Posts tagged neuroscience

July 9, 2012

(Medical Xpress) — Human brain cells showing aspects of Huntington’s Disease have been developed, opening up new research pathways for treating the fatal disorder.

An international consortium, including scientists from the School of Biosciences, has taken cells from Huntington’s Disease patients and generated human brain cells that develop aspects of the disease in the laboratory. The cells and the new technology will speed up research into understanding the disease and also accelerate drug discovery programs aimed at treating this terminal, genetic disorder.

Huntington’s Disease is an aggressive, neurodegenerative disorder which causes loss of co-ordination, psychiatric problems, dementia and death. Scientists have known the genetic cause of this disease for more than 20 years but research has been hampered by the lack of human brain cells with which to study the disease and screen for effective drugs.

The new breakthrough involves taking skin cells from patients with Huntington’s disease. The scientific team reprogrammed these cells into stem cells which were then turned into the brain cells affected by the disorder. The brain cells demonstrate characteristics of the disease and will allow the consortium to investigate the mechanisms that cause the brain cells to die.

Dr. Nicholas Allen, one of the lead investigators at the School of Biosciences, said: “This breakthrough allows us to generate brain cells with many of the hallmarks of this disease, within just a few weeks. This means that we can study both the normal physiology of these brain cells, and the pathological processes that lead to their death.”

The other Cardiff lead, Professor Paul Kemp, said: “Huntington’s Disease normally takes years to manifest in the human brain. Now we have a fast and reproducible model of this disease, offering fresh hope for the discovery of new therapies.”

The corresponding author of the paper, Professor Clive Svendsen, a UK scientist and now director of the Cedars-Sinai Regenerative Medicine Institute in the USA, said “This Huntington’s ‘disease in a dish’ will enable us for the first time to test therapies on human Huntington’s disease neurons. In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. It’s a new way of doing trailblazing science.”

Director of the School of Biosciences, Professor Ole Petersen said: “This is an extremely important development and I am delighted to see colleagues from the School of Biosciences playing their part in this distinguished international team. I look forward to seeing future stages, when this new technique is put to work modeling the diseases and testing potential treatments.”

Provided by Cardiff University

Source: medicalxpress.com

ScienceDaily (July 9, 2012) — “Attentional blink” is the term psychologists use to describe our inability to recognize a second important object if we see it less than half a second after a first one. It always seemed impossible to overcome, but in a new paper in the Proceedings of the National Academy of Sciences, Brown University psychologists report they’ve found a way.

So far it has seemed an irreparable limitation of human perception that we strain to perceive things in the very rapid succession of, say, less than half a second. Psychologists call this deficit “attentional blink.” We’ll notice that first car spinning out in our path, but maybe not register the one immediately beyond it. It turns out, we can learn to do better after all. In a new study researchers now based at Brown University overcame the blink with just a little bit of training that was never been tried before.

"A color change can be very conspicuous. If all items are black and white and all of a sudden a color item is shown, you pay attention to that." Credit: Mike Cohea/Brown University"Attention is a very important component of visual perception," said Takeo Watanabe, professor of cognitive, linguistic and psychological sciences at Brown. "One of the best ways to enhance our visual ability is to improve our attentional function."

Watanabe and his team were at Boston University when they performed experiments described in a paper published the week of July 9 in the Proceedings of the National Academy of Sciences. The bottom line of the research is that making the second target object a distinct color is enough to train people to switch their attention more quickly than they could before. After that, they can perceive a second target object presented as quickly as a fifth of a second later, even when it isn’t distinctly colored.

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ScienceDaily (July 9, 2012) — Alzheimer’s disease is one of the most dreaded and debilitating illnesses one can develop. Currently, the disease afflicts 6.5 million Americans and the Alzheimer’s Association projects it to increase to between 11 and 16 million, or 1 in 85 people, by 2050.

Cell death in the brain causes one to grow forgetful, confused and, eventually, catatonic. Recently approved drugs provide mild relief for symptoms but there is no consensus on the underlying mechanism of the disease.

"We don’t know what the problem is in terms of toxicity," said Joan-Emma Shea, professor of chemistry and biochemistry at the University of California, Santa Barbara (UCSB). "This makes the disease difficult to cure."

Accumulations of amyloid plaques have long been associated with the disease and were presumed to be its cause. These long knotty fibrils, formed from misfolded protein fragments, are almost always found in the brains of diseased patients. Because of their ubiquity, amyloid fibrils were considered a potential source of the toxicity that causes cell death in the brain. However, the quantity of fibrils does not correspond with the degree of dementia and other symptoms.

New findings support a hypothesis that fibrils are a by-product of the disease rather than the toxic agent itself. This paradigm shift changes the focus of inquiry to smaller, intermediate molecules that form and dissipate quickly. These molecules are difficult to perceive in brain tissue.

Read more …

July 10, 2012 by Anne Trafton

A clinical trial of an Alzheimer’s disease treatment developed at MIT has found that the nutrient cocktail can improve memory in patients with early Alzheimer’s. The results confirm and expand the findings of an earlier trial of the nutritional supplement, which is designed to promote new connections between brain cells.

A graphic depicting a synapse, a connection between brain cells. Graphic: Christine Daniloff

Alzheimer’s patients gradually lose those connections, known as synapses, leading to memory loss and other cognitive impairments. The supplement mixture, known as Souvenaid, appears to stimulate growth of new synapses, says Richard Wurtman, a professor emeritus of brain and cognitive sciences at MIT who invented the nutrient mixture.

“You want to improve the numbers of synapses, not by slowing their degradation — though of course you’d love to do that too — but rather by increasing the formation of the synapses,” Wurtman says.

To do that, Wurtman came up with a mixture of three naturally occurring dietary compounds: choline, uridine and the omega-3 fatty acid DHA. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine is produced by the liver and kidney, and is present in some foods as a component of RNA.

These nutrients are precursors to the lipid molecules that, along with specific proteins, make up brain-cell membranes, which form synapses. To be effective, all three precursors must be administered together.

Results of the clinical trial, conducted in Europe, appear in the July 10 online edition of the Journal of Alzheimer’s Disease. The new findings are encouraging because very few clinical trials have produced consistent improvement in Alzheimer’s patients, says Jeffrey Cummings, director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health.

“Memory loss is the central characteristic of Alzheimer’s, so something that improves memory would be of great interest,” says Cummings, who was not part of the research team.

Plans for commercial release of the supplement are not finalized, according to Nutricia, the company testing and marketing Souvenaid, but it will likely be available in Europe first. Nutricia is the specialized health care division of the food company Danone, known as Dannon in the United States.

Making connections

Wurtman first came up with the idea of targeting synapse loss to combat Alzheimer’s about 10 years ago. In animal studies, he showed that his dietary cocktail boosted the number of dendritic spines, or small outcroppings of neural membranes, found in brain cells. These spines are necessary to form new synapses between neurons.

Following the successful animal studies, Philip Scheltens, director of the Alzheimer Center at VU University Medical Center in Amsterdam, led a clinical trial in Europe involving 225 patients with mild Alzheimer’s. The patients drank Souvenaid or a control beverage daily for three months.

That study, first reported in 2008, found that 40 percent of patients who consumed the drink improved in a test of verbal memory, while 24 percent of patients who received the control drink improved their performance.

The new study, performed in several European countries and overseen by Scheltens as principal investigator, followed 259 patients for six months. Patients, whether taking Souvenaid or a placebo, improved their verbal-memory performance for the first three months, but the placebo patients deteriorated during the following three months, while the Souvenaid patients continued to improve. For this trial, the researchers used more comprehensive memory tests taken from the neuropsychological test battery, often used to assess Alzheimer’s patients in clinical research.

Patients showed a very high compliance rate: About 97 percent of the patients followed the regimen throughout the study, and no serious side effects were seen.

Both clinical trials were sponsored by Nutricia. MIT has patented the mixture of nutrients used in the study, and Nutricia holds the exclusive license on the patent.

Brain patterns

In the new study, the researchers used electroencephalography (EEG) to measure how patients’ brain-activity patterns changed throughout the study. They found that as the trial went on, the brains of patients receiving the supplements started to shift from patterns typical of dementia to more normal patterns. Because EEG patterns reflect synaptic activity, this suggests that synaptic function increased following treatment, the researchers say.

Patients entering this study were in the early stages of Alzheimer’s disease, averaging around 25 on a scale of dementia that ranges from 1 to 30, with 30 being normal. A previous trial found that the supplement cocktail does not work in patients with Alzheimer’s at a more advanced stage. This makes sense, Wurtman says, because patients with more advanced dementia have probably already lost many neurons, so they can’t form new synapses.

A two-year trial involving patients who don’t have Alzheimer’s, but who are starting to show mild cognitive impairment, is now underway. If the drink seems to help, it could be used in people who test positive for very early signs of Alzheimer’s, before symptoms appear, Wurtman says. Such tests, which include PET scanning of the hippocampus, are now rarely done because there are no good Alzheimer’s treatments available.

Provided by Massachusetts Institute of Technology

Source: medicalxpress.com

ScienceDaily (July 6, 2012) — In a forthcoming issue of Topics in Cognitive Science researchers from the University of Amsterdam (UvA) argue that at least two, seemingly trivial musical skills can be considered fundamental to the evolution of music: relative pitch — the skill to recognise a melody independent of its pitch level — and beat induction — the skill to pick up regularity (the beat) from a varying rhythm. Both are considered cognitive mechanisms that are essential to perceive, make and appreciate music, and, as such, could be argued to be conditional to the origin of music.

While it recently became quite popular to address the study of the origins of music from an evolutionary perspective, there is still little agreement on the idea that music is in fact an adaptation, that it influenced our survival, or that it made us sexually more attractive. Music appears to be of little use. It doesn’t quell our hunger, nor do we live a day longer because of it. So why argue that music is an adaptation? There are even researchers who claim that studying the evolution of cognition is virtually impossible (Lewontin, 1998; Bolhuis & Wynne, 2009).

Distinguishing between music and musicality

The alternative that Henkjan Honing and Annemie Ploeger of the UvA propose is, first, to distinguish between the notion of ‘music’ and ‘musicality’, with musicality being defined as a natural, spontaneously developing trait based on and constrained by our cognitive system, and music as a social and cultural construct based on that very musicality. And secondly, to collect accumulative evidence from a variety of sources (e.g., psychological, physiological, genetic, phylogenetic, and cross-cultural evidence) to be able to show that a specific cognitive trait is indeed an adaptation.

Both relative pitch and beat induction are suggested as primary candidates for such cognitive traits, musical skills that are considered trivial by most humans, but that turn out to be quite special in the rest of the animal world.

Once these fundamental cognitive mechanisms are identified, it becomes possible to see how these might have evolved. In short: the study of the evolution of music cognition is conditional on a characterisation of the basic mechanisms that make up musicality.

Source: Science Daily

ScienceDaily (July 6, 2012) — If you’re concerned about losing your hearing because of noise exposure (earbud deafness syndrome), a new discovery published online in the FASEB Journal offers some hope. That’s because scientists from Germany and Canada show that the protein, AMPK, which protects cells during a lack of energy, also activates a channel protein in the cell membrane that allows potassium to leave the cell. This activity is important because this mechanism helps protect sensory cells in the inner ear from permanent damage following acoustic noise exposure.

This information could lead to new strategies and therapies to prevent and treat trauma resulting from extreme noise, especially in people with AMPK gene variants that may make them more vulnerable to hearing loss.

"Future research on the basis of the present study may lead to the development of novel strategies preventing noise-induced hearing loss or accelerating recovery from acoustic trauma," said Florian Lang, Ph.D., a researcher involved in the work from the Department of Physiology at the University of Tübingen, in Tübingen, Germany.

To make this discovery, Lang and colleagues compared two groups of mice. The first group was normal and the second lacked the AMPK protein. Hearing of the mice was tested by measuring sound-induced brain activity. All mice were exposed to well-defined noise causing an acoustic trauma and leading to hearing impairment. Prior to noise exposure, the hearing ability was similar in normal mice and mice lacking AMPK. After exposure, the hearing of the normal mice mostly recovered after two weeks, but the recovery of hearing in AMPK-deficient mice remained significantly impaired.

"When it comes to preventing hearing loss, keeping the volume down is still the best strategy, and this discovery doesn’t prevent loud music from beating on our ear drums," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “This discovery does help explain why some people seem more likely to lose their hearing than others. At the same time, it also provides a target for new preventive strategies — and perhaps even a treatment — for earbud deafness syndrome.”

Source: Science Daily

July 6, 2012

(Medical Xpress) — Scientists at the University of Liverpool have found that a protein produced by a gene identified in fruitflies, is responsible for communication between nerve cells in the brain.

Dr Stephen Royle: “This research is another step towards fully understanding the complexities of the human brain.”

The ‘stoned’ gene was discovered in fruitflies by scientists in the 1970s. When this gene was mutated, the flies had problems walking and flying, giving rise to the term ‘stoned’ gene. The same gene was found in mammals some years later, but until now scientists have not known precisely what this gene is responsible for and why it causes problems with physical functions when it mutates.

‘Packets of chemicals’

Scientists at Liverpool have found that the protein the gene expresses in mammals, called stonin2, is responsible for retrieving ‘packets’ of chemicals that nerve cells in the brain release in order to communicate with each other.  The inability of the gene to express this protein in the fruitfly study, suggests why the insect appeared not to be able to walk or fly normally.

The team used advanced techniques to inactivate stonin2 for short and long periods of time in animal cells grown in the laboratory. The cells used where from an area of the brain associated with learning and memory.  They showed that without stonin2 the nerve cells could not retrieve the ‘packets’ needed to transport the chemicals required for communications between nerve cells.

Dr Stephen Royle, from the University’s Institute of Translational Medicine, explains: “Nerve cells in the brain communicate by releasing ‘packets’ of chemicals.  These ‘packets’ must be retrieved and refilled with chemicals so that they can be used once again. This recycling programme is very important for nerve cells to keep communicating with each other. 

“We have shown that a protein called stonin 2 is needed for the packets to be retrieved. There is currently no evidence to suggest that the gene which expresses this protein is mutated in human disease, but any failure in its function would be disastrous.  The research is another step towards fully understanding the complexities of the human brain.”

The research is published in the journal, Current Biology.

Provided by University of Liverpool

Source: medicalxpress.com

ScienceDaily (July 6, 2012) — Yona Goldshmit, Ph.D., is a former physical therapist who worked in rehabilitation centers with spinal cord injury patients for many years before deciding to switch her focus to the underlying science.

"After a few years in the clinic, I realized that we don’t really know what’s going on," she said.

Now a scientist working with Peter Currie, Ph.D., at Monash University in Australia, Dr. Goldshmit is studying the mechanisms of spinal cord repair in zebrafish, which, unlike humans and other mammals, can regenerate their spinal cord following injury. On June 23 at the 2012 International Zebrafish Development and Genetics Conference in Madison, Wisconsin, she described a protein that may be a key difference between regeneration in fish and mammals.

One of the major barriers to spinal regeneration in mammals is a natural protective mechanism, which incongruously results in an unfortunate side effect. After a spinal injury, nervous system cells called glia are activated and flood the area to seal the wound to protect the brain and spinal cord. In doing so, however, the glia create scar tissue that acts as a physical and chemical barrier, which prevents new nerves from growing through the injury site.

One striking difference between the glial cells in mammals and fish is the resulting shape: mammalian glia take on highly branched, star-like arrangements that appear to intertwine into dense tissue. Fish glia cells, by contrast, adopt a simple elongated shape — called bipolar morphology — that bridges the injury site and appears to help new nerve cells grow through the damaged area to heal the spinal cord.

"Zebrafish don’t have so much inflammation and the injury is not so severe as in mammals, so we can actually see the pro-regenerative effects that can happen," Dr. Goldshmit explained.

Studies in mice have found that mammalian glia can take up the same elongated shape, but in response to the environment around the injury they instead mature into scar tissue that does not allow nerve regrowth.

Dr. Goldshmit and her colleagues have focused on a family of molecules called fibroblast growth factors (Fgf), which have shown some evidence of improving recovery in mice and humans with spinal cord damage. The Monash University group found that Fgf activity around the damage site promotes the bipolar glial shape and encourages nerve regeneration in zebrafish.

Preliminary results in mice show that Fgf injections near a spinal injury increase both the number of glia cells at the site and the elongated morphology. Their evidence suggests that Fgfs may work to create an environment more supportive of regeneration in mammals as well and could be a valuable therapeutic target.

Spinal injury patients usually have few options, Dr. Goldshmit emphasized, and development of new, biologically-based approaches will be critical.

"This is a nice example of how we can use the zebrafish model," she said. "When we learn from the zebrafish what to look at, we can find things that give us hope for finding therapeutic approaches for spinal cord injury in humans."

Source: Science Daily