Neuroscience

Month

June 2013

Enhanced White Blood Cells Heal Mice With MS-like Disease

Genetically engineered immune cells seem to promote healing in mice infected with a neurological disease similar to multiple sclerosis (MS), cleaning up lesions and allowing the mice to regain use of their legs and tails.

The new finding, by a team of University of Wisconsin School of Medicine and Public Health researchers, suggests that immune cells could be engineered to create a new type of treatment for people with MS. Currently, there are few good medications for MS, an autoimmune inflammatory disease that affects some 400,000 people in the United States, and none that reverse progress of the disease.

Dr. Michael Carrithers, assistant professor of neurology, led a team that created a specially designed macrophage – an immune cell whose name means “big eater.” Macrophages rush to the site of an injury or infection, to destroy bacteria and viruses and clear away damaged tissue. The research team added a human gene to the mouse immune cell, creating a macrophage that expressed a sodium channel called NaVI.5, which seems to enhance the cell’s immune response.

But because macrophages can also be part of the autoimmune response that damages the protective covering (myelin) of the nerves in people with MS, scientists weren’t sure whether the NaV1.5 macrophages would help or make the disease worse.

When the mice developed experimental autoimmune encephalomyelitis – the mouse version of MS — they found that the NaV1.5 macrophages sought out the lesions caused by the disease and promoted recovery.

“This finding was unexpected because we weren’t sure how much damage they would do, versus how much cleaning up they would do,” Carrithers says. “Some people thought the mice would get more ill, but we found that it protected them and they either had no disease or a very mild case.”

In follow-up experiments, regular mice that do not express the human gene were treated with the NaV1.5 macrophages after the onset of symptoms, which include weakness of the back and front limbs. The majority of these mice developed complete paralysis of their hindlimbs. Almost all of the mice that were treated with the Na1.5 macrophages regained the ability to walk. Mice treated with placebo solution or regular mouse macrophages that did not have NaV1.5 did not show any recovery or became more ill. In treated mice, the research team also found the NaV1.5 macrophages at the site of the lesions, and found smaller lesions and less damaged tissue in the treated mice.

Because the NaV1.5 variation is present in human immune cells, Carrithers says, “The questions are, ‘Why are these repair mechanisms deficient in patients with MS and what can we do to enhance them?’’’ He says the long-range goal is to develop the NaV1.5 enhanced macrophages as a treatment for people with MS.

The study is being published in the June issue of the Journal of Neuropathology and Experimental Neurology.

Jun 2, 201368 notes
#inflammatory diseases #immune cells #myelin #macrophages #neuroscience #science
Research Shows How Ritalin Affects Brains of Kids With ADHD

Ritalin activates specific areas of the brain in children with attention-deficit/hyperactivity disorder (ADHD), mimicking the brain activity of children without the condition, a new review says.

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"This suggests that Ritalin does bring the brain [of a child with ADHD] back to the brain the typically developing kid has," said study author Constance Moore, associate director of the translational center for comparative neuroimaging at the University of Massachusetts Medical School.

Analyzing data from earlier studies that looked at how children’s brains were affected by doing certain tasks that are sometimes challenging for kids with ADHD, the researchers found that Ritalin (methylphenidate) was having a visible impact on three areas of the brain known to be associated with ADHD: the cortex, the cerebellum and the basal ganglia.

The study could be helpful in diagnosing and treating children with ADHD, Moore said. “It may be helpful to know that in certain children, Ritalin is having a physiological effect in the areas of the brain involved with attention and impulse control,” she said.

The research was published recently in the Harvard Review of Psychiatry.

Nine studies analyzed by the researchers used functional MRI to evaluate brain changes after children had taken a single dose of Ritalin. The children were involved in different types of tasks that tested their ability to focus and inhibit an impulse to act.

For example, to observe the brain’s reaction during a test of what is called “inhibitory control,” a child was told that every time he saw a zero show up on a screen, he should push the button on the right; every time he saw an X appear, he should push the left button. The children would then be asked to flip their responses, pushing the left button when they saw a zero.

"That’s hard to do," Moore said, "because you’ve developed the habit [of pushing the other button], so you have to suppress your impulse. If you do 20 zeros and keep pressing and then you see an X, most kids with ADHD will hit the wrong button."

In three out of five of the inhibitory control studies, Ritalin at least partially normalized brain activation in ADHD children.

To note how the brain reacted to a selective attention test, Moore said, children would first be asked, for example, what word they were seeing. The word would be “red,” and the color of the type also would be red. Then they would be shown the word “red,” but the color of the type would be green. In several studies, Ritalin affected activation in the frontal lobes during such inhibitory control tasks.

Most of the studies included in the review were performed in the United States or the United Kingdom. The majority of participants were adolescent boys, and all studies compared their results to healthy children of the same approximate age.

Because none of the studies looked at the correlation between ADHD symptoms and whether the child was taking Ritalin, there is no way to link the changes in brain activation with clinical improvement, Moore said. “It’s possible that kids who are not responsive to Ritalin may have brain changes too,” she said.

ADHD affects between 3 percent and 7 percent of school-aged children in the United States, according to the American Psychiatric Association. Boys are more likely to have ADHD than girls.

One expert was not surprised by the results.

"The review article shows there is a consensus of well-designed imaging studies showing that [Ritalin] has an impact on the frontal cortex of the brain, where we have long believed these patients have issues," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at the Steven & Alexandra Cohen Children’s Medical Center of New York, in New Hyde Park. Adesman wondered if Ritalin may play a role in helping the brain mature.

"Their data provides partial support for that," he said. "But if anything, the medicine seems to help the brain look more normal and doesn’t seem to do anything bad to it."

Jun 1, 2013168 notes
#ADHD #ritalin #brain activity #neuroimaging #methylphenidate #cortex #neuroscience #science
Jun 1, 2013206 notes
#science #circadian rhythms #immune system #intestinal infections #salmonella #medicine #neuroscience
Exposure to general anaesthesia could increase the risk of dementia in elderly by 35 percent

Exposure to general anaesthesia increases the risk of dementia in the elderly by 35%, says new research presented at Euroanaesthesia, the annual congress of the European Society of Anaesthesiology (ESA). The research is by Dr Francois Sztark, INSERM and University of Bordeaux, France, and colleagues.

Postoperative cognitive dysfunction, or POCD, could be associated with dementia several years later. POCD is a common complication in elderly patients after major surgery. It has been proposed that there is an association between POCD and the development of dementia due to a common pathological mechanism through the amyloid β peptide. Several experimental studies suggest that some anaesthetics could promote inflammation of neural tissues leading to POCD and/or Alzheimer’s disease (AD) precursors including β-amyloid plaques and neurofibrillary tangles. But it remains uncertain whether POCD can be a precursor of dementia.

In this new study, the researchers analysed the risk of dementia associated with anaesthesia within a prospective population-based cohort of elderly patients (aged 65 years and over). The team used data from the Three-City study, designed to assess the risk of dementia and cognitive decline due to vascular risk factors. Between 1999 and 2001, the 3C study included 9294 community-dwelling French people aged 65 years and over in three French cities (Bordeaux, Dijon and Montpellier).

Participants aged 65 years and over were interviewed at baseline and subsequently 2, 4, 7 and 10 years after. Each examination included a complete cognitive evaluation with systematic screening of dementia. From the 2-year follow-up, 7008 non-demented participants were asked at each follow-up whether they have had a history of anaesthesia (general anaesthesia (GA) or local/locoregional anaesthesia (LRA)) since the last follow-up. The data were adjusted to take account of potential confounders such as socioeconomic status and comorbidities.

The mean age of participants was 75 years and 62% were women. At the 2-year follow-up, 33% of the participants (n=2309) reported an anaesthesia over the 2 previous years, with 19% (n=1333) reporting a GA and 14% (n=948) a LRA. A total of 632 (9%) participants developed dementia over the 8 subsequent years of follow-up, among them 284 probable AD and 228 possible AD, and the remaining 120 non-Alzheimer’s dementia. The researchers found that demented patients were more likely to have received anaesthesia (37%) than non-demented patients (32%). This difference in anaesthesia was due to difference in numbers receiving general anaesthetics, with 22% of demented patients reporting a GA compared with 19% of non-demented patients. After adjustment, participants with at least one GA over the follow-up had a 35% increased risk of developing a dementia compared with participants without anaesthesia.

Dr Sztark concludes: “These results are in favour of an increased risk for dementia several years after general anaesthesia. Recognition of POCD is essential in the perioperative management of elderly patients. A long-term follow-up of these patients should be planned.”

Jun 1, 201364 notes
#anaesthesia #dementia #amyloid plaques #cognitive decline #socioeconomic status #neuroscience #science
Are men better than women at acoustic size judgments?

Scientists from the University of Sussex have revealed that men are significantly better than women at using speech ‘formants’ to compare the apparent size of the source. Formants are important phonetic elements of human speech that are used by mammals to assess the body size of potential mates and rivals. This research is the first to indicate that formant perception may have evolved through sexual selection.

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Dr. Benjamin D. Charlton and his team tested 18 males and 37 females, aged between 17 and 20 years. Participants heard 60 unique stimulus pairs with different formants, representing two different animals, and their task was to decide which one sounded ‘larger’. Researchers tested the ability of listeners to detect small differences in apparent size across a wide range of formants which encompassed the range of the human speaking voice.

Speech formants, which give us our particular vowel sounds, are based on the length of the vocal tract, and thus relate directly to body size. But whereas men appear to use formants to judge the physical dominance of potential rivals, formants are not consistently found to predict how women rate the attractiveness of men’s voices. Women have been found to be more reliant on voice pitch rather than formants when rating how attractive they find a male voice.

The researchers conclude that the sex differences they report could be either innate or acquired or both. Hence, while they are compatible with the hypothesis that males rely on size assessment more than females, they do not conclusively demonstrate that these abilities arose through sexual selection. For example, it is possible that males learn this skill because this information is more important to them during their everyday social interactions. There may also be key differences across cultures, particularly in societies where gender roles differ markedly. Thus, they look forward to future studies examining the effects of training and personality as well as social and cultural factors.

Jun 1, 201355 notes
#sex differences #formants #formant perception #speech #vowel sounds #psychology #neuroscience #science
How disease mutations affect the Parkin protein

Researchers at the MRC Laboratory of Molecular Biology in the United Kingdom have determined the crystal structure of Parkin, a protein found in cells that when mutated can lead to a hereditary form of Parkinson’s disease. The results, which are published in The EMBO Journal, define the position of many of the mutations linked to hereditary Parkinson’s disease and explain how these alterations may affect the stability and function of the protein. The findings may in time reveal how the activity of Parkin is affected in patients with this rare but debilitating type of Parkinson’s disease.

Parkinson’s disease is a progressive neurodegenerative disease that affects more than seven million people worldwide. Most cases of the disease occur in older individuals and are sporadic (non-familial), but around 15% of patients develop symptoms early in life because of inherited mutations in a limited number of disease genes. Why Parkin mutations are especially detrimental in nerve cells is not fully understood, but previous research indicates that Parkin regulates the function of mitochondria, the organelles that generate energy in the cell. Some disease mutations in the PARKIN gene can be easily explained since they lead to loss or instability of the Parkin protein, but many others are more difficult to understand.

Around 50% of cases of familial recessive Parkinson’s disease are caused by mutations in the PARKIN gene, which encodes a protein that belongs to the RBR ubiquitin ligase enzyme family. Enzymes in this family couple other proteins in the cell to a molecule called ubiquitin, a step that can alter the function or stability of these target proteins. To understand how Parkin and other RBR ubiquitin ligase enzymes achieve this, EMBO Young Investigator David Komander and his coworker Tobias Wauer crystallized a form of human Parkin and used X-ray diffraction patterns to determine how the Parkin protein chain folds into a three-dimensional structure. Their experiments revealed an in-built control mechanism for Parkin activity, which is lost in the presence of some of the mutations responsible for Parkinson’s disease. Wauer and Komander pinpointed amino acids of Parkin with key functions in ubiquitin ligase activity that are sensitive to blocking by reagents previously characterized in their laboratory. “This sensitivity to inhibitors that were developed for a very different class of enzymes is particularly exciting,” Komander remarked. “We could also show that these inhibitors affect related RBR ubiquitin ligases such as HOIP, which is important for inflammatory immune responses.”

The crystal structure of Parkin is already revealing some of the secrets of this molecule, which under the right conditions can protect cells from the damage that arises during Parkinson’s disease. “In time the structure may also allow development of other compounds that alter Parkin activity, which could serve as ways to limit the progression and impact of Parkinson’s disease,” concluded Komander.

Jun 1, 201332 notes
#parkinson’s disease #parkin gene #neurodegeneration #genetics #neuroscience #science
Jun 1, 2013310 notes
#avatar therapy #schizophrenia #auditory hallucinations #psychology #neuroscience #science
Jun 1, 2013144 notes
#science #schizophrenia #genetics #DISC1 gene #lead exposure #glutamate #neuroscience

May 2013

Gene sequencing project finds new mutations to blame for a majority of brain tumor subtype

The St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project has identified mutations responsible for more than half of a subtype of childhood brain tumor that takes a high toll on patients. Researchers also found evidence the tumors are susceptible to drugs already in development.

The study focused on a family of brain tumors known as low-grade gliomas (LGGs). These slow-growing cancers are found in about 700 children annually in the U.S., making them the most common childhood tumors of the brain and spinal cord. For patients whose tumors cannot be surgically removed, the long-term outlook remains bleak due to complications from the disease and its ongoing treatment. Nationwide, surgery alone cures only about one-third of patients.

Using whole genome sequencing, researchers identified genetic alterations in two genes that occurred almost exclusively in a subtype of LGG termed diffuse LGG. This subtype cannot be cured surgically because the tumor cells invade the healthy brain. Together, the mutations accounted for 53 percent of the diffuse LGG in this study. Researchers also demonstrated that one of the mutations, which had not previously been linked to brain tumors, caused tumors when introduced into the glial brain cells of mice.

The findings appear in the April 14 advance online edition of the scientific journal Nature Genetics.

“This subtype of low-grade glioma can be a nasty chronic disease, yet prior to this study we knew almost nothing about its genetic alterations,” said David Ellison, M.D., Ph.D., chair of the St. Jude Department of Pathology and the study’s corresponding author. The first author is Jinghui Zhang, Ph.D., an associate member of the St. Jude Department of Computational Biology.

The Pediatric Cancer Genome Project is using next-generation whole genome sequencing to determine the complete normal and cancer genomes of children and adolescents with some of the least understood and most difficult to treat cancers. Scientists believe that studying differences in the 3 billion chemical bases that make up the human genome will provide the scientific foundation for the next generation of cancer care.

“We were surprised to find that many of these tumors could be traced to a single genetic alteration,” said co-author Richard K. Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis. “This is a major pathway through which low-grade gliomas develop and it provides new clues to explore as we search for better treatments.”

The study involved whole genome sequencing of 39 paired tumor and normal tissue samples from 38 children and adolescents with different subtypes of LGG and related tumors called low-grade glioneuronal tumors (LGGNTs). Although many cancers develop following multiple genetic abnormalities, 62 percent of the 39 tumors in this study stemmed from a single genetic alteration.

Previous studies have linked LGGs to abnormal activation of the MAPK/ERK pathway. The pathway is involved in regulating cell division and other processes that are often disrupted in cancer. Until now, however, the genetic alterations involved in driving this pathway were unknown for some types of LGG and LGGNT.

This study linked activation in the pathway to duplication of a key segment of the FGFR1 gene, which investigators discovered in brain tumors for the first time. The segment is called a tyrosine kinase domain. It functions like an on-off switch for several cell signaling pathways, including the MAPK/ERK pathway. Investigators also demonstrated that experimental drugs designed to block activity along two altered pathways worked in cells with theFGFR1 tyrosine kinase domain duplication. “The finding suggests a potential opportunity for using targeted therapies in patients whose tumors cannot be surgically removed,” Ellison said.

Researchers also showed that the FGFR1 abnormality triggered an aggressive brain tumor in glial cells from mice that lacked the tumor suppressor gene Trp53.

Whole-genome sequencing found previously undiscovered rearrangements in the MYB and MYBL1 genes in diffuse LGGs. These newly identified abnormalities were also implicated in switching on the MAPK/ERK pathway.

Researchers checked an additional 100 LGGs and LGGNTs for the same FGFR1, MYB and MYBL1 mutations. Overall, MYB was altered in 25 percent of the diffuse LGGs, and 24 percent had alterations in FGFR1. Researchers also turned up numerous other mutations that occurred in just a few tumors. The affected genes included BRAF, RAF1, H3F3A, ATRX, EP300, WHSC1 and CHD2.

“The Pediatric Cancer Genome Project has provided a remarkable opportunity to look at the genomic landscape of this disease and really put the alterations responsible on the map. We can now account for the genetic errors responsible for more than 90 percent of low-grade gliomas,” Ellison said. “The discovery that FGFR1 and MYB play a central role in childhood diffuse LGG also serves to distinguish the pediatric and adult forms of the disease.”

May 31, 201351 notes
#brain tumors #brain cells #genetic alterations #whole-genome sequencing #genetics #neuroscience #science
Healthy lifestyle choices mean fewer memory complaints

Research has shown that healthy behaviors are associated with a lower risk of Alzheimer’s disease and dementia, but less is known about the potential link between positive lifestyle choices and milder memory complaints, especially those that occur earlier in life and could be the first indicators of later problems.

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To examine the impact of these lifestyle choices on memory throughout adult life, UCLA researchers and the Gallup organization collaborated on a nationwide poll of more than 18,500 individuals between the ages of 18 and 99. Respondents were surveyed about both their memory and their health behaviors, including whether they smoked, how much they exercised and how healthy their diet was.

As the researchers expected, healthy eating, not smoking and exercising regularly were related to better self-perceived memory abilities for most adult groups. Reports of memory problems also increased with age. However, there were a few surprises.

Older adults (age 60–99) were more likely to report engaging in healthy behaviors than middle-aged (40–59) and younger adults (18–39), a finding that runs counter to the stereotype that aging is a time of dependence and decline. In addition, a higher-than-expected percentage of younger adults complained about their memory.

"These findings reinforce the importance of educating young and middle-aged individuals to take greater responsibility for their health — including memory — by practicing positive lifestyle behaviors earlier in life," said the study’s first author, Dr. Gary Small, director of the UCLA Longevity Center and a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA who holds the Parlow–Solomon Chair on Aging.

Published in the June issue of International Psychogeriatrics, the study may also provide a baseline for the future study of memory complaints in a wide range of adult age groups.

For the survey, Gallup pollsters conducted land-line and cell phone interviews with 18,552 adults in the U.S. The inclusion of cell phone–only households and Spanish-language interviews helped capture a representative 90 percent of the U.S. population, the researchers said.

"We found that the more healthy lifestyle behaviors were practiced, the less likely one was to complain about memory issues," said senior author Fernando Torres-Gil, a professor at UCLA’s Luskin School of Public Affairs and associate director of the UCLA Longevity Center.

In particular, the study found that respondents across all age groups who engaged in just one healthy behavior were 21 percent less likely to report memory problems than those who didn’t engage in any healthy behaviors. Those with two positive behaviors were 45 percent less likely to report problems, those with three were 75 percent less likely, and those with more than three were 111 percent less likely.

Interestingly, the poll found that healthy behaviors were more common among older adults than the other two age groups. Seventy percent of older adults engaged in at least one healthy behavior, compared with 61 percent of middle-aged individuals and 58 percent of younger respondents.

In addition, only 12 percent of older adults smoked, compared with 25 percent of young adults and 24 percent of middle-aged adults, and a higher percentage of older adults reported eating healthy the day before being interviewed (80 percent) and eating five or more daily servings of fruits and vegetables during the previous week (64 percent).

According to the researchers, older adults may participate in more healthy behaviors because they feel the consequences of unhealthy living and take the advice of their doctors to adopt healthier lifestyles. Or there simply could be fewer older adults with bad habits, since they may not live as long.

While 26 percent of older adults and 22 percent of middle-aged respondents reported memory issues, it was surprising to find that 14 percent of the younger group complained about their memory too, the researchers said.

"Memory issues were to be expected in the middle-aged and older groups, but not in younger people," Small said. "A better understanding and recognition of mild memory symptoms earlier in life may have the potential to help all ages."

Small said that, generally, memory issues in younger people may be different from those that plague older generations. Stress may play more of a role. He also noted that the ubiquity of technology — including the Internet, texting and wireless devices that can result in constant multi-tasking, especially with younger people — may impact attention span, making it harder to focus and remember.

Small noted that further study and polling may help tease out such memory-complaint differences. Either way, he said, the survey reinforces the importance, for all ages, of adopting a healthy lifestyle to help limit and forestall age-related cognitive decline and neurodegeneration.

The Gallup poll used in the study took place between December 2011 and January 2012 and was part of the Gallup–Healthways Well-Being Index, which includes health- and lifestyle-related polling questions. The five questions asked were: (1) Do you smoke? (2) Did you eat healthy all day yesterday? (3) In the last seven days, on how many days did you have five or more servings of vegetables and fruits? (4) In the last seven days, on how many days did you exercise for 30 minutes or more? (5) Do you have any problems with your memory? 

May 31, 2013105 notes
#memory #adults #lifestyle choices #memory problems #poll #psychology #neuroscience #science
Researchers Find Dying Cells Essential to Muscle Development and Repair

Dying cells play an unexpected and vital role in the creation of muscle fibers, researchers at the University of Virginia School of Medicine have determined. The finding could lead to new ways to battle conditions such as muscular dystrophy, facilitate healing after surgery and benefit athletes in their efforts to recover more quickly.

“These dead cells aren’t just a nuisance, which we’ve always considered them to be,” U.Va.’s Kodi S. Ravichandran said. “They have other, important roles before they leave this world.”

Dying cells have long been considered debris that must be removed from the body to avoid causing tissue inflammation. However, the U.Va. research shows that a small number of myoblasts – precursor cells that develop into muscle tissue – must die to allow muscle formation.

The finding suggests that programmed cell death, known as apoptosis, can also influence differentiation of other healthy cells within a tissue. The dying cells express a marker on their surface that signals their death and spurs the body to remove them; that same marker on these dying cells, the U.Va. researchers discovered, cues surrounding cells to develop into muscle fibers. The U.Va. researchers have identified both the membrane marker on the dying cells (a lipid normally hidden on live cells) and a corresponding receptor in the healthy myoblasts that are induced to fuse, said Ravichandran, chairman of the School of Medicine’s Department of Microbiology, Immunology and Cancer Biology.

“It’s been known for a while that there are a few muscle cells that die during exercise, and that building muscle mass depends on a few of those cells dying,” Ravichandran said. “This work puts an interesting spin on that.”

The discovery opens up many intriguing avenues for researchers to explore, including the possibility of producing muscle growth either through the direct application of apoptotic cells or by otherwise stimulating the cellular signaling pathways on the healthy cells. The genes encoding the receptor protein (called BAI1) and some of the components of the signaling pathway are found to be altered in patients with muscular dystrophy and other forms of muscle disorders.

“Because this pathway seems to be involved in muscle repair after injury, this could be relevant for recovery after surgeries, combat injuries in soldiers or any condition that could lead to muscle injury or muscle atrophy,” Ravichandran said. “Take Duchenne muscular dystrophy, for example. One in 3,500 boys that are born have this disease. If we can help alleviate the distress of even a few of these individuals, we would have made significant progress.”

The findings have been published online by the journal Nature and will appear in a forthcoming print edition (along with a News and Views highlighting the impact of the work).

May 31, 201372 notes
#dying cells #muscle cells #muscle tissue #muscular dystrophy #tissue inflammation #cell death #medicine #science
Immune system to fight brain tumours

Research at Lund University in Sweden gives hope that one of the most serious types of brain tumour, glioblastoma multiforme, could be fought by the patients’ own immune system. The tumours are difficult to remove with surgery because the tumour cells grow into the surrounding healthy brain tissue. A patient with the disease therefore does not usually survive much longer than a year after the discovery of the tumour.

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The team has tested different ways of stimulating the immune system, suppressed by the tumour, with a ‘vaccine’. The vaccine is based on tumour cells that have been genetically modified to start producing substances that activate the immune system. The modified tumour cells (irradiated so that they cannot divide and spread the disease) have been combined with other substances that form part of the body’s immune system.

The treatment has produced good results in animal experiments: 75 per cent of the rats that received the treatment were completely cured of their brain tumours.

“Human biology is more complicated, so we perhaps cannot expect such good results in patients. However, bearing in mind the poor prognosis patients receive today, all progress is important”, said doctoral student Sara Fritzell, part of the research group led by consultant Peter Siesjö.

She has previously tested combining the activation of the immune system with chemotherapy. When the chemotherapy was applied directly to the tumour site, the positive effects reinforced each other, and a huge 83 per cent of the mice survived.

“Our idea is in the future to give patients chemotherapy locally in conjunction with the operation to remove as much of the tumour as possible”, said Sara Fritzell.

Peter Siesjö is currently applying for permission to carry out a clinical study on stimulation of the immune system – with or without local chemotherapy – as a treatment for patients with glioblastoma multiforme.

May 31, 2013107 notes
#brain tumor #glioblastoma multiforme #immune system #vaccine #neuroscience #science
May 31, 201359 notes
#stroke #ischemic stroke #blood flow #blood vessels #tissue plasminogen activator #neuroscience #science
Ketamine Cousin Rapidly Lifts Depression Without Side Effects

GLYX-13, a molecular cousin to ketamine, induces similar antidepressant results without the street drug side effects, reported a study funded by the National Institute of Mental Health (NIMH) that was published last month in Neuropsychopharmacology.

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Caption: Neurons in a subsection of the adult rat hippocampus are stained with a monoclonal antibody (yellow) that enhances learning and memory. A portion of this antibody is where GLYX-13 came from. (Source: Dr. Joseph Moskal, Ph.D., Northwestern University)

Background

Major depression affects about 10 percent of the adult population and is the second leading cause of disability in U.S. adults, according to the World Health Organization. Despite the availability of several different classes of antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs), 30 to 40 percent of adults are unresponsive to these medications. Moreover, SSRIs typically take weeks to work, which increases the risk for suicide.

Enter NMDA (N-methyl-D-aspartate) receptor modulators. In the 1970s, researchers linked the receptors to learning and memory. Biotech and pharmaceutical companies in the 1980s attempted to apply chemical blockers to these receptors as a means to prevent stroke. But blocking these receptors led to the opposite effect——the rise of cardiovascular disease. Research in the field dampened until a glutamate receptor antagonist already approved for anesthesia, and known on the streets as “Special K”, ketamine, made headlines in the early 2000s. Human clinical studies demonstrated that ketamine can ward off major and bipolar depressive symptoms within 2 hours of administration and last for several days. Ketamine is fraught with serious side effects including excessive sleepiness, hallucinations, and substance abuse behavior.

“Ketamine lit the field back up,“ said Joseph Moskal, Ph.D., a molecular neurobiologist at Northwestern University and senior study author. “Our drug, GLYX-13, is very different. It does not block the receptor ion channel, which may account for why it doesn’t have the same side effects.”

Moskal’s journey with GLYX-13 came about from his earlier days as a Senior Staff Fellow in NIMH’s Intramural Research Program. While at NIMH, he created specific molecules, monoclonal antibodies, to use as new probes to understand pathways of learning and memory. Some of the antibodies he created were for NMDA receptors. When he moved to Northwestern University, Moskal converted the antibodies to small protein molecules. Comprised of only four amino acids, GLYX-13 is one of these molecules.

Previous electrophysiological and conditioning studies had suggested that GLYX-13, unlike ketamine, enhanced memory and learning in rats, particularly in the brain’s memory hub or hippocampus. GLYX-13 also produced analgesic effects. Using several rat behavioral and molecular experiments, Moskal’s research team tested four compounds: GLYX-13, an inactive, “scrambled” version of GLYX-13 that had its amino acids rearranged, ketamine, and the SSRI fluoxetine.

Results of the Study

GLYX-13 and ketamine produced rapid acting (1 hour) and long-lasting (24 hour) antidepressant-like effects in the rats. Fluoxetine, an SSRI that typically takes from 2–4 weeks to show efficacy in humans, did not produce a rapid antidepressant effect in this study. As expected, the scrambled GLYX-13 showed no antidepressant-like effects at all. The researchers observed none of the aforementioned side effects of ketamine in the GLYX-13–treated rats.

Protein studies indicated an increase in the hippocampus of the NMDA receptor NR2B and a receptor for the chemical messenger glutamate called AMPA. Electrophysiology studies in this brain region showed that GLYX-13 and ketamine promoted long-lasting signal transmission in neurons, known as long-term potentiation/synaptic plasticity. This phenomenon is essential in learning and memory. The researchers propose how GLYX-13 works: GLYX-13 triggers NR2B receptor activation that leads to intracellular calcium influx and the expression of AMPA, which then is responsible for increased communication between neurons.

These results are consistent with data from a recent Phase 2 clinical trial, in which a single administration of GLYX-13 produced statistically significant reductions in depression scores in patients who had failed treatment with current antidepressants. The reductions were evident within 24 hours and persisted for an average of 7 days. After a single dose of GLYX-13, the drug’s antidepressant efficacy nearly doubled that seen with most conventional antidepressants after 4–6 weeks of dosing. GLYX-13 was well tolerated and it did not produce any of the schizophrenia-like effects associated with other NMDA receptor modulating agents.

Significance

NMDA receptors need a molecule each of the amino acid chemical messengers glutamate and glycine to become activated. Moskal speculates that GLYX-13 either directly binds to the glycine site on the NMDA receptor or indirectly modulates how glycine works with the receptor. Resulting activation of more NMDA and AMPA receptors leads to an increase in memory, learning—and antidepressant effects. By contrast, ketamine only blocks the NMDA receptor, but also increases the activity of the AMPA receptor. Knowledge of these mechanisms could lead to the development of more effective antidepressants.

What’s next

GLYX-13 is now being tested in a Phase 2 repeated dose antidepressant trial, where Moskal and his colleagues at Naurex, Inc., a biotechnology company he founded, hope to find in humans the optimal dosing for the drug. They also want to see if this molecule, and others like it, regulate other NMDA receptor subtypes—there are over 20 of them—and whether it will work on other disorders, such as schizophrenia, attention-deficit hyperactivity disorder, and autism.

“One could call NMDA modulators such as GLYX-13 ‘comeback kids,’” said Moskal. “A toolkit that I developed in 1983 is now setting the stage in 2013 for the development of possible new therapeutics that may provide individuals suffering from depression with a valuable new treatment option.”

May 31, 2013285 notes
#depression #antidepressant drugs #ketamine #GLYX-13 #glutamate receptor #ion channel #neuroscience #science
Low Doses of THC Can Halt Brain Damage

Extremely low doses of marijuana’s psychoactive component protect brain before and after injury, says TAU researcher

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Though marijuana is a well-known recreational drug, extensive scientific research has been conducted on the therapeutic properties of marijuana in the last decade. Medical cannabis is often used by sufferers of chronic ailments, including cancer and post-traumatic stress disorder, to combat pain, insomnia, lack of appetite, and other symptoms.

Now Prof. Yosef Sarne of Tel Aviv University’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine says that the drug has neuroprotective qualities as well. He has found that extremely low doses of THC — the psychoactive component of marijuana — protects the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs. Brain damage can have consequences ranging from mild cognitive deficits to severe neurological damage.

Previous studies focused on injecting high doses of THC within a very short time frame — approximately 30 minutes — before or after injury. Prof. Sarne’s current research, published in the journals Behavioural Brain Research and Experimental Brain Research, demonstrates that even extremely low doses of THC — around 1,000 to 10,000 times less than that in a conventional marijuana cigarette — administered over a wide window of 1 to 7 days before or 1 to 3 days after injury can jumpstart biochemical processes which protect brain cells and preserve cognitive function over time.

This treatment, especially in light of the long time frame for administration and the low dosage, could be applicable to many cases of brain injury and be safer over time, Prof. Sarne says.

Conditioning the brain

While performing experiments on the biology of cannabis, Prof. Sarne and his fellow researchers discovered that low doses of the drug had a big impact on cell signalling, preventing cell death and promoting growth factors. This finding led to a series of experiments designed to test the neuroprotective ability of THC in response to various brain injuries.

In the lab, the researchers injected mice with a single low dose of THC either before or after exposing them to brain trauma. A control group of mice sustained brain injury but did not receive the THC treatment. When the mice were examined 3 to 7 weeks after initial injury, recipients of the THC treatment performed better in behavioral tests measuring learning and memory. Additionally, biochemical studies showed heightened amounts of neuroprotective chemicals in the treatment group compared to the control group.

The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers conclude. One explanation for this effect is pre- and post-conditioning, whereby the drug causes minute damage to the brain to build resistance and trigger protective measures in the face of much more severe injury, explains Prof. Sarne. The low dosage of THC is crucial to initiating this process without causing too much initial damage.

Preventative and long-term use

According to Prof. Sarne, there are several practical benefits to this treatment plan. Due to the long therapeutic time window, this treatment can be used not only to treat injury after the fact, but also to prevent injury that might occur in the future. For example, cardiopulmonary heart-lung machines used in open heart surgery carry the risk of interrupting the blood supply to the brain, and the drug can be delivered beforehand as a preventive measure. In addition, the low dosage makes it safe for regular use in patients at constant risk of brain injury, such as epileptics or people at a high risk of heart attack.

Prof. Sarne is now working in collaboration with Prof. Edith Hochhauser of the Rabin Medical Center to test the ability of low doses of THC to prevent damage to the heart. Preliminary results indicate that they will find the same protective phenomenon in relation to cardiac ischemia, in which the heart muscle receives insufficient blood flow.

May 31, 2013291 notes
#cannabis #brain injury #brain cells #brain damage #PTSD #neuroscience #science
May 31, 2013230 notes
#brain #brain activity #neuroimaging #neuromuscular system #vegetative state #neuroscience #science
May 31, 2013172 notes
#mammalian brain #diazepam #nerve cells #receptors #neurons #neuroscience #science
New treatment for stroke set to increase chances of recovery

University of Leicester researchers have contributed to a landmark study which has revealed a new way to treat strokes caused by bleeding inside the brain.

The study found that intensive blood pressure lowering in patients with intracerebral haemorrhage, the most serious type of stroke, reduced the risk of major disability and improved chances of recovery by as much as 20 per cent.

The study, which involved more than 2800 patients from 140 hospitals around the world, was announced today at the European Stroke Conference in London, and published in The New England Journal of Medicine.

Professor Thompson Robinson, Deputy Head of the University of Leicester’s Department of Cardiovascular Sciences, was the UK co-ordinator for the study and co-authored the paper.

The study was led by the George Institute for Global Health, in Sydney, Australia.

Professor Thompson Robinson said: “Stroke is the third most common cause of death in the UK and the most common adult cause of neurological disability. Approximately 1 million people are living with the consequences of stroke in the United Kingdom, a third with life-changing severe disability. Every year an estimated 152,000 people in the UK have a stroke and intracerebral haemorrhage - spontaneous bleeding within the brain most often due to hypertension - accounts for at least 10 per cent of all cases.

“Intracerebral haemorrhage kills about half of those affected within one month and leaves most survivors disabled, and to date there is no specific treatment for this type of stroke.

“The results of the study show that intensively reducing high blood pressure within 6 hours of onset of a bleeding-related stroke is safe, and results in a significant shift from being dead and dependent to being alive and independent after stroke. Because it involves treatment with already available blood pressure-lowering treatments, the results should be easy to implement in all hospitals and be of benefit to patients. It is important to reinforce that stroke is a medical emergency, and individuals who suspect that they may have had a stroke should dial 999 and seek urgent medical attention.

“Leicester has a long-standing interest in acute stroke and blood pressure research, and hosts the NIHR Trent Stroke Local Research Network. There are many opportunities for Leicester patients presenting with stroke to participate in research to improve outcomes for future patients with stroke.”

Professor Bruce Neal of The George Institute and The University of Sydney said the study challenges previous thought about blood pressure lowering in intracerebral haemorrhage.

He said: “The study findings will mean significant changes to guidelines for stroke management worldwide. They show that early intensive blood pressure lowering, using widely available therapies, can significantly improve the outcome of this illness.

“We hope to see hospital emergency departments around the world implement the new treatment as soon as possible. By lowering blood pressure, we can slow bleeding in the brain, reduce damage and enhance recovery.

“The study findings are tremendously exciting because they provide a safe and efficient treatment to improve the likelihood of a recovery without serious disability - a major concern for those who have experienced stroke.

“The only treatment option to date has been risky brain surgery, so this research is a very welcome advance.”

The study found patients who suffered an acute intracerebral haemorrhage and received the blood pressure lowering treatment were better off from both a physical and psychological perspective.

May 30, 201358 notes
#stroke #intracerebral haemorrhage #hypertension #blood pressure #neuroscience #science
A molecular chain reaction in Alzheimer’s disease

Researchers at Lund University in Sweden have identified the molecular mechanism behind the transformation of one of the components in Alzheimer’s disease. They identified the crucial step leading to formations that kill brain cells.

Alzheimer’s disease is associated with memory loss and personality changes. It is still not known what causes the onset of the disease, but once started it cannot be stopped. The accumulation of plaques in the brain is widely considered a hallmark of the disease. The key discovery identified the chemical reaction that causes the plaques to grow exponentially.

Amyloid beta, a protein fragment that occurs naturally in the fluid around the brain, is one of the building blocks of plaques. However, the processes leading from soluble amyloid beta to the form found in the plaques, known as amyloid fibril, have not been known. In the very early part of the process, two protein fragments can create a nucleus that then grows into a fibril.

In solution this is a slow process, but the rate can be enhanced on surfaces. The current study shows that fibrils present a catalytic surface where new nuclei form and this reaction increases the speed of the process. As soon as the first fibrils are formed, amyloid-beta fragments attach at its surface and form new fibrils that subsequently detach.

This process is thus self-perpetuating, and autocatalytic, and the more fibrils are present, the quicker the new ones are created, says Sara Snogerup Linse, Professor of Chemistry at Lund University and one of the researchers behind the study.

The findings also show that the chemical reaction on the fibril surface creates cell-killing formations. It is hoped that the research could lead to a new type of medication targeting early stages of the disease in the future.

The results have emerged from several years of laboratory work by Professor Snogerup Linse and her colleague in Lund, Erik Hellstrand, including development of extensive methods to obtain amyloid beta in highly pure form and to study its transformation in a highly reproducible manner. Additional methodology based on isotope labelling and spin filters was developed to monitor the surface catalysis and pin-point the origin of the forms that kill brain cells. The collaboration with the theoretical group and cell biologists at Cambridge University has been absolutely crucial for all the findings.

May 30, 201339 notes
#alzheimer’s disease #amyloid beta #amyloid fibril #brain cells #neuroscience #science
May 30, 201393 notes
#brain activity #ADHD #emotional memory #memory consolidation #neuroscience #science
Genetic Engineering Alters Mosquitoes’ Sense of Smell

In one of the first successful attempts at genetically engineering mosquitoes, HHMI researchers have altered the way the insects respond to odors, including the smell of humans and the insect repellant DEET. The research not only demonstrates that mosquitoes can be genetically altered using the latest research techniques, but paves the way to understanding why the insect is so attracted to humans, and how to block that attraction.

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“The time has come now to do genetics in these important disease-vector insects. I think our new work is a great example that you can do it,” says Leslie Vosshall, an HHMI investigator at The Rockefeller University who led the new research, published May 29, 2013 in the journal Nature.

In 2007, scientists announced the completion of the full genome sequence of Aedes aegypti, the mosquito that transmits dengue and yellow fever. A year later, when Vosshall became an HHMI investigator, she shifted the focus of her lab from Drosophila flies to mosquitoes with the specific goal of genetically engineering the insects. Studying mosquitoes appealed to her because of their importance as disease carriers, as well as their unique attraction to humans.

Vosshall’s first target: a gene called orco, which her lab had deleted in genetically engineered flies 10 years earlier. “We knew this gene was important for flies to be able to respond to the odors they respond to,” says Vosshall. “And we had some hints that mosquitoes interact with smells in their environment, so it was a good bet that something would interact with orco in mosquitoes.”

Vosshall’s team turned to a genetic engineering tool called zinc-finger nucleases to specifically mutate the orco gene in Aedes aegypti. They injected the targeted zinc-finger nucleases into mosquito embryos, waited for them to mature, identified mutant individuals, and generated mutant strains that allowed them to study the role of orco in mosquito biology. The engineered mosquitoes showed diminished activity in neurons linked to odor-sensing. Then, behavioral tests revealed more changes.

When given a choice between a human and any other animal, normal Aedes aegypti will reliably buzz toward the human. But the mosquitoes with orco mutations showed reduced preference for the smell of humans over guinea pigs, even in the presence of carbon dioxide, which is thought to help mosquitoes respond to human scent. “By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans,” says Vosshall. But they don’t yet know whether the confusion stems from an inability to sense a “bad” smell coming from the guinea pig, a “good” smell from the human, or both.

Next, the team tested whether the mosquitoes with orco mutations responded differently to DEET. When exposed to two human arms—one slathered in a solution containing 10 percent DEET, the active ingredient in many bug repellants, and the other untreated—the mosquitoes flew equally toward both arms, suggesting they couldn’t smell the DEET. But once they landed on the arms, they quickly flew away from the DEET-covered one. “This tells us that there are two totally different mechanisms that mosquitoes are using to sense DEET,” explains Vosshall. “One is what’s happening in the air, and the other only comes into action when the mosquito is touching the skin.” Such dual mechanisms had been discussed but had never been shown before.

Vosshall and her collaborators next want to study in more detail how the orco protein interacts with the mosquitoes’ odorant receptors to allow the insects to sense smells. “We want to know what it is about these mosquitoes that makes them so specialized for humans,” she says. “And if we can also provide insights into how existing repellants are working, then we can start having some ideas about what a next-generation repellant would look like.”

May 30, 201360 notes
#mosquitos #olfactory receptors #orco gene #smell #odors #genetics #neuroscience #science
May 30, 201364 notes
#ASD #autism #brain responses #language skills #social interaction #ERPs #neuroscience #science
May 30, 2013176 notes
#neuronal development #synapses #neocortex #plasticity #learning #psychology #neuroscience #science
May 30, 201375 notes
#TBI #brain injury #tau protein #oligomers #neurofibrillary tangles #nerve cells #neuroscience #science
May 30, 201380 notes
#science #alzheimer’s disease #memory loss #heparan sulphates #amyloid protein #neuroscience
Little less protein may be answer in neurodegenerative disorders

In some neurodegenerative diseases, and specifically in a devastating inherited condition called spinocerebellar ataxia 1 (SCA1), the answer may not be an “all-or-nothing,” said a collaboration of researchers from Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and the University of Minnesota in a report that appears online in the journal Nature. The problem might be solved with just a little less.

"If you can only decrease the levels of ataxin-1 (the protein involved in SCA1) by 20 percent, you can reduce many symptoms of the disease," said Dr. Huda Zoghbi, professor of molecular and human genetics and pediatrics at BCM and director of the Neurological Research Institute. She is also a Howard Hughes Medical Institute Investigator.

Her long-time colleague Dr. Harry Orr, director of the University of Minnesota Institute for Translational Neuroscience, echoed that sentiment: “Perhaps, if you decrease the levels of the protein, you will decrease the severity of the disease.” In this report, the laboratories of Zoghbi, Dr. Juan Botas, also of BCM and the Neurological Researcher Institute, Dr. Thomas Westbrook, assistant professor of molecular and human genetics at BCM, and Orr identified a molecular pathway in the cell (RAS/MAPK/MSK1) with components that can be modulated slightly to reduce the levels of defective ataxin-1, the protein that causes disease in patients with the disorder.

Spinocerebellar ataxia 1 occurs when the ataxin-1 gene is mutated, with three letters of the DNA alphabet repeating many, many times. The abnormal protein that results cannot fold correctly and piles up in the cell, eventually killing it. As with many neurodegenerative disorders, the process can take over a decade. A person usually does not develop symptoms of this form of ataxia until he or she is 30 years old or older. The person develops gait problems, eventually loses the ability to speak and function and dies. Zoghbi and Orr teamed to find the gene associated with the disorder in 1993. Their work on the disease has spanned 20 years.

Totally eliminating the protein would not work. Mice that lack the gene have problems with learning and memory, indicating that ataxin-1 plays a role in those activities. Reducing the levels of ataxin-1 does not cure the disease, but it can significantly delay onset.

A Collaborative Innovation Award from the Howard Hughes Medical Institute enabled Zoghbi to put together the team that could screen for the genes or the gene pathway that could be manipulated to result in less ataxin-1.

"Harry and I had studied the disease and we had animal models. Botas, professor of molecular and human genetics at BCM, had a fruit fly model and Dr. Westbrook had a nice technology that enabled us to monitor ataxin-1 levels."

They began with a screen for genes that could affect the levels of ataxin-1 produced in the cell, said Dr. Ismail Al-Ramahi, a postdoctoral fellow in the lab of Botas. Dr. Jeehye Park, a post-doctoral fellow in Zoghbi’s laboratory, and Al-Ramahi are co-first authors of the report. Park and her colleagues carried out the screen in human cell lines and Al-Ramahi and his colleagues carried out the screen in fruit flies (Drosophila melanogaster).

The screen in human cells focused on forms of enzymes called kinases because they are susceptible to the effects of drugs. Using a special technique called RNA silencing, they targeted each known human kinase. At the same, Botas and Al-Ramahi screened kinase genes in fruit flies with a form of SCA1. When the two laboratories compared results, they found 10 genes in common that when inhibited could reduce the levels of ataxin-1 as well as the toxicity associated with it. The genes were part of the RAS/MAPK/MSKI signaling cascade within the cell.

Then the researchers focused on one protein in this pathway called MSK1 and found that when its levels were decreased in mice that were laboratory models of SCA1, the levels of ataxin-1 dropped and the animals improved. That was the final experiment that proved that reducing levels of the protein could stave off the disease.

"We want to look for more pathways," said Zoghbi. If they find more pathways, they may be able to reduce toxicity. "If you have a pain and you take acetaminophen all the time, you have a risk of toxicity. Similarly, if you took a nonsteroidal anti-inflammatory all the time, you would have another toxicity. If you alternate between them, there is less toxicity. If we hit only one pathway with a big inhibition, we risk some toxicity. If we find two or three pathways and hit each only a little, the rest of the body should not be hurt. Each little hit should help us reduce ataxin-1 by a respectable amount."

"I think what is novel about this paper is the integration of the screen in cells that was done in Huda’s lab and the screen in fruit flies done in our lab to look for targets for genes about which we knew nothing ahead of time," said Botas.

While the finding in spinocerebellar ataxia 1 is exciting, its potential application in other diseases is even more provocative.

"Now that we know that it works with ataxin-1, we can revisit many proteins whose levels drive neurodegeneration in sporadic and inherited diseases such as Alzheimer’s, Parkinson’s, Huntington’s and other neurological disorders," said Zoghbi. "This is a pilot study and the results from it are as important as a new pathway in neurodegenerative disease research."

"These are diseases that take a long time to develop," said Park. "Most Alzheimer’s occurs after the age of 85. If we could delay it until age 95, that would be very helpful."

"This is getting us really close, not only for SCA1, but I think it’s going to be a guidepost for work on a lot of other neurodegenerative diseases," said Orr. "It sets us a beautiful research strategy to get at that goal."

May 30, 201358 notes
#neurodegenerative diseases #spinocerebellar ataxia #ataxia #fruit flies #protein #neuroscience #science
May 29, 2013366 notes
#science #bilingualism #learning patterns #individual differences #language learning #language acquisition #psychology #neuroscience
May 29, 2013136 notes
#brain #brain activity #art appreciation #art #psychology #neuroscience #science
May 29, 201383 notes
#robots #robotics #human action #neuroscience #technology #science
May 29, 2013234 notes
#brain function #brain activity #emotion #probiotic bacteria #prefrontal cortex #neuroimaging #psychology #neuroscience #science
May 29, 201384 notes
#ALS #Lou Gehrig’s disease #animal model #stem cells #GDNF #neurobiology #neuroscience #science
May 29, 2013152 notes
#peripheral nervous system #neuropathy #schwann cells #myelin #genetics #neuroscience #science
May 29, 2013107 notes
#nerve cells #alzheimer's disease #protein #presenilin #fruit fly #motor proteins #neuroscience #science
Study shows emotional contagion increases in Alzheimer's patients

A team of researchers working at the University of California’s Memory and Aging Center has found that emotional contagion appears to increase in a linear progression with patients who have Alzheimer’s disease (AD). In their paper published in the journal Proceedings of the National Academy of Sciences, the team says their findings indicate that emotional contagion grows stronger in patients with both the precursor Mild Cognitive Impairment (MCI) and full-blown AD.

Emotional contagion is where one person mimics the emotions of another. The phenomenon is very common in human infants—upon seeing someone else smile, they tend to smile too. Babies have also been found to cry upon hearing other babies cry. The tendency to mimic others’ emotions regresses as people age, but this new study suggests it makes a reappearance in people who experience some forms of cognitive impairment later on in life.

Prior research has shown that AD causes damage to parts of the brain that are responsible for emotion—thus not all emotional problems with AD patients can be attributed to a natural human response to mental adversity. Both MCI and AD patients have been found to experience higher rates of depression and anxiety. Until now however, little research has been done to find out if people revert to mimicking the emotions of others as a type of response mechanism.

To learn more, the researchers performed psychological surveys on 120 people diagnosed with AD or MCI. Their inquiries focused mostly on emotional empathy. The team also enlisted the assistance of 111 healthy volunteers to serve as a control group. All of the participants also underwent MRI exams to test for levels of disease progression.

The brain scans revealed damage to the medial temporal lobe—known to be associated with emotional control—in those with dementia and also in the hippocampus, the part of the brain responsible for memory and recall.

An analysis of the results of the surveys and brain scans showed that emotional contagion became apparent in patients with MCI and grew more pronounced at each stage of the progression of AD. They also found that there appeared to be more of a connection between the degree of emotional contagion and damage to the right side of the medial temporal lobe, as compared to the left.

The researchers suggest that patients with dementia may mimic the emotions of others as their ability to gauge their own emotional state deteriorates. Doing so, they suggest, may help patients cope with their ailment. They add they it may also help patients hide their condition from others.

May 29, 201361 notes
#emotional contagion #alzheimer's disease #cognitive impairment #medial temporal lobe #hippocampus #neuroscience #science
May 29, 2013195 notes
#science #neurological disorders #NMDA receptors #learning #synapses #drug development #neuroscience
May 28, 2013167 notes
Down syndrome neurons grown from stem cells show signature problems

Down syndrome, the most common genetic form of intellectual disability, results from an extra copy of one chromosome. Although people with Down syndrome experience intellectual difficulties and other problems, scientists have had trouble identifying why that extra chromosome causes such widespread effects.

In new research published this week, Anita Bhattacharyya, a neuroscientist at the Waisman Center at UW-Madison, reports on brain cells that were grown from skin cells of individuals with Down syndrome.

"Even though Down syndrome is very common, it’s surprising how little we know about what goes wrong in the brain," says Bhattacharyya. "These new cells provide a way to look at early brain development."

The study began when those skin cells were transformed into induced pluripotent stem cells, which can be grown into any type of specialized cell. Bhattacharyya’s lab, working with Su-Chun Zhang and Jason Weick, then grew those stem cells into brain cells that could be studied in the lab.

One significant finding was a reduction in connections among the neurons, Bhattacharyya says. “They communicate less, are quieter. This is new, but it fits with what little we know about the Down syndrome brain.”  Brain cells communicate through connections called synapses, and the Down neurons had only about 60 percent of the usual number of synapses and synaptic activity. “This is enough to make a difference,” says Bhattacharyya. “Even if they recovered these synapses later on, you have missed this critical window of time during early development.”

The researchers looked at genes that were affected in the Down syndrome stem cells and neurons, and found that genes on the extra chromosome were increased 150 percent, consistent with the contribution of the extra chromosome.

However, the output of about 1,500 genes elsewhere in the genome was strongly affected. “It’s not surprising to see changes, but the genes that changed were surprising,” says Bhattacharyya. The predominant increase was seen in genes that respond to oxidative stress, which occurs when molecular fragments called free radicals damage a wide variety of tissues.

"We definitely found a high level of oxidative stress in the Down syndrome neurons," says Bhattacharyya. "This has been suggested before from other studies, but we were pleased to find more evidence for that. We now have a system we can manipulate to study the effects of oxidative stress and possibly prevent them."

Down syndrome includes a range of symptoms that could result from oxidative stress, Bhattacharyya says, including accelerated aging. “In  their 40s, Down syndrome individuals age very quickly. They suddenly get gray hair; their skin wrinkles, there is rapid aging in many organs, and a quick appearance of Alzheimer’s disease. Many of these processes may be due to increased oxidative stress, but it remains to be directly tested.”

Oxidative stress could be especially significant, because it appears right from the start in the stem cells. “This suggests that these cells go through their whole life with oxidative stress,” Bhattacharyya adds, “and that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer’s.”

Other researchers have created neurons with Down syndrome from induced pluripotent stem cells, Bhattacharyya notes. “However, we are the first to report this synaptic deficit, and to report the effects on genes on other chromosomes in neurons. We are also the first to use stem cells from the same person that either had or lacked the extra chromosome. This allowed us to look at the difference just caused by extra chromosome, not due to the genetic difference among people.”

The research, published the week of May 27 in the Proceedings of the National Academy of Sciences, was a basic exploration of the roots of Down syndrome. Bhattacharyya says that while she did not intend to explore treatments in the short term, “we could potentially use these cells to test or intelligently design drugs to target symptoms of Down syndrome.”

May 28, 2013172 notes
#down syndrome #stem cells #brain cells #brain development #synapses #oxidative stress #neuroscience #science
May 28, 201388 notes
#preterm children #cognitive development #cognitive performance #cognitive deficits #neuroscience #science
May 28, 2013134 notes
#rats #eye movements #binocular vision #double vision #visual system #neuroscience #science
Pitt team finds mechanism that causes noise-induced tinnitus and drug that can prevent it

An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study by researchers at the University of Pittsburgh School of Medicine. The findings, reported this week in the early online version of the Proceedings of the National Academy of Sciences, reveal for the first time the reason the chronic and sometimes debilitating condition occurs.

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An estimated 5 to 15 percent of Americans hear whistling, clicking, roaring and other phantom sounds of tinnitus, which typically is induced by exposure to very loud noise, said senior investigator Thanos Tzounopoulos, Ph.D., associate professor and member of the auditory research group in the Department of Otolaryngology, Pitt School of Medicine.

"There is no cure for it, and current therapies such as hearing aids don’t provide relief for many patients," he said. "We hope that by identifying the underlying cause, we can develop effective interventions."

The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells — they fire impulses even when there is no actual sound to perceive. For the new experiments, they took a close look at the biophysical properties of tiny channels, called KCNQ channels, through which potassium ions travel in and out of the cell.

"We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity," Dr. Tzounopoulos said. "These KCNQ channels act as effective "brakes" that reduce excitability or activity of neuronal cells."

In the model, sedated mice are exposed in one ear to a 116-decibel sound, about the loudness of an ambulance siren, for 45 minutes, which was shown in previous work to lead to the development of tinnitus in 50 percent of exposed mice. Dr. Tzounopoulos and his team tested whether an FDA-approved epilepsy drug called retigabine, which specifically enhances KCNQ channel activity, could prevent the development of tinnitus. Thirty minutes into the noise exposure and twice daily for the next five days, half of the exposed group was given injections of retigabine.

Seven days after noise exposure, the team determined whether the mice had developed tinnitus by conducting startle experiments, in which a continuous, 70 dB tone is played for a period, then stopped briefly and then resumed before being interrupted with a much louder pulse. Mice with normal hearing perceive the gap in sounds and are aware something had changed, so they are less startled by the loud pulse than mice with tinnitus, which hear phantom noise that masks the moment of silence in between the background tones.

The researchers found that mice that were treated with retigabine immediately after noise exposure did not develop tinnitus. Consistent with previous studies, 50 percent of noise-exposed mice that were not treated with the drug exhibited behavioral signs of the condition.

"This is an important finding that links the biophysical properties of a potassium channel with the perception of a phantom sound," Dr. Tzounopoulos said. "Tinnitus is a channelopathy, and these KCNQ channels represent a novel target for developing drugs that block the induction of tinnitus in humans."

The KCNQ family is comprised of five different subunits, four of which are sensitive to retigabine. He and his collaborators aim to develop a drug that is specific for the two KCNQ subunits involved in tinnitus to minimize the potential for side effects.

"Such a medication could be a very helpful preventive strategy for soldiers and other people who work in situations where exposure to very loud noise is likely," Dr. Tzounopoulos said. "It might also be useful for other conditions of phantom perceptions, such as pain in a limb that has been amputated."

May 28, 201370 notes
#tinnitus #noise exposure #potassium channels #dorsal cochlear nucleus #animal model #neuroscience #science
May 28, 201379 notes
#neurodegenerative diseases #glia cells #antioxidant enzymes #copper #copper oxidation #neuroscience #science
May 27, 2013141 notes
#brain #synapses #calyx of held synapses #neurons #auditory system #psychiatric disorders #neuroscience #science
Researchers identify genetic suspects in sporadic Lou Gehrig's disease

Researchers at the Stanford University School of Medicine have identified mutations in several new genes that might be associated with the development of spontaneously occurring cases of the neurodegenerative disease known as amyotrophic lateral sclerosis, or ALS. Also known as Lou Gehrig’s disease, the progressive, fatal condition, in which the motor neurons that control movement and breathing gradually cease to function, has no cure.

Although researchers know of some mutations associated with inherited forms of ALS, the majority of patients have no family history of the disease, and there are few clues as to its cause. The Stanford researchers compared the DNA sequences of 47 patients who have the spontaneous form of the disease, known as sporadic ALS, with those of their unaffected parents. The goal was to identify new mutations that were present in the patient but not in either parent that may have contributed to disease development.

Several suspects are mutations in genes that encode chromatin regulators — cellular proteins that govern how DNA is packed into the nucleus of a cell and how it is accessed when genes are expressed. Protein members of one these chromatin-regulatory complexes have recently been shown to play roles in normal development and some forms of cancer.

"The more we know about the genetic causes of the disorder, the greater insight we will have as to possible therapeutic targets," said Aaron Gitler, PhD, associate professor of genetics. "Until now, researchers have primarily relied upon large families with many cases of inherited ALS and attempted to pinpoint genetic regions that seem to occur only in patients. But more than 90 percent of ALS cases are sporadic, and many of the genes involved in these cases are unknown."

Gitler is the senior author of the study, published online May 26 in Nature Neuroscience. Postdoctoral scholar Alessandra Chesi, PhD, is the lead author. Gitler and Chesi collaborated with members of the laboratory of Gerald Crabtree, MD, professor of developmental biology and of pathology. Crabtree, a Howard Hughes Medical Institute investigator, is also a co-author of the study.

Chesi and Gitler combined deductive reasoning with recent advances in sequencing technology to conduct the work, which relied on the availability of genetic samples from not only ALS patients, but also the patients’ unaffected parents. Such trios can be difficult to obtain for diseases like sporadic ALS that strike well into adulthood when a patient’s parents may no longer be alive. Gitler and Chesi collaborated with researchers from Emory University and Johns Hopkins University to collect these samples.

The researchers compared the sequences of a portion of the genome called the exome, which directly contributes to the amino acid sequences of all the proteins in a cell. (Many genes contain intervening, non-protein-coding regions of DNA called introns that are removed prior to protein production.) Mutations found only in the patient’s exome, but not in that of his or her parents’, were viewed as potential disease-associated candidates - particularly if they affected the composition or structure of the resulting protein made from that gene.

Focusing on just the exome, which is about 1 percent of the total amount of DNA in each human cell, vastly reduced the total amount of DNA that needed to be sequenced and allowed the researchers to achieve relatively high coverage (or repeated sequencing to ensure accuracy) of each sample.

"We wanted to find novel changes in the patients," Chesi said. "These represent a class of mutations called de novo mutations that likely occurred during the production of the parents’ reproductive cells." As a result, these mutations would be carried in all the cells of patients, but not in their parents or siblings.

Using the exome sequencing technique, the researchers identified 25 de novo mutations in the ALS patients. Of these, five are known to be in genes involved in the regulation of the tightly packed form of DNA called chromatin — a proportion that is much higher than would have been expected by chance, according to Chesi.

Furthermore, one of the five chromatin regulatory proteins, SS18L1, is a member of a neuron-specific complex called nBAF, which has long been studied in Crabtree’s laboratory. This complex is strongly expressed in the brain and spinal cord, and affects the ability of the neurons to form branching structures called dendrites that are essential to nerve signaling.

"We found that, in one sporadic ALS case, the last nine amino acids of this protein are missing," Gitler said. "I knew that Gerald Crabtree’s lab had been investigating SS18L1, so I asked him about it. In fact, they had already identified these amino acids as being very important to the function of the protein."

When the researchers expressed the mutant SS18L1 in motor neurons isolated from mouse embryos, they found the neurons were unable to extend and grow new dendrites as robustly as normal neurons in response to stimuli. They also showed that SS18L1 appears to physically interact with another protein known to be involved in cases of familial, or inherited, ALS.

Although the results are intriguing, the researchers caution that more work is necessary to conclusively prove whether and how mutations in SS18L1 contribute to sporadic cases of ALS. But now they have an idea of where to look in other patients, without requiring the existence of patient and parent trios. They are planning to sequence SS18L1 and other candidates in an additional few thousand sporadic ALS cases.

"This is the first systematic analysis of ALS triads for the presence of de novo mutations," Chesi said. "Now we have a list of candidate genes we can pursue. We haven’t proven that these mutations cause ALS, but we’ve shown, at least in the context of SS18L1, that the mutation carried by some patients is damaging to the protein and affects the ability of mouse motor neurons to form dendrites."

May 27, 201340 notes
#ALS #Lou Gehrig's disease #DNA sequence #mutations #neurodegenerative diseases #neuroscience #science
May 27, 201381 notes
#anterior cingulate cortex #prefrontal cortex #foraging behavior #animal model #neurons #neuroscience #science
Old schooled: You never stop learning like a child

The adult brain is far more malleable that we thought, and so learning can be child’s play if you know how.

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Some 36-year-olds choose to collect vintage wine, vinyl records or sports memorabilia. For Richard Simcott, it is languages. His itch to learn has led him to study more than 30 foreign tongues – and he’s not ready to give up.

During our conversation in a London restaurant, he reels off sentences in Spanish, Turkish and Icelandic as easily as I can name the pizza and pasta on our menu. He has learned Dutch on the streets of Rotterdam, Czech in Prague and Polish during a house share with some architects. At home, he talks to his wife in fluent Macedonian.

What’s remarkable about Simcott isn’t just the number and diversity of languages he has mastered. It’s his age. Long before grey hairs appear and waistlines expand, the mind’s cogs are meant to seize up, making it difficult to pick up any new skill, be it a language, the flute, or archery. Even if Simcott had primed his mind for new languages while at school, he should have faced a steep decline in his abilities as the years went by – yet he still devours unfamiliar grammars and strange vocabularies to a high level. “My linguistic landscape is always changing,” he says. “If you’re school-aged, or middle-aged – I don’t think there’s a big difference.”

A decade ago, few neuroscientists would have agreed that adults can rival the learning talents of children. But we needn’t be so defeatist. The mature brain, it turns out, is more supple than anyone thought. “The idea that there’s a critical period for learning in childhood is overrated,” says Gary Marcus, a psychologist at New York University. What’s more, we now understand the best techniques to accelerate knowledge and skill acquisition in adults, so can perhaps unveil a few tricks of the trade of super-learners like Simcott. Whatever you want to learn, it’s never too late to charge those grey cells.

The idea that the mind fossilises as it ages is culturally entrenched. The phrase “an old dog will learn no tricks" is recorded in an 18th century book of proverbs and is probably hundreds of years older.

When researchers finally began to investigate the adult brain’s malleability in the 1960s, their results appeared to agree with the saying. Most insights came indirectly from studies of perception, which suggested that an individual’s visual abilities were capped at a young age. For example, restricting young animals’ vision for a few weeks after birth means they will never manage to see normally. The same is true for people born with cataracts or a lazy eye – repair too late, and the brain fails to use the eye properly for life. “For a very long time, it seemed that those constraints were set in stone after that critical period,” says Daphne Bavelier at the University of Rochester, New York.

These are extreme circumstances, of course, but the evidence suggested that the same neural fossilisation would stifle other kinds of learning. Many of the studies looked at language development – particularly in families of immigrants. While the children picked up new tongues with ease, their parents were still stuttering broken sentences. But if there is a critical period for foreign language learning, everyone should be affected equally; Simcott’s ability to master a host of languages should be as impossible as a dog playing the piano.

Bearing this in mind, Ellen Bialystok at York University in Toronto, Canada, recently turned to the US census records, which detailed the linguistic skills of more than 2 million Hispanic and Chinese immigrants. A “critical period” for learning a second language in infancy should have created a sharp difference between those who had moved country in early childhood and those who were uprooted in adolescence. In reality? “There was absolutely no discontinuity,” Bialystok says. Instead, she saw a very gradual decline with age among immigrants – which could reflect differences in environment as much as the adults’ rusty brain circuits. “People talk more slowly and clearly to children in short, simple sentences,” she says. “And the child’s entire social and educational network is organised around that language.”

Yet while Bialystok’s study suggested that adult brains are more pliable than had once been imagined, there was still the suspicion that children might have the edge in certain skills. Adult learners sometimes find it harder to learn to sing in tune, hit a home run or mimic an accent convincingly. At first glance, the problem might seem to lie in adults’ perception and motor skills. Learning involving these abilities differs from the acquisition of factual knowledge, because it needs us to rewire the eyes, ears and muscles.

It’s something that Marcus can identify with. At the age of 38, he devoted himself to learning the guitar, an experience he detailed in his book Guitar Zero. “My family’s initial response was laughter – but they soon saw I was making progress,” he says. Still, during his research, he attended a musical summer camp for 8 to 15-year-olds. He says he was quicker to catch on to the structure of songs, but his younger bandmates had better coordination and sense of pitch.

Yet the available evidence hints that children may not always be inherently better at such tasks. One study by Yang Zhang at the University of Minnesota in Minneapolis that focused on the acquisition of foreign accents in adults suggests we may simply be suffering from poor tuition. When the researchers gave them recordings that mimicked the exaggerated baby talk of cooing mothers, the adult learners progressed rapidly.

Nor do adults necessarily fumble over the intricate movements that are crucial for music or sport. When volunteers visiting Virginia Penhune's lab at Concordia University in Montreal, Canada, learned to press keys in a certain sequence, at certain times – essentially a boiled-down version of keyboard practice – the adults tended to outshine the younger volunteers.

During a more challenging test of hand-eye coordination, nearly 1000 volunteers of all age groups learned to juggle over a series of six training sessions. As you might expect, the senior citizens aged 60 to 80 began with some hesitation, but they soon caught up with the 30-year-olds and by the end of the trials all the adults were juggling more confidently than the 5 to 10-year-olds.

Old dogs, then, are much more adaptable than folklore would have it – and if we do have deficits, they aren’t insurmountable. The reason that children appear to be better learners may have more to do with their environment, and factors such as physical fitness (see “Faster body, faster mind”).

Indeed, many researchers believe that an adult’s lifestyle may be the biggest obstacle. “A child’s sole occupation is learning to speak and move around,” says Ed Cooke, a cognitive scientist who has won many memory contests. “If an adult had that kind of time to spend on attentive learning, I’d be very disappointed if they didn’t do a good job.”

A glut of free time and a carefree existence are out of reach for most of us, but there are other behaviours that boost children’s learning, and these habits can be easily integrated into even an adult’s schedule. For example, children are continually quizzed on what they know – and for good reason: countless studies have shown that testing doubles long-term recall, outperforming all other memory tactics. Yet most adults attempting to learn new skills will rely more on self-testing which, let’s be honest, happens less often.

That’s why Cooke developed a website, called Memrise, which helps take some of the pain out of testing and, crucially, can integrate learning into the adult day. It is designed to track your learning curve with cunningly timed tests that force you to retrieve the information just as you are about to forget it.

"Memrise engages your brain to the greatest possible extent," says Cooke, who has himself used the site to learn thousands of words of foreign vocabulary. Users can create their own courses – the topics range from art to zoology – and importantly, it is easy to load the site in the few spare minutes of your lunch break or while you are waiting for a train. Cooke also plans to launch a smartphone app.

What about tasks that involve perceptual learning or motor skills – like battling against a lifetime of tone deafness, or perfecting that golf swing? Here too, there are guiding principles that can help you rediscover the seemingly effortless learning of youth.

Adults can hamper progress with their own perfectionism: whereas children throw themselves into tasks, adults often agonise over the mechanics of the movements, trying to conceptualise exactly what is required. This could be one of our biggest downfalls. “Adults think so much more about what they are doing,” says Gabriele Wulf at the University of Nevada, Las Vegas. “Children just copy what they see.”

Wulf’s work over the past decade shows that you should focus on the outcome of your actions rather than the intricacies of the movements. She applies this finding in her own life: as a keen golfer, she has found it is better to think about the swing of the club, for instance, rather than the position of her hands. “I’m always trying to find where best to focus my attention,” she says. Similarly, if you are learning to sing, then you should concentrate on the tone of the voice, rather than on the larynx or the placement of the tongue. Study after study shows that simply shifting your mindset in this way accelerates your learning– perhaps by encouraging the subconscious, automatic movements that mark proficiency.

Misplaced conscientiousness may also lead adults to rely on overly rigid practice regimes that stifle long-term learning. The adult talent for perseverance, it seems, is not always a virtue. Left to their own devices, most people segment their sessions into separate blocks – when learning basketball, for instance, they may work on each shot in turn, perhaps because they feel a desire to master it. The approach may bring rapid improvements at first, but a host of studies have found that the refined technique is soon forgotten.

Instead, you do better to take a carousel approach, quickly rotating through the different skills to be practised without lingering too long on each one. Although the reason is still unclear, it seems that jumping between skills makes your mind work a little harder when applying what you’ve learned, helping you to retain the knowledge in the long term – a finding that has helped people improve in activities ranging from tennis and kayaking to pistol shooting.

Such an approach might not be to everyone’s taste – with intricate skills, it might feel like you are making no progress. But even if you do revert to stints of lengthy practice, you can still reap some of the same benefits by occasionally trying out your skills in an unfamiliar situation. In tennis, you might move to a different part of the court for a couple of serves before returning to the regular position; while playing scales on a musical instrument, you might switch hands temporarily. According to work by Arnaud Boutin at the Leibniz Research Centre for Working Environment and Human Factors in Dortmund, Germany, venturing out of your comfort zone in this way helps to ensure that you improve your overall performance rather than confining your progress to the single task at hand. “Otherwise, the longer you practise, the harder it becomes to transfer the skills that you’ve learned to new situations,” says Boutin.

If none of that helps you learn like a child, simply adopting the arrogance of youth may do no harm. “As we get older, we lose our confidence, and I’m convinced that has a big impact on performance,” says Wulf. To test the assumption, she recently trained a small group of people to pitch a ball. While half were given no encouragement, she offered the others a sham test, rigged to demonstrate that their abilities were above average. They learned to pitch on target with much greater accuracy than those who didn’t get an ego boost.

Whether your itch to learn will ever match Simcott’s appetite for foreign languages is another matter. “What I do – it’s like an extreme sport. There’s no need to learn that many languages,” he says. He has recently turned to Chinese, and has no plans to stop after that. “I’m like a linguistic butterfly. There’s always another, really far away, that suddenly feels appealing.”

Still, embrace the idea that your mind is as capable as Simcott’s, and the lure of extreme learning might take hold of you too.

-by David Robson, New Scientist

May 26, 2013536 notes
#adult brain #learning #perception #linguistic skills #critical period #psychology #neuroscience #science
May 26, 2013196 notes
#BCI #brainwaves #ALS #art #brain painting device #neuroscience #science
Play
May 26, 2013132 notes
#schizophrenia #auditory cortex #auditory hallucinations #hallucinations #neuroscience #science
May 26, 2013115 notes
#science #cerebellum #nerve signals #nerve cells #movement disorders #neurotransmitters #interneurons #neuroscience
Hormone levels may provide key to understanding psychological disorders in women

Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.

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The results suggest a monthly window of opportunity that could potentially be targeted in efforts to prevent common mental health problems developing in women. The research is the first to show a potential link between psychological vulnerability and the timing of a biological cycle, in this case ovulation.

A common symptom of mood and anxiety problems is the tendency to experience repetitive and unwanted thoughts. These ‘intrusive thoughts’ often occur in the days and weeks after a stressful experience.

In this study, the researchers examined whether the effects of a stressful event are linked to different stages of the menstrual cycle. The participants were 41 women aged between 18 and 35 who had regular menstrual cycles and were not using the pill as a form of contraception. Each woman watched a 14-minute stressful film containing death or injury and provided a saliva sample so that hormone levels could be assessed. They were then asked to record instances of unwanted thoughts about the video over the following days.

“We found that women in the ‘early luteal’ phase, which falls roughly 16 to 20 days after the start of their period, had more than three times as many intrusive thoughts as those who watched the video in other phases of their menstrual cycle,” explains author Dr Sunjeev Kamboj, Lecturer in UCL’s Department of Clinical, Educational and Health Psychology.

“This indicates that there is actually a fairly narrow window within the menstrual cycle when women may be particularly vulnerable to experiencing distressing symptoms after a stressful event.”

The findings could have important implications for mental health problems and their treatment in women who have suffered trauma.

“Asking women who have experienced a traumatic event about the time since their last period might help identify those at greatest risk of developing recurring symptoms similar to those seen in psychological disorders such as depression and post-traumatic stress disorder (PTSD),” said Dr Kamboj.

“This work might have identified a useful line of enquiry for doctors, helping them to identify potentially vulnerable women who could be offered preventative therapies,” continued Dr Kamboj.

“However, this is only a first step. Although we found large effects in healthy women after they experienced a relatively mild stressful event, we now need to see if the same pattern is found in women who have experienced a real traumatic event. We also need further research to investigate how using the contraceptive pill affects this whole process.”

May 25, 2013180 notes
#hormones #ovulation #menstrual cycle #psychological disorders #anxiety #psychology #neuroscience #science
May 25, 201370 notes
#alzheimer's disease #amyloid beta #amyloid precursor protein #plaques #fruit flies #neuroscience #science
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