Neuroscience

March 12th, 2012

Scientists from the Monell Center report that seven of 12 related mammalian species have lost the sense of sweet taste. As each of the sweet-blind species eats only meat, the findings demonstrate that a liking for sweets is frequently lost during the evolution of diet specialization.

Previous research from the Monell team had revealed the remarkable finding that both domestic and wild cats are unable to taste sweet compounds due to defects in a gene that controls structure of the sweet taste receptor.

Cats are obligate carnivores, meaning that they subsist only on meat. In the current study, published online in Proceedings of the National Academy of Sciences USA, the Monell scientists next asked whether other strict carnivores have also lost the sweet taste receptor.

To do this, they examined sweet taste receptor genes from 12 related mammalian species with varying dietary habits. They once again found taste loss and to their surprise, it was widespread in the meat-eating species.

Senior author Gary Beauchamp, Ph.D., a behavioral biologist at Monell, comments, “Sweet taste was thought to be nearly a universal trait in animals. That evolution has independently led to its loss in so many different species was quite unexpected.”

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ScienceDaily (Mar. 8, 2012) — A new study in Science suggests that thrill-seeking is not limited to humans and other vertebrates. Some honey bees, too, are more likely than others to seek adventure. The brains of these novelty-seeking bees exhibit distinct patterns of gene activity in molecular pathways known to be associated with thrill-seeking in humans, researchers report.

A new study in Science suggests that thrill-seeking is not limited to humans and other vertebrates. Some honey bees, too, are more likely than others to seek adventure. (Credit: L. Brian Stauffer)

The findings offer a new window on the inner life of the honey bee hive, which once was viewed as a highly regimented colony of seemingly interchangeable workers taking on a few specific roles (nurse or forager, for example) to serve their queen. Now it appears that individual honey bees actually differ in their desire or willingness to perform particular tasks, said University of Illinois entomology professor and Institute for Genomic Biology director

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ScienceDaily (Mar. 8, 2012) — How do neurons in the brain communicate with each other? One common theory suggests that individual cells do not exchange signals among each other, but rather that exchange takes place between groups of cells. Researchers from Japan, the United States and Germany have now developed a mathematical model that can be used to test this assumption. Their results have been published in the current issue of the journal “PLoS Computational Biology.”

A neuron in the neocortex, the part of the brain that deals with higher brain functions, contacts thousands of other neurons and receives as many inputs from other neurons. Previously, it has been very difficult to use measured signals to interpret the way the cells work together. Scientists at the RIKEN Brain Science Institute (BSI) in Japan have now joined forces with researchers at the Forschungszentrum Jülich, Germany, and MIT in Boston, USA, to develop a mathematical model that can clarify the way neurons collaborate.

"From the many signals measured in parallel, the novel method filters the information on whether the neurons communicate individually or as a group," explains Dr. Hideaki Shimazaki from BSI. "Furthermore it takes into account that these groups of cells are not fixed but, instead, can organize themselves flexibly within milliseconds into groups of different composition, depending on the current requirements of the brain."

Prof. Sonja Grün from Forschungszentrum Jülich hopes that the method can help researchers to prove the existence of dynamic cell assemblies and clearly assign their activities to certain behaviors. The scientists already demonstrated that neurons work together when an animal anticipates a signal, which may allow it to have a more rapid or more sensitive response.

In future, the scientists hope to learn how to use their methods on the signals recorded from hundreds of neurons simultaneously. This would raise the probability of observing cell assemblies involved in planning and controlling behavior.

Source: Science Daily

ScienceDaily (Mar. 8, 2012) — UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs. (Credit: © rolffimages / Fotolia)

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants — meaning they needed lower doses of the drugs to affect ‘mood’ — and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in The Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain’s hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain’s synapses," said Dr. Parada, an elected member of the National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. “Older mice lacking the protein responded as if they had been taking antidepressants all their lives,” said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada’s laboratory has published a series of studies that link the Nf1 gene — best known for mutations that cause tumors to grow around nerves — to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body’s immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease.

Source: Science Daily

March 9, 2012

(Medical Xpress) — Despite a century of research, memory encoding in the brain has remained mysterious. Neuronal synaptic connection strengths are involved, but synaptic components are short-lived while memories last lifetimes. This suggests synaptic information is encoded and hard-wired at a deeper, finer-grained molecular scale.

In an article in the March 8 issue of the journal PLoS Computational Biology, physicists Travis Craddock and Jack Tuszynski of the University of Alberta, and anesthesiologist Stuart Hameroff of the University of Arizona demonstrate a plausible mechanism for encoding synaptic memory in microtubules, major components of the structural cytoskeleton within neurons.

Microtubules are cylindrical hexagonal lattice polymers of the protein tubulin, comprising 15 percent of total brain protein. Microtubules define neuronal architecture, regulate synapses, and are suggested to process information via interactive bit-like states of tubulin. But any semblance of a common code connecting microtubules to synaptic activity has been missing. Until now.

The standard experimental model for neuronal memory is long term potentiation (LTP) in which brief pre-synaptic excitation results in prolonged post-synaptic sensitivity. An essential player in LTP is the hexagonal enzyme calcium/calmodulin-dependent protein kinase II (CaMKII). Upon pre-synaptic excitation, calcium ions entering post-synaptic neurons cause the snowflake-shaped CaMKII to transform, extending sets of 6 leg-like kinase domains above and below a central domain, the activated CaMKII resembling a double-sided insect. Each kinase domain can phosphorylate a substrate, and thus encode one bit of synaptic information. Ordered arrays of bits are termed bytes, and 6 kinase domains on one side of each CaMKII can thus phosphorylate and encode calcium-mediated synaptic inputs as 6-bit bytes. But where is the intra-neuronal substrate for memory encoding by CaMKII phosphorylation? Enter microtubules.

Using molecular modeling, Craddock et al reveal a perfect match among spatial dimensions, geometry and electrostatic binding of the insect-like CaMKII, and hexagonal lattices of tubulin proteins in microtubules. They show how CaMKII kinase domains can collectively bind and phosphorylate 6-bit bytes, resulting in hexagonally-based patterns of phosphorylated tubulins in microtubules. Craddock et al calculate enormous information capacity at low energy cost, demonstrate microtubule-associated protein logic gates, and show how patterns of phosphorylated tubulins in microtubules can control neuronal functions by triggering axonal firings, regulating synapses, and traversing scale.

Microtubules and CaMKII are ubiquitous in eukaryotic biology, extremely rich in brain neurons, and capable of connecting membrane and cytoskeletal levels of information processing. Decoding and stimulating microtubules could enable therapeutic intervention in a host of pathological processes, for example Alzheimer’s disease in which microtubule disruption plays a key role, and brain injury in which microtubule activities can repair neurons and synapses.

Hameroff, senior author on the study, said: “Many neuroscience papers conclude by claiming their findings may help understand how the brain works, and treat Alzheimer’s, brain injury and various neurological and psychiatric disorders. This study may actually do that. We may have a glimpse of the brain’s biomolecular code for memory.”

Provided by University of Arizona

Source: medicalxpress.com

ScienceDaily (Mar. 8, 2012) — The hair cells of the inner ear have a previously unknown “root” extension that may allow them to communicate with nerve cells and the brain to regulate sensitivity to sound vibrations and head position, researchers at the University of Illinois at Chicago College of Medicine have discovered.

Type 2 hair cell with hair cell rootlets ending as expected in the cuticular plate. (Credit: Copyright University of Illinois Board of Trustees/Artist, Anna Lysakowski)

Their finding is reported online in advance of print in the Proceedings of the National Academy of Sciences.

The hair-like structures, called stereocilia, are fairly rigid and are interlinked at their tops by structures called tip-links.

When you move your head, or when a sound vibration enters your ear, motion of fluid in the ear causes the tip-links to get displaced and stretched, opening up ion channels and exciting the cell, which can then relay information to the brain, says Anna Lysakowski, professor of anatomy and cell biology at the UIC College of Medicine and principal investigator on the study.

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ScienceDaily (Mar. 8, 2012) — In both animals and humans, vocal signals used for communication contain a wide array of different sounds that are determined by the vibrational frequencies of vocal cords. For example, the pitch of someone’s voice, and how it changes as they are speaking, depends on a complex series of varying frequencies. Knowing how the brain sorts out these different frequencies — which are called frequency-modulated (FM) sweeps — is believed to be essential to understanding many hearing-related behaviors, like speech. Now, a pair of biologists at the California Institute of Technology (Caltech) has identified how and where the brain processes this type of sound signal.

This diagram shows areas in the midbrain region where direction- selective neurons were found. (Credit: Guangying Wu/Caltech)

Their findings are outlined in a paper published in the March 8 issue of the journal Neuron.

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ScienceDaily (Mar. 8, 2012) — A new study led by the Neuroscience Institute of Alicante reveals how manipulating the endocannabinoid system can modulate high levels of impulsivity. This is the main problem in psychiatric illnesses such a schizophrenia, bipolar disorder and substance abuse.

Spanish researchers have for the first time demonstrated that the CB2 receptor, which has modulating functions in the nervous system, is involved in regulating impulsive behaviour.

"Such a result proves the relevance that manipulation of the endocannabinoid system can have in modulating high levels of impulsivity present in a wide range of psychiatric and neurological illness," explains Jorge Manzanares Robles, a scientist at the Alicante Neuroscience Institute and director of the study.

Carried out on mice, the study suggests the possibility of undertaking future clinical trials using drugs that selectively act on the CB2 and thus avoid the psychoactive effects deriving from receptor CB1 manipulation, whose role in impulsivity has already been proven.

However, the authors of the study published in the British Journal of Pharmacology remain cautious. Francisco Navarrete, lead author of the study, states that “it is still very early to be able to put forward a reliable therapeutic tool.”

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March 8, 2012

New research from the University of Calgary’s Hotchkiss Brain Institute shows that by using a CT scan (computerized tomography), doctors can predict which patients are at risk of continued bleeding in the brain after a stroke. This vital information will allow doctors to utilize the most powerful blood clotting medications for those with the highest risk.

One in three individuals will continue to accumulate blood in the brain from a leak in a small artery. Pooling blood in the brain has serious consequences, and could lead to disability or even death. Previously, doctors in emergency stroke situations could not discern whether or not a patient’s brain bleeding had stopped. Using CT scan images, researchers can now identify “spot signs” that are seen as a small area of contrast on the CT scan. This spot sign is the actual location of bleeding within an artery in the brain.

"Technology that has emerged has allowed us to see the brain’s blood flow system in exquisite detail to precisely identify the source of the problem," explains Dr. Andrew Demchuk, Professor in the departments of clinical neurosciences and radiology, and lead author of this study. "We are now at a point where we can harness this technology to develop better treatments for patients with a blockage or breakage in a brain artery. Ultimately this research will confirm when immediate treatment is necessary – essentially, as soon as you see the spot sign."

This research provides validation of a new imaging marker to identify patients that may need to be treated with clotting medications versus those that don’t. “We must be very careful when and to whom these drugs are administered because they are so powerful at forming clots. These drugs can cause clots not only where there are holes and leaks – but also in intact arteries –potentially causing stroke and heart attacks,” says Demchuk. “Therefore this CT scan selection is critical for targeting only those patients at highest risk of continued bleeding.”

Clinical trials have now begun to test powerful clotting drugs in these patients.

This University of Calgary-led “PREDICT” study was coordinated with researchers at the Universities of Ottawa and Toronto, along with collaboration amongst nine other centres around the world. Their results were published in the March 8th online edition of the prestigious journal Lancet Neurology.

Provided by University of Calgary

Source: medicalxpress.com

March 8, 2012

The left image shows GABA inhibitory neurons (labeled green) in the brain’s reward pathway. The right panel shows electrical activity of GABA inhibitory neuron in a saline-injected or methamphetamine (METH)-injected mouse. Activation of the GABA type B receptor normally silences electrical activity, but has no effect in a mouse 24 hours after a single injection of methamphetamine Credit: Courtesy of Kelly Tan and Claire Padgett, Salk Institute for Biological Studies

A single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure, and these cellular changes lasted for at least a week, according to research by scientists at the Salk Institute for Biological Studies.

Their findings, reported March 7 in Neuron, suggest this powerful reaction to the drug assault may be a protective, anti-addiction response. The scientists theorize that it might be possible to mimic this response to treat addiction to these drugs and perhaps others, although more experiments are required to explore this possibility.

"It was stunning to discover that one exposure to these drugs could promote such a strong response that lasts well after the drug has left the body," says Paul Slesinger, an associate professor in the Clayton Foundation Laboratories for Peptide Biology. "We believe this could be the brain’s immediate response to counteract the stimulation of these drugs."

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ScienceDaily (Mar. 7, 2012) — While the thought of any type of surgery can be disconcerting, the thought of brain surgery can be downright frightening. But for people with a particular form of epilepsy, surgical intervention can literally be life-restoring.

A PET scan of a brain from a patient with epiepsy, between seizures. The red indicates healthy tissue. On the right side of the image, there is less red in the mesial temporal area. This is hypometabolism, reflecting decreased brain function in the area where seizures begin. (Credit: Image courtesy of University of California - Los Angeles)

Yet among people who suffer from what’s known as medically intractable epilepsy, in which seizures are resistant to drugs, only a small fraction will seek surgery, seeing it only as a last resort. As a result, they continue to suffer seizures year after year. They can’t drive, they can’t work and they lose cognitive function as the years pass. Premature death is not uncommon.

But a multi-center study led by researchers at UCLA shows that for people suffering from intractable temporal lobe epilepsy, the most common form of intractable epilepsy, early surgical intervention followed by antiepileptic drugs stopped their seizures, improved their quality of life and helped them avoid decades of disability.

The report appears in the March 7 edition of the Journal of the American Medical Association.

"In short, they got their lives back," said Dr. Jerome Engel, the study’s principal investigator and director of the UCLA Seizure Disorder Center.

But the frustration of Engel and his colleagues is this: Few patients are referred to them for surgical evaluation, and those who are have had epilepsy for an average of 22 years.

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ScienceDaily (Mar. 7, 2012) — Stimulating the brain with a weak electrical current is a safe and effective treatment for depression and could have other surprise benefits for the body and mind, a major Australian study of transcranial Direct Current Stimulation (tDCS) has found.

Medical researchers from the University of New South Wales (UNSW) and the Black Dog Institute have carried out the largest and most definitive study of tDCS and found up to half of depressed participants experienced substantial improvements after receiving the treatment.

A non-invasive form of brain stimulation, tDCS passes a weak depolarising electrical current into the front of the brain through electrodes on the scalp. Patients remain awake and alert during the procedure.

"We are excited about these results. This is the largest randomised controlled trial of transcranial direct current stimulation ever undertaken and, while the results need to be replicated, they confirm previous reports of significant antidepressant effects," said trial leader, Professor Colleen Loo, from UNSW’s School of Psychiatry.

The trial saw 64 depressed participants who had not benefited from at least two other depression treatments receive active or sham tDCS for 20 minutes every day for up to six weeks.

"Most of the people who went into this trial had tried at least two other antidepressant treatments and got nowhere. So the results are far more significant than they might initially appear — we weren’t dealing with people who were easy to treat," Professor Loo said.

Significantly, results after six weeks were better than at three weeks, suggesting the treatment is best applied over an extended period. Participants who improved during the trial were offered follow up weekly ‘booster’ treatments, with about 85 percent showing no relapse after three months.

"These results demonstrate that multiple tDCS sessions are safe and not associated with any adverse cognitive outcomes over time," Professor Loo said, adding tDCS is simple and cost effective to deliver, requiring a short visit to a clinic.

The study also turned up additional unexpected physical and mental benefits, including improved attention and information processing.

"One participant with a long-standing reading problem said his reading had improved after the trial and others commented that they were able to think more clearly.

"Another participant with chronic neck pain reported that the pain had disappeared during the trial. We think that is because tDCS actually changes the brain’s perception of pain. We believe these cognitive benefits are another positive aspect of the treatment worthy of investigation," Professor Loo said.

The researchers are now looking at an additional trial to include people with bipolar disorder, with early results from overseas suggesting tDCS is just as effective in this group.

Source: Science Daily

March 8, 2012 By Katie Neith

(Medical Xpress) — In both animals and humans, vocal signals used for communication contain a wide array of different sounds that are determined by the vibrational frequencies of vocal cords. For example, the pitch of someone’s voice, and how it changes as they are speaking, depends on a complex series of varying frequencies. Knowing how the brain sorts out these different frequencies—which are called frequency-modulated (FM) sweeps—is believed to be essential to understanding many hearing-related behaviors, like speech. Now, a pair of biologists at the California Institute of Technology (Caltech) has identified how and where the brain processes this type of sound signal.

Their findings are outlined in a paper published in the March 8 issue of the journal Neuron.

Knowing the direction of an FM sweep—if it is rising or falling, for example—and decoding its meaning, is important in every language. The significance of the direction of an FM sweep is most evident in tone languages such as Mandarin Chinese, in which rising or dipping frequencies within a single syllable can change the meaning of a word.

In their paper, the researchers pinpointed the brain region in rats where the task of sorting FM sweeps begins.

"This type of processing is very important for understanding language and speech in humans," says Guangying Wu, principal investigator of the study and a Broad Senior Research Fellow in Brain Circuitry at Caltech. "There are some people who have deficits in processing this kind of changing frequency; they experience difficulty in reading and learning language, and in perceiving the emotional states of speakers. Our research might help us understand these types of disorders, and may give some clues for future therapeutic designs or designs for prostheses like hearing implants."

This diagram shows areas in the midbrain region where direction- selective neurons were found.Credit: Guangying Wu/Caltech

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March 7, 2012

Neurons (nerve cells) are labeled with green fluorescent protein, and other neurons in the brain are labeled in the background with either red or blue tracers. The small bulbs (i.e., dendritic spines) on the spidery dendrites show places where nerve cells connect and communicate, called synapses, and when these spines shrank over time, this predicted vocal degradation in the songbirds. Credit: Katie Tschida, Duke Department of Neurobiology

Portions of a songbird’s brain that control how it sings have been shown to decay within 24 hours of the animal losing its hearing.

The findings, by researchers at Duke University Medical Center, show that deafness penetrates much more rapidly and deeply into the brain than previously thought. As the size and strength of nerve cell connections visibly changed under a microscope, researchers could even predict which songbirds would have worse songs in coming days.

"When hearing was lost, we saw rapid changes in motor areas in that control song, the bird’s equivalent of speech," said senior author Richard Mooney, Ph.D., professor of neurobiology at Duke. "This study provided a laser-like focus on what happens in the living songbird brain, narrowed down to the particular cell type involved."

The study was published in Neuron journal online on March 7, 2012.

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ScienceDaily (Mar. 6, 2012) — A team of academic researchers has identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the main component of plaques associated with Alzheimer’s disease.

Published in the March 6 issue of the Journal of Alzheimer’s Disease, the early findings show that vitamin D3 may activate key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein.

Previous laboratory work by the team demonstrated that specific types of immune cells in Alzheimer’s patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta. But the researchers didn’t know how it worked.

"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer’s disease," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

For the study, scientists drew blood samples from Alzheimer’s patients and healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.

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ScienceDaily (Mar. 6, 2012) — Antibodies that block the process of synapse disintegration in Alzheimer’s disease have been identified, raising hopes for a treatment to combat early cognitive decline in the disease.

Amyloid beta (cyan blue) binds to nerve cells of the hippocampus (red) and attacks synapses resulting in the loss of memories in Alzheimer’s disease. New research has led to important insights into the mechanisms that induce synapse loss. The discovery brings hope for the development of new therapies that protect synapses and therefore prevent memory loss in Alzheimer’s disease. (Credit: Silvia Purro/Patricia Salinas/UCL)

Alzheimer’s disease is characterized by abnormal deposits in the brain of the protein Amyloid-ß, which induces the loss of connections between neurons, called synapses.

Now, scientists at UCL have discovered that specific antibodies that block the function of a related protein, called Dkk1, are able to completely suppress the toxic effect of Amyloid-ß on synapses. The findings are published March 6 in the Journal of Neuroscience.

Professor Patricia Salinas (UCL Department of Cell & Developmental Biology) who led the study, said: “These novel findings raise the possibility that targeting this secreted Dkk1 protein could offer an effective treatment to protect synapses against the toxic effect of Amyloid-ß.

"Importantly, these results raise the hope for a treatment and perhaps the prevention of cognitive decline early in Alzheimer’s disease."

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March 6, 2012

Schematic diagrams of a normal brain (left) and an autistic brain (right) highlight the white matter alterations in autism. Credit: Carnegie Mellon University

New research from Carnegie Mellon University’s Marcel Just provides an explanation for some of autism’s mysteries — from social and communication disorders to restricted interests — and gives scientists clear targets for developing intervention and treatment therapies.

Autism has long been a scientific enigma, mainly due to its diverse and seemingly unrelated symptoms until now.

Published in the journal Neuroscience and Biobehavioral Reviews, Just and his team used brain imaging and computer modeling to show how the brain’s white matter tracts — the cabling that connects separated brain areas — are altered in autism and how these alterations can affect brain function and behavior. The deficiencies affect the tracts’ bandwidth — the speed and rate at which information can travel along the pathways.

"White matter is the unsung hero of the human brain," said Just, the D.O. Hebb Professor of Psychology within CMU’s Dietrich College of Humanities and Social Sciences and director of the university’s Center for Cognitive Brain Imaging. "In autistic individuals, we can measure the quality of the white matter, and our computer model can predict how coordinated their brain activity will be. This gives us a precise account of the underlying alterations affecting autistic thought."

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March 6, 2012

Thromboembolic stroke, caused by a blood clot in the brain, results in damage to the parts of the brain starved of oxygen. Breaking up the clot with tissue plasminogen activator (tPA) reduces the amount of damage, however, there is a very short time window when the value of the treatment outweighs the side effects. New research published in BioMed Central’s open access journal Experimental & Translational Stroke Medicine shows that, during the first 24 hours after a stroke, mild hypothermia (34C) can reduce the side effects of tPA and potentially increase the window of opportunity for tPA treatment.

When a blood clot blocks off blood flow in the brain (ischemic stroke) the part starved of oxygen quickly begins to die. In order to prevent significant damage tPA must be given to the patient as early as possible after the onset of symptoms - doctors recommend that it must be administered within the first four and a half hours. Delayed treatment also increases the patient’s risk of intracerebral hemorrhage and brain swelling (edema).

Mild hyperthermia is known to be neuroprotective and to reduce damage caused by the return of blood flow to an area of the brain starved of oxygen by a clot. Researchers from the University of Erlangen, led by Dr Rainer Kollmar, tested whether mild hyperthermia could also prevent damage to the brain due to tPA treatment in rats. After 24 hours they found that, while hypothermia reduced the amount of swelling and damaged tissue in the brain after a stroke, tPA (administered 90 minutes after the onset of stroke) increased it. However, they also discovered that hypothermia therapy was able to offset the damage due to tPA.

This seemed to be true for all the measurements they looked at. Dr Kollmar explained, “Patients often loose brain function such as control over parts of their body, speech or memory after stroke. We looked at ‘neuroscore’, to examine how much control of the body had been affected, and at markers for inflammation (TIMP-1 and sICAM) or evidence of damage to the blood brain barrier. In all cases hypothermia was able to offset the side effects of tPA.”

While these results are still experimental, new techniques which prevent shivering mean that this technique is easier to administer in conscious patients. Preliminary clinical trials are also beginning to show that it is possible to treat patients, who have had a stroke, with tPA plus hypothermia. Our results suggest that hypothermia can offset the side effects of tPA and further studies will show if it is also able to increase the window of opportunity of tPA treatment in patients.

Provided by BioMed Central

Source: medicalxpress.com

March 6, 2012

Getting rid of a protein increases the birth of new nerve cells and shortens the time it takes for antidepressants to take effect, according to an animal study in the March 7 issue of The Journal of Neuroscience. The protein, neurofibromin 1, normally helps prevent uncontrolled cell growth. The findings suggest therapeutic strategies aimed at stimulating new nerve cell birth may help treat depression better than current antidepressants that commonly take several weeks to reach full efficacy.

Throughout life, a section of the hippocampus — the brain’s learning and memory center — produces new nerve cells. This process, called neurogenesis, is made possible by specialized cells called neural progenitor cells (NPCs). While previous studies show adult neurogenesis declines with age and stress, therapies known to alleviate symptoms of depression, such as exercise and antidepressants, increase neurogenesis.

In the new study, a team of scientists directed by Luis Parada, PhD, of the University of Texas Southwestern, examined neurogenesis after deleting the neurofibromin 1 (Nf1) gene from NPCs in adult mice. Removal of Nf1 increased the number and maturation of newborn nerve cells in the adult hippocampus. Nf1 mutant mice showed reductions in depressive- and anxiety-like behaviors following 7 days of antidepressant treatment, whereas mice without the mutation took longer to show improvements.

"Our findings establish an important role for Nf1 in controlling neurogenesis in the hippocampus and demonstrate that activation of adult NPCs is enough to regulate depression- and anxiety-like behaviors," said study co-author Renee McKay, PhD, of the University of Texas Southwestern. "Our work is among the first to demonstrate the feasibility of altering mood via direct manipulation of adult neurogenesis," McKay added.

To determine if deleting Nf1 in adult NPCs leads to long-term behavioral changes in mice, the scientists ran 8-month-old mice through a battery of tests designed to measure anxiety- and depressive-like behaviors. Compared with other mice, the mutant mice showed less signs of anxiety and demonstrated resistance to the effects of chronic mild, unpredictable stress. The finding shows even without antidepressants, the deletion of Nf1 from NPCs in adult mice decreases symptoms of depression and anxiety.

"This study demonstrates that inducing neurogenesis is sufficient to produce antidepressant behavioral actions, and provides novel targets for therapeutic interventions," said Ronald Duman, PhD, a neurogenesis expert from Yale University.

Provided by Society for Neuroscience

Source: medicalxpress.com

ScienceDaily (Mar. 5, 2012) — A new marker of Alzheimer’s disease can predict how rapidly a patient’s memory and other mental abilities will decline after the disorder is diagnosed, researchers at Washington University School of Medicine in St. Louis have found.

In 60 patients with early Alzheimer’s disease, higher levels of the marker, visinin-like protein 1 (VILIP-1), in the spinal fluid were linked to a more rapid mental decline in the years that followed.

Scientists need to confirm the results in larger studies, but the new data suggest that VILIP-1 potentially may be a better predictor of Alzheimer’s progression than other markers.

“VILIP-1 appears to be a strong indicator of ongoing injury to brain cells as a result of Alzheimer’s disease,” says lead author Rawan Tarawneh, MD, now an assistant professor of neurology at the University of Jordan. “That could be very useful in predicting the course of the disease and in evaluating new treatments in clinical trials.”

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March 5, 2012 by Bob Yirka

(Medical Xpress) — A group of Australian neuroscientists have been reviewing the results of many studies done over the years regarding the parts of the brain that are thought to be used in different real world scenarios and have found that many of them appear to be involved when people go into what is called a default network - more commonly known as daydreaming, or running on auto-pilot. Their findings suggest, as they write in their paper published in Nature Reviews Neurology, that the default network is tied very closely with the same areas of the brain generally thought of as those used for social skills.

To find connections, the team looked at studies of elderly people that had fallen victim to two distinct forms of early onset dementia. One involved damage to the frontal lobe, the other to the temporal lobe. Damage to the frontal lobe, they point out, generally results in patients displaying an inability to understand why they should curb their language. They’re impulsive and aren’t able to understand the repercussions of their words or actions as they pertain to other people. Those with damage to the temporal lobe on the other hand, have trouble understanding the subtle cues that go on between people when interacting. They generally run into trouble in trying to read emotion in others and also tend to have difficulty remembering faces or other everyday objects. Both conditions obviously have a very direct and troublesome impact on social interaction.

They also found that when people without dementia are placed in an fMRI machine and who are allowed to daydream, various parts of their brain light up, indicating that the default network is quite complicated and involved. But of specific interest to this group of researchers was the fact that many of those areas that light up when transitioning to the default network, are the same ones that are used for social interaction, memory and imagination.

This means, they say, that the default network is more than just daydreaming because for it to occur, there needs to be memory of events that have transpired, imagination to guess about things that might happen in the future and the consequences of different happenings. Not coincidentally, they add, all these things are necessary for social interaction as well. This, they say, is why it’s time to stop looking at individual brain functions as separate events and instead to start looking at events as multi-brain activities that all together add up to the richness of thought we all experience as thinking human beings.

Source: medicalxpress.com

March 5, 2012

The brain has a remarkable ability to learn new cognitive tasks while maintaining previously acquired knowledge about various functions necessary for everyday life. But exactly how new information is incorporated into brain systems that control cognitive functions has remained a mystery.

A study by researchers at Wake Forest Baptist Medical Center and the McGovern Institute of the Massachusetts Institute of Technology shows how new information is encoded in neurons of the prefrontal cortex, the area of the brain involved in planning, decision making, working memory and learning.

"In this study we were able to isolate activity directly from the brain, allowing us to ‘see’ what was happening in the prefrontal cortex before and after a new task was learned," said Christos Constantinidis, Ph.D., associate professor of neurobiology and anatomy at Wake Forest Baptist and senior author of the study, published in the March 5 online edition of Proceedings of the National Academy of Sciences.

To gain insight into how learning a new task affects the prefrontal cortex, the researchers analyzed the electrical activity of neurons before and after training for the performance in two short-term memory tests. Two monkeys initially looked at a computer screen while various shapes, such as squares and circles, were displayed, and researchers recorded the electrical activity occurring in the brain. The same animals were then trained to recognize the various shapes, and to remember whether two symbols matched each other.

Using computational analysis of the neuronal recordings, the researchers compared data to assess what information was present before training and what new information arose while learning a new task. They found that learning was associated with activation of a small number of neurons that were highly specialized for the new task, while the same neurons maintained the existing information that was present before training.

"In essence, this select group of neurons was able to multitask by learning new information while retaining information they were already specialized for," Constantinidis said. "Our results show that although there was little change in the amount of basic stimulus information that neurons encoded before training, more complex information about whether the symbols matched became incorporated throughout the prefrontal cortex after training."

Overall these findings shed light on how new information is incorporated into the prefrontal cortex activity and how neural activity codes information, which should lead to richer theories of how the prefrontal cortex controls behavior and how information is encoded in neural activity more generally.

"We hope that our findings will help others who work with patients who have short-term memory problems resulting from strokes or traumatic brain injuries," Constantinidis said. "Computerized training to perform cognitive tasks, like those used in our study, has shown promise in cognitive rehabilitation, and for treatment of mental illnesses and conditions, such as schizophrenia and ADHD."

Provided by Wake Forest Baptist Medical Center

Source: medicalxpress.com

When the rings of dynamic patterns are presented to the same eye (left column), the subject is able to consciously perceive the target pattern-the stripes in the center of the ring. When the two are presented to different eyes (right column), the dynamic pattern suppresses perception of the target pattern. Under both conditions, participants were asked to perform a task that focused attention on the target (top row) or on letters presented outside the target area (bottom row). Credit: 2012 Masataka Watanabe

From a purely intuitive point of view, it is easy to believe that our ability to actively pay attention to a target is inextricably connected with our capacity to consciously perceive it. However, this proposition remains the subject of extensive debate in the research community, and surprising new findings from a team of scientists in Japan and Europe promise to fuel the debate.

Resolving how these aspects of perception are managed requires a detailed understanding of how the visual centers in our brain process information. A region known as V1 has been investigated as it represents the first portion of the visual cortex to receive and process signals transmitted from the retina.

Many researchers favor a model in which functions pertaining consciousness are widely spread among the whole visual system, including V1. The classical model, which assumes that the neural mechanism of consciousness is integrated into a narrow subset of brain structures, referred to as a homunculus, or ‘little human’, is almost defunct. However, a modern version of this model is under debate. It proposes that the neural mechanism of consciousness is a privileged set of cortical areas, a subpopulation of neurons, or certain neural dynamics (e.g. oscillations); while there are also visual systems that have nothing to do with conscious vision, explains Masataka Watanabe a researcher investigating brain function at the University of Tokyo, Japan.

Watanabe cites studies proposing that visual attention as processed within V1 may be only minimally impacted by conscious perception; but, the experimental data have been contradictory. For example, studies using a technique called functional magnetic resonance imaging (fMRI) to map brain activity have indicated that V1 contributes to both attention and awareness in humans. However, invasive electrophysiological studies in non-human primates yielded different results. “You would find only 10 to 15% of neurons in V1 that are barely modulated by awareness, and 85% or so that are not modulated at all,” says Watanabe. To resolve this ambiguity, he, Kang Cheng from the RIKEN Brain Science Institute, Wako, and their colleagues designed an experiment that examined both processes independently. Surprisingly, their results may lend support the modern homunculus model. 

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ScienceDaily (Mar. 5, 2012) — Studying tiny bits of genetic material that control protein formation in the brain, Johns Hopkins scientists say they have new clues to how memories are made and how drugs might someday be used to stop disruptions in the process that lead to mental illness and brain wasting diseases.

Neuron (red) accumulates messages (green) when treated with BDNF. (Credit: Image courtesy of Johns Hopkins Medicine)

In a report published in the March 2 issue of Cell, the researchers said certain microRNAs — genetic elements that control which proteins get made in cells — are the key to controlling the actions of so-called brain-derived neurotrophic factor (BDNF), long linked to brain cell survival, normal learning and memory boosting.

During the learning process, cells in the brain’s hippocampus release BDNF, a growth-factor protein that ramps up production of other proteins involved in establishing memories. Yet, by mechanisms that were never understood, BDNF is known to increase production of less than 4 percent of the different proteins in a brain cell.

That led Mollie Meffert, M.D., Ph.D., associate professor of biological chemistry and neuroscience at the Johns Hopkins University School of Medicine to track down how BDNF specifically determines which proteins to turn on, and to uncover the role of regulatory microRNAs.

MicroRNAs are small molecules that bind to and block messages that act as protein blueprints from being translated into proteins. Many microRNAs in a cell shut down protein production, and, conversely, the loss of certain microRNAs can cause higher production of specific proteins.

The researchers measured microRNA levels in brain cells treated with BDNF and compared them to microRNA levels in neurons not treated with BDNF. The researchers noticed that levels of certain microRNAs were lower in brain cells treated with BDNF, suggesting that BDNF controls the levels of these microRNAs and, through this control, also affects protein production. Homing in on those specific microRNAS that disappeared when cells were treated with BDNF, the team found all were of the same type, so-called Let-7 microRNAs, and that all shared a common genetic sequence.

"This short genetic sequence has been shown by other researchers to behave like a bar code that can selectively prevent production of Let-7 microRNAs," says Meffert.

To test if the loss of Let-7 microRNAs lets BDNF increase production of specific proteins, Meffert’s team genetically engineered neurons so they could no longer decrease Let-7 microRNAs. They found that treating these neurons with BDNF no longer resulted in decreased microRNA levels or an increase in learning and memory proteins.

In measuring microRNA levels in cells treated with BDNF, the researchers also found more than 174 microRNAs that increased with BDNF treatment. This suggested to the research team that BNDF treatment also can increase other microRNAs and, thereby, decrease production of certain proteins. Says Meffert, some of these proteins may need to be decreased during learning and memory, whereas others may not contribute to the process at all.

To confirm that BDNF, via microRNA action, halts the production of certain proteins, the researchers monitored living brain cells to find out where messages go in response to BDNF. Messages that aren’t translated into proteins can accumulate inside small formations within cells. Using a microscope, the researchers watched a lab dish containing brain cells that had been marked with a fluorescent molecule that labels these formations as glowing spots. Treating cells with BDNF caused the number and size of the glowing spots to increase. The researchers determined that BDNF uses microRNA to send messages to these spots where they can be exiled away from the translating machinery that turns them into protein.

"Monitoring these fluorescent complexes gave us a window that we needed to understand how BDNF is able to target the production of only certain proteins that help neurons to grow and make learning possible," Meffert says.

Adds Meffert, “Now that we know how BDNF boosts production of learning and memory proteins, we have an opportunity to explore whether therapeutics can be designed to enhance this mechanism for treatment of patients with mental disorders and neurodegenerative diseases like Alzheimer’s disease.”

Source: Science Daily

March 4, 2012 

Brain diagram. Credit: dwp.gov.uk

Opening the door to the development of thought-controlled prosthetic devices to help people with spinal cord injuries, amputations and other impairments, neuroscientists at the University of California, Berkeley, and the Champalimaud Center for the Unknown in Portugal have demonstrated that the brain is more flexible and trainable than previously thought.

Their new study, to be published Sunday, March 4, in the advanced online publication of the journal Nature, shows that through a process called plasticity, parts of the brain can be trained to do something it normally does not do. The same brain circuits employed in the learning of motor skills, such as riding a bike or driving a car, can be used to master purely mental tasks, even arbitrary ones.

Over the past decade, tapping into brain waves to control disembodied objects has moved out of the realm of parlor tricks and parapsychology and into the emerging field of neuroprosthetics. This new study advances work by researchers who have been studying the brain circuits used in natural movement in order to mimic them for the development of prosthetic devices.

"What we hope is that our new insights into the brain’s wiring will lead to a wider range of better prostheses that feel as close to natural as possible," said Jose Carmena, UC Berkeley associate professor of electrical engineering, cognitive science and neuroscience. "They suggest that learning to control a BMI (brain-machine interface), which is inherently unnatural, may feel completely normal to a person, because this learning is using the brain’s existing built-in circuits for natural motor control."

Carmena and co-lead author Aaron Koralek, a UC Berkeley graduate student in Carmena’s lab, collaborated on this study with Rui Costa, co-principal investigator of the study and principal investigator at the Champalimaud Neuroscience Program, and co-lead author Xin Jin, a post-doctoral fellow in Costa’s lab.

Previous studies have failed to rule out the role of physical movement when learning to use a prosthetic device.

"This is key for people who can’t move," said Carmena, who is also co-director of the UC Berkeley-UCSF Center for Neural Engineering and Prostheses. "Most brain-machine interface studies have been done in healthy, able-bodied animals. What our study shows is that neuroprosthetic control is possible, even if physical movement is not involved." 

To clarify these issues, the scientists set up a clever experiment in which rats could only complete an abstract task if overt physical movement was not involved. The researchers decoupled the role of the targeted motor neurons needed for whisker twitching with the action necessary to get a food reward.

The rats were fitted with a brain-machine interface that converted brain waves into auditory tones. To get the food reward – either sugar-water or pellets – the rats had to modulate their thought patterns within a specific brain circuit in order to raise or lower the pitch of the signal.

Auditory feedback was given to the rats so that they learned to associate specific thought patterns with a specific pitch. Over a period of just two weeks, the rats quickly learned that to get food pellets, they would have to create a high-pitched tone, and to get sugar water, they needed to create a low-pitched tone.

If the group of neurons in the task were used for their typical function – whisker twitching – there would be no pitch change to the auditory tone, and no food reward.

"This is something that is not natural for the rats," said Costa. "This tells us that it’s possible to craft a prosthesis in ways that do not have to mimic the anatomy of the natural motor system in order to work."

The study was also set up in a way that demonstrated intentional, as opposed to habitual, behavior. The rats were able to vary the amount of pellets or sugar water received based upon their own level of hunger or thirst.

"The rats were aware; they knew that controlling the pitch of the tone was what gave them the reward, so they controlled how much sugar water or how many pellets to take, when to do it, and how to do it in absence of any physical movement," said Costa.

Researchers hope these findings will lead to a new generation of prosthetic devices that feel natural.

"We don’t want people to have to think too hard to move a robotic arm with their brain," said Carmena.

Provided by University of California - Berkeley 

Source: medicalxpress.com

This undated handout artist rendering provided by the Schneider Lab, University of Pittsburgh shows an experimental type of scan showing damage to the brain’s nerve fibers after a traumatic brain injury. The yellow shows missing fibers on one side of the brain, as compared to the uninjured side in green, in a man left with limited use of his left arm and hand. The soldier on the fringes of an explosion. The survivor of a car wreck. The football player who took yet another skull-rattling hit. Too often, only time can tell when a traumatic brain injury will leave lasting harm _ there’s no good way to diagnose the damage. Now scientists are testing a tool that promises to light up breaks that these injuries leave in the brain’s wiring, much like X-rays show broken bones. (AP Photo/Schneider Lab, University of Pittsburgh)

The soldier on the fringes of an explosion. The survivor of a car wreck. The football player who took yet another skull-rattling hit. Too often, only time can tell when a traumatic brain injury will leave lasting harm - there’s no good way to diagnose the damage.

Now scientists are testing a tool that lights up the breaks these injuries leave deep in the brain’s wiring, much like X-rays show broken bones.

Research is just beginning in civilian and military patients to learn if this new kind of MRI-based test really could pinpoint their injuries and one day guide rehabilitation. It’s an example of the hunt for better brain scans, maybe even a blood test, to finally tell when a blow to the head causes damage that today’s standard testing simply can’t see.

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ScienceDaily (Mar. 2, 2012) — A powerful new imaging technique called High Definition Fiber Tracking (HDFT) will allow doctors to clearly see for the first time neural connections broken by traumatic brain injury (TBI) and other neurological disorders, much like X-rays show a fractured bone, according to researchers from the University of Pittsburgh in a report published online in the Journal of Neurosurgery.

High definition fiber-tracking map of a million brain fibers. (Credit: Walt Schneider Laboratory)

In the report, the researchers describe the case of a 32-year-old man who wasn’t wearing a helmet when his all-terrain vehicle crashed. Initially, his CT scans showed bleeding and swelling on the right side of the brain, which controls left-sided body movement. A week later, while the man was still in a coma, a conventional MRI scan showed brain bruising and swelling in the same area. When he awoke three weeks later, the man couldn’t move his left leg, arm and hand.

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ScienceDaily (Mar. 2, 2012) — Impaired social function is a cardinal symptom of autism spectrum disorders (ASDs). One of the brain circuits that enable us to relate to other people is the “mirror neuron” system. This brain circuit is activated when we watch other people, and allows our brains to represent the actions of others, influencing our ability to learn new tasks and to understand the intentions and experiences of other people.

This mirror neuron system is impaired in individuals with ASD and better understanding the neurobiology of this system could help in the development of new treatments.

In their new study, Dr. Peter Enticott at Monash University and his colleagues used transcranial magnetic stimulation to stimulate the brains of individuals with ASD and healthy individuals while they observed different hand gestures. This allowed the researchers to measure the activity of each individual’s mirror neuron system with millisecond precision in response to each observed action.

They found that the individuals with ASD showed a blunted brain response to stimulation of the motor cortex when viewing a transitive hand gesture. In other words, the mirror neuron system in the ASD individuals became less activated when watching the gestures, compared to the healthy group. In addition, among people with ASD, less mirror neuron activity was associated with greater social impairments. This finding adds to the evidence that deficits in mirror neuron system functioning contribute to the social deficits in ASD.

This finding also directly links a specific type of brain dysfunction in people with autism spectrum disorder to a specific symptom. This is important because “we do not have a substantial understanding of the brain basis of autism spectrum disorder, or a validated biomedical treatment for the disorder,” said Dr. Enticott. “If we can develop a substantial understanding of the biology of specific symptoms, this will allow us to develop treatments targeted specifically to the symptoms.”

"This study is an example of the effort to break down the component problems associated with autism spectrum disorder and to map these problems on to particular brain circuits," commented Dr. John Krystal, editor of Biological Psychiatry.

Enticott added, “We are currently investigating whether non-invasive brain stimulation can be used to improve mirror neuron activity in autism spectrum disorder, which would have substantial potential therapeutic implications.”

Source: Science Daily

ScienceDaily (Mar. 2, 2012) — Millions of people suffer from Parkinson’s disease, a disorder of the nervous system that affects movement and worsens over time. As the world’s population ages, it’s estimated that the number of people with the disease will rise sharply. Yet despite several effective therapies that treat Parkinson’s symptoms, nothing slows its progression.

Artist’s rendering of neurons. (Credit: iStockphoto)

While it’s not known what exactly causes the disease, evidence points to one particular culprit: a protein called α-synuclein. The protein, which has been found to be common to all patients with Parkinson’s, is thought to be a pathway to the disease when it binds together in “clumps,” or aggregates, and becomes toxic, killing the brain’s neurons.

Now, scientists at UCLA have found a way to prevent these clumps from forming, prevent their toxicity and even break up existing aggregates.

UCLA professor of neurology Jeff Bronstein and UCLA associate professor of neurology Gal Bitan, along with their colleagues, report the development of a novel compound known as a “molecular tweezer,” which in a living animal model blocked α-synuclein aggregates from forming, stopped the aggregates’ toxicity and, further, reversed aggregates in the brain that had already formed. And the tweezers accomplished this without interfering with normal brain function.

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(Medical Xpress) — As scientists struggle to find an effective way to prevent Alzheimer’s disease, researchers at the University of Wisconsin School of Medicine and Public health may have found a new approach to interrupting the process that leads to the devastating disease.

The image shows that the enzymes ATase1 and ATase2 are abundantly present in the brains of Alzheimer’s disease patients. The green color labels the ATases while the blue labels the nuclei. Both neurons and glial cells are shown.

Building on their knowledge of two enzymes that control an “uber” enzyme critical to the development of the disease, the scientists found that the two enzymes are present in the brains of Alzheimer’s patients. And by screening some 15,000 compounds, they discovered two that lower activity of the enzymes in test tubes. 

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Article Date: 02 Mar 2012 - 1:00 PST

Scientists from Seattle Children’s Research Institute and the University of Washington, in collaboration with the Genomic Disorders Group Nijmegen in the Netherlands, have identified two new genes that cause Baraitser-Winter syndrome, a rare brain malformation that is characterized by droopy eyelids and intellectual disabilities.

“This new discovery brings the total number of genes identified with this type of brain defect to eight,” said William Dobyns, MD, a geneticist at Seattle Children’s Research Institute. Identification of the additional genes associated with the syndrome make it possible for researchers to learn more about brain development. The study, “De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome,” was published online in Nature Genetics.

The brain defect found in Baraitser-Winter syndrome is a smooth brain malformation or “lissencephaly,” as whole or parts of the surface of the brain appear smooth in scans of patients with the disorder. Previous studies by Dr. Dobyns and other scientists identified six genes that cause the smooth brain malformation, accounting for approximately 80% of affected children. Physicians and researchers worldwide have identified to date approximately 20 individuals with Baraitser-Winter syndrome.

While the condition is rare, Dr. Dobyns said the team’s findings have broad scientific implications. “Actins, or the proteins encoded by the ACTB and ACTG1 genes, are among the most important proteins in the function of individual cells,” he said. “Actins are critical for cell division, cell movement, internal movement of cellular components, cell-to-cell contact, signaling and cell shape,” said Dr. Dobyns, who is also a University of Washington professor of pediatrics. “The defects we found occur in the only two actin genes that are expressed in most cells,” he said. Gene expression is akin to a “menu” for conditions like embryo development or healing from an injury. The correct combination of genes must be expressed at the right time to allow proper development. Abnormal expression of genes can lead to a defect or malformation.

“Birth defects associated with these two genes also seem to be quite severe,” said Dr. Dobyns. “Children and people with these genes have short stature, an atypical facial appearance, birth defects of the eye, and the smooth brain malformation along with moderate mental retardation and epilepsy. Hearing loss occurs and can be progressive,” he said.

Dr. Dobyns is a renowned researcher whose life-long work has been to try to identify the causes of children’s developmental brain disorders such as Baraitser-Winter syndrome. He discovered the first known chromosome abnormality associated with lissencephaly (Miller-Dieker syndrome) while still in training in child neurology at Texas Children’s Hospital in 1983. That research led, 10 years later, to the discovery by Dobyns and others of the first lissencephaly gene known as LIS1.

Source: Medical News Today  

ScienceDaily (Mar. 1, 2012) — The association of the inhaled anesthetic isoflurane with Alzheimer’s-disease-like changes in mammalian brains may by caused by the drug’s effects on mitochondria, the structures in which most cellular energy is produced. In a study that will appear in Annals of Neurology and has received early online release, Massachusetts General Hospital (MGH) researchers report that administration of isoflurane impaired the performance of mice on a standard test of learning and memory — a result not seen when another anesthetic, desflurane, was administered. They also found evidence that the two drugs have significantly different effects on mitochondrial function.

"These are the first results indicating that isoflurane, but not desflurane, may induce neuronal cell death and impair learning and memory by damaging mitochondria," says Yiying (Laura) Zhang, MD, a research fellow in the MGH Department of Anesthesia, Critical Care and Pain Medicine and the study’s lead author. "This work needs to be confirmed in human studies, but it’s looking like desflurane may be a better anesthetic to use for patients susceptible to cognitive dysfunction, such as Alzheimer’s patients."

Previous studies have suggested that undergoing surgery and general anesthesia may increase the risk of Alzheimer’s, and it is well known that a small but significant number of surgical patients experience a transient form of cognitive dysfunction in the postoperative period. In 2008, members of the same MGH research team showed that isoflurane induced Alzheimer’s-like changes — increasing activation of enzymes involved with cell death and generation of the A-beta plaques characteristic of the disease — in the brains of mice. The current study was designed to explore the underlying mechanism and behavioral consequences of isoflurane-induced brain cell death and to compare isoflurane’s effects with those of desflurane, another common anesthetic that has not been associated with neuronal damage.

In a series of experiments, the investigators found that the application of isoflurane to cultured cells and mouse neurons increased the permeability of mitochondrial membranes; interfered with the balance of ions on either side of the mitochondrial membrane; reduced levels of ATP, the enzyme produced by mitochondria that powers most cellular processes; and increased levels of the cell-death enzyme caspase. The results also suggested that the first step toward isoflurane-induced cell death was increased generation of reactive oxygen species — unstable oxygen-containing molecules that can damage cellular components. The performance of mice on a standard behavioral test of learning and memory declined significantly two to seven days after administration of isoflurane, compared with the results of a control group. None of the cellular or behavioral effects of isoflurane were seen when the administered agent was desflurane.

In another study by members of the same research team — appearing in the February issue of Anesthesia and Analgesia and published online in November — about a quarter of surgical patients receiving isoflurane showed some level of cognitive dysfunction a week after surgery, while patients receiving desflurane or spinal anesthesia had no decline in cognitive performance. That study, conducted in collaboration with investigators from Beijing Friendship Hospital in China, enrolled only 45 patients — 15 in each treatment group — so its results need to be confirmed in significantly larger groups.

"Approximately 8.5 million Alzheimer’s disease patients worldwide will need anesthesia and surgical care every year," notes Zhongcong Xie, MD, PhD, corresponding author of both studies and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine. "Developing guidelines for safer anesthesia care for these patients will require collaboration between specialists in anesthesia, neurology, geriatric medicine and other specialties. As the first step, we need to identify anesthetics that are less likely to contribute to Alzheimer’s disease neuropathogenesis and cognitive dysfunction." Xie is an associate professor of Anesthesia at Harvard Medical School (HMS)

Source: Science Daily

ScienceDaily (Mar. 1, 2012) — Down syndrome (DS) is the most common genetic disorder in live born children arising as a consequence of a chromosomal abnormality. It occurs as a result of having three copies of chromosome 21, instead of the usual two. It causes substantial physical and behavioral abnormalities, including life-long cognitive dysfunction that can range from mild to severe but which further deteriorates as individuals with DS age.

It is not currently possible to effectively treat the cognitive impairments associated with DS. However, these deficits are an increasing focus of research. In this issue of Biological Psychiatry, researchers at Stanford University, led by Dr. Ahmad Salehi, have published a review which highlights potential strategies for the treatment of these cognitive deficits.

The authors focus on insights emerging from animal models of Down syndrome and outline the structural abnormalities in the DS brain. They also discuss studies that have linked the over-expression of the amyloid precursor protein gene, called APP, to the degeneration of neurons in mice. These findings have led to the development of therapeutic treatments in mice, which now must be tested in humans.

"For more than a decade, we have been working on identifying a strategy to treat cognitive disabilities in our Down syndrome mouse models," said Dr. Salehi. "Considering the research and results with mouse models as an indication of success of a strategy in humans, we are ever closer to finding ways to at least partially restore cognitive function in children and adults with Down syndrome."

Interestingly, this research is also providing insights into Alzheimer’s disease (AD), the archetypal disorder of late life. All adults with Down syndrome develop AD pathology by age 40, and there are some remarkable similarities in the brain degeneration and cognitive dysfunction of individuals with DS and those with AD.

The leading AD hypothesis posits that it is caused by increasingly elevated levels of amyloid-related proteins, which are toxic to nerve cells in the brain. These same proteins also accumulate in the brains of people with DS because they are made by the APP gene, which is located on chromosome 21. Individuals with AD don’t have the extra chromosome, of course; rather, it is mutations in APP that appear to cause the brain degeneration associated with AD.

Dr. John Krystal, editor of Biological Psychiatry, commented: “The convergence of research on Down syndrome and Alzheimer’s disease highlights a central point that cannot be overstated. When we understand the fundamental biology of the brain, important new conceptual bridges emerge that guide new treatment approaches.”

Salehi added, “In the near future, we may very likely look back with the perspective that Down syndrome represents an example of how families of affected individuals came together and by supporting basic research, changed the course of a disorder that was considered untreatable for more than a century.”

Source: Science Daily

ScienceDaily (Mar. 1, 2012) — Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell has-until now-eluded scientists.

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We’ll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton’s study, on the other hand, reveals that a complex interplay of several molecules controls the “switch” that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell research-figuring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health’s National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an “off” position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton’s team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

But Wnt doesn’t work alone. Other molecules, such as insulin-like growth factor (Igf), fibroblast growth factor (Fgf2) and Activin A also play a role. To complicate things further, these signaling molecules amplify each other so that a two-fold increase in one can result in a 10-fold increase in another. The timing with which the signals are introduced matters, too.

"One of the things that surprised us was how all of the pathways ‘talk’ to each other," Dalton said. "You can’t do anything to the Igf pathway without affecting the Fgf2 pathway, and you can’t do anything to Fgf2 without affecting Wnt. It’s like a house of cards; everything is totally interconnected."

Dalton and his team spent a painstaking five years creating hypotheses about the how the signaling molecules function, testing those hypotheses, and-when faced with an unexpected result-rebuilding their hypotheses and re-testing. This process continued until the entire system was resolved.

Their finding gives scientists a more complete understanding of the first step that stem cells take as they differentiate, and Dalton is confident that the same approach can be used to understand subsequent developmental steps that occur as the cells in an embryo divide into ever-more specific cell types.

"Hopefully this type of approach will give us a greater understanding of cells and how they can be manipulated so that we can progress much more rapidly toward the routine use of stem cells in therapeutic settings," Dalton said.

The research was funded by the National Institute of Child Health and Human Development and the National Institute of General Medical Sciences.

Source: Science Daily

(Medical Xpress) — Researchers from Western University have utilized their own game-changing technology – previously developed for use with patients in a vegetative state – to assess a more prevalent group of brain-injured patients, those in the minimally conscious state (MCS). Their findings were released today in Neurology, the medical journal of the American Academy of Neurology.

The study, led by Adrian Owen, Canada Excellence Research Chair in Cognitive Neuroscience and Imaging, and Damian Cruse of Western’s Brain and Mind Institute, is a follow-up to the team’s groundbreaking Lancet publication from November 2011 that used electroencephalography (EEG) to show that some vegetative state patients were able to reliably follow commands, even though this ability was entirely undetectable from their external behaviour. 

In the new paper, titled “The relationship between aetiology and covert cognition in the minimally-conscious state,” the MCS patients showed some inconsistent but reproducible external signs of awareness, such as being able to follow their eyes in a mirror.  Cruse says, however, that currently very little is known about their ‘internal’ state of awareness that may be hidden from their external behaviour. 

"Using our EEG approach, we found that 22 per cent of 23 MCS patients were able to complete a complex task which required them to imagine particular types of movement," says Cruse, a Post-Doctoral Fellow at the Brain and Mind Institute and the lead writer of the paper. "This tells us that these patients have a much higher level of cognitive ability than what you could detect from their behaviour."

Cruse adds that the cause of the brain injury was a determining factor in finding these cognitive abilities as 33 per cent of traumatically injured patients (e.g. traffic accident, fall) returned positive EEG results compared to zero per cent of non-traumatically injured patients (e.g. heart attack, stroke).

The research team, in collaboration with Steven Laureys at the University of Liège, Belgium, asked patients approximately 100 times each to imagine moving his or her right-hand and toes. By making recordings of the patients’ EEG, a measure of the electrical activity of the brain, the team showed that 22 per cent of the MCS patients were able to produce patterns of brain activity that were indistinguishable from a healthy individual following the same commands. 

"There are a large number of patients in the MCS worldwide, and our approach highlights the importance of using EEG and other forms of brain imaging when assessing the mental capabilities of patients following brain injury," says Cruse "It reinforces our understanding that the externally observable abilities of a patient are not necessarily a true reflection of their internal state."

Provided by University of Western Ontario

Source: medicalxpress.com

A major downside of the medical use of marijuana is the drug’s ill effects on working memory, the ability to transiently hold and process information for reasoning, comprehension and learning. Researchers reporting in the March 2 print issue of the Cell Press journal Cell provide new insight into the source of those memory lapses. The answer comes as quite a surprise: Marijuana’s major psychoactive ingredient (THC) impairs memory independently of its direct effects on neurons. The side effects stem instead from the drug’s action on astroglia, passive support cells long believed to play second fiddle to active neurons.

The findings offer important new insight into the brain and raise the possibility that marijuana’s benefits for the treatment of pain, seizures and otherailments might some day be attained without hurting memory, the researchers say.

With these experiments in mice, “we have found that the starting point for this phenomenon – the effect of marijuana on working memory – is the astroglialcells,” said Giovanni Marsicano of INSERM in France.

"This is the first direct evidence that astrocytes modulate working memory," added Xia Zhang of the University of Ottawa in Canada.

The new findings aren’t the first to suggest astroglia had been given short shrift. Astroglial cells (also known as astrocytes) have been viewed as cells that support, protect and feed neurons for the last 100 to 150 years, Marsicano explained. Over the last decade, evidence has accumulated that these cells play a more active role in forging the connections from one neuron to another.

The researchers didn’t set out to discover how marijuana causes its cognitive side effects. Rather, they wanted to learn why receptors that respond to both THC and signals naturally produced in the brain are found on astroglial cells. These cannabinoid type-1 (CB1R) receptors are very abundant in the brain, primarily on neurons of various types.

Zhang and Marsicano now show that mice lacking CB1Rs only on astroglial cells of the brain are protected from the impairments to spatial working memory that usually follow a dose of THC. In contrast, animals lacking CB1Rs in neurons still suffer the usual lapses. Given that different cell types express different variants of CB1Rs, there might be a way to therapeutically activate the receptors on neurons while leaving the astroglial cells out, Marsicano said.

"The study shows that one of the most common effects of cannabinoid intoxication is due to activation of astroglial CB1Rs," the researchers wrote.

The findings further suggest that astrocytes might be playing unexpected roles in other forms of memory in addition to spatial working memory, Zhang said.

The researchers hope to explore the activities of endogenous endocannabinoids, which naturally trigger CB1Rs, on astroglial and other cells. The endocannabinoid system is involved in appetite, pain, mood, memory and many other functions. “Just about any physiological function you can think of in the body, it’s likely at some point endocannabinoids are involved,” Marsicano said.

And that means an understanding of how those natural signaling molecules act on astroglial and other cells could have a real impact. For instance, Zhang said, “we may find a way to deal with working memory problems in Alzheimer’s.”

Source: medicalxpress.com

(PhysOrg.com) — Geraldo Barbosa, professor of electrical engineering and computer science at Northwestern University has posed an interesting challenge. He wonders if the human eye and brain together are capable of actually seeing entangled images. This is not a philosophical question, as he has phrased the query as part of a practical experiment that someone with the proper lab could actually carry out. To that end, he’s posted a paper on the preprint server arXiv with the hope that a physics team will take up the challenge.

The whole idea is based on entanglement and the means by which researchers make it come about. What they do is shoot a laser at a non-linear crystal causing the photons in the beam to be converted into lower frequency entangled pairs. Those pairs are then directed to sensors which individually are able to measure a fuzzy or blurred “image”. But when both of the entangled photons are taken together as a single measurement, the image sharpens. These images are of course far too small for the human eye to see, plus they don’t last long enough for them to be seen anyway. To address these issues, researchers have taken to firing lasers that are formed into patterns such as a doughnut shape in a continuous sequence. The result is a steady stream of entangled pairs being created in the shape of a doughnut.

Barbosa wants to know what would happen if instead of forming a doughnut shape, the lasers were made to look like a letter in the alphabet, such as the letter A, and then of course if it were made large enough to be seen by the human eye. Two entangled letter As should be created and seeable albeit in a lower frequency. If that happened, would the human eye when paired with the brain’s abilities, be able to merge the two into a sharp readable image, or would we see just the individual blurred images captured by just one sensor?

Barbosa doesn’t know, and neither does anyone else, thus he suggests someone or some group build an experiment to find out.

The ability to see things differently than we are accustomed to seeing isn’t anything new of course. Some animals can see things in the infrared spectrum for example and evidence has been slowly emerging as described here, here and here, suggesting that some migrating birds are able to “see” the Earth’s magnetic field. So maybe it’s possible that we see entangled images every day, and just don’t know it.

Hopefully someone will take Barbosa up on his challenge, and then we’ll all find out if it’s possible or not.

More information: Can humans see beyond intensity images? by Geraldo A. Barbosa, arXiv:1202.5434v1 [q-bio.NC] http://arxiv.org/abs/1202.5434

Source: PHYSORG.com

Decreased cerebral blood flow (CBF) after psilocybin imaged by fMRI. Regions where there was significantly decreased CBF after psilocybin versus after placebo are shown in blue. No CBF increases in any region were observed. Image Copyright © PNAS, doi:10.1073/pnas.1119598109

(Medical Xpress) — Psychedelic substances have long been used for healing, ceremonial, or mind-altering subjective experiences due to compounds that, when ingested or inhaled, generate hallucinations, perceptual distortions, or altered states of awareness. Of these, the psychedelic substance psilocybin, the prodrug (a precursor of a drug that must in vivo chemical conversion by metabolic processes before becoming an active pharmacological agent) of psilocin (4-hydroxy-dimethyltryptamine) and the key hallucinogen found in so-called magic mushrooms, is widely used not only in healing ceremonies, but, more recently, in psychotherapy as well – but little has been known about its specific activity in the brain.

Recently, however, scientists in the Neuropsychopharmacology Unit at Imperial College London used complementary blood-oxygen level dependent (BOLD) functional MRI, or fMRI, in conjunction with a technique for imaging the transition from normal waking consciousness to the psychedelic state. The study found decreased blood flow and BOLD in the thalamus, anterior and posterior cingulate cortex, and medial prefrontal cortex. The researchers concluded that the surprising results strongly suggest that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.

Lead researcher Dr. Robin L. Carhart-Harris, working in the Neuropsychopharmacology Unit created by Prof. David J. Nutt, recounts the team’s main challenges in establishing an fMRI methodology that would be specific enough to highly correlate neurophysiological activity with the neuronal presence or absence of psilocybin. “There were a number of considerations,” Carhart-Harris tells Medical Xpress. “In terms of experimental design, we had to determine the precise dose and delivery protocol that would be appropriate for obtaining clear fMRI results. “For example,” he explains, “we had to consider temporal dynamics: If the drug was administered orally, the protracted period of time between ingestion, metabolism, and crossing of the blood-brain barrier would fall outside of the short scanning window needed to capture induced brain activity.” They therefore had to rely on intravenous administration.

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ScienceDaily (Feb. 29, 2012) — A repression of gene activity in the brain appears to be an early event affecting people with Alzheimer’s disease, researchers funded by the National Institutes of Health have found. In mouse models of Alzheimer’s disease, this epigenetic blockade and its effects on memory were treatable.

In a mouse model of Alzheimer’s disease (right), HDAC2 levels in the hippocampus are higher than in the normal mouse hippocampus (left). Credit: (Credit: Dr. Li-Huei Tsai, MIT)

"These findings provide a glimpse of the brain shutting down the ability to form new memories gene by gene in Alzheimer’s disease, and offer hope that we may be able to counteract this process," said Roderick Corriveau, Ph.D., a program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which helped fund the research.

The study was led by Li-Huei Tsai, Ph.D., who is director of The Picower Institute for Learning and Memory at the Massachusetts Institute of Technology and an investigator at the Howard Hughes Medical Institute. It was published online February 29 in Nature.

Dr. Tsai and her team found that a protein called histone deacetylase 2 (HDAC2) accumulates in the brain early in the course of Alzheimer’s disease in mouse models and in people with the disease. HDAC2 is known to tighten up spools of DNA, effectively locking down the genes within and reducing their activity, or expression.

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ScienceDaily (Feb. 29, 2012) — In a mouse model of Alzheimer’s disease, memory problems stem from an overactive enzyme that shuts off genes related to neuron communication, a new study says.

When researchers genetically blocked the enzyme, called HDAC2, they ‘reawakened’ some of the neurons and restored the animals’ cognitive function. The results, published February 29, 2012, in the journal Nature, suggest that drugs that inhibit this particular enzyme would make good treatments for some of the most devastating effects of the incurable neurodegenerative disease.

"It’s going to be very important to develop selective chemical inhibitors against HDAC2," says Howard Hughes Medical Institute investigator Li-Huei Tsai, whose team at the Massachusetts Institute of Technology performed the experiments. "If we could delay the cognitive decline by a certain period of time, even six months or a year, that would be very significant."

In every cell, DNA wraps itself around proteins called histones. Chemical groups such as methyl and acetyl can bind to histones and affect DNA expression. HDAC2 is a histone deacetylase, an enzyme that removes acetyl groups from the histone, effectively turning off nearby genes.

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A DRUG which minimises brain damage when given three hours after stroke has proved successful in monkeys and humans.

A lack of oxygen in the brain during a stroke can cause fatal brain damage. There is only one approved treatment - tissue plasminogen activator - but it is most effective when administered within 90 minutes after the onset of stroke. Immediate treatment isn’t always available, however, so drugs that can be given at a later time have been sought.

In a series of experiments, Michael Tymianski and colleagues at Toronto Western Hospital in Ontario, Canada, replicated the effects of stroke in macaques before intravenously administering a PSD-95 inhibitor, or a placebo. PSD-95 inhibitors interfere with the process that triggers cell death when the brain is deprived of oxygen.

To test its effectiveness the team used MRI to measure the volume of damaged brain for 30 days following the treatment, and conducted behavioural tests at various intervals within this time.

Monkeys treated with the PSD-95 inhibitor one hour after stroke had 55 per cent less damaged tissue in the brain after 24 hours and 70 per cent less after 30 days, compared with those that took a placebo. These animals also did better in behavioural tests. Importantly, the drug was also effective three hours after stroke (Nature, DOI: 10.1038/nature10841).

An early stage clinical trial in humans, run by firm NoNO in Ontario has also seen positive results.

Source: New Scientist

ScienceDaily (Feb. 28, 2012) — Slowing or preventing the development of Alzheimer’s disease, a fatal brain condition expected to hit one in 85 people globally by 2050, may be as simple as ensuring a brain protein’s sugar levels are maintained.

Slowing or preventing the development of Alzheimer’s disease, a fatal brain condition expected to hit one in 85 people globally by 2050, may be as simple as ensuring a brain protein’s sugar levels are maintained. (Credit: © ktsdesign / Fotolia)

That’s the conclusion seven researchers, including David Vocadlo, a Simon Fraser University chemistry professor and Canada Research Chair in Chemical Glycobiology, make in the latest issue of Nature Chemical Biology.

The journal has published the researchers’ latest paper “Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation.”

Vocadlo and his colleagues describe how they’ve used an inhibitor they’ve chemically created — Thiamet-G — to stop O-GlcNAcase, a naturally occurring enzyme, from depleting the protein Tau of sugar molecules.

"The general thinking in science," says Vocadlo, "is that Tau stabilizes structures in the brain called microtubules. They are kind of like highways inside cells that allow cells to move things around."

Previous research has shown that the linkage of these sugar molecules to proteins, like Tau, in cells is essential. In fact, says Vocadlo, researchers have tried but failed to rear mice that don’t have these sugar molecules attached to proteins.

Vocadlo, an accomplished chess player in his spare time, is having great success checkmating troublesome enzymes with inhibitors he and his students are creating in the SFU chemistry department’s Laboratory of Chemical Glycobiology.

Research prior to Vocadlo’s has shown that clumps of Tau from an Alzheimer brain have almost none of this sugar attached to them, and O-GlcNAcase is the enzyme that is robbing them.

Such clumping is an early event in the development of Alzheimer’s and the number of clumps correlate with the disease’s severity.

Scott Yuzwa and Xiaoyang Shan, grad students in Vocadlo’s lab, found that Thiamet-G blocks O-GlcNAcase from removing sugars off Tau in mice that drank water with a daily dose of the inhibitor. Yuzwa and Shan are co-first authors on this paper.

The research team found that mice given the inhibitor had fewer clumps of Tau and maintained healthier brains.

"This work shows targeting the enzyme O-GlcNAcase with inhibitors is a new potential approach to treating Alzheimer’s," says Vocadlo. "This is vital since to date there are no treatments to slow its progression.

"A lot of effort is needed to tackle this disease and different approaches should be pursued to maximize the chance of successfully fighting it. In the short term, we need to develop better inhibitors of the enzyme and test them in mice. Once we have better inhibitors, they can be clinically tested.

Source: Science Daily

Yale University researchers have discovered a key cellular mechanism that may help the brain control how much we eat, what we weigh, and how much energy we have.

The findings, published in the Feb. 28 issue of the Journal of Neuroscience, describe the regulation of a family of cells that project throughout the nervous system and originate in an area of the brain call the hypothalamus, which has been long known to control energy balances.

Scientists and pharmaceutical companies are closely investigating the role of melanin-concentrating hormone (MCH) neurons in controlling food intake and energy. Previous studies have shown that MCH makes lab animals eat more, sleep more, and have less energy. In contrast, other hypothalamic neurons use the thyrotropin-releasing hormone (TRH) as a neurotransmitter, and these neurons reduce food intake and body weight, and increase physical activity.

The Yale study of brains of mice shows that the two systems appear to act in direct opposition, to help the organism keep these crucial functions in balance.

Although TRH is normally an excitatory neurotransmitter, the Yale study shows that in mice TRH inhibits MCH cells by increasing inhibitory synaptic input. In contrast, TRH had little effect on other types of neurons also involved in energy regulation.

“That these two types of neurons interact at the synaptic level gives us clues as to how the brain controls the amount of food we eat, and how much we sleep,” said Anthony van den Pol, senior author and professor of neurosurgery at Yale School of Medicine.

Three MCH neurons in the hypothalamus region of a mouse brain are highlighted in green. In animals, these neurons are associated with high calorie intake and lower energy levels. Yale researchers have shown how the effects of these key cells are reversed. Image adapted from Yale press release image.

Source: Neuroscience News

By SUSAN GREENFIELD

Human identity, the idea that defines each and every one of us, could be facing an unprecedented crisis. It is a crisis that would threaten long-held notions of who we are, what we do and how we behave. It goes right to the heart -or the head- of us all. This crisis could reshape how we interact with each other, alter what makes us happy, and modify our capacity for reaching our full potential as individuals. And it’s caused by one simple fact: the human brain, that most sensitive of organs, is under threat from the modern world.

PROFESSOR SUSAN GREENFIELD

Unless we wake up to the damage that the gadget-filled, pharmaceutically-enhanced 21st century is doing to our brains, we could be sleepwalking towards a future in which neuro-chip technology blurs the line between living and non-living machines, and between our bodies and the outside world.

It would be a world where such devices could enhance our muscle power, or our senses, beyond the norm, and where we all take a daily cocktail of drugs to control our moods and performance.

Already an electronic chip is being developed that could allow a paralysed patient to move a robotic limb just by thinking about it. As for drug manipulated moods, they’re already with us - although so far only to a medically prescribed extent.

Increasing numbers of people already take Prozac for depression, Paxil as an antidote for shyness, and give Ritalin to children to improve their concentration. But what if there were still more pills to enhance or “correct” a range of other specific mental functions?

Read more: Daily Mail

Article Date: 27 Feb 2012 - 10:00 PST

In a study, due to appear in the March 30 issue of Cell, researchers at MIT’s Picower Institute for Learning and Memory have discovered, for the first time, that neurons at different stages of their life cycles potentially perform two separate functions, such as forming distinct memories of almost identical situations, and the ability to recall an entire event when prompted by a tiny detail.

The study describes a brain structure that produces new neurons in adults as a possible vital target for developing drugs for the treatment of memory disorders. 


Lead author, Toshiaki Nakashiba at the Picower Institute said that an imbalance between young and old neurons in the brain region, called dentate gyrus can potentially disrupt memory formation, recalling and potentially affect cognitive dysfunctions related to post-traumatic stress disorder (PTSD), as well as aging. In dentate gyrus, only one of the two brain sites continuously generates new neurons throughout adult life.

Co-author Susumu Tonegawa, Picower Professor of Neuroscience at the Picower Institute explained:

"In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging."

The brain detects small differences between similar experiences by pattern separation. Humans are able to recall explicit content of earlier memories with only limited clues related to the original experience when these patterns are complete. For instance, a person who has dinner at the same French restaurant two nights in a row makes similar experiences or observations on both occasions, like the menu, the surroundings, the time of their visit, etc.

The distinct memories that the person’s brains forms for each event are called pattern separation. If a friend, for instance, mentions a liking for onion soup some time later, the person may recall not only the dish they had at the restaurant, but the entire experience of which people were at the restaurant, what they did after the meal, etc. This process is recalled by pattern completion. 


Whilst pattern separation forms a unique new memory based on differences between experiences, pattern completion recalls memories by identifying similarities. People who have suffered severe brain injury or trauma are often unable to recognize their family and friends’ faces that they see on a regular basis, whilst others with PTSD are unable to forget harrowing events.

Tonegawa explains:

"Impaired pattern separation due to loss of young neurons may shift the balance in favor of pattern completion, which may underlie recurrent traumatic memory recall observed in PTSD patients."

For a long time, neuroscientists believed that these two opposing and competing processes occur in different neural circuits within the hippocampus, thinking that the dentate gyrus, a structure of significant interest for its plasticity within the nervous system and its impact on conditions ranging from depression and epilepsy to traumatic brain injury, is involved in pattern separation, whilst the CA3 region is involved in pattern completion. However, the MIT researchers discovered that the neurons spawned by the dentate gyrus alone could potentially have distinct roles as they age.

The MIT researchers explored a pattern separation in mice that learned to distinguish between two chambers, of which one was safe and the other gave them an unpleasant shock to their feet. To assess the mice pattern completion abilities, the researchers gave the mice limited cues in finding their way out of a maze they knew how to negotiate earlier. They compared normal mice with mice that lacked young or old neurons, and discovered that the mice exhibited defects in pattern completion or separation, depending on which set of neurons was depleted. Previous research supported the idea that the dentate gyrus or young neurons performed pattern separation when examining pattern separation, by manipulating the entire dentate gyrus or only adult-born young neurons.

Nakashiba concluded:

"By studying mice genetically modified to block neuronal communication from old neurons—or by wiping out their adult-born young neurons—we found that old neurons were dispensable for pattern separation, whereas young neurons were required for it. Our data also demonstrated that mice devoid of old neurons were defective in pattern completion, suggesting that the balance between pattern separation and completion may be altered as a result of loss of old neurons."

Written by Petra Rattue  

Source: Medical News Today