June 28, 2012

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Provided by Vanderbilt University

Source: medicalxpress.com

June 28, 2012

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

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

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

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

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

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

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

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

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

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

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

Provided by University of Melbourne

Source: medicalxpress.com

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

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

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

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

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

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

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

Source: Science Daily

June 27th, 2012

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

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

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

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

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

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

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

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

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

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

Source: Neuroscience News

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

RTC 13 effectively counteracts ‘nonsense’ mutation that causes disorder.

Scientists at UCLA have identified a new compound that could treat certain types of genetic disorders in muscles. It is a big first step in what they hope will lead to human clinical trials for Duchenne muscular dystrophy.

Duchenne muscular dystrophy, or DMD, is a degenerative muscle disease that affects boys almost exclusively. It involves the progressive degeneration of voluntary and cardiac muscles, severely limiting the life span of sufferers.

In a new study, senior author Carmen Bertoni, an assistant professor in the UCLA Department of Neurology, first author Refik Kayali, a postgraduate fellow in Bertoni’s lab, and their colleagues demonstrate the efficacy of a new compound known as RTC13, which suppresses so-called “nonsense” mutations in a mouse model of DMD.

The findings appear in the current online edition of the journal Human Molecular Genetics.

“We are excited about these new findings because they represent a major step toward the development of a drug that could potentially treat this devastating disease in humans,” Bertoni said. “We knew that the compounds were effective in cells isolated from the mouse model for DMD, but we did not know how they would behave when administered in a living organism.”

Histopathology of gastrocnemius muscle from patient who died of pseudohypertrophic muscular dystrophy, Duchenne type. Cross section of muscle shows extensive replacement of muscle fibers by adipose cells.

Nonsense mutations are generally caused by a single change in DNA that disrupts the normal cascade of events that changes a gene into messenger RNA, then into a protein. The result is a non-functioning protein. Approximately 13 percent of genetic defects known to cause diseases are due to such mutations. In the case of DMD, the “missing” protein is called dystrophin.

For the study, Bertoni and Kayali collaborated with the laboratory of Dr. Richard Gatti, a professor of pathology and laboratory medicine and of human genetics at UCLA. Working with the UCLA Molecular Shared Screening Resource facility at the campus’s California NanoSystems Institute, the Gatti lab screened some 35,000 small molecules in the search for new compounds that could ignore nonsense mutations. Two were identified as promising candidates: RTC13 and RTC14.

The Bertoni lab tested RTC13 and RTC14 in a mouse model of DMD carrying a nonsense mutation in the dystrophin gene. While RTC14 was not found to be effective, RTC13 was able to restore significant amounts of dystrophin protein, making the compound a promising drug candidate for DMD. When RTC13 was administered to mice for five weeks, the investigators found that the compound partially restored full-length dystrophin, which resulted in a significant improvement in muscle strength. The loss of muscle strength is a hallmark of DMD.

The researchers also compared the level of dystrophin achieved to the levels seen with another experimental compound, PTC124, which has proved disappointing in clinical trials; RTC13 was found to be more effective in promoting dystrophin expression. Just as important, Bertoni noted, the study found that RTC13 was well tolerated in animals, which suggests it may also be safe to use in humans.

The next step in the research is to test whether an oral formulation of the compound would be effective in achieving therapeutically relevant amounts of dystrophin protein. If so, planning can then begin for clinical testing in patients and for expanding these studies to other diseases that may benefit from this new drug.

Source: Neuroscience News

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