Posts tagged psychology

ScienceDaily (June 27, 2012) — An international team including scientists from the University of Saskatchewan-Saskatoon Health Region and University of British Columbia, with the help of Saskatchewan Mennonite families, has identified an abnormal gene which leads to Parkinson’s disease.

"This discovery paves the way for further research to determine the nature of brain abnormalities which this gene defect produces," says Dr. Ali Rajput, a world expert in Parkinson’s disease who has been studying the disease for 45 years and working with the main family in the study since 1983.

"It also promises to help us find ways to detect Parkinson’s disease early, and to develop drugs which will one day halt the progression of the disease."

The abnormal gene is a mutated version of a gene called DNAJC13, identified by UBC medical genetics professor Matthew Farrer, who led the study.

Thirteen of 57 members of one extended Saskatchewan family in the study had been previously diagnosed with Parkinson’s disease. Three other single cases from Saskatchewan and one family from British Columbia were also found to have the same mutation. All were of Mennonite background, a Christian group who share Dutch-German-Russian ancestry.

The findings were presented last week to the more than 5,000 delegates at the 16th International Congress of Parkinson’s Disease and Movement Disorders in Dublin, Ireland.

Rajput and his son, fellow neurologist and researcher Alex Rajput, are long-time collaborators of Farrer. The research drew on the Rajputs’ work over the past four decades. The research team also includes scientists from McGill University, the Mayo Clinic in Florida, and St. Olav’s Hospital in Norway.

A key contribution is the Rajputs’ collection of more than 500 brains and nearly 2,200 blood samples from Parkinson’s patients. Farrer explains that confirmation of the gene’s linkage with Parkinson’s disease required DNA samples from thousands of patients with the disease and healthy individuals. He adds that the contributions of the Saskatchewan Mennonite family, who have asked to remain anonymous, were critical.

"A breakthrough like this would not be possible without their involvement and support. They gave up considerable time, contributed clinical information, donated blood samples, participated in PET imaging studies and — on more than one occasion following the death of a family member — donated brain samples," says Farrer, who holds the Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience.

"The whole-hearted and unselfish commitment of this family is remarkable," Rajput says. "They went out of their way in every conceivable manner to help solve this mystery. We, on behalf of all the Parkinson’s disease patients in this province, Canada, and around the world, are grateful to them for making this discovery possible."

In a Parkinson’s patient, cells in an area of the brain called the substantia nigra (black substance) die and there are abnormal, round clumps of protein known as Lewy bodies inside the brain cells. Examination of the brains from the Mennonite family revealed the same Lewy body Parkinson’s disease as seen in other patients.

Parkinson’s disease is a progressive condition that causes symptoms such as tremors, slowness of movement, stiffness, and mental impairment. In most cases, symptoms appear after age 40. It is estimated that about one million people in North America and more than four million people worldwide are affected by the disease.

Source: Science Daily

June 27th, 2012

Weill Cornell researchers develop novel antibody vaccine that blocks addictive nicotine chemicals from reaching the brain.

Researchers at Weill Cornell Medical College have developed and successfully tested in mice an innovative vaccine to treat nicotine addiction.

In the journal Science Translational Medicine, the scientists describe how a single dose of their novel vaccine protects mice, over their lifetime, against nicotine addiction. The vaccine is designed to use the animal’s liver as a factory to continuously produce antibodies that gobble up nicotine the moment it enters the bloodstream, preventing the chemical from reaching the brain and even the heart.

“As far as we can see, the best way to treat chronic nicotine addiction from smoking is to have these Pacman-like antibodies on patrol, clearing the blood as needed before nicotine can have any biological effect,” says the study’s lead investigator, Dr. Ronald G. Crystal , chairman and professor of Genetic Medicine at Weill Cornell Medical College.

“Our vaccine allows the body to make its own monoclonal antibodies against nicotine, and in that way, develop a workable immunity,” Dr. Crystal says.

The new vaccine has been tested in mice and could one day help people to quit smoking cigarettes, should they choose. Much testing remains until the vaccine can be tested in humans. Image is in the public domain.

Previously tested nicotine vaccines have failed in clinical trials because they all directly deliver nicotine antibodies, which only last a few weeks and require repeated, expensive injections, Dr. Crystal says. Plus, this kind of impractical, passive vaccine has had inconsistent results, perhaps because the dose needed may be different for each person, especially if they start smoking again, he adds.

“While we have only tested mice to date, we are very hopeful that this kind of vaccine strategy can finally help the millions of smokers who have tried to stop, exhausting all the methods on the market today, but find their nicotine addiction to be strong enough to overcome these current approaches,” he says. Studies show that between 70 and 80 percent of smokers who try to quit light up again within six months, Dr. Crystal adds.

About 20 percent of adult Americans smoke, and while it is the 4,000 chemicals within the burning cigarette that causes the health problems associated with smoking — diseases that lead to one out of every five deaths in the U.S. — it is the nicotine within the tobacco that keeps the smoker hooked.

A new kind of vaccine

There are, in general, two kinds of vaccines. One is an active vaccine, like those used to protect humans against polio, the mumps, and so on. This kind of vaccine presents a bit of the foreign substance (a piece of virus, for example) to the immune system, which “sees” it and activates a lifetime immune response against the intruder. Since nicotine is a small molecule, it is not recognized by the immune system and cannot be built into an active vaccine.

The second type of vaccine is a passive vaccine, which delivers readymade antibodies to elicit an immune response. For example, the delivery of monoclonal (identically produced) antibodies that bind on to growth factor proteins on breast cancer cells shut down their activity.

The Weill Cornell research team developed a new, third kind — a genetic vaccine — that they initially tested in mice to treat certain eye diseases and tumor types. The team’s new nicotine vaccine is based on this model.

The researchers took the genetic sequence of an engineered nicotine antibody, created by co-author Dr. Jim D. Janda, of The Scripps Research Institute, and put it into an adeno-associated virus (AAV), a virus engineered to not be harmful. They also included information that directed the vaccine to go to hepatocytes, which are liver cells. The antibody’s genetic sequence then inserts itself into the nucleus of hepatocytes, and these cells start to churn out a steady stream of the antibodies, along with all the other molecules they make.

In mice studies, the vaccine produced high levels of the antibody continuously, which the researchers measured in the blood. They also discovered that little of the nicotine they administered to these mice reached the brain. Researchers tested activity of the experimental mice, treated with both a vaccine and nicotine, and saw that it was not altered; infrared beams in the animals’ cages showed they were just as active as before the vaccine was delivered. In contrast, mice that received nicotine and not treated with the vaccine basically “chilled out” — they relaxed and their blood pressure and heart activity were lowered — signs that the nicotine had reached the brain and cardiovascular system.

The researchers are preparing to test the novel nicotine vaccine in rats and then in primates — steps needed before it can be tested ultimately in humans.

Dr. Crystal says that, if successful, such a vaccine would best be used in smokers who are committed to quitting. “They will know if they start smoking again, they will receive no pleasure from it due to the nicotine vaccine, and that can help them kick the habit,” he says.

He adds that it might be possible, given the complete safety of the vaccine, to use it to preempt nicotine addiction in individuals who have never smoked, in the same way that vaccines are used now to prevent a number of disease-producing infections. “Just as parents decide to give their children an HPV vaccine, they might decide to use a nicotine vaccine. But that is only theoretically an option at this point,” Dr. Crystal says. “We would of course have to weight benefit versus risk, and it would take years of studies to establish such a threshold.”

“Smoking affects a huge number of people worldwide, and there are many people who would like to quit, but need effective help,” he says. “This novel vaccine may offer a much-needed solution.”

Source: Neuroscience News

June 27, 2012

Smoking, head injury, pesticide exposure, farming and less education may be risk factors for a rare sleep disorder that causes people to kick or punch during sleep, according to a study published in the June 27, 2012, online issue of Neurology, the medical journal of the American Academy of Neurology.

People with the disorder, called REM sleep behavior disorder, do not have the normal lack of muscle tone that occurs during rapid eye movement (REM) sleep, causing them to act out their dreams. The movements can sometimes be violent, causing injury to the person or their bed partner. The disorder is estimated to occur in 0.5 percent of adults.

"Until now, we didn’t know much about the risk factors for this disorder, except that it was more common in men and in older people," said study author Ronald B. Postuma, MD, MSc, with the Research Institute of the McGill University Health Centre (MUHC) in Montreal and a member of the American Academy of Neurology. "Because it is a rare disorder, it was difficult to gather information about enough patients for a full study. For this study, we worked with 13 institutions in 10 countries to get a full picture of the disorder."

The disorder can also be a precursor to neurodegenerative diseases such as Parkinson’s disease and a type of dementia. Studies have shown that more than 50 percent of people with REM sleep behavior disorder go on to develop a neurodegenerative disorder years or even decades later.

"Due to this connection, we wanted to investigate whether the risk factors for REM sleep behavior disorder were similar to those for Parkinson’s disease or dementia," Postuma said.

The results were mixed. While smoking has found to be a protective factor for Parkinson’s disease, people who smoked were found to be more likely to develop REM sleep behavior disorder. Pesticide use, on the other hand, is a risk factor for both disorders. Studies have shown that people who drink coffee are less likely to develop Parkinson’s, but this study found no relationship between coffee drinking and REM sleep behavior disorder.

For the study, 347 people with REM sleep behavior disorder were compared to 347 people who did not have the disorder. Of those, 218 had other sleep disorders and 129 had no sleep disorders.

Those with REM sleep behavior disorder were 43 percent more likely to be smokers, with 64 percent of those with the disorder having ever smoked, compared to 56 percent of those without the disorder. They were 59 percent more likely to have had a previous head injury with loss of consciousness, 67 percent more likely to have worked as farmers, and more than twice as likely to have been exposed to pesticides through work. Those with the disorder also had fewer years of education, with an average of 11.1 years, compared to 12.7 years for those without the disorder.

More information: To learn more about sleep disorders, visit http://www.aan.com/patients

Provided by American Academy of Neurology

Source: medicalxpress.com

June 27, 2012 by Bob Yirka

(Medical Xpress) — Research teams from the US and Korea have together been studying depression and other mood disorders and have found that chronic stress can block a gene whose job it is to maintain healthy neuron connections in the brain, which in turn can lead to mental ailments. In lab experiments they have found that rats show lowered levels of neuritin gene activity when driven to depression, and that rats with depression tended to do better when given treatment that boosted neuritin activity, suggesting that another means of treating people with mood disorders might be on the horizon. The team has published a paper describing their experiments and results in the Proceedings of the National Academy of Sciences.

Prior research has shown that people who suffer from chronic depression tend to lose plasticity, or the ability to organize new information in their brains, specifically in the hippocampus, leading to a degree of atrophy, a condition that makes it difficult for such people to recover from their disorder even when given drugs to help treat the symptoms. Until now however, most drugs that are used to treat mood disorders work by blocking the re-absorption of the brain chemical serotonin. In this new research, the team looked at the role of neuritin gene activity instead.

In lab experiments they first caused rats to become depressed by exposing them to a constantly stressful environment, e.g. putting them alone in a sterile environment, limiting food and alternating their night/day cycle. After about three weeks the rats became lethargic and unresponsive to normal stimuli. Once that was done, they tested them for the degree of neuritin gene activity, and found that such levels had dropped in all of them. They then treated some of the rates with standard mood stabilizers which helped reduced symptoms as it has in previous research. But then, they treated some of the other rats by infecting them with a virus that causes an increase in neuritin gene activity and found doing so helped the rats just as much as standard therapies and also served to protect their brains from atrophy.

In another experiment the team forced lowered neuritin gene activity in a group of rats but didn’t subject them to stress and found the rats became just as depressed as had those in the first experiment.

The team notes that while their results look very promising on paper, assuming the same results would occur with people is premature as there are differences in biology. Their results do however support the notion that stress itself contributes to mood disorders, which is information people can use to help them live more mentally healthy lives right now.

More information: Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress, PNAS, Published online before print June 25, 2012, doi: 10.1073/pnas.1201191109

Source: medicalxpress.com

June 27th, 2012

Researchers from the Huck Institutes’ Center for Cellular Dynamics, led by Center director Melissa Rolls, have found that a neuroprotective pathway initiated in response to injured or stressed neural axons serves to stabilize and protect the nerve cell against further degeneration.

Neurons, or nerve cells, typically have a single axon that transmits signals to other neurons or to output cells such as muscle tissue, and as these axons extend for long distances within the cell, they are thus at risk for injury.

Furthermore, if an axon is damaged, its parent neuron can no longer function; and since many animals develop only one set of neurons, those neurons will mount major responses to axon injury.

“Neurons are quite remarkable cells,” says Dr. Rolls. “Most of them need to survive and function for your entire lifetime. Maybe then it shouldn’t be a surprise that they do not give up easily when damaged or stressed, but it is amazing to be able to watch them fight back and stabilize themselves.”

Neurons expressing a toxic form of spinocerebellar ataxia type 3 (SCA3) with protective pathway enabled (left) and blocked (right). Image adapted from Penn State press release image with credit to Melissa Rolls. Click for larger view and original image from Penn State.

Dissecting Drosophila

Dr. Rolls and her team set out to understand these cellular responses to axon injury by observing the effects of severing fruit fly axons with a laser.

What they found was that the neurons responded to the injury by increasing production of microtubules — cytoskeletal components responsible for maintaining cell structure and providing platforms for intracellular transport — in order to stabilize the neural dendrites, which are the branched structures responsible for transmitting signals to the nerve cell body.

In addition to acute injury response, the team also investigated neurons’ response to long-term axon stress — and found similar results.

Accumulation of misfolded proteins or protein aggregates — responsible for neurodegenerative diseases such as Huntington’s disease and spinocerebellar ataxia — induced the same type of cytoskeletal changes as acute axon injury.

Dr. Rolls elaborates: “The assays that we use are all in vivo, so we can literally watch what the neurons do in different scenarios, including cutting of their axon. Being able to observe the cellular responses gave us some ideas we would not have come up with otherwise. For example, it is not intuitive that expressing a protein that causes degeneration would trigger the cell to turn on a pathway that delays degeneration.”

The neuroprotective pathway

The video below shows the difference in microtubule dynamics between cells expressing a non-toxic form of the huntingtin protein (left) and cells expressing a disease-causing form (right).

[Video: Axon injury and stress trigger a microtubule-based neuroprotective pathway]
Credit: Melissa Rolls, Director, Center for Cellular Dynamics

Conclusions and implications

Based on their observations, the authors suggest that this pathway represents an endogenous neuroprotective response to axon stress — and could potentially be developed into a diagnostic tool for the detection of early stages of neurodegenerative disease, or even utilized in novel therapies for such illnesses.

“We don’t yet know if all types of neurodegenerative disease trigger this type of stabilization pathway; but if there are some diseases in which it is off, then it may be beneficial to try to turn it on to help the neurons resist degeneration,” says Dr. Rolls.

The results of the study have been published in Proceedings of the National Academy of Sciences.

Source: Neuroscience News

ScienceDaily (June 27, 2012) — A new study shows significant differences in brain development in high-risk infants who develop autism starting as early as age 6 months. The findings published in the American Journal of Psychiatry reveal that this abnormal brain development may be detected before the appearance of autism symptoms in an infant’s first year of life. Autism is typically diagnosed around the age of 2 or 3.

The study offers new clues for early diagnosis, which is key, as research suggests that the symptoms of autism — problems with communication, social interaction and behavior — can improve with early intervention. “For the first time, we have an encouraging finding that enables the possibility of developing autism risk biomarkers prior to the appearance of symptoms, and in advance of our current ability to diagnose autism,” says co-investigator Dr. Alan Evans at the Montreal Neurological Institute and Hospital — the Neuro, McGill University, which is the Data Coordinating Centre for the study.

"Infancy is a time when the brain is being organized and connections are developing rapidly," says Dr. Evans. "Our international research team was able to detect differences in the wiring by six months of age in those children who went on to develop autism. The difference between high-risk infants that developed autism and those that did not was specifically in white matter tract development — fibre pathways that connect brain regions." The study followed 92 infants from 6 months to age 2. All were considered at high-risk for autism, as they had older siblings with the developmental disorder. Each infant had a special type of MRI scan, known as diffusion tensor imaging, at 6 months and a behavioral assessment at 24 months. The majority also had additional scans at either or both 12 and 24 months.

At 24 months, 30% of infants in the study were diagnosed with autism. White matter tract development for 12 of the 15 tracts examined differed significantly between the infants that developed autism and those who did not. Researchers evaluated fractional anisotropy (FA), a measure of white matter organization based on the movement of water through tissue. Differences in FA values were greatest at 6 and 24 months. Early in the study, infants who developed autism showed elevated FA values along these tracts, which decreased over time, so that by 24 months autistic infants had lower FA values than infants without autism.

The study characterizes the dynamic age-related brain and behavior changes underlying autism — vital for developing tools to aid autistic children and their families. This is the latest finding from the on-going Infant Brain Imaging Study (IBIS), which is funded by the National Institutes of Health (NIH) and brings together the expertise of a network of researchers from institutes across North America. The IBIS study is headquartered at the University of North Carolina, and The Neuro is the Data Coordinating Centre where all IBIS data is centralized.

Source: Science Daily

June 26, 2012

Researchers at the University of Michigan have found that the Apple iPad 2 can interfere with settings of magnetically programmable shunt devices, which are often used to treat children with hydrocephalus. The iPad 2 contains magnets that can change valve settings in the shunt if the tablet computer is held too close to the valve (within 2 inches). Such a change may result in shunt malfunction until the problem is recognized and the valve adjusted to the proper setting. Patients and their caregivers should monitor use of the tablet computer to ensure that no change is made to the valve settings. The results of this study can be found in the article “Programmable shunt valve affected by exposure to a tablet computer. Laboratory investigation,” by Strahle and colleagues, published in the August 2012 issue of the Journal of Neurosurgery: Pediatrics and available online today.

The researchers first thought of performing this study because a tablet computer seemed to affect a programmable shunt in one of their patients, a 4-month-old girl with hydrocephalus. Three weeks after the baby had received the shunt, she was examined for shunt malfunction due to a changed setting in the magnetically programmable valve that regulates the flow of cerebrospinal fluid. The baby’s mother stated that she had held an iPad 2 while holding the infant. Programmable shunt valve settings can be altered by exposure to magnetic fields. Indeed, specialized magnets are used by physicians to adjust the settings on these valves. Since in this case no other environmental factor could be identified that would have led to a shift in the valve settings, the authors decided to test whether the iPad 2 might be implicated because, unlike the initial iPad, the iPad 2 contains several magnets and is often used with an Apple Smart Cover, which contains additional magnets.

The researchers tested 10 programmable shunt valves with a variety of settings. They exposed the valves to an iPad 2 with and without the Smart Cover at different distances: less than 1 centimeter (cm), 1 to 2.5 cm, 2.5 to 5 cm, 5 to 10 cm, and greater than 10 cm. Each exposure lasted 10 seconds. Overall, the valves were tested 100 times for each of the five distances during exposures to the iPad 2 with the Smart Cover closed and 30 times for distances less than 1 cm for the tablet computer without the cover.

After exposure of the programmable valves to the iPad 2 and Smart Cover at distances between 0 and 1 cm, the researchers found that the settings had changed in 58 percent of the valves. After exposure at distances between 1 and 2.5 cm the settings had changed in 5 percent of valves, and after exposure at distances between 2.5 and 5 cm the settings had changed in only 1 percent of valves. No changes in valve settings were identified after exposures at higher distances.

After exposure of programmable valves to the iPad 2 without a cover, which was only tested at distances between 0 and 1 cm, the researchers found that the settings had changed in 67 percent of the valves.

Although no change in setting was found past a distance of 5 cm (2 inches), the authors caution that patients and caregivers should be made aware of the potential for a change in the settings of a magnetically programmable shunt valve if an iPad 2 is placed very near. This is not to say that the iPad 2 cannot be safely used in the vicinity of patients with programmable shunts. A variety of magnets can be found in households today, and the authors state that the magnetic field strength of the iPad 2 lies within the range of these everyday magnets. Therefore, patients and caregivers should regard precautions surrounding the use of the iPad 2 to be the same as those taken with other household magnets. Cormac Maher, M.D., a pediatric neurosurgeon and lead author of the report, said that he hopes to raise awareness of this potential interaction through publication of this study.

Provided by Journal of Neurosurgery Publishing Group

Source: medicalxpress.com

ScienceDaily (June 26, 2012) — In the brains of humans and non-human primates, over 100 billion nerve cells build up complicated neural circuits and produce higher brain functions. When an attempt is made to perform gene therapy for neurological diseases like Parkinson’s disease, it is necessary to specify a responsible neural circuit out of many complicated circuits. Until now, however, it was difficult to introduce a target gene into this particular circuit selectively.

The collaborative research group consisting of Professor Masahiko Takada from Primate Research Institute, Kyoto University, Professor Atsushi Nambu from National Institute for Physiological Sciences, National Institutes of Natural Sciences, and Professor Kazuto KOBAYASHI from Fukushima Medical University School of Medicine have now developed a gene transfer technique that can “eliminate”a specific neural circuit in non-human primates for the first time.

They applied this technique to the basal ganglia, the brain region that is affected in movement disorders such as Parkinson’s disease, and successfully eliminated a particular circuit selectively to elucidate its functional role. This technique can be applied to gene therapy for various neurological diseases in humans. This research achievement was supported by the Strategic Research Program of Brain Sciences by MEXT of Japan.

The research group developed a special viral vector, NeuRet-IL-2R alpha-GFP viral vector, expressing human interleukin type 2 alpha receptor, which the cell death inducer immunotoxin binds. Nerve cells transfected with this viral vector cause cell death by immunotoxin. First, the research group injected the viral vector into the subthalamic nucleus that is a component of the basal ganglia. Then, they injected immunotoxin into the motor cortex, an area of the cerebral cortex that controls movement, and succeed in selective elimination of the “hyperdirect pathway” that is one of the major circuits connecting the motor cortex to the basal ganglia. As a result, they have discovered that neuronal excitation observed at the early stage occurs through this hyperdirect pathway when motor information derived from the cortex enters the basal ganglia.

Professors Takada and Nambu expect that this gene transfer technique enables us to elucidate higher brain functions in primates and to develop primate models of various psychiatric/neurological disorders and their potential treatments including gene therapy. They think that this should provide novel advances in the field of neuroscience research that originate from Japan.

Source: Science Daily