase inflammation, significantly contributed to the protective effects on neurons.

"The spin-labeled fluorenes demonstrated a number of extremely important qualities: They are excellent for detecting amyloid in imaging studies, they disrupt Aβ formation, and they reduce inflammation," said Voss. "This makes them potentially useful in the areas of research, diagnostics and treatment of Alzheimer’s disease."

Alzheimer’s disease is the most common form of dementia and affects some 5 million Americans. Current medications used to fight the disease usually have only small and temporary benefits, and commonly have many side effects.

A major obstacle in developing Alzheimer’s disease therapy is that most molecules will not cross the blood-brain barrier, so that potential treatments given orally or injected into the bloodstream cannot enter the brain where they are needed. Fluorene compounds are small molecules that have been shown to penetrate the brain well.

"We have brought together expertise from diverse fields to get to this point, and what was once a side interest has become a major focus," said Voss. "We are very excited and hopeful that these unique compounds can become extremely important."

Voss’ group next plans to study the safety of spin-labeled fluorene compounds as well as their efficacy for treating models of Alzheimer’s disease in small animals.

Source: Science Daily

April 30, 2012

A Northwestern University study that will be published in the Proceedings of the National Academy of Sciences (PNAS) provides the first biological evidence that bilinguals’ rich experience with language in essence “fine-tunes” their auditory nervous system and helps them juggle linguistic input in ways that enhance attention and working memory.

Northwestern bilingualism expert Viorica Marian teamed up with auditory neuroscientist Nina Kraus to investigate how bilingualism affects the brain. In particular, they looked at subcortical auditory regions that are bathed with input from cognitive brain areas. In extensive research, Kraus has already shown that lifelong music training enhances language processing, and an examination of subcortical auditory regions helped to tell that tale.

"For our first collaborative study, we asked if bilingualism could also promote experience-dependent changes in the fundamental encoding of sound in the brainstem — an evolutionarily ancient part of the brain," said Marian, professor of communication sciences in Northwestern’s School of Communication. The answer, according to their study, is a resounding yes.

The researchers found that the experience of bilingualism changes how the nervous system responds to sound. “People do crossword puzzles and other activities to keep their minds sharp,” Marian said. “But the advantages we’ve discovered in dual language speakers come automatically simply from knowing and using two languages. It seems that the benefits of bilingualism are particularly powerful and broad, and include attention, inhibition and encoding of sound.”

Co-authored by Kraus, Marian and researchers Jennifer Krizman, Anthony Shook and Erika Skoe, “Bilingualism and the Brain: Subcortical Indices of Enhanced Executive Function” underscores the pervasive impact of bilingualism on brain development. The article will appear in the April 30 issue of PNAS.

"Bilingualism serves as enrichment for the brain and has real consequences when it comes to executive function, specifically attention and working memory," said Kraus, Hugh Knowles Professor at Northwestern. In future studies, she and Marian will investigate whether these results can be achieved by learning a language later in life.

In the study, the researchers recorded the brainstem responses to complex sounds (cABR) in 23 bilingual English-and-Spanish-speaking teenagers and 25 English-only-speaking teens as they heard speech sounds in two conditions.

Under a quiet condition, the groups responded similarly. But against a backdrop of background noise, the bilingual brains were significantly better at encoding the fundamental frequency of speech sounds known to underlie pitch perception and grouping of auditory objects. This enhancement was linked with advantages in auditory attention.

"Through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound," Kraus explained.

"Bilinguals are natural jugglers," said Marian. "The bilingual juggles linguistic input and, it appears, automatically pays greater attention to relevant versus irrelevant sounds. Rather than promoting linguistic confusion, bilingualism promotes improved ‘inhibitory control,’ or the ability to pick out relevant speech sounds and ignore others."

The study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. “The bilingual’s enhanced experience with sound results in an auditory system that is highly efficient, flexible and focused in its automatic sound processing, especially in challenging or novel listening conditions,” Kraus added.

Provided by Northwestern University

Source: medicalxpress.com

ScienceDaily (Apr. 30, 2012) — University of Iowa biologists have advanced the knowledge of human neurodevelopmental disorders by finding that a lack of a particular group of cell adhesion molecules in the cerebral cortex — the outermost layer of the brain where language, thought and other higher functions take place — disrupts the formation of neural circuitry.

Reconstructions of single wildtype (left) and gamma-protocadherin mutant (right) cortical neurons are superimposed upon a low magnification view of fluorescently-labeled neurons in the corresponding animals. (Credit: Image courtesy of University of Iowa Health Care)

Andrew Garrett, former neuroscience graduate student and current postdoctoral fellow at the Jackson Laboratory, Bar Harbor, Maine; Dietmar Schreiner, former postdoctoral fellow currently at the University of Basel, Switzerland; Mark Lobas, current neuroscience graduate student; and Joshua A. Weiner, associate professor in the UI College of Liberal Arts and Sciences Department of Biology, published their findings in the April 26 issue of the journal Neuron.

Cell adhesion is the way in which cells “hold hands” — how one cell binds itself to another cell using specific molecules that protrude from cell membranes and bind each other together. The process is necessary to form all body tissues. The UI researchers studied a clustered family of 22 genes (gamma-protocadherins) that make such cellular hand-holding possible by encoding cell adhesion molecules.

In their previous work, they found that mice lacking the molecules exhibited death of neurons and loss of synapses in the spinal cord. So, they knew the gamma-protocadherins were important for neurons in the spinal cord, but not whether this was true in the cortex. However, in the current study, they found that an absence of the cell adhesion molecules had a significant and much different effect.

"We found that mice lacking the gamma-protocadherins in the cortex do not exhibit the severe loss of synapses and increased neuronal death that we observed in the spinal cord," says Weiner. "Instead, we found that the cortical neurons had severely reduced development of their dendrites, tree-like branched structures that receive input from other neurons.

"We discovered the reason for this: gamma-protocadherins normally inhibit a key signaling pathway within neurons that acts to reduce dendrite branching. In the absence of the gamma-protocadherins, this signaling pathway was hyperactive, leading to defective branching of cortical neuron dendrites," says Weiner.

In their previous work, the researchers showed that these molecules — the 22 distinct adhesion molecules, the gamma-protocadherins — are critical for the development of the animal, because when all of the genes are deleted from mice, they die shortly after birth with a variety of neurological defects including loss of connections (synapses) and excessive neuronal cell death in the spinal cord — an early-developing part of the nervous system.

Because those mutants die so young, the researchers could not assess a role for the gamma-protocadherins in the cerebral cortex. The reason is that the cortex develops only after birth. They used new genetic technologies to remove the gamma-protocadherins only from the cerebral cortex, which allowed the animals to survive to adulthood.

Weiner says that the latest research findings may help researchers to better understand the causes of various human developmental disorders.

"Human neurodevelopmental disorders such as autism, mental retardation, and schizophrenia all involve dysregulation of dendrite branching and synaptogenesis," he says. "Our identification of a large family of 22 cell adhesion molecules — which we previously showed interact with each other in very complex and specific ways — as new regulators of dendrite branching raises the question of whether specific interactions between distinct neuronal groups during development is important for the spreading of dendritic branches. If so, the gamma-protocadherins and/or the signaling pathways they regulate might be disrupted in a variety of human brain disorders."

Now that the researchers have shown that the gamma-protocadherin family, as a whole, is critical for dendrite branching, they plan to become more focused in their research. Next, they plan to ask whether specific interactions between individual members of the family are important for instructing neurons on the location and size of dendrite growth.

Source: Science Daily

April 30, 2012

Neuropathic pain, caused by nerve or tissue damage, is the culprit behind many cases of chronic pain. It can be the result of an accident or caused by a variety of medical conditions and diseases such as tumors, lupus, and diabetes. Typically resistant to common types of pain management including ibuprofen and even morphine, neuropathic pain can lead to lifelong disability for many sufferers.

Now a drug developed by Tel Aviv University researchers, known as BL-7050, is offering new hope to patients with neuropathic pain. Developed by Prof. Bernard Attali and Dr. Asher Peretz of TAU’s Department of Physiology and Pharmacology at the Sackler Faculty of Medicine, the medication inhibits the transmission of pain signals throughout the body. In both in-vitro and in-vivo experiments measuring electrical activity of neurons, the compound has been shown to prevent the hyper-excitability of neurons — protecting not only against neuropathic pain, but epileptic seizures as well.

The medication has been licensed by Ramot, TAU’s technology transfer company, for development and commercialization by BioLineRx, an Israeli biopharmaceutical development company.

Targeting potassium for pain control

According to Prof. Attali, the medication works by targeting a group of proteins which act as a channel for potassium. Potassium has a crucial role in the excitability of cells, specifically those in the nervous system and the heart. When potassium channels don’t function properly, cells are prone to hyper-excitability, leading to neurological and cardiovascular disorders such as epilepsy and arrhythmias. These are also the channels that convey pain signals caused by nerve or tissue damage, known as neuropathic pain.

With few treatment options available for neuropathic pain, Prof. Attali set out to develop a medication that could bind to and stabilize the body’s potassium channels, controlling their hyper-excitability and preventing the occurrence of pain by keeping the channels open for the outflow of potassium. This novel targeting approach has been recently reported in the journal PNAS.

Inducing calm in the neurons

Understanding the mechanism that controls these channels has been crucial to the development of the drug. By successfully controlling the excitability of the neurons, Prof. Attali believes that BL-7050 could bring relief to hundreds of millions of patients around the world who suffer from neuropathic pain. The medication will reach the first phase of clinical trials in the near future.

In pre-clinical trials, BL-7050 was tested in rats experiencing both epilepsy and neuropathic pain and was found to be efficient in protecting against both when taken as a pill. While on the medication, rats were no longer affected by stimuli that had previously caused pain. Measures in the electrical activities of neurons also revealed that the medication was able to induce “calm” in the neurons, inhibiting pain pathways.

Provided by Tel Aviv University

Source: medicalxpress.com

April 30, 2012

(Medical Xpress) — Scientists at the UCSF-affiliated Gladstone Institutes have determined how specific circuitry in the brain controls not only body movement, but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson’s disease — and psychiatric disorders such as addiction and depression.

Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, PhD, discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson’s.

Now, in a paper published online today in Nature Neuroscience, Kreitzer, who is also an assistant professor of physiology at UCSF, and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson’s symptoms — and mark an important step in finding new treatments for those who suffer from addiction or depression.

“The physical symptoms that affect people with Parkinson’s — including tremors and rigidity of movement — are caused by an imbalance between two types of medium spiny neurons in the brain,” said Kreitzer, whose lab studies how Parkinson’s disease affects brain functions. “In this paper we showed that psychiatric disorders — specifically addiction and depression —might be caused by this same neural imbalance.”

Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake. And while researchers have long known about the link between a chemical in the brain called dopamine and Parkinson’s, Gladstone researchers recently clarified that dopamine maintains the balance between these two MSN types.

But abnormal dopamine levels are implicated not only in Parkinson’s, but also in addiction and depression. Kreitzer and his team hypothesized that the same circuitry that controlled movement might also control the process of learning to repeat pleasurable experiences and avoid unpleasant ones—and that an imbalance in this process could lead to addictive or depressive behaviors.

Kreitzer and his team genetically modified two sets of mice so that they could control which specific type of MSN was activated. They placed mice one at a time in a box with two triggers — one that delivered a laser pulse to stimulate the neurons and one that did nothing. They then monitored which trigger each mouse preferred.

“The mice that had only dMSNs activated gravitated toward the laser trigger, pushing it again and again to get the stimulation — reminiscent of addictive behavior,” said Alexxai Kravitz, PhD, Gladstone postdoctoral fellow and a lead author of the paper. “But the mice that had only iMSNs activated did the opposite. Unlike their dMSN counterparts, the iMSN mice avoided the laser stimulation, which suggests that they found it unpleasant.” These findings reveal a precise relationship between the two MSN types and how behaviors are learned. They also show how an MSN imbalance can throw normal learning processes out of whack, potentially leading to addictive or depressive behavior.

“People with Parkinson’s disease often show signs of depression before the onset of significant movement problems, so it’s likely that the neural imbalance in Parkinson’s is also responsible for some behavioral changes associated with the disease,” said Kreitzer, who is also an assistant professor of physiology at UCSF.. “Future research could discover how MSNs are activated in those suffering from addiction or depression—and whether tweaking them could reduce their symptoms and improve their quality of life.

Graduate student Lynne Tye was also a lead author on this paper. Funding came from a variety of sources, including the W.M. Keck Foundation, the Pew Biomedical Scholars Program, the McKnight Foundation and the National Institutes of Health.

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Provided by University of California, San Francisco 

Source: medicalxpress.com

April 30, 2012

Children with developmental delay or autism may have unrecognized epilepsy-like brain activity during sleep, report researchers at Boston Children’s Hospital. These nighttime electrical spikes, detectable only on EEGs, occur even in some children without known epilepsy and appear to result from early strokes or other early life injuries to the developing brain, the study found. Results were published online April 25 by the journal Neurology.

“Kids can have an almost normal EEG while awake, but may show increased spikes during sleep,” says lead investigator Tobias Loddenkemper, MD, a neurologist in the Epilepsy Center at Boston Children’s. “If nighttime spiking remains undiagnosed and untreated, it may interfere with learning and development. This has been frequently overlooked in the past.”

Based on their findings, the researchers suggest that sleep EEG monitoring should be considered more often in children not meeting developmental milestones, and that bedtime medications to suppress nighttime seizures may be beneficial if heightened brain electrical activity is found. In a preliminary treatment trial, such nighttime dosing before times of greatest spike or seizure activity has been found to be beneficial.

The study involved sleep EEG monitoring in 147 patients who were suspected of having excess brain electrical activity during sleep, based on loss of developmental milestones, and, in some cases, known seizures. All children had at least one brain MRI available for review. The EEGs and MRIs were read by physicians who did not know details of the patients’ history.

Of the 147 patients, seen at Boston Children’s over a 14-year period, 100 had prominent EEG spikes during sleep; the other 47 (controls) did not. Although there was no significant difference between groups in the percentage of patients with recognized seizures (78 percent of the “spike” group versus 64 percent of controls) or on most clinical measures, the “spike” group had significantly more patients with brain lesions on MRI (48 vs. 19 percent).

Children with EEG spikes were especially more likely than controls (14 vs. 2 percent) to have damage in the thalamus, the structure that relays sensory and motor signals to the cortex and regulates sleep and consciousness. The most common type of brain injury was early stroke (found in 14 vs. 0 percent, respectively).

The authors speculate that these early injuries disrupt circuit formation in the developing brain and lead to over-excitability – too much communication that is reflected in the EEG spikes and that may impinge on learning and development. “We know that children lose skills when these spikes appear,” says Loddenkemper. “These children lose out on a critical period of brain development and may never fully catch up later in life.”

Loddenkemper notes that up to 20 percent of children with heightened nighttime brain electrical activity do not have seizures or recognizable epilepsy. “Developmental delay may be the only clinical finding in some children,” he says. “Children at age 2 or 3, and sometimes older, may suddenly lose developmental milestones such as language, walking skills or fine motor movement.”

In the future, Loddenkemper and colleagues hope to conduct a prospective, multicenter trial in which they follow children with known early brain injury and monitor their nighttime EEG activity. They will then try different drugs to suppress nighttime spiking to see how the children’s long-term learning and development are affected.

Provided by Children’s Hospital Boston 

Source: medicalxpress.com

April 29, 2012

Why do some teenagers start smoking or experimenting with drugs—while others don’t?

Newly discovered networks in the brain, shown here in color, go a long way toward explaining why some teenagers are more likely to start experimenting with drugs and alcohol. Diminished activity in some of these networks, discovered by two scientists at the University of Vermont and their European colleagues, makes some teens more impulsive — and less able to inhibit urges to try alcohol, cigarettes and illegal drugs in early adolescence. Credit: Robert Whelan, University of Vermont, Nature Neuroscience, 2012

In the largest imaging study of the human brain ever conducted—involving 1,896 14-year-olds—scientists have discovered a number of previously unknown networks that go a long way toward an answer.

Robert Whelan and Hugh Garavan of the University of Vermont, along with a large group of international colleagues, report that differences in these networks provide strong evidence that some teenagers are at higher risk for drug and alcohol experimentation—simply because their brains work differently, making them more impulsive.

Their findings are presented in the journal Nature Neuroscience, published online April 29, 2012.

This discovery helps answer a long-standing chicken-or-egg question about whether certain brain patterns come before drug use—or are caused by it.

"The differences in these networks seem to precede drug use," says Garavan, Whelan’s colleague in UVM’s psychiatry department, who also served as the principal investigator of the Irish component of a large European research project, called IMAGEN, that gathered the data about the teens in the new study.

In a key finding, diminished activity in a network involving the “orbitofrontal cortex” is associated with experimentation with alcohol, cigarettes and illegal drugs in early adolescence.

"These networks are not working as well for some kids as for others," says Whelan, making them more impulsive.

Faced with a choice about smoking or drinking, the 14-year-old with a less functional impulse-regulating network will be more likely to say, “yeah, gimme, gimme, gimme!” says Garavan, “and this other kid is saying, ‘no, I’m not going to do that.’”

Testing for lower function in this and other brain networks could, perhaps, be used by researchers someday as “a risk factor or biomarker for potential drug use,” Garavan says.

The researchers were also able to show that other newly discovered networks are connected with the symptoms of attention-deficit hyperactivity disorder. These ADHD networks are distinct from those associated with early drug use.

In recent years, there has been controversy and extensive media attention about the possible connection between ADHD and drug abuse. Both ADHD and early drug use are associated with poor inhibitory control—they’re problems that plague impulsive people.

But the new research shows that these seemingly related problems are regulated by different networks in the brain—even though both groups of teens can score poorly on tests of their “stop-signal reaction time,” a standard measure of overall inhibitory control used in this study and other similar ones. This strengthens the idea that risk of ADHD is not necessarily a full-blown risk for drug use as some recent studies suggest.

The impulsivity networks—connected areas of activity in the brain revealed by increased blood flow—begin to paint a more nuanced portrait of the neurobiology underlying the patchwork of attributes and behaviors that psychologists call impulsivity—as well as the capacity to put brakes on these impulses, a set of skills sometimes called inhibitory control.

Edythe London, Professor of Addiction Studies and Director of the UCLA Laboratory of Molecular Pharmacology, who was not part of the new study, described it as “outstanding,” noting that the work by Whelan and others “substantially advances our understanding of the neural circuitry that governs inhibitory control in the adolescent brain.”

Using a complex mathematical approach called factor analysis, Whelan and colleagues were able to fish out seven networks involved when impulses were successfully inhibited and six networks involved when inhibition failed—from the vast and chaotic actions of a teenage brain at work. These networks “light up,” Whelan says, in a functional MRI scanner during trials when the teenagers were asked to perform a repetitive task that involved pushing a button on a keyboard, but then were able to successfully stop—or inhibit—the act of pushing the button in mid-action. Those teens with better inhibitory control were able to succeed at this task faster.

But the underlying networks behind these tasks could not have been detectable in a “typical fMRI study of about 16 or 20 people,” says Whelan. “This study was orders of magnitude bigger, which lets us overcome much of the randomness and noise—and find the brain regions that actually vary together.”

"The take-home message is that impulsivity can be decomposed, broken down into different brain regions," says Garavan, "and the functioning of one region is related to ADHD symptoms, while the functioning of other regions is related to drug use.

The new study draws on the multi-year work of the IMAGEN Consortium, funded by the European Union, and headed by Prof. Gunter Schumann at the Institute of Psychiatry, King’s College London. IMAGEN, lead by a team of scientists across Europe, carried out neuroimaging, genetic and behavioral analyses in 2000 teenage volunteers in Ireland, England, France, and Germany and will be following them for several years, investigating the roots of risk-taking behavior and mental health in teenagers.

That teenagers push against boundaries—and sometimes take risks—is as predictable as the sunrise. It happens in all cultures and even across all mammal species: adolescence is a time to test limits and develop independence.

But death among teenagers in the industrialized world is largely caused by preventable or self-inflicted accidents that are often launched by impulsive risky behaviors, often associated with alcohol and drug use. Additionally, “addiction in the western world is our number one health problem,” says Garavan. “Think about alcohol, cigarettes or harder drugs and all the consequences that has in society for people’s health.” Understanding brain networks that put some teenagers at higher risk for starting to use them could have large implications for public health.

Provided by University of Vermont

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — In a new study, scientists at the University of Copenhagen show that a specific type of carbohydrate plays an important role in the intercellular signalling that controls the growth and development of the nervous system. In particular, defects in that carbohydrate may result in the uninhibited cell growth that characterizes the genetic disease neurofibromatosis and certain types of cancer.

Egghead to the right: Changes in cellular growth. (Credit: Klaus Qvortrup)

The results have just been published in the well-reputed journal PNAS.

Scientists from The Faculty of Health and Medical Sciences at the University of Copenhagen have put a special type of fruit fly under the microscope. The new research results turn the spotlight on a certain group of carbohydrates — the so-called glycolipids — and their influence on the cells’ complicated communication system. In the long term, this model study can shine new light on the disease neurofibromatosis for the benefit of patients the world over.

"The most important thing about our discovery right now is that we document a new function for carbohydrates in the communication between cells. We also show how disturbances in the signalling pathways cause changes in cellular growth. This is knowledge that cancer researchers can develop," says Ole Kjærulff, doctor and associate professor at the Department of Neuroscience and Pharmacology, who has conducted the study together with Dr. Katja Dahlgaard, and Hans Wandall, associate professor at the Copenhagen Center for Glycomics.

Sugar chains control cell growth

Glycolipids are compounds consisting of fats linked to long chains of sugar molecules. They are located in the cell membrane, where they serve various functions, such as protecting the cell or making it recognizable to the immune system.

"In the fruit fly model, if we prevent the sugar chains from lengthening, we can show that carbohydrate plays an important role in controlling the growth of normal cells. When the sugar chains are shortened, the tissue grows dramatically on account of increased cell division. In particular, it appears that the nervous system’s support cells — the glia cells — are influenced," explains Hans Wandall, associate professor.

Neurofibromatosis can cause deformity

The new results also influence our understanding of neurofibromatosis. This is a heritable disorder that results in unsightly tumours — so-called neurofibromas — in the nerves and skin. The disease affects approximately 20 people out of 100,000 and varies from mild to severe cases with decided deformities. The condition also affects the bones and often causes learning problems:

"When you get closer to an understanding of the mechanisms that result in a certain disease, naturally it is easier to influence the disease process in the form of drug development in the longer term. Neurofibromatosis is not a terminal disease, but it very much affects the life quality of the people who have it because the symptoms are so noticeable," explains Ole Kjærulff. Hans Wandall adds that the disease is also associated with certain types of cancer, particularly in the brain.

Source: Science Daily