Posts tagged science

ScienceDaily (May 21, 2012) — Johns Hopkins scientists have discovered a protein that appears to play an important regulatory role in deciding whether stem cells differentiate into the cells that make up the brain, as well as countless other tissues. This finding, published in the April Developmental Cell, could eventually shed light on developmental disorders as well as a variety of conditions that involve the generation of new neurons into adulthood, including depression, stroke, and posttraumatic stress disorder.

Researchers have long known that a small group of proteins called Notch plays a pivotal role in helping the immature cells present in embryos to develop into the variety of cells present throughout the body, including those that make up the brain, blood, kidneys and muscles.

"Notch signaling is involved in almost all aspects of tissue development," explains study leader Valina Dawson, Ph.D., a professor in the departments of Neurology, Neuroscience, and Physiology and co-director of the Stem Cell and Neuroregeneration Programs at the Institute for Cell Engineering at the Johns Hopkins University School of Medicine.

However, she says, even for researchers who have been studying Notch for decades, how this small group of proteins manages the development of such a diverse array of tissues and organs in the body remains unknown. It’s a pivotal mystery to solve, Dawson adds, since problems in Notch signaling seem to be involved in various cancers, Alzheimer’s disease, juvenile stroke and many other health problems.

In their new study, Dawson and her colleagues shed light on one way Notch proteins might be regulated, through a protein they recently discovered in the lab. This protein seemed to be involved in development, but at first, the researchers didn’t know its function.

To determine what purpose this protein serves in cells, Dawson, postdoctoral fellow Zhikai Chi, M.D., Ph.D., and their colleagues started by trying to determine what other proteins it’s able to bind to. By adding the mystery protein to cell cultures that expressed a variety of other proteins, they determined that the unknown protein altered cellular activity in those expressing Notch.

Since Notch is involved intimately in determining the fate of brain precursor cells, driving neural stem cells to proliferate and determining whether they become neurons or supporting cells known as glia, the researchers next examined how this mystery protein affected brain development in mouse embryos. They found that by increasing expression of the unknown protein, more neurons developed in certain parts of the developing brain, including the intermediate zone and cortical plate. In contrast, decreasing expression led to fewer neurons. Taken together, Dawson says, these experiments provided even more evidence that their unknown protein was somehow influencing Notch.

To determine exactly how the mystery protein was affecting Notch, the researchers examined the effect of the protein on neural stem cells in the process of differentiating into mature cell types. Increasing the amount of the unknown protein swayed development as if Notch wasn’t working. Since the unknown protein appeared to prevent Notch from acting on cells, the researchers named it Botch for “blocks Notch.”

With Botch’s role now clear, the researchers turned next to the mechanism behind how this protein exerts its influence. A series of experiments suggests that Botch interacts with Notch in the Golgi body, a cellular organelle involved in modifying proteins. For Notch to act in development, an immature version of this protein needs to be cleaved in order for the protein to be rearranged. Botch appears to prevent this pivotal modification from taking place, reducing the amount of mature Notch available to do its job.

Because Botch appears to play such an important role in regulating Notch, Dawson says, it could be involved in a number of diseases in which the generation of new neurons is misregulated. She and her colleagues are already performing some preliminary experiments to determine whether Botch expression might vary from the norm in diseases such as depression, which has been linked to a decrease in neurogenesis in the brain’s hippocampus. Eventually, researchers might be able to develop drugs that act on Botch to restart stalled neurogenesis, potentially treating depression and other diseases in which a lack of neurogenesis is thought to play a role.

"There are potentially some very large neurological problems that could be addressed through changing Botch activity," Dawson says.

Source: Science Daily

May 21, 2012

New nerve cells formed in a select part of the brain could hold considerable sway over how much you eat and consequently weigh, new animal research by Johns Hopkins scientists suggests in a study published in the May issue of Nature Neuroscience.

The idea that the brain is still forming new nerve cells, or neurons, into adulthood has become well-established over the past several decades, says study leader Seth Blackshaw, Ph.D., an associate professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine. However, he adds, researchers had previously thought that this process, called neurogenesis, only occurs in two brain areas: the hippocampus, involved in memory, and the olfactory bulb, involved in smell.

More recent research suggests that a third area, the hypothalamus — associated with a variety of bodily functions, including sleep, body temperature, hunger and thirst — also produces new neurons. However, the precise source of this neurogenesis and the function of these newborn neurons remained a mystery.

To answer these questions, Blackshaw and his colleagues used mice as a model system. The researchers started by investigating whether any particular part of the hypothalamus had a high level of cell growth, suggesting that neurogenesis was occurring. They injected the animals with a compound called bromodeoxyuridine (BrdU), which selectively incorporates itself into newly replicating DNA of dividing cells, where it’s readily detectable. Within a few days, the researchers found high levels of BrdU in an area of the hypothalamus called the median eminence, which lies on the base of the brain’s fluid-filled third ventricle.

Further tests showed that these rapidly proliferating cells were tanycytes, a good candidate for producing new neurons since they have many characteristics in common with cells involved in neurogenesis during early development. To confirm that tanycytes were indeed producing new neurons and not other types of cells, Blackshaw and his colleagues selectively bred mice that produced a fluorescent protein only in their tanycytes. Within a few weeks, they found neurons that also fluoresced, proof that these cells came from tanycyte progenitors.

With the source of hypothalamic neurogenesis settled, the researchers turned to the question of function. Knowing that many previous studies have suggested that animals raised on a high-fat diet are at significantly greater risk of obesity and metabolic syndrome as adults, Blackshaw’s team wondered whether hypothalamic neurogenesis might play a role in this phenomenon.

The researchers fed mice a diet of high-fat chow starting at weaning and looked for evidence of neurogenesis at several different time points. While very young animals showed no difference compared with mice fed normal chow, neurogenesis quadrupled in adults that had consistently eaten the high-fat chow since weaning. These animals gained more weight and had higher fat mass than animals raised on normal chow.

When Blackshaw and his colleagues killed off new neurons in the high-fat eaters by irradiating just their median eminences with precise X-ray beams, the mice gained significantly less weight and fat than animals who had eaten the same diet and were considerably more active, suggesting that these new neurons play a critical role in regulating weight, fat storage and energy expenditure.

"People typically think growing new neurons in the brain is a good thing — but it’s really just another way for the brain to modify behavior," Blackshaw explains. He adds that hypothalamic neurogenesis is probably a mechanism that evolved to help wild animals survive and helped our ancestors do the same in the past. Wild animals that encounter a rich and abundant food source would be well-served to eat as much as possible, since such a resource is typically scarce in nature.

Being exposed to such a resource during youth, and consequently encouraging the growth of neurons that would promote more food intake and energy storage in the future, would be advantageous. However, Blackshaw explains, for lab animals as well as people in developed countries, who have nearly unlimited access to abundant food, such neurogenesis isn’t necessarily beneficial — it could encourage excessive weight gain and fat storage when they’re not necessary.

If the team’s work is confirmed in future studies, he adds, researchers might eventually use these findings as a basis to treat obesity by inhibiting hypothalamic neurogenesis, either by irradiating the median eminence or developing drugs that inhibit this process.

Provided by Johns Hopkins University School of Medicine

Source: medicalxpress.com

May 21, 2012

A substance in human mesenchymal stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found.

Their study appeared in the online version of Nature Neuroscience on Sunday, May 20.

In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease.

"The importance of this work is we think we’ve identified the driver of the recovery," said Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University.

Miller, neurosciences instructor Lianhua Bai and biology professor Arnold I. Caplan, designed the study. They worked with Project Manager Anne DeChant, and research assistants Jordan Hecker, Janet Kranso and Anita Zaremba, from the School of Medicine; and Donald P. Lennon, a research assistant from the university’s Skeletal Research Center.

In MS, the immune system attacks myelin, risking injury to exposed nerves’ intricate wiring. When damaged, nerve signals can be interrupted, causing loss of balance and coordination, cognitive ability and other functions. Over time, intermittent losses may become permanent.

Miller and Caplan reported in 2009 that when they injected human mesenchymal stem cells into rodent models of MS, the animals recovered from the damage wrought by the disease. Based on their work, a clinical trial is underway in which MS patients are injected with their own stem cells.

In this study, the researchers first wanted to test whether the presence of stem cells or something cells produce promotes recovery. They injected mice with the medium in which mesenchymal stem cells, culled from bone marrow, grew.

All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits.

Analysis showed that the disease remained on course unless the molecules injected were of a certain size; that is, the molecular weight ranged between 50 and 100 kiloDaltons.

Research by others and results of their own work indicated hepatocyte growth factor, which is secreted by mesenchymal stem cells, was a likely instigator.

The scientists injected animals with 50 or 100 nanograms of the growth factor every other day for five days. The level of signaling molecules that promote inflammation decreased while the level of signaling molecules that counter inflammation increased. Neural cells grew and nerves laid bare by MS were rewrapped with myelin. The 100-nanogram injections appeared to provide slightly better recovery.

To test the system further, researchers tied up cell-surface receptors, in this case cMet receptors that are known to work with the growth factor.

When they jammed the receptors with a function-blocking cMet antibody, neither the mesenchymal stem cell medium nor the hepatocyte growth factor injections had any effect on the disease. In another test, injections of an anti-hepatocyte growth factor also blocked recovery.

The researchers will continue their studies, to determine if they can screen mesenchymal stem cells for those that produce the higher amounts of hepatocyte growth factor needed for effective treatment. That could lead to a more precise cell therapy.

"Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor?” Miller asked. “We’ve shown we can do that in an animal but it’s not clear if we can do that in a patient.”

They also plan to test whether other factors may be used to stimulate the cMet receptors and induce recovery.

Provided by Case Western Reserve University

Source: medicalxpress.com

May 21, 2012

Max Planck scientists discover brain cells in monkeys that may be linked to self-awareness and empathy in humans.

The anterior insular cortex is a small brain region that plays a crucial role in human self-awareness and in related neuropsychiatric disorders. A unique cell type – the von Economo neuron (VEN) – is located there. For a long time, the VEN was assumed to be unique to humans, great apes, whales and elephants. Henry Evrard, neuroanatomist at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, now discovered that the VEN occurs also in the insula of macaque monkeys. The morphology, size and distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN. This finding offers new and much-needed opportunities to examine in detail the connections and functions of a cell and brain region that could have a key role in human self-awareness and in mental disorders including autism and specific forms of dementia.

The insular cortex, or simply insula, is a hidden cortical region folded and tucked away deep in the brain – an island within the cortex. Within the last decade, the insula has emerged from darkness as having a key role in diverse functions usually linked to our internal bodily states, to our emotions, to our self-awareness, and to our social interactions. The very anterior part of the insula in particular is where humans consciously sense subjective emotions, such as love, hate, resentment, self-confidence or embarrassment. In relation to these feelings, the anterior insula is involved in various psychopathologies. Damage of the insula leads to apathy, and to the inability to tell what feelings we or our conversational partner experience. These inabilities and alteration of the insula are also encountered in autism and other highly detrimental neuropsychiatric disorders including the behavioural variant of frontotemporal dementia (bvFTD).

The von Economo neuron (VEN) occurs almost exclusively in the anterior insula and anterior cingulate cortex. Until recently it was believed that the VEN is only present in humans, great apes and some large-brained mammals with complex social behaviour such as whales and elephants. In contrast to the typical neighbouring pyramidal neuron that is present in all mammals and all brain regions, the VEN has a peculiar spindle shape and is about three times as large. Their numeral density is selectively altered in autism and bvFTD. Henry Evrard and his team, at the Max Planck Institute for Biological Cybernetics in Tübingen now discovered VENs in the anterior insula in macaque monkeys. His present work provides compelling evidence that monkeys possess at least a primitive form of the human VEN although they do not have the ability to recognize themselves in a mirror, a behavioural hallmark of self-awareness.

"This means, other than previously believed, that highly concentrated VEN populations are not an exclusivity of hominids, but also occurs in other primate species", explains Henry Evrard. "The VEN phylogeny needs to be reexamined. Most importantly, the very much-needed analysis of the connections and physiology of these specific neurons is now possible.” Knowing the functions of the VEN and its connections to other regions of the brain in monkeys could give us clues on the evolution of the anatomical substrate of self-awareness in humans and may help us in better understanding serious neuropsychiatric disabilities including autism, or even addictions such as to drugs or smoking.

Provided by Max Planck Society

Source: medicalxpress.com

May 21, 2012

(Medical Xpress) — People with a curious condition that causes them to apply make-up on only one side of their face, or ignore food on half of their plate, are playing a new role in understanding stroke recovery.

Researchers from the Queensland Brain Institute (QBI) at The University of Queensland have found the condition, a subset of the stroke called ‘unilateral spatial neglect’, tend to have the worst recovery outcomes in regaining lost functioning in their bodies, leading them to believe attention may have an important impact on recovering successfully.

Unilateral spatial neglect is typically caused by strokes on the right hand side of the brain and manifests in patients ignoring the left side of their body.

People with the condition may ignore food on the left hand side of their plate or, if asked to draw a clock, squash all 12 numbers into the right side of the clock face, leaving the other side blank.

They may also fail to shave, or to put make-up on the left side of their faces and. In severe cases, they behave as though the left side of their world does not exist.

“We know that brain plasticity plays a critical role in recovering from stroke,” says Professor Jason Mattingley, who holds the Foundation Chair in Cognitive Neuroscience at The University of Queensland.

“The fact that people with spatial neglect tend to have poorer recovery of motor function suggested to us that attention may be important for guiding plasticity following stroke.”

Current research being undertaken by the Mattingley laboratory is exploring this link.

“What we’re trying to do is explore what effect attention has on brain plasticity, and how attention might be used in neurorehabilitation” says Professor Mattingley.

Volunteers first undergo a magnetic resonance imaging (MRI) scan, which provides researchers with a three-dimensional picture of the brain.

“In terms of their structure, brains are like fingerprints – no two are exactly the same, even though superficially they seem very similar,” Professor Mattingley explains.

The MRI scan allows researchers to guide a transcranial magnetic stimulation (TMS) coil into position upon a volunteer’s scalp.

The device induces a small electrical current in the underlying brain tissue, causing it to become more active.

The researchers specifically target a part of the motor cortex that controls the thumb muscle in the left hand.

“It’s well established that the more often neurons activate at the same time, the more likely they are to communicate efficiently in the future. This is how the brain learns,” says Professor Mattingley.

“We’re exploiting that general principle in this research.”

Dr Marc Kamke, Research Fellow at QBI explains: “By adjusting the type of brain stimulation delivered we can artificially induce short-term changes that resemble naturally-occurring plasticity.”

But what the researchers have found is that the effects of stimulation upon a brain’s plasticity are dependent on attention.

“When we ask people to undertake a visual task that is irrelevant to the brain stimulation, but that demands a great deal of their attention, we observe a reduction in plasticity,” Dr Marc Kamke explains.

“When the task does not require much attention, however, the brain’s plastic response is apparent.”

“These results show that attention plays an important role in guiding brain plasticity,” says Professor Mattingley.

He adds, “while practical applications remain several steps away, this knowledge may ultimately help us develop more effective strategies for physical therapy after stroke.”

The results of the research, which was funded by the National Health and Medical Research Council of Australia, are published this week in The Journal of Neuroscience.

Provided by University of Queensland 

Source: medicalxpress.com

ScienceDaily (May 20, 2012) — To learn its signature melody, the male songbird uses a trial-and-error process to mimic the song of its father, singing the tune over and over again, hundreds of times a day, making subtle changes in the pitch of the notes. For the male Bengalese finch, this rigorous training process begins around the age of 40 days and is completed about day 90, just as he becomes sexually mature and ready to use his song to woo females.

To learn its signature melody, the male songbird uses a trial-and-error process to mimic the song of its father, singing the tune over and over again, hundreds of times a day, making subtle changes in the pitch of the notes. (Credit: © fasphotographic / Fotolia)

To accomplish this feat, the finch’s brain must receive and process large quantities of information about its performance and use that data to precisely control the complex vocal actions that allow it to modify the pitch and pattern of its song.

Now, scientists at UCSF have shown that a key brain structure acts as a learning hub, receiving information from other regions of the brain and figuring out how to use that information to improve its song, even when it’s not directly controlling the action. These insights may help scientists figure out new ways to treat neurological disorders that impair movement such as Huntington’s disease and Parkinson’s disease.

The research is reported as an advanced online publication on May 20, 2012 by the journal Nature, and will appear at a later date in the journal’s print edition.

Years of research conducted in the lab of Michael Brainard, PhD, an associate professor of physiology at UCSF, has shown that adult finches can keep track of slight differences in the individual “syllables,” or notes, they play and hear, and make mental computations that allow them to alter the pitch.

For previous experiments, Brainard and his colleagues developed a training process that induced adult finches to calibrate their song. They created a computer program that could recognize the pitch of every syllable the bird sang. The computer also delivered a sound the birds didn’t like — a kind of white noise — at the very moment they uttered a specific note. Within a few hours, the finches learned to alter the pitch of that syllable to avoid hearing the unpleasant sound.

In the new research, the UCSF neuroscientists used their technology to investigate how the learning process is controlled by the brain. A prevailing theory suggests that new learning is controlled by a “smart” brain structure called the basal ganglia, a cluster of interconnected brain regions involved in motor control and learning.

"It’s the first place where the brain is putting two and two together," said Jonathan Charlesworth, a recent graduate of UCSF’s neuroscience PhD program and the first author of the new paper. "If you remove the basal ganglia in a bird that hasn’t yet learned to sing, it will never learn to do so."

Once a basic, frequently repeated skill such as typing, singing the same song or shooting a basketball from the free-throw line is learned, the theory suggests, control of that activity is carried out by the motor pathway, the part of the nervous system that transmits signals from the brain to muscles. But for the basic routine to change — for a player to shoot from another spot on the basketball court or a bird to sing at a different pitch — the basal ganglia must again get involved, providing feedback that allows learning based on trial and error, the theory suggests.

What remained unclear is what makes the basal ganglia so “smart” and enables them to support such detailed trial-and-error learning. Was it something to do with their structure? Or were they getting information from elsewhere?

The scientists sought to answer this question by blocking the output of a key basal ganglia circuit while training male finches to alter their song using the white-noise blasts. As long as the basal ganglia were kept from sending signals to the motor pathway, the finches didn’t change their tune or show signs of learning. But when Brainard’s team stopped blocking the basal ganglia, something surprising happened: the finches immediately changed the pitch of their song, with no additional practice.

"It’s as if a golfer went to the driving range and was terrible, hitting the ball into the trees all day and not getting any better," said Charlesworth. "Then, at the end of the day, you throw a switch and all of a sudden you’re hitting the fairway like you’re Tiger Woods."

Normally, you’d expect improvement in skill performance like this to take time as the basal ganglia evaluates information, makes changes and gets new feedback, Brainard said.

"The surprise here is that the basal ganglia can pay attention, observe what other motor structures are doing and get information even when they aren’t involved in motor control," Brainard said. "They covertly learned how to improve skill performance and this explains how they did it."

These findings suggest that the basal ganglia’s “smartness” is due in large part to the steady flow of information they receive about the commands of other motor structures. It also portrays the basal ganglia as far more versatile than previously understood, able to learn how to calibrate fine-motor skills by acting as a specialized hub that receives information from various parts of the brain and responds to that information with new directives.

The findings also support the notion that problems in the basal ganglia circuit’s ability to receive information and learn from it may help trigger the movement disorders that are symptoms of Huntington’s and Parkinson’s, Brainard said.

Source: Science Daily

ScienceDaily (May 19, 2012) — Preliminary results from an ongoing, large-scale study by Yale School of Medicine researchers shows that oxytocin — a naturally occurring substance produced in the brain and throughout the body — increased brain function in regions that are known to process social information in children and adolescents with autism spectrum disorders (ASD).

Preliminary results from an ongoing, large-scale study by Yale School of Medicine researchers shows that oxytocin — a naturally occurring substance produced in the brain and throughout the body— increased brain function in regions that are known to process social information in children and adolescents with autism spectrum disorders (ASD). (Credit: Image courtesy of Yale University)

A Yale Child Study Center research team that includes postdoctoral fellow Ilanit Gordon and Kevin Pelphrey, the Harris Associate Professor of Child Psychiatry and Psychology, will present the results on May 19 at the International Meeting for Autism Research.

"Our findings provide the first, critical steps toward devising more effective treatments for the core social deficits in autism, which may involve a combination of clinical interventions with an administration of oxytocin," said Gordon. "Such a treatment approach will fundamentally improve our understanding of autism and its treatment."

Social-communicative dysfunctions are a core characteristic of autism, a neurodevelopmental disorder that can have an enormous emotional and financial burden on the affected individual, their families, and society.

Gordon said that while a great deal of progress has been made in the field of autism research, there remain few effective treatments and none that directly target the core social dysfunction. Oxytocin has recently received attention for its involvement in regulating social abilities because of its role in many aspects of social behavior and social cognition in humans and other species.

To assess the impact of oxytocin on the brain function, Gordon and her team conducted a first-of-its-kind, double-blind, placebo-controlled study on children and adolescents aged 7 to 18 with ASD. The team members gave the children a single dose of oxytocin in a nasal spray and used functional magnetic resonance brain imaging to observe its effect.

The team found that oxytocin increased activations in brain regions known to process social information. Gordon said these brain activations were linked to tasks involving multiple social information processing routes, such as seeing, hearing, and processing information relevant to understanding other people.

Source: Science Daily

ScienceDaily (May 18, 2012) — Exercise clears the mind. It gets the blood pumping and more oxygen is delivered to the brain. This is familiar territory, but Dartmouth’s David Bucci thinks there is much more going on.

Exercise clears the mind. It gets the blood pumping and more oxygen is delivered to the brain. This is familiar territory, but Dartmouth’s David Bucci thinks there is much more going on. (Credit: © Galina Barskaya / Fotolia)

"In the last several years there have been data suggesting that neurobiological changes are happening — [there are] very brain-specific mechanisms at work here," says Bucci, an associate professor in the Department of Psychological and Brain Sciences.

From his studies, Bucci and his collaborators have revealed important new findings:

• The effects of exercise are different on memory as well as on the brain, depending on whether the exerciser is an adolescent or an adult.
• A gene has been identified which seems to mediate the degree to which exercise has a beneficial effect. This has implications for the potential use of exercise as an intervention for mental illness.

Bucci began his pursuit of the link between exercise and memory with attention deficit hyperactivity disorder (ADHD), one of the most common childhood psychological disorders. Bucci is concerned that the treatment of choice seems to be medication.

"The notion of pumping children full of psycho-stimulants at an early age is troublesome," Bucci cautions. "We frankly don’t know the long-term effects of administering drugs at an early age — drugs that affect the brain — so looking for alternative therapies is clearly important."

Anecdotal evidence from colleagues at the University of Vermont started Bucci down the track of ADHD. Based on observations of ADHD children in Vermont summer camps, athletes or team sports players were found to respond better to behavioral interventions than more sedentary children. While systematic empirical data is lacking, this association of exercise with a reduction of characteristic ADHD behaviors was persuasive enough for Bucci.

Coupled with his interest in learning and memory and their underlying brain functions, Bucci and teams of graduate and undergraduate students embarked upon a project of scientific inquiry, investigating the potential connection between exercise and brain function. They published papers documenting their results, with the most recent now available in the online version of the journal Neuroscience.

Bucci is quick to point out that “the teams of both graduate and undergraduates are responsible for all this work, certainly not just me.” Michael Hopkins, a graduate student at the time, is first author on the papers.

Early on, laboratory rats that exhibit ADHD-like behavior demonstrated that exercise was able to reduce the extent of these behaviors. The researchers also found that exercise was more beneficial for female rats than males, similar to how it differentially affects male and female children with ADHD.

Moving forward, they investigated a mechanism through which exercise seems to improve learning and memory. This is “brain derived neurotrophic factor” (BDNF) and it is involved in growth of the developing brain. The degree of BDNF expression in exercising rats correlated positively with improved memory, and exercising as an adolescent had longer lasting effects compared to the same duration of exercise, but done as an adult.

"The implication is that exercising during development, as your brain is growing, is changing the brain in concert with normal developmental changes, resulting in your having more permanent wiring of the brain in support of things like learning and memory," says Bucci. "It seems important to [exercise] early in life."

Bucci’s latest paper was a move to take the studies of exercise and memory in rats and apply them to humans. The subjects in this new study were Dartmouth undergraduates and individuals recruited from the Hanover community.

Bucci says that, “the really interesting finding was that, depending on the person’s genotype for that trophic factor [BDNF], they either did or did not reap the benefits of exercise on learning and memory. This could mean that you may be able to predict which ADHD child, if we genotype them and look at their DNA, would respond to exercise as a treatment and which ones wouldn’t.”

Bucci concludes that the notion that exercise is good for health including mental health is not a huge surprise. “The interesting question in terms of mental health and cognitive function is how exercise affects mental function and the brain.” This is the question Bucci, his colleagues, and students continue to pursue.

Source: Science Daily

May 18, 2012

University of Iowa neuroscientist John Wemmie, M.D., Ph.D., is interested in the effect of acid in the brain. His studies suggest that increased acidity or low pH, in the brain is linked to panic disorders, anxiety, and depression. But his work also suggests that changes in acidity are important for normal brain activity too.

University of Iowa researchers have developed an MRI-based method to detect and monitor pH changes in living brains. The image shows MRI brain scans of human subject breathing air (left) or air containing 7.5 percent carbon dioxide (middle). The difference between the two scans (shown right) shows increased brain acidity in red caused by carbon dioxide inhalation as measured by the new MRI-based strategy. Credit: Vincent Magnotta, University of Iowa

"We are interested in the idea that pH might be changing in the functional brain because we’ve been hot on the trail of receptors that are activated by low pH,” says Wemmie, a UI associate professor of psychiatry. “The presence of these receptors implies the possibility that low pH might be playing a signaling role in normal brain function.”

Wemmie’s studies have shown that these acid-sensing proteins are required for normal fear responses and for learning and memory in mice. However, while you can buy a kit to measure the pH (acidity) of your garden soil, there currently is no easy way to measure pH changes in the brain.

Wemmie teamed up with Vincent Magnotta, Ph.D., UI associate professor of radiology, psychiatry, and biomedical engineering, and using Magnotta’s expertise in developing MRI (magnetic resonance imaging)-based brain imaging techniques, the researchers developed and tested a new, non-invasive method to detect and monitor pH changes in living brains.

According to Wemmie, the new imaging technique provides the best evidence so far that pH changes do occur with normal function in the intact human brain. The findings were published May 7 in the Proceedings of the National Academy of Sciences (PNAS) Early Edition.

Specifically, the study showed the MRI-based method was able to detect global changes in brain pH in mice. Breathing carbon dioxide, which lowers pH (makes the brain more acidic), increased the signal, while bicarbonate injections, which increases brain pH, decreased the MRI signal. The relationship between the signal and the pH was linear over the range that was tested.

Importantly, the method also seems able to detect localized brain activity. When human volunteers viewed a flashing checkerboard — a classic experiment that activates a particular brain region involved in vision — the MRI method detected a drop in pH in that region. The team also confirmed the pH drop using other methods.

"Our study tells us, first, we have a technique that we believe can measure pH changes in the brain, and second, this MRI-based technique suggests that pH changes do occur with brain function,” Magnotta says.

"The results support our original idea that brain activity can change local pH in human brains during normal activity, meaning that pH change in conjunction with the pH-sensitive receptors could be part of a signaling system that affects brain activity and cognitive function," Wemmie adds

A new way to view brain activity

Importantly, this technique may also provide a new way to image the brain

Currently, functional MRI (fMRI) measures brain activity by detecting a signal that’s due to oxygen levels in the blood flowing to active brain regions. The UI team showed that their method responds to pH changes but is not influenced by changes in blood oxygenation. Conversely, fMRI does not respond to changes in pH.

"What we show is our method of detecting brain activity probably depends on pH changes and, more than that, it is distinct from the signal that fMRI measures," says Wemmie. "This gives us another tool to study brain activity."

pH and brain function

Wemmie’s previous studies have suggested a role for pH changes in certain psychiatric diseases, including anxiety and depression. With the new method, he and his colleagues hope to explore how pH is involved in these conditions.

“Brain activity is likely different in people with brain disorders, such as bipolar or depression and that might be reflected in this measure,” Wemmie says. “And perhaps most important, at the end of the day; could this signal be abnormal or perturbed in human psychiatric disease? And if so, it might be a target for manipulation and treatment?”

Provided by University of Iowa

Source: medicalxpress.com

May 18, 2012

It has been known for years that eating too many foods containing “bad” fats, such as saturated fats or trans fats, isn’t healthy for your heart. However, according to new research from Brigham and Women’s Hospital (BWH), one “bad” fat—saturated fat—was found to be associated with worse overall cognitive function and memory in women over time. By contrast, a “good” fat—mono-unsaturated fat was associated with better overall cognitive function and memory.

This study is published online by Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, on May 18, 2012.

The research team analyzed data from the Women’s Health Study—originally a cohort of nearly 40,000 women, 45 years and older. The researchers focused on data from a subset of 6,000 women, all over the age of 65. The women participated in three cognitive function tests, which were spaced out every two years for an average testing span of four years. These women filled out very detailed food frequency surveys at the start of the Women’s Health Study, prior to the cognitive testing.

"When looking at changes in cognitive function, what we found is that the total amount of fat intake did not really matter, but the type of fat did,” explained Olivia Okereke, MD, MS, BWH Department of Psychiatry.

Women who consumed the highest amounts of saturated fat, which can come from animal fats such as red meat and butter, compared to those who consumed the lowest amounts, had worse overall cognition and memory over the four years of testing. Women who ate the most of the monounsaturated fats, which can be found in olive oil, had better patterns of cognitive scores over time.

"Our findings have significant public health implications," said Okereke. "Substituting in the good fat in place of the bad fat is a fairly simple dietary modification that could help prevent decline in memory."

Okereke notes that strategies to prevent cognitive decline in older people are particularly important. Even subtle declines in cognitive functioning can lead to higher risk of developing more serious problems, like dementia and Alzheimer disease.

Provided by Brigham and Women’s Hospital

Source: medicalxpress.com