Posts tagged neuroscience

ScienceDaily (July 2, 2012) — Using an in vitro cell model of Huntington’s disease (HD), researchers at Florida Atlantic University’s Charles E. Schmidt College of Medicine have discovered a novel mechanism and potential link between mutant huntingtin, cell loss and cell death or apoptosis in the brain, which is responsible for the devastating effects of this disease. Apoptosis has been proposed as one of the mechanisms leading to neuronal death in HD.

Dr. Jianning Wei, Ph.D., assistant professor of biomedical science in the Schmidt College of Medicine, has received a $428,694 grant from the National Institutes of Health (NIH) for a project titled “Regulation of BimEL phosphorylation in the pathogenesis of Huntington’s disease.” With this grant, she will further her research and investigation of the molecular and physiological functions of BimEL, a protein known to promote cell death, in a rodent HD model to better understand the pathogenesis of this disease and develop treatments and therapies to prevent or slow down its progression. Wei’s previous findings may also represent a universal mechanism in the pathogenesis of neurodegenerative diseases that are involved with protein misfolding and aggregation — a phenomenon that occurs in many highly debilitating disorders including neurodegenerative diseases.

HD is a fatal, inherited disease caused by abnormal repeats of a small segment in an individual’s DNA or genetic code. The production of malfunctioning proteins in the body are results of this mutation, and the more repeat the protein contains, the worse the disease. A person who has the disease carries one normal copy of the gene and one mutated copy in his or her cells. Although the mutated forms of these genes are known for their devastating effects, their normal forms are critical for nerve function, embryonic development and other bodily processes. Similar mutations in other proteins are involved in several other neurodegenerative diseases.

"HD is a highly complex genetic, neurological disorder that causes certain nerve cells in the brain to waste away, and the underlying molecular mechanism of this disease still remains elusive," said Wei. "We are continuing our research to identify the pathways in the brain that are altered in response to mutant proteins, as well as to understand the cellular processes impacted by the disease in order to facilitate the development of effective pharmacological interventions."

Named after American physician George Huntington, HD is characterized by a selective loss of neurons in the brain and affects the basal ganglia, which controls motor control, cognition, learning and emotions. It also affects the outer surface of the brain or the cortex, which controls thought, perception, and memory. It is estimated that more than 250,000 Americans have HD or are at risk of inheriting the disease from an affected parent.

"The vital research that Dr. Wei and her colleagues are conducting at Florida Atlantic University will help to shed light on a very devastating and difficult disease for which there are currently no treatments available to stop or reverse its course," said Dr. David J. Bjorkman, M.D., M.S.P.H., dean of FAU’s Charles E. Schmidt College of Medicine.

Source: Science Daily

ScienceDaily (July 2, 2012) — Research published July 2 in Biomed Central’s open access journal Journal of Neuroinflammation suggests that chronic inflammation can predispose the brain to develop Alzheimer’s disease.

To date it has been difficult to pin down the role of inflammation in Alzheimer’s disease (AD), especially because trials of NSAIDs appeared to have conflicting results. Although the ADAPT (The Alzheimer`s Disease Anti-inflammatory Prevention Trial) trial was stopped early, recent results suggest that NSAIDs can help people with early stages of AD but that prolonged treatment is necessary to see benefit.

Researchers from the University of Zurich, in collaboration with colleagues from the ETH Zurich and University of Bern investigated what impact immune system challenges (similar to having a severe viral infection) would have on the development of AD in mice. Results showed that a single infection before birth (during late gestation) was enough to induce long-term neurological changes and significant memory problems at old age.

These mice had a persistent increase in inflammatory cytokines, increased levels of amyloid precursor protein (APP), and altered cellular localization of Tau. If this immune system challenge was repeated during adulthood the effect was strongly exacerbated, resulting in changes similar to those seen for pathological aging.

Dr Irene Knuesel who led this research explained, “The AD-like changes within the brain of these mice occurred without an increase in amyloid β (Aβ). However, in mice genetically modified to produce the human version of Aβ, the viral-like challenge drastically increased the amount of Aβ at precisely the sites of inflammation-induced APP deposits. Based on the similarity between these APP/AƒÒ aggregates in mice and those found in human AD, it seems likely that chronic inflammation due to infection could be an early event in the development of AD.

Source: Science Daily

ScienceDaily (July 2, 2012) — Growing evidence suggests that Parkinson’s disease (PD) often starts with non-motor symptoms that precede diagnosis by several years. In the first study to examine patterns in the quality of life of Parkinson’ disease patients prior to diagnosis, researchers have documented declines in physical and mental health, pain, and emotional health beginning several years before the onset of the disease and continuing thereafter.

Their results are reported in the latest issue of Journal of Parkinson’s Disease.

"We observed a decline in physical function in PD patients relative to their healthy counterparts beginning three years prior to diagnosis in men and seven and a half years prior to diagnosis in women," says lead investigator Natalia Palacios, PhD, Department of Nutrition, Harvard School of Public Health. "The decline continues at a rate that is five to seven times faster than the average yearly decline caused by normal aging in individuals without the disease."

The study included 51,350 male health professionals enrolled in the Health Professionals Follow Up Study (HPFS) and 121,701 female registered nurses enrolled in the Nurses’ Health Study (NHS). In both ongoing studies, participants fill out biannual questionnaires about a variety of lifestyle characteristics and document the occurrence of major chronic disease. In the NHS study, questionnaires measured health-related quality of life in eight areas: physical functioning, role limitations due to physical problems, role limitations due to emotional problems, vitality, bodily pain, social functioning, mental health, and general health perceptions. In the HPFS, only physical functioning was assessed.

Researchers identified 454 men and 414 women with PD in the two cohorts. At 7.5 years prior to diagnosis, physical function among PD cases, in both men and women, was comparable to that in the overall cohort. A decline began approximately 3 years prior to diagnosis in men and approximately 7.5 years prior to diagnosis in women. Physical function continued to decline thereafter at a rate of 1.43 and 2.35 points per year in men and women, respectively. In comparison, the average yearly decline in individuals without PD was 0.23 in men and 0.42 in women. Other measures of quality of life, available only in women, declined in a similar pattern.

Dr. Palacios notes that a strength of the study is the availability of prospective data on both PD patients and a healthy comparison group, and the ability to chart the deterioration in functioning and quality of life over the whole study follow-up, which included many years prior to diagnosis.

"This result provides support to the notion that the pathological process leading to PD may start several years before PD diagnosis," says Dr. Palacios. "Our hope is that, with future research, biological markers of the disease process may be recognizable in this preclinical phase."

Source: Science Daily

ScienceDaily (July 2, 2012) — There was a time when a belief was widely held that premature neonates did not perceive pain. That, of course, has been refuted but measurements of neonate pain tend to rely on inexact measures, such as alertness and ability to react expressively to pain sensations. Researchers at Loma Linda University reported in The Journal of Pain that there is a significant relationship between procedural pain and detectable oxidative stress in neonates.

Previous studies have shown an approach involving measurement of systemic biochemical reactions to pain offers the benefit of providing an objective method for measuring pain in premature neonates. Exposure to painful procedures often results in reductions in oxygen saturations and tachycardia, but few studies have quantified the effects of increased pain oxygen consumption. No studies have examined the relationship between pain scores that reflect behavioral and physiological markers of pain and plasma markers of ATP utilization and oxidative stress.

In this study, 80 preterm neonates were evaluated. In about half, tape was taken off the skin following removal of catheters, and they were evaluated for oxidative stress by measuring uric acid and malondialdehyde (MDA) concentration in plasma before and after the procedure. These subjects were compared with a control group not experiencing tape removal. Pain scores were assessed using the Premature Infant Pain Profile. The data showed there was a significant relationship between procedural pain and MDA, which is a well accepted marker of oxidative stress.

There were increases in MDA in preterm neonates exposed to the single painful procedure and not in the control group. Since premature neonates undergo several painful procedures a day, the researchers concluded that if exposure to multiple painful procedures is shown to contribute to oxidative stress, biochemical markers might be useful in evaluating mechanism-based interventions that could decrease adverse effects of painful procedures.

Source: Science Daily

ScienceDaily (July 2, 2012) — While many small studies have shown a relationship between infertility and psychological distress, reporting a high prevalence of anxiety, mood disorders and depressive symptoms, few have studied the psychological effect of childlessness on a large population basis. Now, based on the largest cohort of women with fertility problems compiled to date, Danish investigators have shown that women who remained childless after their first investigation for infertility had more hospitalisations for psychiatric disorders than women who had at least one child following their investigation.

The results of the study were presented July 1 at the annual meeting of ESHRE (European Society of Human Reproduction and Embryology) by Dr Birgitte Baldur-Felskov, an epidemiologist from the Danish Cancer Research Center in Copenhagen.

Most studies of this kind have been based on single clinics and self-reported psychological effects. This study, however, was a nationwide follow-up of 98,737 Danish women investigated for infertility between 1973 and 2008, who were then cross-linked via Denmark’s population-based registries to the Danish Psychiatric Central Registry. This provided information on hospitalisations for psychiatric disorders, which were divided into an inclusive group of “all mental disorders,” and six discharge sub-groups which comprised “alcohol and intoxicant abuse,” “schizophrenia and psychoses,” “affective disorders including depression,” “anxiety, adjustment and obsessive compulsive disorder,” “eating disorders,” and “other mental disorders.”

All women were followed from the date of their initial fertility investigation until the date of psychiatric event, date of emigration, date of death, date of hospitalisation or 31st December 2008, whichever came first. Such studies, said Dr Baldur-Felskov, could only be possible in somewhere like Denmark, where each citizen has a personal identification number which can be linked to any or all of the country’s diagnostic registries.

Results of the study showed that, over an average follow-up time of 12.6 years (representing 1,248,243 woman-years), 54% of the 98,737 women in the cohort did have a baby. Almost 5000 women from the entire cohort were hospitalised for a psychiatric disorder, the most common discharge diagnosis being “anxiety, adjustment and obsessive compulsive disorders” followed by “affective disorders including depression.”

However, those women who remained childless after their initial fertility investigation had a statistically significant (18%) higher risk of hospitalisations for all mental disorders than the women who went on to have a baby; the risk was also significantly greater for alcohol/substance abuse (by 103%), schizophrenia (by 47%) and other mental disorders (by 43%). The study also showed that childlessness increased the risk of eating disorders by 47%, although this was not statistically significant.

However, the most commonly seen discharge diagnosis in the entire cohort (anxiety, adjustment and obsessive compulsive disorders) was not affected by fertility status.

Commenting on the study’s results, Dr Baldur-Felskov said: “Our study showed that women who remained childless after fertility evaluation had an 18% higher risk of all mental disorders than the women who did have at least one baby. These higher risks were evident in alcohol and substance abuse, schizophrenia and eating disorders, although appeared lower in affective disorders including depression.

"The results suggest that failure to succeed after presenting for fertility investigation may be an important risk modifier for psychiatric disorders. This adds an important component to the counselling of women being investigated and treated for infertility. Specialists and other healthcare personnel working with infertile patients should also be sensitive to the potential for psychiatric disorders among this patient group."

Source: Science Daily

ScienceDaily (July 2, 2012) — As each day passes, the pace of life seems to accelerate — demands on productivity continue ever upward and there is hardly ever a moment when we aren’t, in some way, in touch with our family, friends, or coworkers. While moments for reflection may be hard to come by, a new article suggests that the long-lost art of introspection — even daydreaming — may be an increasingly valuable part of life.

The long-lost art of introspection — even daydreaming — may be an increasingly valuable part of life. (Credit: © HaywireMedia / Fotolia)

In the article, published in the July issue of Perspectives on Psychological Science, a journal of the Association for Psychological Science, psychological scientist Mary Helen Immordino-Yang and colleagues survey the existing scientific literature from neuroscience and psychological science, exploring what it means when our brains are ‘at rest.’

In recent years, researchers have explored the idea of rest by looking at the so-called ‘default mode’ network of the brain, a network that is noticeably active when we are resting and focused inward. Findings from these studies suggest that individual differences in brain activity during rest are correlated with components of socioemotional functioning, such as self-awareness and moral judgment, as well as different aspects of learning and memory. Immordino-Yang and her colleagues believe that research on the brain at rest can yield important insights into the importance of reflection and quiet time for learning.

"We focus on the outside world in education and don’t look much at inwardly focused reflective skills and attentions, but inward focus impacts the way we build memories, make meaning and transfer that learning into new contexts," says Immordino-Yang, a professor of education, psychology and neuroscience at the University of Southern California. "What are we doing in schools to support kids turning inward?"

Accumulated research suggests that the networks that underlie a focus inward versus outward likely are interdependent, and our ability to regulate and move between them probably improves with maturity and practice. While outward attention is essential for carrying out tasks and learning from classroom lessons, for example, the reflection and consolidation that may accompany mind wandering is equally important, fostering healthy development and learning in the longer term.

"Balance is needed between outward and inward attention, since time spent mind wandering, reflecting and imagining may also improve the quality of outward attention that kids can sustain," says Immordino-Yang.

She and her colleagues argue that mindful introspection can become an effective part of the classroom curriculum, providing students with the skills they need to engage in constructive internal processing and productive reflection. Research indicates that when children are given the time and skills necessary for reflecting, they often become more motivated, less anxious, perform better on tests, and plan more effectively for the future.

And mindful reflection is not just important in an academic context — it’s also essential to our ability to make meaning of the world around us. Inward attention is an important contributor to the development of moral thinking and reasoning and is linked with overall socioemotional well-being.

Immordino-Yang and her colleagues worry that the high attention demands of fast-paced urban and digital environments may be systematically undermining opportunities for young people to look inward and reflect, and that this could have negative effects on their psychological development. This is especially true in an age when social media seems to be a constant presence in teens’ day-to-day lives.

"Consistently imposing overly high-attention demands on children, either in school, through entertainment, or through living conditions, may rob them of opportunities to advance from thinking about ‘what happened’ or ‘how to do this’ to constructing knowledge about ‘what this means for the world and for the way I live my life,’ " Immordino-Yang writes.

According to the authors, perhaps the most important conclusion to be drawn from research on the brain at rest is the fact that all rest is not idleness. While some might be inclined to view rest as a wasted opportunity for productivity, the authors suggest that constructive internal reflection is critical for learning from past experiences and appreciating their value for future choices, allowing us to understand and manage ourselves in the social world.

Source: Science Daily

ScienceDaily (July 2, 2012) — Researchers at Moffitt Cancer Center working with colleagues at three other institutions have validated a link between a rare genetic variant and the risk of glioma, the most common and lethal type of brain tumor. The validation study also uncovered an association between the same rare genetic variant and improved rates of survival for patients with glioma.

The study, the first to confirm a rare susceptibility variant in glioma, appeared in a recent issue of the Journal of Medical Genetics, a journal published by the British Medical Association.

"Glioma is a poorly understood cancer with high morbidity and devastating outcomes," said study lead author Kathleen M. Egan, Sc.D., interim program leader of Cancer Epidemiology and vice chair of the Department of Cancer Epidemiology. "However, the discovery of the association of the TP53 genetic variant rs78378222 with glioma provides new insights into these tumors and offers better prospects for identifying people at risk."

According to the authors, their study “genotyped’ the single nucleotide polymorphism (SNP, or “snip”) rs78378222 in TP53, an important tumor suppressor gene. The researchers said the SNP disrupts the TP53 signal and, because of its activity, has been linked to a variety of cancers. This study linked the presence of the rare form of rs78378222 to deadly glioma.

The researchers conducted a large, clinic-based, case-control study of individuals age 18 and older with a recent glioma diagnosis. A total of 566 glioma cases and 603 controls were genotyped for the rs78378222 variant.

Study results reveal that the odds of developing glioma were increased 3.5 times among the rare variant allele carriers. However, when researchers examined the impact of rs78378222 on survival, they found an approximately 50 percent reduction in death rates for those who were variant allele carriers.

"That the variant increased survival chances was an unexpected finding," Egan said. "It is tempting to speculate that the presence of the risk allele could direct tumor development into a less aggressive path."

The researchers concluded that their study results “may shed light on the etiology and progression of these tumors.”

Source: Science Daily

ScienceDaily (July 2, 2012) — Researchers are closer to understanding the biology behind GHB, a transmitter substance in the brain, best known in its synthetic form as the illegal drug fantasy.

In the 1960s, gamma-hydroxybutyric acid (GHB) was first discovered as a naturally occurring substance in the brain. Since then it has been manufactured as a drug with a clinical application and has also developed a reputation as the illegal drug fantasy and as a date rape drug. Its physiological function is still unknown.

Now a team of researchers at the Department of Drug Design and Pharmacology at the University of Copenhagen has shown for the first time exactly where the transmitter substance binds in the brain under physiologically relevant conditions. The results have recently been published in the Proceedings of the National Academy of Sciences.

"We have discovered that GHB binds to a special protein in the brain — more specifically a GABA_A-receptor. The binding is strong even at very low dosage. This suggests that we have found the natural receptor, which opens new and exciting research opportunities, in that we have identified an important unknown that can provide the basis for a full explanation of the biological significance of the transmitter,” says Laura Friis Eghorn, PhD student.

Illegal use and possible antidote

Fantasy is also used as a so-called date rape drug, because in moderate amounts it has sedative, sexually stimulating and soporific effects. The compound is also abused for its euphoric effect, but in combination with alcohol, for example, it is a deadly cocktail that can lead to a state of deep unconsciousness or coma.

"GHB is registered for use as a drug to treat alcoholism and certain types of sleep disorders, but the risk of abuse presents difficulties. In the long-term, understanding how GHB works will enable us to develop new and better pharmaceuticals with a targeted effect in the brain, without the dangerous side-effects of fantasy," explains Laura Friis Eghorn, Department of Drug Design and Pharmacology.

Fantasy is an extremely toxic euphoriant, because the difference between a normal intoxicating dose and a fatal dose is so small. A better understanding of the biological mechanisms behind GHB-binding in the brain will benefit research into a life-saving antidote for this drug. Today there is no known antidote.

Statistics from Denmark in 2010 show that 8-10 percent of young people who frequent night clubs have had experience with Fantasy. However, since the drug is often also used in private for its sedative effect, it is difficult to estimate the extent of abuse.

Researchers on a targeted fishing expedition

The new research findings are the result of a collaboration between researchers at the University of Sydney in Australia and medicinal chemists at the Faculty of Health and Medical Sciences:

"Our chemist colleagues designed and produced special ligands — that are mimics of GHB in several variations. This enabled us to go on a targeted fishing expedition in the brain. We have slowly found our way to the receptor, which we have also been able to test pharmacologically. In itself, it is not unusual to find new receptors in the brain for known compounds. However, when we find a natural match rooted in the brain’s transmitter system, the biological implications are extremely interesting," explains Petrine Wellendorph, associate professor and head of the responsible research group that produced the pioneering results.

Source: Science Daily

July 2, 2012

The medication fingolimod reduced inflammatory lesion activity and reduced brain volume loss in patients with multiple sclerosis who participated in a two-year placebo-controlled clinical trial and were assessed by magnetic resonance imaging (MRI) measures, according to a report published Online First by Archives of Neurology.

Fingolimod is the first in a new class of drugs called the sphingosine 1-phosphate receptor (S1PR) modulators that was recently approved at 0.5 mg once daily for the treatment of relapsing multiple sclerosis (MS), a debilitating disease of the central nervous system, according to the study background.

The inflammatory pathology of MS can be seen by counting gadolinium (Gd)-enhancing lesions on T1-weighted images or new and enlarging T2 lesions on serial MRI scans. The extent of hyperintense areas on T2-weighted images provides an indication of the overall burden of disease, the study background explains.

The study by Ernst-Wilhelm Radue, M.D., of the Medical Image Analysis Center, University Hospital, Basel, Switzerland, and colleagues included 1,272 patients who were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial, a worldwide, multicenter effort. Patients received once-daily fingolimod capsules of 0.5 mg or 1.25 mg, or placebo.

"The anti-inflammatory effects of fingolimod therapy, as depicted by Gd-enhancing lesions and new/newly enlarged T2 lesions, were evident as early as 6 months after treatment initiation and were sustained over two years. Approximately half the patients receiving fingolimod therapy were free from any new inflammatory lesions throughout this 2-year study, compared with only 21 percent of patients receiving placebo," the authors comment.

Fingolimod, 0.5 mg (licensed dose), “significantly reduced” brain volume loss during the trial versus placebo, according to the study results. Brain atrophy is recognized as a useful way to monitor MS disease progression.

"These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution," the study concludes.

Provided by JAMA and Archives Journals

Source: medicalxpress.com

ScienceDaily (July 2, 2012) — Botulinum toxin may help prevent shaking or tremor in the arms and hands of people with multiple sclerosis (MS), according to new research published in the July 3, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.

"Treatments in use for tremor in MS are not sufficiently effective and new alternatives are needed," said study author Anneke van der Walt, MD, consultant neurologist at The Royal Melbourne Hospital and research fellow with the University of Melbourne in Australia.

For the study 23 people with MS were given botulinum toxin type A injections or a saline placebo for three months. Then they received the opposite treatment for the next three months. Scientists measured the tremor severity and their ability to write and draw before, during and after receiving the treatments. Video assessments were also taken every six weeks for six months.

The study found that people saw significant improvement in tremor severity, writing and drawing at six weeks and three months after the botulinum toxin treatment compared to after placebo. In tremor severity, the participants improved an average of two points on a 10-point scale, bringing their tremor from moderate to mild. In writing and drawing, participants improved by an average of one point on a 10-point scale.

"Our study suggests a new way to approach arm tremor related to MS where there are currently major treatment challenges and it also sets the framework for larger studies," said van der Walt.

Muscle weakness developed in 42 percent of people after treatment with botulinum toxin compared to six percent after placebo. The weakness was generally mild and went away within two weeks.

Source: Science Daily