Neuroscience

July 16th, 2012

Spinal Muscular Atrophy affects one in 6,000 children and has no known cure.

A team of University of Missouri researchers has found that introducing a missing gene into the central nervous system could help extend the lives of patients with Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile death in the world.

SMA is a rare genetic disease that is inherited by one in 6,000 children who often die young because there is no cure. Children who inherit SMA are missing a gene that produces a protein which directs nerves in the spine to give commands to muscles.

The MU team, led by Christian Lorson, professor in the Department of Veterinary Pathobiology and the Department of Molecular Microbiology and Immunology, introduced the missing gene into mice born with SMA through two different methods: intravenously and directly into the mice’s central nervous systems. While both methods were effective in extending the lives of the mice, Lorson found that introducing the missing gene directly into the central nervous system extended the lives of the mice longer.

Mice born with spinal muscular atrophy typically only live five or six days. Researchers introduced the SMN gene into the mice’s central nervous systems and were able to extend their lives 10-25 days longer. The mice in the picture have spinal muscular atrophy.

“Typically, mice born with SMA only live five or six days, but by introducing the missing SMN gene into the mice’s central nervous systems, we were able to extend their lives 10-25 days longer than SMA mice who go untreated,” said Lorson, who works in the MU Bond Life Sciences Center and the College of Veterinary Medicine. “While this system is still not perfect, what our study did show is that the direct administration of the missing gene into the central nervous system provides some degree of rescue and a profound extension of survival.”

There are several different types of SMA that appear in humans, depending on the age that symptoms begin to appear. Lorson believes that introducing the missing gene through the central nervous system is a way to potentially treat humans regardless of what SMA type they have.

“This is a treatment method that is very close to being a reality for human patients,” Lorson said. “Clinical trials of SMA treatment using gene therapy are likely to begin in next 12-18 months, barring any unforeseen problems.”

Source: Neuroscience News

July 16, 2012

Can you teach an old dog (or human) new tricks? Yes, but it might take time, practice, and hard work before he or she gets it right, according to Hans Schroder and colleagues from Michigan State University in the US. Their work shows that when rules change, our attempts to control our actions are accompanied by a loss of attention to detail. Their work is published online in the Springer journal Cognitive, Affective, & Behavioral Neuroscience.

In order to adapt to changing conditions, humans need to be able to modify their behavior successfully. Overriding the rules we adhere to on a daily basis requires substantial attention and effort, and we do not always get it right the first time. When we switch between two or more tasks, we are slower and more likely to commit errors, which suggests switching tasks is a costly process. This may explain why it is so hard to learn from our mistakes when rules change.

The authors explain: “Switching the rules we use to perform a task makes us less aware of our mistakes. We therefore have a harder time learning from them. That’s because switching tasks is mentally taxing and costly, which leads us to pay less attention to the detail and therefore make more mistakes.”

A total of 67 undergraduates took part in the study. They were asked to wear a cap, which recorded electrical activity in the brain. They then performed a computer task that is easy to make mistakes on. Specifically, the participants were shown letter strings like “MMMMM” or “NNMNN” and were told to follow a simple rule: if ‘M’ is in the middle, press the left button; if ‘N’ is in the middle, press the right button. After they had followed this rule for almost 50 trials, they were instructed to perform the same task, but with the rules reversed i.e. now if ‘M’ is in the middle, press the right button; and if ‘N’ is in the middle, press the left button.

When the rules were reversed, participants made more consecutive errors. They were more likely to get it wrong twice in a row. This showed they were less apt to bounce back and learn from their mistakes. Reversing the rules also produced greater control-related and less error-awareness brain activity.

These results suggest that when rules are reversed, our brain works harder to juggle the two rules - the new rule and the old rule - and stay focused on the new rule. When we spend brain energy juggling these two rules, we have less brain power available for recognizing our mistakes.

Provided by Springer

Source: medicalxpress.com

ScienceDaily (July 16, 2012) — Far from processing every word we read or hear, our brains often do not even notice key words that can change the whole meaning of a sentence, according to new research from the Economic and Social Research Council (ESRC).

After a plane crash, where should the survivors be buried?

If you are considering where the most appropriate burial place should be, you are not alone. Scientists have found that around half the people asked this question, answer it as if they were being asked about the victims not the survivors.

Similarly, when asked “Can a man marry his widow’s sister?” most people answer “yes” — effectively answering that it would indeed be possible for a dead man to marry his bereaved wife’s sister.

What makes researchers particularly interested in people’s failure to notice words that actually don’t make sense, so called semantic illusions, is that these illusions challenge traditional models of language processing which assume that we build understanding of a sentence by deeply analysing the meaning of each word in turn.

Instead semantic illusions provide a strong line of evidence that the way we process language is often shallow and incomplete.

Professor Leuthold at University of Glasgow led a study using electroencephalography (EEG) to explore what is happening in our brains when we process sentences containing semantic illusions.

By analysing the patterns of brain activity when volunteers read or listened to sentences containing hard-to-detect semantic anomalies — words that fit the general context even though they do not actually make sense — the researchers found that when a volunteer was tricked by the semantic illusion, their brain had not even noticed the anomalous word.

Analyses of brain activity also revealed that we are more likely to use this type of shallow processing under conditions of higher cognitive load — that is, when the task we are faced with is more difficult or when we are dealing with more than one task at a time.

The research findings not only provide a better understanding of the processes involved in language comprehension but, according to Professor Leuthold, knowing what is happening in the brain when mistakes occur can help us to avoid the pitfalls,such as missing critical information in textbooks or legal documents, and communicate more effectively.

There are a number of tricks we can use to make sure we get the correct message across: “We know that we process a word more deeply if it is emphasised in some way. So, for example in a news story, a newsreader can stress important words that may otherwise be missed and these words can be italicised to make sure we notice them when reading,” said Professor Leuthold.

The way we construct sentences can also help reduce misunderstandings, he explained: “It’s a good idea to put important information first because we are more likely to miss unusual words when they are near the end of a sentence. Also, we often use an active sentence construction such as ‘Bob ate the apple’ because we make far more mistakes answering questions about a sentence with a passive construction — for example ‘The apple was eaten by Bob’.”

The study findings also suggest that we should avoid multi-tasking when we are reading or listening to an important message: “For example, talking to someone on the phone while driving on a busy motorway or in town, or doing some homework while listening to the newsmight lead to more shallow processing,” said Professor Leuthold.

Source: Science Daily

July 16, 2012

A nationwide consortium of scientists at 20 institutions, led by a principal faculty member at the Harvard Stem Cell Institute (HSCI), has used stem cells to take a major step toward developing personalized medicine to treat Parkinson’s disease.

This study points the way to screening patients with Parkinson’s for their particular variation of the disease, and then treating them with drugs shown effective to work on that variation, rather than trying to treat all patients with the same drugs, as is generally done now, notes Ole Isacson, a leader of the study. Credit: B. D. Colen/Harvard Staff

In part supported by the Harvard Miller Consortium for the Development of Nervous System Therapies, the team of scientists created induced pluripotent stem cells (iPS cells) from the skin cells of patients and at-risk individuals carrying genetic mutations implicated in Parkinson’s disease, and used those cells to derive neural cells, providing a platform for studying the disease in human cells outside of patients.

In a paper published in the journal Science Translational Medicine, the researchers report that although approximately 15 genetic mutations are linked to forms of Parkinson’s, many seem to affect the mitochondria, the cell unit that produces most of its energy.

“This is the first comprehensive study of how human neuronal cells can be models of Parkinson’s, and how it might be treated,” said Ole Isacson, a leader of the study, an HSCI principal faculty member, and a Harvard Medical School professor of neurology, based at McLean Hospital’s Neuroregeneration Laboratory.

The researchers determined that certain compounds or drugs could reverse some signs of disease in the cultured cells with specific genetic mutations, and not in cells with other types of mutations, making real the concept of developing drugs that would be prescribed to patients or individuals at risk for Parkinson’s.

The study was launched with federal stimulus funding provided by the National Institutes of Health (NIH) and was continued with funding from HSCI.

“These findings suggest new opportunities for clinical trials of Parkinson’s disease, wherein cell reprogramming technology could be used to identify the patients most likely to respond to a particular intervention,” said Margaret Sutherland, a program director at NIH’s National Institute of Neurological Disorders and Stroke, in a press release.

The new research indicates that compounds that previously have shown promise in treating Parkinson’s in animal studies, including the antioxidant coenzyme Q10, together with the immunosuppressant rapamycin, have differing levels of effectiveness on various genetic forms of Parkinson’s.

Researchers hope that such findings can provide the basis for more specific drugs for individuals with sporadic forms of Parkinson’s.

As Isacson explained in an interview, this study points the way to screening patients with Parkinson’s for their particular variation of the disease, and then treating them with drugs shown effective to work on that variation, rather than trying to treat all patients with the same drugs, as is generally done now.

“We believe that using human stem cells to study the disease is the correct way to go,” Isacson said. “We have the cell type most vulnerable to the disease in a dish. We can study the most vulnerable cells and compare them to the least vulnerable cells. Traditionally, in neurology,” he said, “all patients with the same disease get the same drugs. But they may have the disease for different reasons. This gives us a way to tease out those different reasons, and find different ways to treat them.”

Provided by Harvard University

Source: medicalxpress.com

July 16, 2012

For more than 20 years, doctors have been using cells from blood that remains in the placenta and umbilical cord after childbirth to treat a variety of illnesses, from cancer and immune disorders to blood and metabolic diseases.

This microscope image shows a colony of neurons derived from cord-blood cells using stem cell reprogramming technology. The green and red glow indicates that the cells are producing protein makers found in neurons, evidence that the cord-blood cells did in fact morph into neurons. The blue glow marks the nuclei of the neurons. Credit: Image: Courtesy of Alessandra Giorgetti

Now, scientists at the Salk Institute for Biological Studies have found a new way-using a single protein, known as a transcription factor-to convert cord blood (CB) cells into neuron-like cells that may prove valuable for the treatment of a wide range of neurological conditions, including stroke, traumatic brain injury and spinal cord injury.

The researchers demonstrated that these CB cells, which come from the mesoderm, the middle layer of embryonic germ cells, can be switched to ectodermal cells, outer layer cells from which brain, spinal and nerve cells arise. “This study shows for the first time the direct conversion of a pure population of human cord blood cells into cells of neuronal lineage by the forced expression of a single transcription factor,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, who led the research team. The study, a collaboration with Fred H. Gage, a professor in Salk’s Laboratory of Genetics, and his team, was published on July 16 in the Proceedings of the National Academy of Sciences.

"Unlike previous studies, where multiple transcription factors were necessary to convert skin cells into neurons, our method requires only one transcription factor to convert CB cells into functional neurons," says Gage.

The Salk researchers used a retrovirus to introduce Sox2, a transcription factor that acts as a switch in neuronal development, into CB cells. After culturing them in the laboratory, they discovered colonies of cells expressing neuronal markers. Using a variety of tests, they determined that the new cells, called induced neuronal-like cells (iNC), could transmit electrical impulses, signaling that the cells were mature and functional neurons. Additionally, they transferred the Sox2-infused CB cells to a mouse brain and found that they integrated into the existing mouse neuronal network and were capable of transmitting electrical signals like mature functional neurons.

"We also show that the CB-derived neuronal cells can be expanded under certain conditions and still retain the ability to differentiate into more mature neurons both in the lab and in a mouse brain," says Mo Li, a scientist in Belmonte’s lab and a co-first author on the paper with Alessandra Giorgetti, of the Center for Regenerative Medicine, in Barcelona, and Carol Marchetto of Gage’s lab. "Although the cells we developed were not for a specific lineage-for example, motor neurons or mid-brain neurons-we hope to generate clinically relevant neuronal subtypes in the future."

Importantly, says Marchetto, “We could use these cells in the future for modeling neurological diseases such as autism, schizophrenia, Parkinson’s or Alzheimer’s disease.”

Cord blood cells, says Giorgetti, offer a number of advantages over other types of stem cells. First, they are not embryonic stem cells and thus they are not controversial. They are more plastic, or flexible, than adult stem cells from sources like bone marrow, which may make them easier to convert into specific cell lineages. The collection of CB cells is safe and painless and poses no risk to the donor, and they can be stored in blood banks for later use.

"If our protocol is developed into a clinical application, it could aid in future cell-replacement therapies," says Li. "You could search all the cord blood banks in the country to look for a suitable match."

Provided by Salk Institute

Source: medicalxpress.com

ScienceDaily (July 16, 2012) — A team of scientists at The New York Stem Cell Foundation (NYSCF) Laboratory led by Scott Noggle, PhD, NYSCF-Charles Evans Senior Research Fellow for Alzheimer’s Disease, has developed the first cell-based model of Alzheimer’s disease (AD) by reprogramming skin cells of Alzheimer’s patients to become brain cells that are affected in Alzheimer’s. This will allow researchers to work directly on living brain cells suffering from Alzheimer’s, which until now had not been possible. Andrew Sproul, PhD, a postdoctoral associate in Dr. Noggle’s laboratory, will present this work on July 19 at the Alzheimer’s Association International Conference (AAIC) held in Vancouver.

Dr. Noggle and his team reprogrammed skin cell samples taken from twelve patients diagnosed with early-onset Alzheimer’s and from healthy, genetically related individuals into induced pluripotent stem (iPS) cells, which can differentiate into any cell type. The team of scientists used these iPS cells to create cholinergic basal forebrain neurons, the brain cells that are affected in Alzheimer’s. These cells recapitulate the features and cellular-level functions of patients suffering from Alzheimer’s, a devastating disease that affects millions of people globally but for which there is currently no effective treatment.

NYSCF has pioneered the creation of disease models based on the derivation of human cells. Four years ago, a NYSCF-funded team created a cell-based model for ALS, or motor neuron disease, the first patient-specific stem cells created for any disease. The cell-based model for Alzheimer’s builds on this earlier work.

"Patient derived AD cells will prove invaluable for future research advances, as they already have with patient-derived ALS cells," said NYSCF CEO Susan Solomon. "They will be a critical tool in the drug discovery process, as potential drugs could be tested directly on these cells. Although research on animals has provided valuable insight into AD, we aren’t mice, and animals don’t properly reflect the features of the disease we are trying to cure. As we work to find new drugs and treatments our research should focus on actual human sufferers of Alzheimer’s disease," emphasized Ms. Solomon

This cell-based model has already led to important findings. Preliminary results of this NYSCF research, done in collaboration with Sam Gandy, MD, PhD, an international expert in the pathology of Alzheimer’s at Mount Sinai School of Medicine, demonstrated differences in cellular function in Alzheimer’s patients. Specifically, Alzheimer’s neurons produce more of the toxic form of beta amyloid, the protein fragment that makes up amyloid plaques, than in disease-free neurons.

"iPS cell technology, along with whole genome sequencing, provide our best chance at unravelling the causes of common forms of Alzheimer’s disease," noted Dr. Gandy.

"This collaboration is a great example of how NYSCF is bringing together experts in stem cell technology and clinicians to save and enhance lives by finding better treatments," Ms. Solomon explained.

The research to be reported at the AAIC by Andrew Sproul focused on stem cell models of individuals with presenilin-1 (PSEN1) mutations, a genetic cause of AD. As Dr. Sproul has said, this cell-based model could “revolutionize how we discover drugs to potentially cure Alzheimer’s disease.”

Source: Science Daily

July 16, 2012

Activity lingers longer in certain areas of the brain in those with Alzheimer’s than it does in healthy people, Mayo Clinic researchers who created a map of the brain found. The results suggest varying brain activity may reduce the risk of Alzheimer’s disease. The study, “Non-stationarity in the “Resting Brain’s” Modular Architecture,” was presented at the Alzheimer’s Association International Conference and recently published in the journal PLoS One.

Researchers compared brain activity to a complex network, with multiple objects sharing information along pathways.

"Our understanding of those objects and pathways is limited," says lead author David T. Jones, M.D. "There are regions in the brain that correspond to those objects, and we are not really clear exactly what those are. We need a good mapping or atlas of those regions that make up the network in the brain, which is part of what we were doing in this study."

Researchers examined 892 cognitively normal people taking part in the Mayo Clinic Study of Aging, and set out to create an active map of their brains while the people were “at rest,” not engaged in a specific task. To do this, they employed task-free, functional magnetic resonance imaging to construct an atlas of 68 functional regions of the brain, which correspond to the cities on the road map.

Researchers filled in the roads between these regions by creating dynamic graphic representations of brain connectivity within a sliding time window.

This analysis revealed that there were many roads that could be used to exchange information in the brain, and the brain uses different roads at different times. The question to answer then, said Dr. Jones, is whether or not Alzheimer’s patients used this map and these roads in a different way than their healthy peers.

"What we found in this study was that Alzheimer’s patients tended to spend more time using some roads and less time using other roads, biasing one over the other," he says.

While more research is needed, the researchers say one implication is that how we use our brains may protect us from Alzheimer’s. Dr. Jones says exercise, education, and social contacts may help balance activity in the brain.

"Diversifying the mental space that you explore may actually decrease your risk for Alzheimer’s," he says.

Provided by Mayo Clinic

Source: medicalxpress.com

July 16, 2012

One of the marvels of brain development is the mass migration of nerve cells to their functional position. European research has investigated the molecules required for their successful navigation.

Credit: Thinkstock

Formation of the cerebral cortex during embryonic development requires the migration of billions of cells from their birth position to their final destination. A motile nerve cell must have internal polarity to move in the specified direction. What is more, neurons then have to extend neurites or projections from the cell body to communicate with each other.

The key to this extraordinary feat of organisation lies in cell signalling pathways. The EU-funded Neuronal Polarity project aimed to characterise these cascades important in cerebral cortex development. At a later stage, defective cortical architecture can be responsible for brain pathologies including microcephaly, epilepsy and schizophrenia.

Project scientists showed that in vivo the guanine triphosphatase GTPase Ras-proximate-1 (Rap 1) caused an accumulation of neurons halfway to their destination. The team used time-lapse video microscopy and immunostaining to show that the problem does not lie with motility of the neurons but in a defect in their polarity. Other evidence from motility tests in vitro and the fact that some neurons do actually make it to their destination, albeit slowly, suggest Rap 1 is important for initial polarisation of the neurons.

The transmembrane receptor N-cadherin (Ncad) also has an important function in polarising cortical neurons. Experimental data confirmed that this receptor is involved downstream from Rap 1. Overall, inhibition of Rap 1 reduces Ncad presence.

Neuronal Polarity scientists suggest that Rap 1 activity is important in migrating neurons to maintain a high level of Ncad at the plasma membrane for nerve cells to polarise correctly.

Exactly how Ncad interacts with molecular cascades for neuron polarisation is still under investigation. The Neuronal Polarity project accumulated data on which to base a concrete research path for future investigation.

Provided by CORDIS

Source: medicalxpress.com

ScienceDaily (July 16, 2012) — Mayo Clinic researchers have found a novel way to monitor real-time chemical changes in the brains of patients undergoing deep brain stimulation (DBS). The groundbreaking insight will help physicians more effectively use DBS to treat brain disorders such as Parkinson’s disease, depression and Tourette syndrome.

The findings are published in the journal Mayo Clinic Proceedings.

Researchers hope to use the discovery to create a DBS system that can instantly respond to chemical changes in the brain. Parkinson’s, Tourette syndrome and depression all involve a surplus or deficiency of neurochemicals in the brain. The idea is to monitor those neurochemicals and adjust them to appropriate levels.

"We can learn what neurochemicals can be released by DBS, neurochemical stimulation, or other stimulation. We can basically learn how the brain works," says author Su-Youne Chang, Ph.D., of the Mayo Clinic Neurosurgery Department. As researchers better understand how the brain works, they can predict changes, and respond before those changes disrupt brain functioning.

Researchers observed the real-time changes of the neurotransmitter adenosine in the brains of tremor patients undergoing deep brain stimulation. Neurotransmitters such as dopamine and serotonin are chemicals that transmit signals from a neuron to a target cell across a synapse.

The team used fast scan cyclic voltammetry (FSCV) to quantify concentrations of adenosine released in patients during deep brain stimulation. The data was recorded using Wireless Instantaneous Neurotransmitter Concentration Sensing, a small wireless neurochemical sensor implanted in the patient’s brain. The sensor, combined with FSCV, scans for the neurotransmitter and translates that information onto a laptop in the operating room. The sensor has previously identified neurotransmitters serotonin and dopamine in tests in brain tissue. This was the first time researchers used this technique in patients.

Tremors are a visual cue that the technique is working; researchers suspect adenosine plays a role in reducing tremors.

Researchers also hope to learn more about conditions without such external manifestations.

"We can’t watch pain as we do tremors," says Kendall Lee, M.D., Ph.D., a Mayo Clinic neurosurgeon. "What is exciting about this electrochemical feedback is that we can monitor the brain without external feedback. So now, we can monitor neurochemicals in the brain and learn about brain processes like pain."

DBS has been used successfully worldwide to treat patients with tremors. However, physicians do not fully understand why DBS works in patients. They know that when DBS electrodes are inserted before electrical stimulation, there is an immediate tremor reduction. Known as the microthalamotomy effect, it is reported in up to 53 percent of patients and known to last as long as a year.

Researchers hope to use the study findings to create a self-contained “smart” DBS system.

"With the stimulator and detection, we can create algorithms and then raise neurotransmitters to a specified level," says Kevin Bennet, a Mayo Clinic engineer who helped create the system. "We can raise these chemicals to appropriate levels, rising and falling with each person throughout their life. Within milliseconds, we can measure, calculate and respond. From the patient’s perspective, this would be essentially instantaneous."

Source: Science Daily

FRIDAY, July 13 (HealthDay News) — Movies often stereotype people with schizophrenia as being violent and unpredictable, says a researcher who claims Hollywood dispenses misinformation about symptoms, causes and treatment of this mental illness.

Hollywood portrayals are often inaccurate, misleading, study shows.

For the study, published in the July issue of Psychiatric Services, Patricia Owen of the psychology department at St. Mary’s University in San Antonio, Texas, reviewed 41 English-language films released between 1990 and 2010 that featured at least one main character with schizophrenia.

Owen found that 83 percent of those characters were portrayed as dangerous or violent to others or themselves. Almost one-third engaged in homicidal behavior, and one-quarter committed suicide, the researcher said.

According to the U.S. National Institute of Mental Health, the risk of violence is small among people with schizophrenia. But suicide risk is higher than average. About 10 percent, mostly young men, do kill themselves, the agency notes.

Delusions, auditory and visual hallucinations, and disorganized speech or thought were displayed by most of the characters, the study author pointed out in a news release from the American Psychiatric Association.

But much more common symptoms of schizophrenia — such as flat affect, lack of speech and lack of motivation — were seen much less frequently.

Although schizophrenia incidence is nearly equal among women and men, almost 80 percent of the characters with schizophrenia were male, the study found.

The review noted, however, the movies did get some characterizations of schizophrenia right. Specifically, about half of the characters had low socioeconomic status, which is consistent with data on the illness. Moreover, about half of the movies depicted or alluded to the use of medication to treat the mental illness. Psychotherapy and group therapy were not portrayed often.

Owen suggested that more research is needed to understand how films influence public perceptions about schizophrenia, and to determine how to increase empathy and understanding.

Films featuring a character with schizophrenia include A Beautiful Mind and Donnie Darko.

Source: DoctorsLounge

ScienceDaily (July 13, 2012) — A new study by University of North Carolina School of Medicine researchers found that 31 percent of children identified as at risk for autism spectrum disorders (ASD) at 12 months received a confirmed diagnosis of ASD by age 3 years.

In addition, 85 percent of the children found to be at risk for ASD based on results from the First Year Inventory (FYI), a 63-item questionnaire filled out by their parents, had some other developmental disability or concern by age three, said Grace Baranek, PhD, senior author of the study and an autism researcher with the Program for Early Autism, Research, Leadership and Service (PEARLS) in the Department of Allied Health Sciences at the UNC School of Medicine.

"These results indicate that an overwhelming majority of children who screen positive on the FYI indeed experience some delay in development by age three that may warrant early intervention," she said.

Lead author of the study, Lauren Turner-Brown, PhD, also a researcher with PEARLS and the Carolina Institute for Developmental Disabilities said, “Identification of children at risk for ASD at 12 months could provide a substantial number of children and their families with access to intervention services months or years before they would otherwise receive a traditional diagnosis.”

The First Year Inventory was developed by Grace Baranek, PhD, Linda Watson, EdD, Elizabeth Crais, PhD and J. Steven Reznick, PhD, who are all researchers with PEARLS. All are also co-authors of the study with Turner-Brown, published online ahead of print on July 10, 2012 by Autism: The International Journal of Research & Practice.

In the study, parents of 699 children who had completed the FYI when their child was 12 months old completed additional screening questionnaires when their child reached age 3. In addition, children who were found to be at risk for ASD based on these measures were invited for in-person diagnostic evaluations.

"These findings are encouraging and suggest promise in the approach of using parent report of infant behaviors as a tool for identifying 12-month-olds who are at risk for an eventual diagnosis of ASD," Turner-Brown said.

Source: Science Daily

ScienceDaily (July 12, 2012) — Millions of people suffering from multiple sclerosis, Parkinson’s, muscular dystrophy, spinal cord injuries or amputees could soon interact with their computers and surroundings using just their eyes, thanks to a new device that costs less than £40.

Researchers from Imperial College London demonstrated the functionality of the new system by getting a group of people to play the classic computer game Pong without any kind of handset. (Credit: Image courtesy of Institute of Physics (IOP))

Composed from off-the-shelf materials, the new device can work out exactly where a person is looking by tracking their eye movements, allowing them to control a cursor on a screen just like a normal computer mouse.

The technology comprises an eye-tracking device and “smart” software that have been presented July 13, in IOP Publishing’s Journal of Neural Engineering. Researchers from Imperial College London demonstrated its functionality by getting a group of people to play the classic computer game Pong without any kind of handset. In addition users were able to browse the web and write emails “hands-off.”

A video of somebody using the device to play Pong can be viewed here (https://www.youtube.com/watch?v=zapK5wvYU84)

The GT3D device is made up of two fast video game console cameras, costing less than £20 each, that are attached, outside of the line of vision, to a pair of glasses that cost just £3. The cameras constantly take pictures of the eye, working out where the pupil is pointing, and from this the researchers can use a set of calibrations to work out exactly where a person is looking on the screen.

Even more impressively, the researchers are also able to use more detailed calibrations to work out the 3D gaze of the subjects — in other words, how far into the distance they were looking. It is believed that this could allow people to control an electronic wheelchair simply by looking where they want to go or control a robotic prosthetic arm.

To demonstrate the effectiveness of the eye-tracker, the researchers got subjects to play the video game Pong. In this game, the subject used his or her eyes to move a bat to hit a ball that was bouncing around the screen — a feat that is difficult to accomplish with other read-out mechanisms such as brain waves (EEG).

Dr Aldo Faisal, Lecturer in Neurotechnology at Imperial’s Department of Bioengineering and the Department of Computing, is confident in the ability to utilise eye movements given that six of the subjects, who had never used their eyes as a control input before, could still register a respectable score within 20 per cent of the able bodied users after just 10 minutes of using the device for the first time.

The commercially viable device uses just one watt of power and can transmit data wirelessly over Wi-Fi or via USB into any Windows or Linux computer.

The GT3D system has also solved the ‘Midas touch problem’, allowing users to click on an item on the screen using their eyes, instead of a mouse button.

This problem has previously been resolved by staring at an icon for a prolonged period or blinking; however, the latter is part of our natural behaviour and happens unintentionally. Instead, the researchers calibrated the system so that a simple wink would represent a mouse click, which only occurs voluntarily unlike the blink.

Dr Faisal said: “Crucially, we have achieved two things: we have built a 3D eye tracking system hundreds of times cheaper than commercial systems and used it to build a real-time brain machine interface that allows patients to interact more smoothly and more quickly than existing invasive technologies that are tens of thousands of times more expensive.

"This is frugal innovation; developing smarter software and piggy-backing existing hardware to create devices that can help people worldwide independent of their healthcare circumstances."

Source: Science Daily

ScienceDaily (July 12, 2012) — Negative suggestion can induce symptoms of illness. Nocebo effects are the adverse events that occur during sham treatment and/or as a result of negative expectations. While the positive counterpart — the placebo effect — has been intensively studied in recent years, the scientific literature contains few studies on nocebo phenomena. In the latest issue of Deutsches Ärzteblatt International, Winfried Häuser of the Technical University of Munich and his co-authors present the underlying neurobiological mechanisms and highlight the relevance of the nocebo effect in everyday clinical practice.

Nocebo responses can, for instance, be brought about by unintended negative suggestion on the part of doctors or nurses, e.g., when informing the patient about the possible complications of a proposed treatment. It is also assumed that a certain proportion of the undesired effects of drugs can be attributed to nocebo effects. The mechanisms behind this phenomenon are — as with placebo effects — learning by Pavlovian conditioning and reaction to induced expectations.

What are the consequences for clinical practice? Doctors find themselves in an ethical dilemma between their obligation to tell the patient about the possible side effects of a treatment and their duty to minimize the risk of a medical intervention and thus to avoid triggering nocebo effects. As one possible strategy to solve this dilemma, Häuser et al. suggest emphasizing the tolerability of therapeutic measures. Another option, with the patient’s permission, would be to desist from discussing undesired effects during the patient briefing.

Source: Science Daily

ScienceDaily (July 12, 2012) — University of Kansas researchers have found larger resting pupil size and lower levels of a salivary enzyme associated with the neurotransmitter norepinephrine in children with autism spectrum disorder.

However, even though the levels of the enzyme, salivary alpha-amylase (sAA), were lower than those of typically-developing children in samples taken in the afternoon in the lab, samples taken at home throughout the day showed that sAA levels were higher in general across the day and much less variable for children with ASD.

"What this says is that the autonomic system of children with ASD is always on the same level," Christa Anderson, assistant research professor, said. "They are in overdrive."

The sAA levels of typically-developing children gradually rise and fall over the day, said Anderson, who co-directed the study with John Colombo, professor of psychology.

Norepinephrine (NE) has been found in the blood plasma levels of individuals with ASD but some researchers have questioned whether these levels were just related to the stress from blood draws.

The KU study addressed this by collecting salivary measures by simply placing a highly absorbent sponge swab under the child’s tongue and confirmed that this method of collection did not stress the children by assessing their stress levels through cortisol, another hormone.

Collecting sAA levels has the potential for physicians to screen children for ASD much earlier, noninvasively and relatively inexpensively, said Anderson.

But Anderson and Colombo also see pupil size and sAA levels as biomarkers that could be the physiological signatures of a possible dysfunction in the autonomic nervous system.

"Many theories of autism propose that the disorder is due to deficits in higher-order brain areas," said Colombo. "Our findings, however, suggest that the core deficits may lie in areas of the brain typically associated with more fundamental, vital functions."

The study, published online in the May 29, 2012 Developmental Psychobiology compared children between the ages of 20 and 72 months of age diagnosed with ASD to a group of typically developing children and a third group of children with Down Syndrome.

Both findings address the Centers for Disease Control’s urgent public health priority goals for ASD: to find biological indicators that can both help screen children earlier and lead to better understanding of how the nervous system develops and functions in the disorder.

Source: Science Daily

ScienceDaily (July 12, 2012) — Researchers at Emory University School of Medicine have identified five rare mutations in a single gene that appear to increase the chances that a boy will develop an autism spectrum disorder (ASD).

Mutations in the AFF2 gene, and other genes like it on the X chromosome, may explain why autism spectrum disorders affect four times as many boys as girls.

The mutations in AFF2 appeared in 2.5 percent (5 out of 202) boys with an ASD. Mutations in X chromosome genes only affect boys, who have one X chromosome. Girls have a second copy of the gene that can compensate.

The results were published July 5 in the journal Human Molecular Genetics.

"Our data suggest that AFF2 could be one of the major X-linked risk factors for ASD’s," says senior author Michael Zwick, PhD, assistant professor of human genetics at Emory University School of Medicine.

The finding bolsters a growing consensus among geneticists that rare variants in many different genes contribute significantly to risk for autism spectrum disorders.

The mutations in the AFF2 gene probably do not cause ASDs all by themselves, Zwick says.

"We do not think that the variants we have identified are monogenic causes of autism," he says. "Our data does support the idea that this is an autism susceptibility gene."

In some situations, mutations in a single gene are enough by themselves to lead to a neurodevelopmental disorder with autistic features, such as fragile X syndrome or tuberous sclerosis complex. But these types of mutations are thought to account for a small number of ASD cases.

Recent large-scale genetic studies of autism spectrum disorders have identified several “rare variants” that sharply increase ASD risk. Scientists believe rare variants could explain up to 15 or 20 percent of ASD cases. However, until now no single variant has been found in more than one percent of ASD cases.

Working with Zwick, postdoctoral fellow Kajari Mondal and her colleagues read the sequence of the AFF2 gene in DNA from 202 boys diagnosed with autism spectrum disorders. The patient samples came from the Autism Genetic Resource Exchange and the Simons Simplex Collection.

Tests showed that in four cases, the affected boys had inherited the risk-conferring mutations from their mothers. One boy had a “de novo” (not coming from the parents) mutation. Compared with X-linked genes in unaffected people, mutations in AFF2 were five times more abundant in the boys with ASDs.

The AFF2 gene had already been identified as responsible for a rare inherited form of intellectual disability with autistic features. This effect is seen when the AFF2 gene is deleted or silenced completely.

AFF2 has some similarity to FMR1, the gene responsible for fragile X syndrome. Like FMR1, it can be silenced by a triplet repeat. In these cases, the presence of the triplet repeat (three genetic bases repeated dozens of times) triggers a change in chromosomal structure that prevents the gene from being turned on.

In contrast, the mutations Zwick’s team found are more subtle, slightly changing the sequence of the protein AFF2 encodes. Little is known about the precise function of the AFF2 protein. A related gene in fruit flies called lilliputian also appears to regulate the development of neurons.

Zwick says one of his laboratory’s projects is to learn more about the function of the AFF2 gene, and to probe how the mutations identified by his team affect the function. His team is also working on gauging the extent to which other genes on the X chromosome contribute to autism risk.

Source: Science Daily

ScienceDaily (July 12, 2012) — Diagnosing multiple sclerosis (MS) is a challenge even for experienced neurologists. This autoimmune disease has many symptoms and rarely presents a uniform clinical picture. New scientific findings on the immune response involved in MS could now help improve the diagnosis of this illness. Scientists analyzing the blood of MS patients have discovered antibodies that attack a specific potassium channel in the cell membrane. Potassium channels play an important role in transmitting impulses to muscle and nerve cells and it is exactly these processes that are inhibited in MS patients.

Right: The autoantibody can be seen binding to the membrane of glial cells in the MS serum. By comparison, the image on the left shows a blood sample from a patient with another neurological disease. (Credit: KKNMS)

The results are published in the current issue of the New England Journal of Medicine.

For the first time, scientists in Germany’s multiple sclerosis competence network have been able to identify an antibody that bonds with the potassium channel KIR4.1. “We found this autoantibody in almost half of the MS patients in our study,” explains Bernhard Hemmer, Professor of Neurology at the Klinikum rechts der Isar hospital at Technische Universität München (TUM). The biomarker was not present in healthy patients. The findings could therefore indicate that KIR4.1 is one of the targets of the autoimmune response in MS. Humans and animals without the KIR4.1 channel experience neurological failure and cannot coordinate their movements properly. Furthermore, their bodies do not create sufficient amounts of myelin, a layer of insulation that protects the nerve cells.

KIR4.1 is primarily present in the membrane of glial cells, which are responsible for controlling metabolism in the brain and forming myelin. The neurologists will now be conducting follow-up studies into how KIR4.1 antibodies influence the development of MS. This autoantibody is extremely rare in people with other neurological diseases, making it an important potential diagnostic marker for MS in the future. “This autoantibody could improve diagnosis of MS and help us differentiate it more clearly from other neurological diseases,” continues Hemmer. This will also be the focus of further research.

Source: Science Daily

July 12, 2012

(HealthDay) — A supplement mixture (Souvenaid) containing dietary precursors and specific nutrients can improve memory in drug-naive patients with mild Alzheimer’s disease (AD), according to a study published in the July issue of the Journal of Alzheimer’s Disease.

Philip Scheltens, M.D., from the VU University Medical Center in Amsterdam, and colleagues conducted a 24-week, randomized, controlled trial in which drug-naive patients with mild AD were randomized in a 1:1 ratio to receive Souvenaid or an iso-caloric control product once daily. Memory function was assessed using the domain z-score of the Neuropsychological Test Battery (NTB).

The researchers found that, over the intervention period, the NTB memory domain z-score was significantly increased in patients taking Souvenaid versus the control group (P = 0.023), with a trend toward improvement in the NTB total composite z- score (P = 0.053). Functional connectivity in the delta band, as measured by an electroencephalography, was significantly different between the study groups in favor of the active group. There was very high adherence to the intervention (96.6 percent for the control and 97.1 percent for the active group). Both products were well tolerated and there was no between-group difference in the occurrence of serious adverse events.

"In conclusion, this study confirms that Souvenaid is well tolerated and improves memory performance,” the authors write. “Our results warrant further investigation of the clinical potential of Souvenaid in preclinical or clinical conditions characterized by synaptic loss, in particular AD.”

Several authors disclosed financial ties to Danone Research BV and Nutricia Advanced Medical Nutrition, which sponsored the study and manufacture Souvenaid.

Source: medicalxpress.com

ScienceDaily (July 12, 2012) — Obesity is not to blame for poor educational performance, according to early findings from research funded by the Economic and Social Research Council (ESRC). In a study that combines statistical methods with genetic information, researchers dispel the false idea that being overweight has damaging educational consequences.

Previous studies have shown that children who are heavier are less likely to do well at school. However, Dr Stephanie von Hinke Kessler Scholder from University of York argues it’s vital to understand what drives this association. “We sought to test whether obesity ‘directly’ hinders performance due to bullying or health problems, or whether kids who are obese do less well because of other factors that are associated with both obesity and lower exam results, such as coming from a disadvantaged family,” Dr Scholder explains.

Researchers examined data on almost 4,000 members of the Children of the 90s Birth Cohort Study. These data include the children’s DNA. It is well known that genes are randomly allocated within a population, irrespective of factors such as socio-economic position. The researchers combined the latest developments from genetic epidemiology with statistical methodologies in economic and econometric research. Using two carefully chosen ‘genetic markers’, the research team was able to identify children with a slightly higher genetic pre-disposition to obesity.

“Based on a simple correlation between children’s obesity as measured by their fat mass and their exam results, we found that heavier children did do slightly worse in school,” Dr Scholder points out. “But, when we used children’s genetic markers to account for potentially other factors, we found no evidence that obesity causally affects exam results. So, we conclude that obesity is not a major factor affecting children’s educational outcomes.”

These findings suggest that the previously found negative relationship between weight and educational performance is driven by factors that affect both weight and educational attainment. Future research should focus on other determinants of poor educational outcomes, such as social class or a family’s socio-economic circumstances, Dr Scholder points out.

The finding that obesity is not a cause of poorer educational performance is, the researchers suggest, a positive thing. “Clearly there are reasons why there are differences in educational outcomes, but our research shows that obesity is not one of them,” Dr Scholder argues.

Source: Science Daily

July 12, 2012

Biologists at UC San Diego have discovered a chemical that offers a completely new and promising direction for the development of drugs to treat metabolic disorders such as type 2 diabetes—a major public health concern in the United States due to the current obesity epidemic.

Their discovery, detailed in a paper published July 13 in an advance online issue of the journal Science, initially came as a surprise because the chemical they isolated does not directly control glucose production in the liver, but instead affects the activity of a key protein that regulates the internal mechanisms of our daily night and day activities, which scientists call our circadian rhythm or biological clock.

Scientists had long suspected that diabetes and obesity could be linked to problems in the biological clock. Laboratory mice with altered biological clocks, for example, often become obese and develop diabetes. Two years ago, a team headed by Steve Kay, dean of the Division of Biological Sciences at UC San Diego, discovered the first biochemical link between the biological clock and diabetes. It found that a key protein, cryptochrome, that regulates the biological clocks of plants, insects and mammals also regulates glucose production in the liver and that altering the levels of this protein could improve the health of diabetic mice.

Now Kay and his team have discovered a small molecule—one that can be easily developed into a drug—that controls the intricate molecular cogs or timekeeping mechanisms of cryptochrome in such a manner that it can repress the production of glucose by the liver. Like mice and other animals, humans have evolved biochemical mechanisms to keep a steady supply of glucose flowing to the brain at night, when we’re not eating or otherwise active.

"At the end of the night, our hormones signal that we’re in a fasting state," said Kay. "And during the day, when we’re active, our biological clock shuts down those fasting signals that tell our liver to make more glucose because that’s when we’re eating."

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ScienceDaily (July 11, 2012) — Widely held beliefs about Neuro-Linguistic Programming and lying are unfounded.

Twenty portrait of a woman with different expressions. (Credit: © gemenacom / Fotolia)

Proponents of Neuro-Linguistic Programming (NLP) have long claimed that it is possible to tell whether a person is lying from their eye movements.  Research published July 11 in the journal PLoS ONE reveals that this claim is unfounded, with the authors calling on the public and organisations to abandon this approach to lie detection.

For decades many NLP practitioners have claimed that when a person looks up to their right they are likely to be lying, whilst a glance up to their left is indicative of telling the truth.

Professor Richard Wiseman (University of Hertfordshire, UK) and Dr Caroline Watt (University of Edinburgh, UK) tested this idea by filming volunteers as they either lied or told the truth, and then carefully coded their eye movements.  In a second study another group of participants was asked to watch the films and attempt to detect the lies on the basis of the volunteers’ eye movements.

"The results of the first study revealed no relationship between lying and eye movements, and the second showed that telling people about the claims made by NLP practitioners did not improve their lie detection skills,” noted Wiseman. 

A final study involved moving out of the laboratory and was conducted in collaboration with Dr Leanne ten Brinke and Professor Stephen Porter from the University of British Columbia, Canada.  The team analysed films of liars and truth tellers from high profile press conferences in which people were appealing for missing relatives or claimed to have been the victim of a crime. 

"Our previous research with these films suggests that there are significant differences in the behaviour of liars and truth tellers," noted Dr Leanne ten Brinke. "However, the alleged tell-tale pattern of eye movements failed to emerge."

"A large percentage of the public believes that certain eye movements are a sign of lying, and this idea is even taught in organisational training courses.  Our research provides no support for the idea and so suggests that it is time to abandon this approach to detecting deceit" remarked Watt.

Source: Science Daily

ScienceDaily (July 11, 2012) — When humans learn, their brains relate new information with past experiences to derive new knowledge, according to psychology research from The University of Texas at Austin.

The study, led by Alison Preston, assistant professor of psychology and neurobiology, shows this memory-binding process allows people to better understand new concepts and make future decisions. The findings could lead to better teaching methods, as well as treatment of degenerative neurological disorders, such as dementia, Preston says.

"Memories are not just for reflecting on the past; they help us make the best decisions for the future," says Preston, a research affiliate in the Center for Learning and Memory, which is part of the university’s College of Natural Sciences. "Here, we provide a direct link between these derived memories and the ability to make novel inferences."

The paper was published online in July in the journal Neuron. The authors include University of Texas at Austin researchers Dagmar Zeithamova and April Dominick.

In the study, 34 subjects were shown a series of paired images composed of different elements (for example, an object and an outdoor scene). Each of the paired images would then reappear in more presentations. A backpack, paired with a horse in the first presentation, would appear alongside a field in a later presentation. The overlap between the backpack and outdoor scenery (horse and field) would cause the viewer to associate the backpack with the horse and field. The researchers used this strategy to see how respondents would delve back to a recent memory while processing new information.

Using functional Magnetic Resonance Imaging (fMRI) equipment, the researchers were able to look at the subjects’ brain activity as they looked at image presentations. Using this technique, Preston and her team were able to see how the respondents thought about past images while looking at overlapping images. For example, they studied how the respondents thought about a past image (a horse) when looking at the backpack and the field. The researchers found the subjects who reactivated related memories while looking at overlapping image pairs were able to make associations between individual items (i.e. the horse and the field) despite the fact that they had never studied those images together.

To illustrate the ways in which this cognitive process works, Preston describes an everyday scenario.

Imagine you see a new neighbor walking a Great Dane down the street. At a different time and place, you may see a woman walking the same dog in the park. When experiencing the woman walking her dog, the brain conjures images of the recent memory of the neighbor and his Great Dane, causing an association between the dog walkers to be formed in memory. The derived relationship between the dog walkers would then allow you to infer the woman is also a new neighbor even though you have never seen her in your neighborhood.

"This is just a simple example of how our brains store information that goes beyond the exact events we experience," Preston says. "By combining past events with new information, we’re able to derive new knowledge and better anticipate what to expect in the future."

During the learning tasks, the researchers were able to pinpoint the brain regions that work in concert during the memory-binding process. They found the hippocampal-ventromedial prefrontal cortex (VMPFC) circuit is essential for binding reactivated memories with current experience.

Source: Science Daily

July 11, 2012

Two powerful brain chemical systems work together to paralyze skeletal muscles during rapid eye movement (REM) sleep, according to new research in the July 11 issue of The Journal of Neuroscience. The finding may help scientists better understand and treat sleep disorders, including narcolepsy, tooth grinding, and REM sleep behavior disorder.

During REM sleep — the deep sleep where most recalled dreams occur — your eyes continue to move but the rest of the body’s muscles are stopped, potentially to prevent injury. In a series of experiments, University of Toronto neuroscientists Patricia L. Brooks and John H. Peever, PhD, found that the neurotransmitters gamma-aminobutyric acid (GABA) and glycine caused REM sleep paralysis in rats by “switching off” the specialized cells in the brain that allow muscles to be active. This finding reversed earlier beliefs that glycine was a lone inhibitor of these motor neurons.

"The study’s findings are relevant to anyone who has ever watched a sleeping pet twitch, gotten kicked by a bed partner, or has known someone with the sleep disorder narcolepsy," said Dennis J. McGinty, PhD, a behavioral neuroscientist and sleep researcher at the University of California, Los Angeles, who was not involved in the study. "By identifying the neurotransmitters and receptors involved in sleep-related paralysis, this study points us to possible molecular targets for developing treatments for sleep-related motor disorders, which can often be debilitating," he said

The researchers measured electrical activity in the facial muscles responsible for chewing of sleeping rats. Brain cells called trigeminal motor neurons communicate the brain’s message to move to these muscles. Previous research suggested neurotransmitter receptors called ionotropic GABAA/glycine receptors in the motor neurons caused REM sleep paralysis. However, when the researchers blocked these receptors, REM sleep paralysis still occurred.

The researchers found that to prevent REM sleep paralysis, they had to block both the ionotropic receptors and metabotropic GABAB receptors, a different receptor system. In other words, when the motor cells were cut off from all sources of GABA and glycine, the paralysis did not occur, allowing the rats to exhibit high levels of muscle activity when their muscles should have been inactive. The data suggest the two neurotransmitters must both be present together to maintain motor control during sleep, rather than working separately.

The finding could be especially helpful for those with REM sleep disorder, a disease that causes people to act out their dreams. This can cause serious injuries to patients and others around them. It is also often an early indicator of neurodegenerative diseases, such as Parkinson’s.

"Understanding the precise mechanism behind these chemicals’ role in REM sleep disorder is particularly important because about 80 percent of people who have it eventually develop a neurodegenerative disease, such as Parkinson’s disease," study author Peever added. "REM sleep behavior disorder could be an early marker of these diseases, and curing it may help prevent or even stop their development,” he said.

Provided by University of Toronto

Source: medicalxpress.com

July 11, 2012

A new study shows that taking part in a stress management program may help people with multiple sclerosis (MS) prevent new disease activity. The study is published in the July 11, 2012, online issue of Neurology, the medical journal of the American Academy of Neurology.

A weekly stress management program for patients with multiple sclerosis (M.S.) prevented the development of new brain lesions, a marker of the disease’s activity in the brain, according to new Northwestern Medicine research. Brain lesions in M.S. often precede flare-ups of symptoms such as loss of vision or use of limbs or pain.

"This is the first time counseling or psychotherapy has been shown to affect the development of new brain lesions," said David Mohr, principal investigator of the study and professor of preventive medicine at Northwestern University Feinberg School of Medicine. "In M.S., the prevention of new brain lesions is an important marker used to judge how effective medications are."

"The new finding is an important step and the strongest evidence we have to date that stress is involved in M.S.," Mohr added.

The results indicate that stress management therapy may be a useful adjunct treatment with drug therapy for M.S., but a larger clinical trial is needed to confirm this, Mohr said.

The study is published in the July 11, 2012 issue of Neurology, the medical journal of the American Academy of Neurology.

Mohr’s previous research showed a connection between psychological distress and the development of new brain lesions. Stress is one of many factors, he said, that influence whether the underlying M.S. disease processes escalate to the point of a new lesion or a relapse. Mohr has spent more than a decade studying the link between emotional distress, including a study on depression, and M.S.

For an event to be stressful, a person has to feel it is a threat to something important, and that he or she doesn’t have any control over it.

"We taught patients strategies to evaluate how much of a threat something truly is," Mohr said. "When people overestimate the threat of an event or underestimate their ability to manage it, we teach them how to evaluate their own thinking about the stress and how to challenge and change that thinking to a more realistic and helpful appraisal of the actual threat. That often leads to improved ability to manage stressful events."

Patients also were taught how to calm their physical reactions to stress through relaxation and meditation to cope with stressful events that couldn’t be avoided.

In the national clinical trial, 121 patients were randomized to receive stress management therapy for M.S. or be in a control group. Those in the therapy group received 16 sessions over a 24-week period during which they were taught coping skills to enhance their ability to prevent stressful events from occurring and to improve their capacity to manage their responses to stressful events that did arise. They also received a 24-week post-treatment follow-up. Two-thirds of the patients were women, who have a higher incidence of M.S.

MRI neuroimaging showed the stress management therapy reduced two types of new brain lesions common in multiple sclerosis.

The first type, gadolinium-enhancing brain lesions, indicates a breakdown of the blood-brain barrier, allowing the immune system access to attack and damage brain cells. Gadolinium is injected into an M.S. patient during the MRI and can be observed passing through the blood-brain barrier, if these types of lesions are present. These lesions may disappear over time or may leave more permanent damage in the brain.

The second type, a T2 brain lesion, is a more global marker of the effect of M.S. on the brain and is a more permanent lesion. These markers are commonly used in evaluating M.S. medications in Phase II trials. If the lesions are decreased, the implication is the drug is working.

Among patients who received stress management therapy, 55 percent had a new gadolinium-enhancing brain lesion during the treatment period, compared to 77 percent of those in the control group. Similarly, 43 percent receiving stress management therapy had a new T2 brain lesion during the treatment period, compared to 70 percent in the control group. The stress reduction prevented new lesions whether or not the patients were taking M.S. disease-modifying medications (e.g., beta-interferons or glatiramer acetate).

But the improvement in brain lesions didn’t last after the stress management program ended.

"This suggests that we will need to develop treatments that are more sustainable over longer periods of time," Mohr said. "It’s difficult for people to come in for treatment once a week over long periods of time, due both to cost and time constraints. We are looking at telemedicine programs that can be delivered via a computer or a smartphone to people in their environment at much lower costs than traditional therapy."

The study did not show a statistical difference in the rate of clinical M.S. symptoms, but Mohr said he didn’t expect one in such a small number of participants. The outcome goal of this trial was only to see if the stress reduction affected the brain lesions.

While the results are positive, Mohr said, it’s premature to make recommendations for patients regarding use of stress management therapy. “I don’t want to see patients decide not to take their medication and use this instead,” he emphasized.

Provided by American Academy of Neurology

Source: medicalxpress.com

July 11, 2012

Communication between the brain and muscle must be strong for us to eat, breathe or walk. Now scientists have found that a protein known to be on the surface of muscle cells must be present in both tissues to ensure the conversation is robust.

Communication between the brain and muscle must be strong for us to eat, breathe or walk. Now scientists have found that a protein known to be on the surface of muscle cells must be present in both tissues to ensure the conversation is robust. Credit: Phil Jones

Scientists at the Medical College of Georgia at Georgia Health Sciences University have shown that without LRP4 in muscle cells and neurons, communication between the two cells types is inefficient and short-lived.

Problems with the protein appear to contribute to disabling disorders such as myasthenia gravis and other forms of muscular dystrophy. The MCG scientists reported finding antibodies to LRP4 in the blood of about 2 percent of patients with muscle-degenerating myasthenia gravis in Archives of Neurology earlier this year.

Scientists know that LRP4 plays an important role in the muscle cell, where it receives cues from the brain cell that it’s time to form the receptors that will be enable ongoing communication between the two, said Dr. Lin Mei, Director of the GHSU Institute of Molecular Medicine and Genetics and corresponding author of the study in the journal Neuron.

However when Dr. Haitao Wu deleted LRP4 just from muscle cells, a connection – albeit a weak one – still formed between muscle and brain cells. The mice survived several days during which they experienced some of the same muscle weakness as patients with myasthenia gravis. “That’s against the dogma,” Mei said. “If LRP4 is essential only in the muscle cells, how could the mice survive?” When they totally eliminated LRP4, neuromuscular junctions never formed and the mice didn’t survive.

Additional evidence suggests that LRP4 in the neurons is vital, said Wu, postdoctoral fellow and the study’s first author. “When we knocked out the LRP4 gene in the muscles, there was some redundant function coming from the motor neuron, like a rescue attempt,” he said. They documented the neuron reaching out to share LRP4 with the muscle cell. Unfortunately, the gesture was not sufficient.

"The nerve does not get the stop signal," Mei said, referencing images of too-long neurons that never got the message from the muscle that they have gone far enough. When they cut the elongated nerves, they found they didn’t contain enough vesicles, little packages of chemical messengers that are the hallmark of brain cell communication. On the receiving end, muscle cells developed receptors that were too small and too few – hence, the tenuous communication network. "When LRP4 in the muscle is taken out, not surprisingly, the muscle has some kind of a problem," Mei said. "What was very surprising was that the motor neurons also have problems.”

"The talk between motor neurons and muscle cells is very critical to the synapse formation and the very precise action between the two," Wu said. Mei’s lab earlier established that the conversation goes both ways.

The scientists believe about 60 percent of the LRP4 comes from muscle cells, about 20 percent from brain cells – which helps explain why the brain’s effort to share is insufficient – and the remainder from cells in spaces between the two. In addition to better explaining nerve-muscle communication, the scientists hope their findings will eventually enable gene therapy that delivers LRP4 to bolster insufficient levels in patients.

Other early and key players in establishing nerve-muscle conversation include agrin, a protein that motor neurons release to direct construction of the synapse, a sort of telephone line between the nerve and muscle. MuSK on the muscle cell surface initiates critical internal cell talk so synapses can form and receptors that enable specific commands will cluster at just the right spot.

Mei’s lab reported in Neuron in 2008 that agrin starts talking with LRP4 on the muscle cell surface, then recruits the enzyme MuSK to join the conversation. LRP4 and MuSK become major components of the receptor needed for the muscle cell to receive the message agrin is sending.

The agrin-MuSK signaling pathway has been implicated in muscular dystrophy, a group of genetic diseases that lead to loss of muscle control because of problems with neurons, muscle cells and/or their communication. Some reports have implicated a mutant MuSK as a cause of muscular dystrophy and autoantibodies (antibodies the body makes against itself) to MuSK have been found in the blood of some patients.

Provided by Georgia Health Sciences University

Source: medicalxpress.com

July 11, 2012

An inflated sense of memory function in people with dementia may influence their likelihood of seeking help, new Flinders University research shows.

As part of her PhD, Flinders research associate Dr. Chris Materne studied the disparity between memory perception and performance in people with dementia.

In the first stage of the project, Dr. Materne analysed data from the Australian Longitudinal Study of Aging which showed that most survey participants believed their memory had remained stable over the 11-year assessment, despite tests showing a decline in memory performance.

She then conducted an intervention with 13 individuals, from a larger group of 23 people with dementia, using spaced retrieval memory training to help them achieve a specific task or activity, such as remembering to lock the front door or keep their glasses in the same spot.

“Spaced retrieval works by helping people remember specific information or tasks by getting them to respond to a prompt question over progressively increasing intervals of time,” Dr. Materne said.

“In one case we helped a man remember to put his glasses in the same place because he was always losing them which made both him and his wife quite distressed,” she said.

“We think the training taps into procedural memory so it becomes habitual rather than explicit memory, such as memory for facts, which tends to decline before procedural memory when you have dementia.”

The technique was conducted once a week for six weeks, with seven out of the 13 participants still able to perform their nominated activity or task after six months.

The 23 participants were also asked to rate their performance based on a specific question, such as how many people they could name in a photo with 10 faces.

While most respondents were initially over-confident in their abilities, with some claiming to be able to name all 10 faces, their perceptions did change over time to more accurately reflect their cognitive function.

About one third of family carers, however, initially considered their loved ones memory to be better than what the person with dementia actually reported.

“In the longitudinal sample people didn’t feel their memory had changed over time because the questions were more general but when we asked specific, detailed questions about memory in the smaller study, the respondents came to recognise their declining performance.”

Dr. Materne said the research highlighted the need for more comprehensive assessments when diagnosing dementia to increase the accuracy of peoples’ perceptions, and therefore their likelihood of seeking help.

Provided by Flinders University

Source: medicalxpress.com

ScienceDaily (July 11, 2012) — Stanford University School of Medicine scientists have laid bare a novel molecular mechanism responsible for the most important symptom of major depression: anhedonia, the loss of the ability to experience pleasure. While their study was conducted in mice, the brain circuit involved in this newly elucidated pathway is largely identical between rodents and humans, upping the odds that the findings point toward new therapies for depression and other disorders.

Additionally, opinion leaders hailed the study’s inventive methodology, saying it may offer a much sounder approach to testing new antidepressants than the methods now routinely used by drug developers.

While as many as one in six Americans is likely to suffer a major depression in their lifetimes, current medications either are inadequate or eventually stop working in as many as 50 percent of those for whom they’re prescribed.

"This may be because all current medications for depression work via the same mechanisms," said Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences. "They increase levels of one or another of two small molecules that some nerve cells in the brain use to signal one another. To get better treatments, there’s a great need to understand in greater detail the brain biology that underlies depression’s symptoms." The study’s first author is Byung Kook Lim, PhD, a postdoctoral scholar in Malenka’s laboratory.

Malenka is senior author of the new study, published July 12 in Nature, which reveals a novel drug target by showing how a hormone known to affect appetite turns off the brain’s ability to experience pleasure when an animal is stressed. This hormone, melanocortin, signals to an ancient and almost universal apparatus deep in the brain called the reward circuit, which has evolved to guide animals toward resources, behaviors and environments — such as food, sex and warmth — that enhance their prospects for survival.

"This is the first study to suggest that we should look at the role of melanocortin in depression-related syndromes," said Eric Nestler, MD, PhD, professor and chair of neuroscience and director of the Friedman Brain Institute at Mount Sinai School of Medicine in New York. Nestler was not involved in the study but is familiar with its contents.

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ScienceDaily (July 11, 2012) — In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder.

"A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes," said Gregory A. Light, PhD, associate professor of psychiatry and the study’s first author. "Diagnoses are currently based on a clinician’s ability to make inferences about patients’ inner experiences."

Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors.

"Schizophrenia is among the most severe and disabling conditions across all categories of medicine," said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System.

The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families.

Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient’s inner experiences. That is, their ability to describe what’s happening inside their minds.

"But even the best clinicians struggle with diagnostic complexities based on sometimes fuzzy clinical phenomenology," said Light. The clinical challenge is compounded by the fact that "many schizophrenia patients have cognitive and functional impairments," said Light. They may not be able to reasonably explain how or what they think.

Light and colleagues investigated whether a select battery of neurophysiological and neurocognitive biomarkers could provide clinicians with reliable, accurate, long-term indicators of brain dysfunction, even when overt symptoms of the disorder were not apparent. These markers ranged from tests of attention and memory to physiological assessments of basic perceptual processes using scalp sensors to measure brain responses to simple sounds.

The researchers measured the biomarkers in 550 schizophrenia patients, and then re-tested 200 of the patients one year later. They found that most of the markers were significantly abnormal in schizophrenia patients, were relatively stable between the assessments and were not affected by modest fluctuations in clinical status of the patient.

Light said further research is required, including whether the endophenotypes can differentiate other psychiatric disorders, be used to anticipate patient response to different kinds of drugs or non-pharmacological interventions or even be used to predict which subjects are at high risk of developing a psychotic illness.

"We believe this paper is an important step towards validating laboratory-based biomarkers for use in future genomic and clinical treatment studies of schizophrenia," Light said.

Source: Science Daily

July 11, 2012

(Medical Xpress) — Johns Hopkins researchers say they have discovered that the central nervous system’s oligodendroglia cells, long believed to simply insulate nerves as they “fire” signals, are unexpectedly also vital to the survival of neurons. Damage to these insulators appears to contribute to brain injury in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease for the Yankee baseball great who died from the disease.

The discovery, described online in the journal Nature, suggests that a previously unknown — and unexpected — function of these cells is to supply nutrition to the principal brain cells, neurons. This new pathway may prove to be an important and novel therapeutic target for ALS, the researchers say, and potentially other diseases that attack the body’s nerve fibers, such as multiple sclerosis.

"More than 100 years after their discovery, we have now found a fundamentally new property in the way oligodendroglia work in the brain, laying the foundation for a new approach to try to treat debilitating neurodegenerative diseases,” says Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine, and the study’s leader. “We’ve added a whole new category to what they do in the brain.”

The cells responsible for the transfer of information and electrical impulses around the body, neurons work by transferring electrical charges from neuron to neuron. Axons, the wire-like extensions of the neurons, help move the messages, in some cases over many feet, from cell to cell. Oligodendroglia insulate axons, like rubber coating around an electrical wire, to speed up the conduction of information. Axonal death is a hallmark of ALS and most other neurodegenerative disorders, Rothstein says.

Rothstein and his colleagues say the other principal brain cells, the astroglia, were believed to be primarily responsible for providing energy to neurons in the form of glucose, but their experiments show that oligodendroglia are surprisingly crucial in feeding neurons — in the form of less energy-rich lactate, without which neurons and their axons die. Lactate has long been seen as a minor player in this process, but the Johns Hopkins team says it appears to be far more important to nerve cell survival. Moreover, they found that the protein MCT1, the dominant transporter of lactate in the brain, is only found in oligodendroglia.

Rothstein says their discovery was rooted in experiments during which scientists, using mice, knocked out the gene that makes the MCT1 protein and saw axons begin to die, even though they were still getting plenty of glucose.

As part of these experiments, the researchers engineered mice whose cells would light up if they were expressing MCT1. The scientists then determined that only oligodendroglia cells lit up, showing that MCTI is located on this type of cell alone. They also knocked out the MCT1 in cell cultures and found that neurons would begin to die, but would recover when fed lactate, proving the importance of MCT1 in providing this nutritional compound. They conducted the same experiments in mice and got similar results.

Finally, the researchers turned their attention to ALS, a disease where they had recently uncovered abnormalities related to oligodendroglia. In ALS mice, they found that MCT1 was missing in brain cells well before the disease developed, and they found similar results in ALS patients. Rothstein says the findings suggest that oligodendroglia injury — specifically injury to the mechanism that produces MCT1 — may be an important event in the onset and progression of ALS.

Rothstein, who is director of the Johns Hopkins University School of Medicine’s Brain Science Institute, says he hopes further research can establish that the activation of MCT1 in people will protect axons in those with ALS and other degenerative diseases.

Provided by Johns Hopkins University School of Medicine

Source: medicalxpress.com

July 11, 2012

In a paper published in the July 11 online issue of Science Translational Medicine, researchers at the University of California, San Diego School of Medicine have identified two key regulatory proteins critical to clearing away misfolded proteins that accumulate and cause the progressive, deadly neurodegeneration of Huntington’s disease (HD).

This is a human neuron. UC San Diego scientists have identified a pair of proteins that help clear away other misfolded proteins responsible for the progressive degeneration of brain cells in Huntington’s disease. Credit: UC San Diego School of Medicine

The findings explain a fundamental aspect of how HD wreaks havoc within cells and provides “clear, therapeutic opportunities,” said principal investigator Albert R. La Spada, MD, PhD, professor of cellular and molecular medicine, chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic Medicine at UC San Diego.

"We think the implications are significant," said La Spada. "It’s a lead we can vigorously pursue, not just for Huntington’s disease, but also for similar neurodegenerative conditions like Parkinson’s disease and maybe even Alzheimer’s disease.”

In HD, an inherited mutation in the huntingtin (htt) gene results in misfolded htt proteins accumulating in certain central nervous system cells, leading to progressive deterioration of involuntary movement control, cognitive decline and psychological problems. More than 30,000 Americans have HD. There are no effective treatments currently to either cure the disease or slow its progression.

La Spada and colleagues focused on a protein called PGC-1alpha, which helps regulate the creation and operation of mitochondria, the tiny organelles that generate the fuel required for every cell to function.

"It’s all about energy," La Spada said. "Neurons have a constant, high demand for it. They’re always on the edge for maintaining adequate levels of energy production. PGC-1alpha regulates the function of transcription factors that promote the creation of mitochondria and allow them to run at full capacity.”

Previous studies by La Spada and others discovered that the mutant form of the htt gene interfered with normal levels and functioning of PGC-1alpha. “This study confirms that,” La Spada said. More surprising was the discovery that elevated levels of PGC-1alpha in a mouse model of HD virtually eliminated the problematic misfolded proteins.

Specifically, PGC-1alpha influenced expression of another protein vital to autophagy – the process in which healthy cells degrade and recycle old, unneeded or dangerous parts and products, including oxidative, damaging molecules generated by metabolism. For neurons, which must last a lifetime, the self-renewal is essential to survival.

"Mitochondria get beat up and need to be recycled," La Spada said. "PGC-1alpha drives this pathway through another protein called transcription factor EB or TFEB. We were unaware of this connection before, because TFEB is a relatively new player, though clearly emerging as a leading actor. We discovered that even without PGC-1alpha induction, TFEB can prevent htt aggregation and neurotoxicity."

In their experiments, HD mice crossbred with mice that produced greater levels of PGC-1alpha showed dramatic improvement. Production of misfolded proteins was essentially eliminated and the mice behaved normally. “Degeneration of brain cells is prevented. Neurons don’t die,” said La Spada.

PGC-1alpha and TFEB provide two new therapeutic targets for Huntington’s disease, according to La Spada. “If you can induce the bioenergetics and protein quality control pathways of nervous system cells to function properly, by activating the PGC-1alpha pathway and promoting greater TFEB function, you stand a good chance of maintaining neural function for an extended period of time. If we could achieve the level of increased function necessary to eliminate misfolded proteins, we might nip the disease process in the bud. That would go a long way toward treating this devastating condition.”

Provided by University of California - San Diego

Source: medicalxpress.com

July 11, 2012

Among patients with mild or no cognitive impairment, brain scans using a new radioactive dye can detect early evidence of Alzheimer’s disease that may predict future decline, according to a multi-center study led by researchers at Duke University Medical Center.

PET images using florbetapir dye to highlight beta-amyloid plaques show (A), a cognitively normal subject; (B) an amyloid-positive patient with Alzheimer’s disease; (C) a patient with mild cognitive impairment; and (D) a patient with mild cognitive impairment who progressed to dementia during the study. Credit: Slide courtesy of the journal Neurology.

The finding is published online July 11, 2012, in the journal Neurology, the medical journal of the American Academy of Neurology. It expands on smaller studies demonstrating that early detection of tell-tale plaques could be a predictive tool to help guide care and treatment decisions for patients with Alzheimer’s disease.

"Even at a short follow-up of 18 months we can see how the presence of amyloid plaques affects cognitive function," said P. Murali Doraiswamy, M.D., professor of psychiatry at Duke who co-led the study with R. Edward Coleman, M.D., professor of radiology at Duke . "Most people who come to the doctor with mild impairment really want to know the short-term prognosis and potential long-term effect."

Doraiswamy said such knowledge also has some pitfalls. There is no cure for Alzheimer’s disease, which afflicts 5.4 million people in the United States and is the sixth-leading cause of death among U.S. adults. But he said numerous drugs are being investigated, and identifying earlier disease would improve research into their potential benefits and speed new discoveries, while also enhancing care and treatment of current patients.

In the Neurology study, 151 people who had enrolled in a multi-center test of a new radioactive dye called florbetapir (Amyvid) were recruited to participate in a 36-month analysis. Of those participants, 69 had normal cognitive function at the start of the study, 51 had been diagnosed with mild impairment, and 31 had Alzheimer’s dementia.

All completed cognitive tests and underwent a brain scan using Positron Emission Tomography, or PET imaging. The technology uses radioactive tracers designed to highlight specific tissue to create a three-dimensional picture of an organ or a biological function.

The dye used in the study, florbetapir, was recently approved by the U.S. Food and Drug Administration for PET imaging of the brain to estimate beta-amyloid plaque density in patients who are being evaluated for cognitive impairment. It binds to the amyloid plaques that characterize Alzheimer’s disease, providing a window into the brain to see if the plaques have formed, and how extensively.

Patients in the study were reassessed with additional cognitive exams at 18 months and 36 months. At the 18-month point, patients with mild cognitive impairment who had PET evidence of plaque at the trial’s start worsened to a great degree on cognitive tests than patients who had no evidence of plaque at the trial’s start. Twenty-nine percent of the plaque-positive patients in this group developed Alzheimer’s dementia, compared to 10 percent who started with no plaque.

Cognitively normal patients with a plaque-positive PET scan at the start of the study also showed more mental decline at 18 months compared to those who were negative for plaque.

The study additionally found that people with negative scans reversed from minimally impaired to normal more often than people with positive PET scan, suggesting test anxiety or concentration problems could have affected their initial performance.

"For the most part we have been blind about who would progress and who wouldn’t, so this approach is a step toward having a biomarker that predicts risk of decline in people who are experiencing cognitive impairment," Doraiswamy said.

He said the study’s results provide initial data that needs to be verified by additional research. Final, 36-month data from the study has been completed and will be presented at the Alzheimer’s Association International Conference this week in Vancouver, Canada. Doraiswamy also cautioned that florbetapir is currently not approved to predict the development of dementia or other neurologic conditions and stressed that it should not be used as a screening tool in otherwise normal or minimally impaired people. Likewise, a positive scan is not necessarily diagnostic for Alzheimer’s by itself.

Provided by Duke University Medical Center

Source: medicalxpress.com

July 11, 2012

What can explain extreme differences in altruism among individuals, from Ebenezer Scrooge to Mother Teresa? It may all come down to variation in the size and activity of a brain region involved in appreciating others’ perspectives, according to a study published in the July 12th issue of the journal Neuron. The findings also provide a neural explanation for why altruistic tendencies remain stable over time.

The junction (yellow) between the parietal and the temporal lobes, in which the relative proportion of gray matter is significantly positively correlated with the propensity for altruistic behavior. Credit: University of Zurich

"This is the first study to link both brain anatomy and brain activation to human altruism,” says senior study author Ernst Fehr of the University of Zurich. “The findings suggest that the development of altruism through appropriate training or social practices might occur through changes in the brain structure and the neural activations that we identified in our study.”

Individuals who excel at understanding others’ intents and beliefs are more altruistic than those who struggle at this task. The ability to understand others’ perspectives has previously been associated with activity in a brain region known as the temporoparietal junction (TPJ). Based on these past findings, Fehr and his team reasoned that the size and activation of the TPJ would relate to individual differences in altruism.

In the new study, subjects underwent a brain imaging scan and played a game in which they had to decide how to split money between themselves and anonymous partners. Subjects who made more generous decisions had a larger TPJ in the right hemisphere of the brain compared with subjects who made stingy decisions.

Moreover, activity in the TPJ reflected each subject’s specific cutoff value for the maximal cost the subject was willing to endure to increase the partner’s payoff. Activity in the TPJ was higher during hard decisions—when the personal cost of an altruistic act was just below the cutoff value—than during easy decisions associated with a very low or very high cost.

"The structure of the TPJ strongly predicts an individual’s setpoint for altruistic behavior, while activity in this brain region predicts an individual’s acceptable cost for altruistic actions," says study author Yosuke Morishima of the University of Zurich. "We have elucidated the relationship between the hardware and software of human altruistic behavior."

Provided by Cell Press

Source: medicalxpress.com

July 10th, 2012

Guillain-Barre syndrome (GBS) is usually characterized by rapidly developing motor weakness and areflexia (the absence of reflexes). “The disease is thought to be autoimmune and triggered by a stimulus of external origin.

In 1976-1977, an unusually high rate of GBS was identified in the United States following the administration of inactivated ‘swine’ influenza A(H1N1) vaccines. In 2003, the Institute of Medicine (IOM) concluded that the evidence favored acceptance of a causal relationship between the 1976 swine influenza vaccines and GBS in adults.

Studies of seasonal influenza vaccines administered in subsequent years have found small or no increased risk,” according to background information in the article. “In a more recent assessment of epidemiologic studies on seasonal influenza vaccines, experimental studies in animals, and case reports in humans, the IOM Committee to Review Adverse Effects of Vaccines concluded that the evidence was inadequate to accept or reject a causal relationship.”

Analysis of recent H1N1 vaccination data indicated a small but significant risk of GBS following influenza A(H1N1) vaccinations.

Philippe De Wals, M.D., Ph.D., of Laval University, Quebec City, Canada and colleagues conducted a study to assess the risk of GBS following pandemic influenza vaccine administration. In fall 2009 in Quebec an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain. By the end of the year, 4.4 million residents had been vaccinated. The study included follow-up over the 6-month period of October 2009 through March 2010 for suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Immunization status was verified.

Over the 6-month period, 83 confirmed GBS cases were identified. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. Analysis of data indicated a small but significant risk of GBS following influenza A(H1N1) vaccination. The number of cases attributable to vaccination was approximately 2 per 1 million doses. The excess risk was observed only in persons 50 years of age or older.

“In Quebec, the individual risk of hospitalization following a documented influenza A(H1N1) infection was 1 per 2,500 and the risk of death was 1/73,000. The H1N1 vaccine was very effective in preventing infections and complications. It is likely that the benefits of immunization outweigh the risks,” the authors write.

Source: Neuroscience News

ScienceDaily (July 10, 2012) — Researchers at Georgetown University Medical Center appear to have solved the mystery of why some patients infected with HIV, who are using antiretroviral therapy and show no signs of AIDS, develop serious depression as well as profound problems with memory, learning, and motor function. The finding might also provide a way to test people with HIV to determine their risk for developing dementia.

They say the answer, published in the July 11 issue of the Journal of Neuroscience, may ultimately lead to a therapeutic solution that helps these patients as well as others suffering from brain ailments that appear to develop through the same pathway, including those that occur in the aged.

"We believe we have discovered a general mechanism of neuronal decline that even explains what happens in some elderly folks," says the study’s lead investigator, Italo Mocchetti, Ph.D., professor and vice chair of the department of neuroscience at Georgetown University Medical Center. "The HIV-infected patients who develop this syndrome are usually quite young, but their brains act old."

The research team found that even though HIV does not infect neurons, it tries to stop the brain from producing a protein growth factor — mature brain derived neurotrophic factor (mature BDNF) — that Mocchetti says acts like “food” for brain neurons. Reduced mature BDNF results in the shortening of the axons and their branches that neurons use to connect to each other, and when they lose this communication, the neurons die.

"The loss of neurons and their connections is profound in these patients," Mocchetti says. HIV-associated dementia occurs in two to three percent of HIV-infected patients using retroviral therapies, all of who appear to be otherwise healthy, and in 30 percent of HIV-positive patients who are not on medication.

Mocchetti believes that HIV stops production of mature BDNF because that protein interferes with the ability of the virus to attack other brain cells. It does this through the potent gp120 envelope protein that sticks out from the viral shell — the same protein that hooks on to brain macrophages and microglial cells to infect them. “In earlier experiments, when we dumped gp120 into neuronal tissue culture, there was a 30-40 percent loss of neurons overnight. That makes gp120 a remarkable neurotoxin.”

This study is the product of years of work that has resulted in a string of publications. It began when Mocchetti and his colleagues were given a grant from the National Institutes on Drug Abuse to determine whether there was a connection between the use of cocaine and morphine, and dementia. (A substantial number of HIV-positive patients have been or currently are intravenous drugs users.)

They found that it was the virus that was responsible for the dementia, not the drugs, and so they set out to discover how the virus was altering neuronal function.

Their scientific break came when the researchers were able to study the blood of 130 women who were enrolled in the 17 year-old, nationwide WIHS (Women’s Interagency HIV Study, directed at Georgetown by Mary Young, M.D.), which has focused on the effects of HIV in infected females. In one seminal discovery, Mocchetti and colleagues found that when there was less BDNF in the blood, patients were at risk of developing brain abnormalities. He published this finding in 2011 in the May 15 issue of AIDS.

In this study, Mocchetti, Alessia Bachis, Ph.D., and their colleagues studied the brains of HIV-positive patients who had died, and who had developed HIV-associated dementia. They also found that neurons had shrunk, and that mature BDNF had substantially decreased.

He and his colleagues then worked out the mechanism responsible for this destruction of neurons.

Normally, neurons release a long form of BDNF known as proBDNF, and then certain enzymes, including one called furin, cleave proBDNF to produce mature BDNF, which then nurtures brain neurons. When uncut, proBDNF is toxic, leading to “synaptic simplification,” or the shortening of axons. It does this by binding to a receptor, p75NTR, that contains a death domain.

"HIV interferes with that normal process of cleaving proBDNF, resulting in neurons primarily secreting a toxic form of BDNF," Mocchetti says. The same imbalance between mature BDNF and proBDNF occurs as we age, he says, although no one knows how that happens. "The link between depression and lack of mature BDNF is also known, as is the link to issues of learning and memory. That’s why I say HIV-associated dementia resembles the aging brain."

Loss of mature BDNF has also been suggested to be a risk factor in chronic diseases such as Parkinson’s and Huntington’s diseases, Mocchetti says.

The findings suggest a possible therapeutic intervention, he adds. “One way would be to use a small molecule to block the p75NTR receptor that proBDNF uses to kill neurons. A small molecule like that could get through the blood-brain barrier.

"If this works in HIV-dementia, it may also work in other brain issues caused by proBDNF, such as aging," Mocchetti adds.

The finding also suggests that measuring proBDNF in HIV-positive patients may provide a biomarker of risk for development of dementia, he adds.

"This finding is extremely important for both basic scientists and physicians, because it suggests a new avenue to understand, and treat, a fairly widespread cause of dementia," Mocchetti says.

Source: Science Daily

July 10, 2012

The ability for substances to pass through the blood-brain barrier is increased after adult stroke, but not after neonatal stroke, according to a new study the UCSF that will be published July 11 in the Journal of Neuroscience.

The blood-brain barrier is selectively permeable and blocks unwanted molecules from entering into the brain. The selectivity is achieved through fine coordination in function of many transporting systems in endothelial cells, which line the interior of blood vessels, and communication between endothelial cells and several types of cells in the brain. When blood flow in an artery to the brain is blocked by a blood clot, as occurs in arterial stroke, brain energy metabolism is compromised, and ion and other transporting systems malfunction, leading to blood-brain disruption.

The new finding suggests, the researchers said, that drugs used to treat stroke need to be tailored to the specific makeup of the neonate blood-brain barrier.

"How the blood-brain barrier responds to stroke in adults and neonates currently is poorly understood,” said senior author Zinaida Vexler, PhD, director of research at the Neonatal Brain Disorders Center at the Department of Neurology at UCSF.

"The assumption has been that at birth the blood-brain barrier is immature and thus permeable and that a neonatal brain responds in the same way to injury as an adult brain. This would mean that, after a stroke, the blood-brain barrier is an open gate and different molecules could go in and out, like a floodgate,” she said. “But in neonatal stroke the situation is very different, and this study shows that the neonatal brain has the ability to protect itself by limiting blood-brain barrier permeability.”

In the study, the scientists examined the structural and functional aspects of the blood-brain barrier in live rats that had acute stroke, and found that the blood-brain barrier was markedly more intact in neonatal rats than in adult rats.

The study compared vascular responses to injury in an adult arterial stroke model and an age-appropriate model of neonatal arterial stroke using several blood-brain barrier permeability procedures. Injected molecules that remained in blood vessels under normal conditions leaked into the injured tissue of the adult rats, but the same molecules remained in vessels of neonatal injured rats within 24 hours after injury.

Importantly, the vessels remained intact for molecules of various sizes. The study also showed a different composition of several barrier structural proteins in neonates versus adults, as well as a differential response to stroke at both ages, findings that likely are to contribute to the higher resistance of the neonatal blood-brain barrier after stroke. The study also showed age-related differences in communication between circulating white blood cells and the blood-brain barrier. Neutrophils — a subtype of leukocytes — stuck to injured vasculature and entered the adult brain shortly after stroke, releasing toxic molecules and reactive oxidants and producing damage. In contrast, only a few neutrophils were able to enter the injured neonatal brain. However, pharmacological change – in communication of neutrophils with injured vessels in the neonate made injury worse.

"This study is a very critical step towards developing therapeutics, but these findings are a tip of the iceberg and a lot is still to be learned," said Vexler. "We’re moving to characterize the potential for neonatal repair. Some brain damage can’t be diagnosed early, but might show up later. Now we are experimenting with postponing certain treatments or tweaking some signaling mechanisms to see if we can enhance the capacity of the immature brain to repair itself."

Provided by University of California, San Francisco

Source: medicalxpress.com

ScienceDaily (July 10, 2012) — People who are born deaf process the sense of touch differently than people who are born with normal hearing, according to research funded by the National Institutes of Health. The finding reveals how the early loss of a sense — in this case hearing — affects brain development. It adds to a growing list of discoveries that confirm the impact of experiences and outside influences in molding the developing brain.

People who are born deaf process the sense of touch differently than people who are born with normal hearing, according to research funded by the National Institutes of Health. The finding reveals how the early loss of a sense — in this case hearing — affects brain development. (Credit: © James Steidl / Fotolia)

The study is published in the July 11 online issue of The Journal of Neuroscience.

The researchers, Christina M. Karns, Ph.D., a postdoctoral research associate in the Brain Development Lab at the University of Oregon, Eugene, and her colleagues, show that deaf people use the auditory cortex to process touch stimuli and visual stimuli to a much greater degree than occurs in hearing people. The finding suggests that since the developing auditory cortex of profoundly deaf people is not exposed to sound stimuli, it adapts and takes on additional sensory processing tasks.

"This research shows how the brain is capable of rewiring in dramatic ways," said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. "This will be of great interest to other researchers who are studying multisensory processing in the brain."

Previous research, including studies performed by the lab director, Helen Neville Ph.D., has shown that people who are born deaf are better at processing peripheral vision and motion. Deaf people may process vision using many different brain regions, especially auditory areas, including the primary auditory cortex. However, no one has tackled whether vision and touch together are processed differently in deaf people, primarily because in experimental settings, it is more difficult to produce the kind of precise tactile stimuli needed to answer this question.

Dr. Karns and her colleagues developed a unique apparatus that could be worn like headphones while subjects were in a magnetic resonance imaging (MRI) scanner. Flexible tubing, connected to a compressor in another room, delivered soundless puffs of air above the right eyebrow and to the cheek below the right eye. Visual stimuli — brief pulses of light — were delivered through fiber optic cables mounted directly below the air-puff nozzle. Functional MRI was used to measure reactions to the stimuli in Heschl’s gyrus, the site of the primary auditory cortex in the human brain’s temporal lobe as well as other brain areas.

The researchers took advantage of an already known perceptual illusion in hearing people known as the auditory induced double flash, in which a single flash of light paired with two or more brief auditory events is perceived as multiple flashes of light. In their experiment, the researchers used a double puff of air as a tactile stimulus to replace the auditory stimulus, but kept the single flash of light. Subjects were also exposed to tactile stimuli and light stimuli separately and time-periods without stimuli to establish a baseline for brain activity.

Hearing people exposed to two puffs of air and one flash of light claimed only to see a single flash. However, when exposed to the same mix of stimuli, the subjects who were deaf saw two flashes. Looking at the brain scans of those who saw the double flash, the scientists observed much greater activity in Heschl’s gyrus, although not all deaf brains responded to the same degree. The deaf individuals with the highest levels of activity in the primary auditory cortex in response to touch also had the strongest response to the illusion.

"We designed this study because we thought that touch and vision might have stronger interactions in the auditory cortices of deaf people," said Dr. Karns." As it turns out, the primary auditory cortex in people who are profoundly deaf focuses on touch, even more than vision, in our experiment."

There are several ways the finding may help deaf people. For example, if touch and vision interact more in the deaf, touch could be used to help deaf students learn math or reading. The finding also has the potential to help clinicians improve the quality of hearing after cochlear implants, especially among congenitally deaf children who are implanted after the ages of 3 or 4. These children, who have lacked auditory input since birth, may struggle with comprehension and speech because their auditory cortex has taken on the processing of other senses, such as touch and vision. These changes may make it more challenging for the auditory cortex to recover auditory processing function after cochlear implantation. Being able to measure how much the auditory cortex has been taken over by other sensory processing could offer doctors insights into the kinds of intervention programs that would help the brain retrain and devote more capacity to auditory processing.

Source: Science Daily

July 10, 2012

A new study published in the July 11 issue of the Journal of Neuroscience details the development of the first mouse model engineered to carry the most common mutation in Usher syndrome III causative gene (Clarin-1) in North America. Further, the research team from Case Western Reserve University School of Medicine used this new model to understand why mutation in Clarin-1 leads to hearing loss.

Usher Syndrome is an incurable genetic disease and it is the most common cause of the dual sensory deficits of deafness and blindness. It affects an estimated 50,000 Americans and many more worldwide. Clinically it is subdivided into types I-III based on the degree of deafness and the presence of balance disorder and each type is associated with distinct genes. While the progression of the disease is different with each type, all patients ultimately arrive at the same consequence. The focus of this study is Usher type III. More than a dozen genetic mutations are associated with Usher III, with ‘N48K’ mutation in Clarin-1 being the most prevalent mutation in Usher III patients in North America. Since N48K mutation originated in Europe, results of this study will be of significance to a subset of Usher III patients in Europe as well.

"With the prospective of designing and exploring therapies for Usher III patients with N48K mutation, this is a significant preclinical finding," says Kumar Alagramam, PhD, associate professor of otolaryngology head & neck surgery, genetics, and neurosciences and senior author of the manuscript. "This key understanding of how deafness occurs in Usher III is based on three years of collaborative work."

This new study reports on the first mouse model that mimicked the N48K mutation in Usher III patients. The genetically engineered mouse developed hearing loss similar to clinical presentations observed in Usher III patients with N48K mutation. This model allowed researchers to understand the pathophysiology in fine detail, as there is no non-invasive way to evaluate soft tissue pathology in the human inner ear.

The new study explains why the mutation in the N48K mutation in Clarin-1 leads to hearing loss – mislocalization of mutant protein in mechanosensory hair cells of the inner ear. Using this new Usher III model, researchers can now explore prospective therapeutics to rescue mutant protein localization and hearing. If successful, this approach could serve as a model to treat Usher I and II associated with missense mutation.

In 2009, Alagramam et al reported on the first mouse model of Usher III. The first mouse model was gene knockout mutation and most recent mouse model is a missense mutation, the first model of its kind for Usher III.

Provided by Case Western Reserve University

Source: medicalxpress.com

July 9, 2012

In the last ten years, a new understanding of pediatric brain injury and recovery has emerged. Professionals now understand that recovery may be a lifelong process for the child’s entire circle of family, friends, and healthcare providers. The latest efforts to advance medical and rehabilitative services to move children from medical care and rehabilitation to community reintegration are discussed by the leading experts in a recently published special issue of NeuroRehabilitation.

“Recovery extends well beyond the technical period of rehabilitation,” say guest editors and noted authorities Peter D. Patrick, PhD, MS, Associate Professor Emeritus of the University of Virginia School of Medicine in Charlottesville, and Ronald C. Savage, EdD, Chairman, North American Brain Injury Society and International Pediatric Brain Injury Society. “Children, adolescents, and families struggle to regain the momentum of their life so as to reduce problems, increase opportunity, and support increased participation in work, play, home, and relationships.”

Neural plasticity introduces unknown challenges in the care of the recovering brain, and the issue addresses the most challenging and demanding medical conditions that children may confront following severe brain injury. However, children do most of their recovery at home, in school, and in the community, beyond medical surveillance. “Family-centered” approaches to developing interventions are emerging. For example, Dr. Damith T. Woods and colleagues report on a novel telephone support program to help parents manage challenging behavior associated with brain injury.

Children and adolescents with brain injuries have difficulty adjusting to their injuries and altered abilities, and frequently suffer from low self-esteem and loss of confidence. A study by Carol A. Hawley finds that children with traumatic brain injury have significantly lower self-esteem than normal children, and recommends that rehabilitation strategies promote a sense of self-worth.

Re-entry into school is a major milestone of recovery and the issue highlights a number of efforts to help children improve and return to a positive developmental trajectory. An article by Beth Wicks describes an innovative program in Britain that looks at “education as rehabilitation,” translating successful adult vocational programs into educational rehabilitation programs for children. Lucia Willadino Braga and colleagues report on a program based on cooperative learning that helped preadolescents with acquired brain injury develop metacognitive strategies and improve self-concept, thereby helping empower the preadolescents in their social relationships.

"Over the years and in multiple places around the world, innovative and creative efforts have slowly revealed effective interventions for recovery," comment Dr. Patrick and Dr. Savage. "Increasingly the interventions are evidence-based. This issue is a contribution to the effort to improve outcomes for children and families."

Provided by IOS Press

Source: medicalxpress.com

ScienceDaily (July 9, 2012) — Scientists showed in mice that disabling a gene linked to a common pediatric tumor disorder, neurofibromatosis type 1 (NF1), made stem cells from one part of the brain proliferate rapidly. But the same genetic deficit had no effect on stem cells from another brain region.

The results can be explained by differences in the way stem cells from these regions of the brain respond to cancer-causing genetic changes.

NF1 is among the world’s most common genetic disorders, occurring in about one of every 3,000 births. It causes a wide range of symptoms, including brain tumors, learning disabilities and attention deficits.

Brain tumors in children with NF1 typically arise in the optic nerve and do not necessarily require treatment. If optic gliomas keep growing, though, they can threaten the child’s vision. By learning more about the many factors that contribute to NF1 tumor formation, scientists hope to develop more effective treatments.

"To improve therapy, we need to develop better ways to identify and group tumors based not just on the way they look under the microscope, but also on innate properties of their stem cell progenitors," says David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology.

The study appears July 9 in Cancer Cell. Gutmann also is the director of the Washington University Neurofibromatosis Center.

In the new study, researchers compared brain stem cells from two primary sources: the third ventricle, located in the midbrain, and the nearby lateral ventricles. Before birth and for a time afterward, both of these areas in the brain are lined with growing stem cells.

First author Da Yong Lee, PhD, a postdoctoral research associate, showed that the cells lining both ventricles are true stem cells capable of becoming nerve and support cells (glia) in the brain. Next, she conducted a detailed analysis of gene expression in both stem cell types.

"There are night-and-day differences between these two groups of stem cells," Gutmann says. "These results show that stem cells are not the same everywhere in the brain, which has real consequences for human neurologic disease."

The third ventricle is close to the optic chiasm, the point where the optic nerves cross and optic gliomas develop in NF1 patients. Lee and Gutmann postulated that stem cells from this ventricle might be the source of progenitor cells that can become gliomas in children with NF1.

To test the theory, they disabled the Nf1 gene in neural stem cells from the third and lateral ventricles in the mice. This same gene is mutated in patients with NF1, increasing their risk of developing tumors.

Lee found that loss of Nf1 activity had little effect on stem cells from the lateral ventricle, but stem cells from the third ventricle began to divide rapidly, a change that puts them closer to becoming tumors.

The third ventricle usually stops supplying stem cells to the brain shortly after birth. When researchers inactivated the Nf1 gene before the third ventricle closed, the mice developed optic gliomas. When they waited until the third ventricle had closed to inactivate the Nf1 gene, gliomas did not develop.

Gutmann plans further studies to determine whether all NF1-related optic gliomas form in cells descended from the third ventricle. He suspects that additional factors are necessary for optic gliomas to form in cooperation with Nf1 gene loss in third-ventricle stem cells.

"We have to recognize that cancers which appear very similar actually represent a collection of quite different diseases," he says. "Tumors are like us — they’re defined by where they live, what their families are like, the traumas they experience growing up, and a variety of other factors. If we can better understand the interplay of these factors, we’ll be able to develop treatments that are much more likely to succeed, because they’ll target what is unique about a specific patient’s tumor."

Source: Science Daily

ScienceDaily (July 9, 2012) — Nearly a third of adults with the most common type of brain cancer develop recurrent, invasive tumors after being treated with a drug called bevacizumab. The molecular underpinnings behind these detrimental effects have now been published by Cell Press in the July issue of Cancer Cell. The findings reveal a new treatment strategy that could reduce tumor invasiveness and improve survival in these drug-resistant patients.

"Understanding how and why these tumors adopt this invasive behavior is critical to being able to prevent this recurrence pattern and maximizing the benefits of bevacizumab," says study author Kan Lu of the University of California, San Francisco (UCSF).

Glioblastoma multiforme (GBM) is the most aggressive type of tumor originating in the brain. GBM tumors express high levels of vascular endothelial growth factor (VEGF), a protein that promotes the growth of new blood vessels that provide nutrients that allow tumors to expand. In 2009, the Food and Drug Administration approved bevacizumab, a VEGF inhibitor, for GBM patients who don’t respond to first-line therapies. Although the drug is initially effective, up to 30% of patients develop tumors that infiltrate deep into the brain, making surgery and treatment difficult.

To study how bevacizumab can lead to adverse effects, senior study author Gabriele Bergers of UCSF and her collaborators focused on hepatocyte growth factor (HGF), a protein that controls the growth and movement of cells, because they previously found a link between VEGF and HGF in GBM cells. In the new study, they found that VEGF inhibits the migration of GBM cells by decreasing HGF signaling through its receptor MET. Moreover, tumors were much less invasive — and survival improved — in mice with GBM tumors lacking both VEGF and MET rather than just VEGF alone. The results suggest that MET plays a critical role in GBM invasion when VEGF is blocked.

"These findings provide a rationale for therapeutically combining VEGF and MET inhibition so that patients can benefit from bevacizumab without developing more invasive tumors," Lu says. Because the VEGF and HGF/MET signaling pathways are active in a variety of tumors, this combined treatment strategy may also be applied to other types of cancer.

Source: Science Daily

ScienceDaily (July 9, 2012) — A hormone with anti-diabetic properties also reduces depression-like symptoms in mice, researchers from the School of Medicine at the UT Health Science Center San Antonio reported July 9.

All types of current antidepressants, including tricyclics and selective serotonin reuptake inhibitors, increase the risk for type 2 diabetes. “The finding offers a novel target for treating depression, and would be especially beneficial for those depressed individuals who have type 2 diabetes or who are at high risk for developing it,” said the study’s senior author, Xin-Yun Lu, Ph.D., associate professor of pharmacology and psychiatry and member of the Barshop Institute for Longevity and Aging Studies at the UT Health Science Center.

The hormone, called adiponectin, is secreted by adipose tissue and sensitizes the body to the action of insulin, a hormone that lowers blood sugar. “We showed that adiponectin levels in plasma are reduced in a chronic social defeat stress model of depression, which correlates with the degree of social aversion,” Dr. Lu said.

Facing Goliath over and over

In the study mice were exposed to 14 days of repeated social defeat stress. Each male mouse was introduced to the home cage of an unfamiliar, aggressive resident mouse for 10 minutes and physically defeated. After the defeat, the resident mouse and the intruder mouse each were housed in half of the cage separated by a perforated plastic divider to allow visual, olfactory and auditory contact for the remainder of the 24-hour period. Mice were exposed to a new resident mouse cage and subjected to social defeat each day. Plasma adiponectin concentrations were determined after the last social defeat session. Defeated mice displayed lower plasma adiponectin levels.

Withdrawal, lost pleasure and helplessness

When adiponectin concentrations were reduced by deleting one allele of the adiponectin gene or by a neutralizing antibody, mice were more susceptible to stress-induced social withdrawal, anhedonia (lost capacity to experience pleasure) and learned helplessness.

Mice that were fed a high-fat diet (60 percent calories from fat) for 16 weeks developed obesity and type 2 diabetes. Administration of adiponectin to these mice and mice of normal weight produced antidepressant-like effects.

Possible innovative approach for depression

"These findings suggest a critical role of adiponectin in the development of depressive-like behaviors and may lead to an innovative therapeutic approach to fight depression," Dr. Lu said.

A novel approach would benefit thousands. “So far, only about half of the patients suffering from major depressive disorders are treated to the point of remission with antidepressant drugs,” Dr. Lu said. “The prevalence of depression in the diabetic population is two to three times higher than in the non-diabetic population. Unfortunately, the use of current antidepressants can worsen the control of diabetic patients. Adiponectin, with its anti-diabetic activity, would serve as an innovative therapeutic target for depression treatments, especially for those individuals with diabetes or prediabetes and perhaps those who fail to respond to currently available antidepressants.”

Source: Science Daily

ScienceDaily (July 9, 2012) — A new study of aged female rats found that long-term treatment with estrogen and a synthetic progesterone known as MPA increased levels of a protein marker of synapses in the prefrontal cortex, a brain region known to suffer significant losses in aging.

The new findings appear to contradict the results of the Women’s Health Initiative, a long-term study begun in 1991 to analyze the effects of hormone therapy on a large sample of healthy postmenopausal women aged 50 to 79. Among other negative findings, the WHI found that long-term exposure to estrogen alone or to estrogen and MPA resulted in an increased risk of stroke and dementia. More recent research, however, suggests that starting hormone replacement therapy at the onset of menopause, rather than years or decades afterward, yields different results.

The new study, from researchers at the University of Illinois, is the first to look at the effects of long-term treatment with estrogen and MPA on the number of synapses in the prefrontal cortex of aged animals. The researchers describe their findings in a paper in the journal Menopause.

"The prefrontal cortex is the area of the human brain that loses the most volume with age," said U. of I. psychology professor and Beckman Institute affiliate Janice Juraska, who led the study with doctoral student Nioka Chisholm. "So understanding how anything affects the prefrontal cortex is important."

The prefrontal cortex, just behind the forehead in humans, governs what researchers call “executive function” — planning, strategic thinking, working memory (the ability to hold information in mind just long enough to use it), self-control and other functions that tend to decline with age.

Most studies of the effects of hormone treatments on the brain have focused on the hippocampus, a structure important to spatial navigation and memory consolidation. The studies tend to use young animals exposed to hormones for very brief periods of time (one or two days to a few weeks at the most). They have yielded mixed results, with most research in young female animals indicating an increase in hippocampal synapses and hippocampal function after exposure to estrogen and MPA.

"For some reason, a lot of researchers still look at the effects of hormones in young animals," Chisholm said. "And there’s a lot of evidence now saying that the aged brain is different; the effect of these hormones is not going to be the same."

The new study followed middle-aged rats exposed to estrogen alone, to no additional hormones, or to estrogen in combination with MPA for seven months, a time period that more closely corresponds to the experience of women who start hormone therapy at the onset of menopause and continue into old age. The researchers removed the rats’ ovaries just prior to the hormone treatment (or lack of treatment) to mimic the changes that occur in humans during menopause.

"Our most important finding is that estrogen in combination with MPA can result in a greater number of synapses in the prefrontal cortex than (that seen) in animals that are not receiving hormone replacement," Chisholm said. "Estrogen alone marginally increased the synapses, but it took the combination with MPA to actually see the significant effect."

"Our data indicate that re-examining the effects of estrogen and MPA, when first given to women around the time of menopause, is merited," Juraska said.

Source: Science Daily

July 9, 2012

A study of patients with stroke admitted to English National Health Service public hospitals suggests that patients who were hospitalized on weekends were less likely to receive urgent treatments and had worse outcomes, according to a report published Online First by Archives of Neurology.

Studies from other countries have suggested higher mortality in patients who were admitted to the hospital on weekends for a variety of medical conditions, a phenomenon known as “the weekend effect.” However, other studies have not identified an association between the day of admission and mortality rates due to stroke, so the debate over “the weekend effect” continues, according to the study background.

William L. Palmer, M.A., M.Sc., of Imperial College and the National Audit Office, and colleagues conducted a study of patients admitted to hospitals with stroke from April 2009 through March 2010, accounting for 93,621 admissions.

Performance across five of six measures was lower on weekends, with one of the largest disparities seen in rates of same-day brain scans (43.1 percent on weekends compared with 47.6 percent on weekdays). Also, the rate of seven-day, in-hospital mortality for Sunday admissions was 11 percent compared with a mean (average) of 8.9 percent for weekday admissions, according to study results.

"We calculated that approximately 350 potentially avoidable in-hospital deaths occur within seven days each year and that an additional 650 people could be discharged to their usual place of residence within 56 days if the performance seen on weekdays was replicated on weekends," the authors comment.

Provided by JAMA and Archives Journals

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