Posts tagged psychology

ScienceDaily (June 28, 2012) — We’ve all heard that eating fish is good for our brains and memory. But what is it about DHA, an omega-3 fatty acid found in fish, that makes our memory sharper?

Researchers with the Faculty of Medicine & Dentistry discovered a possible explanation and just published their findings in the peer-reviewed journal Applied Physiology, Nutrition, and Metabolism.

Principal investigator Yves Sauve and his team discovered lab models fed a high-DHA diet had 30 per cent higher levels of DHA in the memory section of the brain, known as the hippocampus, when compared to animal models on a regular, healthy diet.

"We wanted to find out how fish intake improves memory," says Sauve, a medical researcher at the University of Alberta who works in the department of physiology, the department of ophthalmology and the Centre for Neuroscience.

"What we discovered is that memory cells in the hippocampus could communicate better with each other and better relay messages when DHA levels in that region of the brain were higher. This could explain why memory improves on a high-DHA diet."

Sauve noted it is a key finding that when a diet is supplemented with DHA, that additional stores of the omega-3 fatty acid are deposited in the brain. His team confirmed this finding, a discovery other labs have noted as well.

Supplementing your diet with DHA, such as increasing fish intake or taking supplements, could prevent declining DHA levels in the brain as we age, says Sauve.

This research was funded by Alberta Innovates — Health Solutions.

Earlier this year, Sauve and other colleagues discovered DHA prevents the accumulation of a toxic molecule at the back of the eye that causes age-related vision loss. He is continuing his research in this area.

Source: Science Daily

June 28, 2012

Researchers have come up with a device that may enable people who are completely unable to speak or move at all to nevertheless manage unscripted back-and-forth conversation. The key to such silent and still communication is the first real-time, brain-scanning speller, according to the report published online on June 28 in Current Biology.

Researchers have come up with a device that may enable people who are completely unable to speak or move at all to nevertheless manage unscripted back-and-forth conversation. The key to such silent and still communication is the first real-time, brain-scanning speller, according to the report published online on June 28 in Current Biology.

The new technology builds on groundbreaking earlier uses of fMRI brain scans to assess consciousness in people described as being in an unconscious, vegetative state and to enable them to answer yes and no questions. fMRI (or functional magnetic resonance imaging) is typically used for clinical and research purposes to track brain activity by measuring blood flow.

"The work of Adrian Owen and colleagues led me to wonder whether it might even become possible to use fMRI, mental tasks, and appropriate experimental designs to freely encode thoughts, letter-by-letter, and therewith enable back-and-forth communication in the absence of motor behavior,” said Bettina Sorger of Maastricht University in The Netherlands.

[Video]
This video shows mental task-related brain activation patterns. Video (c) Current Biology

The new evidence shows that the answer to that thought question is yes. Sorger’s team came up with a letter-encoding technique that requires almost no pre-training. Participants in their study voluntarily selected letters on a screen, which guided the letter encoding; for each specific character, participants were asked to perform a particular mental task for a set period of time. That produced 27 distinct brain patterns corresponding to each letter of the alphabet and the equivalent of a space bar, which could be automatically decoded in real-time using newly developed data analysis methods.

In each communication experiment, participants held a mini-conversation consisting of two open questions and answers. Everyone the researchers tested was able to successfully produce answers within a single one-hour session.

The results substantially extend earlier uses of fMRI, which allowed individuals to answer the equivalent of multiple-choice questions having four or fewer possible answers, by enabling free-letter spelling. That could make all the difference for people who are completely paralyzed and unable to benefit from other means of alternative communication, Sorger says.

Ultimately, she says their goal is to transfer the fMRI technology they’ve developed to a more portable and affordable method for measuring blood flow, such as functional near-infrared spectroscopy (fNIRS).

Source: medicalxpress.com

ScienceDaily (June 28, 2012) — Mayo Clinic researchers have successfully used smaller, folded DNA molecules to stimulate regeneration and repair of nerve coatings in mice that mimic multiple sclerosis (MS). They say the finding, published June 28 in the journal PLoS ONE, suggests new possible therapies for MS patients.

Laboratory mouse. (Credit: iStockphoto)

"The problem has been to find a way to encourage the nervous system to regenerate its own myelin (the coating on the nerves) so nerve cells can recover from an MS attack," says L. James Maher III, Ph.D., Mayo Clinic biochemist and senior author on the paper. "We show here that these small molecules, called aptamers, can stimulate repair in the mice we are studying."

More than 200,000 people have multiple sclerosis. There is no cure and no effective therapy to stop progression or repair damage to the myelin sheath that surrounds and protects the nerves. Without that protection, nerve fibers will be damaged, leading to declining mobility and cognitive function, and other debilitating complications.

MS researchers, including Mayo neurologist Moses Rodriguez, M.D., a co-author on this paper, have focused on monoclonal antibodies in mice to stimulate myelin repair. The Rodriguez and Maher teams, working together, have determined that the aptamers are not only effective, but they are easy and cheap to synthesize — an important point for drug developers. They also are stable and not likely to cause an immune response. This new approach must be validated in other mouse models to see if it might be a candidate for human clinical trials.

The monoclonal antibodies used in earlier research are large and complex, but were shown to promote both cell signaling and remyelination of central nervous system lesions in mice. The aptamers used in this study are less than one-tenth the size of antibodies and are single-strands of DNA containing only 40 nucleotide units.

Source: Science Daily

June 28, 2012

In a genome-wide association (GWA) study, researchers from Boston University Schools of Medicine (BUSM) and Public Health (BUSPH) have identified several genes which influence degeneration of the hippocampus, the part of the brain most associated with Alzheimer disease (AD). The study, which currently appears online as a Rapid Communication in the Annals of Neurology, demonstrates the efficacy of endophenotypes for broadening the understanding of the genetic basis of and pathways leading to AD.

AD is a progressive neurodegenerative disorder for which there are no prevention methods. Available drugs only marginally affect disease severity and progression, making AD effectively untreatable.

GWA studies using very large samples have increased the number of robust associations to 10 genes, including APOE. However, these genes account for no more than 35 percent of the inherited risk of AD and most of the genetic underpinning of the disorder remains unexplained. According to the researchers, magnetic resonance imaging (MRI) of the brain provides in vivo quantitative measures of neurodegenerative and cerebrovascular brain injury that may represent AD-related changes long before clinical symptoms appear. These measures are more powerful than comparisons of individuals with AD with cognitively healthy persons because they avoid misclassification of normal persons who will develop disease in the future.

BUSM researchers conducted a two-stage GWA study for quantitative measures of hippocampal volume (HV), total cerebral volume (TCV) and white matter hyperintensities (WMH). Brain MRI measures of HV, TCV and WMH were obtained from 981 Caucasian and 419 African-American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer’s Genetic Epidemiology) Study. In addition, similar MRI measures were obtained from 168 AD cases, 336 individuals with mild cognitive impairment and 188 controls (all Caucasian) in the AD Neuroimaging Initiative (ADNI) Study. The MIRAGE Caucasian families and ADNI subjects were included in the first stage and the MIRAGE African American families were added in stage two. Results from the two Caucasians data sets were combined by meta-analysis.

In stage two, one genetic marker (i.e. single nucleotide polymorphism or SNP) from each of the gene regions that were most significantly associated with AD in the Caucasian data sets was evaluated in the African-American data set.

Novel genome-wide significant associations were observed for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set.

"Our two-stage GWAS identified highly significant associations between a measure of degeneration in the brain region most strongly correlated with AD and several genes in both Caucasian and African American samples containing AD, cognitively impaired and cognitively healthy subjects. One of these associations was with the ε4 variant of APOE which is the most well-established genetic risk factor for AD.

Other associations were demonstrated with markers in F5/SELP, LHFP, and GCFC2, genes not previously implicated in this disease” explained senior author Lindsay Farrer, PhD, chief of biomedical genetics at BUSM. He also noted, “previous studies showed that blood level of P-selectin (the protein encoded by SELP) has been correlated with rate of cognitive decline in AD patients.”

Farrer believes it is very likely that the number and specificity of these associations will increase in future studies using larger samples and focused on additional precise structural and functional MRI measures. “These findings will inform experiments designed to increase our understanding of disease-causing mechanism and may lead to new therapeutics targets,” added Farrer.

Provided by Boston University Medical Center

Source: medicalxpress.com

June 28, 2012

In a process akin to belling an infinitesimal cat, scientists have managed to tag a protein that regulates the neurotransmitter serotonin with tiny fluorescent beads, allowing them to track the movements of single molecules for the first time.

This is a microphotograph of neurons with their serotonin transporter protein labeled with red quantum dots. Credit: Jerry Chang, Vanderbilt University

The capability, which took nearly a decade to achieve, makes it possible to study the dynamics of serotonin regulation at a new level of detail, which is important because of the key role that serotonin plays in the regulation of mood, appetite and sleep.

The achievement was reported by an interdisciplinary team of Vanderbilt scientists in the June 27 issue of the Journal of Neuroscience.

The regulatory protein that the scientists successfully tagged is known as the serotonin transporter. This is a protein that extends through the membrane that forms the nerve’s outer surface and acts like a nano-sized vacuum cleaner that sucks serotonin molecules into the cell body and away from serotonin target receptors on other cells. In this fashion it helps regulate the concentration of serotonin in the area around the cell. Serotonin transporters are an important research subject because they are the target for the most common drugs used to treat depression, including Prozac, Paxil and Lexapro.

"If you are interested in mental health, then serotonin transporters are an ideal subject," said Sandra Rosenthal, the Jack and Pamela Egan Chair of Chemistry, who directed the study with Randy Blakely, the Allan D. Bass Professor of Pharmacology and Psychiatry.

Problems with serotonin transporter regulation have also been implicated in autism. Two years ago, Blakely and geneticist James Sutcliffe, associate professor of molecular physiology and biophysics, reported the discovery of multiple changes in the serotonin transporter protein that cause the transporter to become “overactive” in subjects with autism. Recently, Blakely and Assistant Professor of Psychiatry Jeremy Veenstra-VanderWeele reported that mice expressing one of these high-functioning transporters exhibit multiple behavioral changes that resemble changes seen in kids with autism.

The brain’s other key neurotransmitters have their own transporter proteins, so scientists can use the capability to track the motion of individual transporter molecules to determine how they are regulated as well.

Attempts to understand how these transporters work have been limited by the difficulty of studying their dynamic behavior. “In the past, we have been limited to snapshots that show the location of transporter molecules at a specific time,” said chemistry graduate student Jerry Chang, who developed the tagging technique. “Now we can follow their motion on the surface of cells in real time and see how their movements relate to serotonin uptake activity.”

The fluorescent tags that the researchers used are nanoscale beads called quantum dots made from a mixture of cadmium and selenium. These beads are only slightly bigger than the proteins they are tagging: You would have to string 10,000 together to span the width of a human hair.

Quantum dots emit colored light when illuminated and have the useful property that small changes in their size cause them to glow in different colors. Team member Ian D. Tomlinson, assistant research professor of chemistry, developed a special molecular string that attaches to the quantum dot at one end and, on the other end, attaches to a drug derivative that binds exclusively with the serotonin transporter. When a mixture that contains these quantum dots is incubated with cultured nerve cells, the drug attaches to the transporter. As the protein moves around, it drags the quantum dot behind it like a child holding a balloon on a string. When the area is illuminated, the quantum dots show up in a microscope as colored points of light.

"Until now, neurobiologists have had to rely on extremely low resolution approaches where it takes the signals coming from thousands to millions of molecules to be detected," said Blakely, "We really had no idea exactly what we were going to see."

Putting their new procedure to use, the researchers looked at extensions of the nerve cell that are involved in secreting serotonin on the presumption that transporters would be localized there as well. From previous research, the investigators suspected that the transporters would be concentrated in cholesterol-rich parts of these extensions, termed rafts, although the level of resolution with standard approaches was inadequate to provide any clues as to what they were doing there.

The quantum dot studies demonstrated that there were two distinct populations of transporters in these areas: Those that can travel freely around the membrane and those that act as if they are unable to move. They found that the immobile transporters were located in the rafts. When they stimulated the cell to increase transporter activity, they were surprised at what happened. “We found that the transporters in the rafts began to move much faster whereas the motion of the other population didn’t change at all,” Rosenthal reported. Since the mobilized transporters do not leave the rafts, they appear to whizz around inside a confined compartment, as if released from chains that normally keep them subdued. These observations suggest it is likely that the two populations are controlled by different regulatory pathways.

"Now that we can watch transporter regulation actually happening, we should be able to figure out the identity of the anchoring proteins and the signals these proteins respond to that permit transporters to switch back and forth between low and high activity levels," said Blakely.

"Currently, antidepressant drugs must fully shut down the brain’s serotonin transporters to achieve a clinical benefit," the pharmacologist said. Such a manipulation can produce a number of unpleasant side-effects, such as nausea, weight gain, sexual problems, fatigue and drowsiness.

"By understanding the basic mechanisms that naturally turn serotonin transporter activity up and down, maybe we can develop medications that produce milder side-effects and have even greater efficacy," he said. "Our sights are also focused on transferring what we have learned with normal serotonin transporters to an understanding of the hyperactive transporters we have found in kids with autism.”

Provided by Vanderbilt University

Source: medicalxpress.com

June 28, 2012

(Medical Xpress) — New research has shed light on the high risk of fractures, falls, and osteoporosis among epilepsy patients using antiepileptic drugs with most patients unaware of the risks associated with taking the drugs.

The study led by the University of Melbourne and published in the prestigious Neurology journal, found that people taking antiepileptic drugs are up to four times more likely to suffer spine, collarbone and ankle fractures and are more likely to have been diagnosed with osteoporosis.

The study also revealed that these patients are more than four times as likely as non-users of antiepileptic drugs to have been diagnosed with osteoporosis.

In addition, treatment affected balance with results showing almost double the falls rate in female patients taking the medication compared with non-users.

Chief Investigator, Prof John Wark from the University of Melbourne’s Department of Medicine at the Royal Melbourne Hospital said this research revealed new information critical to understanding the higher risk for fractures and falls in epilepsy patients taking antiepileptic medication.

“We believe patients need to be offered better information to help them to avoid these risks and prevent injury,” he said.

More than 70 percent of epilepsy patients who participated in the study were unaware of the increased risk of fractures, decreased bone mineral density and falls associated with taking antiepileptic medications.

“No published studies have explored epilepsy patients’ awareness of the effects of AEDs on bone health, fracture risk and falls.  This study indicates that awareness of these issues is poor, despite our study population attending specialist epilepsy clinics at a centre with a major interest in this area,” said Prof Wark.

“Most patients indicated they would like to be better informed about these issues, suggesting that more effective education strategies are warranted and would be well-received.”

“Epilepsy patients should be assessed regularly for their history of falls and fractures for appropriate management strategies to be offered.”

The study compared 150 drug users with 506 non-users.  All drug users were epilepsy outpatients at the Royal Melbourne Hospital, over 15 years old and had been taking AEDs for a minimum of three months.

Provided by University of Melbourne

Source: medicalxpress.com

ScienceDaily (June 27, 2012) — Modern anesthesia is extremely safe. But as risks to heart, lungs and other organs have waned, another problem has emerged in the elderly: post-operative cognitive dysfunction. Mentally, some patients “just aren’t the same” for months or longer after surgery. Other factors play a role, but a small number of patients deteriorate mentally due to anesthesia per se. Those with Alzheimer’s disease suffer exacerbations, and those without the diagnosis may have it unmasked by anesthesia, suggesting some relationship.

Alzheimer’s disease has two types of brain lesions. Beta-amyloid deposits accumulate outside neurons but don’t cause cognitive problems. Neurofibrillary tangles inside neurons, composed of hyper-phosphorylated ‘tau’, a protein normally attached to microtubules, do correlate with dementia. These same tau tangles are found in post-anesthesia dementia.

Microtubules (MTs) polymerize from ‘tubulin’ proteins to grow, shape and regulate neurons. Synaptic components are transported by motor proteins which move like railroad trains along MT tracks. In branching dendrites, motors change MTs repeatedly to reach their destination. Tau is a traffic signal, telling motors where to get on and off, the route encoded in MT binding sites for tau.

That MTs process information stems from Charles Sherrington in the 1950s, with recent controversial suggestions of MT computing, and even quantum computing mediating consciousness and memory. But whether MTs play a primary, or mere supportive role, their stability and function are essential to cognition and consciousness.

Excessive phosphorylation had been thought the culprit in detaching tau and causing tangles. But destabilized MTs now appear to be the primary problem in both Alzheimer’s and post-anesthesia dementia, releasing tau which then becomes hyperphosphorylated. Anesthetics are known to bind to tubulin, in some cases for days after exposure, and in high doses to cause MT disassembly.

Now, in a study in PLoS ONE, a team from Canada, Portugal and the USA report molecular modeling showing 32 anesthetic binding sites per tubulin, with at least 1 percent (10 million) of the billion tubulins per brain neuron binding an anesthetic molecule at clinical concentration (1 ‘MAC’). Two particular anesthetic binding regions may destabilize MTs, one inactivating tubulin C-termini tails (which otherwise knit together neighboring tubulins). The other weakens side-to-side tubulin couplings, the critical link in MT lattices, but only at high anesthetic concentrations, or perhaps with other MT destabilizing factors (low temperature, low zinc, high calcium, acidosis).

Travis Craddock PhD, lead author on the study said: “The good news is that therapies aimed at microtubule stabilization may help in both Alzheimer’s and post-anesthetic dementias. Clinical trials are underway, or planned, for microtubule stabilizers Epothilone D, NAPVSIPQ, and the zinc ionophore PBT2, as well as brain ultrasound, shown in vitro to excite MT resonances and promote polymerization. However it’s done, ‘tightening the tubules’ may best treat dementia.”

Source: Science Daily

June 27th, 2012

Long-term aim is to develop new treatments to block the spread of damaged proteins in the brain.

Van Andel Institute announces that researchers at Lund University in Sweden have published a study detailing how Parkinson’s disease spreads through the brain. Experiments in rat models uncover a process previously used to explain mad cow disease, in which misfolded proteins travel from sick to healthy cells. This model has never before been identified so clearly in a living organism, and the breakthrough brings researchers one step closer to a disease-modifying drug for Parkinson’s.

“Parkinson’s is the second most common neurodegenerative disorder after Alzheimer’s disease,” said Patrik Brundin M.D., Ph.D., Jay Van Andel Endowed Chair in Parkinson’s Research at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University and senior author of the study. “A major unmet medical need is a therapy that slows disease progression. We aim to better understand how Parkinson’s pathology progresses and thereby uncover novel molecular targets for disease-modifying treatments.”

Previous research demonstrates that a misfolded protein known as alpha-synuclein protein gradually appears in healthy young neurons transplanted to the brains of Parkinson’s patients. This discovery gave rise to the group’s hypothesis of cell-to-cell protein transfer, which has since been demonstrated in laboratory experiments.

In the current study, published this week in the Public Library of Science (PLoS ONE), researchers for the first time were able to follow events in the recipient cell as it accepts the diseased protein by allowing it to pass its outer cell membrane. The experiments also show how the transferred proteins attract proteins in the host cell leading to abnormal folding or “clumping” inside the cells.

Coronal section at the level of the gyrus diagonalis of a rat transplanted with VM tissue six weeks after AAV2/6-huαsyn injection and sacrificed four weeks after grafting. The immunohistochemical analysis with antibodies directed against huαsyn shows the overexpression of this protein in the axon terminals of the right striatum. The center of the bilateral grafts is marked with an asterisk. On the right, the graft is clearly located in the area devoid of signal. The image and description were adapted from a PLoS ONE research paper image credited at the end of this article. doi:10.1371/journal.pone.0039465.g001

“This is a cellular process likely to lead to the disease process as Parkinson’s progresses, and it spreads to an increasing number of brain regions as the patient gets sicker,” said Elodie Angot, Ph.D., of Lund University’s Neuronal Survival Unit, and lead co-author of the study.

“In our experiments, we show a core of unhealthy human alpha-synuclein protein surrounded by alpha-synuclein produced by the rat itself. This indicates that this misfolded protein not only moves between cells but also acts as a “seed” attracting proteins produced by the rat’s brain cells,” said Jennifer Steiner, Ph.D., of Lund University and Van Andel Institute’s Center for Neurodegenerative Science, the study’s other lead author.

These findings are consistent with results from previous laboratory cell models and for the first time extend this observation into a living organism. However, it remains unclear exactly how alpha-synuclein gains access from the extracellular space to the cytoplasm of cells to act as a template for naturally occurring alpha-synuclein, causing the naturally-occurring protein to, in turn, misfold. Further studies are needed to clarify this important step in the process.

The discovery does not reveal the root of Parkinson’s disease, but in conjunction with disease models developed by Lund University researchers and others, could enable scientists to develop new drug targets aimed at mitigating or slowing the effects of the disease, which currently strikes more than 1% of people over the age of 65.

Source: Neuroscience News