Neuroscience

New research from the University of Rochester Medical Center describes how exposure to air pollution early in life produces harmful changes in the brains of mice, including an enlargement of part of the brain that is seen in humans who have autism and schizophrenia.  

As in autism and schizophrenia, the changes occurred predominately in males. The mice also performed poorly in tests of short-term memory, learning ability, and impulsivity.

The new findings are consistent with several recent studies that have shown a link between air pollution and autism in children. Most notably, a 2013 study in JAMA Psychiatry reported that children who lived in areas with high levels of traffic-related air pollution during their first year of life were three times as likely to develop autism.

“Our findings add to the growing body of evidence that air pollution may play a role in autism, as well as in other neurodevelopmental disorders,” said Deborah Cory-Slechta, Ph.D., professor of Environmental Medicine at the University of Rochester and lead author of the study, published in the journal Environmental Health Perspectives.

In three sets of experiments, Cory-Slechta and her colleagues exposed mice to levels of air pollution typically found in mid-sized U.S. cities during rush hour. The exposures were conducted during the first two weeks after birth, a critical time in the brain’s development. The mice were exposed to polluted air for four hours each day for two four-day periods.

In one group of mice, the brains were examined 24 hours after the final pollution exposure. In all of those mice, inflammation was rampant throughout the brain, and the lateral ventricles — chambers on each side of the brain that contain cerebrospinal fluid — were enlarged two-to-three times their normal size.

“When we looked closely at the ventricles, we could see that the white matter that normally surrounds them hadn’t fully developed,” said Cory-Slechta. “It appears that inflammation had damaged those brain cells and prevented that region of the brain from developing, and the ventricles simply expanded to fill the space.”

The problems were also observed in a second group of mice 40 days after exposure and in another group 270 days after exposure, indicating that the damage to the brain was permanent. Brains of mice in all three groups also had elevated levels of glutamate, a neurotransmitter, which is also seen in humans with autism and schizophrenia.

Most air pollution is made up mainly of carbon particles that are produced when fuel is burned by power plants, factories, and cars. For decades, research on the health effects of air pollution has focused on the part of the body where the damage is most obvious — the lungs. That research began to show that different-sized particles produce different effects.  Larger particles — the ones regulated by the Environmental Protection Agency (EPA) — are actually the least harmful because they are coughed up and expelled.  But many researchers believe that smaller particles known as ultrafine particles —  which are not regulated by the EPA — are more dangerous, because they are small enough to travel deep into the lungs and be absorbed into the bloodstream, where they can produce toxic effects throughout the body.

That assumption led Cory-Slechta to design a set of experiments that would show whether ultrafine particles have a damaging effect on the brain, and if so, to reveal the mechanism by which they inflict harm. Her study published today is the first scientific work to do both.

“I think these findings are going to raise new questions about whether the current regulatory standards for air quality are sufficient to protect our children,” said Cory-Slechta.

University of Toronto biologists leading an investigation into the cells that regulate proper brain function, have identified and located the key players whose actions contribute to afflictions such as epilepsy and schizophrenia. The discovery is a major step toward developing improved treatments for these and other neurological disorders.

“Neurons in the brain communicate with other neurons through synapses, communication that can either excite or inhibit other neurons,” said Professor Melanie Woodin in the Department of Cell and Systems Biology at the University of Toronto (U of T), lead investigator of a study published today in Cell Reports. “An imbalance among the levels of excitation and inhibition – a tip towards excitation, for example – causes improper brain function and can produce seizures. We identified a key complex of proteins that can regulate excitation-inhibition balance at the cellular level.”

This complex brings together three key proteins – KCC2, Neto2 and GluK2 – required for inhibitory and excitatory synaptic communication. KCC2 is required for inhibitory impulses, GluK2 is a receptor for the main excitatory transmitter glutamate, and Neto2 is an auxiliary protein that interacts with both KCC2 and GluK2. The discovery of the complex of three proteins is pathbreaking as it was previously believed that KCC2 and GluK2 were in separate compartments of the cell and acted independently of each other.

“Finding that they are all directly interacting and can co-regulate each other’s function reveals for the first time a system that can mediate excitation-inhibition balance among neurons themselves,” said Vivek Mahadevan, a PhD candidate in Woodin’s group and lead author of the study.

Mahadevan and fellow researchers made the discovery via biochemistry, fluorescence imaging and electrophysiology experiments on mice brains. The most fruitful technique was the application of an advanced sensitive gel system to determine native protein complexes in neurons, called Blue Native PAGE. The process provided the biochemical conditions necessary to preserve the protein complexes that normally exist in neurons. Blue Native PAGE is advantageous over standard gel electrophoresis, where proteins are separated from their normal protein complexes based on their molecular weights.

“The results reveal the proteins that can be targeted by drug manufacturers in order to reset imbalances that occur in neurological disorders such as epilepsy, autism spectrum disorder, schizophrenia and neuropathic pain,” said Woodin. “There is no cure for epilepsy; the best available treatments only control its effects, such as convulsions and seizures. We can now imagine preventing them from occurring in the first place.”

“It was the cellular mechanisms that determine the excitation-inhibition balance that needed to be identified. Now that we know the key role played by KCC2 in moderating excitatory activity, further research can be done into its occasional dysfunction and how it can also be regulated by excitatory impulses,” said Mahadevan.

“Where does it hurt?” is the first question asked to any person in pain.

A new UCL study defines for the first time how our ability to identify where it hurts, called “spatial acuity”, varies across the body, being most sensitive at the forehead and fingertips.

Using lasers to cause pain to 26 healthy volunteers without any touch, the researchers produced the first systematic map of how acuity for pain is distributed across the body. The work is published in the journal Annals of Neurology and was funded by the Wellcome Trust.

With the exception of the hairless skin on the hands, spatial acuity improves towards the centre of the body whereas the acuity for touch is best at the extremities. This spatial pattern was highly consistent across all participants.

The experiment was also conducted on a rare patient lacking a sense of touch, but who normally feels pain. The results for this patient were consistent with those for healthy volunteers, proving that acuity for pain does not require a functioning sense of touch.

“Acuity for touch has been known for more than a century, and tested daily in neurology to assess the state of sensory nerves on the body. It is striking that until now nobody had done the same for pain,” says lead author Dr Flavia Mancini of the UCL Institute of Cognitive Neuroscience. “If you try to test pain with a physical object like a needle, you are also stimulating touch. This clouds the results, like taking an eye test wearing sunglasses. Using a specially-calibrated laser, we stimulate only the pain nerves in the upper layer of skin and not the deeper cells that sense touch.”

Volunteers were blindfolded and had specially-calibrated pairs of lasers targeted at various parts of their body. These lasers cause a brief sensation of pinprick pain. Sometimes only one laser would be activated, and sometimes both would be, unknown to participants. They were asked whether they felt one ‘sting’ or two, at varying distances between the two beams. The researchers recorded the minimum distance between the beams at which people were able to accurately say whether it was one sting or two.

“This measure tells us how precisely people can locate the source of pain on different parts of their body,” explains senior author Dr Giandomenico Iannetti of the UCL Department of Neuroscience, Physiology and Pharmacology. “Touch and pain are mediated by different sensory systems. While tactile acuity has been well studied, pain acuity has been largely ignored, beyond the common textbook assertion that pain has lower acuity than touch. We found the opposite: acuity for touch and pain are actually very similar. The main difference is in their gradients across the body. For example, pain acuity across the arm is much higher at the shoulder than at the wrist, whereas the opposite is true for touch.”

Acuity for both touch and pain normally correlates with the density of the relevant nerve fibres in each part of the body. However, the fingertips remain highly sensitive despite having a low density of pain-sensing nerve cells.

“The high pain acuity of the fingertips is something of a mystery that requires further investigation,” says Dr Mancini. “This may be because people regularly use their fingertips, and so the central nervous system may learn to process the information accurately.”

The findings have important implications for the assessment of both acute and chronic pain. Dr Roman Cregg of the UCL Centre for Anaesthesia, who was not involved in the research, is a clinical expert who treats patients with chronic pain.

“Chronic pain affects around 10 million people in the UK each year according to the British Pain Society, but we still have no reliable, reproducible way to test patients’ pain acuity,” says Dr Cregg. “This method offers an exciting, non-invasive way to test the state of pain networks across the body. Chronic pain is often caused by damaged nerves, but this is incredibly difficult to monitor and to treat. The laser method may enable us to monitor nerve damage across the body, offering a quantitative way to see if a condition is getting better or worse. I am excited at the prospect of taking this into the clinic, and now hope to work with Drs Mancini and Iannetti to translate their study to the chronic pain setting.”

In laboratory tests, researchers have used electrical stimulation of retinal cells to produce the same patterns of activity that occur when the retina sees a moving object. Although more work remains, this is a step toward restoring natural, high-fidelity vision to blind people, the researchers say. The work was funded in part by the National Institutes of Health.

(Image caption: Chichilnisky and colleagues used an electrode array to record activity from retinal ganglion cells (yellow and blue) and feed it back to them, reproducing the cells’ responses to visual stimulation. Credit: E.J. Chichilnisky, Stanford.)

Just 20 years ago, bionic vision was more a science fiction cliché than a realistic medical goal. But in the past few years, the first artificial vision technology has come on the market in the United States and Western Europe, allowing people who’ve been blinded by retinitis pigmentosa to regain some of their sight. While remarkable, the technology has its limits. It has enabled people to navigate through a door and even read headline-sized letters, but not to drive, jog down the street, or see a loved one’s face.

A team based at Stanford University in California is working to improve the technology by targeting specific cells in the retina—the neural tissue at the back of the eye that converts light into electrical activity.

"We’ve found that we can reproduce natural patterns of activity in the retina with exquisite precision," said E.J. Chichilnisky, Ph.D., a professor of neurosurgery at Stanford’s School of Medicine and Hansen Experimental Physics Laboratory. The study was published in Neuron, and was funded in part by NIH’s National Eye Institute (NEI) and National Institute of Biomedical Imaging and Bioengineering (NIBIB).

The retina contains several cell layers. The first layer contains photoreceptor cells, which detect light and convert it into electrical signals. Retinitis pigmentosa and several other blinding diseases are caused by a loss of these cells. The strategy behind many bionic retinas, or retinal prosthetics, is to bypass the need for photoreceptors and stimulate the retinal ganglion cell layer, the last stop in the retina before visual signals are sent to the brain.

Several types of retinal prostheses are under development. The Argus II, which was developed by Second Sight Therapeutics with more than $25 million in support from NEI, is the best known of these devices. In the United States, it was approved for treating retinitis pigmentosa in 2013, and it’s now available at a limited number of medical centers throughout the country. It consists of a camera, mounted on a pair of goggles, which transmits wireless signals to a grid of electrodes implanted on the retina. The electrodes stimulate retinal ganglion cells and give the person a rough sense of what the camera sees, including changes in light and contrast, edges, and rough shapes.

"It’s very exciting for someone who may not have seen anything for 20-30 years. It’s a big deal. On the other hand, it’s a long way from natural vision," said Dr. Chichilnisky, who was not involved in development of the Argus II.

Current technology does not have enough specificity or precision to reproduce natural vision, he said. Although much of visual processing occurs within the brain, some processing is accomplished by retinal ganglion cells. There are 1 to 1.5 million retinal ganglion cells inside the retina, in at least 20 varieties. Natural vision—including the ability to see details in shape, color, depth and motion—requires activating the right cells at the right time.

The new study shows that patterned electrical stimulation can do just that in isolated retinal tissue. The lead author was Lauren Jepson, Ph.D., who was a postdoctoral fellow in Dr. Chichilnisky’s former lab at the Salk Institute in La Jolla, California. The pair collaborated with researchers at the University of California, San Diego, the Santa Cruz Institute for Particle Physics, and the AGH University of Science and Technology in Krakow, Poland.

They focused their efforts on a type of retinal ganglion cell called parasol cells. These cells are known to be important for detecting movement, and its direction and speed, within a visual scene. When a moving object passes through visual space, the cells are activated in waves across the retina.

The researchers placed patches of retina on a 61-electrode grid. Then they sent out pulses at each of the electrodes and listened for cells to respond, almost like sonar. This enabled them to identify parasol cells, which have distinct responses from other retinal ganglion cells. It also established the amount of stimulation required to activate each of the cells. Next, the researchers recorded the cells’ responses to a simple moving image—a white bar passing over a gray background. Finally, they electrically stimulated the cells in this same pattern, at the required strengths. They were able to reproduce the same waves of parasol cell activity that they observed with the moving image.

"There is a long way to go between these results and making a device that produces meaningful, patterned activity over a large region of the retina in a human patient," Dr. Chichilnisky said. "But if we can handle the many technical hurdles ahead, we may be able to speak to the nervous system in its own language, and precisely reproduce its normal function."

Such advances could help make artificial vision more natural, and could be applied to other types of prosthetic devices, too, such as those being studied to help paralyzed individuals regain movement. NEI supports many other projects geared toward retinal prosthetics.

"Retinal prosthetics hold great promise, but this research is a marathon, not a sprint," said Thomas Greenwell, Ph.D., a program director in retinal neuroscience at NEI. "This important study helps illustrate the challenges of restoring high-quality vision, one group’s progress toward that goal, and the continued need to for the entire field to keep innovating."

St. Jude Children’s Research Hospital scientists have identified problems in a connection between brain structures that may predispose individuals to hearing the “voices” that are a common symptom of schizophrenia. The work appears in the June 6 issue of the journal Science.

(Image: Getty Images)

Researchers linked the problem to a gene deletion. This leads to changes in brain chemistry that reduce the flow of information between two brain structures involved in processing auditory information.

The research marks the first time that a specific circuit in the brain has been linked to the auditory hallucinations, delusions and other psychotic symptoms of schizophrenia. The disease is a chronic, devastating brain disorder that affects about 1 percent of Americans and causes them to struggle with a variety of problems, including thinking, learning and memory.

The disrupted circuit identified in this study solves the mystery of how current antipsychotic drugs ease symptoms and provides a new focus for efforts to develop medications that quiet “voices” but cause fewer side effects.

“We think that reducing the flow of information between these two brain structures that play a central role in processing auditory information sets the stage for stress or other factors to come along and trigger the ‘voices’ that are the most common psychotic symptom of schizophrenia,” said the study’s corresponding author Stanislav Zakharenko, M.D., Ph.D., an associate member of the St. Jude Department of Developmental Neurobiology. “These findings also integrate several competing models regarding changes in the brain that lead to this complex disorder.”

The work was done in a mouse model of the human genetic disorder 22q11 deletion syndrome. The syndrome occurs when part of chromosome 22 is deleted and individuals are left with one rather than the usual two copies of about 25 genes. About 30 percent of individuals with the deletion syndrome develop schizophrenia, making it one of the strongest risk factors for the disorder. DNA is the blueprint for life. Human DNA is organized into 23 pairs of chromosomes that are found in nearly every cell.

Earlier work from Zakharenko’s laboratory linked one of the lost genes, Dgcr8, to brain changes in mice with the deletion syndrome that affect a structure important for learning and memory. They found evidence that the same mechanism was at work in patients with schizophrenia. Dgcr8 carries instructions for making small molecules called microRNAs that help regulate production of different proteins.

For this study, researchers used state-of-the-art tools to link the loss of Dgcr8 to changes that affect a different brain structure, the auditory thalamus. For decades antipsychotic drugs have been known to work by binding to a protein named the D2 dopamine receptor (Drd2). The binding blocks activity of the chemical messenger dopamine. Until now, however, how that quieted the “voices” of schizophrenia was unclear.

Working in mice with and without the 22q11 deletion, researchers showed that the strength of the nerve impulse from neurons in the auditory thalamus was reduced in mice with the deletion compared to normal mice. Electrical activity in other brain regions was not different.

Investigators showed that Drd2 levels were elevated in the auditory thalamus of mice with the deletion, but not in other brain regions. When researchers checked Drd2 levels in tissue from the same structure collected from 26 individuals with and without schizophrenia, scientists reported that protein levels were higher in patients with the disease.

As further evidence of Drd2’s role in disrupting signals from the auditory thalamus, researchers tested neurons in the laboratory from different brain regions of mutant and normal mice by adding antipsychotic drugs haloperidol and clozapine. Those drugs work by targeting Drd2. Originally nerve impulses in the mutant neurons were reduced compared to normal mice. But the nerve impulses were almost universally enhanced by antipsychotics in neurons from mutant mice, but only in neurons from the auditory thalamus.

When researchers looked more closely at the missing 22q11 genes, they found that mice that lacked the Dgcr8 responded to a loud noise in a similar manner as schizophrenia patients. Treatment with haloperidol restored the normal startle response in the mice, just as the drug does in patients.

Studying schizophrenia and other brain disorders advances understanding of normal brain development and the missteps that lead to various catastrophic diseases, including pediatric brain tumors and other problems.

A team of UCLA researchers has identified a new gene involved in Parkinson’s disease, a finding that may one day provide a target for a new drug to prevent and potentially even cure the debilitating neurological disorder.

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, and there is no cure for the progressive and devastating illness. About 60,000 Americans are diagnosed with Parkinson’s disease each year. It is estimated that as many as 1 million Americans live with Parkinson’s disease, which is more than the number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig’s disease combined.

In Parkinson’s disease, multiple neurons in the brain gradually break down or die. This leads to the movement impairments, such as tremor, rigidity, slowness in movement and difficulty walking, as well as depression, anxiety, sleeping difficulties and dementia, said Dr. Ming Guo, the study team leader, associate professor of neurology and pharmacology and a practicing neurologist at UCLA.

A handful of genes have been identified in inherited cases of Parkinson’s disease. Guo’s team was one of two groups worldwide that first reported in 2006 in the journal Nature that two of these genes, PTEN-induced putative kinase 1 (PINK1) and PARKIN, act together to maintain the health of mitochondria – the power house of the cell that is important in maintaining brain health. Mutations in these genes lead to early-onset Parkinson’s disease.

Guo’s team has further shown that when PINK1 and PARKIN are operating correctly, they help maintain the regular shape of healthy mitochondria and promote elimination of damaged mitochondria. Accumulation of unhealthy or damaged mitochondria in neurons and muscles ultimately results in Parkinson’s disease.

In this study, the team found that the new gene, called MUL1 (also known as MULAN and MAPL), plays an important role in mediating the pathology of the PINK1 and PARKIN. The study, performed in fruit flies and mice, showed that providing an extra amount of MUL1 ameliorates the mitochondrial damage due to mutated PINK/PARKIN, while inhibiting MUL1 in mutant PINK1/PARKIN exacerbates the damage to the mitochondria. In addition, Guo and her collaborators found that removing MUL1 from mouse neurons of the PARKIN disease model results in unhealthy mitochondria and degeneration of the neurons.

The five-year study appears June 4, 2014, in eLife, a new, open access scientific journal for groundbreaking biomedical and life research sponsored by the Howard Hughes Medical Institute (United States), the Wellcome Trust (United Kingdom) and Max Plank Institutes (Germany).

"We are very excited about this finding," Guo said. "There are several implications to this work, including that MUL1 appears to be a very promising drug target and that it may constitute a new pathway regulating the quality of mitochondria."

Guo characterized the work as “a major advancement in Parkinson’s disease research.”

"We show that MUL1 dosage is key and optimizing its function is crucial for brain health and to ward off Parkinson’s disease," she said. "Our work proves that mitochondrial health is of central importance to keep us from suffering from neurodegeneration. Further, finding a drug that can enhance MUL1 function would be of great benefit to patients with Parkinson’s disease."

Going forward, Guo and her team will test these results in more complex organisms, hoping to uncover additional functions and mechanisms of MUL1. Additionally, the team will perform small molecule screens to help identify potential compounds that specifically target MUL1. Further, they will examine if mutations in MUL1 exist in some patients with inherited forms of Parkinson’s.

Neuroscientists at Mayo Clinic in Florida and at Aarhus University in Denmark have shed light on why neurons in the brain’s reward system can be miswired, potentially contributing to disorders such as attention deficit hyperactivity disorder (ADHD).

They say findings from their study, published online today in Neuron, may increase the understanding of underlying causes of ADHD, potentially facilitating the development of more individualized treatment strategies.

The scientists looked at dopaminergic neurons, which regulate pleasure, motivation, reward, and cognition, and have been implicated in development of ADHD.

They uncovered a receptor system that is critical, during embryonic development, for correct wiring of the dopaminergic brain area. But they also discovered that after brain maturation, a cut in the same receptor, SorCS2, produces a two-chain receptor that induces cell death following damage to the peripheral nervous system.

The researchers report that the SorCS2 receptor functions as a molecular switch between apparently opposing effects in proBDNF. ProBDNF is a neuronal growth factor that helps select cells that are most beneficial to the nervous system, while eliminating those that are less favorable in order to create a finely tuned neuronal network.

They found that some cells in mice deficient in SorCS2 are unresponsive to proBDNF and have dysfunctional contacts between dopaminergic neurons.

“This miswiring of dopaminergic neurons in mice results in hyperactivity and attention deficits,” says the study’s senior investigator, Anders Nykjaer, M.D., Ph.D., a neuroscientist at Mayo Clinic in Florida and at Aarhus University in Denmark.

“A number of studies have reported that ADHD patients commonly exhibit miswiring in this brain area, accompanied by altered dopaminergic function. We may now have an explanation as to why ADHD risk genes have been linked to regulation of neuronal growth,” he says.

“SorCS2 is produced as a single-chain protein — one long row of amino acids — but it can be cut into two chains to perform a different function. While the single-chain receptor is essential to tell the neuron that it is time to stop growing, the two-chain form tells cells that support neurons in the developing peripheral nervous system to die when they should,” says Dr. Nykjaer.

Unfortunately, if damage occurs to a nerve in the peripheral nervous system, these cells that wrap around and nourish the neurons will die, preventing efficient regeneration, he says. “Our finding suggests that it may be possible to develop drug therapy to prevent this deadly cut of SorCS2 and treat acute nerve injury,” Dr. Nykjaer says.

New research, published in The Lancet Psychiatry journal, shows that rates of adverse outcomes, including premature death and violent crime, in people with schizophrenia are increasing, compared to the general population.

The results come from a unique study, led by Dr Seena Fazel, at Oxford University, UK, which analyses long-term adverse outcomes – including conviction for a violent crime (such as homicide or bodily harm) premature death (before the age of 56), and death by suicide – between 1972 and 2009 in nearly 25,000 people in Sweden diagnosed with schizophrenia or related disorders.

For the first time, the researchers compared adverse outcomes in people with a diagnosis of schizophrenia to both the general population and to unaffected siblings, allowing them to account for risk factors within families (such as parental criminality or violence) which might be expected to affect the risk of suicide or violent behaviour in siblings.

Overall, the results show that within five years of diagnosis, around 1 in 50 men and women with schizophrenia (2.3% of men and 1.7% of women) died by suicide; around one in 10 (10.7%) of men and around one in 37 (2.7%) of women with schizophrenia were convicted of a violent offence within five years of diagnosis.  Overall, men and women with schizophrenia were eight times more likely to die prematurely than the general population. 

Analysing the changing rate of adverse outcomes across the study period (1972 – 2009), the researchers found that the risk of premature death, suicide, and conviction for a violent offence has increased for men and women with schizophrenia in the last 38 years, compared with both the general population, and their unaffected siblings. 

By tracking the number of nights spent in hospital by people with schizophrenia during the study period, the study shows that these increased rates of adverse outcomes appear to be associated with decreasing levels of inpatient care for these patients, although the study does not provide any evidence for a causal connection between decreasing inpatient care and adverse outcomes.

The researchers also analysed risk factors for adverse outcomes in both people with schizophrenia, the general population, and unaffected siblings.  Across all three groups, the risk factors for violence and premature death were broadly similar, and included drug use disorders, criminality, and self-harm, all before diagnosis – suggesting that improved strategies to address these risk factors have the potential to reduce violence and premature deaths across the population, and not just in those with schizophrenia.

According to Dr Fazel, “In recent years, there has been a lot of focus on primary prevention of schizophrenia – preventing people from getting ill.  While primary prevention is clearly essential and may be some decades away, our study highlights the crucial importance of secondary prevention – treating and managing the risks of adverse outcomes, such as self-harm or violent behaviour, in patients.  Risks of these adverse outcomes relative to others in society appear to be increasing in recent decades, suggesting that there is still much work to be done in developing new treatments and mitigating risks of adverse outcomes in people with schizophrenia.”*

Dr Eric Elbogen and Sally Johnson, at the University of North Carolina-Chapel Hill School of Medicine, USA, write in a linked Comment that, “One of the unique aspects of this study—that violence and suicide were analysed simultaneously—has an important implication for how we as a society perceive people with mental illness. News coverage of schizophrenia and other psychiatric disorders often focuses on violence and crime. Much less attention is paid to suicide and self-harm in people with severe mental illnesses.”

However, they add that, “Importantly, we should remember that, when reporting about the intricate links between schizophrenia and these adverse outcomes, most people with schizophrenia and related disorders are neither violent nor suicidal. Despite the need to ensure people with schizophrenia are provided help to reduce their risks of suicide, violence, or premature death, researchers reporting findings also bear the burden of ensuring that most people with schizophrenia and related disorders, who are not violent, are not left to contend with stigma and discrimination. Policy makers, researchers, and clinicians need to remember the importance of appropriately weighing up the issue of schizophrenia relative to the myriad of other factors that contribute to increased risk of violence and suicide.”

According to new research from the Monell Center, receptors for stress-activated hormones have been localized in oral taste cells responsible for detection of sweet, umami, and bitter. The findings suggest that these hormones, known as glucocorticoids, may act directly on taste receptor cells under conditions of stress to affect how these cells respond to sugars and certain other taste stimuli.

"Sweet taste may be particularly affected by stress," said lead author M. Rockwell Parker, PhD, a chemical ecologist at Monell. "Our results may provide a molecular mechanism to help explain why some people eat more sugary foods when they are experiencing intense stress."

Glucocorticoid (GC) hormones affect the body by activating specialized GC receptors located inside of cells. Knowing that stress can have major effects on metabolism and food choice, the researchers used a mouse model to ask whether taste receptor cells contain these GC receptors.

The findings, published online ahead of print in the journal Neuroscience Letters, revealed that GC receptors are present on the tongue, where they are specifically localized to the cells that contain receptors for sweet, umami and bitter taste. The highest concentrations of GC receptors were found in Tas1r3 taste cells, which are sensitive to sweet and umami taste.

GC hormones act on cells via a multi-step process. After GCs bind to their receptors within target cells, the activated receptor complex moves, or translocates, to the cell nucleus, where it then influences gene expression and protein assembly.

To explore whether GC receptors in taste tissue are activated by stress, the researchers compared the proportion of taste cells with translocated receptors in stressed and non-stressed mice. Compared to controls, the stressed mice had a 77 percent increase of GC receptors within taste cell nuclei.

Together, the results suggest that sweet taste perception and intake, which are known to be altered by stress, may be specifically affected via secretion of GCs and subsequent activation of GC receptors in taste cells.

"Taste provides one of our initial evaluations of potential foods. If this sense can be directly affected by stress-related hormonal changes, our food interaction will likewise be altered," said Parker.

Parker noted that although stress is known to affect intake of salty foods, GC receptors were not found in cells thought to be responsible for detecting sally and sour taste. One explanation, he said, is that stress may influence salt taste processing in the brain.

Implications of the findings extend beyond the oral taste system. Noting that taste receptors are found throughout the body, senior author and Monell molecular neurobiologist Robert Margolskee, MD, PhD, said, “Taste receptors in the gut and pancreas might also be influenced by stress, potentially impacting metabolism of sugars and other nutrients and affecting appetite.”

Future studies will continue to explore how stress hormones act to affect the taste system.

Scientists at NYU Langone Medical Center have identified a compound, called 2-PMAP, in animal studies that reduced by more than half levels of amyloid proteins in the brain associated with Alzheimer’s disease. The researchers hope that someday a treatment based on the molecule could be used to ward off the neurodegenerative disease since it may be safe enough to be taken daily over many years.  

“What we want in an Alzheimer’s preventive is a drug that modestly lowers amyloid beta and is also safe for long term use,” says Martin J. Sadowski, MD, PhD, associate professor of neurology, psychiatry, and biochemistry and molecular pharmacology, who led the research to be published online June 3 in the journal Annals of Neurology. “Statin drugs that lower cholesterol appear to have those properties and have made a big impact in preventing coronary artery disease. That’s essentially what many of us envision for the future of Alzheimer’s medicine.”

The 2-PMAP molecule that Dr. Sadowski’s team identified is non-toxic in mice, gets easily into the brain, and lowers the production of amyloid beta and associated amyloid deposits.

The prime target for Alzheimer’s prevention is amyloid beta. Decades before dementia begins, this small protein accumulates in clumps in the brain. Modestly lowering the production of amyloid beta in late middle age, and thus removing some of the burden from the brain’s natural clearance mechanisms, is believed to be a good prevention strategy. Researchers two years ago reported that something like this happens naturally in about 0.5 percent of Icelanders, due to a mutation they carry that approximately halves amyloid beta production throughout life. These fortunate people show a slower cognitive decline in old age, live longer, and almost never get Alzheimer’s.

Prevention of Alzheimer’s dementia is now considered more feasible than stopping it after it has begun, when brain damage is already severe. Every prospective Alzheimer’s drug in clinical trials has failed even to slow the disease process at that late stage. “The key is to prevent the disease process from going that far,” Dr. Sadowski says.

Dr. Sadowski and colleagues screened a library of compounds and found that 2-PMAP reduced the production of amyloid beta’s mother protein, known as amyloid precursor protein (APP). The APP protein normally is cut by enzymes in a way that leaves amyloid beta as one of the fragments. Dr. Sadowski’s team found that 2-PMAP, even at low, non-toxic concentrations, significantly reduced APP production in test cells, lowering amyloid beta levels by 50 percent or more.

The scientists subsequently found that 2-PMAP had essentially the same impact on APP and amyloid beta in the brains of living mice. The mice were engineered to have the same genetic mutations found in Alzheimer’s patients with a hereditary form of the disease, causing overproduction of APP and Alzheimer’s-like amyloid deposits. A five-day treatment with 2-PMAP lowered brain levels of APP and, even more so, levels of amyloid beta. Four months of treatment sharply reduced the amyloid deposits and prevented the cognitive deficits that are normally seen in these transgenic mice as they get older.

Dr. Sadowski and his laboratory are now working to make chemical modifications to the compound to improve its effectiveness. But 2-PMAP already seems to have advantages over other amyloid-lowering compounds, he says. One is that it can cross efficiently from the bloodstream to the brain, and thus doesn’t require complex modifications that might compromise its effects on APP.

The compound also appears to have a highly selective effect on APP production, by interfering with the translation of APP’s gene transcript into the APP protein itself. The best known candidates for Alzheimer’s preventives lower amyloid by inhibiting the secretase enzymes that cleave amyloid beta from APP, tending to cause unwanted side-effects via their off target interference with the processing of other client proteins cleaved by these enzymes. A clinical trial of one secretase inhibitor was halted in 2010 after it was found to worsen dementia and cause a higher incidence of skin cancer.

Alzheimer’s disease, the most common form of dementia, currently afflicts more than five million Americans, according to the Alzheimer’s Association. Unless preventive drugs or treatments are developed, the prevalence of Alzheimer’s is expected to triple by 2050.

Researchers at King’s College London have discovered how a molecular ‘scaffold’ which allows key parts of cells to interact, comes apart in dementia and motor neuron disease, revealing a potential new target for drug discovery.

The study, published today in Nature Communications, was funded by the UK Medical Research Council, Wellcome Trust, Alzheimer’s Research UK and the Motor Neurone Disease Association.

Researchers looked at two components of cells: mitochondria, the cell ‘power houses’ which produce energy for the cell;and the endoplasmic reticulum (ER) which makes proteins and stores calcium for signalling processes in the cell. ER and mitochondria form close associations and these interactions enable a number of important cell functions. However the mechanism by which ER and mitochondria become linked has not, until now, been fully understood.

Professor Chris Miller, from the Department of Neuroscience at the Institute of Psychiatry at King’s and lead author of the paper, says: “At the molecular level, many processes go wrong in dementia and motor neuron disease,and one of the puzzles we’re faced with is whether there is a common pathway connecting these different processes. Our study suggests that the loosening of this ‘scaffold’ between the mitochondria and ER in the cell may be a key process in neurodegenerative diseases such as dementia or motor neuron disease.”

By studying cells in a dish, the researchers discovered that an ER protein called VAPB binds to a mitochondrial protein called PTPIP51, to form a ‘scaffold’ enabling ER and mitochondria to form close associations. In fact, by increasing the levels of VAPB and PTPIP51, mitochondria and ER re-organised themselves to form tighter bonds.

Many of the cell’s functions that are controlled by ER-mitochondria associations are disrupted in neurodegenerative diseases, so the researchers studied how the strength of this ‘scaffold’ was affected in these diseases. TDP-43 is a protein which is strongly linked to Amyotrophic Lateral Sclerosis (ALS, a form of motor neuron disease) and Fronto-Temporal Dementia (FTD, the second most common form of dementia), but exactly how the protein causes neurodegeneration is not properly understood.

The researchers studied how TDP-43 affected mouse cells in a dish. They found that higher levels of TDP-43 resulted in a loosening of the scaffold which reduced ER-mitochondria bonds,affecting some important cellular functions that are linked to ALS and FTD.

Professor Miller concludes: “Our findings are important in terms of advancing our understanding of basic biology, but may also provide a potential new target for developing new treatments for these devastating disorders.”

Deep sleep promotes our well-being, improves our memory and strengthens the body’s defences. Zurich and Fribourg researchers demonstrate how restorative SWS can also be increased without medication – using hypnosis.

Sleeping well is a crucial factor contributing to our physical and mental restoration. SWS in particular has a positive impact for instance on memory and the functioning of the immune system. During periods of SWS, growth hormones are secreted, cell repair is promoted and the defence system is stimulated. If you feel sick or have had a hard working day, you often simply want to get some good, deep sleep. A wish that you can’t influence through your own will –  so the widely held preconception.  

Sleep researchers from the Universities of Zurich and Fribourg now prove the opposite. In a study that has now been published in the scientific journal “Sleep”, they have demonstrated that hypnosis has a positive impact on the quality of sleep, to a surprising  extent. “It opens up new, promising opportunities for improving the quality of sleep without drugs”, says biopsychologist Björn Rasch who heads the study at the Psychological Institute of the University of Zurich in conjunction with the “Sleep and Learning” project*.

Brain waves ­– an indicator of sleep quality

Hypnosis is a method that can influence processes which are very difficult to control voluntarily. Patients with sleep disturbances can indeed be successfully treated with hypnotherapy. However, up to now it hadn’t been proven that this can lead to an objectively measurable change in sleep. To objectively measure sleep, electrical brain activity is recorded using an electroencephalogram (EEG). The characteristic feature of slow-wave sleep, which is deemed to have high restorative capacity, is a very even and slow  oscillation in electrical brain activity.

70 healthy young women took part in the UZH study. They came to the sleep laboratory for a 90-minute midday nap. Before falling asleep they listened to a special 13-minute slow-wave sleep hypnosis tape over loudspeakers, developed by hypnotherapist Professor Angelika Schlarb, a sleep specialist, or to a neutral spoken text. At the beginning of the experiment the subjects were divided into highly suggestible and low suggestible groups using a standard procedure (Harvard Group Scale of Hypnotic Susceptibility). Around half of the population is moderately suggestible. With this method women achieve on average higher values for hypnotic susceptibility than men. Nevertheless, the researchers expect the same positive effects on sleep for highly suggestible men.

Slow-wave sleep increased by 80 percent

In their study, sleep researchers Maren Cordi and Björn Rasch were able to prove that highly suggestible women experienced 80 percent more slow-wave sleep after listening to the hypnosis tape compared with sleep after listening to the neutral text. In parallel, time spent awake was reduced by around one-third. In contrast to highly suggestible women, low suggestible female participants did not benefit as much from hypnosis. With additional control experiments the psychologists confirmed that the beneficial impact of hypnosis on slow-wave sleep could be attributed to the hypnotic suggestion to “sleep deeper” and could not be reduced to mere expectancy effects.

According to psychologist Maren Cordi “the results may be of major importance for patients with sleep problems and for older adults. In contrast to many sleep-inducing drugs, hypnosis has no adverse side effects”. Basically, everyone who responds to hypnosis could benefit from improved sleep through hypnosis.  

* The project “Sleep and Learning” is headed by Professor Björn Rasch from the University of Fribourg and conducted at the Universities of Zurich and Fribourg. The project is financed by the Swiss National Fund and the University of Zurich (main area of clinical research “Sleep and Health”). The goal of the project is to identify psychological and neurophysiological mechanisms underlying the positive role of sleep for our memory and mental health.  

Fetuses are more likely to show left-handed movements in the womb when their mothers are stressed, according to new research.

Researchers at Durham and Lancaster universities say their findings are an indicator that maternal stress could have a temporary effect on unborn babies, adding that their research highlights the importance of reducing stress during pregnancy.

However, the researchers emphasised that their study was not evidence that maternal stress led to fixed left-handedness in infants after birth. They said that some people might be genetically predisposed to being left-handed and that there are examples where right and left-handedness can switch throughout a person’s life.

Using 4d ultrasound scans, the researchers observed 57 scans of 15 healthy fetuses, recording 342 facial touches.

The fetuses were scanned at four different stages between 24 and 36 weeks of pregnancy. Researchers also asked the mothers of these babies how much stress they had experienced in the four weeks between each of the scans.

The researchers found that the more stress mothers reported, the more frequently fetuses touched their faces with their left hands. They added that a significant number of touches by the fetuses of stressed mothers were done with their left, rather than right hands - therefore fetal touches of their own faces, indicated a left-handed tendency.

As right-handedness is more common in the general population, the researchers had expected to see more of a bias towards right-handed movements in the fetuses as they grew older. The high percentage of left-handed behaviour, observed only when mothers reported being stressed, led them to conclude that maternal stress has an effect on the lateral behaviour of the babies they scanned.

The findings are published in the journal Laterality: Asymmetries of Body, Brain and Cognition.

Lead author Dr Nadja Reissland, in Durham University’s Department of Psychology, said: “Our research suggests that stressed mothers have fetuses who touch their face relatively more with their left hand.

“This suggests maternal stress could be having on effect on the child’s behaviour in the womb and highlights the importance of reducing maternal stress in pregnancy.

“Such measures may include increased emphasis on stopping stressful work early, the inclusion of relaxation classes in pre-natal care and involvement of the whole family in the pre-natal period.

“While we observed a higher degree of left-handed behaviour in the fetuses of stressed mothers than had been expected, we are not saying that maternal stress leads to a child becoming left-handed after birth, as there could be a number of reasons for this.

“The research does suggest, however, that a fetus can detect when a mother is stressed and that it responds to this stress.”

Professor Brian Francis, of Lancaster University, emphasised that the study also showed that overall preference for left or right hand varied considerably from scan to scan within each fetus, though fetuses showed more left-hand movements when mothers reported that they had experienced stress. He said: “Overall, there was no consistent handedness preference being shown by the fetuses, with most fetuses switching in preference at least once over the four scans.”

The researchers added that while mothers were asked to report their stress levels in the four weeks between scans, in practice some might have reported the stress they were experiencing at the time of being surveyed.

Previous research has shown that maternal stress in pregnancy leads to increased levels of cortisol – a hormone produced in response to stress - in mothers that could lead to an altered preference for left-sided or right-sided behaviour in fetuses.

The current study did not assess the stress levels of fetuses and Dr Reissland said that future research could examine cortisol levels in fetuses to further determine the effect of stress on lateral behaviour.

Dr Reissland added that further research was also needed to look at whether or not maternal prenatal stress had longer-term effects on the development of infants and children after birth.

A seven-year study of women who take antipsychotic medication while pregnant, proves it can affect babies.

The observational study, published in the journal PLOS ONE, reveals that whilst most women gave birth to healthy babies, the use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the need for special care after birth with 43 per cent of babies placed in a Special Care Nursery (SCN) or a Neonatal Intensive Care Unit (NICU), almost three times the national rate in Australia.

As well as an increased likelihood of the need for intensive care, the world-first study by experts from the Monash Alfred Psychiatry Research Centre (MAPrc) and Monash University, shows antipsychotic drugs affects babies in other ways; 18 per cent were born prematurely, 37 per cent showed signs of respiratory distress and 15 per cent developed withdrawal symptoms.

Principal investigator, Professor Jayashri Kulkarni, Director of MAPrc, said the study highlights the need for clearer health guidelines when antipsychotic drugs are taken during pregnancy.

“There’s been little research on antipsychotic medication during pregnancy and if it affects babies. The lack of data has made it very difficult for clinicians to say anything conclusively on how safe it is for babies,” Professor Kulkarni said.

“This new research confirms that most babies are born healthy, but many experience neonatal problems such as respiratory distress.”

With no existing data to draw on, MAPrc established the world-first National Register of Antipsychotic Medications in Pregnancy (NRAMP) in 2005. Women who were pregnant and taking antipsychotic medication were recruited from around Australia through clinical networks in each state and territory. In all 147 women were interviewed every six weeks during pregnancy and then followed until their babies were one year old.

Antipsychotic drugs are currently used to treat a range of psychiatric disorders including schizophrenia, major depression and bipolar disorder. About 20 per cent of Australian women experience depression in their lifetime, compared to 10 per cent of men. In Australia 25 per cent of women experience postnatal depression and 20 per cent experience severe menopausal depression.

Women have much higher rates of anxiety disorders and there are equal percentages of men and women with schizophrenia (2 per cent) and bipolar disorder (about 3 per cent).

Professor Kulkarni said the emergence of new antipsychotic drugs means that many women with a well controlled psychiatric disorder are able to contemplate having babies, but there have always been concerns about the effect of treatment on their offspring.

“The potentially harmful effects of taking an antipsychotic drug in pregnancy have to be balanced against the harm of untreated psychotic illness. The good news is we now know there are no clear associations with specific congenital abnormalities and these drugs,” Professor Kulkarni said.

“However clinicians should be particularly mindful of neonatal problems such as respiratory distress, so it’s critical that Neonatal Intensive Care Units, or Special Care Nurseries are available for these babies.”

A team of University of South Carolina researchers led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang have discovered a novel pathway through which marijuana can suppress the body’s immune functions. Their research has been published online in the Journal of Biological Chemistry.

Marijuana is the most frequently used illicit drug in the United States, but as more states legalize the drug for medical and even recreational purposes, research studies like this one are discovering new and innovative potential health applications for the federal Schedule I drug.

Marijuana is now regularly and successfully used to alleviate the nausea and vomiting many cancer patients experience as side effects to chemotherapy, combat the wasting syndrome that causes some AIDS patients to lose significant amounts of weight and muscle mass and ease chronic pain that is unresponsive to opioids, among other applications.

The university study has uncovered yet another potential application for marijuana, in the suppression of immune response to treat autoimmune diseases. The work builds on recent scientific discoveries that the environment in which humans live can actually trigger changes that occur outside of human DNA, but nevertheless can cause alterations to the function of genes controlled by DNA. These outside molecules that have the ability to alter DNA function are known collectively as the epigenome. In this study, the investigators wanted to find out if the tetrahydrocannabinol found in marijuana has the capacity to affect DNA expression through epigenetic pathways outside of the DNA itself.

The recent findings show that marijuana THC can change critical molecules of epigenome called histones, leading to suppression of inflammation. These results suggest that one potential negative impact of marijuana smoking could be suppression of beneficial inflammation in the body. But they also suggest that, because of its epigenetic influence toward inflammation suppression, marijuana use could be efficacious in the treatment of autoimmune diseases such as arthritis, lupus, colitis, multiple sclerosis and the like, in which chronic inflammation plays a central role.

Until now, scientists have not known exactly how inflammation weakens the Blood-Brain Barrier, allowing toxins and other molecules access to the brain. A new research report appearing in the June 2014 issue of The FASEB Journal solves this mystery by showing that a molecule, called “microRNA-155,” is responsible for cleaving epithelial cells to create microscopic gaps that let material through. Not only does this discovery help explain the molecular underpinnings of diseases like multiple sclerosis, but it also opens an entirely new avenue for developing therapies that can help penetrate the Blood-Brain Barrier to deliver lifesaving drugs.

According to Ignacio A, Romero, Ph.D., “We are beginning to understand the mechanisms by which the barrier between the blood and the brain becomes leaky in inflammatory conditions. Based on these and other findings, drugs that reduce the leakiness of the barrier have the potential to improve symptoms in many neurological conditions.” Romero is one of the researchers involved in the work from the Department of Life, Health and Chemical Sciences of the Biomedical Research Network at The Open University in the United Kingdom.

To make this discovery, Romero and colleagues first measured microRNA-155 (miR-155) levels in cultured human cells and compared them to cells under inflammatory conditions. Researchers then measured levels in the blood vessels of inflamed brain areas of patients with multiple sclerosis (MS) and compared them to non-inflamed areas. In both cases, miR-155 was elevated in inflammation. Then, in mice, normal mice were compared with mice that were genetically altered to lose miR-155. When an inflammatory reaction was induced in these two groups of mice, the mice that could not express miR-155 had a much reduced increase in “leakiness” of the Blood-Brain Barrier than normal mice. Finally, scientists investigated in cultured human cells the mechanism by which miR-155 levels cause leakiness of the barrier and concluded that miR-155 affects the organization of the complex structures that form the tight connections between endothelial cells.

"This study has the potential to be a game-changer in terms of how we treat neurological conditions and how we deliver drugs to the brain," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Since it was first discovered, the Blood-Brain Barrier has always been a touch elusive. Now, after careful analysis, we are learning exactly how our bodies keep our brains safe and that microRNA-155 is a key player.”

Twenty years after the hormone leptin was found to regulate metabolism, appetite, and weight through brain cells called neurons, Yale School of Medicine researchers have found that the hormone also acts on other types of cells to control appetite.

Published in the June 1 issue of Nature Neuroscience, the findings could lead to development of treatments for metabolic disorders such as obesity and diabetes.

"Up until now, the scientific community thought that leptin acts exclusively in neurons to modulate behavior and body weight," said senior author Tamas Horvath, the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine. "This work is now changing that paradigm."

Leptin, a naturally occurring hormone, is known for its hunger-blocking effect on the hypothalamus, a region in the brain. Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signal the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese.

Leptin’s effect on metabolism has been found to control the brain’s neuronal circuits, but no previous studies have definitively found that leptin could control the behavior of cells other than neurons.

To test the theory, Horvath and his team selectively knocked out leptin receptors in the adult non-neuronal glial cells of mice. The team then recorded the water and food intake, as well as physical activity every five days. They found that animals responded less to feeding reducing effects of leptin but had heightened feeding responses to the hunger hormone ghrelin.

"Glial cells provide the main barrier between the periphery and the brain," said Horvath. "Thus glial cells could be targeted for drugs that treat metabolic disorders, including obesity and diabetes."

New research reveals that bilingualism has a positive effect on cognition later in life. Findings published in Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, show that individuals who speak two or more languages, even those who acquired the second language in adulthood, may slow down cognitive decline from aging.

Bilingualism is thought to improve cognition and delay dementia in older adults. While prior research has investigated the impact of learning more than one language, ruling out “reverse causality” has proven difficult. The crucial question is whether people improve their cognitive functions through learning new languages or whether those with better baseline cognitive functions are more likely to become bilingual.

"Our study is the first to examine whether learning a second language impacts cognitive performance later in life while controlling for childhood intelligence," says lead author Dr. Thomas Bak from the Centre for Cognitive Aging and Cognitive Epidemiology at the University of Edinburgh.

For the current study, researchers relied on data from the Lothian Birth Cohort 1936, comprised of 835 native speakers of English who were born and living in the area of Edinburgh, Scotland. The participants were given an intelligence test in 1947 at age 11 years and retested in their early 70s, between 2008 and 2010. Two hundred and sixty two participants reported to be able to communicate in at least one language other than English. Of those, 195 learned the second language before age 18, 65 thereafter.

Findings indicate that those who spoke two or more languages had significantly better cognitive abilities compared to what would be expected from their baseline. The strongest effects were seen in general intelligence and reading. The effects were present in those who acquired their second language early as well as late.

The Lothian Birth Cohort 1936 forms the Disconnected Mind project at the University of Edinburgh, funded by Age UK. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1) and has been made possible thanks to funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC).

"The Lothian Birth Cohort offers a unique opportunity to study the interaction between bilingualism and cognitive aging, taking into account the cognitive abilities predating the acquisition of a second language" concludes Dr. Bak. "These findings are of considerable practical relevance. Millions of people around the world acquire their second language later in life. Our study shows that bilingualism, even when acquired in adulthood, may benefit the aging brain."

After reviewing the study, Dr. Alvaro Pascual-Leone, an Associate Editor for Annals of Neurology and Professor of Medicine at Harvard Medical School in Boston, Mass. said, “The epidemiological study by Dr. Bak and colleagues provides an important first step in understanding the impact of learning a second language and the aging brain. This research paves the way for future causal studies of bilingualism and cognitive decline prevention.”

A collaborative effort between Duke Medicine researchers and neurosurgeons and scientists in China has produced new genetic insights into a rare and deadly form of childhood and young adult brain cancer called brainstem glioma.

The researchers identified a genetic mutation in the tumor cells that plays a role in both the growth and the death of a cell. Additionally, the mutation to the newly identified gene may also contribute to the tumor’s resistance to radiation.

The findings, published online in the journal Nature Genetics on June 1, 2014, provide both immediate and long-term benefits. Knowing that this mutation may render radiation ineffective, patients could be spared that therapy. The mutation would also serve as a strong candidate for drug development.

The researchers conducted genetic tests and found that many of the tumor cells had a mutation in a gene called PPM1D, which causes cells to proliferate and avoid natural death. It is the first time this mutation has been found to be a major driving force in the development of brainstem gliomas; it is not evident in other brain tumors.

If tumors have this PPM1D mutation, they do not have another more common genetic mutation to the TP53 gene, a tumor suppressor that, when defective, is linked to half of all cancers.

“This finding has immediate clinical applications, because either mutation - PPM1D or TP53 – cause the tumor cells to be resistant to radiation,” said senior author Hai Yan, M.D., Ph.D., a professor of pathology at Duke University School of Medicine. “Knowing that could spare patients from an ineffective treatment approach.”

Additionally, the PPM1D genetic mutation is a strong candidate for new drug development.

“This finding gives us a clue as to why these particular tumors are growing inappropriately,” said co-author Zachary Reitman, M.D., Ph.D., a research associate at Duke. “These clues may help us to design better treatments for this type of cancer.”

Yan said his lab is working to identify new treatments that could target the PPM1D genetic mutation and shut down its cancer-growing capabilities.

“PPM1D is itself a target for drug development, because the gene mutation causes cells to avoid death and proliferate,” Yan said. “In drug development, it’s easier to turn that growth function off than it is to switch on the cell’s defective tumor suppression mechanism.”

Research by scientists at Albert Einstein College of Medicine of Yeshiva University may help explain how some cases of autism spectrum disorder (ASD) can result from environmental influences rather than gene mutations. The findings, published online today in PLOS Genetics, shed light on why older mothers are at increased risk for having children with ASD and could pave the way for more research into the role of environment on ASD.

The U.S. Centers for Disease Control and Prevention announced in March that one in 68 U.S. children has an ASD—a 30 percent rise from 1 in 88 two years ago. A significant number of people with an ASD have gene mutations that are responsible for their condition. But a number of studies—particularly those involving identical twins, in which one twin has ASD and the other does not—show that not all ASD cases arise from mutations.

In fact, a major study of more than 14,000 children with ASDs published earlier this month in the Journal of the American Medical Association concluded that gene abnormalities could explain only half the risk for developing ASD. The other half of the risk was attributable to “nongenetic influences,” meaning environmental factors that could include the conditions in the womb or a pregnant woman’s stress level or diet. 

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Symmetry is an inherent part of development. As an embryo, an organism’s brain and spinal cord, like the rest of its body, organize themselves into left and right halves as they grow. But a certain set of nerve cells do something unusual: they cross from one side to the other. New research in mice delves into the details of the molecular interactions that help guide these neurons toward this anatomical boundary.

In an embryo, a neuron’s branches, or axons, have special structures on their tips that sense chemical cues telling them where to grow. The new findings, by researchers at Memorial Sloan Kettering Cancer Center and The Rockefeller University, reveal the structural details of how one such cue, Netrin-1, interacts with two sensing molecules on the axons, DCC and a previously less well characterized player known as neogenin, as a part of this process.

“Our work provides the first high-resolution view of the molecular complexes that form on the surface of a developing axon and tell it to move in one direction or another,” says Dimitar Nikolov, a structural biologist at Memorial Sloan Kettering. “This detailed understanding of these assemblies helps us better understand neural wiring, and may one day be useful in the development of drugs to treat spinal cord or brain injuries.”

In a developing nervous system, the signaling molecule, Netrin-1, identified by Rockefeller University Professor Marc Tessier-Lavigne and colleagues, can guide neurons by attracting or repulsing them. In the case of axons that cross from one side to the other, extended by so-called commissural neurons, Netrin-1 attracts them toward the middle.

With a technique that uses X-rays to visualize the structure of crystalized proteins, research scientist Kai Xu and colleagues in Nikolov’s laboratory revealed that Netrin-1 has two separate binding sites on opposite ends, enabling it to simultaneously bind to different receptors. This may explain how Netrin-1, which is an important axon-guiding molecule, can affect in different ways neurons that express different combinations of receptors, Nikolov says.

For some time, scientists have known commissural neurons used the receptor molecule DCC to detect Netrin-1. Neogenin has a structure similar to DCC, and this research, described today in Science, confirms neogenin too acts as a sensing molecule for commissural neurons in mammals.

In experiments that complemented the structural work, conducted by Nicolas Renier and Zhuhao Wu in Tessier-Lavigne’s lab, the researchers confirmed that, like DCC, neogenin senses Netrin-1 for the growing commissural neurons in mice.

These neurons are part of the system by which one side of the brain controls movement on the opposite side of the body. As a result, a mutation in the gene responsible for DCC interferes with this coordination, causing congenital mirror movement disorder. People with this disorder cannot move one side of the body in isolation; for example, a right-handed wave is mirrored by a similar gesture by the left hand.

The work also has implications for understanding why DCC, neogenin and other cell-surface receptors come in slightly different forms, called splice isoforms. The structural research revealed these isoforms bind differently to Netrin-1. However, it is not yet clear what this means for neuron wiring, Nikolov says.

“With this structural knowledge, and with the identification of an additional receptor involved in axon guidance in the spinal cord, we are gaining deeper insight into the mechanisms through which neurons make connections that produce a functioning nervous system, as well as the dysfunction that arises from miswiring of connections” says Tessier-Lavigne.

New research from the Monell Chemical Senses Center reveals that women’s faces are rated as more attractive in the presence of pleasant odors. In contrast, odor pleasantness had less effect on the evaluation of age. The findings suggest that the use of scented products such as perfumes may, to some extent, alter how people perceive one another.

“Odor pleasantness and facial attractiveness integrate into one joint emotional evaluation,” said lead author Janina Seubert, PhD, a cognitive neuroscientist who was a postdoctoral fellow at Monell at the time the research was conducted. “This may indicate a common site of neural processing in the brain.”

Perfumes and scented products have been used for centuries as a way to enhance overall personal appearance. Previous studies had shown perception of facial attractiveness could be influenced when using unpleasant vs. pleasant odors. However, it was not known whether odors influence the actual visual perception of facial features or alternatively, how faces are emotionally evaluated by the brain.

The current study design centered on the principle that judging attractiveness and age involve two distinct perceptual processing methods: attractiveness is regarded as an emotional process while judgments of age are believed to be cognitive, or rationally-based.

In the study, published in open access journal PLOS ONE, 18 young adults, two thirds of whom were female, were asked to rate the attractiveness and age of eight female faces, presented as photographs. The images varied in terms of natural aging features.

While evaluating the images, one of five odors was simultaneously released. These were a blend of fish oil (unpleasant) and rose oil (pleasant) that ranged from predominantly fish oil to predominantly rose oil. The subjects were asked to rate the age of the face in the photograph, the attractiveness of the face and the pleasantness of the odor.

Across the range of odors, odor pleasantness directly influenced ratings of facial attractiveness. This suggests that olfactory and visual cues independently influence judgments of facial attractiveness.

With regard to the cognitive task of age evaluation, visual age cues (more wrinkles and blemishes) were linked to older age perception. However, odor pleasantness had a mixed effect. Visual age cues strongly influenced age perception during pleasant odor stimulation, making older faces look older and younger faces look younger. This effect was weakened in the presence of unpleasant odors, so that younger and older faces were perceived to be more similar in age.

Jean-Marc Dessirier, Lead Scientist at Unilever and a co-author on the study said, “These findings have fascinating implications in terms of how pleasant smells may help enhance natural appearance within social settings. The next step will be to see if the findings extend to evaluation of male facial attractiveness.”